ORCID Profile
0000-0002-4140-7785
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In Research Link Australia (RLA), "Research Topics" refer to ANZSRC FOR and SEO codes. These topics are either sourced from ANZSRC FOR and SEO codes listed in researchers' related grants or generated by a large language model (LLM) based on their publications.
Nanomaterials | Operations Research | Logistics and Supply Chain Management | Business and Management | Photonics, Optoelectronics and Optical Communications | Condensed Matter Physics | Electronic and Magnetic Properties of Condensed Matter; Superconductivity | Post Harvest Horticultural Technologies (incl. Transportation and Storage) |
Expanding Knowledge in the Physical Sciences | Processed Fruit and Vegetable Products (incl. Fruit Juices) | Environmentally Sustainable Transport not elsewhere classified | Expanding Knowledge in Technology
Publisher: Wiley
Date: 02-2011
Publisher: American Association for Cancer Research (AACR)
Date: 30-04-2017
DOI: 10.1158/0008-5472.CAN-16-1663
Abstract: Myc oncoproteins exert tumorigenic effects by regulating expression of target oncogenes. Histone H3 lysine 79 (H3K79) methylation at Myc-responsive elements of target gene promoters is a strict prerequisite for Myc-induced transcriptional activation, and DOT1L is the only known histone methyltransferase that catalyzes H3K79 methylation. Here, we show that N-Myc upregulates DOT1L mRNA and protein expression by binding to the DOT1L gene promoter. shRNA-mediated depletion of DOT1L reduced mRNA and protein expression of N-Myc target genes ODC1 and E2F2. DOT1L bound to the Myc Box II domain of N-Myc protein, and knockdown of DOT1L reduced histone H3K79 methylation and N-Myc protein binding at the ODC1 and E2F2 gene promoters and reduced neuroblastoma cell proliferation. Treatment with the small-molecule DOT1L inhibitor SGC0946 reduced H3K79 methylation and proliferation of MYCN gene– lified neuroblastoma cells. In mice xenografts of neuroblastoma cells stably expressing doxycycline-inducible DOT1L shRNA, ablating DOT1L expression with doxycycline significantly reduced ODC1 and E2F2 expression, reduced tumor progression, and improved overall survival. In addition, high levels of DOT1L gene expression in human neuroblastoma tissues correlated with high levels of MYCN, ODC1, and E2F2 gene expression and independently correlated with poor patient survival. Taken together, our results identify DOT1L as a novel cofactor in N-Myc–mediated transcriptional activation of target genes and neuroblastoma oncogenesis. Furthermore, they characterize DOT1L inhibitors as novel anticancer agents against MYCN- lified neuroblastoma. Cancer Res 77(9) 2522–33. ©2017 AACR.
Publisher: Wiley
Date: 25-01-2011
DOI: 10.1111/J.1440-1746.2010.06466.X
Abstract: Clinicopathological data regarding pancreatic solid pseudopapillary tumors (SPT) in a multiethnic country are limited. The aim of the present study was to characterize pancreatic SPT in Australia. Clinicopathological features, treatment, immunohistochemical findings and outcome data of 34 patients (79% Caucasian, 12% Asian, 6% South Pacific Islander and 3% African) with pancreatic SPT were reviewed. The most presenting complaint was abdominal pain. Median diameter of tumors was 60 mm (range: 20-220) predominantly located in the pancreatic tail (tail : body : head = 23:3:8). All tumors were resected and patients underwent surgery, including a liver resection for metastasis, all patients were alive after a median follow up of 70 months (IQR: 48-178). Two patients underwent repeated surgery for local recurrences with liver metastases after 8 and 18 months, which were successfully managed by surgical resection. Completeness of excision, perineural spread, vascular space invasion, mitotic rate and cellular atypia did not predict recurrence. In all cases, there was aberrant nuclear staining of beta-catenin and a loss of membranous expression of E-cadherin with aberrant nuclear localization of the cytoplasmic domain. Most pancreatic SPT were also strongly positive for CD10 (96%), progesterone receptor (79%), cytokeratin (28%), synapthophysin (26%) and chromogranin (15%). Pancreatic SPT occur in all races and are uniformly indolent. Given complete resection of a pancreatic SPT is usually curative and recurrences can be treated with re-operation, correct diagnosis is important.
Publisher: Cold Spring Harbor Laboratory
Date: 24-07-2200
DOI: 10.1101/713545
Abstract: Continuing recalcitrance to therapy cements pancreatic cancer (PC) as the most lethal malignancy, which is set to become the second leading cause of cancer death in our society. We interrogated the transcriptome, genome, proteome and functional characteristics of 61 novel PC patient-derived cell lines to define novel therapeutic strategies targeting the DNA damage response (DDR) and replication stress. We show that patient-derived cell lines faithfully recapitulate the epithelial component of pancreatic tumors including previously described molecular subtypes. Biomarkers of DDR deficiency, including a novel signature of homologous recombination deficiency, co-segregates with response to platinum and PARP inhibitor therapy in vitro and in vivo . We generated a novel signature of replication stress with potential clinical utility in predicting response to ATR and WEE1 inhibitor treatment. Replication stress and DDR deficiency are independent of each other, creating opportunities for therapy in DDR proficient PC, and post-platinum therapy. We define therapeutic strategies that target subgroups of PC using novel signatures of DNA damage response deficiency and replication stress. This potentially offers patients with DNA repair defects therapeutic options outside standard of care platinum chemotherapy and is being tested in clinical trials on the Precision-Panc platform.
Publisher: Wiley
Date: 06-2015
Abstract: The genus Eucalyptus (Myrtaceae) is mainly native to Australia however, some species are now distributed globally. Eucalyptus has been used in indigenous Australian medicines for the treatment of a range of aliments including colds, flu, fever, muscular aches, sores, internal pains, and inflammation. Eucalyptus oils containing volatile compounds have been widely used in the pharmaceutical and cosmetics industries for a multitude of purposes. In addition, Eucalyptus extracts containing nonvolatile compounds are also an important source of key bioactive compounds, and several studies have linked Eucalyptus extracts with anticancer properties. With the increasing research interest in Eucalyptus and its health properties, this review briefly outlines the botanical features of Eucalyptus, discusses its traditional use as medicine, and comprehensively reviews its phytochemical and anticancer properties and, finally, proposes trends for future studies.
Publisher: MDPI AG
Date: 20-09-2018
DOI: 10.3390/NU10101336
Abstract: The type 2 family of taste receptors (T2Rs) detect and respond to bitter tastants. These receptors are expressed throughout the gastrointestinal (GI) tract, with location dependant roles. In the oral cavity, T2Rs are involved in the conscious perception of bitter tastants, while in the lower GI tract they have roles in chemoreception and regulation of GI function. Through these erse roles, these receptors may be involved in modulating appetite and diet, with consequences for weight regulation and obesity. Interestingly, the concentration of T2Rs in the GI tract is greatest in the large intestine, the organ with the densest colonisation of bacteria. The gut microbiome has been the subject of intense research, as a plethora of roles linking microbiota to human health continue to be uncovered. Of particular interest is the microbial signature associated with obesity. Obesity is a leading health concern, and advances in our understanding of this disease are needed. Diet is a known modifiable factor in the development of obesity. However, diet only partially explains disease risk. Changes in microbial energy harvesting by the microbiota plays a role in obesity, and the composition of these energy harvesting populations may be controlled by taste receptors. This review explores T2Rs as a potential link between obesity and the human GI microbiome.
Publisher: Informa UK Limited
Date: 26-02-2018
Publisher: Elsevier BV
Date: 07-2012
Publisher: Hindawi Limited
Date: 02-06-2016
DOI: 10.1111/JFPP.12719
Publisher: Elsevier BV
Date: 08-2016
Publisher: Wiley
Date: 13-07-2021
Abstract: In silico approaches identified 1 , N ‐(6‐((4‐bromo‐ benzyl)amino)hexyl)‐3,5‐bis(trifluoromethyl)benzene sulfonamide, as a potential inhibitor of the S100A2‐p53 protein‐protein interaction, a validated pancreatic cancer drug target. Subsequent cytotoxicity screening revealed it to be a 2.97 μM cell growth inhibitor of the MiaPaCa‐2 pancreatic cell line. This is in keeping with our hypothesis that inhibiting this interaction would have an anti‐pancreatic cancer effect with S100A2, the validated PC drug target. A combination of focused library synthesis (three libraries, 24 compounds total) and cytotoxicity screening identified a propyl alkyl diamine spacer as optimal the nature of the terminal phenyl substituent had limited impact on observed cytotoxicity, whereas N ‐methylation was detrimental to activity. In total 15 human cancer cell lines were examined, with most analogues showing broad‐spectrum activity. Near uniform activity was observed against a panel of six pancreatic cancer cell lines: MiaPaCa‐2, BxPC‐3, AsPC‐1, Capan‐2, HPAC and PANC‐1. In all cases there was good to excellent correlation between the predicted docking pose in the S100A2‐p53 binding groove and the observed cytotoxicity, especially in the pancreatic cancer cell line with high endogenous S100A2 expression. This supports S100A2 as a pancreatic cancer drug target.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2006
DOI: 10.1002/HEP.21294
Abstract: Proteomic techniques promise to improve the diagnosis of cholangiocarcinoma (CC) in both tissue and serum as histological diagnosis and existing serum markers exhibit poor sensitivities. We explored the use of surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) to identify potential protein biomarkers of CC. Twenty-two resected CC s les were compared with adjacent noninvolved bile duct tissue. Serum from patients with CC (n=20) was compared with patients with benign disease (n=20), and healthy volunteers (n=25). S les were analyzed on hydrophobic protein chips via SELDI-TOF MS, and classification models were developed using logistic regression and cross-validation analysis. Univariate analysis revealed 14 in idual peaks differentially expressed between CC and bile duct tissue, 4 peaks between CC and benign disease, and 12 peaks between CC and sera of healthy volunteers. The 4,462 mass-to-charge serum peak had superior discriminatory ability to carbohydrate antigen 19.9 (CA19.9) and carcinoembryonic antigen (CEA) (P=.004 receiver operating characteristic [ROC] area under the curve [AUC]=0.76, 0.73, and 0.70, respectively). The training models developed panels of peaks that distinguished CC from bile duct tissue (92.5% sensitivity, 92.3% specificity ROC AUC=0.96), CC from benign serum (65.0% sensitivity, 70.0% specificity ROC AUC=0.83), and CC from sera of healthy volunteers (75.0% sensitivity, 100% specificity ROC AUC=0.92). Serum results were further improved with the inclusion of CA19.9 and CEA (ROC AUC=0.86 and 0.99 for CC vs benign and healthy volunteer serum, respectively). In conclusion, biomarker panels are capable of distinguishing CC from nonmalignant tissue serum markers have important diagnostic implications for unknown bile duct stricture.
Publisher: Elsevier BV
Date: 02-2019
Publisher: Springer Science and Business Media LLC
Date: 04-2015
Publisher: Wiley
Date: 28-01-2005
DOI: 10.1111/J.1440-1746.2004.03531.X
Abstract: Overexpression of urokinase-type plasminogen activator (uPA) has been shown to be strongly associated with an increased metastatic potential and poor prognosis in a variety of human malignancies. It was hypothesized that uPA would be overexpressed in highly metastatic pancreatic cancer. The aims of this study were to analyze uPA mRNA expression in pancreatic cancer and to correlate this to the expression of uPA protein and to the stage of the disease. Twenty-one pancreatic adenocarcinoma, six ullary carcinoma and 10 benign mucinous cystadenoma s les, all with adjacent normal tissue, were collected. uPA mRNA was measured using real-time quantitative reverse transcription polymerase chain reaction. Localization of uPA within normal and pancreatic tumor sections was subsequently confirmed using immunohistochemistry. The median and range of the ratios of uPA mRNA measures between tumor tissue and non-involved pancreatic tissue was 17.1 (1.4-653.6) for pancreatic adenocarcinoma (P < 0.001), 3.9 (0.7-7.7) for ullary carcinoma (P = 0.055) and 1.9 (0.6-5.9) for mucinous cystadenoma tissue (P = 0.052). uPA low tumors were associated with an exuberant stromal reaction, whereas uPA high tumors showed little stromal response. Immunohistochemistry confirmed that uPA protein was more prevalent in pancreatic adenocarcinoma tissue than in normal tissue and that it was membrane-bound. uPA mRNA expression was significantly associated with poorly differentiated pancreatic cancers (P < 0.05) and positively associated with tumor stage. These observations suggest that significant overexpression of uPA correlates closely to the rapid progression and invasiveness of pancreatic cancer and that uPA may provide a future therapeutic target for pancreatic cancer treatment.
Publisher: Wiley
Date: 20-02-2017
DOI: 10.1002/APJ.2076
Publisher: Bentham Science Publishers Ltd.
Date: 11-2021
DOI: 10.2174/2665978602666210127110728
Abstract: Scaevola spinescens is an endemic Australian shrub that is linked to various health benefits and traditionally used as medicine by decoction. To date, the extraction efficiency of the plant under various conditions has not been well understood. This study aimed to optimize aqueous extraction conditions of S. spinescens, for maximum extraction of total phenolic compounds, flavonoids and saponins, as well as antioxidant activities. Response surface methodology was used to determine the influence of four independent parameters including temperature, time, s le-to-water ratio and pH. The optimal ranges of temperature (60-90 °C), time (30-60 min), s le-to-water ratio (2-6 g/100 mL) and pH (3-7) were determined in preliminary experiments. Following assessment and optimization of the response surface methodology models, validation experiments were conducted to compare predicted and experimental values. The RSM models showed that extraction temperature, time and s le-to-water ratio significantly affected total phenolic compound yields. Extraction temperature and time significantly affected flavonoid yields, while only s le-to-water ratio significantly affected saponin yields. Optimal conditions for extraction were determined to be: 90 ºC, 53 min, 2:100 (g/mL), and pH of 4.5, if saponins are the target compounds for extraction. For phenolics, flavonoids and antioxidant capacity, a higher s le-to-water ratio of 6:100 (g/mL) is recommended. Response surface methodology proved to be a reliable method for predicting yields of bioactive compounds and antioxidant capacity in S. spinescens. These findings can be used for efficient decoction by practitioners and end users, or by researchers for further isolation and purification of bioactive compounds from S. spinescens extracts.
Publisher: Elsevier BV
Date: 05-2006
DOI: 10.1053/J.GASTRO.2006.02.036
Abstract: Pancreatic adenocarcinoma is a most devastating cancer that presents late and is rapidly progressive. This study aimed to identify unique, tissue-specific protein biomarkers capable of differentiating pancreatic adenocarcinoma (PC) from adjacent uninvolved pancreatic tissue (AP), benign pancreatic disease (B), and nonmalignant tumor tissue (NM). Tissue s les representing PC (n = 31), AP (n = 44), and B (n = 19) tissue were analyzed on hydrophobic protein chip arrays by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. Training models were developed using logistic regression and validated using the 10-fold cross-validation approach. The hydrophobic protein chip array revealed 13 protein peaks differentially expressed between PC and AP (receiver operating characteristic [ROC] area under the curve [AUC], 0.64-0.85), 8 between PC and B (ROC AUC, 0.67-0.78), and 12 between PC and NM tissue (ROC AUC, 0.63-0.81). Logistic regression and cross-validation identified overlapping panels of peaks to develop a training model that distinguished PC from AP (77.4% sensitivity, 84.1% specificity), B (83.9% sensitivity, 78.9% specificity), and NM tissue (58.1% sensitivity, 90.5% specificity). The final panels selected correctly classified 80.6% of PC and 88.6% of AP s les (ROC AUC, 0.92), 93.5% of PC and 89.5% of B s les (ROC AUC, 0.99), and 71.0% of PC and 92.1% of NM s les (ROC AUC, 0.91). This study used surface-enhanced laser desorption/ionization time-of-flight mass spectrometry to discover a number of protein panels that can distinguish effectively between pancreatic adenocarcinoma, benign, and adjacent pancreatic tissue. Identification of these proteins will add to our understanding of the biology of pancreatic cancer. Furthermore, these protein panels may have important diagnostic implications.
Publisher: MDPI AG
Date: 18-05-2020
DOI: 10.3390/NU12051455
Abstract: Elevated homocysteine (Hcy) levels are a risk factor for vascular diseases. Recently, increases in ultraviolet radiation (UVR) have been linked to decreased Hcy levels. This relationship may be mediated by the status of UVR-responsive vitamins, vitamin D and folate, and/or genetic variants influencing their levels however, this has yet to be examined. Therefore, the independent and interactive influences of environmental UVR, vitamin D and folate levels and related genetic variants on Hcy levels were examined in an elderly Australian cohort (n = 619). Red blood cell folate, 25-hydroxyvitamin D (25(OH)D), and plasma Hcy levels were determined, and genotyping for 21 folate and vitamin D-related variants was performed. Erythemal dose rate accumulated over six-weeks (6W-EDR) and four-months (4M-EDR) prior to clinics were calculated as a measure of environmental UVR. Multivariate analyses found interactions between 6W-EDR and 25(OH)D levels (pinteraction = 0.002), and 4M-EDR and MTHFD1-rs2236225 (pinteraction = 0.006) in predicting Hcy levels. The association between 6W-EDR and Hcy levels was found only in subjects within lower 25(OH)D quartiles ( .26 ng/mL), with the association between 4M-EDR and Hcy occurring only in subjects carrying the MTHFD1-rs2236225 variant. 4M-EDR, 6W-EDR, and MTHFD1-rs2236225 were also independent predictors of Hcy. Findings highlight nutrient–environment and gene–environment interactions that could influence the risk of Hcy-related outcomes.
Publisher: Springer Science and Business Media LLC
Date: 09-06-2017
Publisher: Springer Science and Business Media LLC
Date: 09-01-2016
DOI: 10.1515/CHEMPAP-2015-0240
Abstract: Phyllanthus amarus (P. amarus) is a herbal plant used in the treatment of various diseases such as hepatitis, diabetes, and cancer. Efficiency of its bioactive compounds extraction and therefore the biological activity of the extracts are significantly influenced by both solvent character and extraction method. This study is aimed at the determination of the influence of six various solvents (water, acetonitrile, ethanol, methanol, ethyl acetate, and dichloromethane) and nine different extraction methods (conventional, ultrasound-assisted, microwave-assisted, and six novel methods) on the extraction efficiency and antioxidant capacity of P. amarus. The results indicated that water extracted the maximal amount of phenolics from P. amarus and had the highest antioxidant capacity, while microwave-assisted extraction provided the highest yields of phenolics and saponins, and the highest antioxidant capacity with the lowest energy consumption when compared to the other extraction methods. These findings implied that water and microwave-assisted extraction are recommended as the most effective solvent and method for the extraction of bioactive compounds from P. amarus for potential application in the pharmaceutical and nutraceutical industries.
Publisher: MDPI AG
Date: 24-02-2021
DOI: 10.3390/NU13030719
Abstract: Differences in sour-taste thresholds have been identified in cognition-related diseases. Diet is a modulator of cognitive health, and taste perception influences dietary preferences and habits. Heritable genetics and polymorphisms in the KCNJ2 gene involved in the transduction of sour taste have been linked to variations in sour taste and non-gustatory functions. However, relationships between sour taste genetics, mild cognitive impairment, and diet quality are yet to be elucidated. This study investigated the associations between the presence of the KCNJ2-rs236514 variant (A) allele, diet quality indices, and mild cognitive impairment evaluated by the Mini-Mental State Examination (MMSE), in a secondary cross-sectional analysis of data from the Retirement Health & Lifestyle Study. Data from 524 elderly Australians (≥65y) were analyzed, using standard least squares regression and nominal logistic regression modeling, with demographic adjustments applied. Results showed that the presence of the KCNJ2-A allele is associated with increased proportions of participants scoring in the range indicative of mild or more severe cognitive impairment (MMSE score of ≤26) in the total cohort, and males. These associations remained statistically significant after adjusting for age, sex, and diet quality indices. The absence of association between the KCNJ2-A allele and cognitive impairment in women may be related to their higher diet quality scores in all indices. The potential link between sour taste genotype and cognitive impairment scores may be due to both oral and extra-oral functions of sour taste receptors. Further studies are required on the role and relationship of neurotransmitters, sour taste genotypes and sour taste receptors in the brain, and dietary implications, to identify potential risk groups or avenues for therapeutic or prophylactic interventions.
Publisher: Springer Science and Business Media LLC
Date: 23-11-2012
DOI: 10.1038/CDD.2012.147
Publisher: Wiley
Date: 12-07-2021
Abstract: In silico screening predicted 1 ( N ‐(4‐((4‐(3‐(4‐(3‐methoxyphenyl)‐1 H ‐1,2,3‐triazol‐1‐yl)propyl)piperazin‐1‐yl) sulfonyl)‐phenyl)acetamide) as an inhibitor of the S100A2‐p53 protein‐protein interaction. S100A2 is a validated pancreatic cancer drug target. In the MiaPaCa‐2 pancreatic cell line, 1 was a ∼50 μM growth inhibitor. Synthesis of five focused compound libraries and cytotoxicity screening revealed increased activity from the presence of electron withdrawing moieties on the sulfonamide aromatic ring, with the 3,5‐bis‐CF 3 Library 3 analogues the most active, with GI 50 values of 0.91 (3‐ClPh 13 i BxPC‐3, Pancreas) to 9.0 μM (4‐CH 3 13 d PANC‐1, Pancreas). Activity was retained against an expanded pancreatic cancer cell line panel (MiaPaCa‐2, BxPC‐3, AsPC‐1, Capan‐2, PANC‐1 and HPAC) and the normal cell line MCF10A (breast). Bulky 4‐disposed substituents on the terminal phenyl ring enhanced broad spectrum activity with growth inhibition values spanning 1.1 to 3.1 μM (4‐C(CH 3 ) 3 13 e BxPC‐3 and AsPC‐1 (pancreas), respectively). Central alkyl spacer contraction from propyl to ethyl proved detrimental to activity with Library 4 and 5.5‐ to 10‐fold less cytotoxic than the propyl linked Library 2 and Library 3 . The data herein was consistent with the predicted binding poses of the compounds evaluated. The highest levels of cytotoxicity were observed with those analogues best capable of adopting a near identical pose to the p53‐peptide in the S100A2‐p53 binding groove.
Publisher: Springer Science and Business Media LLC
Date: 05-01-2007
DOI: 10.1007/S00268-006-0289-9
Abstract: Recent findings suggest that the urokinase-type plasminogen activator (uPA), its receptor (uPAR), plasminogen activator inhibitor-1 (PAI-1), and -2 (PAI-2) play key roles in cancer invasion. The prognostic value of components of this system is well established in breast cancer. However, little is known of its involvement in pancreatic cancer (PC). Quantitative real-time polymerase chain reaction (Q-RT-PCR) was used on tissue-banked specimens and immunohistochemistry (IHC) on paraffin specimens was used to measure expression of uPA, uPAR, PAI-1, and PAI-2 proteins in 46 PC and 12 cystadenoma specimens. Results were related to survival using Cox's proportional hazards testing. Increased expression of uPA, uPAR, and PAI-1 in PC tissue were independently associated with a higher Union Internationale Contre le Cancer [International Union Against Cancer (UICC)] tumor stage (P < 0.001) and were intercorrelated (P < 0.001). Overexpression of uPAR indicated reduced survival (P = 0.03). Conversely, PAI-2 messenger ribonucleic acid (mRNA) overexpression, which occurred in 21 of 46 tumors, negatively correlated with tumor size (P = 0.008) and survival (P < 0.007) but not with uPA, uPAR, or tumor stage. There was good agreement between PAI-2 mRNA value and IHC score (P < 0.001). Using Cox's stepwise analysis, PAI-2 mRNA value (HR = 0.24 P = 0.001) and UICC tumor stage (HR = 2.014 P = 0.001) independently predicted survival. An IHC score for PAI-2 of 3+ or 4+ also independently predicted improved survival (HR = 2.72 P = 0.025). The uPA/uPAR/PAI-1 system is activated in advanced pancreatic cancer and may account for the tumor's aggressive behavior, whereas PAI-2 expression appears to be independent of uPA/uPAR/PAI-1 and is associated with improved prognosis. Because of its intercorrelation with mRNA expression, PAI-2 IHC may be used as an indicator of survival.
Publisher: Wiley
Date: 21-08-2021
DOI: 10.1002/AJHB.23667
Abstract: To test the “vitamin D‐folate hypothesis for the evolution of human skin pigmentation.” Total ozone mapping spectrometer (TOMS) satellite data were used to examine surface UV‐irradiance in a large ( n = 649) Australian cross‐sectional study population. Genetic analysis was used to score vitamin D‐ and folate‐related gene polymorphisms ( n = 22), along with two pigmentation gene variants ( IRF4 ‐rs12203592/ HERC2‐ rs12913832). Red cell folate and vitamin D 3 were measured by immunoassay and HPLC, respectively. Ultraviolet radiation (UVR) and pigmentation genes interact to modify blood vitamin levels Light skin IRF4 ‐TT genotype has greatest folate loss while light skin HERC2 ‐GG genotype has greatest vitamin D 3 synthesis (reflected in both TOMS and seasonal data). UV‐wavelength exhibits a dose–response relationship in folate loss within light skin IRF4 ‐TT genotype (305 310 324 380 nm). Significant vitamin D 3 photosynthesis only occurs within light skin HERC2 ‐GG genotype, and is maximal at 305 nm. Three dietary antioxidants (vitamins C, E, and β‐carotene) interact with UVR and pigmentation genes preventing oxidative loss of labile reduced folate vitamers, with greatest benefit in light skin IRF4 ‐TT subjects. The putative photosensitiser, riboflavin, did not sensitize red cell folate to UVR and actually afforded protection. Four genes (5xSNPs) influenced blood vitamin levels when stratified by pigmentation genotype MTHFR ‐rs1801133/rs1801131, TS ‐rs34489327, CYP24A ‐rs17216707, and VDR‐ApaI ‐rs7975232. Lightest IRF4 ‐TT/darkest HERC2 ‐AA genotype combination (greatest folate loss/lowest vitamin D 3 synthesis) has 0% occurrence. The opposing, commonest (39%) compound genotype (darkest IRF4 ‐CC/lightest HERC2 ‐GG) permits least folate loss and greatest synthesis of vitamin D 3 . New biophysical evidence supports the vitamin D‐folate hypothesis for evolution of skin pigmentation.
Publisher: Springer Science and Business Media LLC
Date: 08-09-2018
Publisher: MDPI AG
Date: 05-09-2019
DOI: 10.3390/SEPARATIONS6030044
Abstract: Mangiferin has been reported to exhibit anti-viral, anti-cancer, anti-diabetic, immunomodulatory and hepatoprotective properties. This study aimed to develop an HPLC method to isolate mangiferin from Salacia chinensis L. root investigate the impact of solvents on yield optimise the ultrasound-assisted extraction (UAE) technique and compare mangiferin yield with continuously shaking extraction (CSE) and decoction techniques. The results showed that mangiferin, with a purity of over 88%, could be achieved by HPLC using a mixture of solvent A (water: acetonitrile: orthophosphoric acid, 96.8:3:0.2 (v/v/v)) and solvent B (acetonitrile). Solvent type significantly affected the extraction yield of mangiferin, and a mixture of acetone and water gave the highest extraction yield, as compared to other solvents or mixtures. UAE conditions, such as ultrasonic power, temperature, time and concentration of acetone significantly affected the extraction of mangiferin. Optimal UAE conditions were at an ultrasonic power of 250 W, temperature of 50 °C, acetone concentration of 40% and extraction time of 60 min. These optimal conditions could extract approximately 92 mg, whereas CSE and decoction only extracted 89.20 mg and 58.71 mg of mangiferin, respectively, from 1 g of S. chinensis root. Therefore, these UAE conditions are recommended for the extraction of mangiferin from S. chinensis root for further utilisation.
Publisher: Wiley
Date: 26-01-2018
DOI: 10.1111/IJFS.13732
Publisher: Elsevier BV
Date: 03-2018
Publisher: Springer Science and Business Media LLC
Date: 18-02-2019
Publisher: MDPI AG
Date: 23-08-2016
DOI: 10.3390/FOODS5030055
Publisher: Informa UK Limited
Date: 11-10-2018
Publisher: Hindawi Limited
Date: 04-07-2016
DOI: 10.1111/JFPP.13025
Publisher: Springer Science and Business Media LLC
Date: 05-01-2015
DOI: 10.1515/CHEMPAP-2015-0237
Abstract: Eucalyptus species have found their place in traditional medicine and pharmacological research and they have also been shown to possess a large number of phenolic compounds and antioxidants. The present study sought to implement conventional extraction to yield maximal total phenolic content (TPC), total flavonoid content (TFC), proanthocyanidins, antioxidants, and saponins from E. robusta using different solvents. The most suitable extraction solvent was further employed for extracting phytochemicals from E. saligna, E. microcorys, and E. globulus to select the Eucalyptus species with the greatest bioactive compound content. The results emphasised the efficiency of water in extracting TPC ((150.60 ± 2.47) mg of gallic acid equivalents per g), TFC ((38.83 ± 0.23) mg of rutin equivalents per g), proanthocyanidins ((5.14 ± 0.77) mg of catechin equivalents per g), and antioxidants ABTS ((525.67 ± 1.99) mg of trolox equivalents (TE) per g), DPPH ((378.61 ± 4.72) mg of TE per g) CUPRAC ((607.43 ± 6.69) mg of TE per g) from E. robusta. Moreover, the aqueous extract of E. robusta had the highest TPC, TFC and antioxidant values among the other Eucalyptus species tested. These findings highlighted the efficiency of conventional extraction in extracting natural bioactive compounds from Eucalyptus species for pharmaceutical and nutraceutical applications.
Publisher: Informa UK Limited
Date: 10-04-2017
Publisher: Informa UK Limited
Date: 04-10-2016
Publisher: Impact Journals, LLC
Date: 11-11-2015
Publisher: Wiley
Date: 28-11-2017
DOI: 10.1111/IJFS.13571
Publisher: Springer Science and Business Media LLC
Date: 28-08-2020
DOI: 10.1038/S41467-020-17359-2
Abstract: Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research.
Publisher: Springer Science and Business Media LLC
Date: 2016
DOI: 10.1515/CHEMPAP-2016-0009
Abstract: is known as a healing herb which has traditionally been used in the treatment of various diseases such as hepatitis, diabetes and cancer. The extraction parameters have great effects on the extraction efficiency of bioactive compounds and pharmacological activity of the extracts. This study sought to optimise the microwave-assisted extraction parameters for phenolic compounds-enriched extracts and antioxidant capacity from
Publisher: Elsevier BV
Date: 03-2014
DOI: 10.1016/J.JEP.2013.12.023
Abstract: Pancreatic cancer is a devastating cancer that presents late, is rapidly progressive and has current therapeutics with only limited efficacy. Bioactive compounds are ubiquitously present in fruits and numerous studies in vitro are addressing the activity of these compounds against pancreatic cancer, thus studies of specific bioactive compounds could lead to new anti-pancreatic cancer strategies. Australian native fruits have been used as foods and medicines by Australian Aboriginals for thousands of years, and preliminary studies have found these fruits to contain rich and ersified bioactive components with high antioxidant activity. Thus, Australian native fruits may possess key components for preventing or delaying the onset of tumorigenesis, or for the treatment of existing cancers, including pancreatic cancer. Numerous databases including PubMed, SciFinder, Web of Knowledge, Scopus, and Sciencedirect were analysed for correlations between bioactive components from fruits and pancreatic cancer, as well as studies concerning Australian native fruits. In this review, we comprehensively highlight the proposed mechanisms of action of fruit bioactives as anti-cancer agents, update the potential anti-pancreatic cancer activity of various major classes of bioactive compounds derived from fruits, and discuss the existence of bioactive compounds identified from a selection Australian native fruits for future studies. Bioactive compounds derived from fruits possess the potential for the discovery of new anti-pancreatic cancer strategies. Further, Australian native fruits are rich in polyphenols including some flora that contain unique phenolic compounds, thereby warranting further investigations into their anti-cancer properties.
Publisher: JMIR Publications Inc.
Date: 03-05-2018
Abstract: retravel health advice can play a crucial role in improving both travelers’ awareness about disease risk and compliance with preventive measures. General practitioners (GPs) and the internet have been reported internationally to be the main sources of health advice for travelers to non–mass gathering (MG) destinations. However, few studies have attempted to investigate the sources of health advice among travelers to MGs including the Hajj pilgrimage, and none of these studies further investigated the impact of pretravel advice on pilgrims’ health behaviors. he objective of this study was to investigate the impact of the source of pretravel health advice (from GPs and specialized Hajj travel agents) on Hajj pilgrims’ awareness of and compliance with health recommendations, and the incidence of Hajj-associated illnesses. prospective cohort study (before and during Hajj) was conducted among Australian pilgrims aged ≥18 years in 2015. total of 421 pilgrims participated prior to Hajj, and 391 (93%) provided follow-up data during Hajj. All participants obtained pretravel health advice from one or more sources, with Hajj travel agents (46%) and general practitioners (GPs 40%) the most commonly reported sources. In total, 288 (74%) participants reported Hajj-related symptoms, of which 86% (248/288) were respiratory symptoms. Participants who obtained pretravel health advice from travel agents were more likely to be aware of the official Saudi recommendations (adjusted odds ratio [aOR] 2.1, 95% CI 1.2-3.8 i P /i =.01), receive recommended vaccines before travel (aOR 2.4, 95% CI 1.4-3.9 i P /i =.01), use hand sanitizers including soap (aOR 2.5, 95% CI 1.1-6.1 i P /i =.03), and wash their hands after touching an ill person during Hajj (aOR 2.9, 95% CI 1.1-7.1 i P /i =.01), compared to those who sought advice from GPs. However, neither advice from travel agents nor GPs was associated with a lower incidence of Hajj-related illnesses. dvice from travel agents appeared to be accessed by more travelers than that from GPs, and was associated with an increased likelihood of positive travel health behaviors.
Publisher: Elsevier BV
Date: 11-2017
DOI: 10.1016/J.IJBIOMAC.2017.06.051
Abstract: The influence of different plasticizers (glycols, sugars and polyols) on the moisture sorption, mechanical, physical, optical, and microstructure characteristics of pea starch-guar gum (PSGG) film was studied. All plasticizers formed homogeneous, transparent, and smooth films, while PEG-400 did not produce film with suitable characteristics. Fourier transform infrared (FTIR) spectroscopy results indicated some interaction between plasticizers and the polymers. Scanning electron microscopy (SEM) observations of the films presented surfaces without cracks, breaks, or openings which were indicator of the miscibility and compatibility of employed plasticizers with PSGG films. The results showed that the films containing plasticizers with higher functional groups had lower equilibrium moisture content at aw EG > PG > xylitol > fructose > sorbitol > mannitol > galactose > glucose > sucrose > maltitol.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2005
DOI: 10.1097/01.PAS.0000160979.85457.73
Abstract: HER-2 is a transmembrane growth factor receptor recognized in overexpression as an independent adverse prognostic factor in several cancers. This study measured HER-2 overexpression in pancreatic adenocarcinoma at the genetic, transcriptional, and translational level. Expression was gauged with regard to stage, grade, and survival. Pancreatic adenocarcinoma s les (n = 30) were analyzed with immunohistochemical labeling for HER-2 protein, Quantitative real-time reverse transcriptase polymerase chain reaction (Q-RT-PCR) measurement of HER-2 mRNA and fluorescence in situ hybridization (FISH) analysis of HER-2 gene expression. HER-2 expression in benign pancreatic lesions (n = 10) provided a control. Five (17%) of the pancreatic adenocarcinomas scored maximal 3+ immunohistochemistry (IHC) labeling, seven (23%) had significantly increased expression of HER-2 mRNA, while only one (3%) exhibited low level HER-2 gene lification. Ten (33%) tumors demonstrated aneuploidy. In general, concordance between methodologies was poor, but the best agreement was seen between FISH aneuploidy status and Q-RT-PCR mRNA overexpression (80% agreement), followed by IHC and Q-RT-PCR (73% agreement). The least agreement was seen between IHC and FISH aneuploidy status (67% agreement). Tumor stage was positively associated with HER-2 mRNA and protein expression, but tumor grade and other patient characteristics did not reach statistical significance. A poor survival outcome was demonstrated with positive HER-2 status in all three measures of overexpression (Kaplan-Meier log-rank score P < 0.01 [IHC], P = 0.05 [Q-RT-PCR], P = 0.02 [FISH]). Discordance in expression at the nuclear, cytoplasmic, and cell surface levels highlights the limitations of immunohistochemical evaluation alone and stresses the need for further evaluation of response to anti-HER-2 targeted therapies in tumors displaying overexpression in gene copy, mRNA, and receptor protein.
Publisher: Elsevier BV
Date: 12-2018
Publisher: Elsevier BV
Date: 04-2011
Publisher: Elsevier BV
Date: 11-2017
Publisher: Hindawi Limited
Date: 17-11-2016
DOI: 10.1111/JFPP.13148
Publisher: Hindawi Limited
Date: 15-06-2016
DOI: 10.1111/JFPP.12851
Publisher: Springer Science and Business Media LLC
Date: 21-09-2020
DOI: 10.1038/S41467-020-18151-Y
Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA s les, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological ergences between two reproducible somatic variant detection efforts.
Publisher: Hindawi Limited
Date: 17-11-2017
DOI: 10.1111/JFPP.13152
Publisher: Elsevier BV
Date: 2021
Publisher: Wiley
Date: 14-03-2018
Publisher: Springer Science and Business Media LLC
Date: 14-11-2019
DOI: 10.1007/S11033-019-05180-0
Abstract: Pancreatic cancer (PC) is one of the leading causes of cancer death in Western societies. The absence of specific symptoms, late diagnosis and the resistance towards chemotherapy result in significant treatment difficulties. As such, it is important to find more effective therapeutic agents for the treatment of PC. Helicteres hirsuta Lour. (H. hirsuta) has been traditionally used in many countries for the treatment of various ailments, indicating that it contains potential therapeutic agents. This study aimed to derive different fractions from the saponin-enriched extract of H. hirsuta stem using RP-HPLC and examine the in vitro anti-pancreatic cancer activity of the derived fractions (F0-F5). With the exception of F0, the five fractions (F1-F5) possessed strong inhibitory activity against PC cells at IC
Publisher: Springer Science and Business Media LLC
Date: 08-06-2017
Publisher: Springer Science and Business Media LLC
Date: 12-09-2018
DOI: 10.1007/S11033-018-4370-X
Abstract: Helicteres hirsuta Lour. (H. hirsuta) has been considered as a herbal medicine for the treatment of malaria and diabetes but limited studies have been conducted on its anticancer and antibacterial properties. In this study, the in vitro antibacterial and anticancer properties of the leaf and stem extracts and their two sub-fractions (aqueous and saponin-enriched butanol fractions) prepared from H. hirsuta were elucidated. MTT and CCK-8 assays were employed to assess their in vitro anticancer properties against various cancer cell lines. The antibacterial activity was assessed using the disc diffusion method and minimum inhibitory concentration (MIC) values were determined. The results revealed that the saponin-enriched fractions from H. hirsuta leaves and stems showed the highest antibacterial activity against E. coli (MIC values of 2.50 and 5.00 mg/mL, respectively) and S. lugdunensis (MIC values of 0.35 and 0.50 mg/mL, respectively). Importantly, these saponin-enriched fractions possessed strong anticancer activity in vitro towards a range of cancer cell lines including MIA PaCa-2 (pancreas) A2780 (ovarian) H460 (lung) A431 (skin) Du145 (prostate) HT29 (colon) MCF-7 (breast) SJ-G2, U87, SMA (glioblastoma) and BE2-C (neuroblastoma) at low doses (GI
Publisher: Springer Science and Business Media LLC
Date: 25-02-2015
DOI: 10.1038/NATURE14169
Publisher: International Society for Horticultural Science (ISHS)
Date: 03-2020
Publisher: Elsevier BV
Date: 09-2014
Publisher: Spandidos Publications
Date: 16-02-2015
Abstract: Despite incremental advances in the diagnosis and treatment for pancreatic cancer (PC), the 5‑year survival rate remains <5%. Novel therapies to increase survival and quality of life for PC patients are desperately needed. Epigenetic thera-peutic agents such as histone deacetylase inhibitors (HDACi) and DNA methyltransferase inhibitors (DNMTi) have demonstrated therapeutic benefits in human cancer. We assessed the efficacy of these epigenetic therapeutic agents as potential therapies for PC using in vitro and in vivo models. Treatment with HDACi [suberoylanilide hydroxamic acid (SAHA)] and DNMTi [5‑AZA‑2' deoxycytidine (5‑AZA‑dc)] decreased cell proliferation in MiaPaCa2 cells, and SAHA treatment, with or without 5‑AZA‑dc, resulted in higher cell death and lower DNA synthesis compared to 5‑AZA‑dc alone and controls (DMSO). Further, combination treatment with SAHA and 5‑AZA‑dc significantly increased expression of p21WAF1, leading to G1 arrest. Treatment with epigenetic agents delayed tumour growth in vivo, but did not decrease growth of established pancreatic tumours. In conclusion, these data demonstrate a potential role for epigenetic modifier drugs for the management of PC, specifically in the chemoprevention of PC, in combination with other chemotherapeutic agents.
Publisher: MDPI AG
Date: 17-09-2014
Publisher: Hindawi Limited
Date: 29-04-2015
DOI: 10.1111/JFPP.12506
Publisher: American Society of Clinical Oncology (ASCO)
Date: 10-06-2009
Abstract: Current adjuvant therapies for pancreatic cancer (PC) are inconsistently used and only modestly effective. Because a high proportion of patients who undergo resection for PC likely harbor occult metastatic disease, any adjuvant trials assessing therapies such as radiotherapy directed at locoregional disease are significantly underpowered. Stratification based on the probability (and volume) of residual locoregional disease could play an important role in the design of future clinical trials assessing adjuvant radiotherapy. We assessed the relationships between margin involvement, the proximity to operative resection margins and outcome in a cohort of 365 patients who underwent operative resection for PC. Microscopic involvement of a resection margin by tumor was associated with a poor prognosis. Stratifying the minimum clearance of resection margins by 0.5-mm increments demonstrated that although median survival was no different to clear margins based on these definitions, it was not until the resection margin was clear by more than 1.5 mm that optimal long-term survival was achieved. These data demonstrate that a margin clearance of more than 1.5 mm is important for long-term survival in a subgroup of patients. More aggressive therapeutic approaches that target locoregional disease such as radiotherapy may be beneficial in patients with close surgical margins. Stratification of patients for entry onto future clinical trials based on this criterion may identify those patients who benefit from adjuvant radiotherapy.
Publisher: MDPI
Date: 10-11-2020
Publisher: Informa UK Limited
Date: 03-09-2017
Publisher: Wiley
Date: 03-05-2017
Abstract: Xao tam phan (Paramignya trimera) has been used for the treatment of cancer and cancer-like aliments. Among different parts of the P. trimera plant, leaf is considered as a residual part after harvesting of the root. This study aimed to determine the physiochemical properties and the antioxidant and anti-proliferative capacities of P. trimera leaf (PTL) using microwave drying for the preparation of dry s le MeOH and microwave-assisted extraction for the preparation of crude extract and freeze-drying for the preparation of powdered extract. The results showed that total phenolic, total flavonoid, proanthocyanidin, and saponin contents of PTL prepared by microwave drying at 450 W were 25.4 mg gallic acid equiv. (GAE), 86.3 mg rutin equiv. (RE), 5.6 mg catechin equiv. (CE), and 702.1 mg escin equiv. (EE) per gram dried s le, respectively. Gallic acid, protocatechuic acid, ellagic acid, rutin, and quercetin were identified in the PTL MeOH extract. Dried PTL displayed potent antioxidant activity, while the powdered PTL extract exhibited great anti-proliferative capacity on various cancer cell lines including MiaPaCa-2 (pancreas), HT29 (colon), A2780 (ovarian), H460 (lung), A431 (skin), Du145 (prostate), BE2-C (neuroblastoma), MCF-7 (breast), MCF-10A (normal breast), and U87, SJ-G2, and SMA (glioblastoma). Anti-proliferative capacity on pancreatic cancer cells (MiaCaPa2, BxPc3, and CFPAC1) of PTL extract (200 μg/ml) was significantly higher (P < 0.05) than those of ostruthin (20 μg/ml) and gemcitabine (50 nm), and to be comparable to the powdered P. trimera root extract and a saponin-enriched extract from quillajia bark (a commercial product). The findings from this study allow us to conclude that the PTL is a rich source of phytochemicals that possess promising antioxidant and anti-proliferative activities, therefore it shows potential as lead compounds for application in the nutraceutical, medicinal and pharmaceutical industries.
Publisher: Elsevier BV
Date: 07-2015
Publisher: Springer Science and Business Media LLC
Date: 21-09-2017
Publisher: MDPI AG
Date: 24-01-2020
DOI: 10.3390/PR8020151
Abstract: Tuckeroo (Cupaniopsis anacardioides) is an Australian native tree, possessing high level bioactivity and antioxidant activity. To prevent deterioration of active constituents, appropriate drying practices must be determined. This study comparatively evaluates the impact of a range of drying methods including freeze-, microwave-, vacuum-, hot air- and sun-drying on the physical, phytochemical and antioxidant characteristics of Tuckeroo fruit. Experimental results showed that the five drying methods had significant impact on the physicochemical properties and antioxidant activity of the fruits. Of the drying methods assessed, freeze drying best preserved Tuckeroo activity, recording higher total phenolic content (TPC) (81.88 mg gallic acid equivalent (GAE)/g), total flavonoids (TFC) (107.71 mg catechin equivalent (CAE)/g), proanthocyanidins (TPro) (83.86 mg CAE/g) and exhibited the strongest antioxidant capacity. However, vacuum drying at 65 kPa, 100 °C for 5 h is recommended for drying Tuckeroo fruits for further processing in a large scale as it also retained high levels of TPC, TFC and TPro (58 mg GAE/g, 91 mg CAE/g and 74 mg CAE/g, respectively).
Publisher: Elsevier BV
Date: 05-2020
Publisher: Elsevier BV
Date: 12-2019
Publisher: Wiley
Date: 10-01-2017
DOI: 10.1111/IJFS.13351
Publisher: Elsevier BV
Date: 12-2019
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 18-12-2020
Publisher: Wiley
Date: 15-04-2021
Publisher: Informa UK Limited
Date: 28-03-2017
Publisher: Elsevier BV
Date: 12-2016
DOI: 10.1016/J.IJBIOMAC.2016.09.053
Abstract: The main aim of this study was to develop rice starch (RS), ι-carrageenan (ι-car) based film. Different formulations of RS (1-4%, w/w), ι-car (0.5-2%, w/w) was blended with stearic acid (SA 0.3-0.9%, w/w) and glycerol (1%, w/w) as a plasticizer. The effect of film ingredients on the thickness, water vapour permeability (WVP), film solubility (FS), moisture content (MC), colour, film opacity (FO), tensile strength (TS), elongation-at-break (EAB) of film was examined. Interactions and miscibility of partaking components was studied by using Fourier transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD). Hydrocolloid suspension solution of mix polysaccharides imparted a significant impact (p<0.05) on the important attributes of resulting edible film. TS and EAB of film were improved significantly (p<0.05) when ι-car was increased in the film matrix. Formulation F1 comprising 2% ι-car, 2% RS, 0.3% SA, Gly 30% w/w and 0.2% surfactant (tween
Publisher: International Society for Horticultural Science (ISHS)
Date: 03-2020
Publisher: Wiley
Date: 17-07-2007
DOI: 10.1111/J.1445-2197.2007.04179.X
Abstract: The diagnosis of pancreatic cystic lesions is problematical with difficulties arising in the differentiation between malignant, premalignant or benign lesions. This preliminary study aimed to analyse pancreatic cyst fluid, using a proteomic approach, to generate reproducible protein profiles to assist in the classification of malignant and non-carcinoma s les. Pancreatic cyst fluid s les from patients with pancreatic adenocarcinoma and non-carcinoma cystic lesions were analysed on hydrophobic protein chip arrays by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS). Differential protein expression profiles were observed between pancreatic adenocarcinoma and non-carcinoma cyst fluid s les using SELDI-TOF MS, with 12 protein peaks differentially expressed between pancreatic adenocarcinoma and non-carcinoma. Additionally, unique patterns were observed between the different subtypes of non-carcinoma s les as well as malignant adenocarcinoma. In this preliminary study we used SELDI-TOF MS to identify protein expression profiles of pancreatic cyst fluid, showing a potential to aid in the differential diagnosis of pancreatic cystic lesions.
Publisher: Wiley
Date: 16-07-2015
DOI: 10.1111/IJFS.12618
Publisher: Frontiers Media SA
Date: 17-08-2021
Abstract: Single nucleotide polymorphisms (SNPs) in taste receptors influence dietary choices that contribute to health and quality of life. In idual differences in sour taste perception and preference have been linked to heritable genetics, yet the impact of sour taste receptor SNPs on sour taste is under-researched, and studies on sour taste SNP associations to diet and health are lacking. Therefore, this study explored the relationships between the sour taste SNP KCNJ2 -rs236514 and estimated macronutrient, vitamin and mineral intakes, and markers of metabolic health. Associations were explored in 523 participants aged 65 years and older with data analysed using standard least squares and nominal logistic regression modelling with post hoc student's t -tests and Tukey's HSD. Associations were found between the presence of the KCNJ2 -rs236514 variant allele (A) and lower intakes of energy, total fat, monounsaturated fat and saturated fat. The lower fat intakes were significant in female carriers of the variant allele (A), along with lower water intake. Lower retinol, riboflavin, folate, calcium and sodium intakes were found in the KCNJ2 -A allele carriers. In females, the variant allele was associated with lower sodium intake before and after Bonferroni adjustment. Higher body mass index, waist and waist-to-hip ratio measures were found in males carrying the variant allele. Lower levels of liver function biomarkers were associated with the presence of the KCNJ2 -A allele. Overall and in males, the variant's association to lower gamma-glutamyl transferase (GGT) levels remained significant after Bonferroni adjustments. These novel findings suggest the sour taste SNP, KCNJ2 -rs236514, may be modifying macronutrient, vitamin and mineral intakes, and markers of metabolic health. Research on the extra-oral functions of this SNP may improve health outcomes for those with overweight, obesity and liver disease.
Publisher: Springer Science and Business Media LLC
Date: 24-02-2016
DOI: 10.1038/NATURE16965
Abstract: Integrated genomic analysis of 456 pancreatic ductal adenocarcinomas identified 32 recurrently mutated genes that aggregate into 10 pathways: KRAS, TGF-β, WNT, NOTCH, ROBO/SLIT signalling, G1/S transition, SWI-SNF, chromatin modification, DNA repair and RNA processing. Expression analysis defined 4 subtypes: (1) squamous (2) pancreatic progenitor (3) immunogenic and (4) aberrantly differentiated endocrine exocrine (ADEX) that correlate with histopathological characteristics. Squamous tumours are enriched for TP53 and KDM6A mutations, upregulation of the TP63∆N transcriptional network, hypermethylation of pancreatic endodermal cell-fate determining genes and have a poor prognosis. Pancreatic progenitor tumours preferentially express genes involved in early pancreatic development (FOXA2/3, PDX1 and MNX1). ADEX tumours displayed upregulation of genes that regulate networks involved in KRAS activation, exocrine (NR5A2 and RBPJL), and endocrine differentiation (NEUROD1 and NKX2-2). Immunogenic tumours contained upregulated immune networks including pathways involved in acquired immune suppression. These data infer differences in the molecular evolution of pancreatic cancer subtypes and identify opportunities for therapeutic development.
Publisher: Springer Science and Business Media LLC
Date: 14-06-2017
Publisher: Hindawi Limited
Date: 17-06-2016
DOI: 10.1111/JFPP.12879
Publisher: International Society for Horticultural Science (ISHS)
Date: 09-2018
Publisher: MDPI AG
Date: 17-07-2015
Publisher: Elsevier BV
Date: 03-2018
Publisher: Elsevier BV
Date: 2019
DOI: 10.2139/SSRN.3430714
Publisher: Elsevier BV
Date: 08-2009
DOI: 10.1053/J.GASTRO.2009.04.009
Abstract: Current methods of preoperative staging and predicting outcome following pancreatectomy for pancreatic cancer (PC) are inadequate. We evaluated the utility of multiple biomarkers from distinct biologic pathways as potential predictive markers of response to pancreatectomy and patient survival. We assessed the relationship of candidate biomarkers known, or suspected, to be aberrantly expressed in PC, with disease-specific survival and response to therapy in a cohort of 601 patients. Of the 17 candidate biomarkers examined, only elevated expression of S100A2 was an independent predictor of survival in both the training (n = 162) and validation sets (n = 439 hazard ratio [HR], 2.19 95% confidence interval [CI]: 1.48-3.25 P < .0001) when assessed in a multivariate model with clinical variables. Patients with high S100A2 expressing tumors had no survival benefit with pancreatectomy compared with those with locally advanced disease, whereas those without high S100A2 expression had a survival advantage of 10.6 months (19.4 vs 8.8 months, respectively) and a HR of 3.23 (95% CI: 2.39-4.33 P < .0001). Of significance, patients with S100A2-negative tumors had a significant survival benefit from pancreatectomy even in the presence of involved surgical margins (median, 15.7 months P = .0007) or lymph node metastases (median, 17.4 months P = .0002). S100A2 expression is a good predictor of response to pancreatectomy for PC and suggests that high S100A2 expression may be a marker of a metastatic phenotype. Prospective measurement of S100A2 expression in diagnostic biopsy s les has potential clinical utility as a predictive marker of response to pancreatectomy and other therapies that target locoregional disease.
Publisher: MDPI AG
Date: 08-06-2020
Abstract: Intense sweeteners (IS) are often marketed as a healthier alternative to sugars, with the potential to aid in combating the worldwide rise of diabetes and obesity. However, their use has been counterintuitively associated with impaired glucose homeostasis, weight gain and altered gut microbiota. The nature of these associations, and the mechanisms responsible, are yet to be fully elucidated. Differences in their interaction with taste receptors may be a potential explanatory factor. Like sugars, IS stimulate sweet taste receptors, but due to their erse structures, some are also able to stimulate bitter taste receptors. These receptors are expressed in the oral cavity and extra-orally, including throughout the gastrointestinal tract. They are involved in the modulation of appetite, glucose homeostasis and gut motility. Therefore, taste genotypes resulting in functional receptor changes and altered receptor expression levels may be associated with metabolic conditions. IS and taste receptors may both interact with the gastrointestinal microbiome, and their interactions may potentially explain the relationship between IS use, obesity and metabolic outcomes. While these elements are often studied in isolation, the potential interactions remain unexplored. Here, the current evidence of the relationship between IS use, obesity and metabolic outcomes is presented, and the potential roles for interactions with taste receptors and the gastrointestinal microbiota in modulating these relationships are explored.
Publisher: MDPI AG
Date: 19-07-2018
DOI: 10.3390/FOODS7070115
Abstract: The effect of different combinations of maltodextrin (MD) coating agents (MD, MD + soybean protein, and MD + ι-carrageenan) on the encapsulation of lemon by-product aqueous extracts using freeze-drying and spray-drying were investigated. The total phenolic content (TPC), total flavonoid content (TFC), and ferric ion reducing antioxidant power (FRAP) of the microparticles were evaluated. Freeze-drying with the mixture of MD + soybean protein resulted in the highest retention of TPC, TFC, and FRAP (1.66 ± 0.02 mg GAE/g d.b., 0.43 ± 0.02 mg CE/g d.b., and 3.70 ± 0.05 mM TE/g, respectively). Freeze-drying resulted in microparticles with lower moisture content (MC) and water activity (aw) than those produced by spray-drying. Specifically, the MC and aw of the microparticles produced by freeze-drying ranged from 1.15 to 2.15% and 0.13 to 0.14, respectively, while the MC and aw of the microparticles produced by spray-drying ranged from 6.06% to 6.60% and 0.33 to 0.40, respectively. Scanning electron microscopy revealed that spray-drying resulted in the formation of spherical particles of different sizes regardless of the type of coating agent. Although freeze-drying resulted in microparticles with amorphous glassy shapes, the mixture of MD + soybean protein resulted in the formation of spherical porous particles. X-ray diffraction revealed a low degree of crystallinity for the s les produced by both techniques.
Publisher: Elsevier BV
Date: 12-2017
Publisher: Springer Science and Business Media LLC
Date: 19-02-2018
Publisher: International Society for Horticultural Science (ISHS)
Date: 10-2019
Publisher: Informa UK Limited
Date: 02-10-2019
Publisher: Wiley
Date: 26-09-2017
Publisher: MDPI AG
Date: 05-12-2022
Abstract: The commercial production of soy milk renders a large quantity of wet soybean by-product (SMB), which is typically dumped, incinerated, or partially used as animal fodder. This wet SMB has a high moisture content that is rich in nutritional and biologically active compounds. This study aimed to characterise the composition and properties of a flour milled from SMB dried at 100 °C (SMB100) and assess its possible application as a fibre substitute in white bread. The results showed that SMB100 has high levels of dietary fibre (40.6%) and protein (26.5%). It also contains high levels of saponins (31.4 mg/g) and isoflavones (698.0 µg/g). SMB100 has a light-yellow colour with low moisture content and water activity (8.2% and 0.55, respectively). The results also indicated that replacement of wheat flour with SMB100 at 10 or 12.5% by flour weight negatively impacted the raising volume, density, and texture of white bread. Alternatively, substituting wheat flour with 5% of SMB100, did not significantly impact the physical properties of white bread, while significantly improving its dietary fibre content in comparison with the control, revealing that SMB100 is a potential substitute of wheat flour for improvement of dietary fibre in bread. Future studies are needed to optimise bread formulation and improve the processing condition which produces quality white bread with high dietary fibre using SMB100.
Publisher: Elsevier BV
Date: 07-2019
DOI: 10.1016/J.IJBIOMAC.2019.03.190
Abstract: Starch is the most popular plant polysaccharides, which has been widely used for the development of edible coating films because of its abundance, cost-effectiveness, and excellent film-forming abilities. Starch-based films have good optical, organoleptic and gas barrier properties, however, they have poor mechanical properties. Many attempts have been made to overcome these limitations, such as the addition of co-biopolymers or other secondary additives to improve the mechanical and tensile properties of the films. Properties of the starch-based films can be influenced by many factors, including types of starches, temperature and time during film formation, plasticizers, co-biopolymers, and storage conditions. Understanding the mechanisms of these factors is very important for future studies on the development of starch-based films. This review focuses on starch as a film/coating material and comprehensively discusses the effects of major factors on properties of starch-based films.
Publisher: Elsevier BV
Date: 09-2017
Publisher: MDPI AG
Date: 28-02-2020
Abstract: Ultraviolet radiation (UVR) is a ubiquitous exposure which may contribute to decreased folate levels. Skin pigmentation mediates the biological effect of UVR exposure, but its relationship to folate levels is unexamined. Interactions may exist between UVR and pigmentation genes in determining folate status, which may, in turn, impact homocysteine levels, a potential risk factor for multiple chronic diseases. Therefore, independent and interactive influences of environmental UVR and genetic variants related to skin pigmentation (MC1R-rs1805007, IRF4-rs12203592 and HERC2-rs12913832) on folate (red blood cell (RBC) and serum) and homocysteine levels were examined in an elderly Australian cohort (n = 599). Genotypes were assessed by RT/RFLP-PCR, and UVR exposures were assessed as the accumulated erythemal dose rate accumulated over 4 months (4M-EDR). Multivariate analysis found significant negative associations between 4M-EDR and RBC folate (p 0.001, β = −0.19), serum folate (p = 0.045, β = −0.08) and homocysteine levels (p 0.001, β = −0.28). Significant associations between MC1R-rs1805007 and serum folate levels (p = 0.020), and IRF4-rs12203592 and homocysteine levels (p = 0.026) occurred but did not remain significant following corrections with confounders. No interactions between 4M-EDR and pigmentation variants in predicting folate/homocysteine levels were found. UVR levels and skin pigmentation-related variants are potential determinants of folate and homocysteine status, although, associations are mixed and complex, with further studies warranted.
Publisher: Springer Science and Business Media LLC
Date: 27-04-2018
Publisher: Elsevier BV
Date: 09-2013
Publisher: American Society of Clinical Oncology (ASCO)
Date: 04-2013
Abstract: In iduals with adenocarcinoma of the ulla of Vater demonstrate a broad range of outcomes, presumably because these cancers may arise from any one of the three epithelia that converge at that location. This variability poses challenges for clinical decision making and the development of novel therapeutic strategies. We assessed the potential clinical utility of histomolecular phenotypes defined using a combination of histopathology and protein expression (CDX2 and MUC1) in 208 patients from three independent cohorts who underwent surgical resection for adenocarcinoma of the ulla of Vater. Histologic subtype and CDX2 and MUC1 expression were significant prognostic variables. Patients with a histomolecular pancreaticobiliary phenotype (CDX2 negative, MUC1 positive) segregated into a poor prognostic group in the training (hazard ratio [HR], 3.34 95% CI, 1.69 to 6.62 P .001) and both validation cohorts (HR, 5.65 95% CI, 2.77 to 11.5 P .001 and HR, 2.78 95% CI, 1.25 to 7.17 P = .0119) compared with histomolecular nonpancreaticobiliary carcinomas. Further stratification by lymph node (LN) status defined three clinically relevant subgroups: one, patients with histomolecular nonpancreaticobiliary (intestinal) carcinoma without LN metastases who had an excellent prognosis two, those with histomolecular pancreaticobiliary carcinoma with LN metastases who had a poor outcome and three, the remainder of patients (nonpancreaticobiliary, LN positive or pancreaticobiliary, LN negative) who had an intermediate outcome. Histopathologic and molecular criteria combine to define clinically relevant histomolecular phenotypes of adenocarcinoma of the ulla of Vater and potentially represent distinct diseases with significant implications for current therapeutic strategies, the ability to interpret past clinical trials, and future trial design.
Publisher: Elsevier BV
Date: 2017
Publisher: Medknow
Date: 2019
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2008
Publisher: Elsevier BV
Date: 04-2021
Publisher: Wiley
Date: 20-03-2017
Abstract: Xao tam phan (Paramignya trimera (Oliv.) Guillaum) has been used as a medicinal plant for cancer prevention and treatment in recent years. The objective of this study was to determine the physicochemical, antioxidant, and cytotoxic properties of crude P. trimera root (PTR) extract and its fractions using MeOH as a solvent and microwave-assisted extraction as an advanced technique for preparation of the PTR extract. The results showed that the PTR extract had high contents of saponins, phenolics, flavonoids, and proanthocyanidins (7731.05 mg escin equiv. (EE), 238.13 mg gallic acid equiv. (GAE), 81.49 mg rutin equiv., and 58.08 mg catechin equiv. (CE)/g dried extract, resp.). Antioxidant activity of PTR extract was significantly higher (P < 0.05) than those of four its fractions and ostruthin, a key bioactive compound in the P. trimera, while potent cytotoxic capacity of PTR extract on various cancer cell lines in terms of MiaPaCa-2 (pancreas), HT29 (colon), A2780 (ovarian), H460 (lung), A431 (skin), Du145 (prostate), BE2-C (neuroblastoma), MCF-7 (breast), MCF-10A (normal breast), and U87, SJ-G2, SMA (glioblastoma) was observed with GI
Publisher: MDPI AG
Date: 08-10-2015
Publisher: Informa UK Limited
Date: 28-11-2016
Publisher: Springer Science and Business Media LLC
Date: 29-06-2010
Publisher: MDPI AG
Date: 23-10-2014
Publisher: MDPI AG
Date: 21-12-2020
DOI: 10.3390/TECHNOLOGIES8040080
Abstract: Catharanthus roseus (C. roseus) is an important medicinal plant distributed in many countries. It has attracted increasing attention due to it being shown to possess a range of phytochemicals with various biological activities such as antioxidant, antibacterial, antifungal, antidiabetic and anticancer properties. Remarkably, vinblastine and vincristine isolated from this plant were the first plant-derived anticancer agents deployed for clinical use. Recently, new isolated indole alkaloids from this plant including catharoseumine, 14′,15′-didehydrocyclovinblastine, 17-deacetoxycyclovinblastine and 17-deacetoxyvinamidine effectively inhibited human cancer cell lines in vitro. Moreover, vindoline, vindolidine, vindolicine and vindolinine isolated from C. roseus leaf exhibited in vitro antidiabetic property. These findings strongly indicate that this plant is still a promising source of bioactive compounds, which should be further investigated. This paper provides an overview of the traditional use and phytochemical profiles of C. roseus, and summarises updated techniques of the preparation of dried material, extraction and isolation of bioactive compounds from this plant. In addition, purported health benefits of the extracts and bioactive compounds derived from this plant were also addressed to support their potential as therapeutic agents.
Publisher: Informa UK Limited
Date: 18-12-2017
Publisher: Springer Science and Business Media LLC
Date: 30-11-2020
DOI: 10.1038/S41467-020-20128-W
Abstract: Correction to this paper has been published: 0.1038/s41467-020-20128-w
Publisher: Elsevier BV
Date: 2018
Publisher: Elsevier BV
Date: 12-2017
Publisher: Springer Science and Business Media LLC
Date: 03-06-2008
DOI: 10.1007/S00268-008-9499-7
Abstract: Sporadic pancreatic neuroendocrine tumors, which predominantly secrete pancreatic polypeptide (PPoma), are rare and have not been associated with a clinical syndrome. A wider understanding of their pathological features and behavior is needed. Four PPoma patients who presented with nonspecific abdominal pain are described. Their diagnosis was established by the presence of an enhancing solitary pancreatic tumor on computed tomography (CT) and elevated fasting pancreatic polypeptide hormone levels. Patient 1 was treated with a pancreatoduodenectomy because of elevation of serum CEA level. Two of the cases underwent enucleation because of prolonged stable CT appearance. Patient 4 underwent distal pancreatectomy for a pancreatic neck tumor causing ductal obstruction and distal parenchymal atrophy. All cases had benign histological features apart from patient 1 whose tumor demonstrated occasional mitotic activity. These tumors have not recurred after a median of 49 (range, 35-57) months. The protein expression in the tumor tissue was measured by SELDI-TOF MS and was different than the profile of pancreatic adenocarcinoma that was previously demonstrated in our laboratory. This may lead to future helpful diagnostic testing on fine needle aspirates. Resection of sporadic PPomas presenting as a solitary well-defined mass with benign histological features results in good long-term survival.
Publisher: Impact Journals, LLC
Date: 07-12-2017
Publisher: Elsevier BV
Date: 2015
Publisher: MDPI AG
Date: 26-03-2020
Abstract: Breast cancer is the most commonly diagnosed and the second leading cause of cancer-related mortality among women worldwide. miR-518f-5p has been shown to modulate the expression of the metastasis suppressor CD9 in prostate cancer. However, the role of miR-518f-5p and CD9 in breast cancer is unknown. Therefore, this study aimed to elucidate the role of miR-518f-5p and the mechanisms responsible for decreased CD9 expression in breast cancer, as well as the role of CD9 in de novo tumor formation and metastasis. miR-518f-5p function was assessed using migration, adhesion, and proliferation assays. miR-518f-5p was overexpressed in breast cancer cell lines that displayed significantly lower CD9 expression as well as less endogenous CD9 3′UTR activity, as assessed using qPCR and dual luciferase assays. Transfection of miR-518f-5p significantly decreased CD9 protein expression and increased breast cell migration in vitro. Cd9 deletion in the MMTV/PyMT mouse model impaired tumor growth, but had no effect on tumor initiation or metastasis. Therefore, inhibition of miR-518f-5p may restore CD9 expression and aid in the treatment of breast cancer metastasis.
Publisher: Public Library of Science (PLoS)
Date: 14-10-2011
Publisher: Impact Journals, LLC
Date: 20-05-2014
Publisher: MDPI AG
Date: 02-07-2018
DOI: 10.3390/IJMS19071937
Publisher: Public Library of Science (PLoS)
Date: 29-12-2011
Publisher: Springer Science and Business Media LLC
Date: 27-04-2017
DOI: 10.1007/S11626-017-0149-Y
Abstract: In spite of the recent advancements in oncology, the overall survival rate for pancreatic cancer has not improved over the last five decades. Eucalypts have been linked with cytotoxic and anticancer properties in various studies however, there is very little scientific evidence that supports the direct role of eucalypts in the treatment of pancreatic cancer. This study assessed the anticancer properties of aqueous and ethanolic extracts of four Eucalyptus species using an MTT assay. The most promising extracts were further evaluated using a CCK-8 assay. Apoptotic studies were performed using a caspase 3/7 assay in MIA PaCa-2 cells. The aqueous extract of Eucalyptus microcorys leaf and the ethanolic extract of Eucalyptus microcorys fruit inhibited the growth of glioblastoma, neuroblastoma, lung and pancreatic cancer cells by more than 80% at 100 μg/mL. The E. microcorys and Eucalyptus saligna extracts showed lower GI
Publisher: Elsevier BV
Date: 09-2018
DOI: 10.1016/J.BIOPHA.2018.05.150
Abstract: New therapeutic strategies such as the development of novel drugs and combinatorial therapies with existing chemotherapeutic agents are urgently needed to improve the clinical prognosis of pancreatic cancer. We have previously reported the antiproliferative properties of aqueous crude Eucalyptus microcorys extract against pancreatic cancer cell lines. In this study, bioassay-guided fractionation of the aqueous crude E. microcorys extract using RP-HPLC and subsequent assessment of the resultant fractions (F1-F5) for their antioxidant activity and cytotoxicity against pancreatic cancer cell lines were performed. The molecular mechanisms associated with the cytotoxicity was characterised by studying the effects of the most potent fraction-1 (F1) on apoptosis and cell cycle profiles as well as its phytochemical constituents by LC-ESI/MS/MS. F1 displayed significantly greater antioxidant activity in three different assays (p < 0.05). Moreover, F1 exhibited significantly greater antiproliferative activity (IC
Publisher: Springer Science and Business Media LLC
Date: 11-06-2018
DOI: 10.1038/S41598-018-27180-Z
Abstract: To facilitate intercellular communication, cells release nano-sized, extracellular vesicles (EVs) to transfer biological cargo to both local and distant sites. EVs are enriched in tetraspanins, two of which (CD9 and CD151) have altered expression patterns in many solid tumours, including prostate cancer, as they advance toward metastasis. We aimed to determine whether EVs from prostate cells with altered CD9 and CD151 expression could influence cellular behaviour and increase the metastatic capabilities of non-tumourigenic prostate cells. EVs were isolated by ultrafiltration and characterised for their tetraspanin expression and size distribution. iTRAQ was used to identify differences between RWPE1 and tetraspanin-modified RWPE1 EV proteomes, showing an enrichment in protein degradation pathways. Addition of EVs from RWPE1 cells with reduced CD9 or increased CD151 abundance resulted in increased invasion of RWPE1 cells, and increased migration in the case of high CD151 abundance. We have been able to show that alteration of CD9 and CD151 on prostate cells alters the proteome of their resultant EVs, and that these EVs can enhance the migratory and invasive capabilities of a non-tumourigenic prostate cellular population. This work suggests that cellular tetraspanin levels can alter EVs, potentially acting as a driver of metastasis in prostate cancer.
Publisher: Public Library of Science (PLoS)
Date: 28-04-2009
Publisher: Hindawi Limited
Date: 2017
DOI: 10.1155/2017/9305047
Abstract: This study aimed to study the impact of selected common organic solvents on extractable solids, phytochemical composition, and antioxidant capacity of S. chinensis . The results showed that the tested solvents played an important role in extraction of total solid and phytochemical composition as well as antioxidant capacity of S. chinensis . Acetone (50% v/v) was found to be the optimal extraction solvent for extractable solids (12.2%), phenolic compounds (60 mg GAE/g DW), flavonoids (100 mg CE/g DW), proanthocyanidins (47.4 mg CE/g DW), and saponins (754 mg EE/g DW) as well as antioxidant capacity (ABTS 334 mM TE/g DW, DPPH 470 mM TE/g DW, FRAP 347 mM TE/g DW, and CUPRAC 310 mM TE/g DW). The extract prepared from 50% acetone had high levels of bioactive compounds (TPC 555 mg GAE/g CRE, flavonoids 819 mg CE/g CRE, proanthocyanidins 392 mg CE/g CRE, and saponins 1,880 mg EE/g CRE) as well as antioxidant capacity (ABTS 414 mM TE/g, DPPH 407 mM TE/g, FRAP 320 mg TE/g, and CUPRAC 623 mM TE/g), thus further confirming that 50% acetone is the solvent of choice. Therefore, 50% acetone is recommended for extraction of phenolic compounds, their secondary metabolites, saponins, and antioxidant capacity from the root of S. chinensis for further isolation and utilisation.
Publisher: Springer Science and Business Media LLC
Date: 21-11-2014
DOI: 10.1038/BJC.2013.722
Publisher: Wiley
Date: 06-08-2015
DOI: 10.1111/IJFS.12915
Publisher: Springer Science and Business Media LLC
Date: 05-02-2020
DOI: 10.1038/S41586-020-1969-6
Abstract: Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale 1–3 . Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution in acral melanoma, for ex le, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter 4 identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation 5,6 analyses timings and patterns of tumour evolution 7 describes the erse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity 8,9 and evaluates a range of more-specialized features of cancer genomes 8,10–18 .
Publisher: Informa UK Limited
Date: 22-06-2016
Publisher: Elsevier BV
Date: 07-2018
Publisher: MDPI AG
Date: 24-12-2015
DOI: 10.3390/FOODS5010001
Publisher: Springer Science and Business Media LLC
Date: 15-02-2017
DOI: 10.1038/NATURE21063
Abstract: The diagnosis of pancreatic neuroendocrine tumours (PanNETs) is increasing owing to more sensitive detection methods, and this increase is creating challenges for clinical management. We performed whole-genome sequencing of 102 primary PanNETs and defined the genomic events that characterize their pathogenesis. Here we describe the mutational signatures they harbour, including a deficiency in G:C > T:A base excision repair due to inactivation of MUTYH, which encodes a DNA glycosylase. Clinically sporadic PanNETs contain a larger-than-expected proportion of germline mutations, including previously unreported mutations in the DNA repair genes MUTYH, CHEK2 and BRCA2. Together with mutations in MEN1 and VHL, these mutations occur in 17% of patients. Somatic mutations, including point mutations and gene fusions, were commonly found in genes involved in four main pathways: chromatin remodelling, DNA damage repair, activation of mTOR signalling (including previously undescribed EWSR1 gene fusions), and telomere maintenance. In addition, our gene expression analyses identified a subgroup of tumours associated with hypoxia and HIF signalling.
Publisher: Springer Science and Business Media LLC
Date: 23-04-2011
DOI: 10.1007/S00439-011-0990-0
Abstract: Defining key driver mutations in cancer, the resulting aberrations in molecular mechanisms and the subsequent phenotype underpins the development and implementation of novel personalized medicine strategies. The literature is replete with biomarkers of prognosis and therapeutic responsiveness identified in single cohorts of patients that have not been independently validated and as a consequence, not developed. Integrating companion biomarker discovery with therapeutic development at the preclinical stage creates the opportunity to identify candidate biomarkers early, which would significantly facilitate both biomarker and therapeutic development. Advances in "-omic" technologies have led to large-scale efforts in characterizing and cataloguing the full range of aberrations in cancer. These include the International Cancer Genome Consortium and The Cancer Genome Atlas, which aim to comprehensively catalogue the range of genomic aberrations for large numbers of cancers for a progressively increasing range of cancer types and subtypes. The technical challenges associated with achieving these goals in some instances have required the generation of primary xenografts and cell lines. These extensively characterized model systems will provide an unprecedented resource for the discovery of biomarkers of therapeutic responsiveness for established therapies, and the development of companion biomarkers linked with preclinical novel therapeutic development in the future.
Publisher: Springer Science and Business Media LLC
Date: 17-02-2020
Publisher: Informa UK Limited
Date: 07-12-2013
Publisher: Wiley
Date: 17-07-2016
DOI: 10.1111/IJFS.13168
Publisher: Wiley
Date: 17-10-2018
Publisher: Springer Science and Business Media LLC
Date: 09-08-2010
DOI: 10.1038/ONC.2010.332
Abstract: Myc oncoproteins and histone deacetylases (HDACs) modulate gene transcription and enhance cancer cell proliferation, and HDAC inhibitors are among the most promising new classes of anticancer drugs. Here, we show that N-Myc and c-Myc upregulated HDAC2 gene expression in neuroblastoma and pancreatic cancer cells, respectively, which contributed to N-Myc- and c-Myc-induced cell proliferation. Cyclin G2 (CCNG2) was commonly repressed by N-Myc and HDAC2 in neuroblastoma cells and by c-Myc and HDAC2 in pancreatic cancer cells, and could be reactivated by HDAC inhibitors. 5-bromo-2'-deoxyuridine incorporation assays showed that transcriptional repression of CCNG2 was, in part, responsible for N-Myc-, c-Myc- and HDAC2-induced cell proliferation. Dual crosslinking chromatin immunoprecipitation assay demonstrated that N-Myc acted as a transrepressor by recruiting the HDAC2 protein to Sp1-binding sites at the CCNG2 gene core promoter. Moreover, HDAC2 was upregulated, and CCNG2 downregulated, in pre-cancerous and neuroblastoma tissues from N-Myc transgenic mice, and c-Myc overexpression correlated with upregulation of HDAC2 and repression of CCNG2 in tumour tissues from pancreatic cancer patients. Taken together, our data indicate the critical roles of upregulation of HDAC2 and suppression of CCNG2 in Myc-induced oncogenesis, and have significant implications for the application of HDAC inhibitors in the prevention and treatment of Myc-driven cancers.
Publisher: Springer Science and Business Media LLC
Date: 29-01-2008
Publisher: Informa UK Limited
Date: 05-09-2017
Publisher: International Society for Horticultural Science (ISHS)
Date: 10-2019
Publisher: Informa UK Limited
Date: 07-12-2018
Publisher: Informa UK Limited
Date: 11-02-2015
Publisher: Springer Science and Business Media LLC
Date: 08-2016
Publisher: Elsevier BV
Date: 02-2015
Publisher: Hindawi Limited
Date: 07-02-2018
DOI: 10.1111/JFPP.13597
Publisher: Hindawi Limited
Date: 07-02-2017
DOI: 10.1111/JFPP.13199
Publisher: Elsevier BV
Date: 10-2018
Publisher: Oxford University Press (OUP)
Date: 20-09-2023
Publisher: BMJ
Date: 09-04-2014
Publisher: Elsevier BV
Date: 12-2019
Publisher: Elsevier BV
Date: 07-2019
Publisher: Elsevier BV
Date: 12-2016
Publisher: Springer Science and Business Media LLC
Date: 13-03-2020
DOI: 10.1186/S12263-020-00663-3
Abstract: The frequency of vitamin D-associated gene variants appear to reflect changes in long-term ultraviolet B radiation (UVB) environment, indicating interactions exist between the primary determinant of vitamin D status, UVB exposure and genetic disposition. Such interactions could have health implications, where UVB could modulate the impact of vitamin D genetic variants identified as disease risk factors. However, the current understanding of how vitamin D variants differ between populations from disparate UVB environments is limited, with previous work examining a small pool of variants and restricted populations only. Genotypic data for 46 variants within multiple vitamin D-related loci ( DHCR7/NADSYN1 , GC , CYP2R1 , CYP11A1 , CYP27A1 , CYP24A1 , VDR , RXRα and RXRγ ) was collated from 60 s le sets (2633 subjects) with European, East Asian and Sub-Saharan African origin via the NCBI 1000 Genomes Browser and ALFRED (Allele Frequency Database), with the aim to examine for patterns in the distribution of vitamin D-associated variants across these geographic areas. The frequency of all examined genetic variants differed between populations of European, East Asian and Sub-Saharan African ancestry. Changes in the distribution of variants in CYP2R1 , CYP11A1 , CYP24A1 , RXRα and RXRγ genes between these populations are novel findings which have not been previously reported. The distribution of several variants reflected changes in the UVB environment of the population’s ancestry. However, multiple variants displayed population-specific patterns in frequency that appears not to relate to UVB changes. The reported population differences in vitamin D-related variants provides insight into the extent by which activity of the vitamin D system can differ between cohorts due to genetic variance, with potential consequences for future dietary recommendations and disease outcomes.
Publisher: Springer Science and Business Media LLC
Date: 24-10-2012
DOI: 10.1038/NATURE11547
Publisher: Springer Science and Business Media LLC
Date: 19-02-2019
Publisher: Wiley
Date: 22-02-2017
Abstract: While the pharmacological and toxicological properties of eucalypts are well known in indigenous Australian medicinal practice, investigations of the bioactivity of eucalypt extracts against high mortality diseases such as pancreatic cancer in Western medicine have to date been limited, particularly amongst the genera Corymbia and Angophora. Four Angophora and Corymbia species were evaluated for their phytochemical profile and efficacy against both primary and secondary pancreatic cancer cell lines. The aqueous leaf extract of Angophora hispida exhibited statistically higher total phenolic content (107.85 ± 1.46 mg of gallic acid equiv. per g) and total flavonoid content (57.96 ± 1.93 mg rutin equiv. per g) and antioxidant capacity compared to the other tested eucalypts (P < 0.05). Both A. hispida and A. floribunda aqueous extracts showed statistically similar saponin contents. Angophora floribunda extract exerted significantly greater cell growth inhibition of 77.91 ± 4.93% followed by A. hispida with 62.04 ± 7.47% (P < 0.05) at 100 μg/ml in MIA PaCa-2 cells with IC
Publisher: International Society for Horticultural Science (ISHS)
Date: 03-2018
Publisher: Elsevier BV
Date: 10-2004
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2018
DOI: 10.1097/MPA.0000000000001074
Abstract: Pancreatic cancer (PC) is one of the most devastating human cancers, and despite the significant advances in the current therapeutic options, the overall survival rate for PC has remained static for the past 50 years. Plant-derived bioactive compounds play a vital role in cancer therapeutics by providing new lead compounds for future drug development. Therefore, the isolation, characterization, and identification of new bioactive compounds for the prevention and treatment of cancer continue to be an important aspect of natural product research. Many in vitro and in vivo studies published in the last few decades have established strong links between the phytochemical profile of eucalypts and anticancer activity. However, only a small number of these reports have attempted to demonstrate a relationship between the biological activity of eucalypt extracts and PC. This review focuses on potential anti-PC effects of an array of bioactive compounds present in various species of eucalypts. It also highlights the necessity for further in vitro and in vivo studies to develop a complete understanding of the potential this group of plants has for the development of potent and specific chemotherapeutic drugs for PC.
Publisher: Public Library of Science (PLoS)
Date: 16-06-2011
Publisher: Springer Science and Business Media LLC
Date: 03-04-2019
DOI: 10.1007/S11033-019-04786-8
Abstract: Catharanthus roseus (L.) G. Don (C. roseus) is a well-known medicinal plant for its source of alkaloids solely found in the leaves. Other parts including the root are usually discarded after the alkaloid extraction. This study sought to investigate phytochemical profiles, antioxidant, antimicrobial and cytotoxic properties of the C. roseus root extract (RE) and its two sub-fractions including saponin-enriched (SE) and aqueous (AQ) fractions. The results showed that the RE was a rich source of saponins (1744.44 mg ESE/g) and phenolics (51.27 mg GAE/g), which comprised of gallic acid (25.74 mg/g), apigenin (1.45 mg/g) and kaempferol (1.58 mg/g). The SE fraction was enriched with 31% of saponins and 63% of phenolics higher than those of the RE whereas the concentrations of saponins and phenolics of the AQ fraction were lower than those of the RE by 40% and 74%, respectively. The content of gallic acid in the SE fraction was 1.4-fold and 1.5-fold higher than those of the RE or AQ fraction, respectively. The SE fraction demonstrated potent antioxidant capacity, which was significantly higher than the RE or AQ fraction, and also exhibited strong anti-proliferative activity against 11 cancer cell lines including A2780 (ovarian), H460 (lung), A431 (skin), MIA PaCa-2 (pancreas), Du145 (prostate), HT29 (colon), MCF-7 (breast), BE2-C (neuroblastoma), SJ-G2, U87 and SMA (glioblastoma) with low GI
Publisher: MDPI AG
Date: 09-02-2021
DOI: 10.3390/NU13020571
Abstract: Globally, more than one-third of adults are overweight. Overweight and obesity are complex and multifaceted conditions, associated with an increased risk of chronic illness and early mortality. While there are known risk factors, these alone do not fully explain the varying outcomes between in iduals. Recently, taste receptors have been proposed to have a role in the risk for obesity. These receptors are expressed throughout the gastrointestinal tract. In this system, they may be involved in modulating dietary intake and metabolic processes. The taste 2 family of receptors (T2Rs) detects bitter compounds. Receptors T2R4 and T2R5 detect (-)-epicatechin (epicatechin), an antioxidant polyphenol, which may have protective effects against obesity. However, the potential role for taste receptors in this association has not been explored. This study assessed whether polymorphisms in TAS2R4 (rs2233998 and rs2234001) and TAS2R5 (rs2227264) were associated with body mass index (BMI). Genotyping (Taqman qPCR assays) was performed on DNA extracted from blood s les (n = 563) from an elderly cohort. Homozygosity for the minor allele of all polymorphisms was significantly associated with a lower BMI in males. The TAS2R4-rs2233998 CC genotype, the TAS2R4-rs2234001 CC genotype and the TAS2R5-rs2227264 TT genotype were associated with lower BMI (2.1, 2.1 and 2.2 units p = 0.002, 0.003 and 0.001, respectively). Epicatechin intake was not associated with BMI and genotype was not associated with epicatechin intake. This suggests that the association between TAS2R genotype and elevated BMI risk occurs through altered extra-oral responses and not directly via altered epicatechin intake.
Publisher: Elsevier BV
Date: 09-2017
Publisher: Springer Science and Business Media LLC
Date: 07-2013
DOI: 10.1038/ONC.2013.253
Abstract: The N-Myc oncoprotein induces neuroblastoma, which arises from undifferentiated neuroblasts in the sympathetic nervous system, by modulating gene and protein expression and consequently causing cell differentiation block and cell proliferation. The class IIa histone deacetylase 5 (HDAC5) represses gene transcription, and blocks myoblast, osteoblast and leukemia cell differentiation. Here we showed that N-Myc upregulated HDAC5 expression in neuroblastoma cells. Conversely, HDAC5 repressed the ubiquitin-protein ligase NEDD4 gene expression, increased Aurora A gene expression and consequently upregulated N-Myc protein expression. Genome-wide gene expression analysis and protein co-immunoprecipitation assays revealed that HDAC5 and N-Myc repressed the expression of a common subset of genes by forming a protein complex, whereas HDAC5 and the class III HDAC SIRT2 independently repressed the expression of another common subset of genes without forming a protein complex. Moreover, HDAC5 blocked differentiation and induced proliferation in neuroblastoma cells. Taken together, our data identify HDAC5 as a novel co-factor in N-Myc oncogenesis, and provide the evidence for the potential application of HDAC5 inhibitors in the therapy of N-Myc-induced neuroblastoma and potentially other c-Myc-induced malignancies.
Publisher: MDPI AG
Date: 31-01-2019
DOI: 10.3390/MOLECULES24030524
Abstract: Pancreatic cancer (PC) is a complex, heterogeneous disease with a dismal prognosis. Current therapies have failed to improve survival outcomes, urging the need for discovery of novel targeted treatments. Bispidinone derivatives have yet to be investigated as cytotoxic agents against PC cells. The cytotoxic effect of four bispidinone derivatives (BisP1: 1,5-diphenyl-3,7-bis(2-hydroxyethyl)-3,7-diazabicyclo[3.3.1]nonan-9-one BisP2: 3,7-bis-(2-(S)-amino-4-methylsulfanylbutyryl)-1,5-diphenyl-3,7-diazabicyclo[3.3.1]nonan-9-one dihydrochloride BisP3: [2-{7-[2-(S)-tert-butoxycarbonylamino-3-(1H-indol-3-yl)-propionyl]-9-oxo-1,5-diphenyl-3,7-diazabicyclo[3.3.1]non-3-yl}-1-(S)-(1H-indol-3-ylmethyl)-2-oxoethyl]-carbamic acid tertbutyl ester BisP4: 3,7-bis-[2-(S)-amino-3-(1H-indol-3-yl)-propionyl]-1,5-diphenyl-3,7-diazabicyclo[3.3.1]nonan-9-one dihydrochloride) was assessed against PC cell lines (MiaPaca-2, CFPAC-1 and BxPC-3). Cell viability was assessed using a Cell Counting Kit-8 (CCK-8) colorimetric assay, while apoptotic cell death was confirmed using fluorescence microscopy and flow cytometry. Initial viability screening revealed significant cytotoxic activity from BisP4 treatment (1 µM–100 µM) on all three cell lines, with IC50 values for MiaPaca-2, BxPC-3, and CFPAC-1 16.9 µM, 23.7 µM, and 36.3 µM, respectively. Cytotoxic treatment time-response (4 h, 24 h, and 48 h) revealed a 24 h treatment time was sufficient to produce a cytotoxic effect on all cell lines. Light microscopy evaluation (DAPI staining) of BisP4 treated MiaPaca-2 PC cells revealed dose-dependent characteristic apoptotic morphological changes. In addition, flow cytometry confirmed BisP4 induced apoptotic cell death induction of activated caspase-3/-7. The bispidinone derivative BisP4 induced an apoptosis-mediated cytotoxic effect on MiaPaca-2 cell lines and significant cytotoxicity on CFPAC-1 and BxPC-3 cell lines. Further investigations into the precise cellular mechanisms of action of this class of compounds are necessary for potential development into pre-clinical trials.
Publisher: Elsevier BV
Date: 05-2015
Publisher: Elsevier BV
Date: 02-2018
No related organisations have been discovered for Christopher Scarlett.
Start Date: 11-2014
End Date: 12-2019
Amount: $2,119,872.00
Funder: Australian Research Council
View Funded ActivityStart Date: 10-2021
End Date: 09-2023
Amount: $489,250.00
Funder: Australian Research Council
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