Jennifer Anne Byrne

Injection site and regulatory T cells influence durable vaccine-induced tumor immunity to an over-expressed self tumor associated antigen

Publisher: Informa UK Limited

Date: 07-2013

DOI: 10.4161/ONCI.25049

Building Research Support Capacity across Human Health Biobanks during the COVID-19 Pandemic

Publisher: SAGE Publications

Date: 2021

DOI: 10.1177/11772719211024100

Abstract: Human health biobanks are forms of research infrastructure that supply biospecimens and associated data to researchers, and therefore juxtapose the activities of clinical care and biomedical research. The discipline of biobanking has existed for over 20 years and is supported by several international professional societies and dedicated academic journals. However, despite both rising research demand for human biospecimens, and the growth of biobanking as an academic discipline, many in idual biobanks continue to experience sustainability challenges. This commentary will summarize how the COVID-19 pandemic is creating new challenges and opportunities for both the health biobanking sector and the supporting discipline of biobanking. While the challenges for biobanks may be numerous and acute, there are opportunities for both in idual biobanks and the discipline of biobanking to embrace change such that biobanks can continue to support and drive biomedical research. We will therefore describe numerous practical steps that in idual biobanks and/or the discipline of biobanking can take to survive and possibly thrive in response to the COVID-19 pandemic.

Tumor protein D52 expression and Ca²⁺-dependent phosphorylation modulates lysosomal membrane protein trafficking to the plasma membrane

Publisher: American Physiological Society

Date: 03-2010

DOI: 10.1152/AJPCELL.00455.2009

Abstract: Tumor protein D52 (also known as CRHSP-28) is highly expressed in multiple cancers and tumor-derived cell lines however, it is normally abundant in secretory epithelia throughout the digestive system, where it has been implicated in Ca 2+ -dependent digestive enzyme secretion ( 41 ). Here we demonstrate, using site-specific mutations, that Ca 2+ -sensitive phosphorylation at serine 136 modulates the accumulation of D52 at the plasma membrane within 2 min of cell stimulation. When expressed in Chinese hamster ovary CHO-K1 cells, D52 colocalized with adaptor protein AP-3, Rab27A, vesicle-associated membrane protein VAMP7, and lysosomal-associated membrane protein LAMP1, all of which are present in lysosome-like secretory organelles. Overexpression of D52 resulted in a marked accumulation of LAMP1 on the plasma membrane that was further enhanced following elevation of cellular Ca 2+ . Strikingly, mutation of serine 136 to alanine abolished the Ca 2+ -stimulated accumulation of LAMP1 at the plasma membrane whereas phosphomimetic mutants constitutively induced LAMP1 plasma membrane accumulation independent of elevated Ca 2+ . Identical results were obtained for endogenous D52 in normal rat kidney and HeLA cells, where both LAMP1 and D52 rapidly accumulated on the plasma membrane in response to elevated cellular Ca 2+ . Finally, D52 induced the uptake of LAMP1 antibodies from the cell surface in accordance with both the level of D52 expression and phosphorylation at serine 136 demonstrating that D52 altered the plasma membrane recycling of LAMP1-associated secretory vesicles. These findings implicate both D52 expression and Ca 2+ -dependent phosphorylation at serine 136 in lysosomal membrane trafficking to and from the plasma membrane providing a novel Ca 2+ -sensitive pathway modulating the lysosome-like secretory pathway.

TPD52, a candidate gene from genomic studies, is overexpressed in testicular germ cell tumours

Publisher: Elsevier BV

Date: 10-07-2009

DOI: 10.1016/J.MCE.2008.10.043

Abstract: Several genomic regions are recurrently over- or underrepresented in testicular germ cell tumours (TGCTs), but only a fraction of their genes change their expression accordingly. Two publications to date have studied DNA copy numbers and associated gene expression changes on a genome-wide level to identify key players in TGCT tumorigenesis. Here, we compare lists of significant genes in these studies, and show that 17 genes are common to both. These include concomitant gain and over-expression of JUB, NRXN3, and TPD52, and loss and under-expression of C11orf70 and CADM1, in addition to 12 overexpressed genes located on the chromosome arm 12p. We performed immunohistochemical analysis of TPD52 on a tissue microarray, which showed complete absence of TPD52 protein in normal germ cells and most intratubular germ cell neoplasias. TPD52 was expressed in two-thirds of seminomas and embryonal carcinomas, and at intermediate frequencies in the more differentiated non-seminomas.

The hD52 (TPD52) gene is a candidate target gene for events resulting in increased 8q21 copy number in human breast carcinoma

Publisher: Wiley

Date: 09-2000

DOI: 10.1002/1098-2264(2000)9999:9999<::AID-GCC1005>3.0.CO;2-O

Abstract: Chromosome band 8q21 is frequently overrepresented in human cancer, but to date no 8q21 target gene has been proposed. The hD52 (TPD52) gene is of potential significance in breast and other cancers due to its location and expression pattern. Fine mapping of hD52 placed this locus within the peak of the 8q21 licon delineated in the SK-BR-3 breast carcinoma cell line, and a positive association between hD52 gene dosage and transcript levels was subsequently demonstrated in four breast carcinoma cell lines, including SK-BR-3. Increased copy number (ICN) was measured using Southern blot analyses in 3/32 human breast carcinomas at hD52, and the related hD54 gene in 20q13.2-q13.3. Subsequent immunohistochemical analysis of hD52 expression in 19 breast carcinomas with varying hD52 gene dosages demonstrated a significant positive association between hD52 dosage and hD52 expression using a Spearman rank correlation coefficient (r(s) = 0.573, alpha = 0.01) and a Wilcoxon rank-sum test (alpha = 0.05). On the basis of its map location and expression pattern in breast carcinoma, we therefore propose hD52 as a candidate target gene at chromosome band 8q21.

MAL2, a novel raft protein of the MAL family, is an essential component of the machinery for transcytosis in hepatoma HepG2 cells

Publisher: Rockefeller University Press

Date: 07-10-2002

DOI: 10.1083/JCB.200206033

Abstract: Transcytosis is used alone (e.g., hepatoma HepG2 cells) or in combination with a direct pathway from the Golgi (e.g., epithelial MDCK cells) as an indirect route for targeting proteins to the apical surface. The raft-associated MAL protein is an essential element of the machinery for the direct route in MDCK cells. Herein, we present the functional characterization of MAL2, a member of the MAL protein family, in polarized HepG2 cells. MAL2 resided selectively in rafts and is predominantly distributed in a compartment localized beneath the subapical F-actin cytoskeleton. MAL2 greatly colocalized in subapical endosome structures with transcytosing molecules en route to the apical surface. Depletion of endogenous MAL2 drastically blocked transcytotic transport of exogenous polymeric immunoglobulin receptor and endogenous glycosylphosphatidylinositol-anchored protein CD59 to the apical membrane. MAL2 depletion did not affect the internalization of these molecules but produced their accumulation in perinuclear endosome elements that were accessible to transferrin. Normal transcytosis persisted in cells that expressed exogenous MAL2 designed to resist the depletion treatment. MAL2 is therefore essential for transcytosis in HepG2 cells.

Alternative splicing as a mechanism for regulating 14-3-3 binding: Interactions between hD53 (TPD52L1) and 14-3-3 proteins

Publisher: Elsevier BV

Date: 09-2003

DOI: 10.1016/S0022-2836(03)00944-6

Abstract: D52 (TPD52)-like proteins are coiled-coil motif-bearing proteins first identified through their expression in human breast carcinoma, which have been proposed to represent signalling intermediates and regulators of vesicle trafficking. D52-like gene transcripts are subject to alternative splicing, with sequences encoding a region termed insert 3 being affected in all three D52-like genes. We have now identified a 14-3-3 binding motif within one of two alternatively spliced exons encoding insert 3. As predicted from the distribution of 14-3-3 binding motifs in four hD52-like bait proteins tested, only a hD53 isoform encoding a 14-3-3 binding motif bound both 14-3-3beta and 14-3-3zeta preys in the yeast two-hybrid system. Since D53 proteins carrying 14-3-3 binding motifs are predicted to be widely expressed, polyclonal antisera were derived to specifically detect these isoforms. Using soluble protein extracts from breast carcinoma cell lines, pull-down assays replicated interactions between recombinant 14-3-3beta and 14-3-3zeta isoforms and exogenously expressed hD53, and co-immunoprecipitation analyses demonstrated interactions between endogenous 14-3-3 and both endogenously and exogenously-expressed hD53 protein. Co-expressed hD53 and 14-3-3 proteins were similarly demonstrated to co-localise within the cytoplasm of breast carcinoma cell lines. These results identify 14-3-3 proteins as partners for hD53, and alternative splicing as a mechanism for regulating 14-3-3 binding.

Short-term expansion of receptive fields in rat primary somatosensory cortex after hindpaw digit denervation

Publisher: Elsevier BV

Date: 11-1991

DOI: 10.1016/0006-8993(91)91652-H

Abstract: The immediate effect of changing the driving cutaneous input to locations within primary somatosensory cortex (SI) was examined by denervating one or more digits of the rat hindpaw by utation or local anesthesia. When all or part of a receptive field of a cluster of neurons was denervated, it was found that the cortical location recorded from gained responsiveness to cutaneous stimulation of hindpaw areas bordering the denervated region. In 22 of the 29 animals studied this expansion took place within 5 min of the denervation.

The BET bromodomain inhibitor exerts the most potent synergistic anticancer effects with quinone-containing compounds and anti-microtubule drugs

Publisher: Impact Journals, LLC

Date: 13-10-2016

DOI: 10.18632/ONCOTARGET.12640

The thin ret(raction) line: biomedical journal responses to incorrect non-targeting nucleotide sequence reagents in human gene knockdown publications

Publisher: Springer Science and Business Media LLC

Date: 28-02-2021

DOI: 10.1007/S11192-021-03871-9

Abstract: The capacity of the scientific literature to self-correct is of vital importance, but few studies have compared post-publication journal responses to specific error types. We have compared journal responses to a specific reagent error in 31 human gene knockdown publications, namely a non-targeting or negative control nucleotide sequence that is instead predicted to target a human gene. The 31 papers published by 13 biomedical journals generated 26 published responses (14 retractions, 5 expressions of concern, 7 author corrections which included one resolved expression of concern) as well as 6 stated decisions to take no action. Variations in published responses were noted both between journals and by 4 journals that published different responses to at least 2 papers. A subset of published responses revealed conflicting explanations for the wrongly identified control reagent, despite 30/31 papers obtaining their gene knockdown reagents from the same external supplier. Viewed collectively, different journal responses to human gene knockdown publications with a common reagent error type suggest that editorial staff require more support to interpret post-publication notifications of incorrect nucleotide sequence reagents. We propose a draft template to facilitate the communication, interpretation and investigation of published errors, including errors affecting research reagents.

'No Country Bureaucratised its way to Excellence'

Publisher: SAGE Publications

Date: 12-10-2022

DOI: 10.1177/15562646211048268

Abstract: We created a petition for a national inquiry into the Australian system of research ethics and governance, to inform the politicians about the problems with the existing system. We analyzed the reasons that signatories offered for why signing the petition was important to them. A total of 409 comments (by 805 signatories) focused on five major themes: (1) views on previous changes to the system of research ethics and governance (2) drawbacks of the existing system (3) suggested changes to the system (4) anticipated impacts of changing the system and (5) miscellaneous/other comments. Comments ranged from several words to over 400 words in length, and most often focused on the procedural aspects, and commented on theme 2: drawbacks of the existing system.

Tumor protein D52 controls trafficking of an apical endolysosomal secretory pathway in pancreatic acinar cells

Publisher: American Physiological Society

Date: 15-09-2013

DOI: 10.1152/AJPGI.00143.2013

Abstract: Zymogen granule (ZG) formation in acinar cells involves zymogen cargo sorting from trans-Golgi into immature secretory granules (ISGs). ISG maturation progresses by removal of lysosomal membrane and select content proteins, which enter endosomal intermediates prior to their apical exocytosis. Constitutive and stimulated secretion through this mechanism is termed the constitutive-like and minor-regulated pathways, respectively. However, the molecular components that control membrane trafficking within these endosomal compartments are largely unknown. We show that tumor protein D52 is highly expressed in endosomal compartments following pancreatic acinar cell stimulation and regulates apical exocytosis of an apically directed endolysosomal compartment. Secretion from the endolysosomal compartment was detected by cell-surface antigen labeling of lysosome-associated membrane protein LAMP1, which is absent from ZGs, and had incomplete overlap with surface labeling of synaptotagmin 1, a marker of ZG exocytosis. Although culturing (16–18 h) of isolated acinar cells is accompanied by a loss of secretory responsiveness, the levels of SNARE proteins necessary for ZG exocytosis were preserved. However, levels of endolysosomal proteins D52, EEA1, Rab5, and LAMP1 markedly decreased with culture. When D52 levels were restored by adenoviral delivery, the levels of these regulatory proteins and secretion of both LAMP1 (endolysosomal) and amylase was strongly enhanced. These secretory effects were absent in alanine and aspartate substitutions of serine 136, the major D52 phosphorylation site, and were inhibited by brefeldin A, which does not directly affect the ZG compartment. Our results indicate that D52 directly regulates apical endolysosomal secretion and are consistent with previous studies, suggesting that this pathway indirectly regulates ZG secretion of digestive enzymes.

Quality and reporting practices in an Australian cancer biobank cohort

Publisher: Elsevier BV

Date: 04-2016

DOI: 10.1016/J.CLINBIOCHEM.2015.12.007

Abstract: Inadequate research biospecimen quality may adversely impact research translation to clinical practice. Despite the development and endorsement of external quality assurance (QA) programs and biospecimen quality reporting tools, there has been little examination of relevant biobank practices. An online survey was designed to describe the use and communication of QA and quality control (QC) measures within an Australian cancer biobank cohort (n=21), classified according to access policy. Survey questions examined the development and maintenance of Standard Operating Procedures (SOPs), other specific QA and biospecimen QC activities, and communication of biospecimen QC results to researchers. Over three quarters of biobanks utilised regularly-reviewed, best-practice-referenced SOPs, and most biobanks undertook at least one QC activity. Whereas all open-access biobanks (n=11) utilised SOPs and undertook at least one QC activity, these practices were significantly less frequent in restricted-access biobanks (n=10). There were overall low rates of recording the SPREC code, with increased but incomplete recording of Tier 1 BRISQ data. Open-access biobanks were significantly more likely to provide biospecimen QC results to researchers, and to report receiving requests for QC results or additional s le data. Improved resourcing and education may be required to boost current levels of QA and QC activities and reporting by cancer biobanks.

Delayed recruiting of TPD52 to lipid droplets – evidence for a “second wave” of lipid droplet-associated proteins that respond to altered lipid storage induced by Brefeldin A treatment

Publisher: Springer Science and Business Media LLC

Date: 05-07-2019

DOI: 10.1038/S41598-019-46156-1

Abstract: Tumor protein D52 (TPD52) is lified and overexpressed in breast and prostate cancers which are frequently characterised by dysregulated lipid storage and metabolism. TPD52 expression increases lipid storage in mouse 3T3 fibroblasts, and co-distributes with the Golgi marker GM130 and lipid droplets (LDs). We examined the effects of Brefeldin A (BFA), a fungal metabolite known to disrupt the Golgi structure, in TPD52-expressing 3T3 cells, and in human AU565 and HMC-1-8 breast cancer cells that endogenously express TPD52. Five-hour BFA treatment reduced median LD numbers, but increased LD sizes. TPD52 knockdown decreased both LD sizes and numbers, and blunted BFA’s effects on LD numbers. Following BFA treatment for 1–3 hours, TPD52 co-localised with the trans-Golgi network protein syntaxin 6, but after 5 hours BFA treatment, TPD52 showed increased co-localisation with LDs, which was disrupted by microtubule depolymerising agent nocodazole. BFA treatment also increased perilipin (PLIN) family protein PLIN3 but reduced PLIN2 detection at LDs in TPD52-expressing 3T3 cells, with PLIN3 recruitment to LDs preceding that of TPD52. An N-terminally deleted HA-TPD52 mutant (residues 40–184) almost exclusively targeted to LDs in both vehicle and BFA treated cells. In summary, delayed recruitment of TPD52 to LDs suggests that TPD52 participates in a temporal hierarchy of LD-associated proteins that responds to altered LD packaging requirements induced by BFA treatment.

Protection of the human gene research literature from contract cheating organizations known as research paper mills

Publisher: Oxford University Press (OUP)

Date: 28-11-2022

DOI: 10.1093/NAR/GKAC1139

Abstract: Human gene research generates new biology insights with translational potential, yet few studies have considered the health of the human gene literature. The accessibility of human genes for targeted research, combined with unreasonable publication pressures and recent developments in scholarly publishing, may have created a market for low-quality or fraudulent human gene research articles, including articles produced by contract cheating organizations known as paper mills. This review summarises the evidence that paper mills contribute to the human gene research literature at scale and outlines why targeted gene research may be particularly vulnerable to systematic research fraud. To raise awareness of targeted gene research from paper mills, we highlight features of problematic manuscripts and publications that can be detected by gene researchers and/or journal staff. As improved awareness and detection could drive the further evolution of paper mill-supported publications, we also propose changes to academic publishing to more effectively deter and correct problematic publications at scale. In summary, the threat of paper mill-supported gene research highlights the need for all researchers to approach the literature with a more critical mindset, and demand publications that are underpinned by plausible research justifications, rigorous experiments and fully transparent reporting.

The 11p15.5 ribonucleotide reductase M1 subunit locus is not imprinted in Wilms' tumour and hepatoblastoma

Publisher: Springer Science and Business Media LLC

Date: 04-1993

DOI: 10.1007/BF00218271

Human gene function publications that describe wrongly identified nucleotide sequence reagents are unacceptably frequent within the genetics literature

Publisher: Cold Spring Harbor Laboratory

Date: 31-07-2021

DOI: 10.1101/2021.07.29.453321

Abstract: Nucleotide sequence reagents underpin a range of molecular genetics techniques that have been applied across hundreds of thousands of research publications. We have previously reported wrongly identified nucleotide sequence reagents in human gene function publications and described a semi-automated screening tool Seek & Blastn to fact-check the targeting or non-targeting status of nucleotide sequence reagents. We applied Seek & Blastn to screen 11,799 publications across 5 literature corpora, which included all original publications in Gene from 2007-2018 and all original open-access publications in Oncology Reports from 2014-2018. After manually checking the Seek & Blastn screening outputs for over 3,400 human research papers, we identified 712 papers across 78 journals that described at least one wrongly identified nucleotide sequence. Verifying the claimed identities of over 13,700 nucleotide sequences highlighted 1,535 wrongly identified sequences, most of which were claimed targeting reagents for the analysis of 365 human protein-coding genes and 120 non-coding RNAs, respectively. The 712 problematic papers have received over 17,000 citations, which include citations by human clinical trials. Given our estimate that approximately one quarter of problematic papers are likely to misinform or distract the future development of therapies against human disease, urgent measures are required to address the problem of unreliable gene function papers within the literature. This is the first study to have screened the gene function literature for nucleotide sequence errors at the scale that we describe. The unacceptably high rates of human gene function papers with incorrect nucleotide sequences that we have discovered represent a major challenge to the research fields that aim to translate genomics investments to patients, and that commonly rely upon reliable descriptions of gene function. Indeed, wrongly identified nucleotide sequence reagents represent a double concern, as both the incorrect reagents themselves and their associated results can mislead future research, both in terms of the research directions that are chosen and the experiments that are undertaken. We hope that our research will inspire researchers and journals to seek out other problematic human gene function papers, as we are unfortunately concerned that our results represent the tip of a much larger problem within the literature. We hope that our research will encourage more rigorous reporting and peer review of gene function results, and we propose a series of responses for the research and publishing communities.

Overexpression, Amplification, and Androgen Regulation of TPD52 in Prostate Cancer

Publisher: American Association for Cancer Research (AACR)

Date: 06-2004

DOI: 10.1158/0008-5472.CAN-03-3881

Abstract: Gains in the long arm of chromosome 8 (8q) are believed to be associated with poor outcome and the development of hormone-refractory prostate cancer. Based on a meta-analysis of gene expression microarray data from multiple prostate cancer studies (D. R. Rhodes et al., Cancer Res 2002 :4427–33), a candidate oncogene, Tumor Protein D52 (TPD52), was identified in the 8q21 licon. TPD52 is a coiled-coil motif-bearing protein, potentially involved in vesicle trafficking. Both mRNA and protein levels of TPD52 were highly elevated in prostate cancer tissues. Array comparative genomic hybridization and lification analysis using single nucleotide polymorphism arrays demonstrated increased DNA copy number in the region encompassing TPD52. Fluorescence in situ hybridization on tissue microarrays confirmed TPD52 lification in prostate cancer epithelia. Furthermore, our studies suggest that TPD52 protein levels may be regulated by androgens, consistent with the presence of androgen response elements in the upstream promoter of TPD52. In summary, these findings suggest that dysregulation of TPD52 by genomic lification and androgen induction may play a role in prostate cancer progression.

Induction of Tumorigenesis and Metastasis by the Murine Orthologue of Tumor Protein D52

Publisher: American Association for Cancer Research (AACR)

Date: 02-2007

DOI: 10.1158/1541-7786.MCR-06-0245

Abstract: Expression studies have consistently identified tumor protein D52 (TPD52) overexpression in tumor cells. Murine TPD52 (mD52) shares 86% identity with the human orthologue. To study a possible role for TPD52 in transformation, 3T3 fibroblasts were transfected with the full-length cDNA for mD52. Expression of mD52 was confirmed by reverse transcription-PCR (RT-PCR), real-time PCR, and Western blot analysis compared with 3T3 and vector-transfected 3T3 (3T3.V), and the resultant cell line was designated 3T3.mD52. At 4 weeks, 3T3.mD52 gained a 2-fold increase in growth rate, lost contact inhibition, and exhibited a marked phenotype change. Further characterization revealed an acquired ability for anchorage-independent cell growth. To determine whether 3T3.mD52 had become tumorigenic, naïve, healthy, immunocompetent syngeneic mice were inoculated subcutaneously with varying cell doses. Tumors measuring & cm2 were detected 60 days postinoculation with 3T3.mD52, and a 50% subcutaneous tumor incidence was obtained with as few as 5 × 105 3T3.mD52 cells. Remarkably, when lungs from 3T3.mD52 tumor-bearing mice were analyzed, numerous tumor nodules were observed, ranging from nodules less than 10 to nodules too numerous to count (inoculation with 1 × 105 and 5 × 106 cells, respectively). Further support for the metastatic capacity of 3T3.mD52 was the demonstration that transforming growth factor (TGF)-βR1 (receptor) expression decreased and TGF-β1 secretion increased in 3T3.mD52 compared with 3T3 controls. cDNA microarray analysis showed a gene expression pattern that further supported mD52-induced transformation and metastasis. Together, these data suggest that mD52 expression in 3T3 cells initiated cellular transformation, tumorigenesis, and progression to metastasis. (Mol Cancer Res 2007 (2):133–44)

Tumor protein D52 represents a negative regulator of ATM protein levels

Publisher: Informa UK Limited

Date: 15-09-2013

DOI: 10.4161/CC.26146

TPD52 (Tumor Protein D52)

Publisher: Springer New York

Date: 2012

DOI: 10.1007/978-1-4419-0461-4_555

Biobank classification in an australian setting

Publisher: Mary Ann Liebert Inc

Date: 06-2015

DOI: 10.1089/BIO.2015.0007

Abstract: In 2011, Watson and Barnes proposed a schema for classifying biobanks into 3 groups (mono-, oligo-, and poly-user), primarily based upon biospecimen access policies. We used results from a recent comprehensive survey of cancer biobanks in New South Wales, Australia to assess the applicability of this biobank classification schema in an Australian setting. Cancer biobanks were identified using publically available data, and by consulting with research managers. A comprehensive survey was developed and administered through a face-to-face setting. Data were analyzed using Microsoft Excel™ 2010 and IBM SPSS Statistics™ version 21.0. The cancer biobank cohort (n=23) represented 5 mono-user biobanks, 7 oligo-user biobanks, and 11 poly-user biobanks, and was analyzed as two groups (mono-/oligo- versus poly-user biobanks). Poly-user biobanks employed significantly more full-time equivalent staff, and were significantly more likely to have a website, share staff between biobanks, access governance support, utilize quality control measures, be aware of biobanking best practice documents, and offer staff training. Mono-/oligo-user biobanks were significantly more likely to seek advice from other biobanks. Our results further delineate a biobank classification system that is primarily based on access policy, and demonstrate its relevance in an Australian setting.

Automated screening of COVID-19 preprints: can we help authors to improve transparency and reproducibility?

Publisher: Springer Science and Business Media LLC

Date: 2021

DOI: 10.1038/S41591-020-01203-7

Proteomic screening of glutamatergic mouse brain synaptosomes isolated by fluorescence activated sorting

Publisher: Wiley

Date: 2014

DOI: 10.1002/EMBJ.201386120

The Role of the Coiled-Coil Motif in Interactions Mediated by TPD52

Publisher: Elsevier BV

Date: 10-2001

DOI: 10.1006/BBRC.2001.5721

A critical analysis of cancer biobank practices in relation to biospecimen quality

Publisher: Springer Science and Business Media LLC

Date: 22-10-2015

DOI: 10.1007/S12551-015-0178-2

A reliable method for total RNA extraction from frozen human bone marrow samples taken at diagnosis of acute leukaemia

Publisher: BMJ

Date: 11-2002

DOI: 10.1136/JCP.55.11.865

Abstract: This report describes a newly developed method using Trizol LS reagent that can reliably extract high quality total RNA from frozen human leukaemic bone marrow s les. Extraction of total RNA from 71 frozen leukaemic bone marrow s les obtained at the time of diagnosis produced a median yield of 145 micro g/ml leukaemic bone marrow. Total RNA s les could be reverse transcribed into cDNA and used successfully in the reverse transcription polymerase chain reaction lification of B2M transcripts in 68 of 71 cases. A multivariate linear regression analysis revealed that significant predictors of RNA yield were both s le volume ( 1 ml p = 0.003) and peripheral blood white cell count ( or= 5 x 10(9) white blood cells/litre p = 0.011). The percentage of blasts present, leukaemia subtype, and s le storage period at -80 degrees C (up to 945 days) were not predictors of total RNA yield. This method of total RNA extraction should be of interest to diagnostic and research staff using frozen bone marrow s les for molecular analyses. Similarly, the lack of association between s le storage period at -80 degrees C and total RNA yield should be of interest to the administrators of tumour banks housing frozen bone marrow s les.

How Many Health Research Biobanks Are There?

Publisher: Mary Ann Liebert Inc

Date: 06-2022

DOI: 10.1089/BIO.2021.0063

TPD52 represents a survival factor in ERBB2‐amplified breast cancer cells

Publisher: Wiley

Date: 09-05-2013

DOI: 10.1002/MC.22038

Abstract: TPD52 and ERBB2 co-expression has been persistently reported in human breast cancer and animal models of this disease, but the significance of this is unknown. We identified significant positive associations between relative TPD52 and ERBB2 transcript levels in human diagnostic breast cancer s les, and maximal TPD52 expression in the hormone receptor (HR)- and ERBB2-positive sub-group. High-level TPD52 expression was associated with significantly reduced metastasis-free survival, within the overall cohort (log rank test, P = 8.6 × 10(-4), n = 375) where this was an independent predictor of metastasis-free survival (hazard ratio, 2.69, 95% confidence interval 1.59-4.54, P = 2.2 × 10(-4), n = 359), and the HR- and ERBB2-positive sub-group (log rank test, P = 0.035, n = 47). Transient TPD52 knock-down in the ERBB2- lified breast cancer cell lines SK-BR-3 and BT-474 produced significant apoptosis, both singly and in combination with transient ERBB2 knock-down. Unlike ERBB2 knock-down, transient TPD52 knock-down produced no reduction in pAKT levels in SK-BR-3 or BT-474 cells. We then derived multiple SK-BR-3 cell lines in which TPD52 levels were stably reduced, and measured significant inverse correlations between pERBB2 and TPD52 levels in viable TPD52-depleted and control cell lines, all of which showed similar proliferative capacities. Our results therefore identify TPD52 as a survival factor in ERBB2- lified breast cancer cells, and suggest complementary cellular functions for TPD52 and ERBB2.

A Pathway to Precision Medicine for Aboriginal Australians: A Study Protocol

Publisher: MDPI AG

Date: 21-06-2021

DOI: 10.3390/MPS4020042

Abstract: (1) Background: Genomic precision medicine (PM) utilises people’s genomic data to inform the delivery of preventive and therapeutic health care. PM has not been well-established for use with people of Aboriginal and Torres Strait Islander ancestry due to the paucity of genomic data from these communities. We report the development of a new protocol using co-design methods to enhance the potential use of PM for Aboriginal Australians. (2) Methods: This iterative qualitative study consists of five main phases. Phase-I will ensure appropriate governance of the project and establishment of a Project Advisory Committee. Following an initial consultation with the Aboriginal community, Phase-II will invite community members to participate in co-design workshops. In Phase-III, the Chief Investigators will participate in co-design workshops and document generated ideas. The notes shall be analysed thematically in Phase-IV with Aboriginal community representatives, and the summary will be disseminated to the communities. In Phase-V, we will evaluate the co-design process and adapt our protocol for the use in partnership with other communities. (3) Discussion: This study protocol represents a crucial first step to ensure that PM research is relevant and acceptable to Aboriginal Australians. Without fair access to PM, the gap in health outcome between Aboriginal and non-Aboriginal Australians will continue to widen.

Clinical Significance of Tumor Protein D52 Immunostaining in a Large Series of Ewing's Sarcoma Family of Tumors

Publisher: SAGE Publications

Date: 05-2011

DOI: 10.2350/11-01-0956-LET.1

Verification of nucleotide sequence reagent identities in original publications in high impact factor cancer research journals

Publisher: Cold Spring Harbor Laboratory

Date: 03-02-2023

DOI: 10.1101/2023.02.03.526922

Abstract: Human gene research studies that describe wrongly identified nucleotide sequence reagents have been mostly identified in journals of low to moderate impact factor, where unreliable findings could be considered to have limited influence on future research. This study examined whether papers describing wrongly identified nucleotide sequences are also published in high impact factor cancer research journals. We manually verified nucleotide sequence identities in original Molecular Cancer articles published in 2014, 2016, 2018 and 2020, including nucleotide sequence reagents that were claimed to target circRNAs. Using keywords identified in problematic 2018 and 2020 Molecular Cancer papers, we also verified nucleotide sequence identities in 2020 Oncogene papers that studied miRNA(s) and/or circRNA(s). Overall, 3.8% (253/6,647) and 4.3% (50/1,165) nucleotide sequences that were verified in Molecular Cancer and Oncogene papers, respectively, were found to be wrongly identified. These wrongly identified nucleotide sequences were distributed across 18% (92/500) original Molecular Cancer papers, including 38% Molecular Cancer papers from 2020, and 40% (21/52) selected Oncogene papers from 2020. Original papers with wrongly identified nucleotide sequences were therefore unexpectedly frequent in two high impact factor cancer research journals, highlighting the risks of employing journal impact factors or citations as proxies for research quality.

Molecular profiling of childhood cancer: Biomarkers and novel therapies

Publisher: Elsevier BV

Date: 06-2014

DOI: 10.1016/J.BBACLI.2014.06.003

Challenges in Identifying Candidate Amplification Targets in Human Cancers: Chromosome 8q21 as a Case Study

Publisher: SAGE Publications

Date: 02-2012

DOI: 10.1177/1947601912456287

Improving the peer review of narrative literature reviews

Publisher: Springer Science and Business Media LLC

Date: 04-09-2016

DOI: 10.1186/S41073-016-0019-2

Definition of the Tumor Protein D52 (TPD52) Gene Family through Cloning ofD52Homologues in Human (hD53) and Mouse (mD52)

Publisher: Elsevier BV

Date: 08-1996

DOI: 10.1006/GENO.1996.0393

Abstract: Cloning is reported of a cDNA homologue to the breast carcinoma-associated D52 cDNA, termed D53, and of a mouse D52 cDNA (HGMW-approved symbols TPD52L1 and TPD52). Human D53 and mouse D52 proteins are predicted to be 52 and 86% identical to human D52, respectively. Analysis of the three protein sequences identified a coiled-coil domain and N- and C-terminally located PEST domains in each. The conservation of homology between the D52 and the D53 sequences, combined with a lack of homology between these and known proteins, defines a new mammalian gene rotein family, the D52 family. The human D52 locus has been previously mapped to chromosome 8q21, and using in situ mapping in the present study, a human D53 locus was mapped to chromosome 6q22-q23. We observed coexpression of the human D52 and D53 genes in some breast tumors and derivative cell lines and found that maintenance of D52 and D53 transcript levels in estrogen receptor-positive MCF7 breast carcinoma cells depends upon estradiol. However, D52 and D53 genes were specifically expressed in HL-60 and K-562 leukemia cells, respectively, with 12-O-tetra-decanoylphorbol-13-acetate treatment decreasing D52 and D53 transcript levels in these cell lines. The presence of a coiled-coil domain, combined with observed co- or independent expression of the D52 and D53 genes, suggests that D52 and D53 proteins may be capable of hetero- and/or homodimer formation.

In vitro and in vivo drug screens of tumor cells identify novel therapies for high-risk child cancer

Publisher: EMBO

Date: 20-12-2022

DOI: 10.15252/EMMM.202114608

The M1 subunit of ribonucleotide reductase refines mapping of genetic rearrangements at chromosome 11p15

Publisher: Elsevier BV

Date: 04-1992

DOI: 10.1016/0165-4608(92)90216-U

Abstract: We report the first use of the ribonucleotide reductase M1 subunit (RRM1) locus as a marker to assist in defining genetic rearrangements at 11p15. Our s le consisted of 21 Wilms' tumors from 18 patients, and one adrenal adenoma from a patient with Beckwith-Wiedemann syndrome, preexisting chromosome 11 maps being refined by the use of the RRM1 locus in all cases. Significantly, one Wilms' tumor showed loss of heterozygosity at the RRM1 locus only, whereas the adrenal adenoma showed a maintenance of heterozygosity at the RRM1 locus, loss having been previously demonstrated at the c-Ha-ras locus. The relevance of this finding to the location of one or more disease-associated loci at 11p15 is discussed.

Identification of MAL2, a Novel Member of the MAL Proteolipid Family, Though Interactions with TPD52-like Proteins in the Yeast Two-Hybrid System

Publisher: Elsevier BV

Date: 08-2001

DOI: 10.1006/GENO.2001.6610

Cloning of a third member of the D52 gene family indicates alternative coding sequence usage in D52-like transcripts

Publisher: Elsevier BV

Date: 11-1998

DOI: 10.1016/S0167-4781(98)00211-5

Abstract: D52 proteins are emerging as signalling molecules which may be regulators of cell proliferation. Having previously reported the existence of the human D52 gene family, comprising the hD52 and hD53 genes expressed in human breast carcinoma, we report the identification of a novel human gene hD54 (TPD52L2), which represents a third D52 gene family member. In situ mapping placed the hD54 gene on human chromosome 20q13.2-q13.3, a localization distinct from those of both hD52 and hD53 genes. The identified hD54 cDNAs predicted three hD54 isoforms, suggesting that alternatively-spliced transcripts may be produced from D52-like genes. This was confirmed by directly sequencing reverse transcriptase-polymerase chain reaction (RT-PCR) products lified from D52-like gene transcripts expressed in developing and adult rat tissues, and by performing sequence analyses of the expressed sequence tag isions of nucleotide databases. Alternative splicing of sequences encoding two regions, termed ins2 and ins3, was identified in one or more D52-like genes, with these alternative splicing events being differentially regulated. The functional consequences of alternative splicing were examined by characterizing the protein-protein interactions mediated by a truncated hD53 isoform within the yeast two-hybrid system. This hD53 isoform displayed altered interaction capabilities with respect to those of full-length hD53, suggesting that alternative splicing within the D52 gene family functions in part to alter the protein-protein interaction capabilities of encoded isoforms.

Priorities in Biobanking Research: A Report on the 2021 ISBER Round Table

Publisher: Mary Ann Liebert Inc

Date: 02-2023

DOI: 10.1089/BIO.2021.0178

Therapeutic targeting of the MYC signal by inhibition of histone chaperone FACT in neuroblastoma

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

Date: 04-11-2015

DOI: 10.1126/SCITRANSLMED.AAB1803

Abstract: Histone chaperone FACT acts in a positive feedback loop with MYCN and is a therapeutic target in neuroblastoma.

Allelic loss on chromosome 11p is a less frequent event in bilateral than in unilateral Wilms' tumours

Publisher: Elsevier BV

Date: 1992

DOI: 10.1016/0959-8049(92)90027-Y

Abstract: Analyses to detect loss of heterozygosity (LOH) were performed at 11 polymorphic loci on chromosome 11 and, using a polymorphic CA repeat sequence in the WT1 gene, on a series of 39 tumours from 28 unilateral and 10 tumours from 6 bilateral Wilms' tumour (WT) patients. LOH was seen in 13 out of 35 patients including 12 out of 29 unilateral tumours, but only one of 10 bilateral tumours. This suggests that bilateral WT represents a subgroup of WT in which tumour initiating events less frequently involve LOH on chromosome 11 and that either epigenetic events, point mutations or another non-chromosome 11p locus are important in bilateral tumours. The observation of LOH in one WT but not another WT in a bilateral WT patient provides evidence that these tumours arising in the same patient are not monoclonal proliferations and most likely arise via different molecular pathways.

Vaccination with metastasis-related tumor associated antigen TPD52 and CpG/ODN induces protective tumor immunity

Publisher: Springer Science and Business Media LLC

Date: 26-10-2007

DOI: 10.1007/S00262-007-0416-Y

Abstract: Tumor protein D52 (TPD52) is involved in transformation and metastasis and has been shown to be over-expressed in tumor cells compared to normal cells and tissues. Murine TPD52 (mD52) shares 86% protein identity with the human TPD52 orthologue (hD52). To study TPD52 protein as a target for active vaccination recombinant, mD52 was administered as a protein-based vaccine. Naïve mice were immunized with either mD52 protein and CpG/ODN as a molecular adjuvant or CpG/ODN alone. Two weeks following the final immunization, mice were challenged s.c. with syngeneic tumor cells that over-express mD52. Two distinct murine tumor cell lines were used for challenge in this model, mKSA and 3T3.mD52. Half of the mice immunized with mD52 and CpG/ODN rejected or delayed onset of mKSA s.c. tumor cell growth, and 40% of mice challenged with 3T3.mD52 rejected s.c. tumor growth, as well as the formation of spontaneous lethal lung metastases. Mice immunized with mD52 and CpG/ODN generated detectable mD52-specific IgG antibody responses indicating that mD52 protein vaccination induced an adaptive immune response. In addition, mice that rejected tumor challenge generated tumor-specific cytotoxic T lymphocytes' responses. Importantly, microscopic and gross evaluation of organs from mD52 immunized mice revealed no evidence of autoimmunity as assessed by absence of T cell infiltration and absence of microscopic pathology. Together, these data demonstrate that mD52 vaccination induces an immune response that is capable of rejecting tumors that over-express mD52 without the induction of harmful autoimmunity.

Flagging incorrect nucleotide sequence reagents in biomedical papers: To what extent does the leading publication format impede automatic error detection?

Publisher: Springer Science and Business Media LLC

Date: 22-05-2020

DOI: 10.1007/S11192-020-03463-Z

Abstract: In an idealised vision of science the scientific literature is error-free. Errors reported during peer review are supposed to be corrected prior to publication, as further research establishes new knowledge based on the body of literature. It happens, however, that errors pass through peer review, and a minority of cases errata and retractions follow. Automated screening software can be applied to detect errors in manuscripts and publications. The contribution of this paper is twofold. First, we designed the erroneous reagent checking () benchmark to assess the accuracy of fact-checkers screening biomedical publications for dubious mentions of nucleotide sequence reagents. It comes with a test collection comprised of 1679 nucleotide sequence reagents that were curated by biomedical experts. Second, we benchmarked our own screening software called Seek& Blastn with three input formats to assess the extent of performance loss when operating on various publication formats. Our findings stress the superiority of markup formats (a 79% detection rate on XML and HTML) over the prominent PDF format (a 69% detection rate at most) regarding an error flagging task. This is the first published baseline on error detection involving reagents reported in biomedical scientific publications. The benchmark is designed to facilitate the development and validation of software bricks to enhance the reliability of the peer review process.

Overexpressed oncogenic tumor-self antigens

Publisher: Informa UK Limited

Date: 11-2014

DOI: 10.4161/HV.29475

Formin INF2 regulates MAL-mediated transport of Lck to the plasma membrane of human T lymphocytes

Publisher: American Society of Hematology

Date: 23-12-2010

DOI: 10.1182/BLOOD-2010-08-300665

Abstract: Expression of the src-family kinase lymphocyte-specific protein tyrosine kinase (Lck) at the plasma membrane is essential for it to fulfill its pivotal role in signal transduction in T lymphocytes. MAL, an integral membrane protein expressed in specific types of lymphoma, has been shown to play an important role in targeting Lck to the plasma membrane. Here we report that MAL interacts with Inverted Formin2 (INF2), a formin with the atypical property of promoting not only actin polymerization but also its depolymerization. In Jurkat T cells, INF2 colocalizes with MAL at the cell periphery and pericentriolar endosomes and along microtubules. Videomicroscopic analysis revealed that the MAL+ vesicles transporting Lck to the plasma membrane move along microtubule tracks. Knockdown of INF2 greatly reduced the formation of MAL+ transport vesicles and the levels of Lck at the plasma membrane and impaired formation of a normal immunologic synapse. The actin polymerization and depolymerization activities of INF2 were both required for efficient Lck targeting. Cdc42 and Rac1, which bind to INF2, regulate Lck transport in both Jurkat and primary human T cells. Thus, INF2 collaborates with MAL in the formation of specific carriers for targeting Lck to the plasma membrane in a process regulated by Cdc42 and Rac1.

Human polymorphic probe pE1.8 detects SacI polymorphism in the ribonucleotide reductase M1 subunit gene

Publisher: Springer Science and Business Media LLC

Date: 07-1991

DOI: 10.1007/BF00200924

Lipidomics in Breast Cancer

Publisher: Springer India

Date: 2014

DOI: 10.1007/978-81-322-0843-3_11

Neuroblastoma, body mass index, and survival: a retrospective analysis

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 04-2015

DOI: 10.1097/MD.0000000000000713

The Possibility of Systematic Research Fraud Targeting Under-Studied Human Genes: Causes, Consequences, and Potential Solutions

Publisher: SAGE Publications

Date: 2019

DOI: 10.1177/1177271919829162

Abstract: A major reason for biomarker failure is the selection of candidate biomarkers based on inaccurate or incorrect published results. Incorrect research results leading to the selection of unproductive biomarker candidates are largely considered to stem from unintentional research errors. The additional possibility that biomarker research may be actively misdirected by research fraud has been given comparatively little consideration. This review discusses what we believe to be a new threat to biomarker research, namely, the possible systematic production of fraudulent gene knockdown studies that target under-studied human genes. We describe how fraudulent papers may be produced in series by paper mills using what we have described as a ‘theme and variations’ model, which could also be considered a form of salami slicing. We describe features of these single-gene knockdown publications that may allow them to evade detection by journal editors, peer reviewers, and readers. We then propose a number of approaches to facilitate their detection, including improved awareness of the features of publications constructed in series, broader requirements to post submitted manuscripts to preprint servers, and the use of semi-automated literature screening tools. These approaches may collectively improve the detection of fraudulent studies that might otherwise impede future biomarker research.

Expression of tumor protein D52-like genes in childhood leukemia at diagnosis: Clinical and sample considerations

Publisher: Elsevier BV

Date: 11-2006

DOI: 10.1016/J.LEUKRES.2006.03.009

Abstract: The tumor protein D52 gene or protein is frequently overexpressed in several carcinomas, and has been identified as a B cell differentiation marker. D52-like genes are also differentially expressed in particular haematological malignancies, where transcript or protein levels may reflect cellular proliferative or differentiative status. We used RT-PCR to analyse the expression of three D52-like genes in bone marrow at the time of ALL or AML diagnosis in children. Whereas D53 transcripts were undetectable in all s les, D52 and D54 transcripts were frequently detected in ALL and AML, where they were frequently co-expressed. While D52 and D54 transcripts were detected in T-ALL and pre-B ALL at comparable frequencies, D52 was less frequently detected in ALL bone marrow with hyperdiploid karyotypes, compared with s les with normal karyotypes. We also found that total RNA yields significantly differed according to D52 and D54 expression status, and that bone marrow freezer storage time (up to 945 days) differed significantly according to D52 expression status. These results indicate that D52-like genes are not ubiquitously expressed in leukemic bone marrow in children, and that RNA s le parameters may influence measures of gene expression more than commonly appreciated.

TPD52 (tumor protein D52)

Publisher: INIST-CNRS

Date: 11-2011

DOI: 10.4267/2042/45033

Development and Validation of a High Pressure Liquid Chromatography–UV Method for the Determination of Treosulfan and Its Epoxy Metabolites in Human Plasma and Its Application in Pharmacokinetic Studi

Publisher: Oxford University Press (OUP)

Date: 03-10-2015

DOI: 10.1093/CHROMSCI/BMV145

Abstract: Treosulfan (l-threitol-1,4-di-methanesulfonate) is a prodrug of a bifunctional alkylating agent that is being used increasingly in pediatric bone marrow transplantation regimens. The activation pathway is a complex reaction, which consists of two consecutive reactions leading to epoxybutane derivatives which are responsible for DNA alkylation. A simple, sensitive high performance liquid chromatography method for the determination of the sum of treosulfan and its epoxy metabolites by UV detection after derivatization with sodium diethyldithiocarbamate in human plasma was developed and validated. Plasma s les containing treosulfan and epoxy metabolites were converted into thiocarbamate derivative with 10% sodium diethyldithiocarbamate. Dinitrobiphenyl was used as an internal standard. The analysis was carried out using a reversed phase C18 column with a mobile phase consisting of methanol-water (65:35, v/v) at a flow rate of 1 mL/min. The eluent was monitored at 254 nm. The standard calibration curve was established between 2.5 and 50 µg/mL, with a correlation coefficient of 0.9987. Intra- and interday precision and accuracy of the method was <8% and met the analytical criteria. Pharmacokinetic parameters were determined in six children who received intravenous treosulfan (dose range 12-24 g/m(2)) in combination with fludarabine prior to blood or marrow transplantation.

The Availability of Human Biospecimens to Support Biomarker Research

Publisher: SAGE Publications

Date: 2022

DOI: 10.1177/11772719221091750

Abstract: Preserved biospecimens held in biobank inventories and clinical archives are important resources for biomarker research. Recent advances in technologies have led to an increase in use of clinical archives in particular, in order to study retrospective cohorts and to generate data relevant to tissue biomarkers. This raises the question of whether the current sizes of biobank inventories are appropriate to meet the demands of biomarker research. This commentary discusses this question by considering data concerning overall biobank and biospecimen numbers to estimate current biospecimen supply and use. The data suggests that biospecimen supply exceeds current demand. Therefore, it may be important for in idual biobanks to reassess the targets for their inventories, consider culling unused portions of these inventories, and shift resources towards providing prospective custom biobanking services.

Analysis of the CD8+ IL-10+ T cell response elicited by vaccination with the oncogenic tumor-self protein D52

Publisher: Informa UK Limited

Date: 26-11-2019

DOI: 10.1080/21645515.2019.1689746

The LIM Domain Protein LMO4 Interacts with the Cofactor CtIP and the Tumor Suppressor BRCA1 and Inhibits BRCA1 Activity

Publisher: Elsevier BV

Date: 03-2002

DOI: 10.1074/JBC.M110603200

Memory and cellular immunity induced by a DNA vaccine encoding self antigen TPD52 administered with soluble GM-CSF

Publisher: Springer Science and Business Media LLC

Date: 24-01-2009

DOI: 10.1007/S00262-009-0659-X

Abstract: Tumor protein D52 (TPD52) is involved in cellular transformation, proliferation and metastasis. TPD52 over expression has been demonstrated in several cancers including prostate, breast, and ovarian carcinomas. Murine TPD52 (mD52) has been shown to induce anchorage independent growth in vitro and metastasis in vivo, and mirrors the function and normal tissue expression patterns of the human orthologue of TPD52. We believe TPD52 represents a self, non-mutated tumor associated antigen (TAA) important for maintaining a transformed and metastatic cellular phenotype. The transgenic adeno-carcinoma of the mouse prostate (TRAMP) model was employed to study mD52 as a vaccine antigen. Naïve mice were immunized with either recombinant mD52 protein or plasmid DNA encoding the full-length cDNA of mD52. Following immunization, mice were challenged with a subcutaneous, tumorigenic dose of mD52 positive, autochthonous TRAMP-C1 tumor cells. Sixty percent of mice were tumor free 85 days post challenge with TRAMP-C1 when immunized with mD52 as a DNA-based vaccine admixed with soluble granulocyte-macrophage colony stimulating factor (GM-CSF). Survivors of the initial tumor challenge rejected a second tumor challenge given in the opposite flank approximately 150 days after the first challenge, and remained tumor free for more than an additional 100 days. The T cell cytokine secretion patterns from tumor challenge survivors indicated that a T(H)1-type cellular immune response was involved in tumor protection. These data suggest that mD52 vaccination induced a memory, cellular immune response that resulted in protection from murine prostate tumors that naturally over express mD52 protein.

Identification of human gene research articles with wrongly identified nucleotide sequences

Publisher: Life Science Alliance, LLC

Date: 12-01-2022

DOI: 10.26508/LSA.202101203

Abstract: Nucleotide sequence reagents underpin molecular techniques that have been applied across hundreds of thousands of publications. We have previously reported wrongly identified nucleotide sequence reagents in human research publications and described a semi-automated screening tool Seek & Blastn to fact-check their claimed status. We applied Seek & Blastn to screen ,700 publications across five literature corpora, including all original publications in Gene from 2007 to 2018 and all original open-access publications in Oncology Reports from 2014 to 2018. After manually checking Seek & Blastn outputs for ,400 human research articles, we identified 712 articles across 78 journals that described at least one wrongly identified nucleotide sequence. Verifying the claimed identities of ,700 sequences highlighted 1,535 wrongly identified sequences, most of which were claimed targeting reagents for the analysis of 365 human protein-coding genes and 120 non-coding RNAs. The 712 problematic articles have received ,000 citations, including citations by human clinical trials. Given our estimate that approximately one-quarter of problematic articles may misinform the future development of human therapies, urgent measures are required to address unreliable gene research articles.

Tumor protein D52 (TPD52) is overexpressed and a gene amplification target in ovarian cancer

Publisher: Wiley

Date: 28-06-2005

DOI: 10.1002/IJC.21250

Abstract: Recurrent chromosome 8q gain in ovarian carcinoma is likely to reflect the existence of multiple target loci, as the separate gain of chromosome bands 8q21 and 8q24 has been reported in independent studies. Since tumor protein D52 (TPD52) has been identified as a chromosome 8q21 lification target in breast and prostate carcinoma, we compared TPD52 expression in normal ovarian epithelium (n = 9), benign serous adenomas (n = 11), serous borderline tumors (n = 6) and invasive carcinomas of the major histologic subtypes (n = 57) using immunohistochemistry. These analyses revealed that all normal ovarian epithelium s les and benign serous tumors were predominantly TPD52-negative, whereas TPD52 was overexpressed in most (44/57 77%) ovarian carcinomas regardless of histologic subtype. TPD52 subcellular localization was predominantly cytoplasmic, although nuclear localization was also frequently observed in mucinous and clear cell carcinomas. In an independent cohort of stage III serous carcinomas (n = 18), we also directly compared in situ TPD52 expression using immunohistochemistry and TPD52 copy number using interphase FISH analyses. This revealed that TPD52 dosage and TPD52 expression were significantly positively correlated. TPD52 therefore represents a novel molecular marker in ovarian cancer, which is broadly expressed across the different histologic subtypes and whose upregulation frequently reflects increased TPD52 copy number.

Tumor protein D52 (TPD52): a novel B-cell/plasma-cell molecule with unique expression pattern and Ca2+-dependent association with annexin VI

Publisher: American Society of Hematology

Date: 04-2005

DOI: 10.1182/BLOOD-2004-07-2630

Abstract: We generated a murine monoclonal antibody (B28p) detecting an antigenic determinant shared by the immunoglobulin superfamily receptor translocation-associated 1 (IRTA1) receptor (the immunogen used to raise B28p) and an unrelated 28-kDa protein that was subsequently subjected to extensive characterization. The expression of the 28-kDa protein in normal lymphohematopoietic tissues was restricted to B cells and plasma cells and clearly differed from that expected for IRTA1 (selectively expressed by mucosa-associated lymphoid tissue [MALT] marginal zone B cells). Two-dimensional polyacrylamide gel electrophoresis (2D-PAGE)/mass-spectrometry analysis identified the 28-kDa protein as human tumor protein D52 (TPD52), whose expression had been previously described only in normal and neoplastic epithelia. Specific B28p reactivity with TPD52 was confirmed by immunostaining/immunoblotting of TPD52-transfected cells. TPD52 expression pattern in normal and neoplastic B cells was unique. In fact, unlike other B-cell molecules (paired box 5 [PAX5], CD19, CD79a, CD20, CD22), which are down-regulated during differentiation from B cells to plasma cells, TPD52 expression reached its maximum levels at the plasma cell stage. In the Thiel myeloma cell line, TPD52 bound to annexin VI in a Ca(2+)-dependent manner, suggesting that these molecules may act in concert to regulate secretory processes in plasma cells, similarly to what was observed in pancreatic acinar cells. Finally, the anti-TPD52 monoclonal antibody served as a valuable tool for the diagnosis of B-cell malignancies.

What Do Biomedical Researchers Want from Biobanks? Results of an Online Survey.

Publisher: Mary Ann Liebert Inc

Date: 06-2022

DOI: 10.1089/BIO.2021.0084

Biobanking and research quality: think locally, act globally

Publisher: Elsevier BV

Date: 07-2023

DOI: 10.1016/J.TIG.2023.04.001

D53 (TPD52L1) is a cell cycle-regulated protein maximally expressed at the G2-M transition in breast cancer cells

Publisher: Elsevier BV

Date: 10-2005

DOI: 10.1016/J.YEXCR.2005.07.009

Abstract: The cell commits to iding during the G2-M transition, and timing of mitotic entry must be tightly regulated to ensure correct chromosome segregation. Identification of all proteins and molecular events that orchestrate the G2-M transition will be required for a complete understanding of the cell ision cycle, and how its deregulation contributes to cell transformation. We have previously reported D53, a member of the tumor protein D52 family, to be a novel 14-3-3 partner protein in breast cancer cells. We now report that D53 expression is highly upregulated at the G2-M transition in breast cancer cell lines in which D53 is endogenously or exogenously expressed. The timing and subcellular localization of D53 expression paralleled that of cyclin B1, and D53 expression was similarly regulated at both post-transcriptional and post-translational levels. Interactions between D53 and 14-3-3, a negative regulator of the G2-M transition, were increased in synchronized populations enriched for cells in G2/M phases, compared with G1/S arrested cells. Enforced expression of two EGFP-tagged D53 isoforms and the related protein D52 produced high proportions of multinucleated MDA-MB-231 breast carcinoma cells. These results identify D53 as a cell cycle-regulated protein whose deregulated expression can adversely affect the completion of mitosis.

Semi-automated fact-checking of nucleotide sequence reagents in biomedical research publications: The Seek & Blastn tool

Publisher: Public Library of Science (PLoS)

Date: 03-2019

DOI: 10.1371/JOURNAL.PONE.0213266

Striking similarities between publications from China describing single gene knockdown experiments in human cancer cell lines

Publisher: Springer Science and Business Media LLC

Date: 28-12-2016

DOI: 10.1007/S11192-016-2209-6

University Of Sydney

Location: Australia

View Organisation

NSW Health Pathology

Location: Australia

View Organisation

Linkage Infrastructure, Equipment And Facilities - Grant ID: LE100100150

Start Date: 2010

End Date: 12-2012

Amount: $500,000.00

Funder: Australian Research Council