Judith Clements

Kallikrein-related Peptidase 15 (Prostinogen)

Publisher: Elsevier

Date: 2013

DOI: 10.1016/B978-0-12-382219-2.00619-0

Kallikrein gene expression in estrogen-induced pituitary tumors

Publisher: Elsevier BV

Date: 12-1988

DOI: 10.1016/0303-7207(88)90182-7

Abstract: Anterior pituitary kallikrein-like enzyme activity, immunoreactivity and mRNA levels have previously been shown to be regulated by estrogen, in parallel with prolactin. In this study, we have examined the relationship between kallikrein and prolactin mRNA levels in estrogen-induced pituitary tumors. Treatment of Fischer 344 rats with diethylstilbestrol implants for 3, 5 and 7 weeks produced a dramatic increase in kallikrein mRNA levels and a modest increase in prolactin mRNA levels. These changes were partially reversed by bromocriptine treatment, and completely reversed by bromocriptine plus estrogen withdrawal. Using a panel of oligonucleotide probes specific for various members of the rat kallikrein gene family, we have shown that the kallikrein-like gene expressed appears to be true kallikrein.

A large-scale analysis of genetic variants within putative miRNA binding sites in prostate cancer

Publisher: American Association for Cancer Research (AACR)

Date: 04-2015

DOI: 10.1158/2159-8290.CD-14-1057

Abstract: Prostate cancer is the second most common malignancy among men worldwide. Genome-wide association studies have identified 100 risk variants for prostate cancer, which can explain approximately 33% of the familial risk of the disease. We hypothesized that a comprehensive analysis of genetic variations found within the 3′ untranslated region of genes predicted to affect miRNA binding (miRSNP) can identify additional prostate cancer risk variants. We investigated the association between 2,169 miRSNPs and prostate cancer risk in a large-scale analysis of 22,301 cases and 22,320 controls of European ancestry from 23 participating studies. Twenty-two miRSNPs were associated (P & 2.3 × 10−5) with risk of prostate cancer, 10 of which were within 7 genes previously not mapped by GWAS studies. Further, using miRNA mimics and reporter gene assays, we showed that miR-3162-5p has specific affinity for the KLK3 rs1058205 miRSNP T-allele, whereas miR-370 has greater affinity for the VAMP8 rs1010 miRSNP A-allele, validating their functional role. Significance: Findings from this large association study suggest that a focus on miRSNPs, including functional evaluation, can identify candidate risk loci below currently accepted statistical levels of genome-wide significance. Studies of miRNAs and their interactions with SNPs could provide further insights into the mechanisms of prostate cancer risk. Cancer Discov 5(4) 368–79. ©2015 AACR. See related commentary by Yousef, p. 351 This article is highlighted in the In This Issue feature, p. 333

Zwitterionic versus organic ionic plastic crystal electrolytes with mixed anions: probing the unique physicochemical and electrolyte properties

Publisher: Royal Society of Chemistry (RSC)

Date: 2022

DOI: 10.1039/D1TA10024F

Abstract: Novel solid-state electrolytes based on zwitterionic plastic crystals with Li salts are reported and their application in Li batteries demonstrated. Their properties are compared with those of analogous plastic crystal/Li salt systems.

Tissue engineered humanized bone supports human hematopoiesis in vivo

Publisher: Elsevier BV

Date: 08-2015

DOI: 10.1016/J.BIOMATERIALS.2015.04.057

Abstract: Advances in tissue-engineering have resulted in a versatile tool-box to specifically design a tailored microenvironment for hematopoietic stem cells (HSCs) in order to study diseases that develop within this setting. However, most current in vivo models fail to recapitulate the biological processes seen in humans. Here we describe a highly reproducible method to engineer humanized bone constructs that are able to recapitulate the morphological features and biological functions of the HSC niches. Ectopic implantation of biodegradable composite scaffolds cultured for 4 weeks with human mesenchymal progenitor cells and loaded with rhBMP-7 resulted in the development of a chimeric bone organ including a large number of human mesenchymal cells which were shown to be metabolically active and capable of establishing a humanized microenvironment supportive of the homing and maintenance of human HSCs. A syngeneic mouse-to-mouse transplantation assay was used to prove the functionality of the tissue-engineered ossicles. We predict that the ability to tissue engineer a morphologically intact and functional large-volume bone organ with a humanized bone marrow compartment will help to further elucidate physiological or pathological interactions between human HSCs and their native niches.

Investigation of Unusual Conductivity Behavior and Ion Dynamics in Hexamethylguanidinium Bis(fluorosulfonyl)imide-Based Electrolytes for Sodium Batteries

Publisher: American Chemical Society (ACS)

Date: 02-06-2021

DOI: 10.1021/ACS.JPCC.1C01777

Temporal and tissue-specific expression of kallikrein (Klk) genes and identification of a novel Klk messenger ribonucleic acid transcript during early development in the mouse

Publisher: Oxford University Press (OUP)

Date: 09-1999

DOI: 10.1095/BIOLREPROD61.3.621

Abstract: The kallikreins are a multigene family of serine proteases that act on a erse number of substrates, including several growth factors and extracellular matrix (ECM) glycoproteins and proteinases. Recently, this family has been implicated in the process of early development and embryo implantation. In this study, we used reverse transcription-polymerase chain reaction with gene-specific primers and Southern hybridization to elucidate the temporal and tissue-specific expression patterns of the mouse kallikreins Klk1, Klk3, Klk5, Klk9, and Klk21 during early development in the embryo, uterus, and decidua. We observed the expression of Klk1 (tissue kallikrein), Klk3 (gamma-nerve growth factor), Klk9 (epidermal growth factor-binding protein), and Klk21 in the early conceptus (until the 2-cell stage). Only Klk21 continued to be expressed in the blastocyst until Day 7.5 of pregnancy. Expression of Klk9 reappeared at Day 7.5 and was consistently detected until Day 11, the last day studied Klk1 was again expressed in the embryo from Day 9.5, with decreased levels by Day 11. In contrast, in the uterus or decidua, there was no expression of Klk1 until Day 7.5, when mRNA transcripts were abundant transcripts then decreased in the Day 9.5 and Day 11 uterus. Expression of Klk21 in the uterus and decidua displayed a similar pattern but was detected at much lower levels. Interestingly, a novel Klk21-like mRNA was also detected in uterine tissue s les but not in embryonic s les Klk3, Klk5, and Klk9 were not consistently expressed in the uterus or decidua over this time. This is the first report of the expression of specific kallikreins during early development. The distinct gene- and tissue-specific expression patterns presented in this study, in conjunction with the well-characterized roles of kallikreins in regulation of protein activation, ECM degradation, and proliferative events, suggests the involvement of the kallikrein gene family during early development.

Kallikrein gene expression in the gonadotrophin-stimulated rat ovary

Publisher: Bioscientifica

Date: 07-2001

DOI: 10.1677/JOE.0.1700243

Abstract: The kallikreins (KLKs) are a highly conserved multi-gene family of serine proteases that are expressed in a wide variety of tissues and act on a erse range of substrates. KLK-like enzyme activity has variously been reported to increase or decrease during the period leading up to ovulation in the equine chorionic gonadotrophin (eCG)primed, human chorionic gonadotrophin (hCG)-stimulated immature rat ovary. These earlier studies, which used biochemical assays to detect enzyme activity, lacked the specificity and sensitivity necessary to characterise conclusively the activity of the in idual KLK gene family members. In this study, we have used a gene-specific RT-PCR/Southern hybridisation strategy to delineate the expression patterns of six of the in idual KLK genes expressed in the rat ovary (rKLK1-3 and rKLK7-9). We have identified three broad patterns of expression in the eCG/hCG-stimulated ovary in which there is either a post-eCG increase re-ovulatory decrease in rKLK expression (rKLK1, rKLK3), a peri-ovulatory decrease in expression (rKLK2, rKLK8) or a relatively unchanged pattern of expression (rKLK7, rKLK9). In addition to clarifying the earlier biochemical studies, these findings support a differential role for the in idual KLKs in the ovulatory process.

The kallikrein-related peptidase family: Dysregulation and functions during cancer progression

Publisher: Elsevier BV

Date: 03-2016

DOI: 10.1016/J.BIOCHI.2015.09.002

Abstract: Cancer is the second leading cause of death with 14 million new cases and 8.2 million cancer-related deaths worldwide in 2012. Despite the progress made in cancer therapies, neoplastic diseases are still a major therapeutic challenge notably because of intra- and inter-malignant tumour heterogeneity and adaptation/escape of malignant cells to/from treatment. New targeted therapies need to be developed to improve our medical arsenal and counter-act cancer progression. Human kallikrein-related peptidases (KLKs) are secreted serine peptidases which are aberrantly expressed in many cancers and have great potential in developing targeted therapies. The potential of KLKs as cancer biomarkers is well established since the demonstration of the association between KLK3/PSA (prostate specific antigen) levels and prostate cancer progression. In addition, a constantly increasing number of in vitro and in vivo studies demonstrate the functional involvement of KLKs in cancer-related processes. These peptidases are now considered key players in the regulation of cancer cell growth, migration, invasion, chemo-resistance, and importantly, in mediating interactions between cancer cells and other cell populations found in the tumour microenvironment to facilitate cancer progression. These functional roles of KLKs in a cancer context further highlight their potential in designing new anti-cancer approaches. In this review, we comprehensively review the biochemical features of KLKs, their functional roles in carcinogenesis, followed by the latest developments and the successful utility of KLK-based therapeutics in counteracting cancer progression.

A Kallikrein 15 (KLK15) single nucleotide polymorphism located close to a novel exon shows evidence of association with poor ovarian cancer survival

Publisher: Springer Science and Business Media LLC

Date: 04-2011

DOI: 10.1186/1471-2407-11-119

Abstract: KLK15 over-expression is reported to be a significant predictor of reduced progression-free survival and overall survival in ovarian cancer. Our aim was to analyse the KLK15 gene for putative functional single nucleotide polymorphisms (SNPs) and assess the association of these and KLK15 HapMap tag SNPs with ovarian cancer survival. In silico analysis was performed to identify KLK15 regulatory elements and to classify potentially functional SNPs in these regions. After SNP validation and identification by DNA sequencing of ovarian cancer cell lines and aggressive ovarian cancer patients, 9 SNPs were shortlisted and genotyped using the Sequenom iPLEX Mass Array platform in a cohort of Australian ovarian cancer patients (N = 319). In the Australian dataset we observed significantly worse survival for the KLK15 rs266851 SNP in a dominant model (Hazard Ratio (HR) 1.42, 95% CI 1.02-1.96). This association was observed in the same direction in two independent datasets, with a combined HR for the three studies of 1.16 (1.00-1.34). This SNP lies 15bp downstream of a novel exon and is predicted to be involved in mRNA splicing. The mutant allele is also predicted to abrogate an HSF-2 binding site. We provide evidence of association for the SNP rs266851 with ovarian cancer survival. Our results provide the impetus for downstream functional assays and additional independent validation studies to assess the role of KLK15 regulatory SNPs and KLK15 isoforms with alternative intracellular functional roles in ovarian cancer survival.

Unravelling the Role of Iroquois Homeobox 4 and its Interplay with Androgen Receptor in Prostate Cancer

Publisher: Research Square Platform LLC

Date: 24-10-2023

DOI: 10.21203/RS.3.RS-3295914/V1

Mineralized human primary osteoblast matrices as a model system to analyse interactions of prostate cancer cells with the bone microenvironment

Publisher: Elsevier BV

Date: 11-2010

DOI: 10.1016/J.BIOMATERIALS.2010.06.055

Abstract: Prostate cancer metastasis is reliant on the reciprocal interactions between cancer cells and the bone niche/micro-environment. The production of suitable matrices to study metastasis, carcinogenesis and in particular prostate cancer/bone micro-environment interaction has been limited to specific protein matrices or matrix secreted by immortalised cell lines that may have undergone transformation processes altering signaling pathways and modifying gene or receptor expression. We hypothesize that matrices produced by primary human osteoblasts are a suitable means to develop an in vitro model system for bone metastasis research mimicking in vivo conditions. We have used a decellularized matrix secreted from primary human osteoblasts as a model for prostate cancer function in the bone micro-environment. We show that this collagen I rich matrix is of fibrillar appearance, highly mineralized, and contains proteins, such as osteocalcin, osteonectin and osteopontin, and growth factors characteristic of bone extracellular matrix (ECM). LNCaP and PC3 cells grown on this matrix, adhere strongly, proliferate, and express markers consistent with a loss of epithelial phenotype. Moreover, growth of these cells on the matrix is accompanied by the induction of genes associated with attachment, migration, increased invasive potential, Ca(2+) signaling and osteolysis. In summary, we show that growth of prostate cancer cells on matrices produced by primary human osteoblasts mimics key features of prostate cancer bone metastases and thus is a suitable model system to study the tumor/bone micro-environment interaction in this disease.

Interactions between the seminiferous tubules and leydig cells of the testis

Publisher: CSIRO Publishing

Date: 1990

DOI: 10.1071/RD9900219

Ontogenesis of Gonadotropin-Releasing Hormone in the Human Fetal Hypothalamus

Publisher: SAGE Publications

Date: 03-1980

DOI: 10.3181/00379727-163-40793

Abstract: Knowing how to adapt your behavior based on feedback lies at the core of successful learning. We investigated the relation between brain function, grey matter volume, educational level and IQ in a Dutch adolescent s le. In total 45 healthy volunteers between ages 13 and 16 were recruited from schools for pre-vocational and pre-university education. For each in idual, IQ was estimated using two subtests from the WISC-III-R (similarities and block design). While in the magnetic resonance imaging (MRI) scanner, participants performed a probabilistic learning task. Behavioral comparisons showed that participants with higher IQ used a more adaptive learning strategy after receiving positive feedback. Analysis of neural activation revealed that higher IQ was associated with increased activation in DLPFC and dACC when receiving positive feedback, specifically for rules with low reward probability (i.e., unexpected positive feedback). Furthermore, VBM analyses revealed that IQ correlated positively with grey matter volume within these regions. These results provide support for IQ-related in idual differences in the developmental time courses of neural circuitry supporting feedback-based learning. Current findings are interpreted in terms of a prolonged window of flexibility and opportunity for adolescents with higher IQ scores.

A genetic variant of MDM4 influences regulation by multiple microRNAs in prostate cancer

Publisher: Bioscientifica

Date: 10-02-2015

DOI: 10.1530/ERC-15-0013

Abstract: The oncogene MDM4 , also known as MDMX or HDMX , contributes to cancer susceptibility and progression through its capacity to negatively regulate a range of genes with tumour-suppressive functions. As part of a recent genome-wide association study it was determined that the A-allele of the rs4245739 SNP (A C), located in the 3′-UTR of MDM4 , is associated with an increased risk of prostate cancer. Computational predictions revealed that the rs4245739 SNP is located within a predicted binding site for three microRNAs (miRNAs): miR-191-5p, miR-887 and miR-3669. Herein, we show using reporter gene assays and endogenous MDM4 expression analyses that miR-191-5p and miR-887 have a specific affinity for the rs4245739 SNP C-allele in prostate cancer. These miRNAs do not affect MDM4 mRNA levels, rather they inhibit its translation in C-allele-containing PC3 cells but not in LNCaP cells homozygous for the A-allele. By analysing gene expression datasets from patient cohorts, we found that MDM4 is associated with metastasis and prostate cancer progression and that targeting this gene with miR-191-5p or miR-887 decreases in PC3 cell viability. This study is the first, to our knowledge, to demonstrate regulation of the MDM4 rs4245739 SNP C-allele by two miRNAs in prostate cancer, and thereby to identify a mechanism by which the MDM4 rs4245739 SNP A-allele may be associated with an increased risk for prostate cancer.

Insights into the Interaction between Immobilized Biocatalysts and Metal-Organic Frameworks: A Case Study of PCN-333

Publisher: American Chemical Society (ACS)

Date: 15-11-2021

DOI: 10.1021/JACSAU.1C00226

Prostate cancer-associated kallikrein-related peptidase 4 activates matrix metalloproteinase-1 and thrombospondin-1

Publisher: American Chemical Society (ACS)

Date: 27-07-2016

DOI: 10.1021/ACS.JPROTEOME.5B01148

Abstract: Prostate cancer metastasis to bone is terminal thus, novel therapies are required to prevent end-stage disease. Kallikrein-related peptidase 4 (KLK4) is a serine protease that is overproduced in localized prostate cancer and is abundant in prostate cancer bone metastases. In vitro, KLK4 induces tumor-promoting phenotypes however, the underlying proteolytic mechanism is undefined. The protein topography and migration analysis platform (PROTOMAP) was used for high-depth identification of KLK4 substrates secreted by prostate cancer bone metastasis-derived PC-3 cells to delineate the mechanism of KLK4 action in advanced prostate cancer. Thirty-six putative novel substrates were determined from the PROTOMAP analysis. In addition, KLK4 cleaved the established substrate, urokinase-type plasminogen activator, thus validating the approach. KLK4 activated matrix metalloproteinase-1 (MMP1), a protease that promotes prostate tumor growth and metastasis. MMP1 was produced in the tumor compartment of prostate cancer bone metastases, highlighting its accessibility to KLK4 at this site. KLK4 further liberated an N-terminal product, with purported angiogenic activity, from thrombospondin-1 (TSP1) and cleaved TSP1 in an osteoblast-derived matrix. This is the most comprehensive analysis of the proteolytic action of KLK4 in an advanced prostate cancer model to date, highlighting KLK4 as a potential multifunctional regulator of prostate cancer progression.

The role of kallikrein-related peptidases in prostate cancer: Potential involvement in an epithelial to mesenchymal transition

Publisher: Walter de Gruyter GmbH

Date: 2006

DOI: 10.1515/BC.2006.089

Structure and interactions of novel ether-functionalised morpholinium and piperidinium ionic liquids with lithium salts

Publisher: Royal Society of Chemistry (RSC)

Date: 2023

DOI: 10.1039/D2YA00348A

Abstract: Investigation of the thermodynamic and transport properties of four novel ether-functionalised piperidinium and morpholinium ionic liquids with LiFSI and LiTFSI salts, and Li-ion coordination in ionic liquids.

Proopiomelanocortin (Pomc) gene expression, as identified by in situ hybridization, in purified populations of interstitial macrophages and leydig cells of the adult rat testis

Publisher: CSIRO Publishing

Date: 1993

DOI: 10.1071/RD9930545

Abstract: The presence of testicular pro-opiomelanocortin (POMC) mRNA and POMC-derived peptides has recently been demonstrated in purified preparations of interstitial macrophages and in Leydig cells of the adult rat testis by Northern blot analysis and immunocytochemistry. In the present study, in situ hybridization provided further evidence that the POMC gene is expressed by both purified interstitial macrophages and Leydig cells. The cellular localization of the POMC transcripts was similar for both cell types, silver grains being predominantly located in the cytoplasm. The specificity of the labelling was demonstrated by the lack of silver grains in the preparations pretreated with RNAase or hybridized with an insulin cDNA probe, a gene known not to be expressed in these cell types. An additional control was provided by hybridization with a sense POMC RNA probe, which gave a less intense signal when compared with the antisense RNA probe under the same experimental conditions. The results confirm POMC gene expression in both macrophages and Leydig cells in the adult rat testis.

Post-translational processing of pro-opiomelanocortin in the brattleboro (Di/di) rat pituitary

Publisher: S. Karger AG

Date: 1988

DOI: 10.1159/000125069

Abstract: In homozygous (di/di) Brattleboro rats, pro-opiomelanocortin (POMC) synthesis and processing, and the release of its products, is by definition not under the control of hypothalamic arginine vasopressin (AVP) in contrast with normal rats or heterozygote (di/+) littermates. To explore the role of AVP on these parameters, we have compared homozygotes and heterozygotes in terms of POMC mRNA levels, pituitary content of immunoreactive (ir)-ACTH, ir-beta-endorphin (beta-EP), alpha-melanocyte-stimulating hormone (alpha-MSH) and ir-N-acetyl-EP (NacEP), plasma levels of ir-ACTH and ir-beta-EP, and RP-HPLC profiles of the various forms of ir-alpha-MSH and ir-NacEP. Homozygous rats had immeasurably low levels of hypothalamic ir-AVP, in contrast with their heterozygote littermates hypothalamic ir-corticotropin releasing factor did not differ between strains. No difference between-strains was seen in levels of POMC mRNA elevated levels of all pituitary peptides, except ir-ACTH, were found in di/di rats plasma levels of both ir-ACTH and ir-beta-EP were lower in di/di rats pituitary ir-alpha-MSH RP-HPLC profiles were similar in both strains, but those for ir-NacEP showed a striking increase in Nac alpha-EP in di/di rats. We interpret these data as evidence for decreased degradation/retarded release of POMC products from the di/di anterior pituitary, for increased processing of POMC products to shorter forms in both anterior pituitary and neuro-intermediate lobe, and thus for a role of AVP in the processing of POMC, as well as POMC synthesis and ACTH/beta-EP release.

Kallikrein 4 is a potential mediator of cellular interactions between cancer cells and osteoblasts in metastatic prostate cancer

Publisher: Wiley

Date: 2007

DOI: 10.1002/PROS.20465

Abstract: Prostate cancer (PCa) and bone cell interactions are critical in the metastatic phase. Kallikrein 4 (KLK4/hK4) is expressed in both PCa and mineralized tissues. We determined if KLK4/hK4 expression was associated with, and influenced by, the bone environment of metastatic PCa. Immunohistochemistry, in vitro co-culture, cell migration, and attachment assays. hK4 was localized to tumor cells and osteoblasts in bone metastases. KLK4/hK4 increased in LNCaP and PC3 cells co-cultured with SaOs2 cells SaOs2 KLK4/hK4 was unchanged. Co-culture did not affect cell proliferation but altered alkaline phosphatase activity/mRNA levels in SaOs2 cells. KLK4-transfected PC3 cells had increased migration towards SaOs2 conditioned medium and greater attachment to the bone-matrix proteins, collagens I and IV. hK4 expression and interaction with both tumor cells and osteoblasts suggests a role for hK4 in PCa bone metastasis. Whether this observation is unique to bone metastasis or reflects a role for hK4 in PCa metastasis generally is yet to be established.

Kallikrein-related peptidase (KLK) family mRNA variants and protein isoforms in hormone-related cancers: Do they have a function?

Publisher: Walter de Gruyter GmbH

Date: 2006

DOI: 10.1515/BC.2006.088

Nanoscale 2D semi-conductors – Impact of structural properties on light propagation depth and photocatalytic performance

Publisher: Elsevier BV

Date: 03-2021

DOI: 10.1016/J.SEPPUR.2020.118011

Epithelial-mesenchymal transition in prostate cancer and the potential role of kallikrein serine proteases

Publisher: S. Karger AG

Date: 2007

DOI: 10.1159/000101311

Abstract: Prostate cancer is associated with significant mortality once the tumour has spread outside the gland. Epithelial-mesenchymal transition (EMT) has been proposed to facilitate this dissemination of tumour cells. In this article we summarize the evidence for EMT in prostate cancer, drawing on the expression of EMT-related markers and the functions of factors known to induce EMT in other systems. We also discuss our recent findings that two members of the tissue kallikrein family of serine proteases, prostate-specific antigen (PSA/KLK3) and kallikrein-related peptidase 4 (KLK4), lead to EMT-like changes in PC3 prostate cancer cells.

Estrogen regulation of kallikrein gene expression in the rat anterior pituitary

Publisher: The Endocrine Society

Date: 07-1986

DOI: 10.1210/ENDO-119-1-268

Abstract: Using a rat pancreatic kallikrein cDNA probe (pcXP39), previously shown to hybridize to kallikrein mRNA in a variety of tissues, we have explored the control of kallikrein gene expression in rat anterior pituitary. Intact female rats have substantially higher levels of AP kallikrein mRNA than intact males male levels are unaffected by castration, whereas female levels fall markedly postovariectomy. Administration of estradiol benzoate to intact male or ovariectomized female rats causes an increase in anterior pituitary levels of kallikrein mRNA. Since the pattern of responsiveness parallels that of PRL, we have studied GH3 cells grown in the presence and absence of estradiol in neither instance was kallikrein mRNA above detection limits. Parallel changes were seen on Northern blots and by hybridization histochemistry on emulsion autoradiography of pituitary sections, scattered positive cells were seen, but precise definition was not possible. We conclude that whereas in the submaxillary gland kallikrein gene expression appears androgen dependent and in the kidney is postulated to be mineralocorticoid regulated, in the anterior pituitary expression of the gene is under estrogen control and that the local role(s) of pituitary kallikrein, whether precursor processing, control of blood flow, or other effects, would, in turn, appear to be modulated by estrogen in vivo.

Identification of a novel prostate cancer susceptibility variant in the KLK3 gene transcript

Publisher: Springer Science and Business Media LLC

Date: 05-04-2011

DOI: 10.1007/S00439-011-0981-1

A comprehensive nomenclature for serine proteases with homology to tissue kallikreins

Publisher: Walter de Gruyter GmbH

Date: 2006

DOI: 10.1515/BC.2006.082

Unraveling Ion Dynamics and Interactions in an Ionic Liquid Electrolyte with a Protonated Anion for Lithium Batteries

Publisher: American Chemical Society (ACS)

Date: 30-06-2021

DOI: 10.1021/ACS.JPCC.1C03288

Expression of PSA-RP2, an alternatively spliced variant from the PSA gene, is increased in prostate cancer tissues but the protein is not secreted from prostate cancer cells

Publisher: Walter de Gruyter GmbH

Date: 04-2010

DOI: 10.1515/BC.2010.043

Abstract: PSA-RP2 is a variant transcript expressed from the PSA gene that is conserved in gorillas, chimpanzees and humans suggesting a particular relevance for this transcript in these primates. We demonstrated by qRT-PCR that PSA-RP2 is upregulated in prostate cancer compared with benign prostatic hyperplasia tissues. The PSA-RP2 protein was not detected in seminal fluid and was cytoplasmically localised but not secreted from LNCaP or transfected PC3 prostate cells, despite secretion from transfected Cos-7 and HEK293 kidney cell lines. PSA-RP2-transfected PC3 cells showed slightly decreased proliferation and increased migration towards PC3-conditioned medium that could suggest a functional role in prostate cancer.

Inactive free: Total prostate specific antigen ratios in ejaculate from men with suspected and known prostate cancer, compared with young control men

Publisher: Wiley

Date: 09-2000

DOI: 10.1046/J.1464-410X.2000.00835.X

Abstract: To measure free : total prostate specific antigen (PSA) ratios in ejaculate from men with suspected and known prostate cancer, and in young control men, to determine if this ratio might be useful in discriminating benign from malignant prostatic conditions. Patients, subjects and methods Forty-seven men with prostate cancer (positive biopsies), 52 men with suspected prostate cancer but who had negative biopsies and 28 young men (< 30 years old) and with no family history of cancer, provided either a single ejaculate specimen (total 59) or multiple specimens (total 193) on subsequent occasions. Free and total PSA were measured using appropriate assays. All specimens were diluted in a PSA-negative female serum pool. The median free : total PSA ratios were 0.76-0.81 among the patient groups and control men, and there was no statistical difference between the groups. These data presumably only reflect the inactive component of free PSA, given that any alpha2-macroglobulin or alpha1-antichymotrypsin in the assay serum diluent was likely to have bound the active free PSA component in these s les. Similar results were obtained from those providing single and multiple s les, suggesting that a single specimen is sufficient to reflect the seminal plasma free : total PSA ratio over that period. There was no relationship between seminal plasma free : total PSA ratio and age for the controls or the positive biopsy group, although there was a negative relationship (i.e. a decline with age) that almost reached significance in those with negative biopsies (P = 0.058, R2 = 0.07). This is the first report of free : total PSA ratios in the ejaculate of men with suspected and known prostate cancer compared with young control men. Although no significant changes were detected in the free : total PSA ratios in ejaculate, these results may be confounded by differences in ratios with age, as is the case for serum PSA or different molecular forms of PSA. Indeed, these data suggest that a large proportion of free PSA in seminal plasma may be inactive. Further studies are needed to determine the potential utility of measuring free : total PSA, or other candidate markers, in ejaculate to better discriminate benign from malignant prostate disease.

Seminal fluid characterization for male fertility and prostate cancer: Kallikrein-related serine proteases and whole proteome approaches

Publisher: Georg Thieme Verlag KG

Date: 02-2007

DOI: 10.1055/S-2006-958467

Abstract: The kallikrein-related ( KLK) protease gene family encodes a subgroup of 15 serine proteases that includes prostate-specific antigen (PSA) or KLK3, the well-known biomarker for prostate cancer. PSA is also a major component of seminal fluid. To date, 10 other KLK serine proteases have been documented as present in seminal fluid (KLKs 1, 2, 4, 5, 6, 8, 10, 11, 13, and 14) and, like PSA, have the potential to contribute to male fertility, either directly or indirectly, by means of their proteolytic activity on seminal coagulum proteins. These KLK enzymes arise predominantly from the glandular epithelium of the prostate and are secreted into the lumen of the prostatic ducts that empty into the urethra upon ejaculation. Given their prostatic origin, they are also being considered increasingly as diagnostic rognostic targets for prostate cancer. This article reviews the literature on seminal fluid PSA and more recent reports on the detection of other KLKs enzymes in this milieu, and their potential roles in male fertility and prostate cancer. We also discuss recent efforts to determine the proteomic profile of seminal fluid to identify new biomarkers for prostate disease.

Correction: 3D cultures of prostate cancer cells cultured in a novel high-throughput culture platform are more resistant to chemotherapeutics compared to cells cultured in monolayer

Publisher: Public Library of Science (PLoS)

Date: 22-04-2015

DOI: 10.1371/JOURNAL.PONE.0125641

Investigation of the Physicochemical Properties of Pyrrolidinium-Based Mixed Plastic Crystal Electrolytes

Publisher: American Chemical Society (ACS)

Date: 16-06-2023

DOI: 10.1021/ACS.JPCC.3C02249

Tuning the hydrophobicity of plasma polymer coated silica particles

Publisher: Elsevier BV

Date: 11-2013

DOI: 10.1016/J.POWTEC.2013.09.018

Kallikrein-related peptidase 4 induces cancer-associated fibroblast features in prostate-derived stromal cells

Publisher: Wiley

Date: 10-08-2017

DOI: 10.1002/1878-0261.12075

Exploring the homopolar dehydrocoupling of ammonia borane by solid-state multinuclear NMR spectroscopy

Publisher: Royal Society of Chemistry (RSC)

Date: 2021

DOI: 10.1039/D0CC06184K

Abstract: Solid-state 1 H– 14 N OT HMQC, 11 B MQMAS and 1 H– 11 B HETCOR NMR experiments are used to explore the role of homopolar B–B interaction in the thermal dehydrogenation of pure and supported ammonia borane, for it's potential hydrogen storage applications.

The human tissue kallikreins (KLKs 1-3) and a novel KLK1 mRNA transcript are expressed in a renal cell carcinoma cDNA library

Publisher: Elsevier BV

Date: 12-1999

DOI: 10.1016/S0162-3109(99)00059-4

Abstract: Renal cell carcinoma (RCC) is the most common form of kidney cancer, for which there is no biochemical marker. We and others have previously shown that a prostate specific antigen (PSA)-like protein is elevated in the serum of women with RCC. PSA is a member of the tissue kallikrein (KLK) gene family of enzymes. We have constructed a RCC cDNA expression library and screened it for PSA and KLK expression to determine whether they may be responsible for this PSA-like activity. Since immunoscreening of the RCC library for expressed PSA-like proteins was unsuccessful, polymerase chain reaction (PCR) analysis of the RCC cDNA library was performed using universal KLK primers, directed to the common regions in exon 3 and exon 5 of KLK1, KLK2 and KLK3. Sequences identical to all three KLKs were present in the RCC cDNA library. In addition, a novel KLK1 transcript with a 104 base pair deletion in exon 4 that predicted a C terminal sequence minus the crucial Ser190, was detected. The role of these tissue kallikreins in RCC and the significance of the variant KLK1 transcript is yet to be established. It is still unclear which of these gene products, if any, was detected in the sera of the women with RCC.

Regulation of liver angiotensinogen mRNA by glucocorticoids and thyroxine

Publisher: Elsevier BV

Date: 02-1989

DOI: 10.1016/0303-7207(89)90125-1

Abstract: This study examines the immediate and longer-term changes in angiotensinogen mRNA and in plasma angiotensinogen which follow the withdrawal and replacement of glucocorticoids or thyroxine. RNA from rat liver was analysed by Northern blot and dot-blot hybridization with a 40-mer oligodeoxynucleotide probe specific for angiotensinogen mRNA. Adrenalectomy decreased plasma angiotensinogen and angiotensinogen mRNA to 55 and 50% of control values respectively over a period of 16 days. Similar decreases were obtained after propylthiouracil (1 mg/kg for 16 days) treatment, except when injected simultaneously with T3 (3 micrograms/kg/day). Over the same period plasma renin activity increased in adrenalectomized rats from 4.1 +/- 0.8 to 7.0 +/- 1.5 pmol angiotensin I (AI)/ml/h, and decreased in propylthiouracil-treated rats from 3.8 +/- 0.4 to 1.6 +/- 0.4 pmol AI/ml/h. Approximate half-times of 2-3 days were calculated for both plasma angiotensinogen and angiotensinogen mRNA post-adrenalectomy or after propylthiouracil treatment. Dexamethasone (400 micrograms/kg, i.m.) given to intact rats rapidly increased angiotensinogen mRNA to a maximum of 250% of control by 8 h and with a half-maximal response of 2.8 h. Plasma angiotensinogen responded similarly, apart from an initial delay of 2 h. Treatment with different doses of propylthiouracil and dexamethasone showed that responses were dose-related. We conclude that changes in plasma angiotensinogen and angiotensinogen mRNA are closely correlated, and that under various physiological circumstances angiotensinogen mRNA has a rapid rate of accumulation but a slow rate of decay.

Standard preanalytical coding for biospecimens: Review and implementation of the sample PREanalytical Code (SPREC)

Publisher: Mary Ann Liebert Inc

Date: 08-2012

DOI: 10.1089/BIO.2012.0012

Two for the price of one: a keystone design equals two conjoined V-Y flaps

Publisher: Wiley

Date: 06-2011

DOI: 10.1111/J.1445-2197.2011.05772.X

Oestrogen administration and the expression of the kallikrein gene family in the rat submandibular gland

Publisher: Elsevier BV

Date: 1990

DOI: 10.1016/0022-4731(90)90145-I

Abstract: Using a series of oligonucleotide probes (18-21 mers) specific for members of the rat kallikrein/tonin (arginyl-esteropeptidase) gene family (PS, S1, S2, S3, K1, P1), we have shown by Northern blot analysis that all six genes are expressed in the submandibular gland (SMG), with PS (true kallikrein) the most abundant in both male and female rats. Though female levels of PS mRNA are similar to that in the male, levels of mRNA from both the kallikrein-like (S1, K1, P1) and tonin (S2)/tonin-like (S3) genes are all substantially lower in the female than in the male rat. In contrast with the oestrogen dependence of anterior pituitary kallikrein (PS) gene expression, oestrogen administration (6 micrograms/day for 8 days) to castrate male or female rats is without effect on PS or S1, S2, S3, K1, P1 mRNA levels in the SMG. These findings suggest a tissue-specificity in the oestrogen regulation of true kallikrein gene expression in the two tissues. In intact male rats, oestrogen administration lowers SMG levels of S1, S2, S3, K1, and P1 but not PS mRNA to castrate levels, presumably by suppression of the pituitary/gonadal axis, consistent with the previously reported androgen dependence of SMG expression of these genes with the exception of PS.

Probing the molecular interactions and physicochemical properties of a cobalt-based redox electrolyte system for thermo-electrochemical cells

Publisher: Royal Society of Chemistry (RSC)

Date: 2022

DOI: 10.1039/D2CP01149B

Abstract: Revealing the molecular-level interactions and dynamics of the Co 2+/3+ (bpy) 3 (NTf 2 ) 2/3 redox electrolyte system, which is promising for thermo-electrochemical devices.

A replication study examining novel common single nucleotide polymorphisms identified through a prostate cancer genome-wide association study in a Japanese population

Publisher: Oxford University Press (OUP)

Date: 15-11-2011

DOI: 10.1093/AJE/KWR271

Abstract: Five novel prostate cancer risk loci were identified in a recent genome-wide association study (GWAS) of Japanese persons (Takata et al., Nat Genet. 2010 (9):751-754). Those authors proposed that apart from population-specific linkage disequilibrium patterns, limitations of GWAS single nucleotide polymorphism (SNP) prioritization and/or study design could explain the lack of identification of these loci in GWAS previously conducted among Caucasians. Thus, the authors undertook a replication study in 1,357 prostate cancer patients and 1,403 healthy Australian males of European descent (2004-2008). The rs12653946 SNP at 5p15 was found to be significantly associated with prostate cancer risk (odds ratio = 1.20, 95% confidence interval: 1.07, 1.34 P = 0.002). On the basis of linkage disequilibrium calculations, the rs12653946 SNP represents an independent locus, distinct from the previously identified TERT-CLPTM1L cancer nexus region. Further, analysis from AceView (Thierry-Mieg and Thierry-Mieg, Genome Biol. 2006 (suppl 1):S12) indicated that rs12653946 falls within the intron of a testis-expressed gene strongly predicted to translate a conceptual 8.1-kilodalton protein named tojy.aApr07. The authors' findings suggest that follow-up of apparently ethnicity-specific risk associations are warranted in order to highlight risk-associated loci for experimental studies and for incorporation into future risk prediction models for prostate cancer.

Translating tissue engineering technology platforms into cancer research

Publisher: Wiley

Date: 08-2009

DOI: 10.1111/J.1582-4934.2009.00853.X

Paclitaxel Resistance and Multicellular Spheroid Formation Are Induced by Kallikrein-Related Peptidase 4 in Serous Ovarian Cancer Cells in an Ascites Mimicking Microenvironment

Publisher: Public Library of Science (PLoS)

Date: 25-02-2013

DOI: 10.1371/JOURNAL.PONE.0057056

Coffee contains potent opiate receptor binding activity

Publisher: Springer Science and Business Media LLC

Date: 1983

DOI: 10.1038/301246A0

Abstract: Opiate receptor-active peptide fragments (exorphins) have been identified recently in casein and gluten hydrolysates, and morphine has been found in bovine and human milk. To determine whether similar peptides or alkaloids occur in other foodstuffs, we have screened potential sources using a rat brain homogenate assay to detect opiate receptor activity. We report here that instant coffee powders from a variety of manufacturers compete with tritiated naloxone for binding to opiate receptors in the rat brain membrane preparations, with no significant difference between normal and decaffeinated coffee. The receptor binding activity resembles that seen with opiate antagonists, in that there was no change in the half-maximal effective dose (ED50) in the presence of 100 mM Na+ on bioassay, the activity was similarly shown to be antagonistic and specific for opiate-induced inhibition of twitch. Preliminary characterization of the activity reveals that it has a molecular weight (MW) in the range 1,000-3,500, is heat-stable, ether-extractable, not modified by enzymatic digestion with papain, and clearly separable from caffeine and morphine on TLC. As its concentration in an average cup of coffee is five times the ED50, these data suggest that drinking coffee may be followed by effects mediated via opiate receptors, as well as effects of caffeine.

High-rate formation protocol enables a high ionic conductivity SEI for sodium-ion batteries

Publisher: Elsevier BV

Date: 2023

DOI: 10.1016/J.JPOWSOUR.2022.232298

A wide-temperature superior ionic conductive polymer electrolyte for lithium metal battery

Publisher: Elsevier BV

Date: 07-2020

DOI: 10.1016/J.NANOEN.2020.104786

Kallikrein-related peptidase 10 (KLK10) expression and single nucleotide polymorphisms in ovarian cancer survival

Publisher: BMJ

Date: 05-2010

DOI: 10.1111/IGC.0B013E3181D9273E

Expression of the prolactin gene in human decidua-chorion

Publisher: The Endocrine Society

Date: 03-1983

DOI: 10.1210/ENDO-112-3-1133

Abstract: Messenger RNA (mRNA) purified from human decidua-chorion hybridizes with a 32P-cDNA probe for human prolactin. In contrast, mRNA from human trophoblast and amnion does not hybridize to prolactin cDNA. The migration position on agarose gels of prolactin-specific mRNA from human decidua-chorion is similar to that for mRNA from ovine pituitary, suggesting a similar sized mRNA coding for prolactin in these different tissues and species. These data demonstrate unambiguously that the prolactin gene is expressed in human decidua-chorion, confirming previous immunochemical reports of prolactin production by this tissue in culture.

Direct progesterone receptor and indirect androgen receptor interactions with the kallikrein-related peptidase 4 gene promoter in breast and prostate cancer

Publisher: American Association for Cancer Research (AACR)

Date: 2009

DOI: 10.1158/1541-7786.MCR-08-0218

Abstract: Kallikrein 4 (KLK4) is a member of the human KLK gene family of serine proteases, many of which are implicated in hormone-dependent cancers. Like other KLKs, such as KLK3/PSA and KLK2, KLK4 gene expression is also regulated by steroid hormones in hormone-dependent cancers, although the transcriptional mechanisms are ill defined. Here, we have investigated the mechanisms mediating the hormonal regulation of KLK4 in breast (T47D) and prostate (LNCaP and 22Rv1) cancer cells. We have shown that KLK4 is only expressed in breast and prostate cancers that express the progesterone receptor (PR) and androgen receptor (AR), respectively. Expression analysis in PR- and AR-positive cells showed that the two predominant KLK4 variants that use either TIS1 or TIS2a/b are both up-regulated by progesterone in T47D cells and androgens in LNCaP cells. Two putative hormone response elements, K4.pPRE and K4.pARE at −2419 bp and −1005 bp, respectively, were identified in silico. Electrophoretic mobility shift assays and luciferase reporter experiments suggest that neither K4.pARE nor ∼2.8 kb of the KLK4 promoter interacts directly with the AR to mediate KLK4 expression in LNCaP and 22Rv1 cells. However, we have shown that K4.pPRE interacts directly with the PR to up-regulate KLK4 gene expression in T47D cells. Further, chromatin immunoprecipitation experiments showed a time-dependent recruitment of the PR to the KLK4 promoter (−2496 to −2283), which harbors K4.pPRE. This is the first study to show that progesterone-regulated KLK4 expression in T47D cells is mediated partly by a hormone response element (K4.pPRE) at −2419 bp. (Mol Cancer Res 2009 (1):129–41)

Selective cleavage of human sex hormone-binding globulin by kallikrein-related peptidases and effects on androgen action in LNCaP prostate cancer cells

Publisher: The Endocrine Society

Date: 30-04-2012

DOI: 10.1210/EN.2012-1011

Abstract: Stimulation of the androgen receptor via bioavailable androgens, including testosterone and testosterone metabolites, is a key driver of prostate development and the early stages of prostate cancer. Androgens are hydrophobic and as such require carrier proteins, including sex hormone-binding globulin (SHBG), to enable efficient distribution from sites of biosynthesis to target tissues. The similarly hydrophobic corticosteroids also require a carrier protein whose affinity for steroid is modulated by proteolysis. However, proteolytic mechanisms regulating the SHBG/androgen complex have not been reported. Here, we show that the cancer-associated serine proteases, kallikrein-related peptidase (KLK)4 and KLK14, bind strongly to SHBG in glutathione S-transferase interaction analyses. Further, we demonstrate that active KLK4 and KLK14 cleave human SHBG at unique sites and in an androgen-dependent manner. KLK4 separated androgen-free SHBG into its two laminin G-like (LG) domains that were subsequently proteolytically stable even after prolonged digestion, whereas a catalytically equivalent amount of KLK14 reduced SHBG to small peptide fragments over the same period. Conversely, proteolysis of 5α-dihydrotestosterone (DHT)-bound SHBG was similar for both KLKs and left the steroid binding LG4 domain intact. Characterization of this proteolysis fragment by [(3)H]-labeled DHT binding assays revealed that it retained identical affinity for androgen compared with full-length SHBG (dissociation constant = 1.92 nM). Consistent with this, both full-length SHBG and SHBG-LG4 significantly increased DHT-mediated transcriptional activity of the androgen receptor compared with DHT delivered without carrier protein. Collectively, these data provide the first evidence that SHBG is a target for proteolysis and demonstrate that a stable fragment derived from proteolysis of steroid-bound SHBG retains binding function in vitro.

Height, selected genetic markers and prostate cancer risk: results from the PRACTICAL consortium

Publisher: Springer Science and Business Media LLC

Date: 08-2017

DOI: 10.1038/BJC.2017.231

Abstract: Evidence on height and prostate cancer risk is mixed, however, recent studies with large data sets support a possible role for its association with the risk of aggressive prostate cancer. We analysed data from the PRACTICAL consortium consisting of 6207 prostate cancer cases and 6016 controls and a subset of high grade cases (2480 cases). We explored height, polymorphisms in genes related to growth processes as main effects and their possible interactions. The results suggest that height is associated with high-grade prostate cancer risk. Men with height cm are at a 22% increased risk as compared to men with height cm (OR 1.22, 95% CI 1.01–1.48). Genetic variants in the growth pathway gene showed an association with prostate cancer risk. The aggregate scores of the selected variants identified a significantly increased risk of overall prostate cancer and high-grade prostate cancer by 13% and 15%, respectively, in the highest score group as compared to lowest score group. There was no evidence of gene-environment interaction between height and the selected candidate SNPs. Our findings suggest a role of height in high-grade prostate cancer. The effect of genetic variants in the genes related to growth is seen in all cases and high-grade prostate cancer. There is no interaction between these two exposures.

DC therapy for prostate cancer

Publisher: Elsevier BV

Date: 04-2004

DOI: 10.1080/14653240410006103

Rapid and specific lowering of pituitary FSHβ mRNA levels by inhibin

Publisher: Elsevier BV

Date: 10-1987

DOI: 10.1016/0303-7207(87)90181-X

Abstract: Hypothalamo-pituitary disconnected sheep were given gonadotropin releasing hormone pulses every 2 h for 1 week, and the effects of inhibin on mRNA for FSH beta, LH beta, alpha-subunit and prolactin examined. Levels of FSH beta mRNA were reduced to approximately 20% 6 h after administration, and to approximately 10% by 30 h no change was seen in LH beta, alpha-subunit or prolactin mRNA. These data show that inhibin has a very rapid and specific effect on FSH beta mRNA levels directly at the level of the pituitary gland.

Molecular detection of prostate cells in ejaculate and urethral washings in men with suspected prostate cancer

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 04-1999

DOI: 10.1016/S0022-5347(01)61680-X

Seven prostate cancer susceptibility loci identified by a multi-stage genome-wide association study

Publisher: Springer Science and Business Media LLC

Date: 10-07-2011

DOI: 10.1038/NG.882

Proteomic and other analyses to determine the functional consequences of deregulated kallikrein-related peptidase (KLK) expression in prostate and ovarian cancer

Publisher: Wiley

Date: 11-05-2014

DOI: 10.1002/PRCA.201300098

Abstract: Rapidly developing proteomic tools are improving detection of deregulated kallikrein-related peptidase (KLK) expression, at the protein level, in prostate and ovarian cancer, as well as facilitating the determination of functional consequences downstream. MS-driven proteomics uniquely allows for the detection, identification, and quantification of thousands of proteins in a complex protein pool, and this has served to identify certain KLKs as biomarkers for these diseases. In this review, we describe applications of this technology in KLK biomarker discovery and elucidate MS-based techniques that have been used for unbiased, global screening of KLK substrates within complex protein pools. Although MS-based KLK degradomic studies are limited to date, they helped to discover an array of novel KLK substrates. Substrates identified by MS-based degradomics are reported with improved confidence over those determined by incubating a purified or recombinant substrate and protease of interest, in vitro. We propose that these novel proteomic approaches represent the way forward for KLK research, in order to correlate proteolysis of biological substrates with tissue-related consequences, toward clinical targeting of KLK expression and function for cancer diagnosis, prognosis, and therapies.

Reactivation of embryonic nodal signaling is associated with tumor progression and promotes the growth of prostate cancer cells

Publisher: Wiley

Date: 12-01-2011

DOI: 10.1002/PROS.21335

Stimuli-responsive heterojunctions based photo-electrocatalytic membrane reactors for reactive filtration of persistent organic pollutants

Publisher: Elsevier BV

Date: 2023

DOI: 10.1016/J.CEJ.2022.139374

Kallikrein-related Peptidase 4 (KLK4) Initiates Intracellular Signaling via Protease-activated Receptors (PARs)

Publisher: Elsevier BV

Date: 05-2008

DOI: 10.1074/JBC.M709493200

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Publisher: Oxford University Press (OUP)

Date: 29-05-2015

DOI: 10.1093/HMG/DDV203

Secretome and degradome profiling shows that Kallikrein-related peptidases 4, 5, 6, and 7 induce TGFβ-1 signaling in ovarian cancer cells

Publisher: Wiley

Date: 10-2014

DOI: 10.1016/J.MOLONC.2013.09.003

Human kallikrein 4 signal peptide induces cytotoxic T cell responses in healthy donors and prostate cancer patients

Publisher: Springer Science and Business Media LLC

Date: 27-08-2012

DOI: 10.1007/S00262-011-1095-2

Abstract: Immunotherapy is a promising new treatment for patients with advanced prostate and ovarian cancer, but its application is limited by the lack of suitable target antigens that are recognized by CD8+ cytotoxic T lymphocytes (CTL). Human kallikrein 4 (KLK4) is a member of the kallikrein family of serine proteases that is significantly overexpressed in malignant versus healthy prostate and ovarian tissue, making it an attractive target for immunotherapy. We identified a naturally processed, HLA-A*0201-restricted peptide epitope within the signal sequence region of KLK4 that induced CTL responses in vitro in most healthy donors and prostate cancer patients tested. These CTL lysed HLA-A*0201+ KLK4 + cell lines and KLK4 mRNA-transfected monocyte-derived dendritic cells. CTL specific for the HLA-A*0201-restricted KLK4 peptide were more readily expanded to a higher frequency in vitro compared to the known HLA-A*0201-restricted epitopes from prostate cancer antigens prostate-specific antigen (PSA), prostate-specific membrane antigen (PSMA) and prostatic acid phosphatase (PAP). These data demonstrate that KLK4 is an immunogenic molecule capable of inducing CTL responses and identify it as an attractive target for prostate and ovarian cancer immunotherapy.

N-Acetylated endorphins in ovine anterior pituitary and neuro-intermediate lobe

Publisher: Elsevier BV

Date: 11-1987

DOI: 10.1016/0196-9781(87)90134-3

Abstract: We have used an antiserum for immunohistochemistry and RIA/RP-HPLC which recognizes all fragments of N-acetylated endorphin (NacEP). In the rat neuro-intermediate lobe (N-IL), in addition to the N-acetylated forms of immunoreactive-beta-endorphin (ir-beta EP) already reported, we have demonstrated Nac beta EP as a minor component. In the sheep pituitary processing of beta EP is markedly different. In the anterior pituitary (AP), staining was indistinguishable with beta EP and NacEP antisera, in contrast with the rat where many fewer AP cells stained with the NacEP antiserum. Secondly, as in the rat, all N-IL cells stained with both antisera on RP-HPLC, however, the major forms of NacEP in the sheep N-IL were Nac beta EP (approximately 40%), Nac beta EP (approximately 25%) and Nac beta EP (approximately 20%), with Nac beta EP (approximately 2%) as a minor component. A similar profile was seen on RP-HPLC of sheep AP. These data suggest that (1) patterns of processing in sheep AP are similar to those in N-IL, though the extent of acetylation is less and (2) in the sheep pituitary low molecular weight acetylated fragments predominate, in contrast with the rat.

Highlight: Remodelling the KLK landscape down under

Publisher: Walter de Gruyter GmbH

Date: 04-11-2016

DOI: 10.1515/HSZ-2016-0301

Re: Malignant cytological washings from radical prostatectomy specimens: A possible mechanism for local recurrence of prostate cancer following surgical treatment of organ confined disease

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 09-1997

DOI: 10.1016/S0022-5347(01)64358-1

Long terminal repeats act as androgen-responsive enhancers for the PSA-kallikrein locus

Publisher: The Endocrine Society

Date: 17-05-2012

DOI: 10.1210/EN.2012-1267

Abstract: The androgen receptor (AR) signaling pathway is a common therapeutic target for prostate cancer, because it is critical for the survival of both hormone-responsive and castrate-resistant tumor cells. Most of the detailed understanding that we have of AR transcriptional activation has been gained by studying classical target genes. For more than two decades, Kallikrein 3 (KLK3) (prostate-specific antigen) has been used as a prototypical AR target gene, because it is highly androgen responsive in prostate cancer cells. Three regions upstream of the KLK3 gene, including the distal enhancer, are known to contain consensus androgen-responsive elements required for AR-mediated transcriptional activation. Here, we show that KLK3 is one of a specific cluster of androgen-regulated genes at the centromeric end of the kallikrein locus with enhancers that evolved from the long terminal repeat (LTR) (LTR40a) of an endogenous retrovirus. Ligand-dependent recruitment of the AR to in idual LTR-derived enhancers results in concurrent up-regulation of endogenous KLK2, KLK3, and KLKP1 expression in LNCaP prostate cancer cells. At the molecular level, a kallikrein-specific duplication within the LTR is required for maximal androgen responsiveness. Therefore, KLK3 represents a subset of target genes regulated by repetitive elements but is not typical of the whole spectrum of androgen-responsive transcripts. These data provide a novel and more detailed understanding of AR transcriptional activation and emphasize the importance of repetitive elements as functional regulatory units.

The glandular kallikrein family of enzymes: Tissue specific expression and hormonal regulation

Publisher: The Endocrine Society

Date: 11-1989

DOI: 10.1210/EDRV-10-4-393

Abstract: The dentate gyrus (DG) is the central input region to the hippoc us and is known to play an important role in learning and memory. Previous studies have shown that prenatal alcohol is associated with hippoc al-dependent learning deficits and a decreased ability to elicit long-term potentiation (LTP) in the DG in adult animals. Given that activation of the extracellular signal-regulated kinase 1/2 (ERK1/2) signaling cascade by NMDA receptors is required for various forms of learning and memory, as well as LTP, in hippoc al regions, including the DG, we hypothesized that fetal alcohol-exposed adult animals would have deficits in hippoc al NMDA receptor-dependent ERK1/2 activation. We used immunoblotting and immunohistochemistry techniques to detect NMDA-stimulated ERK1/2 activation in acute hippoc al slices prepared from adult fetal alcohol-exposed mice. We present the first evidence linking prenatal alcohol exposure to deficits in NMDA receptor-dependent ERK1/2 activation specifically in the DG of adult offspring. This deficit may account for the LTP deficits previously observed in the DG, as well as the life-long cognitive deficits, associated with prenatal alcohol exposure.

A common nomenclature for members of the tissue (glandular) kallikrein gene families

Publisher: Springer Science and Business Media LLC

Date: 1992

DOI: 10.1007/BF02027208

Interactions between human osteoblasts and prostate cancer cells in a novel 3D in vitro model

Publisher: Informa UK Limited

Date: 07-2010

DOI: 10.4161/ORG.6.3.12041

Inhibin a-subunit gene expression in the ovaries of immature female rats is stimulated by pregnant mare serum gonadotrophin

Publisher: Elsevier BV

Date: 08-1986

DOI: 10.1016/S0006-291X(86)80408-9

Abstract: We have used a bovine cDNA probe for the A-subunit of inhibin to demonstrate the presence of inhibin in the ovaries of immature female rats: the levels of mRNA were increased following treatment of the rats with pregnant mare serum gonadotrophin (PMSG), suggesting modulation by PMSG of ovarian inhibin synthesis at least at the level of transcription. Furthermore, we report the unexpected finding of significant levels of inhibin mRNA in the corpora lutea of mature female rats. No inhibin mRNA was demonstrable in the uterus or placenta.

Murine, but not human, ephrin-B2 can be efficiently cleaved by the serine protease kallikrein-4: Implications for xenograft models of human prostate cancer

Publisher: Elsevier BV

Date: 04-2015

DOI: 10.1016/J.YEXCR.2015.02.014

Abstract: Ephrin-B2 is the sole physiologically-relevant ligand of the receptor tyrosine kinase EphB4, which is over-expressed in many epithelial cancers, including 66% of prostate cancers, and contributes to cancer cell survival, invasion and migration. Crucially, however, the cancer-promoting EphB4 signalling pathways are independent of interaction with its ligand ephrin-B2, as activation of ligand-dependent signalling causes tumour suppression. Ephrin-B2, however, is often found on the surface of endothelial cells of the tumour vasculature, where it can regulate angiogenesis to support tumour growth. Proteolytic cleavage of endothelial cell ephrin-B2 has previously been suggested as one mechanism whereby the interaction between tumour cell-expressed EphB4 and endothelial cell ephrin-B2 is regulated to support both cancer promotion and angiogenesis. An in silico approach was used to search accessible surfaces of 3D protein models for cleavage sites for the key prostate cancer serine protease, KLK4, and this identified murine ephrin-B2 as a potential KLK4 substrate. Mouse ephrin-B2 was then confirmed as a KLK4 substrate by in vitro incubation of recombinant mouse ephrin-B2 with active recombinant human KLK4. Cleavage products were visualised by SDS-PAGE, silver staining and Western blot and confirmed by N-terminal sequencing. At low molar ratios, KLK4 cleaved murine ephrin-B2 but other prostate-specific KLK family members (KLK2 and KLK3/PSA) were less efficient, suggesting cleavage was KLK4-selective. The primary KLK4 cleavage site in murine ephrin-B2 was verified and shown to correspond to one of the in silico predicted sites between extracellular domain residues arginine 178 and asparagine 179. Surprisingly, the highly homologous human ephrin-B2 was poorly cleaved by KLK4 at these low molar ratios, likely due to the 3 amino acid differences at this primary cleavage site. These data suggest that in in vivo mouse xenograft models, endogenous mouse ephrin-B2, but not human tumour ephrin-B2, may be a downstream target of cancer cell secreted human KLK4. This is a critical consideration when interpreting data from murine explants of human EphB4+/KLK4+ cancer cells, such as prostate cancer cells, where differential effects may be seen in mouse models as opposed to human clinical situations.

Fusion transcript loci share many genomic features with non-fusion loci

Publisher: Springer Science and Business Media LLC

Date: 12-2015

DOI: 10.1186/S12864-015-2235-4

Glandular kallikreins and prostate-specific antigen are expressed in the human endometrium

Publisher: The Endocrine Society

Date: 06-1994

DOI: 10.1210/JCEM.78.6.7515392

Abstract: Glandular or tissue kallikrein and prostate-specific antigen (PSA) are members of the human kallikrein (KLK) multigene family of enzymes. Various components of the glandular kallikrein-kinin system (kallikrein, low molecular weight kininogen, bradykinin) have been recently shown to be present or active in the human endometrium. We have used the reverse transcriptase-polymerase chain reaction (RT-PCR) with universal KLK primers to demonstrate kallikrein gene expression in this tissue. On Southern blot analysis with gene-specific oligonucleotide probes, we have detected expression of the three human KLK genes--KLK1 (kallikrein), KLK2 (or hGK1) and KLK3 (PSA). The expression of KLK1 and KLK3 was further confirmed by sequence analysis of three different endometrial PCR products. These findings confirm the presence of a local kallikrein-kinin system in the human endometrium. The significance of the novel expression of KLK2 and KLK3 (PSA), previously thought to be prostate-specific genes, in the endometrium is unclear. This family of enzymes must now be considered potential local regulators of uterine function.

Operando magnetic resonance imaging for mapping of temperature and redox species in thermo-electrochemical cells

Publisher: Springer Science and Business Media LLC

Date: 08-11-2021

DOI: 10.1038/S41467-021-26813-8

Abstract: Low-grade waste heat is an abundant and underutilised energy source. In this context, thermo-electrochemical cells (i.e., systems able to harvest heat to generate electricity) are being intensively studied to deliver the promises of efficient and cost-effective energy harvesting and electricity generation. However, despite the advances in performance disclosed in recent years, understanding the internal processes occurring within these devices is challenging. In order to shed light on these mechanisms, here we report an operando magnetic resonance imaging approach that can provide quantitative spatial maps of the electrolyte temperature and redox ion concentrations in functioning thermo-electrochemical cells. Time-resolved images are obtained from liquid and gel electrolytes, allowing the observation of the effects of redox reactions and competing mass transfer processes such as thermophoresis and diffusion. We also correlate the physicochemical properties of the system with the device performance via simultaneous electrochemical measurements.

Mass spectrometry-based determination of Kallikrein-related peptidase 7 (KLK7) cleavage preferences and subsite dependency

Publisher: Springer Science and Business Media LLC

Date: 28-07-2017

DOI: 10.1038/S41598-017-06680-4

Abstract: The cleavage preferences of Kallikrein-related peptidase 7 (KLK7) have previously been delineated using synthetic peptide libraries of fixed length, or single protein chains and have suggested that KLK7 exerts a chymotryptic-like cleavage preference. Due to the short length of the peptides utilised, only a limited number of subsites have however been assessed. To determine the subsite preferences of KLK7 in a global setting, we used a mass spectrometry (MS)-based in-depth proteomics approach that utilises human proteome-derived peptide libraries of varying length, termed Proteomic Identification of protease Cleavage Sites (PICS). Consistent with previous findings, KLK7 was found to exert chymotryptic-like cleavage preferences. KLK7 subsite preferences were also characterised in the P2-P2′ region, demonstrating a preference for hydrophobic residues in the non-prime and hydrophilic residues in the prime subsites. Interestingly, single catalytic triad mutant KLK7 (mKLK7 S195A) also showed residual catalytic activity (k cat /K M = 7.93 × 10 2 s −1 M −1 ). Catalytic inactivity of KLK7 was however achieved by additional mutation in this region (D102N). In addition to characterising the cleavage preferences of KLK7, our data thereby also suggests that the use of double catalytic triad mutants should be employed as more appropriate negative controls in future investigations of KLK7, especially when highly sensitive MS-based approaches are employed.

Bone and prostate cancer cell interactions in metastatic prostate cancer

Publisher: Wiley

Date: 13-12-2007

DOI: 10.1111/J.1464-410X.2006.06670.X

Mass spectrometry based proteomics analyses in kallikrein-related peptidase research: implications for cancer research and therapy

Publisher: Informa UK Limited

Date: 17-10-2017

DOI: 10.1080/14789450.2017.1389637

Abstract: Kallikrein-related peptidases (KLKs) are a family of serine peptidases that are deregulated in numerous pathological conditions, with a multitude of KLK-mediated functional roles implicated in the progression of cancer. Advances in multidimensional mass spectrometry (MS)-based proteomics have facilitated the quantitative measurement of deregulated KLK expression in cancer, identifying certain KLKs, as well as their substrates, as potential cancer biomarkers. Areas covered: In this review, we discuss how these approaches have been utilized for KLK biomarker discovery and unbiased substrate determination in complex protein pools that mimic the in vivo extracellular microenvironment. Expert commentary: Although a limited number of studies have been performed, the quantity of information generated has greatly improved our understanding of the functional roles of KLKs in cancer progression. In addition, these data suggest additional means through which deregulated KLK expression may be targeted in cancer treatment, highlighting the potential therapeutic value of these state-of-the-art MS-based studies.

Tissue kallikrein and the bradykinin B2 receptor are expressed in endometrial and prostate cancers

Publisher: Elsevier BV

Date: 06-1997

DOI: 10.1016/S0162-3109(97)00024-6

Abstract: KLK1/tissue kallikrein is a member of a family of structurally related serine proteases which exhibit a erse range of enzymic activities. Other members of this family of genes and the bradykinin (B2) receptor have been implicated in cancer processes. The KLK genes are expressed in various organs of the reproductive tract, including the prostate and uterus. In this study, we have examined whether KLK1/tissue kallikrein and the B2 receptor were both expressed in cancers emanating from these organs. We have shown that KLK1/tissue kallikrein and the B2 receptor are expressed, to varying degrees, in prostate disease and 2 human prostate cancer cell-lines, LNCaP and DU145. KLK1 is also expressed in a range of endometrial cancers, although at lower levels than that observed for normal human endometrial tissues. These findings suggest that a functional kallikrein-kinin system is present in prostate disease, in particular, which may be important in the process of tumorigenesis in this tissue.

A variant of the KLK4 gene is expressed as a cis sense-antisense chimeric transcript in prostate cancer cells

Publisher: Cold Spring Harbor Laboratory

Date: 20-04-2010

DOI: 10.1261/RNA.2019810

Abstract: In humans, more than 30,000 chimeric transcripts originating from 23,686 genes have been identified. The mechanisms and association of chimeric transcripts arising from chromosomal rearrangements with cancer are well established, but much remains unknown regarding the biogenesis and importance of other chimeric transcripts that arise from nongenomic alterations. Recently, a SLC45A3 – ELK4 chimera has been shown to be androgen-regulated, and is overexpressed in metastatic or high-grade prostate tumors relative to local prostate cancers. Here, we characterize the expression of a KLK4 cis sense–antisense chimeric transcript, and show other ex les in prostate cancer. Using non-protein-coding microarray analyses, we initially identified an androgen-regulated antisense transcript within the 3′ untranslated region of the KLK4 gene in LNCaP cells. The KLK4 cis -NAT was validated by strand-specific linker-mediated RT-PCR and Northern blotting. Characterization of the KLK4 cis -NAT by 5′ and 3′ rapid lification of cDNA ends (RACE) revealed that this transcript forms multiple fusions with the KLK4 sense transcript. Lack of KLK4 antisense promoter activity using reporter assays suggests that these transcripts are unlikely to arise from a trans -splicing mechanism. 5′ RACE and analyses of deep sequencing data from LNCaP cells treated ±androgens revealed six high-confidence sense–antisense chimeras of which three were supported by the cDNA databases. In this study, we have shown complex gene expression at the KLK4 locus that might be a hallmark of cis sense–antisense chimeric transcription.

Engineered microenvironments provide new insights into ovarian and prostate cancer progression and drug responses

Publisher: Elsevier BV

Date: 12-2014

DOI: 10.1016/J.ADDR.2014.06.001

Abstract: Tissue engineering technologies, which have originally been designed to reconstitute damaged tissue structure and function, can mimic not only tissue regeneration processes but also cancer development and progression. Bioengineered approaches allow cell biologists to develop sophisticated experimentally and physiologically relevant cancer models to recapitulate the complexity of the disease seen in patients. Tissue engineering tools enable three-dimensionality based on the design of biomaterials and scaffolds that re-create the geometry, chemistry, function and signalling milieu of the native tumour microenvironment. Three-dimensional (3D) microenvironments, including cell-derived matrices, biomaterial-based cell culture models and integrated co-cultures with engineered stromal components, are powerful tools to study dynamic processes like proteolytic functions associated with cancer progression, metastasis and resistance to therapeutics. In this review, we discuss how biomimetic strategies can reproduce a humanised niche for human cancer cells, such as peritoneal or bone-like microenvironments, addressing specific aspects of ovarian and prostate cancer progression and therapy response.

Studies on Human Sexual Development. III. Fetal Pituitary and Serum, and Amniotic Fluid Concentrations of LH, CG, and FSH

Publisher: The Endocrine Society

Date: 1976

DOI: 10.1210/JCEM-42-1-9

Abstract: Fetal sera (9-20 weeks fetal age, n = 80) and pituitary glands (9.5-20 weeks, n = 36) obtained from hysterotomy specimens, and amniotic fluids (amniocentesis 8-40 weeks, n = 123) were assayed for FSH, LH (betaLH assay) and CG (betaCG assay). Results are expressed as mass of pure hormone. Prior to 12 weeks fetal age, pituitary, serum and amniotic fluid concentrations of LH and FSH were low or unmeasurable. In contrast, levels of CG in serum and in amniotic fluid were clearly measurable prior to 12 weeks. There was a definite CG peak at 11-14 weeks with levels up to 550 ng/ml in serum and 7400 ng/ml in amniotic fluid. Although LH levels began to rise at 12 weeks, when CG levels started to decline, serum levels of LH from 14-20 weeks in males (2-13 ng/ml) were still lower than the majority of CG levels at this time (6-115 ng/ml). These observations suggest that CG is the primary stimulus to the fetal Leydig cell which results in testosterone secretion (peak 11-17 weeks) and masculine differentiation of the genital tract. Significantly lower concentrations of both FSH and LH were observed in pituitary, serum and amniotic fluid between 12-20 weeks fetal age in males compared to females. This may be a result of feedback inhibition by the higher concentrations of testosterone in males at this time. Amniotic fluid FSH and LH concentrations correlated with their respective serum and pituitary values (P less than 0.01) indicating that amniotic fluid may provide a convenient index of fetal serum concentrations.

Fine-Mapping the HOXB Region Detects Common Variants Tagging a Rare Coding Allele: Evidence for Synthetic Association in Prostate Cancer

Publisher: Public Library of Science (PLoS)

Date: 13-02-2014

DOI: 10.1371/JOURNAL.PGEN.1004129

Phenotypic Characterization of Prostate Cancer LNCaP Cells Cultured within a Bioengineered Microenvironment

Publisher: Public Library of Science (PLoS)

Date: 05-09-2012

DOI: 10.1371/JOURNAL.PONE.0040217

A computational analysis of the genetic and transcript diversity at the kallikrein locus

Publisher: Walter de Gruyter GmbH

Date: 10-06-2016

DOI: 10.1515/HSZ-2016-0161

Abstract: The kallikrein related peptidase gene family (KLKs) comprises 15 genes located between 19q13.3-13.4. KLKs have chymotrypsin and/or trypsin like activity, but the tissue/organ expression profile of each KLK varies considerably. Thus, the role of KLKs in human biology is also very erse, and the deregulation of their function results in a wide-range of diseases. Here, we have cataloged the transcript (variants and fusions) and genetic (single nucleotide polymorphisms, small insertions/deletions, copy number variations (CNVs), and short tandem repeats) ersity at the KLK locus, providing a data set for researchers to explore the mechanisms through which KLK function may be deregulated. We reveal that the KLK locus hosts 85 fusion transcripts, and 80 variant transcripts. Interestingly, some fusion transcripts comprise up to 6 KLK genes. Our analysis of genetic variations of 2504 in iduals from the 1000 Genome Project indicated that the KLK locus is rich in genetic ersity, with some fusion transcripts harboring over 1000 single nucleotide variations. We also found evidence from the literature linking 2387 KLK genetic variants with many types of diseases. Finally, genotyping data from the 131 KLK genetic variants in the NCI-60 cancer cell lines is provided as a resource for the cancer and KLK field.

In vitro evidence that KLK14 regulates the components of the HGF/Met axis, pro-HGF and HGF-activator inhibitor 1A and 1B

Publisher: Walter de Gruyter GmbH

Date: 17-08-2016

DOI: 10.1515/HSZ-2016-0163

Abstract: Kallikrein-related peptidase (KLK) 14 is a serine protease linked to several pathologies including prostate cancer. We show that KLK14 has biphasic effects in vitro on activating and inhibiting components of the prostate cancer associated hepatocyte growth factor (HGF)/Met system. At 5–10 n m , KLK14 converts pro-HGF to the two-chain heterodimer required for Met activation, while higher concentrations degrade the HGF α-chain. HGF activator-inhibitor (HAI)-1A and HAI-1B, which inhibit pro-HGF activators, are degraded by KLK14 when protease:inhibitor stoichiometry is 1:1 or the protease is in excess. When inhibitors are in excess, KLK14 generates HAI-1A and HAI-1B fragments known to inhibit pro-HGF activating serine proteases. These in vitro data suggest that increased KLK14 activity could contribute at multiple levels to HGF/Met-mediated processes in prostate and other cancers.

Iroquois homeobox 4 (IRX4) Derived Micropeptide Promotes Prostate Cancer Progression and Chemoresistance Through Wnt Signaling Dysregulation

Publisher: Research Square Platform LLC

Date: 28-10-2023

DOI: 10.21203/RS.3.RS-3154829/V1

Determining Protease Substrates Within a Complex Protein Background Using the PROtein TOpography and Migration Analysis Platform (PROTOMAP)

Publisher: Springer New York

Date: 2017

DOI: 10.1007/978-1-4939-6850-3_11

Abstract: The PROtein TOpography and Migration Analysis Platform (PROTOMAP) approach is a degradomics technique used to determine protease substrates within complex protein backgrounds. The method involves protein separation according to protein relative mobility, using sodium dodecyl sulfate polyacrylamide gel electrophoresis. Gel lanes are then sliced into horizontal sections, and in-gel trypsin digestion performed for each gel slice. Extracted peptides and corresponding proteins are identified using liquid chromatography-tandem mass spectrometry and bioinformatics. Results are compiled in silico to generate a peptograph for every identified protein, being a pictorial representation of sodium dodecyl sulfate polyacrylamide gel electrophoresis. Proteins shown by their peptograph to have migrated further through the gel (i.e., to a lower gel slice) in the lane containing the active protease(s) of interest, as compared to the control, are deemed putative protease substrates. PROTOMAP has broad applicability to a range of experimental conditions and protein pools. Coupling this with its simple and robust methodology, the PROTOMAP approach has emerged as a valuable tool with which to determine protease substrates in complex systems.

PITX2 and non-canonical Wnt pathway interaction in metastatic prostate cancer

Publisher: Springer Science and Business Media LLC

Date: 26-10-2014

DOI: 10.1007/S10585-013-9620-7

Abstract: The non-canonical Wnt pathway, a regulator of cellular motility and morphology, is increasingly implicated in cancer metastasis. In a quantitative PCR array analysis of 84 Wnt pathway associated genes, both non-canonical and canonical pathways were activated in primary and metastatic tumors relative to normal prostate. Expression of the Wnt target gene PITX2 in a prostate cancer (PCa) bone metastasis was strikingly elevated over normal prostate (over 2,000-fold) and primary prostate cancer (over 200-fold). The elevation of PITX2 protein was also evident on tissue microarrays, with strong PITX2 immunostaining in PCa skeletal and, to a lesser degree, soft tissue metastases. PITX2 is associated with cell migration during normal tissue morphogenesis. In our studies, overexpression of in idual PITX2A/B/C isoforms stimulated PC-3 PCa cell motility, with the PITX2A isoform imparting a specific motility advantage in the presence of non-canonical Wnt5a stimulation. Furthermore, PITX2 specific shRNA inhibited PC-3 cell migration toward bone cell derived chemoattractant. These experimental results support a pivotal role of PITX2A and non-canonical Wnt signaling in enhancement of PCa cell motility, suggest PITX2 involvement in homing of PCa to the skeleton, and are consistent with a role for PITX2 in PCa metastasis to soft and bone tissues. Our findings, which significantly expand previous evidence that PITX2 is associated with risk of PCa biochemical recurrence, indicate that variation in PITX2 expression accompanies and may promote prostate tumor progression and metastasis.

Association between single-nucleotide polymorphisms in growth factor genes and quality of life in men with prostate cancer and the general population

Publisher: Springer Science and Business Media LLC

Date: 28-02-2015

DOI: 10.1007/S11136-015-0950-6

Abstract: Improved survival for men with prostate cancer has led to increased attention to factors influencing quality of life (QOL). As protein levels of vascular endothelial growth factor (VEGF) and insulin-like growth factor 1 (IGF-1) have been reported to be associated with QOL in people with cancer, we sought to identify whether single-nucleotide polymorphisms (SNPs) of these genes were associated with QOL in men with prostate cancer. Multiple linear regression of two data sets (including approximately 750 men newly diagnosed with prostate cancer and 550 men from the general population) was used to investigate SNPs of VEGF and IGF-1 (10 SNPs in total) for associations with QOL (measured by the SF-36v2 health survey). Men with prostate cancer who carried the minor 'T' allele for IGF-1 SNP rs35767 had higher mean Role-Physical scale scores (≥0.3 SD) compared to non-carriers (p < 0.05). While this association was not identified in men from the general population, one IGF-1 SNP rs7965399 was associated with higher mean Bodily Pain scale scores in men from the general population that was not found in men with prostate cancer. Men from the general population who carried the rare 'C' allele had higher mean Bodily Pain scale scores (≥0.3 SD) than non-carriers (p < 0.05). Through identifying SNPs that are associated with QOL in men with prostate cancer and men from the general population, this study adds to the mapping of complex interrelationships that influence QOL and suggests a role for IGF-I in physical QOL outcomes. Future research may identify biomarkers associated with increased risk of poor QOL that could assist in the provision of pre-emptive support for those identified at risk.

Adipocytes promote prostate cancer stem cell self-renewal through amplification of the cholecystokinin autocrine loop

Publisher: Impact Journals, LLC

Date: 17-12-2016

DOI: 10.18632/ONCOTARGET.6643

Thermal, structural and dynamic properties of ionic liquids and organic ionic plastic crystals with a small ether-functionalised cation

Publisher: Royal Society of Chemistry (RSC)

Date: 2022

DOI: 10.1039/D2QM00045H

Abstract: A series of new salts with a small ether-functionalised trimethylammonium cation are synthesised and characterised to probe their unique structure–property relationships.

The tissue kallikrein family of serine proteases: Functional roles in human disease and potential as clinical biomarkers

Publisher: Informa UK Limited

Date: 2004

DOI: 10.1080/10408360490471931

Abstract: Prostate specific antigen (PSA) or human kallikrein 3 (hK3) has long been an effective biomarker for prostate cancer. Now, other members of the tissue kallikrein (KLK) gene family are fast becoming of clinical interest due to their potential as prognostic biomarkers. particularly for hormone dependent cancers. The tissue kallikreins are serine proteases that are encoded by highly conserved multi-gene family clusters in rodents and humans. The rat and mouse loci contain 10 and 25 functional genes, respectively, while the human locus at 19q 13.4 contains 15 genes. The structural organization and size of these genes are similar across species all genes have 5 coding exons that encode a prepro-enzyme. Although the physiological activators of these zymogens have not been described, in vitro biochemical studies show that some kallikreins can auto-activate and others can activate each other, suggesting that the kallikreins may participate in an enzymatic cascade similar to that of the coagulation cascade. These genes are expressed, to varying degrees, in a wide range of tissues suggesting a functional involvement in a erse range of physiological and pathophysiological processes. These include roles in normal skin desquamation and psoriatic lesions, tooth development, neural plasticity, and Alzheimer's disease (AD). Of particular interest is the expression of many kallikreins in prostate, ovarian, and breast cancers where they are emerging as useful prognostic indicators of disease progression.

The potential role of lycopene for the prevention and therapy of prostate cancer: From molecular mechanisms to clinical evidence

Publisher: MDPI AG

Date: 12-07-2013

DOI: 10.3390/IJMS140714620

Genomic and Phenotypic Biomarkers for Precision Medicine Guidance in Advanced Prostate Cancer

Publisher: Springer Science and Business Media LLC

Date: 10-08-2023

DOI: 10.1007/S11864-023-01121-Z

Abstract: Prostate cancer (PCa) is the second most diagnosed malignant neoplasm and is one of the leading causes of cancer-related death in men worldwide. Despite significant advances in screening and treatment of PCa, given the heterogeneity of this disease, optimal personalized therapeutic strategies remain limited. However, emerging predictive and prognostic biomarkers based on in idual patient profiles in combination with computer-assisted diagnostics have the potential to guide precision medicine, where patients may benefit from therapeutic approaches optimally suited to their disease. Also, the integration of genotypic and phenotypic diagnostic methods is supporting better informed treatment decisions. Focusing on advanced PCa, this review discusses polygenic risk scores for screening of PCa and common genomic aberrations in androgen receptor (AR), PTEN-PI3K-AKT, and DNA damage response (DDR) pathways, considering clinical implications for diagnosis, prognosis, and treatment prediction. Furthermore, we evaluate liquid biopsy, protein biomarkers such as serum testosterone levels, SLFN11 expression, total alkaline phosphatase (tALP), neutrophil-to-lymphocyte ratio (NLR), tissue biopsy, and advanced imaging tools, summarizing current phenotypic biomarkers and envisaging more effective utilization of diagnostic and prognostic biomarkers in advanced PCa. We conclude that prognostic and treatment predictive biomarker discovery can improve the management of patients, especially in metastatic stages of advanced PCa. This will result in decreased mortality and enhanced quality of life and help design a personalized treatment regimen.

Compartmentalized expression of kallikrein 4 (KLK4/hK4) isoforms in prostate cancer: nuclear, cytoplasmic and secreted forms

Publisher: Bioscientifica

Date: 12-2005

DOI: 10.1677/ERC.1.01062

Abstract: The prostate-specific antigen-related serine protease gene, kallikrein 4 ( KLK4 ), is expressed in the prostate and, more importantly, overexpressed in prostate cancer. Several KLK4 mRNA splice variants have been reported, but it is still not clear which of these is most relevant to prostate cancer. Here we report that, in addition to the full-length KLK4 ( KLK4-254 ) transcript, the exon 1 deleted KLK4 transcripts, in particular, the 5′-truncated KLK4-205 transcript, is expressed in prostate cancer. Using V5/His6 and green fluorescent protein (GFP) carboxy terminal tagged expression constructs and immunocytochemical approaches, we found that hK4-254 is cytoplasmically localized, while the N-terminal truncated hK4-205 is in the nucleus of transfected PC-3 prostate cancer cells. At the protein level, using anti-hK4 peptide antibodies specific to different regions of hK4-254 (N-terminal and C-terminal), we also demonstrated that endogenous hK4-254 (detected with the N-terminal antibody) is more intensely stained in malignant cells than in benign prostate cells, and is secreted into seminal fluid. In contrast, for the endogenous nuclear-localized N-terminal truncated hK4-205 form, there was less difference in staining intensity between benign and cancer glands. Thus, KLK4-254 /hK4-254 may have utility as an immunohistochemical marker for prostate cancer. Our studies also indicate that the expression levels of the truncated KLK4 transcripts, but not KLK4-254 , are regulated by androgens in LNCaP cells. Thus, these data demonstrate that there are two major isoforms of hK4 ( KLK4-254 /hK4-254 and KLK4-205 /hK4-205) expressed in prostate cancer with different regulatory and expression profiles that imply both secreted and novel nuclear roles.

Metastasis of ovarian cancer is mediated by kallikrein related peptidases

Publisher: Springer Science and Business Media LLC

Date: 17-09-2014

DOI: 10.1007/S10585-013-9615-4

Paracrine interactions between LNCaP prostate cancer cells and bioengineered bone in 3D in vitro culture reflect molecular changes during bone metastasis

Publisher: Elsevier BV

Date: 06-2014

DOI: 10.1016/J.BONE.2014.02.001

Abstract: As microenvironmental factors such as three-dimensionality and cell-matrix interactions are increasingly being acknowledged by cancer biologists, more complex 3D in vitro models are being developed to study tumorigenesis and cancer progression. To better understand the pathophysiology of bone metastasis, we have established and validated a 3D indirect co-culture model to investigate the paracrine interactions between prostate cancer (PCa) cells and human osteoblasts. Co-culture of the human PCa, LNCaP cells embedded within polyethylene glycol hydrogels with human osteoblasts in the form of a tissue engineered bone construct (TEB), resulted in reduced proliferation of LNCaP cells. LNCaP cells in both monoculture and co-culture were responsive to the androgen analog, R1881, as indicated by an increase in the expression (mRNA and/or protein induction) of androgen-regulated genes including prostate specific antigen and fatty acid synthase. Microarray gene expression analysis further revealed an up-regulation of bone markers and other genes associated with skeletal and vasculature development and a significant activation of transforming growth factor β1 downstream genes in LNCaP cells after co-culture with TEB. LNCaP cells co-cultured with TEB also unexpectedly showed similar changes in classical androgen-responsive genes under androgen-deprived conditions not seen in LNCaP monocultures. The molecular changes of LNCaP cells after co-culturing with TEBs suggest that osteoblasts exert a paracrine effect that may promote osteomimicry and modulate the expression of androgen-responsive genes in LNCaP cells. Taken together, we have presented a novel 3D in vitro model that allows the study of cellular and molecular changes occurring in PCa cells and osteoblasts that are relevant to metastatic colonization of bone. This unique in vitro model could also facilitate cancer biologists to dissect specific biological hypotheses via extensive genomic or proteomic assessments to further our understanding of the PCa-bone crosstalk.

INSULIN HYPOGLYCAEMIA AND CHOLINERGIC BLOCKADE: RESPONSE OF PLASMA IMMUNOREACTIVE β‐ENDORPHIN

Publisher: Wiley

Date: 11-1983

DOI: 10.1111/J.1365-2265.1983.TB00033.X

Abstract: Six normal subjects were studied to investigate the mechanisms involved in the release of immunoreactive beta-endorphin (ir-beta EP) in response to insulin hypoglycaemia. Insulin alone (0.2 U/kg body weight) was followed after a 30 min lag period by a congruent to 2.5 fold elevation of plasma ir-beta EP, with a return to basal levels by 90 min. Concurrent infusion of 10% dextrose at 250 ml/h for 2 h prevented the increase in plasma ir-beta EP levels, suggesting an effect of hypoglycaemia rather than a direct effect of insulin. Premedication with atropine 0.6 mg at -30 min was followed by hypoglycaemia equivalent to that seen with insulin alone, but no increase in plasma ir-beta EP, suggesting the involvement of cholinergic mechanisms in the neural mediation of ir-beta EP release in response to hypoglycaemia.

Development of anti-hlh antibodies after therapy with posterior pituitary extract

Publisher: The Endocrine Society

Date: 07-1978

DOI: 10.1210/JCEM-47-1-1

Abstract: This report describes the appearance of high affinity antibodies to human LH in a girl who had been treated for diabetes insipidus with injections of pitressin tannate, plus occasional nasal insufflations of posterior pituitary powder. Immunological studies indicated that the antibody was a 7S IgG directed against the beta subunit of LH, which is not species-specific. The demonstration of immunoassayable LH in a commercially available pitressin preparation strongly suggests that this patient was immunized by bovine or porcine LH. Although studies of her urinary LH excretion and serum LH (by an interstitial cell bioassay system) suggest that at least some of her endogenous LH is not bound by the antibody, the possibility remains that this type of immunization may have important implications for the development and maintenance of normal adult pituitary-ovarian relationships.

Can tissue engineering concepts advance tumor biology research?

Publisher: Elsevier BV

Date: 03-2010

DOI: 10.1016/J.TIBTECH.2009.12.001

Abstract: Advances in tissue engineering have traditionally led to the design of scaffold- or matrix-based culture systems that better reflect the biological, physical and biochemical environment of the natural extracellular matrix. Although their clinical applications in regenerative medicine tend to receive most of the attention, it is obvious that other areas of biomedical research could be well served by the powerful tools that have already been developed in tissue engineering. In this article, we review the recent literature to demonstrate how tissue engineering platforms can enhance in vitro and in vivo models of tumorigenesis and thus hold great promise to contribute to future cancer research.

The use of predictive or prognostic genetic biomarkers in endometrial and other hormone-related cancers: Justification for extensive candidate gene single nucleotide polymorphism studies of the matrix metalloproteinase family and their inhibitors

Publisher: American Association for Cancer Research (AACR)

Date: 09-2009

DOI: 10.1158/1055-9965.EPI-08-1184

Abstract: Genome-wide association studies have accelerated the discovery of single nucleotide polymorphisms (SNP) associated with susceptibility to complex diseases, including many malignancies. The matrix metalloproteinase (MMP) family of proteases are involved in many cell processes, most notably the degradation of the extracellular matrix, and differences in gene and protein expression have been reported to be associated with many cancers. Surprisingly, none of the SNPs located within these genes have been identified to be associated with cancer in the genome-wide association studies published to date. This may be in part due to the proportion and the tagging efficiency of MMP SNPs covered by high-throughput genotyping chips. This review will provide an overview of current evidence for MMPs and associated SNPs in endometrial and other hormone-related cancers, to provide justification for the further detailed studies of MMP SNPs as cancer markers. (Cancer Epidemiol Biomarkers Prev 2009 (9):2352–65)

Single nucleotide polymorphisms (SNPs)

Publisher: Springer New York

Date: 2014

DOI: 10.1007/978-1-4899-8050-2_5

Immuno- and bioactive inhibin and inhibin α-subunit expression in rat Leydig cell cultures

Publisher: Elsevier BV

Date: 09-1989

DOI: 10.1016/0303-7207(89)90056-7

Abstract: The rise in serum immunoactive inhibin levels in male rats following hCG stimulation raised the possibility that Leydig cells may produce inhibin. This study therefore evaluated whether Percoll-purified Leydig cells from adult male rats synthesized and secreted inhibin in vitro as measured by Northern blot analysis, radioimmunoassay and in vitro bioassay. Northern blot analysis demonstrated the presence of alpha-inhibin subunit mRNA in the Leydig cell and inhibin bioactivity was detected in Leydig cell culture media. Levels of immunoactive inhibin increased in culture over 20 h and were directly dependent on the number of Leydig cells in culture. rLH (NIADDK-rLH-I-6) and not rFSH (NIADDK-rFSH-I-6) stimulated immunoactive inhibin levels in a dose-dependent manner. This study demonstrates that Leydig cells express mRNA for the alpha-subunit of inhibin and produce inhibin which is biologically and immunologically active prompting a re-evaluation of our concepts of testicular inhibin production.

Kallikreins on steroids: Structure, function, and hormonal regulation of prostate-specific antigen and the extended kallikrein locus

Publisher: The Endocrine Society

Date: 08-2010

DOI: 10.1210/ER.2009-0034

Abstract: The 15 members of the kallikrein-related serine peptidase (KLK) family have erse tissue-specific expression profiles and putative proteolytic functions. The kallikrein family is also emerging as a rich source of disease biomarkers with KLK3, commonly known as prostate-specific antigen, being the current serum biomarker for prostate cancer. The kallikrein locus is also notable because it is extraordinarily responsive to steroids and other hormones. Indeed, at least 14 functional hormone response elements have been identified in the kallikrein locus. A more comprehensive understanding of the transcriptional regulation of kallikreins may help the field make more informed hypotheses about the physiological functions of kallikreins and their effectiveness as biomarkers. In this review, we describe the organization of the kallikrein locus and the structure of kallikrein genes and proteins. We also focus on the transcriptional regulation of kallikreins by androgens, progestins, glucocorticoids, mineralocorticoids, estrogens, and other hormones in animal models and human prostate, breast, and reproductive tract tissues. The interaction of the androgen receptor with androgen response elements in the promoter and enhancer of KLK2 and KLK3 is also summarized in detail. There is evidence that all kallikreins are regulated by multiple nuclear receptors. Yet, apart from KLK2 and KLK3, it is not clear whether all kallikreins are direct transcriptional targets. Therefore, we argue that gaining more detailed information about the mechanisms that regulate kallikrein expression should be a priority of future studies and that the kallikrein locus will continue to be an important model in the era of genome-wide analyses.

ACTIVATION OF THE KALLIKREIN KININ SYSTEM IN INTERSTITIAL CYSTITIS

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 07-1999

DOI: 10.1097/00005392-199907000-00030

Abstract: We investigated whether the kallikrein kinin system is activated in interstitial cystitis by measuring urinary excretion rates of kinin peptides, active and total kallikrein, and the kininase neutral endopeptidase in women with interstitial cystitis. We compared these excretion rates to a control group of women with stress incontinence and normal bladder function. Catheter urine was collected from subjects during a water diuresis (approximately 10 ml. per minute) before and after distention of the bladder with 100 ml. water. The contribution of the bladder wall to urinary kinins was assessed by measuring the change in kinin levels after 2 minutes of bladder stasis before and after distention. Absolute bradykinin and kallidin excretion rates were similar in women with interstitial cystitis and control subjects. Two minutes of bladder stasis after bladder distention increased urinary bradykinin (p = 0.02) but not kallidin excretion rates. Active and total kallikrein excretion rates were similar in patients with interstitial cystitis and control subjects. Neutral endopeptidase excretion rates were reduced in the initial urine collection from subjects with interstitial cystitis but were similar in both groups during later collection periods. These data provide evidence for increased bradykinin levels in the bladder wall of subjects with interstitial cystitis, which may be due in part to reduced neutral endopeptidase levels. These increased bradykinin levels may participate in the pathogenesis and symptomatology of interstitial cystitis.

Single nucleotide polymorphisms in clinics: Fantasy or reality for cancer?

Publisher: Informa UK Limited

Date: 23-09-2016

DOI: 10.3109/10408363.2015.1075469

Abstract: Single nucleotide polymorphisms (SNPs) have been classically used for dissecting various human complex disorders using candidate gene studies. During the last decade, large scale SNP analysis, i.e. genome-wide association studies (GWAS) have provided an agnostic approach to identify possible genetic loci associated with heterogeneous disease such as cancer susceptibility, prognosis of survival or drug response. Further, the advent of new technologies, including microarray-based genotyping as well as high throughput next generation sequencing has opened new avenues for SNPs to be used in clinical practice. It is speculated that the utility of SNPs to understand the mechanisms, biology of variable drug response and ultimately treatment in idualization based on the in idual's genome composition will be indispensable in the near future. In the current review, we discuss the advantages and disadvantages of the clinical utility of genetic variants in disease risk-prediction, prognosis, clinical outcome and pharmacogenomics. The lessons and challenges for the utility of SNP-based biomarkers are also discussed, including the need for additional functional validation studies.

Tie-2 regulates the stemness and metastatic properties of prostate cancer cells

Publisher: Impact Journals, LLC

Date: 29-04-2016

DOI: 10.18632/ONCOTARGET.3950

Adrenocorticotropin, β-endorphin, and β-mipotropin in normal thyroid and lung: Possible implications for ectopic hormone secretion

Publisher: The Endocrine Society

Date: 12-1982

DOI: 10.1210/ENDO-111-6-2097

Abstract: The expression of the proopiomelanocortin (POMC) gene by normal lung and thyroid was examined by measurement of the content of ACTH, beta-lipotropin (beta LPH), and beta-endorphin (beta EP) in porcine lung and thyroid tissue. Acid extracts of normal porcine lung and thyroid tissue each contained appreciable amounts of immunoreactive (ir) ACTH, ir-beta LPH, and ir-beta EP. The content of ir-beta LPH in both tissues exceeded by severalfold, on a molar basis, the content of ir-ACTH and ir-beta EP, suggesting that the common precursor POMC was processed predominantly to peptides other than ir-ACTH and ir-beta EP. A porcine thyroid extract (Calcitare, porcine calcitonin, Armour) showed equivalent levels of beta EP-like immunoreactivity and bioactivity, measured by opiate radioreceptor assay in contrast, ACTH-like bioactivity, measured by rat zona fasciculata steroidogenesis, was only 4% of ACTH-like immunoreactivity. On reversed phase high performance liquid chromatography, Calcitare showed multiple peaks of ACTH-like immunoreactivity, one of which coeluted with porcine ACTH-(1-39), and two much smaller peaks of beta EP-like immunoreactivity, of which the smaller coeluted with porcine beta EP. These data suggest that both lung and thyroid gland synthesize POMC, which in normal tissue is usually predominantly processed to species other than ACTH and beta EP. Ectopic secretion of ACTH and beta EP by lung and thyroid neoplasms may thus represent the loss of a system(s) normally responsible for processing the precursor beyond ACTH and beta EP.

Studies on Human Sexual Development IV. Fetal Pituitary and Serum, and Amniotic Fluid Concentrations of Prolactin

Publisher: The Endocrine Society

Date: 02-1977

DOI: 10.1210/JCEM-44-2-408

Abstract: Prolactin concentrations were measured in 161 amniotic fluid specimens from 8-40 weeks fetal age and the levels compared with those observed in 45 fetal and neonatal cord sera and in 42 fetal pituitary specimens. Amniotic fluid prolactin levels rose steeply between 12-16 weeks gestation, and then declined to term the calculated total amniotic fluid content of prolactin showed a similar pattern, but the peak was later, at about 26 weeks gestation. Amniotic fluid concentrations consistently exceeded fetal serum prolactin levels, even during the last trimester, when fetal serum and pituitary levels were highest. The data are compatible with a fetal origin for amniotic fluid prolactin, but only if one assumes that flux of prolactin out of amniotic fluid compartment is negligible, that the fetal kidney in mid-pregnancy clears prolactin at a rate virtually equal to the glomerular filtration rate, and the fetal pituitary shows secretion characteristics quite different from those of the adult gland.

Glucocorticoid regulation of proopiomelanocortin gene expression in the pituitary gland of hypothalamopituitary intact and hypothalamopituitary disconnected sheep

Publisher: S. Karger AG

Date: 1989

DOI: 10.1159/000125234

Abstract: Proopiomelanocortin (POMC) gene expression in the anterior pituitary (AP) gland has previously been shown to be positively regulated by CRF and AVP and negatively regulated by glucocorticoids. In the neurointermediate lobe (NIL) of the pituitary, however, POMC gene expression is under tonic inhibitory dopaminergic control. In the present study we have used hypothalamopituitary intact (HPI), ovariectomized (OVX), and OVX/hypothalamopituitary disconnected (OVX/HPD) ewes to examine direct (i.e. nonhypothalamic) effects of glucocorticoids on POMC gene expression in both the AP and the NIL. There was no difference between POMC mRNA levels in intact and OVX sheep. In intact animals treated with dexamethasone, AP POMC mRNA levels were half those of controls. POMC mRNA levels were increased 3-fold in OVX/HPD sheep, compared with OVX, and lowered by dexamethasone to half OVX/HPD levels. In the NIL, hypothalamopituitary disconnection resulted in slightly higher mean POMC mRNA levels than in intact animals but the large intragroup variation did not allow a significant change. Dexamethasone administration had no effect on NIL levels of POMC mRNA in intact or OVX/HPD sheep.

Properties of hybrid sol-gel coatings with the incorporation of lanthanum 4-hydroxy cinnamate as corrosion inhibitor on carbon steel with different surface finishes

Publisher: Elsevier BV

Date: 09-2021

DOI: 10.1016/J.APSUSC.2021.149881

Kallikreins and kinins in inflammatory-like events in the reproductive tract

Publisher: Elsevier BV

Date: 06-1997

DOI: 10.1006/PHRS.1997.0183

Abstract: The normal reproductive events of proliferation of the endometrial lining of the uterus during the menstrual cycle and ovulation have been likened to inflammatory-like events. The kallikrein-kinin system is involved in inflammatory processes in many tissues. In this review, we identify which components of the kallikrein-kinin system--the enzyme, tissue kallikrein the substrate, low molecular weight kininogen and the effector receptor for the generated bradykinin peptide, the B2 receptor--have been identified in the uterus and ovary and their known involvement in the function of these organs. All three components have been localized to the glandular epithelial cells of the human endometrium. Tissue kallikrein gene expression is elevated midcycle when estrogens levels are also rising. This is also a time of extensive endometrial proliferation and tissue remodelling in preparation for embryo implantation, an event which is likened to other inflammatory processes. Similarly, tissue kallikrein gene expression was elevated following the estrogen surge at proestrous in the rat uterus, suggesting tissue kallikrein gene expression may be regulated by estrogens. Tissue kallikrein enzyme activity and gene expression has been demonstrated in the rat ovary and shown to be variously altered at the time of ovulation. Bradykinin has also been implicated in the expulsion of the ovum at the time of ovulation. These findings show that various components of the kallikrein-kinin system are present in the uterus and ovary. Further studies are required to more fully delineate their role in reproductive function.

Global levels of specific histone modifications and an epigenetic gene signature predict prostate cancer progression and development

Publisher: American Association for Cancer Research (AACR)

Date: 10-2010

DOI: 10.1158/1055-9965.EPI-10-0555

Abstract: Background: Epigenetic alterations are common in prostate cancer, yet how these modifications contribute to carcinogenesis is poorly understood. We investigated whether specific histone modifications are prognostic for prostate cancer relapse, and whether the expression of epigenetic genes is altered in prostate tumorigenesis. Methods: Global levels of histone H3 lysine-18 acetylation (H3K18Ac) and histone H3 lysine-4 dimethylation (H3K4diMe) were assessed immunohistochemically in a prostate cancer cohort of 279 cases. Epigenetic gene expression was investigated in silico by analysis of microarray data from 23 primary prostate cancers (8 with biochemical recurrence and 15 without) and 7 metastatic lesions. Results: H3K18Ac and H3K4diMe are independent predictors of relapse-free survival, with high global levels associated with a 1.71-fold (P & 0.0001) and 1.80-fold (P = 0.006) increased risk of tumor recurrence, respectively. High levels of both histone modifications were associated with a 3-fold increased risk of relapse (P & 0.0001). Epigenetic gene expression profiling identified a candidate gene signature (DNMT3A, MBD4, MLL2, MLL3, NSD1, and SRCAP), which significantly discriminated nonmalignant from prostate tumor tissue (P = 0.0063) in an independent cohort. Conclusions: This study has established the importance of histone modifications in predicting prostate cancer relapse and has identified an epigenetic gene signature associated with prostate tumorigenesis. Impact: Our findings suggest that targeting the epigenetic enzymes specifically involved in a particular solid tumor may be a more effective approach. Moreover, testing for aberrant expression of epigenetic genes such as those identified in this study may be beneficial in predicting in idual patient response to epigenetic therapies. Cancer Epidemiol Biomarkers Prev 19(10) 2611–22. ©2010 AACR.

Exploring the active site binding specificity of kallikrein-related peptidase 5 (KLK5) guides the design of new peptide substrates and inhibitors

Publisher: Walter de Gruyter GmbH

Date: 19-02-2016

DOI: 10.1515/HSZ-2016-0112

Abstract: Kallikrein-related peptidase 5 (KLK5) is a promising therapeutic target in several skin diseases, including Netherton syndrome, and is emerging as a potential target in various cancers. In this study, we used a sparse matrix library of 125 in idually synthesized peptide substrates to characterize the binding specificity of KLK5. The sequences most favored by KLK5 were GRSR, YRSR and GRNR, and we identified sequence-specific interactions involving the peptide N-terminus by analyzing kinetic constants ( k cat and K M ) and performing molecular dynamics simulations. KLK5 inhibitors were subsequently engineered by substituting substrate sequences into the binding loop (P1, P2 and P4 residues) of sunflower trypsin inhibitor-1 (SFTI-1). These inhibitors were effective against KLK5 but showed limited selectivity, and performing a further substitution at P2′ led to the design of a new variant that displayed improved activity against KLK5 ( K i =4.2±0.2 n m ), weak activity against KLK7 and 12-fold selectivity over KLK14. Collectively, these findings provide new insight into the design of highly favored binding sequences for KLK5 and reveal several opportunities for modulating inhibitor selectivity over closely related proteases that will be useful for future studies aiming to develop therapeutic molecules targeting KLK5.

Remodelling of the tumour microenvironment by the kallikrein-related peptidases

Publisher: Springer Science and Business Media LLC

Date: 31-01-2022

DOI: 10.1038/S41568-021-00436-Z

Abstract: Kallikrein-related peptidases (KLKs) are critical regulators of the tumour microenvironment. KLKs are proteolytic enzymes regulating multiple functions of bioactive molecules including hormones and growth factors, membrane receptors and the extracellular matrix architecture involved in cancer progression and metastasis. Perturbations of the proteolytic cascade generated by these peptidases, and their downstream signalling actions, underlie tumour emergence or blockade of tumour growth. Recent studies have also revealed their role in tumour immune suppression and resistance to cancer therapy. Here, we present an overview of the complex biology of the KLK family and its context-dependent nature in cancer, and discuss the different therapeutic strategies available to potentially target these proteases.

Exceptional lithium diffusion through porous aromatic framework (PAF) interlayers delivers high capacity and long-life lithium–sulfur batteries

Publisher: Royal Society of Chemistry (RSC)

Date: 2022

DOI: 10.1039/D1TA07523C

Abstract: Sulfonated porous aromatic frameworks (SPAFs) accelerate Li-ion diffusion while retarding the polysulfide shuttle effect in Li–S batteries. This leads to high residual capacity above 1000 mA h g −1 and coulombic efficiency ( .5%) after 500 cycles.

Identification of evidence-based biospecimen quality-control tools: A report of the international society for biological and environmental repositories (ISBER) biospecimen science working group

Publisher: Elsevier BV

Date: 2013

DOI: 10.1016/J.JMOLDX.2012.06.008

Effect of ethane dimethane sulphonate on proopiomelanocortin (POMC) mRNA and POMC-derived peptides in the rat testis

Publisher: Elsevier BV

Date: 08-1989

DOI: 10.1016/0303-7207(89)90181-0

Abstract: Recent studies have shown that both proopiomelanocortin (POMC)-derived peptides and a range of POMC gene transcripts are present in the testis. Previous immunocytochemical studies have reported immunoreactive (ir)-beta-endorphin (EP) and ir-ACTH to be localized in the Leydig cells, and ir-NacEP in spermatogonia and primary spermatocytes. In the present study, we have further examined the hypothesis that testicular Leydig cells are the principal site of synthesis of these peptides, by determining the effects of the administration of the cytotoxic drug ethane dimethane sulphonate (EDS) which selectively destroys the Leydig cells of the testis. As expected, serum testosterone levels fell and serum FSH/LH levels increased within 3 days of EDS administration, returning to normal levels 4-8 weeks later. In contrast, the testicular content of POMC-derived peptides and POMC mRNA levels in these animals was not significantly altered throughout the experimental period. In addition, POMC mRNA was not detected in a purified Leydig cell preparation derived from adult male rats, and POMC-derived peptides were also undetectable in the media of a similar preparation following cell culture. These data suggest that in the adult the predominant site of rat POMC gene expression is in testicular interstitial cells other than Leydig cells.

New Insights into Decoupled Cation and Anion Transport and Dynamic Heterogeneity in a Diethyl(methyl)(isobutyl)phosphonium Hexafluorophosphate Organic Ionic Plastic Crystal

Publisher: American Chemical Society (ACS)

Date: 04-10-2021

DOI: 10.1021/ACS.JPCLETT.1C02943

The Expression of the Kallikrein Gene Family in the Rat Pituitary: Oestrogen Effects and the Expression of an Additional Family Member in the Neurointermediate Lobe

Publisher: Wiley

Date: 06-1989

DOI: 10.1111/J.1365-2826.1989.TB00103.X

Abstract: Abstract Using a series of oligonucleotide probes (18 to 21 mers) specific for members of the rat kallikrein/tonin gene family (PS, S1, S2, S3, K1, P1), we have shown by Northern blot analysis that the oestrogen-dependent kallikrein gene expressed in the male and female rat anterior pituitary is true kallikrein (PS). In addition, we have demonstrated that oestrogen treatment may also induce PS gene expression in the male and female rat neurointermediate lobe. None of the other five rat arginyl-esteropeptidase genes so far described (S1, S2, S3, K1, P1) was found to be expressed in the anterior pituitary or neurointermediate lobe under these conditions. However, the demonstration of an additional hybridization signal in the male neurointermediate lobe using a relatively non-specific PS gene probe suggests the expression of another, as yet uncharacterized, kallikrein gene family member in this tissue.

The kallikrein 14 gene is down-regulated by androgen receptor signalling and harbours genetic variation that is associated with prostate tumour aggressiveness

Publisher: Walter de Gruyter GmbH

Date: 05-2012

DOI: 10.1515/HSZ-2011-0268

Abstract: Kallikrein 14 (KLK14) has been proposed as a useful prognostic marker in prostate cancer, with expression reported to be associated with tumour characteristics such as higher stage and Gleason score. KLK14 tumour expression has also shown the potential to predict prostate cancer patients at risk of disease recurrence after radical prostatectomy. The KLKs are a remarkably hormone-responsive family of genes, although detailed studies of androgen regulation of KLK14 in prostate cancer have not been undertaken to date. Using in vitro studies, we have demonstrated that unlike many other prostatic KLK genes that are strictly androgen responsive, KLK14 is more broadly expressed and inversely androgen regulated in prostate cancer cells. Given these results and evidence that KLK14 may play a role in prostate cancer prognosis, we also investigated whether common genetic variants in the KLK14 locus are associated with risk and/or aggressiveness of prostate cancer in approximately 1200 prostate cancer cases and 1300 male controls. Of 41 single nucleotide polymorphisms assessed, three were associated with higher Gleason score (≥7): rs17728459 and rs4802765, both located upstream of KLK14 , and rs35287116, which encodes a p.Gln33Arg substitution in the KLK14 signal peptide region. Our findings provide further support for KLK14 as a marker of prognosis in prostate cancer.

Nuclear magnetic resonance characterisation of ionic liquids and organic ionic plastic crystals: common approaches and recent advances

Publisher: Royal Society of Chemistry (RSC)

Date: 2021

DOI: 10.1039/D1CC02151F

Abstract: This article provides an overview of nuclear magnetic resonance methods and applications to ionic liquids and organic ionic plastic crystals.

Prostatic trypsin-like kallikrein-related peptidases (KLKs) and other prostate-expressed tryptic proteinases as regulators of signalling via proteinase-activated receptors (PARs)

Publisher: Walter de Gruyter GmbH

Date: 15-05-2008

DOI: 10.1515/BC.2008.078

Abstract: The prostate is a site of high expression of serine proteinases including members of the kallikrein-related peptidase (KLK) family, as well as other secreted and membrane-anchored serine proteinases. It has been known for some time that members of this enzyme family elicit cellular responses by acting directly on cells. More recently, it has been recognised that for serine proteinases with specificity for cleavage after arginine and lysine residues (trypsin-like or tryptic enzymes) these cellular responses are often mediated by cleavage of members of the proteinase-activated receptor (PAR) family – a four member sub-family of G protein-coupled receptors. Here, we review the expression of PARs in prostate, the ability of prostatic trypsin-like KLKs and other prostate-expressed tryptic enzymes to cleave PARs, as well as the prostate cancer-associated consequences of PAR activation. In addition, we explore the dysregulation of trypsin-like serine proteinase activity through the loss of normal inhibitory mechanisms and potential interactions between these dysregulated enzymes leading to aberrant PAR activation, intracellular signalling and cancer-promoting cellular changes.

IMMUNOREACTIVE β‐ENDORPHIN LEVELS IN PLASMA AND PITUITARY TISSUE FROM GENETICALLY HYPERTENSIVE AND NORMOTENSIVE RATS

Publisher: Wiley

Date: 09-1981

DOI: 10.1111/J.1440-1681.1981.TB00748.X

Abstract: 1. Levels of immunoreactive beta-endorphin were measured in neurointermediate lobes, anterior lobes and plasma from the Japanese and New Zealand strains of genetically hypertensive rats and their normotensive controls. 2. No significant differences were observed in beta-endorphin between the hypertensive and normotensive rats of the New Zealand strain. 3. The hypertensive rats of the Japanese strain showed significantly higher levels of beta-endorphin in neurointermediate lobe and lower levels in plasma than their normotensive controls. 4. These results suggest that the differences in beta-endorphin levels in the Japanese strain reflect a genetic difference not necessarily related to elevated blood pressure.

Exploration of phase diagram, structural and dynamic behavior of [HMG][FSI] mixtures with NaFSI across an extended composition range

Publisher: Royal Society of Chemistry (RSC)

Date: 2022

DOI: 10.1039/D2CP01910H

Abstract: In this study we present a detailed exploration of the complex structural and dynamic behavior of [HMG][FSI] mixtures with the sodium salt NaFSI across the whole composition range from 0 to 100 mol%.

GelMA and Biomimetic Culture Allow the Engineering of Mineralized, Adipose, and Tumor Tissue Human Microenvironments for the Study of Advanced Prostate Cancer In Vitro and In Vivo

Publisher: Wiley

Date: 21-02-2023

DOI: 10.1002/ADHM.202201701

Abstract: Increasing evidence shows bone marrow (BM)‐adipocytes as a potentially important contributor in prostate cancer (PCa) bone metastases. However, a lack of relevant models has prevented the full understanding of the effects of human BM‐adipocytes in this microenvironment. It is hypothesized that the combination of tunable gelatin methacrylamide (GelMA)‐based hydrogels with the biomimetic culture of human cells would offer a versatile 3D platform to engineer human bone tumor microenvironments containing BM‐adipocytes. Human osteoprogenitors, adipocytes, and PCa cells are in idually cultured in vitro in GelMA hydrogels, leading to mineralized, adipose, and PCa tumor 3D microtissues, respectively. Osteoblast mineralization and tumor spheroid formation are tailored by hydrogel stiffness with lower stiffnesses correlating with increased mineralization and tumor spheroid size. Upon coculture with tumor cells, BM‐adipocytes undergo morphological changes and delipidation, suggesting reciprocal interactions between the cell types. When brought in vivo, the mineralized and adipose microtissues successfully form a humanized fatty bone microenvironment, presenting, for the first time, with human adipocytes. Using this model, an increase in tumor burden is observed when human adipocytes are present, suggesting that adipocytes support early bone tumor growth. The advanced platform presented here combines natural aspects of the microenvironment with tunable properties useful for bone tumor research.

Erratum: Phenotypic characterization of prostate cancer LNCaP Cells cultured within a bioengineered microenvironment (PLoS ONE (2013) 8:1 DOI: 10.1371/annotation/a26f1a2e-2765-4c10-942e-d2a738b80bf9)

Publisher: Public Library of Science (PLoS)

Date: 17-01-2013

DOI: 10.1371/ANNOTATION/A26F1A2E-2765-4C10-942E-D2A738B80BF9

Arginine vasopressin (avp) and avp-like immunoreactivity in peripheral tissues

Publisher: The Endocrine Society

Date: 11-1986

DOI: 10.1210/EDRV-7-4-449

Abstract: People encounter large amounts of sometimes-inconsistent information about risks and benefits of alcohol consumption, and about what constitutes "low-risk" or "moderate" drinking. We used 150 in-depth interviews linked to questionnaire data to learn how people define moderate drinking and to describe the relationships between definitions, attitudes, and beliefs about moderate drinking and in iduals' drinking patterns. People adhere to definitions of moderate alcohol consumption that could put them, or others, at risk for short- or long-term negative consequences of drinking. Definitions that confused increased tolerance of alcohol with moderate drinking, and those that defined moderate drinking by the absence of short-term negative consequences or ability to maintain control over drinking, ignore long-term risks of heavy consumption. In iduals with risky attitudes were also more likely to report at-risk drinking practices. Americans have complex beliefs about benefits and risks of alcohol consumption, and public health officials have not succeeded in conveying strong or clear messages about what constitutes low-risk drinking or about dose-response effects. Different (but more consistent) approaches to public education may be needed to increase knowledge about drinking-related risks. The prevalence of erse norm-based definitions suggests that alternative normative information could help people reassess their own consumption.

Kallikrein gene expression in the rat anterior pituitary

Publisher: Elsevier BV

Date: 02-1985

DOI: 10.1016/0303-7207(85)90125-X

Abstract: The report of 'kallikrein-like' activity in the rat neuro-intermediate lobe (N-IL) and its possible involvement in pro-opiomelanocortin processing led us to explore the expression of the kallikrein gene(s) in the pituitary. Using 32P-labelled rat pancreatic kallikrein cDNA, we have shown positive hybridization for rat anterior pituitary poly(A)+ RNA, of identical size on Northern blots (approximately 1.0 kb) to rat kidney poly(A)+ RNA run in parallel. Prior adrenalectomy or ovariectomy decreased the level of kallikrein mRNA seen in the anterior pituitary total RNA from rat N-IL showed no significant hybridization. On hybridization histochemistry the anterior pituitary was strongly positive, and the neural and intermediate lobes negative. The previously reported kallikrein-like activity in the N-IL is therefore probably due to a non-kallikrein kininogenase in the anterior pituitary, kallikrein may have a physiological role in limited precursor proteolysis, but lack kininogen activity.

Gonadal steroids and anterior lobe dynorphin in the male rat

Publisher: Elsevier BV

Date: 02-1989

DOI: 10.1016/0022-4731(89)90268-9

Abstract: Immunoreactive (ir)-dynorphin levels were measured, and the species characterized by high performance liquid chromatography (HPLC), in the pituitary and hypothalamus of intact and castrate male rats. On HPLC, ir-dynorphin co-eluted with authentic dynorphin A 1-8, dynorphin A 1-17 and dynorphin 1-32 in the hypothalamus and intermediate lobe in two different reversed phase (RP)-HPLC systems, anterior lobe ir-dynorphin co-eluted uniquely with dynorphin 32 (4K dynorphin). Anterior lobe levels of total ir-dynorphin were significantly lowered 7 days after castration, while HPLC profiles in all tissues remained unchanged. The change in anterior pituitary ir-dynorphin levels was reversed in a dose-related manner by dihydrotestosterone (15-500 micrograms/100 g b. wt/day) estradiol benzoate (3 micrograms/100 g/day) was without effect. The changes on castration and androgen administration suggest that gonadal steroids play a role in the regulation of dynorphin, as well as gonadotrophins and prolactin, within the anterior pituitary gland.

Humanised xenograft models of bone metastasis revisited: Novel insights into species-specific mechanisms of cancer cell osteotropism

Publisher: Springer Science and Business Media LLC

Date: 09-05-2013

DOI: 10.1007/S10555-013-9437-5

Abstract: The determinants and key mechanisms of cancer cell osteotropism have not been identified, mainly due to the lack of reproducible animal models representing the biological, genetic and clinical features seen in humans. An ideal model should be capable of recapitulating as many steps of the metastatic cascade as possible, thus facilitating the development of prognostic markers and novel therapeutic strategies. Most animal models of bone metastasis still have to be derived experimentally as most syngeneic and transgeneic approaches do not provide a robust skeletal phenotype and do not recapitulate the biological processes seen in humans. The xenotransplantation of human cancer cells or tumour tissue into immunocompromised murine hosts provides the possibility to simulate early and late stages of the human disease. Human bone or tissue-engineered human bone constructs can be implanted into the animal to recapitulate more subtle, species-specific aspects of the mutual interaction between human cancer cells and the human bone microenvironment. Moreover, the replication of the entire "organ" bone makes it possible to analyse the interaction between cancer cells and the haematopoietic niche and to confer at least a partial human immunity to the murine host. This process of humanisation is facilitated by novel immunocompromised mouse strains that allow a high engraftment rate of human cells or tissue. These humanised xenograft models provide an important research tool to study human biological processes of bone metastasis.

Quantitative analyses of the plant cytoskeleton reveal underlying organizational principles

Publisher: The Royal Society

Date: 06-08-2014

DOI: 10.1098/RSIF.2014.0362

Abstract: The actin and microtubule (MT) cytoskeletons are vital structures for cell growth and development across all species. While in idual molecular mechanisms underpinning actin and MT dynamics have been intensively studied, principles that govern the cytoskeleton organization remain largely unexplored. Here, we captured biologically relevant characteristics of the plant cytoskeleton through a network-driven imaging-based approach allowing us to quantitatively assess dynamic features of the cytoskeleton. By introducing suitable null models, we demonstrate that the plant cytoskeletal networks exhibit properties required for efficient transport, namely, short average path lengths and high robustness. We further show that these advantageous features are maintained during temporal cytoskeletal rearrangements. Interestingly, man-made transportation networks exhibit similar properties, suggesting general laws of network organization supporting erse transport processes. The proposed network-driven analysis can be readily used to identify organizational principles of cytoskeletons in other organisms.

The roles of proteases in prostate cancer

Publisher: Wiley

Date: 04-01-2023

DOI: 10.1002/IUB.2700

Abstract: Since the proposition of the pro‐invasive activity of proteolytic enzymes over 70 years ago, several roles for proteases in cancer progression have been established. About half of the 473 active human proteases are expressed in the prostate and many of the most well‐characterized members of this enzyme family are regulated by androgens, hormones essential for development of prostate cancer. Most notably, several kallikrein‐related peptidases, including KLK3 (prostate‐specific antigen, PSA), the most well‐known prostate cancer marker, and type II transmembrane serine proteases, such as TMPRSS2 and matriptase, have been extensively studied and found to promote prostate cancer progression. Recent findings also suggest a critical role for proteases in the development of advanced and aggressive castration‐resistant prostate cancer (CRPC). Perhaps the most intriguing evidence for this role comes from studies showing that the protease‐activated transmembrane proteins, Notch and CDCP1, are associated with the development of CRPC. Here, we review the roles of proteases in prostate cancer, with a special focus on their regulation by androgens.

The Molecular Biology of the Kallikreins and their Roles in Inflammation

Publisher: Elsevier

Date: 1997

DOI: 10.1016/B978-012249340-9/50007-3

The cell surface glycoprotein CUB domain-containing protein 1 (CDCP1) contributes to epidermal growth factor receptor-mediated cell migration

Publisher: Elsevier BV

Date: 03-2012

DOI: 10.1074/JBC.M111.335448

Factors controlling the physical properties of an organic ionic plastic crystal

Publisher: Elsevier BV

Date: 2022

DOI: 10.1016/J.MTPHYS.2022.100603

Combined expression of KLK4, KLK5, KLK6, and KLK7 by ovarian cancer cells leads to decreased adhesion and paclitaxel-induced chemoresistance

Publisher: Elsevier BV

Date: 12-2012

DOI: 10.1016/J.YGYNO.2012.09.001

Abstract: Chemoresistance is a critical feature of advanced ovarian cancer with only 30% of patients surviving longer than 5 years. We have previously shown that four kallikrein-related (KLK) peptidases, KLK4, KLK5, KLK6 and KLK7 (KLK4-7), are implicated in peritoneal invasion and tumour growth, but underlying mechanisms were not identified. We also reported that KLK7 overexpression confers chemoresistance to paclitaxel, and cell survival via integrins. In this study, we further explored the functional consequenses of overexpression of all four KLKs (KLK4-7) simultaneously in the ovarian cancer cell line, OV-MZ-6, and its impact on integrin expression and signalling, cell adhesion and survival as contributors to chemoresistance and metastatic progression. Quantitative gene and protein expression analyses, confocal microscopy, cell adhesion and chemosensitivity assays were performed. Expression of α5β1/αvβ3 integrins was downregulated upon combined stable KLK4-7 overexpression in OV-MZ-6 cells. Accordingly, the adhesion of these cells to vitronectin and fibronectin, the extracellular matrix binding proteins of α5β1/αvβ3 integrins and two predominant proteins of the peritoneal matrix, was decreased. KLK4-7-transfected cells were more resistant to paclitaxel (10-100 nmol/L: 38-54%), but not to carboplatin, which was associated with decreased apoptotic stimuli. However, the KLK4-7-induced paclitaxel resistance was not blocked by the MEK1/2 inhibitor, U0126. This study demonstrates that combined KLK4-7 expression by ovarian cancer cells promotes reduced integrin expression with consequently less cell-matrix attachment, and insensitivity to paclitaxel mediated by complex integrin and MAPK independent interactions, indicative of a malignant phenotype and disease progression suggesting a role for these KLKs in this process.

Fine-mapping identifies multiple prostate cancer risk loci at 5p15, one of which associates with TERT expression

Publisher: Oxford University Press (OUP)

Date: 27-02-2013

DOI: 10.1093/HMG/DDT095

Abstract: Parkinson's disease (PD) is a common neurodegenerative disorder characterized by selective dopaminergic cell loss in the substantia nigra, but its pathogenesis remains unclear. The recessively inherited familial PD genes PARK2 and PARK6 have been attributed to mutations in the Parkin and PTEN-induced kinase 1 (PINK1) genes, respectively. Recent reports suggest that PINK1 works upstream of Parkin in the same pathway to regulate mitochondrial dynamics and/or conduct autophagic clearance of damaged mitochondria. This phenomenon is preserved from Drosophila to human cell lines but has not been demonstrated in a vertebrate animal model in vivo. Here, we developed a medaka fish (Oryzias latipes) model that is deficient in Pink1 and Parkin. We found that despite the lack of a conspicuous phenotype in single mutants for Pink1 or Parkin, medaka that are deficient in both genes developed phenotypes similar to that of human PD: late-onset locomotor dysfunction, a decrease in dopamine levels and a selective degeneration of dopaminergic neurons. Further analysis also revealed defects in mitochondrial enzymatic activity as well as cell death. Consistently, PINK1 and Parkin double-deficient MEF showed a further decrease in mitochondrial membrane potential and mitochondrial complex I activity as well as apoptosis compared with single-deficient MEF. Interestingly, these mitochondrial abnormalities in Parkin-deficient MEF were compensated by exogenous PINK1, but not by disease-related mutants. These results suggest that PINK1 and Parkin work in a complementary way to protect dopaminergic neurons by maintaining mitochondrial function in vertebrates.

Characterisation of cell lines derived from prostate cancer patients with localised disease

Publisher: Springer Science and Business Media LLC

Date: 06-2023

DOI: 10.1038/S41391-023-00679-X

Abstract: Prostate cancer is a broad-spectrum disease, spanning from indolent to a highly aggressive lethal malignancy. Prostate cancer cell lines are essential tools to understanding the basic features of this malignancy, as well as in identifying novel therapeutic strategies. However, most cell lines routinely used in prostate cancer research are derived from metastatic disease and may not fully elucidate the molecular events underlying the early stages of cancer development and progression. Thus, there is a need for new cell lines derived from localised disease to better span the disease spectrum. Prostatic tissue from the primary site, and adjacent non-cancerous tissue was obtained from four patients with localised disease undergoing radical prostatectomy. Epithelial cell outgrowths were immortalised with human papillomavirus type 16 (HPV16) E6 and E7 to establish monoclonal cell lines. Chromosomal ploidy was imaged and STR profiles were determined. Cell morphology, colony formation and cell proliferation characteristics were assessed. Androgen receptor (AR) expression and AR-responsiveness to androgen treatment were analysed by immunofluorescence and RT-qPCR, respectively. RNA-seq analysis was performed to identify prostate lineage markers and expression of prostate cancer tumorigenesis-related genes. Two benign cell lines derived from non-cancer cells (AQ0420 and AQ0396) and two tumour tissue derived cancer cell lines (AQ0411 and AQ0415) were immortalised from four patients with localised prostatic adenocarcinoma. The cell lines presented an epithelial morphology and a slow to moderate proliferative rate. None of the cell lines formed anchorage independent colonies or displayed AR-responsiveness. Comparative RNA-seq expression analysis confirmed the prostatic lineage of the four cell lines, with a distinct gene expression profile from that of the metastatic prostate cancer cell lines, PC-3 and LNCaP. Comprehensive characterization of these cell lines may provide new in vitro tools that could bridge the current knowledge gap between benign, early-stage and metastatic disease.

The effect of sample size on polygenic hazard models for prostate cancer

Publisher: Cold Spring Harbor Laboratory

Date: 21-06-2019

DOI: 10.1101/679092

Abstract: We aimed to determine the effect of s le size on performance of polygenic hazard score (PHS) models in predicting the age at onset of prostate cancer. Age and genotypes were obtained for 40,861 men from the PRACTICAL consortium. The dataset included 201,590 SNPs per subject, and was split into training (34,444 s les) and testing (6,417 s les) sets. Two PHS model-building strategies were investigated. Established-SNP model considered 65 SNPs that had been associated with prostate cancer in the literature. A stepwise SNP selection was used to develop Discovery-SNP models. The performance of each PHS model was calculated for random sizes of the training set (1 to 30 thousand). The performance of a representative Established-SNP model was estimated for random sizes of the testing set (0.5 to 6 thousand). Mean HR 98/50 (hazard ratio of top 2% to the average in the test set) of the Established-SNP model increased from 1.73[95%CI: 1.69-1.77] to 2.41[2.40-2.43] when the number of training s les was increased from 1 to 30 thousand. The corresponding HR 98/50 of the Discovery-SNP model increased from 1.05[0.93-1.18] to 2.19[2.16-2.23]. HR 98/50 of a representative Established-SNP model using testing set s le sizes of 0.6 and 6 thousand observations were 1.78[1.70-1.85] and 1.73[1.71-1.76], respectively. We estimate that a study population of 20 to 30 thousand men is required to develop Discovery-SNP PHS models for prostate cancer. The required s le size could be reduced to 10 thousand s les, if a set of SNPs associated with the disease has already been established. Polygenic hazard scores represent a recent advancement in polygenic prediction to model the age of onset of various diseases, such as Alzheimer’s disease or prostate cancer. These scores accumulate small effect sizes from several tens of genetic variants and can be used to establish an in idual’s risk of experiencing an event relative to a control population across time. The largest barrier to the development of polygenic hazard scores is the large number of study subjects needed to develop the underlying models. We sought to understand the effect of varying the total number of s les on the performance of a polygenic hazard score in the context of prostate cancer. We found that the performance of the score did not appreciably change beyond 20 to 30 thousand observations when developing the model from scratch. However, when the discovery of the genetic variants can be borrowed from those already identified in the literature to be associated with the disease, the required number of s les is reduced to 10 thousand with no appreciable detriment in performance. We hope that these results can guide the design of future studies of polygenic scores in other diseases and demonstrate the importance of genome-wide association studies.

Delineating breast cancer cell interactions with engineered bone microenvironments

Publisher: Wiley

Date: 21-05-2013

DOI: 10.1002/JBMR.1875

Abstract: The mechanisms leading to colonization of metastatic breast cancer cells (BCa) in the skeleton are still not fully understood. Here, we demonstrate that mineralized extracellular matrices secreted by primary human osteoblasts (hOBM) modulate cellular processes associated with BCa colonization of bone. A panel of four BCa cell lines of different bone-metastatic potential (T47D, SUM1315, MDA-MB-231, and the bone-seeking subline MDA-MB-231BO) was cultured on hOBM. After 3 days, the metastatic BCa cells had undergone morphological changes on hOBM and were aligned along the hOBM's collagen type I fibrils that were decorated with bone-specific proteins. In contrast, nonmetastatic BCa cells showed a random orientation on hOBM. Atomic force microscopy-based single-cell force spectroscopy revealed that the metastatic cell lines adhered more strongly to hOBM compared with nonmetastatic cells. Function-blocking experiments indicated that β1 -integrins mediated cell adhesion to hOBM. In addition, metastatic BCa cells migrated directionally and invaded hOBM, which was accompanied by enhanced MMP-2 and -9 secretion. Furthermore, we observed gene expression changes associated with osteomimickry in BCa cultured on hOBM. As such, osteopontin mRNA levels were significantly increased in SUM1315 and MDA-MB-231BO cells in a β1 -integrin-dependent manner after growing for 3 days on hOBM compared with tissue culture plastic. In conclusion, our results show that extracellular matrices derived from human osteoblasts represent a powerful experimental platform to dissect mechanisms underlying critical steps in the development of bone metastases.

Localization of a new prostate-specific antigen-related serine protease gene, KLK4, is evidence for an expanded human kallikrein gene family cluster on chromosome 19q13.3-13.4

Publisher: Elsevier BV

Date: 08-1999

DOI: 10.1074/JBC.274.33.23210

Highlight: Proteolytic networks across cellular boundaries

Publisher: Walter de Gruyter GmbH

Date: 10-08-2016

DOI: 10.1515/HSZ-2016-0256

Localization of arginine vasopressin-neurophysin II messenger ribonucleic acid in the hypothalamus of control and brattleboro rats by hybridization histochemistry with a synthetic pentadecamer oligonucleotide probe

Publisher: The Endocrine Society

Date: 06-1985

DOI: 10.1210/ENDO-116-6-2366

Abstract: By using 32P-labeled oligonucleotide probes for in situ DNA-RNA hybridization, we have defined the distribution of messenger RNA (MRNA) for arginine vasopressin-neurophysin II (AVP-NPII) in the rat hypothalamus. With a specific pentadecamer nucleotide probe, strong specific hybridization is seen in supraoptic, suprachiasmatic, and paraventricular nuclei in both Sprague-Dawley and Brattleboro rats. This finding, of equivalent distribution of AVP-NPII mRNA in Brattleboro and control hypothalami, confirms and extends the recent report of equivalent levels of AVP-NPII mRNA by Northern blot analysis.

In vitro engineering of a bone metastases model allows for study of the effects of antiandrogen therapies in advanced prostate cancer

Publisher: American Association for the Advancement of Science (AAAS)

Date: 02-07-2021

DOI: 10.1126/SCIADV.ABG2564

Abstract: In vitro engineering of a bone metastases model allows us to study the effects of antiandrogens in advanced prostate cancer.

Correlation of the expression of human kallikrein-related peptidases 4 and 7 with the prognosis in oral squamous cell carcinoma

Publisher: Wiley

Date: 21-03-2011

DOI: 10.1002/HED.21496

Abstract: Very few articles have been written about the expression of kallikreins (KLK4 and KLK7) in oral cancers. Therefore, the purpose of this study was to examine and report on their prognostic potential. Eighty archival blocks of primary oral cancers were sectioned and stained for KLK4 and KLK7 by immunohistochemistry. The percentage and the intensity of malignant keratinocyte staining were correlated with patient survival using Cox regression analysis. Both kallikreins were expressed strongly in the majority of tumor cells in 68 of 80 cases: these were mostly moderately or poorly differentiated neoplasms. Staining was particularly intense at the infiltrating front. Patients with intense staining had significantly shorter overall survival (p < .05). This is the first observation on the patient survival influenced by kallikrein expression in oral carcinoma. The findings are consistent with those for carcinomas at other sites, in particular the prostate and ovary. KLK4 and/or KLK7 immunohistochemistry seems to have diagnostic and prognostic potential in this disease.

Genome-wide association study of prostate cancer-specific survival

Publisher: American Association for Cancer Research (AACR)

Date: 11-2015

DOI: 10.1158/1055-9965.EPI-15-0543

Abstract: Background: Unnecessary intervention and overtreatment of indolent disease are common challenges in clinical management of prostate cancer. Improved tools to distinguish lethal from indolent disease are critical. Methods: We performed a genome-wide survival analysis of cause-specific death in 24,023 prostate cancer patients (3,513 disease-specific deaths) from the PRACTICAL and BPC3 consortia. Top findings were assessed for replication in a Norwegian cohort (CONOR). Results: We observed no significant association between genetic variants and prostate cancer survival. Conclusions: Common genetic variants with large impact on prostate cancer survival were not observed in this study. Impact: Future studies should be designed for identification of rare variants with large effect sizes or common variants with small effect sizes. Cancer Epidemiol Biomarkers Prev 24(11) 1796–800. ©2015 AACR.

Kallikrein 4 (hK4) and prostate-specific antigen (PSA) are associated with the loss of E-cadherin and an epithelial-mesenchymal transition (EMT)-like effect in prostate cancer cells

Publisher: Bioscientifica

Date: 09-2005

DOI: 10.1677/ERC.1.00958

Abstract: Prostate-specific antigen (PSA) and the related kallikrein family of serine proteases are current or emerging biomarkers for prostate cancer detection and progression. Kallikrein 4 ( KLK4 /hK4) is of particular interest, as KLK4 mRNA has been shown to be elevated in prostate cancer. In this study, we now show that the comparative expression of hK4 protein in prostate cancer tissues, compared with benign glands, is greater than that of PSA and kallikrein 2 ( KLK2 /hK2), suggesting that hK4 may play an important functional role in prostate cancer progression in addition to its biomarker potential. To examine the roles that hK4, as well as PSA and hK2, play in processes associated with progression, these kallikreins were separately transfected into the PC-3 prostate cancer cell line, and the consequence of their stable transfection was investigated. PC-3 cells expressing hK4 had a decreased growth rate, but no changes in cell proliferation were observed in the cells expressing PSA or hK2. hK4 and PSA, but not hK2, induced a 2.4-fold and 1.7-fold respective increase, in cellular migration, but not invasion, through Matrigel, a synthetic extracellular matrix. We hypothesised that this increase in motility displayed by the hK4 and PSA-expressing PC-3 cells may be related to the observed change in structure in these cells from a typical rounded epithelial-like cell to a spindle-shaped, more mesenchymal-like cell, with compromised adhesion to the culture surface. Thus, the expression of E-cadherin and vimentin, both associated with an epithelial-mesenchymal transition (EMT), was investigated. E-cadherin protein was lost and mRNA levels were significantly decreased in PC-3 cells expressing hK4 and PSA (10-fold and 7-fold respectively), suggesting transcriptional repression of E-cadherin, while the expression of vimentin was increased in these cells. The loss of E-cadherin and associated increase in vimentin are indicative of EMT and provides compelling evidence that hK4, in particular, and PSA have a functional role in the progression of prostate cancer through their promotion of tumour cell migration.

SEI Formation on Sodium Metal Electrodes in Superconcentrated Ionic Liquid Electrolytes and the Effect of Additive Water

Publisher: American Chemical Society (ACS)

Date: 26-01-2021

DOI: 10.1021/ACSAMI.0C18119

MicroRNA theranostics in prostate cancer precision medicine

Publisher: Oxford University Press (OUP)

Date: 10-2016

DOI: 10.1373/CLINCHEM.2015.242800

Abstract: Prostate cancer is the second most frequently diagnosed cancer in men worldwide. Theranostics, a combination of diagnostics and therapeutics, is an emerging concept in the field of precision medicine, and microRNAs (miRNAs) are predictive pioneers in this area. miRNAs are small endogenous noncoding RNA molecules that regulate gene expression posttranscriptionally by targeting messenger RNAs. More than 60% of all protein coding genes are controlled by miRNAs, which makes them powerful regulators of the different cellular processes involved in the pathogenesis of various types of cancer, including prostate cancer. Growing evidence indicates the differential expression of miRNAs in tumor tissues. In addition, miRNAs in body fluids, known as circulating miRNAs, are present in remarkably stable forms and their alteration in prostate cancer has been well documented. Circulating miRNAs are known to originate from tumor tissues, thereby enabling intercellular communication via carriers to promote tumorigenesis and malignancy. In addition, fueled by recent advances, the use of miRNA-based anticancer therapies has been proposed with the onset of early phase clinical trials to assess the therapeutic efficacy of miRNAs. In this review, we summarize the theranostic utility of miRNAs and outline their diagnostic and prognostic potential in prostate cancer. In addition, we discuss the current detection methodologies and emerging innovative strategies for the detection of miRNAs in body fluids and tumor tissues in the clinical setting. We also provide insight into the current and future therapeutic potential of miRNAs in prostate cancer.

Genetic polymorphisms in the human tissue kallikrein (KLK) locus and their implication in various malignant and non-malignant diseases

Publisher: Walter de Gruyter GmbH

Date: 13-11-2012

DOI: 10.1515/HSZ-2012-0211

Abstract: The Kallikrein ( KLK ) gene locus encodes a family of serine proteases and is the largest contiguous cluster of protease-encoding genes attributed an evolutionary age of 330 million years. The KLK locus has been implicated as a high susceptibility risk loci in numerous cancer studies through the last decade. The KLK3 gene already has established clinical relevance as a biomarker in prostate cancer prognosis through its encoded protein, prostate-specific antigen. Data mined through genome-wide association studies (GWAS) and next-generation sequencing point to many important candidate single nucleotide polymorphisms (SNPs) in KLK3 and other KLK genes. SNPs in the KLK locus have been found to be associated with several diseases including cancer, hypertension, cardiovascular disease and atopic dermatitis. Moreover, introducing a model incorporating SNPs to improve the efficiency of prostate-specific antigen in detecting malignant states of prostate cancer has been recently suggested. Establishing the functional relevance of these newly-discovered SNPs, and their interactions with each other, through in silico investigations followed by experimental validation, can accelerate the discovery of diagnostic and prognostic biomarkers. In this review, we discuss the various genetic association studies on the KLK loci identified either through candidate gene association studies or at the GWAS and post-GWAS front to aid researchers in streamlining their search for the most significant, relevant and therapeutically promising candidate KLK gene and/or SNP for future investigations.

Expression of PTRF in PC-3 cells modulates cholesterol dynamics and the actin cytoskeleton impacting secretion pathways

Publisher: Elsevier BV

Date: 02-2012

DOI: 10.1074/MCP.M111.012245

Preservation of Biospecimens at Ambient Temperature: Special Focus on Nucleic Acids and Opportunities for the Biobanking Community

Publisher: Mary Ann Liebert Inc

Date: 04-2016

DOI: 10.1089/BIO.2015.0022

Abstract: Several approaches to the preservation of biological materials at ambient temperature and the relative impact on s le stability and degradation are reviewed, with a focus on nucleic acids. This appraisal is undertaken within the framework of biobank risk, quality management systems, and accreditation, with a view to assessing how best to apply ambient temperature s le storage to ensure stability, reduce costs, improve handling logistics, and increase the efficiency of biobank procedures.

STRESS, DOPAMINERGIC BLOCKADE AND MEDIAN EMINENCE‐NEUROINTERMEDIATE LOBE CATECHOLAMINE DEPLETION: EFFECTS ON HYPOTHALAMIC, PITUITARY AND PLASMA IMMUNOREACTIVE β‐ENDORPHIN

Publisher: Wiley

Date: 06-1984

DOI: 10.1111/J.1440-1681.1984.TB00259.X

Abstract: We have compared immunoreactive beta-endorphin (ir-beta EP) levels in plasma, hypothalamus, anterior pituitary and neurointermediate lobe of adult female Sprague-Dawley rats, in studies in which levels of catecholamines were manipulated. Whole-brain catecholamines were manipulated by intraperitoneal haloperidol and/or bromocriptine median eminence and neurointermediate lobe catecholamines were manipulated specifically and differentially by intravenous 6-hydroxydopamine (6-OHDA), with and without pretreatment with intraperitoneal desipramine changes in amine neurons were assessed by fluorescence histochemistry. Haloperidol and 6-OHDA administration produced a selective reduction of neurointermediate lobe ir-beta EP, to levels equivalent to those seen with prolonged stress the haloperidol effect was blocked by bromocriptine and the 6-OHDA effect by desipramine. Specific depletion of catecholamine nerve terminals in the median eminence and the neurointermediate lobe was associated with elevated plasma ir-beta EP, with no changes in pituitary or hypothalamic levels. These studies confirm and extend previous reports documenting that ir-beta EP levels in different tissues are modulated by different neural stimuli.

Species-specific homing mechanisms of human prostate cancer metastasis in tissue engineered bone

Publisher: Elsevier BV

Date: 04-2014

DOI: 10.1016/J.BIOMATERIALS.2014.01.062

Abstract: The development of effective therapeutic strategies against prostate cancer bone metastases has been impeded by the lack of adequate animal models that are able to recapitulate the biology of the disease in humans. Bioengineered approaches allow researchers to create sophisticated experimentally and physiologically relevant in vivo models to study interactions between cancer cells and their microenvironment under reproducible conditions. The aim of this study was to engineer a morphologically and functionally intact humanized organ bone which can serve as a homing site for human prostate cancer cells. Transplantation of biodegradable tubular composite scaffolds seeded with human mesenchymal progenitor cells and loaded with rhBMP-7 resulted in the development of a chimeric bone construct including a large number of human mesenchymal cells which were shown to be metabolically active and capable of producing extracellular matrix components. Micro-CT analysis demonstrated that the newly formed ossicle recapitulated the morphological features of a physiological organ bone with a trabecular network surrounded by a cortex-like outer structure. This microenvironment was supportive of the lodgement and maintenance of murine haematopoietic cell clusters, thus mimicking a functional organ bone. Bioluminescence imaging demonstrated that luciferase-transduced human PC3 cells reproducibly homed to the humanized tissue engineered bone constructs, proliferated, and developed macro-metastases. This model allows the analysis of interactions between human prostate cancer cells and a functional humanized bone organ within an immuno-incompetent murine host. The system can serve as a reproducible platform to study effects of therapeutics against prostate cancer bone metastases within a humanized microenvironment.

Breast Cancer Cells Induce Osteolytic Bone Lesions In vivo through a Reduction in Osteoblast Activity in Mice

Publisher: Public Library of Science (PLoS)

Date: 12-09-2013

DOI: 10.1371/JOURNAL.PONE.0068103

Kallikrein-related peptidase 7 promotes multicellular aggregation via the α5β1 Integrin pathway and paclitaxel chemoresistance in serous epithelial ovarian carcinoma

Publisher: American Association for Cancer Research (AACR)

Date: 31-03-2010

DOI: 10.1158/0008-5472.CAN-09-3415

Abstract: Kallikrein-related peptidase 7 (KLK7) is upregulated in epithelial ovarian carcinoma (EOC) with high levels correlated with poor prognosis. However, the mechanisms underlying this relationship and the role of KLK7 in EOC progression are unknown. We report that two different KLK7 transcripts, KLK7-253 and KLK7-181, are simultaneously expressed in high-grade serous EOC. Multicellular aggregates (MCA), which promote cell survival and chemoresistance, were observed in SKOV-3 cells stably overexpressing KLK7-253 in particular. Importantly, these MCAs invade into a monolayer of mesothelial cells and form cancer cell foci. Blocking MCA using antibodies against KLK7 and α5β1 and β1 integrins confirmed the involvement of KLK7 and integrin-regulated cell adhesion. Increased levels of α5/β1 integrins and enhanced attachment to fibronectin and vitronectin, which was blocked with an anti–β1 integrin antibody, were also observed. Finally, Western blot and immunohistochemistry showed higher KLK7 and α5/β1 integrin levels in serous EOC cells from ascites and tumor s les from chemotherapy nonresponders with short postsurvival times. Additionally, both KLK7-253 and KLK7-181 clones were more resistant to paclitaxel treatment in vitro. These findings suggest a mechanism for the association of high KLK7 levels with chemoresistance and poor prognosis for serous EOC patients by promotion of peritoneal dissemination and reinvasion via increased MCA and α5β1 integrin–dependent cell adhesion. Cancer Res 70(7) 2624–33

Macrophase-Separated Organic Ionic Plastic Crystals/PAMPS-Based Ionomer Electrolyte: A New Design Perspective for Flexible and Highly Conductive Solid-State Electrolytes

Publisher: American Chemical Society (ACS)

Date: 03-02-2020

DOI: 10.1021/ACSOMEGA.9B03773

Opiate binding sites in bovine adrenal medulla

Publisher: Informa UK Limited

Date: 1983

DOI: 10.3109/10799898309041853

Abstract: Previous studies using a variety of opiate ligands have suggested the existence of several subclasses of opiate receptors in crude membrane fractions of rat brain, and a similar ersity in bovine adrenal medulla. To examine the receptor profile of bovine adrenal medulla in detail we have studied the binding of classical ligands for mu (mu), delta (delta) and kappa (kappa) opiate receptors. [3H]naloxone ([3H]NAL), [3H]morphine ([3H]MOR), [3H]D-Ala2-D-Leu5-enkephalin ([3H]DAL) and [3H]ethyl-ketocyclazocine ([3H]EKCZ) were used as tracers unlabeled competitors were NAL, MOR, DAL and ketocyclazocine (KCZ). In adrenal medulla [3H]NAL was specifically bound with a hierarchy of displacement NAL greater than MOR greater than KCZ much greater than DAL. No specific binding of [3H]DAL or [3H]EKCZ was found for [3H]MOR very low levels of binding were seen, with no displacement by NAL or DAL, inconsistent displacement by KCZ and substantial displacement by MOR with an ED50 of 1.5 nM. In parallel studies rat brain membranes bound each labeled ligand with affinity and specificity consistent with previously published reports. Identical results were obtained in membranes from both tissues prepared with a preincubation step including 100 mM Na+, suggesting that the results were not influenced by occupation of binding sites by endogenous ligands. We interpret these data as supporting the existence of opiate receptors of the mu subtype in bovine adrenal medulla. We find, however, no evidence of delta or kappa sites in this tissue.

Regulation of follicle-stimulating hormone β and common α-subunit messenger ribonucleic acid by gonadotropin-releasing hormone and estrogen in the sheep pituitary

Publisher: S. Karger AG

Date: 1989

DOI: 10.1159/000125240

Abstract: The effect of gonadotropin-releasing hormone (GnRH) and/or estradiol (E2) on pituitary messenger ribonucleic acid (mRNA) levels of luteinizing hormone beta (LH beta), follicle-stimulating hormone beta (FSH beta) and the common alpha-subunit were determined in anterior pituitary glands from ovariectomized (OVX) ewes. Hypothalamo-pituitary disconnected (HPD) ewes receiving appropriate hormonal treatment were used to assess the relative roles of GnRH and E2 in directly regulating FSH beta and alpha-subunit mRNA levels. Levels of LH beta mRNA were increased in OVX animals compared with intact controls, and E2 treatment of OVX animals significantly reduced mRNA levels of LH beta and FSH beta. HPD substantially reduced FSH beta and alpha-subunit mRNA levels. Treatment of OVX/HPD animals with pulses of GnRH (250 ng/2 h) for 1 week restored FSH beta and alpha-subunit mRNA to OVX levels. Combined GnRH and E2 treatment significantly lowered FSH beta mRNA levels, but resulted in a rise in alpha-subunit mRNA levels. Treatment of OVX/HPD ewes with E2 alone had no effect on FSH beta and alpha-subunit mRNA levels. These findings indicate that E2 acts directly on the pituitary to negatively regulate FSH beta mRNA levels, and to positively regulate alpha-subunit mRNA levels in the presence of GnRH.

Hybrid Artificial Solid Electrolyte Interphase with Dendrite-Free Lithium Deposition and High Ion Transport Kinetics

Publisher: American Chemical Society (ACS)

Date: 15-11-2022

DOI: 10.1021/ACSAMI.2C16604

Characterization of a novel gene,STAG1/PMEPA1, upregulated in renal cell carcinoma and other solid tumors

Publisher: Wiley

Date: 2001

DOI: 10.1002/MC.1063

Abstract: Using differential display-polymerase chain reaction, we identified a novel gene sequence, designated solid tumor-associated gene 1 (STAG1), that is upregulated in renal cell carcinoma (RCC). The full-length cDNA (4839 bp) encompassed the recently reported androgen-regulated prostatic cDNA PMEPA1, and so we refer to this gene as STAG1/PMEPA1. Two STAG1/PMEPA1 mRNA transcripts of approximately 2.7 and 5 kb, with identical coding regions but variant 3' untranslated regions, were predominantly expressed in normal prostate tissue and at lower levels in the ovary. The expression of this gene was upregulated in 87% of RCC s les and also was upregulated in stomach and rectal adenocarcinomas. In contrast, STAG1/PMEPA1 expression was barely detectable in leukemia and lymphoma s les. Analysis of expressed sequence tag databases showed that STAG1/PMEPA1 also was expressed in pancreatic, endometrial, and prostatic adenocarcinomas. The STAG1/PMEPA1 cDNA encodes a 287-amino-acid protein containing a putative transmembrane domain and motifs that suggest that it may bind src homology 3- and tryptophan tryptophan domain-containing proteins. This protein shows 67% identity to the protein encoded by the chromosome 18 open reading frame 1 gene. Translation of STAG1/PMEPA1 mRNA in vitro showed two products of 36 and 39 kDa, respectively, suggesting that translation may initiate at more than one site. Comparison to genomic clones showed that STAG1/PMEPA1 was located on chromosome 20q13 between microsatellite markers D20S183 and D20S173 and spanned four exons and three introns. The upregulation of this gene in several solid tumors indicated that it may play an important role in tumorigenesis.

Erratum to Fusion transcript loci share many genomic features with non-fusion loci [BMC Genomics. 2015;16: 1201] Doi: 10.1186/s12864-015-2235-4.

Publisher: Springer Science and Business Media LLC

Date: 03-06-2016

DOI: 10.1186/S12864-016-2751-X

Towards a high-flux separation layer from hexagonal lyotropic liquid crystals for thin-film composite membranes

Publisher: MDPI AG

Date: 29-10-2021

DOI: 10.3390/MEMBRANES11110842

Abstract: Hexagonal lyotropic liquid crystals (HLLC) with uniform pore size in the range of 1~5 nm are highly sought after as promising active separation layers of thin-film composite (TFC) membranes, which have been confirmed to be efficient for water purification. The potential interaction between an hiphile-based HLLC layer and the substrate surface, however, has not been fully explored. In this research, hydrophilic and hydrophobic microporous polyvinylidene fluoride (PVDF) substrates were chosen, respectively, to prepare TFC membranes with the active layers templated from HLLC, consisting of dodecyl trimethylammonium bromide, water, and a mixture of poly (ethylene glycol) diacrylate and 2-hydroxyethyl methacrylate. The pore size of the active layer was found to decrease by about 1.6 Å compared to that of the free-standing HLLC after polymerization, but no significant difference was observable by using either hydrophilic or hydrophobic substrates (26.9 Å vs. 27.1 Å). The water flux of the TFC membrane with the hydrophobic substrate, however, was higher than that with the hydrophilic one. A further investigation confirmed that the increase in water flux originated from a much higher porosity was due to the synergistic effect of the hydrophilic HLLC nanoporous material and the hydrophobic substrate.

Bioengineered 3D platform to explore cell-ECM interactions and drug resistance of epithelial ovarian cancer cells

Publisher: Elsevier BV

Date: 11-2010

DOI: 10.1016/J.BIOMATERIALS.2010.07.064

Abstract: The behaviour of cells cultured within three-dimensional (3D) structures rather than onto two-dimensional (2D) culture plastic more closely reflects their in vivo responses. Consequently, 3D culture systems are becoming crucial scientific tools in cancer cell research. We used a novel 3D culture concept to assess cell-matrix interactions implicated in carcinogenesis: a synthetic hydrogel matrix equipped with key biomimetic features, namely incorporated cell integrin-binding motifs (e.g. RGD peptides) and the ability of being degraded by cell-secreted proteases (e.g. matrix metalloproteases). As a cell model, we chose epithelial ovarian cancer, an aggressive disease typically diagnosed at an advanced stage when chemoresistance occurs. Both cell lines used (OV-MZ-6, SKOV-3) proliferated similarly in 2D, but not in 3D. Spheroid formation was observed exclusively in 3D when cells were embedded within hydrogels. By exploiting the design flexibility of the hydrogel characteristics, we showed that proliferation in 3D was dependent on cell-integrin engagement and the ability of cells to proteolytically remodel their extracellular microenvironment. Higher survival rates after exposure to the anti-cancer drug paclitaxel were observed in cell spheroids grown in hydrogels (40-60%) compared to cell monolayers in 2D (20%). Thus, 2D evaluation of chemosensitivity may not reflect pathophysiological events seen in patients. Because of the design flexibility of their characteristics and their stability in long-term cultures (28 days), these biomimetic hydrogels represent alternative culture systems for the increasing demand in cancer research for more versatile, physiologically relevant and reproducible 3D matrices.

Kallikrein gene family expression in the rat ovary: Localization to the granulosa cell

Publisher: The Endocrine Society

Date: 03-1995

DOI: 10.1210/ENDO.136.3.7867567

Abstract: The glandular or tissue kallikreins are a multigene family of serine proteases, of which 13 genes (rKLK1-13) have been identified in the rat and are expressed in a wide variety of tissues. Kallikrein-like enzyme activity has been detected during the periovulatory period in the gonadotropin-primed immature female rat ovary and suggested to play a role in the inflammatory-like response at ovulation. In this study, we examined whether this enzyme activity was due to local expression of a rat KLK gene family member. Ovarian RNA, prepared from gonadotropin-treated animals, was assessed for rKLK gene expression by reverse transcriptase-polymerase chain reaction (RT-PCR) with universal rKLK primers derived from highly conserved regions in the rat KLK genes. Southern blot analysis of the RT-PCR products, using oligonucleotide probes specific for the in idual genes, indicated that five rKLK gene family members, rKLK1 (encoding true kallikrein), rKLK3, rKLK7, rKLK8, and rKLK9, were expressed at varying levels in the ovaries of both untreated control and gonadotropin-treated immature female rats. The identities of these five rKLK messenger RNAs were further confirmed by DNA sequence analysis of the PCR products. In situ hybridization of gonadotropin-treated ovaries localized rKLK3 and rKLK7 gene expression to the luteinizing granulosa cells of periovulatory follicles. In an enriched population of nonluteinizing granulosa cells prepared from estrogen-primed animals, we also demonstrated rKLK3, rKLK7, rKLK9, and rKLK12 (but not rKLK1 or rKLK8) expression, whereas all six genes were expressed in the ovaries of these animals. In summary, we have reported the expression of six KLK gene family members in the rat ovary and localized this expression primarily to the granulosa cell. The potential roles of these enzymes in ovulation or other aspects of ovarian, particularly granulosa cell, function are yet to be elucidated.

Enter the Dragon: The Dynamic and Multifunctional Evolution of Anguimorpha Lizard Venoms

Publisher: MDPI AG

Date: 06-08-2017

DOI: 10.3390/TOXINS9080242

Functional Binders Based on Polymeric Ionic Liquids for Sodium Oxygen Batteries Using Ionic Liquid Electrolytes

Publisher: American Chemical Society (ACS)

Date: 11-01-2021

DOI: 10.1021/ACSAEM.0C02352

High-Performance Cycling of Na Metal Anodes in Phosphonium and Pyrrolidinium Fluoro(sulfonyl)imide Based Ionic Liquid Electrolytes

Publisher: American Chemical Society (ACS)

Date: 22-03-2022

DOI: 10.1021/ACSAMI.1C24812

Abstract: We have investigated the sodium electrochemistry and the evolution and chemistry of the solid-electrolyte interphase (SEI) upon cycling Na metal electrodes in two ionic liquid (IL) electrolytes. The effect of the IL cation chemistry was determined by examining the behavior of a phosphonium IL (P

Hypermethylation of the 5′ CpG island of the gene encoding the serine protease Testisin promotes its loss in testicular tumorigenesis

Publisher: Springer Science and Business Media LLC

Date: 02-2005

DOI: 10.1038/SJ.BJC.6602373

A meta-analysis of 87,040 individuals identifies 23 new susceptibility loci for prostate cancer

Publisher: Springer Science and Business Media LLC

Date: 14-09-2014

DOI: 10.1038/NG.3094

TTYH2, a human homologue of the Drosophila melanogaster gene tweety, is located on 17q24 and upregulated in renal cell carcinoma

Publisher: Elsevier BV

Date: 10-2001

DOI: 10.1006/GENO.2001.6629

Assays for Qualification and Quality Stratification of Clinical Biospecimens Used in Research: A Technical Report from the ISBER Biospecimen Science Working Group

Publisher: Mary Ann Liebert Inc

Date: 10-2016

DOI: 10.1089/BIO.2016.0018

Genetic Association of the KLK4 Locus with Risk of Prostate Cancer

Publisher: Public Library of Science (PLoS)

Date: 06-09-2012

DOI: 10.1371/JOURNAL.PONE.0044520

Epithelial - Mesenchymal and mesenchymal - Epithelial transitions in carcinoma progression

Publisher: Wiley

Date: 06-08-2007

DOI: 10.1002/JCP.21223

Abstract: Like a set of bookends, cellular, molecular, and genetic changes of the beginnings of life mirror those of one of the most common cause of death--metastatic cancer. Epithelial to mesenchymal transition (EMT) is an important change in cell phenotype which allows the escape of epithelial cells from the structural constraints imposed by tissue architecture, and was first recognized by Elizabeth Hay in the early to mid 1980's to be a central process in early embryonic morphogenesis. Reversals of these changes, termed mesenchymal to epithelial transitions (METs), also occur and are important in tissue construction in normal development. Over the last decade, evidence has mounted for EMT as the means through which solid tissue epithelial cancers invade and metastasize. However, demonstrating this potentially rapid and transient process in vivo has proven difficult and data connecting the relevance of this process to tumor progression is still somewhat limited and controversial. Evidence for an important role of MET in the development of clinically overt metastases is starting to accumulate, and model systems have been developed. This review details recent advances in the knowledge of EMT as it occurs in breast development and carcinoma and prostate cancer progression, and highlights the role that MET plays in cancer metastasis. Finally, perspectives from a clinical and translational viewpoint are discussed.

The human kallikrein gene family: a diversity of expression and function

Publisher: Elsevier BV

Date: 02-1994

DOI: 10.1016/0303-7207(94)90138-4

Kallikrein-related peptidase 3 (KLK3/PSA) single nucleotide polymorphisms and ovarian cancer survival

Publisher: Cambridge University Press (CUP)

Date: 08-2011

DOI: 10.1375/TWIN.14.4.323

Abstract: There is substantial evidence suggesting a role for hormone-regulated kallikrein-related peptidases (KLKs) in carcinogenesis and tumour metastasis. KLKs are considered to have potential as prognostic biomarkers for hormone dependent cancers, particularly ovarian cancer. The purpose of this study was to evaluate the association between Kallikrein-related peptidase 3 (KLK3) gene single nucleotide polymorphisms (SNPs) located in hormone response elements and ovarian cancer survival. DNA s les were analyzed from 304 Australian women diagnosed with epithelial ovarian cancer. The KLK3 rs266882 and rs11084033 SNPs were genotyped by the Sequenom iPLEX Mass Array platform. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox regression models. An association was observed with ovarian cancer survival for homozygote carriers of the rare allele of rs11084033 (adjusted HR 2.12, 95% CI 1.08–4.15). This finding is consistent with bioinformatic analysis predicting the rs11084033 rare allele to be responsible for the loss of a confirmed androgen response element, and with published expression data suggesting that aggressive ovarian cancers show decreased KLK3 tumor expression. The rs11084033 has potential prognostic significance in ovarian cancer. However, this finding requires replication, and further investigation regarding the functional significance of rs11084033 and correlated SNPs.

Activation of membrane-bound proteins and receptor systems: A link between tissue kallikrein and the KLK-related peptidases

Publisher: Walter de Gruyter GmbH

Date: 18-04-2014

DOI: 10.1515/HSZ-2014-0147

Abstract: The 15 members of the kallikrein-related serine peptidase (KLK) family have erse tissue-specific expression profiles and roles in a range of cellular processes, including proliferation, migration, invasion, differentiation, inflammation and angiogenesis that are required in both normal physiology as well as pathological conditions. These roles require cleavage of a range of substrates, including extracellular matrix proteins, growth factors, cytokines as well as other proteinases. In addition, it has been clear since the earliest days of KLK research that cleavage of cell surface substrates is also essential in a range of KLK-mediated cellular processes where these peptidases are essentially acting as agonists and antagonists. In this review we focus on these KLK-regulated cell surface receptor systems including bradykinin receptors, proteinase-activated receptors, as well as the plasminogen activator, ephrins and their receptors, and hepatocyte growth factor/Met receptor systems and other plasma membrane proteins. From this analysis it is clear that in many physiological and pathological settings KLKs have the potential to regulate multiple receptor systems simultaneously an important issue when these peptidases and substrates are targeted in disease.

The Human Tissue Kallikrein and Kallikrein-related Peptidase Family

Publisher: Elsevier

Date: 2013

DOI: 10.1016/B978-0-12-382219-2.00606-2

Expression analysis of ?-catenin and prostate-specific membrane antigen: Their potential as diagnostic markers for prostate cancer

Publisher: Wiley

Date: 14-06-2002

DOI: 10.1002/IJC.10468

Abstract: The current approach to prostate cancer diagnosis has major limitations including the inability of prostate-specific antigen (PSA) assays to accurately differentiate between prostate cancer and benign prostate hyperplasia (BPH) and the imprecision of transrectal ultrasound (TRUS) biopsy s ling. We have employed cDNA microarray screening to compare gene expression patterns in BPH and tumour s les to identify expression markers that may be useful in discriminating between these conditions. Screening of 3 in idual cDNA arrays identified 8 genes with expression 3-fold greater in 6 tumour tissues than in 1 nontumour s le and 1 BPH s le. Real-time PCR was used to confirm the overexpression of these 8 genes and 12 genes selected from the literature against a panel of 17 tumours and 11 BPH s les. Two genes, delta-catenin (delta-catenin CTNND2) and prostate-specific membrane antigen (PSMA FOLH1), were significantly overexpressed in prostate cancer compared to BPH. Prostate epithelial cells stained positively for delta-catenin and PSMA in our prostate cancer tissues, whereas the majority of our BPH tissues were negative for both markers. Thus we have identified delta-catenin (not previously associated with prostatic adenocarcinoma) and confirmed the potential of PSMA as potential candidates for the diagnosis and management of prostate cancer.

Substrate-Guided Design of a Potent and Selective Kallikrein-Related Peptidase Inhibitor for Kallikrein 4

Publisher: Elsevier BV

Date: 06-2009

DOI: 10.1016/J.CHEMBIOL.2009.05.008

Abstract: Human kallikrein-related peptidase 4 (KLK4 rostase), a trypsin-like serine protease, is a potential target for prostate cancer treatment because of its proteolytic ability to activate many tumorigenic and metastatic pathways including the protease activated receptors (PARs). Currently there are no KLK4-specific small-molecule inhibitors available for therapeutic development. Here we re-engineer the naturally occurring sunflower trypsin inhibitor to selectively block the proteolytic activity of KLK4 and prevent stimulation of PAR activity in a cell-based system. The re-engineered inhibitor was designed using a combination of molecular modeling and sparse matrix substrate screening.

Analysis of androgen and anti-androgen regulation of KLK-related peptidase 2, 3, and 4 alternative transcripts in prostate cancer

Publisher: Walter de Gruyter GmbH

Date: 06-08-2014

DOI: 10.1515/HSZ-2014-0149

Abstract: We assessed whether alternative transcripts (using KLK2 , KLK3 and KLK4 as models) are differentially regulated by androgens and anti-androgens as an indicator of prostate cancers as they acquire treatment resistance. Using RNAseq of LNCaP cells treated with dihydrotestosterone, bicalutamide and enzalutamide, we show that the expression of variant KLK transcripts is markedly different to other variant transcripts at those loci. We also reveal that KLK variants are also over 2-fold more highly expressed in prostate cancers compared to their corresponding normal prostate. We propose that androgens and anti-androgens can activate specific variant transcripts of critical prostate cancer genes during treatment resistance.

Engineering Schottky-like and heterojunction materials for enhanced photocatalysis performance – a review

Publisher: Royal Society of Chemistry (RSC)

Date: 2022

DOI: 10.1039/D1MA01062J

Abstract: Photocatalysis with nanostructured semiconductors is emerging for environmental remediation.

Association between prostinogen (KLK15) genetic variants and prostate cancer risk and aggressiveness in australia and a meta-analysis of GWAS data

Publisher: Public Library of Science (PLoS)

Date: 23-11-2011

DOI: 10.1371/JOURNAL.PONE.0026527

Risk analysis of prostate cancer in practical, a multinational consortium, using 25 known prostate cancer susceptibility loci

Publisher: American Association for Cancer Research (AACR)

Date: 07-2015

DOI: 10.1158/1055-9965.EPI-14-0317

Abstract: Background: Genome-wide association studies have identified multiple genetic variants associated with prostate cancer risk which explain a substantial proportion of familial relative risk. These variants can be used to stratify in iduals by their risk of prostate cancer. Methods: We genotyped 25 prostate cancer susceptibility loci in 40,414 in iduals and derived a polygenic risk score (PRS). We estimated empirical odds ratios (OR) for prostate cancer associated with different risk strata defined by PRS and derived age-specific absolute risks of developing prostate cancer by PRS stratum and family history. Results: The prostate cancer risk for men in the top 1% of the PRS distribution was 30.6 (95% CI, 16.4–57.3) fold compared with men in the bottom 1%, and 4.2 (95% CI, 3.2–5.5) fold compared with the median risk. The absolute risk of prostate cancer by age of 85 years was 65.8% for a man with family history in the top 1% of the PRS distribution, compared with 3.7% for a man in the bottom 1%. The PRS was only weakly correlated with serum PSA level (correlation = 0.09). Conclusions: Risk profiling can identify men at substantially increased or reduced risk of prostate cancer. The effect size, measured by OR per unit PRS, was higher in men at younger ages and in men with family history of prostate cancer. Incorporating additional newly identified loci into a PRS should improve the predictive value of risk profiles. Impact: We demonstrate that the risk profiling based on SNPs can identify men at substantially increased or reduced risk that could have useful implications for targeted prevention and screening programs. Cancer Epidemiol Biomarkers Prev 24(7) 1121–9. ©2015 AACR.

A bioengineered 3D ovarian cancer model for the assessment ofpeptidase-mediated enhancement of spheroid growth andintraperitoneal spread

Publisher: Elsevier BV

Date: 10-2013

DOI: 10.1016/J.BIOMATERIALS.2013.06.009

Abstract: Cancer-associated proteases promote peritoneal dissemination and chemoresistance in malignant progression. In this study, kallikrein-related peptidases 4, 5, 6, and 7 (KLK4-7)-cotransfected OV-MZ-6 ovarian cancer cells were embedded in a bioengineered three-dimensional (3D) microenvironment that contains RGD motifs for integrin engagement to analyze their spheroid growth and survival after chemotreatment. KLK4-7-cotransfected cells formed larger spheroids and proliferated more than controls in 3D, particularly within RGD-functionalized matrices, which was reduced upon integrin inhibition. In contrast, KLK4-7-expressing cell monolayers proliferated less than controls, emphasizing the relevance of the 3D microenvironment and integrin engagement. In a spheroid-based animal model, KLK4-7-overexpression induced tumor growth after 4 weeks and intraperitoneal spread after 8 weeks. Upon paclitaxel administration, KLK4-7-expressing tumors declined in size by 91% (controls: 87%) and showed 90% less metastatic outgrowth (controls: 33%, P < 0.001). KLK4-7-expressing spheroids showed 53% survival upon paclitaxel treatment (controls: 51%), accompanied by enhanced chemoresistance-related factors, and their survival was further reduced by combination treatment of paclitaxel with KLK4/5/7 (22%, P = 0.007) or MAPK (6%, P = 0.006) inhibition. The concomitant presence of KLK4-7 in ovarian cancer cells together with integrin activation drives spheroid formation and proliferation. Combinatorial approaches of paclitaxel and KLK/MAPK inhibition may be more efficient for late-stage disease than chemotherapeutics alone as these inhibitory regimens reduced cancer spheroid growth to a greater extent than paclitaxel alone.

Pubertal development and prostate cancer risk: Mendelian randomization study in a population-based cohort

Publisher: Springer Science and Business Media LLC

Date: 04-04-2016

DOI: 10.1186/S12916-016-0602-X

Development of tris(amino)phosphonium electrolytes for high performing sodium batteries

Publisher: Royal Society of Chemistry (RSC)

Date: 2023

DOI: 10.1039/D3TA03741J

Simplified Radioimmunoassay for Serum Aldosterone Utilizing Increased Antibody Specificity

Publisher: The Endocrine Society

Date: 04-1974

DOI: 10.1210/JCEM-38-4-622

Abstract: Acute kidney injury is a severe complication of cardiac surgery associated with increased morbidity and mortality yet, acute kidney injury classification for neonates remains challenging. We characterized patterns of postoperative fluid overload as a surrogate marker for acute kidney injury and as a risk factor of poor postoperative outcomes in neonates undergoing cardiac surgery. Retrospective cohort study. Single, congenital heart center destination program. Four hundred thirty-five neonates undergoing cardiac surgery with cardiopulmonary bypass from January 2006 through December 2010. None. Demographics, diagnosis, and perioperative clinical variables were collected, including daily weights and serum creatinine levels. A composite poor clinical outcome (death, need for renal replacement therapy or extracorporeal life support within 30 postoperative days) was considered the primary outcome measure. Twenty-one neonates (5%) had a composite poor outcome with 7 (2%) requiring renal replacement therapy, 8 (2%) requiring extracorporeal life support, and 14 (3%) dying between 3 and 30 days post surgery. Neonates with a composite poor outcome had significantly higher maximum fluid overload (> 20%) and were slower to diurese. A receiver-operating characteristic curve determined that fluid overload greater than or equal to 16% and serum creatinine greater than or equal to 0.9 on postoperative day 3 were the optimal cutoffs for significant discrimination on the primary outcome (area under the curve = 0.71 and 0.76, respectively). In multivariable analysis, fluid overload greater than or equal to 16% (adjusted odds ratio = 3.7) and serum creatinine adjusted odds ratio 0.9 (adjusted odds ratio = 6.6) on postoperative day 3 remained an independent risk factor for poor outcome. Fluid overload greater than or equal 16% was also significantly associated with cardiac arrest requiring cardiopulmonary resuscitation, prolonged ICU stay, and chest reexploration. This study highlights the importance of monitoring fluid balance in the neonatal cardiac surgical population and suggests that daily fluid overload, a readily available, noninvasive marker of renal function, may be a sensitive and specific predictor of adverse outcomes.

Naloxone, Adrenalectomy, and Steroid Replacement:Evidence against a Role for Circulating β-Endorphin in Food Intake

Publisher: The Endocrine Society

Date: 1981

DOI: 10.1210/ENDO-108-1-189

Abstract: Naloxone has a dose-dependent, significant anorectic effect when administered to normal rats, consistent with an antagonism of central or peripheral enkephalinergic or endorphinergic mechanisms. Mean levels of circulating immunoreactive beta-endorphin were similar in intact rats (0.5 ng/ml) and dexamethasone-treated adrenalectomized rats (0.5 ng/ml). In contrast, plasma levels were high in adrenalectomized rats with no replacement steroid (1.3 ng/ml) and in adrenalectomized rats given the mineralocorticoid deoxycorticosterone (0.9 ng/ml). In sharp distinction to the clear changes in circulating immunoreactive beta-endorphin produced by adrenalectomy and selective steroid replacement, no differences were seen in baseline food intake or anorectic response to naloxone. We conclude that a physiological role for circulating beta-endorphin in the regulation of food intake appears unlikely.

Atomic Layer Deposition of the Geometry Separated Lewis and Brønsted Acid Sites for Cascade Glucose Conversion

Publisher: American Chemical Society (ACS)

Date: 06-09-2023

DOI: 10.1021/JACSAU.3C00396

Candidate gene association studies: A comprehensive guide to useful in silico tools

Publisher: Springer Science and Business Media LLC

Date: 09-05-2013

DOI: 10.1186/1471-2156-14-39

Abstract: The candidate gene approach has been a pioneer in the field of genetic epidemiology, identifying risk alleles and their association with clinical traits. With the advent of rapidly changing technology, there has been an explosion of in silico tools available to researchers, giving them fast, efficient resources and reliable strategies important to find casual gene variants for candidate or genome wide association studies (GWAS). In this review, following a description of candidate gene prioritisation, we summarise the approaches to single nucleotide polymorphism (SNP) prioritisation and discuss the tools available to assess functional relevance of the risk variant with consideration to its genomic location. The strategy and the tools discussed are applicable to any study investigating genetic risk factors associated with a particular disease. Some of the tools are also applicable for the functional validation of variants relevant to the era of GWAS and next generation sequencing (NGS).

Electro-catalytic membrane reactors for the degradation of organic pollutants-A review

Publisher: Royal Society of Chemistry (RSC)

Date: 2021

DOI: 10.1039/D1RE00091H

Abstract: Electro-catalytic membrane reactor exhibiting electro-oxidation degradation of organic pollutants on anodic membrane.

Lycopene's effects on cancer cell functions within monolayer and spheroid cultures

Publisher: Informa UK Limited

Date: 17-02-2016

DOI: 10.1080/01635581.2016.1150498

Abstract: Lycopene, a compound that blocks the action of free radicals and oxygen molecules, is found in tomatoes and tomato-based products and linked to a reduced incidence of cancer. Increasing willingness of patients to maintain a healthy lifestyle by supplemental intake of nutrients and acceptance of alternative therapeutics has boosted research into nutraceuticals. The potential of lycopene to prevent or treat cancer has been investigated, but outcomes are inconsistent and its mode of action is still unknown. Further studies are needed to understand the role of lycopene in cancer prevention and treatment. The impact of lycopene on viability, proliferation, migration, and invasion of five different cancer cell lines was determined using monolayer and spheroid cultures. Cell viability was significantly reduced upon lycopene treatment at physiologically attainable concentrations. Cell proliferation, migration, and invasion did not change upon lycopene treatment. Ovarian cancer spheroids initially showed a decreased proliferation and after 14 days increased cell viability upon lycopene treatment, confirming the potential of lycopene to reduce cancer cell growth in short-term cultures and also indicate enhanced cell viability over prolonged exposure. This study cannot substantiate that lycopene inhibits cell functions associated with tumor growth, even in a 3D cancer model that mimics the natural tumor microenvironment.

Selective Substrates and Inhibitors for Kallikrein-Related Peptidase 7 (KLK7) Shed Light on KLK Proteolytic Activity in the Stratum Corneum

Publisher: Elsevier BV

Date: 02-2017

DOI: 10.1016/J.JID.2016.09.017

Abstract: Proteases have pivotal roles in the skin's outermost layer, the epidermis. In the stratum corneum, serine proteases from the kallikrein-related peptidase (KLK) family have been implicated in several key homeostatic processes, including desquamation. However, the precise contribution of specific KLKs to each process remains unclear. To address this, we used a chemical biology approach and designed selective substrates and inhibitors for KLK7, the most abundant KLK protease in the stratum corneum. The resulting KLK7 inhibitor is the most potent inhibitor of this protease reported to date (K

Transforming the Future of Treatment for Ovarian Cancer

Publisher: OMICS Publishing Group

Date: 2014

DOI: 10.4172/2161-1459.1000157

Elevated plasma levels of pro-opiomelanocortin-derived peptides in sheep following hypothalamo-pituitary disconnection

Publisher: S. Karger AG

Date: 1986

DOI: 10.1159/000124693

Abstract: We have studied the control of the pituitary-adrenal axis in ovariectomized sheep following hypothalamo-pituitary disconnection (HPD) by following plasma levels of immunoreactive (ir-) products of pro-opiomelanocortin (POMC). In ovariectomized HPD ewes, gonadotropin levels were below detection limits. In contrast, levels of ir-ACTH were modestly but significantly elevated over those in matched ovariectomized control ewes, though cortisol levels were not significantly different levels of ir-alpha MSH and ir-beta EP (beta-endorphin) were substantially and significantly raised in HPD compared with control plasma. Size exclusion HPLC showed plasma beta EP/beta LPH (beta-lipotropin) levels to be higher in HPD than control ewes. Dexamethasone administration lowered plasma ir-ACTH but not ir-beta EP in contrast, bromocriptine lowered ir-beta EP but not ir-ACTH. We interpret these data as evidence (1) that the elevated plasma levels of ir-beta EP and ir-alpha MSH post-HPD reflect the release of the intermediate lobe from tonic inhibitory dopaminergic control and (2) that, unlike the gonadotrope, hypothalamic releasing factors are not required for the maintenance of the corticotrope, or for baseline secretion of ACTH from these cells.

Single‐ion conducting polymer as lithium salt additive in polymerized ionic liquid block copolymer electrolyte

Publisher: Wiley

Date: 02-03-2023

DOI: 10.1002/APP.53809

Abstract: Herein, we describe the use of single‐ion conducting block copolymer (SIC) as an additional lithium salt additive to a ternary solid polymer electrolyte (SPE), consisting of a poly(styrene‐ b ‐1‐((2‐acryloyloxy)ethyl)‐3‐butylimidazolium bis(trifluoromethanesulfo‐nyl)imide) (S‐ImTFSI 64‐16 ) block copolymer, a N ‐propyl‐ N ‐methylpyrrolidinium bis(fluorosulfonyl)imide (C 3 mpyrFSI) ionic liquid (IL) and a lithium bis(fluorosulfonyl) imide (LiFSI) salt. For this purpose, the S‐ImTFSI 64‐16 was substituted by a SIC, based on poly(styrene‐ b ‐((4‐styrenesulfonyl)(trifluoromethanesulfonyl)imide lithium salt)) (S‐STFSILi 64‐16 ), at various molar ratios. The impact of the SIC concentration on the phase behavior and transport properties of the SPEs was investigated by means of differential scanning calorimetry, electrochemical impedance spectroscopy, and diffusion NMR. In addition, the electrochemical performance of the SPEs was assessed in lithium symmetrical cell at 50 and 80°C. Finally, the cycling performance of a selected SPE was also assessed at 80°C in a Li│NMC 111 cell with capacity loading of 1.3 mAh.cm −2 at a C‐rate of 0.1 C. The Li│NMC 111 full cell was able to deliver a stable capacity of 0.94 mAh.cm −2 after 20 cycles, corresponding to a capacity of 117 mAh.g −1 . These results demonstrates that PIL block copolymer—IL—salt composites represent a promising choice of electrolyte for the next generation of solid‐state high energy density lithium metal batteries.

A humanised tissue-engineered bone model allows species-specific breast cancer-related bone metastasis in vivo

Publisher: Hindawi Limited

Date: 29-11-2018

DOI: 10.1002/TERM.2517

Abstract: Bone metastases frequently occur in the advanced stages of breast cancer. At this stage, the disease is deemed incurable. To date, the mechanisms of breast cancer-related metastasis to bone are poorly understood. This may be attributed to the lack of appropriate animal models to investigate the complex cancer cell-bone interactions. In this study, two established tissue-engineered bone constructs (TEBCs) were applied to a breast cancer-related metastasis model. A cylindrical medical-grade polycaprolactone-tricalcium phosphate scaffold produced by fused deposition modelling (scaffold 1) was compared with a tubular calcium phosphate-coated polycaprolactone scaffold fabricated by solution electrospinning (scaffold 2) for their potential to generate ectopic humanised bone in NOD/SCID mice. While scaffold 1 was found not suitable to generate a sufficient amount of ectopic bone tissue due to poor ectopic integration, scaffold 2 showed excellent integration into the host tissue, leading to bone formation. To mimic breast cancer cell colonisation to the bone, MDA-MB-231, SUM1315, and MDA-MB-231BO breast cancer cells were cultured in polyethylene glycol-based hydrogels and implanted adjacent to the TEBCs. Histological analysis indicated that the breast cancer cells induced an osteoclastic reaction in the TEBCs, demonstrating analogies to breast cancer-related bone metastasis seen in patients.

Plastic crystal-based electrolytes using novel dicationic salts

Publisher: Royal Society of Chemistry (RSC)

Date: 2022

DOI: 10.1039/D1CP04314E

Abstract: The thermal and structural properties of novel pyrrolidinium dicationic salts with varying alkyl-chain lengths are investigated, neat and in combination with lithium salts.

Study of Ion Transport in Novel Protic Polymerized Ionic Liquids and Composites

Publisher: Wiley

Date: 10-07-2022

DOI: 10.1002/MACP.202200124

Abstract: In this work, a novel protic polymerized ionic liquid [PSTFSI][Im] is synthesized. The [PSTFSI][Im] polymer presents moderate ionic conductivity and evidences proton activity. Incorporating protic ionic liquid (Protic IL) [MIm][TFSI], the composites present enhanced ionic conductivity, up to 10 −3 S cm −1 at 120 °C upon addition of 60 wt% [MIm][TFSI]. It is found that the [PSTFSI][Im] polymer matrix can promote ion dissociation of the [MIm][TFSI] IL, leading to a larger cation/anion relative mobility compared to the neat Protic IL. This work demonstrates the potential of protic PolyIL as a polymer matrix for proton conductors.

3D cultures of prostate cancer cells cultured in a novel high-throughput culture platform are more resistant to chemotherapeutics compared to cells cultured in monolayer

Publisher: Public Library of Science (PLoS)

Date: 07-11-2014

DOI: 10.1371/JOURNAL.PONE.0111029

Anion-Derived Solid-Electrolyte Interphase Enables Long Life Na-Ion Batteries Using Superconcentrated Ionic Liquid Electrolytes

Publisher: American Chemical Society (ACS)

Date: 14-06-2021

DOI: 10.1021/ACSENERGYLETT.1C00816

Comparative biomarker expression and RNA integrity in biospecimens derived from radical retropubic and robot-assisted laparoscopic prostatectomies

Publisher: American Association for Cancer Research (AACR)

Date: 07-2010

DOI: 10.1158/1055-9965.EPI-10-0059

Abstract: Background: Knowledge of preanalytic conditions that biospecimens are subjected to is critically important because novel surgical procedures, tissue s ling, handling, and storage might affect biomarker expression or invalidate tissue s les as analytes for some technologies. Methods: We investigated differences in RNA quality, gene expression by quantitative real-time PCR, and immunoreactive protein expression of selected prostate cancer biomarkers between tissues from retropubic radical prostatectomy (RRP) and robot-assisted laparoscopic prostatectomy (RALP). Sections of tissue microarray of 23 RALP and 22 RRP s les were stained with antibodies to androgen receptor (AR) and prostate-specific antigen (PSA) as intersite controls, and 14 other candidate biomarkers of research interest to three laboratories within the Australian Prostate Cancer BioResource tissue banking network. Quantitative real-time PCR was done for AR, PSA (KLK3), KLK2, KLK4, and HIF1A on RNA extracted from five RALP and five RRP frozen tissue cores. Results: No histologic differences were observed between RALP and RRP tissue. Biomarker staining grouped these s les into those with increased (PSA, CK8/18, CKHMW, KLK4), decreased (KLK2, KLK14), or no change in expression (AR, ghrelin, Ki67, PCNA, VEGF-C, PAR2, YB1, p63, versican, and chondroitin 0-sulfate) in RALP compared with RRP tissue. No difference in RNA quality or gene expression was detected between RALP and RRP tissue. Conclusions: Changes in biomarker expression between RALP and RRP tissue exist at the immunoreactive protein level, but the etiology is unclear. Impact: Future studies should account for changes in biomarker expression when using RALP tissues, and mixed cohorts of RALP and RRP tissue should be avoided. Cancer Epidemiol Biomarkers Prev 19(7) 1755–65. ©2010 AACR.

Common variation in Kallikrein genes KLK5, KLK6, KLK12, and KLK13 and risk of prostate cancer and tumor aggressiveness

Publisher: Elsevier BV

Date: 07-2013

DOI: 10.1016/J.UROLONC.2011.05.011

Abstract: The human tissue Kallikrein family consists of 15 genes with the majority shown to be differentially expressed in cancers and/or indicators of cancer prognosis. We sought to elucidate the role of common genetic variation in four of the Kallikrein genes, KLK5, KLK6, KLK12, and KLK13, in prostate cancer risk and tumor aggressiveness. Genotyping of all 22 tagging single nucleotide polymorphisms (tagSNPs) in the KLK5, KLK6, KLK12, and KLK13 genes was performed in approximately 1,000 prostate cancer cases and 1,300 male controls from Australia. Data from any positive results were also accessed for 1,844 cases and 1,886 controls from a previously published prostate cancer genome-wide association study set from the United Kingdom. For one SNP in KLK12, rs3865443, there was evidence for association with prostate cancer risk of similar direction and magnitude in the replication set to that seen in the Australian cohort. We conducted genotyping of a further 309 prostate cancer cases, and combined analyses revealed an increased risk of prostate cancer for carriers of the rare homozygous genotype for rs3865443 (OR 1.28, 95% CI 1.04-1.57 P = 0.018). No other tagSNPs in the KLK5, KLK6, and KLK13 genes were consistently associated with prostate cancer risk or tumor aggressiveness. Analysis of a combined s le of 3,153 cases and 3,199 controls revealed the KLK12 tagSNP rs3865443 to be marginally statistically significantly associated with risk of prostate cancer. Considering the total number of SNPs investigated in this study, this finding should be interpreted cautiously and requires additional validation from very large datasets such as those of the Prostate Cancer Association group to investigate cancer associated alterations (PRACTICAL) Consortium.

Growth of confined cancer spheroids: A combined experimental and mathematical modelling approach

Publisher: Oxford University Press (OUP)

Date: 2013

DOI: 10.1039/C3IB20252F

Abstract: A critical step in the dissemination of ovarian cancer is the formation of multicellular spheroids from cells shed from the primary tumour. The objectives of this study were to apply bioengineered three-dimensional (3D) microenvironments for culturing ovarian cancer spheroids in vitro and simultaneously to build on a mathematical model describing the growth of multicellular spheroids in these biomimetic matrices. Cancer cells derived from human epithelial ovarian carcinoma were embedded within biomimetic hydrogels of varying stiffness and grown for up to 4 weeks. Immunohistochemistry, imaging and growth analyses were used to quantify the dependence of cell proliferation and apoptosis on matrix stiffness, long-term culture and treatment with the anti-cancer drug paclitaxel. The mathematical model was formulated as a free boundary problem in which each spheroid was treated as an incompressible porous medium. The functional forms used to describe the rates of cell proliferation and apoptosis were motivated by the experimental work and predictions of the mathematical model compared with the experimental output. This work aimed to establish whether it is possible to simulate solid tumour growth on the basis of data on spheroid size, cell proliferation and cell death within these spheroids. The mathematical model predictions were in agreement with the experimental data set and simulated how the growth of cancer spheroids was influenced by mechanical and biochemical stimuli including matrix stiffness, culture duration and administration of a chemotherapeutic drug. Our computational model provides new perspectives on experimental results and has informed the design of new 3D studies of chemoresistance of multicellular cancer spheroids.

A humanized tissue-engineered in vivo model to dissect interactions between human prostate cancer cells and human bone

Publisher: Springer Science and Business Media LLC

Date: 08-02-2014

DOI: 10.1007/S10585-014-9638-5

Abstract: Currently used xenograft models for prostate cancer bone metastasis lack the adequate tissue composition necessary to study the interactions between human prostate cancer cells and the human bone microenvironment. We introduce a tissue engineering approach to explore the interactions between human tumor cells and a humanized bone microenvironment. Scaffolds, seeded with human primary osteoblasts in conjunction with BMP7, were implanted into immunodeficient mice to form humanized tissue engineered bone constructs (hTEBCs) which consequently resulted in the generation of highly vascularized and viable humanized bone. At 12 weeks, PC3 and LNCaP cells were injected into the hTEBCs. Seven weeks later the mice were euthanized. Micro-CT, histology, TRAP, PTHrP and osteocalcin staining results reflected the different characteristics of the two cell lines regarding their phenotypic growth pattern within bone. Microvessel density, as assessed by vWF staining, showed that tumor vessel density was significantly higher in LNCaP injected hTEBC implants than in those injected with PC3 cells (p < 0.001). Interestingly, PC3 cells showed morphological features of epithelial and mesenchymal phenotypes suggesting a cellular plasticity within this microenvironment. Taken together, a highly reproducible humanized model was established which is successful in generating LNCaP and PC3 tumors within a complex humanized bone microenvironment. This model simulates the conditions seen clinically more closely than any other model described in the literature to date and hence represents a powerful experimental platform that can be used in future work to investigate specific biological questions relevant to bone metastasis.

A comparison of the impact of cation chemistry in ionic liquid-based lithium battery electrolytes

Publisher: Royal Society of Chemistry (RSC)

Date: 2023

DOI: 10.1039/D3YA00336A

Reflections on the tissue kallikrein and kallikrein-related peptidase family - From mice to men - What have we learnt in the last two decades?

Publisher: Walter de Gruyter GmbH

Date: 09-10-2008

DOI: 10.1515/BC.2008.174

Abstract: The genes encoding the kininogenase, glandular tissue kallikrein, in rodents and man were first described in the mid-1980s. Remarkably, they appeared to be part of a much larger highly conserved family of genes ( GK ) in rodents, but only had two paralogs in man. This discrepancy was not rectified until the late 1990s/2000 with the identification of a cluster of 12 more kallikrein-related ( KLK ) genes in the human 19q13 locus and the subsequent identification of their rodent homologs. Interestingly, there are remarkable similarities in expression patterns, hormonal regulation and functional attributes of the old ( GK ) and new ( KLK ) families which underscore the evolutionary conservation across these loci and species. This historical perspective focuses on the lessons learned from earlier studies on the rodent GK gene families and the striking similarities of some attributes, yet uniqueness, of others. These earlier findings have all contributed to the current status of the KLK serine peptidase-encoding gene family as an exciting source of new biomarkers and therapeutic targets.

Prediction of individual genetic risk to prostate cancer using a polygenic score

Publisher: Wiley

Date: 14-07-2015

DOI: 10.1002/PROS.23037

A novel transcript from the KLKP1 gene is androgen regulated, down-regulated during prostate cancer progression and encodes the first non-serine protease identified from the human kallikrein gene locus

Publisher: Wiley

Date: 2008

DOI: 10.1002/PROS.20685

Abstract: The kallikrein-related (KLK) serine protease, prostate specific antigen is the current marker for prostate cancer (PCa). Other members of the KLK family are also emerging as potential adjunct biomarkers for this disease. Our aim was to identify and characterize novel KLK-related genes with potential as PCa bio-markers. Low stringency DNA screening was coupled with lification techniques to identify novel sequences. Transcripts were examined by Northern blot, RT-PCR, and in situ hybridization analysis and in silico bioinformatics approaches. Protein characterization was performed by Western blot and confocal microscopy analysis. Gene regulation studies were performed by quantitative PCR and promoter reporter assays. We identified a novel kallikrein-related mRNA designated KRIP1 (kallikrein-related, expressed in prostate 1) which, together with the recently reported PsiKLK1 and KLK31P transcripts, is transcribed from KLKP1 a gene evolved from, and located within, the KLK locus. Significantly, in contrast to these other non-coding KLKP1 transcripts, the KRIP1 mRNA generates an approximately 18 kDa intracellular protein-the first non-serine protease identified from the KLK locus. KRIP1 mRNA is abundant only in normal prostate and is restricted to cells of epithelial origin in normal and diseased glands. Ligand binding of the androgen receptor increases transcription from the KLKP1 gene. Consistently, KRIP1 mRNA levels are lower in PCa s les compared to benign prostatic hyperplasia. Transcription from KLKP1 is reduced as cells de-differentiate on the pathway to malignancy. KLKP1/KRIP1 has potential as a marker of both PCa progression and recent evolutionary events within the KLK locus.

Zwitterionic materials with disorder and plasticity and their application as non-volatile solid or liquid electrolytes

Publisher: Springer Science and Business Media LLC

Date: 18-11-2022

DOI: 10.1038/S41563-021-01130-Z

Anion-cation interactions in novel ionic liquids based on an asymmetric sulfonimide anion observed by NMR and MD simulations

Publisher: Elsevier BV

Date: 04-2021

DOI: 10.1016/J.MOLLIQ.2020.114879

Concomitant dopaminergic and glucocorticoid control of pituitary proopiomelanocortin messenger ribonucleic acid and β-endorphin levels

Publisher: The Endocrine Society

Date: 11-1987

DOI: 10.1210/ENDO-121-5-1689

Abstract: Synthesis and secretion of POMC-derived peptides appear to be differentially regulated in the anterior pituitary (AP) and neurointermediate lobe (NIL). In the AP, glucocorticoids inhibit, and CRF and arginine vasopressin stimulate, synthesis of POMC and release of immunoreactive (ir)-beta-endorphin (beta EP) in the NIL, synthesis and release of POMC and its derivatives are under tonic inhibitory dopaminergic control. There is, however, evidence for some overlap of these control mechanisms under certain circumstances. In the present study we have used specific RIA and Northern blot analysis to examine the effects of chronic treatment with dopaminergic agents and dexamethasone (DM) (both alone and in combination) on AP and NIL content of ir-beta EP and POMC messenger RNA (mRNA), and/or hypothalamic ir-arginine vasopressin and ir-CRF content. In the NIL, the dopamine agonist bromocriptine reduced and the antagonist haloperidol raised both POMC mRNA and ir-beta EP content. Long term DM treatment did not alter NIL ir-beta EP content in the intact rat, but increased levels of POMC mRNA. DM abolished the haloperidol-induced increase in NIL ir-beta EP content but further increased the haloperidol-induced rise in POMC mRNA. DM treatment lowered both ir-beta EP and POMC mRNA in the AP as well as lowering levels of hypothalamic ir-CRF. In DM-treated rats, haloperidol partially restored AP ir-beta EP and POMC mRNA to control untreated levels. These findings further support the proposition that both dopaminergic agents and glucocorticoids can modulate POMC mRNA levels and/or tissue content of ir-beta EP in both the NIL and AP of the rat. The effects of DM on the NIL, both alone or with haloperidol, suggest that glucocorticoids may have both direct and indirect effects on POMC gene expression in this tissue.

PSA/KLK3 AREI promoter polymorphism alters androgen receptor binding and is associated with prostate cancer susceptibility

Publisher: Oxford University Press (OUP)

Date: 27-11-2007

DOI: 10.1093/CARCIN/BGL236

Abstract: The proximal promoter of the kallikrein-related peptidase 3 gene (KLK3/PSA) contains a single-nucleotide polymorphism (G-158A) located within the second canonical half-site for the prostate-specific antigen (PSA) androgen response element 1 (AREI). Previous studies suggest that this polymorphism may be associated with higher PSA levels and increase prostate cancer risk. We have investigated the potential functional significance of this polymorphism and its association with prostate cancer susceptibility by genotyping the G-158A polymorphism in 209 men diagnosed with prostate cancer and 223 healthy control men in an Australian Caucasian population. Functional analyses of PSA AREI demonstrated that the A allele increased binding of AREI to the androgen receptor, as well as increasing transcriptional response to androgens. Association studies of the G-158A polymorphism demonstrated that men with an A/A genotype had a 3-fold increased risk for developing prostate cancer [95% confidence intervals (CIs) = 1.36-6.52] and men with an A/G genotype had a 2.4-fold increased risk (95% CIs = 1.23-4.81). Under a dominant model, the A allele conferred a 2.6-fold increased risk for prostate cancer (95% CIs = 1.37-4.96, P = 0.004). Taken together with the finding that the G-158A polymorphism is associated with an increased risk of prostate cancer in Australian men, our functional data suggest that the presence of the A allele in AREI may, in part, account for the altered PSA regulation seen in prostate cancer.

Understanding the interfacial region in organic ionic plastic crystal composite electrolyte materials by solid-state NMR

Publisher: Elsevier BV

Date: 10-2022

DOI: 10.1016/J.COCIS.2022.101632

Type II transmembrane serine proteases. Insights into an emerging class of cell surface proteolytic enzymes

Publisher: Elsevier BV

Date: 2001

DOI: 10.1074/JBC.R000020200

Tissue Kallikrein-Kinin System

Publisher: Wiley

Date: 12-2000

DOI: 10.1002/CPHY.CP070309

Abstract: The sections in this article are:

Foot shock analgesia: Lack of correlation with pituitary and plasma immunoreactive-β-endorphin

Publisher: S. Karger AG

Date: 1982

DOI: 10.1159/000123388

Abstract: Effects of inescapable foot shock on pain threshold and on levels of immunoreactive beta-endorphin (ir-beta EP) in anterior pituitary, neuro-intermediate lobe and plasma were determined by hot plate test and radioimmunoassay respectively. Whereas handling and conditioned stress failed to alter baseline pain threshold, 20 min inescapable foot shock produced modest and transient analgesia. Levels of plasma ir-beta EP and corticosterone were significantly and concurrently raised by all treatments and remained elevated 40 min after foot shock. Changes in plasma levels of ir-beta EP and corticosterone were found to parallel one another but did not correlate with changes in pain threshold. AP content of ir-beta EP was significantly reduced 60 min after the cessation of inescapable foot shock, and N-IL content from 20 min after. The findings suggest that (i) plasma levels of ir-beta EP and corticosterone do not reflect changes in pain threshold, and (ii) ir-beta EP levels in anterior pituitary, neurointermediate lobe and plasma probably are not causally related to foot shock analgesia.

Exploring the influence of the cation type and polymer support in bis(fluorosulfonyl)imide-based plastic crystal composite membranes for CO₂/N₂separation

Publisher: Royal Society of Chemistry (RSC)

Date: 2021

DOI: 10.1039/D1TA07831C

Abstract: A range of organic ionic plastic crystal-based composites for CO 2 separation are reported. A variety of analytical techniques were used to elucidate the influence of ion and polymer type on the properties and gas separation performance.

Unravelling the Role of Speciation in Glyme:Ionic Liquid Hybrid Electrolytes for Na−O₂ Batteries

Publisher: Wiley

Date: 10-12-2020

DOI: 10.1002/BATT.202000261

Controlling phase and rheological behaviours of hexagonal lyotropic liquid crystalline templates for nanostructural administration and retention

Publisher: Elsevier BV

Date: 02-2022

DOI: 10.1016/J.JCIS.2021.09.019

Royal Melbourne Institute Of Technology University

Location: Australia

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Queensland University Of Technology Faculty Of Health

Location: Australia

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Queensland University Of Technology

Location: Australia

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Prince Henry's Institute Of Medical Research

Location: Australia

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Monash University

Location: Australia

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RMIT University

Location: Australia

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Lattice Light Sheet Microscopy For Imaging Biology In Real Space And Time

Start Date: 2017

End Date: 2017

Funder: Australian Research Council

The Australian Protease Network

Start Date: 2003

End Date: 2003

Funder: Australian Research Council

Comprehensive Cell Imaging Facility

Start Date: 2011

End Date: 2011

Funder: Australian Research Council

Development And Validation Of Virtual Epithelial Cancer Models Using An Integrated Modelling And Experimental Three-dimensional Approach

Start Date: 2011

End Date: 2014

Funder: Australian Research Council

E-Services For Comparative Studies In Molecular Biology

Start Date: 2005

End Date: 2006

Funder: Australian Research Council

Biomolecular Discovery And Analysis Facility

Start Date: 2006

End Date: 2006

Funder: Australian Research Council

Australian Prostate Cancer Collaboration (APCC) Bio - Resource

Start Date: 2010

End Date: 2015

Funder: National Health and Medical Research Council

Australian Prostate Cancer Collaboration (APCC) Bio-Resource

Start Date: 2004

End Date: 2009

Funder: National Health and Medical Research Council

Special Research Initiatives - Grant ID: SR0567493

Start Date: 09-2005

End Date: 06-2007

Amount: $99,146.00

Funder: Australian Research Council

Linkage Infrastructure, Equipment And Facilities - Grant ID: LE170100206

Start Date: 05-2017

End Date: 12-2017

Amount: $550,000.00

Funder: Australian Research Council

Linkage Infrastructure, Equipment And Facilities - Grant ID: LE110100172

Start Date: 2011

End Date: 12-2011

Amount: $330,000.00

Funder: Australian Research Council

Discovery Projects - Grant ID: DP110103890

Start Date: 2011

End Date: 12-2014

Amount: $500,000.00

Funder: Australian Research Council

Special Research Initiatives - Grant ID: SR0354892

Start Date: 2004

End Date: 12-2004

Amount: $40,000.00

Funder: Australian Research Council

Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0668526

Start Date: 2006

End Date: 12-2007

Amount: $542,000.00

Funder: Australian Research Council