https://nova.newcastle.edu.au/vital/access/manager/Index ${session.getAttribute("locale")} 5 https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:24833 A, del5395, I157T), NBS1 (657del5) and PALB2 (509-510delGA, 172-175delTTGT). A statistically significant association between the 657del5 mutation and an increased risk of pancreatic cancer was observed for NBS1 gene. The Slavic NBS1 gene mutation (657delACAAA) was detected in 8 of 383 (2.09%) unselected cases compared with 22 of 4,000 (0.55%) controls (OR: 3.80, p = 0.002). The PALB2 509_510delGA and 172-175delTTGT mutations combined were seen in 2 (0.52%) unselected cases of PaCa and in 8 (0.20%) of 4,000 controls (OR: 2.61, p = 0.49). For BRCA1, the three mutations combined were detected in 4 of 383 (1.04%) PaCa patients and in 17 of 4,000 (0.42%) controls (OR: 2.46, p = 0.20). CHEK2 mutations were not associated with the risk of pancreatic cancer (OR: 1.11, p = 0.72). The founder mutation in NBS1 (657del5) was associated with an increased risk of PaCa in heterozygous carriers, indicating that this mutation appears to predispose to cancer of the pancreas. By identifying pancreatic cancer risk groups, founder mutation testing in Poland should be considered for people at risk for PaCa.]]> Wed 24 Nov 2021 15:53:13 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:25832 Wed 24 Nov 2021 15:52:52 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:29799 Wed 15 Dec 2021 16:09:48 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:29194 Wed 11 Apr 2018 15:59:14 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:16940 −2 d1 + d15 q28) and oxaliplatin (100 mg m⁻² d2 + d16 q28) in induction (one cycle) and consolidation (three cycles), and 5FU 200 mg m⁻² per day over 6 weeks during 3DCRT 54 Gy. Results: Median duration of sustained local control (LC) was 15.8 months, progression-free survival (PFS) was 11.0 months, and overall survival was 15.7 months. Survival rates for 1, 2, and 3 years were 70.2%, 21.3%, and 12.8%, respectively. Global quality of life did not significantly decline from baseline during treatment, which was associated with modest treatment-related toxicity. Conclusion: Fixed-dose gemcitabine and oxaliplatin, combined with an effective and safe regimen of 5FU and 3DCRT radiotherapy, was feasible and reasonably tolerated. The observed improved duration of LC and PFS with more intensive therapy over previous trials may be due to patient selection, but suggest that further evaluation in phase III trials is warranted.]]> Wed 11 Apr 2018 15:02:24 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:26931 Olea europaea L. leaves are an agricultural waste product with a high concentration of phenolic compounds; especially oleuropein. Oleuropein has been shown to exhibit anti-proliferative activity against a number of cancer types. However, they have not been tested against pancreatic cancer, the fifth leading cause of cancer related death in Western countries. Therefore, water, 50% ethanol and 50% methanol extracts of Corregiola and Frantoio variety Olea europaea L. leaves were investigated for their total phenolic compounds, total flavonoids and oleuropein content, antioxidant capacity and anti-proliferative activity against MiaPaCa-2 pancreatic cancer cells. The extracts only had slight differences in their phytochemical properties, and at 100 and 200 μg/mL, all decreased the viability of the pancreatic cancer cells relative to controls. At 50 μg/mL, the water extract from the Corregiola leaves exhibited the highest anti-proliferative activity with the effect possibly due to early eluting HPLC peaks. For this reason, olive leaf extracts warrant further investigation into their potential anti-pancreatic cancer benefits.]]> Wed 11 Apr 2018 14:54:42 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:16805 Wed 11 Apr 2018 11:29:15 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:15687 Wed 11 Apr 2018 11:09:30 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:29841 n = 116) then follow-up surveys 2 (n = 82) and 4 months (n = 50) later. The validated survey measured 34 needs across five domains. Weighted generalised estimating equations were used to identify factors associated with having ≥1 current or future moderate-to-high unmet need. Results: The overall proportion of patients reporting ≥1 moderate-or-high-level need did not significantly change over time (baseline = 70 % to 4 months = 75 %), although there was a non-significant reduction in needs for patients who had a complete resection (71 to 63 %) and an increase in patients with locally advanced (73 to 85 %) or metastatic (66 to 88 %) disease. Higher levels of pain (OR 6.1, CI 2.4–15.3), anxiety (OR 3.3, CI 1.5–7.3) and depression (OR 3.2, CI 1.7–6.0) were significantly associated with current needs. People with pain (OR 4.9, CI 1.5–15.4), metastatic disease (OR 2.7, CI 0.7–10.0) or anxiety (OR 2.5, CI 0.7–8.6) had substantially higher odds of reporting needs at their next survey. The prevalence of needs was highest in the physical/daily living and psychological domains (both 53 % at baseline). Pain and anxiety had respectively the strongest associations with these domains. Conclusions: Careful and continued attention to pain control and psychological morbidity is paramount in addressing significant unmet needs, particularly for people with metastatic disease. Research on how best to coordinate this is crucial.]]> Wed 11 Apr 2018 10:08:14 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:18744 Wed 11 Apr 2018 10:05:26 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:20668 Wed 11 Apr 2018 09:35:51 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:23842 Wed 09 Mar 2022 16:01:18 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:55022 Wed 03 Apr 2024 15:28:17 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:37505 Wed 02 Mar 2022 14:28:59 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:54455 Tue 27 Feb 2024 13:53:27 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:47647 P = 0.007) and for those under 65 (19.0%; 95% CI, 8.1–28.6%) than for older people (6.6%; 95% CI, 1.9–11.1%; P = 0.030). There were no independent relationships between body mass index or alcohol consumption and pancreatic cancer. Conclusions: Strategies that reduce the uptake of smoking and encourage current smokers to quit could substantially reduce the future incidence of pancreatic cancer in Australia, particularly among men.]]> Tue 24 Jan 2023 14:51:37 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:25817 90 U/ml did not benefit from adjuvant chemotherapy (P = 0.7194) compared with those with a CA19.9 of ≤90 U/ml (median 26.0 vs 16.7 months, P = 0.0108). Normalization of CA19.9 within 6 months of resection was also an independent favorable prognostic factor (median 29.9 vs 14.8 months, P = 0.0004) and normal perioperative CA19.9 levels identified a good prognostic group, which was associated with a 5-year survival of 42%. Conclusions: Perioperative serum CA19.9 measurements are informative in patients with detectable CA19.9 (defined by serum levels of >5 U/ml) and have potential clinical utility in predicting outcome and response to adjuvant chemotherapy. Future clinical trials should prioritize incorporation of CA19.9 measurement at key decision points to prospectively validate these findings and facilitate implementation.]]> Tue 24 Aug 2021 14:31:04 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:43084 Tue 23 Apr 2024 16:00:38 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:50314 Tue 18 Jul 2023 11:37:22 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:36453 Tue 05 May 2020 16:02:57 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:43873 Tue 04 Oct 2022 12:29:00 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:33468 Thu 24 Mar 2022 11:35:57 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:37858 P = 0.0014). Sortilin inhibition by siRNA and the pharmacologic inhibitor AF38469 strongly reduced the adhesion and invasion of pancreatic cancer cells without affecting cell survival and viability. Sortilin inhibition also decreased the phosphorylation of the focal adhesion kinase in Tyr925. Together, these data show that sortilin contributes to pancreatic cancer invasion and could eventually be targeted in therapy.]]> Thu 24 Mar 2022 11:34:45 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:26066 Thu 20 Aug 2020 09:19:59 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:47517 Thu 20 Apr 2023 09:27:04 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:34760 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.]]> Thu 17 Mar 2022 14:34:42 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:48035  47 (3-Cl) > 46 (2-Cl)) against the cell lines examined. The introduction of bulky aromatic moieties was well tolerated, e.g. dihydrobenzo[b][1,4]dioxine (51) returned cohort-2 GI50 values of 1.2-3.4 μM. In all instances the observed docked binding poses and binding scores were consistent with the observed cytotoxicity. This in turn supports, but does not prove, that these analogues function via S100A2-p53 binding groove inhibition.]]> Thu 16 Feb 2023 11:04:01 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:34276 MLH1 and MSH2. Defining mutation load in individual pancreatic cancers and the optimal assay for patient selection may inform clinical trial design for immunotherapy in pancreatic cancer.]]> Thu 13 Jan 2022 10:31:35 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:33408 Thu 04 Nov 2021 10:39:25 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:1481 1 kg lost) or weight stable (≤1 kg lost) after an 8 week nutrition intervention period. Group survival duration (Kaplan Meier) and QoL (EORTC QLQ-C30) were compared. Predictors of weight stability were determined using logistic regression analysis. Results: Patients with weight stabilisation survived longer from baseline (log rank test 5.53, P=0.019). They also reported higher QoL scores (P=0.037) and a greater mean energy intake (P<0.001) at Week 8 than those who continued to lose weight. The absence of nausea and vomiting (OR 6.5, P=0.010) and female gender (OR 5.2, P=0.020) were independent determinants of weight stabilisation. Conclusions: Weight stabilisation over an 8 week period in weight-losing patients with unresectable pancreatic cancer was associated with improved survival duration and QoL.]]> Sat 24 Mar 2018 08:28:12 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:2259 Sat 24 Mar 2018 08:27:17 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:18742 2 years) was associated with poor survival in both groups.Conclusions: FPC represents 9% of PC, and the risk of malignancy in kindred does not appear to be confined to the pancreas. Patients with FPC have more precursor lesions and include fewer active smokers, but other clinicopathologic factors and outcome are similar to those in patients with SPC. Furthermore, some FPC kindreds may exhibit anticipation. A better understanding of the clinical features of PC will facilitate efforts to uncover novel susceptibility genes and the development of early detection strategies.]]> Sat 24 Mar 2018 08:02:49 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:20556 Sat 24 Mar 2018 08:02:35 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:18398 Sat 24 Mar 2018 07:52:36 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:5290 Sat 24 Mar 2018 07:46:30 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:27354 Sat 24 Mar 2018 07:39:39 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:27326 Sat 24 Mar 2018 07:38:36 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:29890 Sat 24 Mar 2018 07:29:53 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:27522 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 p21^WAF1, 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.]]> Sat 24 Mar 2018 07:28:54 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:25904 Sat 24 Mar 2018 07:27:53 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:27570 Sat 24 Mar 2018 07:23:30 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:24459 Sat 24 Mar 2018 07:17:25 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:24886 Sat 24 Mar 2018 07:14:55 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:32409 Mon 23 Sep 2019 11:18:26 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:31978 Mon 23 Sep 2019 10:49:25 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:53783 Mon 15 Jan 2024 10:24:12 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:37621 Mon 01 Mar 2021 13:14:35 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:33232 Fri 30 Aug 2019 09:23:50 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:41096 Fri 22 Jul 2022 18:07:18 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:40015 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 IC50 values of 3.11–17.12 μg/mL. The flow cytometry assays revealed the active fractions caused cell cycle arrest at S phase and promoted apoptosis in MIAPaCa-2 PC cells. The LC/MS analysis revealed that the isolated fractions contained bioactive compounds, such as caffeic acid, rosmarinic acid, sagerinic acid, usnic acid, cucurbitacins and absinthin. It can be concluded that the fractions isolated from H. hirsuta stem exhibit potent in vitro anti-pancreatic cancer activity and thus warrant further in vivo studies to assess their activity against PC followed by isolation of individual bioactive compounds and the evaluation of their anti-pancreatic cancer activity.]]> Fri 22 Jul 2022 13:06:36 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:41710 HNF4A and GATA6, switch metabolic profiles from classical (pancreatic) to predominantly squamous, with glycogen synthase kinase 3 beta (GSK3β) a key regulator of glycolysis. Pharmacological inhibition of GSK3β results in selective sensitivity in the squamous subtype; however, a subset of these squamous patient-derived cell lines (PDCLs) acquires rapid drug tolerance. Using chromatin accessibility maps, we demonstrate that the squamous subtype can be further classified using chromatin accessibility to predict responsiveness and tolerance to GSK3β inhibitors. Our findings demonstrate that distinct patterns of chromatin accessibility can be used to identify patient subgroups that are indistinguishable by gene expression profiles, highlighting the utility of chromatin-based biomarkers for patient selection in the treatment of PDAC.]]> Fri 12 Aug 2022 08:35:16 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:46079 50 currently under investigation. These compounds inhibit biological targets spanning protein kinases, STAT3, BET, HDACs and Bcl-2 family proteins. Unsurprisingly, protein kinase inhibitors are overrepresented. Some trials show promise; a phase I combination trial of vorinostat 11 and capecitabine 17 gave a median overall survival (MoS) of 13 months and a phase II study of pazopanib 15 showed a MoS of 25 months. The current standard of care for metastatic pancreatic ductal adenocarcinoma, fluorouracil/folic acid (5-FU, Adrucil®), and gemcitabine (GEMZAR®) afforded a MoS of 23 and 23.6 months (EPAC-3 study), respectively. In patients who can tolerate the FOLFIRINOX regime, this is becoming the standard of treatment with a MoS of 11.1 months. Clinical study progress has been slow with limited improvement in patient survival relative to gemcitabine 1 monotherapy. A major cause of low PC survival is the late stage of diagnosis, occurring in patients who consider typical early stage warning signs of aches and pains normal. The selection of patients with specific disease phenotypes, the use of improved efficient drug combinations, the identification of biomarkers to specific cancer subtypes and more effective designs of investigation have improved outcomes. To move beyond the current dire condition and paucity of PC treatment options, determination of the best regimes and new treatment options is a challenge that must be met. The reasons for poor PC prognosis have remained largely unchanged for 20 years. This is arguably a consequence of significant changes in the drug discovery landscape, and the increasing pressure on academia to deliver short term ‘media’ friendly short-term news ‘bites’. PC research sits at a pivotal point. Perhaps the greatest challenge is enacting a culture change that recognises that major breakthroughs are a result of blue sky, truly innovative and curiosity driven research.]]> Fri 11 Nov 2022 10:04:19 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:46225 Fri 09 Dec 2022 14:48:55 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:47861 Fri 03 Feb 2023 13:26:00 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:37726 Fri 03 Dec 2021 10:33:48 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:34474 Fri 01 Apr 2022 09:29:15 AEDT ]]>