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Pancreatic Neoplasms: HELP
Articles by David Goldstein
Based on 38 articles published since 2009
(Why 38 articles?)
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Between 2009 and 2019, David Goldstein wrote the following 38 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
Pages: 1 · 2
26 Article A Rationally Optimized Nanoparticle System for the Delivery of RNA Interference Therapeutics into Pancreatic Tumors in Vivo. 2016

Teo, Joann / McCarroll, Joshua A / Boyer, Cyrille / Youkhana, Janet / Sagnella, Sharon M / Duong, Hien T T / Liu, Jie / Sharbeen, George / Goldstein, David / Davis, Thomas P / Kavallaris, Maria / Phillips, Phoebe A. ·Tumour Biology and Targeting Program, Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Australia , Sydney, New South Wales 2052, Australia. · Australian Centre for NanoMedicine, UNSW Australia , Sydney, New South Wales 2052, Australia. · Centre for Advanced Macromolecular Design, School of Chemical Engineering, UNSW Australia , Sydney, New South Wales 2052, Australia. · Pancreatic Cancer Translational Research Group, Lowy Cancer Research Centre, Prince of Wales Clinical School, UNSW Australia , Sydney, New South Wales 2052, Australia. · Prince of Wales Hospital, Prince of Wales Clinical School , Sydney, New South Wales 2052, Australia. · ARC Centre of Excellence in Convergent Bio-Nano Science and Technology Monash Institute of Pharmaceutical Sciences, Monash University , Clayton, Victoria 3800, Australia. · Department of Chemistry, University of Warwick , Coventry CV4 7AL, United Kingdom. · ARC Centre of Excellence in Convergent Bio-Nano Science and Technology UNSW Australia , Sydney, New South Wales 2052, Australia. ·Biomacromolecules · Pubmed #27305597.

ABSTRACT: Pancreatic cancer is a devastating disease with a dismal prognosis. Short-interfering RNA (siRNA)-based therapeutics hold promise for the treatment of cancer. However, development of efficient and safe delivery vehicles for siRNA remains a challenge. Here, we describe the synthesis and physicochemical characterization of star polymers (star 1, star 2, star 3) using reversible addition-fragmentation chain transfer polymerization (RAFT) for the delivery of siRNA to pancreatic cancer cells. These star polymers were designed to contain different lengths of cationic poly(dimethylaminoethyl methacrylate) (PDMAEMA) side-arms and varied amounts of poly[oligo(ethylene glycol) methyl ether methacrylate] (POEGMA). We showed that star-POEGMA polymers could readily self-assemble with siRNA to form nanoparticles. The star-POEGMA polymers were nontoxic to normal cells and delivered siRNA with high efficiency to pancreatic cancer cells to silence a gene (TUBB3/βIII-tubulin) which is currently undruggable using chemical agents, and is involved in regulating tumor growth and metastases. Notably, systemic administration of star-POEGMA-siRNA resulted in high accumulation of siRNA to orthotopic pancreatic tumors in mice and silenced βIII-tubulin expression by 80% at the gene and protein levels in pancreatic tumors. Together, these novel findings provide strong rationale for the use of star-POEGMA polymers as delivery vehicles for siRNA to pancreatic tumors.

27 Article Determinants of Outcomes Following Resection for Pancreatic Cancer-a Population-Based Study. 2016

Waterhouse, Mary A / Burmeister, Elizabeth A / O'Connell, Dianne L / Ballard, Emma L / Jordan, Susan J / Merrett, Neil D / Goldstein, David / Wyld, David / Janda, Monika / Beesley, Vanessa L / Payne, Madeleine E / Gooden, Helen M / Neale, Rachel E. ·QIMR Berghofer Medical Research Institute, Brisbane, Australia. · The University of Queensland, Brisbane, Australia. · Cancer Council New South Wales, Sydney, Australia. · University of Newcastle, Sydney, Australia. · University of Sydney, Sydney, Australia. · Western Sydney University, Sydney, Australia. · University of New South Wales, Sydney, Australia. · Prince of Wales Hospital, Sydney, Australia. · Royal Brisbane and Women's Hospital, Brisbane, Australia. · Queensland University of Technology, Brisbane, Australia. · QIMR Berghofer Medical Research Institute, Brisbane, Australia. rachel.neale@qimrberghofer.edu.au. ·J Gastrointest Surg · Pubmed #27184672.

ABSTRACT: BACKGROUND: Patient and health system determinants of outcomes following pancreatic cancer resection, particularly the relative importance of hospital and surgeon volume, are unclear. Our objective was to identify patient, tumour and health service factors related to mortality and survival amongst a cohort of patients who underwent completed resection for pancreatic cancer. METHODS: Eligible patients were diagnosed with pancreatic adenocarcinoma between July 2009 and June 2011 and had a completed resection performed in Queensland or New South Wales, Australia, with either tumour-free (R0) or microscopically involved margins (R1) (n = 270). Associations were examined using logistic regression (for binary outcomes) and Cox proportional hazards or stratified Cox models (for time-to-event outcomes). RESULTS: Patients treated by surgeons who performed <4 resections/year were more likely to die from a surgical complication (versus ≥4 resections/year, P = 0.04), had higher 1-year mortality (P = 0.03), and worse overall survival up to 1.5 years after surgery (adjusted hazard ratio 1.58, 95 % confidence interval 1.07-2.34). Amongst patients who had ≥1 complication within 30 days of surgery, those aged ≥70 years had higher 1-year mortality compared to patients aged <60 years. Adjuvant chemotherapy treatment improved recurrence-free survival (P = 0.01). There were no significant associations between hospital volume and mortality or survival. CONCLUSIONS: Systems should be implemented to ensure that surgeons are completing a sufficient number of resections to optimize patient outcomes. These findings may be particularly relevant for countries with a relatively small and geographically dispersed population.

28 Article Risk factors for current and future unmet supportive care needs of people with pancreatic cancer. A longitudinal study. 2016

Beesley, Vanessa L / Wockner, Leesa F / O'Rourke, Peter / Janda, Monika / Goldstein, David / Gooden, Helen / Merrett, Neil D / O'Connell, Dianne L / Rowlands, Ingrid J / Wyld, David K / Neale, Rachel E. ·Population Health Department, QIMR Berghofer Medical Research Institute, Brisbane, Australia. Vanessa.Beesley@qimrberghofer.edu.au. · Population Health Department, QIMR Berghofer Medical Research Institute, Brisbane, Australia. · School of Public Health and Social Work, Queensland University of Technology, Brisbane, Australia. · Department of Medical Oncology, Prince of Wales Hospital, Sydney, Australia. · University of New South Wales, Sydney, Australia. · Cancer Nursing Research Unit, University of Sydney, Sydney, Australia. · Discipline of Surgery, Western Sydney University, Sydney, Australia. · South Western Sydney Upper GI Surgical Unit, Bankstown Hospital, Sydney, Australia. · Cancer Research Division, Cancer Council New South Wales, Sydney, Australia. · School of Public Health, The University of Queensland, Brisbane, Australia. · Department of Medical Oncology, Royal Brisbane and Women's Hospital, Brisbane, Australia. · University of Queensland, Brisbane, Australia. ·Support Care Cancer · Pubmed #27086312.

ABSTRACT: PURPOSE: This study aims to determine if the supportive care needs of people with pancreatic cancer change over time and identify the factors associated with current and future unmet needs. METHODS: Australian pancreatic cancer patients completed a self-administered survey at 0-6 months post-diagnosis (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.

29 Article Using a Delphi process to determine optimal care for patients with pancreatic cancer. 2016

Burmeister, Elizabeth A / Jordan, Susan J / O'Connell, Dianne L / Beesley, Vanessa L / Goldstein, David / Gooden, Helen M / Janda, Monika / Merrett, Neil D / Wyld, David / Neale, Rachel E / Anonymous130856. ·QIMR Berghofer Medical Research Institute. · School of Public Health. · Cancer Council NSW. · University of Newcastle. · University of New South Wales. · University of Sydney. · Prince of Wales Hospital. · Queensland University of Technology. · University of Western Sydney. · Bankstown Hospital, NSW, Australia. · Royal Brisbane and Women's Hospital, Brisbane. · School of Medicine, University of Queensland, Queensland. ·Asia Pac J Clin Oncol · Pubmed #26800012.

ABSTRACT: AIM: Overall 5-year survival for pancreatic cancer is ∼5%. Optimizing the care that pancreatic cancer patients receive may be one way of improving outcomes. The objective of this study was to establish components of care which Australian health professionals believe important to optimally manage patients with pancreatic cancer. METHODS: Using a Delphi process, a multidisciplinary panel of 250 health professionals were invited to provide a list of factors they considered important for optimal care of pancreatic cancer patients. They were then asked to score and then rescore (from one [no importance/disagree] to 10 [very important/agree]) the factors. The mean and coefficient of variation scores were calculated and categorized into three levels of importance. RESULTS: Overall, 63 (66% of those sent the final questionnaire; 25% of those initially invited) health professionals from nine disciplines completed the final scoring of 55 statements/factors encompassing themes of presentation/staging, surgery and biliary obstruction, multidisciplinary team details and oncology. Mean scores ranged from 3.7 to 9.7 with the highest related to communication and patient assessment. There was substantial intra- and interdisciplinary variation in views about MDT membership and roles. CONCLUSION: Overall, the opinions of Australian health professionals reflect international guideline recommended care; however, they identified a number of additional factors focusing on where patients should be treated, the importance of clear communication and the need for multidisciplinary care which were not included in current clinical practice guidelines. Differences in priorities between specialty groups were also identified.

30 Article Hepatocyte growth factor inhibition: a novel therapeutic approach in pancreatic cancer. 2016

Pothula, Srinivasa P / Xu, Zhihong / Goldstein, David / Biankin, Andrew V / Pirola, Romano C / Wilson, Jeremy S / Apte, Minoti V. ·Pancreatic Research Group, South Western Sydney Clinical School, Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia. · Ingham Institute for Applied Medical Research, Liverpool, New South Wales, Australia. · Department of Medical Oncology, Prince of Wales Hospital, Sydney, New South Wales, Australia. · Cancer Research Division, The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, New South Wales, Australia. ·Br J Cancer · Pubmed #26766740.

ABSTRACT: BACKGROUND: Pancreatic stellate cells (PSCs, which produce the stroma of pancreatic cancer (PC)) interact with cancer cells to facilitate PC growth. A candidate growth factor pathway that may mediate this interaction is the HGF-c-MET pathway. METHODS: Effects of HGF inhibition (using a neutralising antibody AMG102) alone or in combination with gemcitabine were assessed (i) in vivo using an orthotopic model of PC, and (ii) in vitro using cultured PC cells (AsPC-1) and human PSCs. RESULTS: We have shown that human PSCs (hPSCs) secrete HGF but do not express the receptor c-MET, which is present predominantly on cancer cells. HGF inhibition was as effective as standard chemotherapy in inhibiting local tumour growth but was significantly more effective than gemcitabine in reducing tumour angiogenesis and metastasis. HGF inhibition has resulted in reduced metastasis; however, interestingly this antimetastatic effect was lost when combined with gemcitabine. This suggests that gemcitabine treatment selects out a subpopulation of cancer cells with increased epithelial-mesenchymal transition (EMT) and stem-cell characteristics, as supported by our findings of increased expression of EMT and stem-cell markers in tumour sections from our animal model. In vitro studies showed that hPSC secretions induced proliferation and migration, but inhibited apoptosis, of cancer cells. These effects were countered by pretreatment of hPSC secretions with a HGF-neutralising antibody but not by gemcitabine, indicating a key role for HGF in PSC-PC interactions. CONCLUSIONS: Our studies suggest that targeted therapy to inhibit stromal-tumour interactions mediated by the HGF-c-MET pathway may represent a novel therapeutic approach in PC that will require careful modelling for optimal integration with existing treatment modalities.

31 Article A tsunami of unmet needs: pancreatic and ampullary cancer patients' supportive care needs and use of community and allied health services. 2016

Beesley, Vanessa L / Janda, Monika / Goldstein, David / Gooden, Helen / Merrett, Neil D / O'Connell, Dianne L / Rowlands, Ingrid J / Wyld, David / Neale, Rachel E. ·Gynaecological Cancers Group, QIMR Berghofer Medical Research Institute, Brisbane, Australia. · School of Public Health and Social Work, Queensland University of Technology, Brisbane, Australia. · Department of Medical Oncology, Prince of Wales Hospital, Sydney, Australia. · University of New South Wales, Sydney, Australia. · Sydney Nursing School, University of Sydney, Sydney, Australia. · Discipline of Surgery, University of Western Sydney, Sydney, Australia. · South Western Sydney Upper GI Surgical Unit, Bankstown Hospital, Sydney, Australia. · Cancer Research Division, Cancer Council NSW, Sydney, Australia. · School of Public Health, University of Queensland, Brisbane, Australia. · Department of Medical Oncology, Royal Brisbane and Women's Hospital, Brisbane, Australia. · University of Queensland, Brisbane, Australia. · Cancer Aetiology and Prevention Group, QIMR Berghofer Medical Research Institute, Brisbane, Australia. ·Psychooncology · Pubmed #26123474.

ABSTRACT: OBJECTIVE: People diagnosed with pancreatic cancer have the worst survival prognosis of any cancer. No previous research has documented the supportive care needs of this population. Our objective was to describe people's needs and use of support services and to examine whether these differed according to whether or not patients had undergone surgical resection. METHODS: Queensland pancreatic or ampullary cancer patients (n = 136, 54% of those eligible) completed a survey, which assessed 34 needs across five domains (Supportive Care Needs Survey-Short Form) and use of health services. Differences by resection were compared with Chi-squared tests. RESULTS: Overall, 96% of participants reported having some needs. More than half reported moderate-to-high unmet physical (54%) or psychological (52%) needs, whereas health system/information (32%), patient care (21%) and sexuality needs (16%) were described less frequently. The three most frequently reported moderate-to-high needs included 'not being able to do things they used to do' (41%), 'concerns about the worries of those close' (37%) and 'uncertainty about the future' (30%). Patients with non-resectable disease reported greater individual information needs, but their needs were otherwise similar to patients with resectable disease. Self-reported use of support was low; only 35% accessed information, 28%, 18% and 15% consulted a dietician, complementary medicine practitioner or mental health practitioner, respectively. Palliative care access was greater (59% vs 27%) among those with non-resectable disease. CONCLUSION: Very high levels of needs were reported by people with pancreatic or ampullary cancer. Future work needs to elucidate why uptake of appropriate supportive care is low and which services are required.

32 Article Describing Patterns of Care in Pancreatic Cancer: A Population-Based Study. 2015

Burmeister, Elizabeth A / OʼConnell, Dianne L / Beesley, Vanessa L / Goldstein, David / Gooden, Helen M / Janda, Monika / Jordan, Susan J / Merrett, Neil D / Payne, Madeleine E / Wyld, David / Neale, Rachel E / Anonymous1070839. ·From the *Population Health, QIMR Berghofer Medical Research Institute; †University of Queensland, Brisbane, Queensland; ‡Cancer Research Division, Cancer Council NSW, Sydney; §University of Newcastle, Newcastle; ║Department of Medical Oncology, Prince of Wales Hospital; ¶University of New South Wales; #Sydney Nursing School, University of Sydney, Sydney, New South Wales; **Queensland University of Technology, Brisbane, Queensland; ††School of Medicine, University of Western Sydney, Sydney, New South Wales; and ‡‡Department of Medical Oncology, Royal Brisbane and Women's Hospital, Brisbane, Queensland. ·Pancreas · Pubmed #26262591.

ABSTRACT: OBJECTIVES: Despite pancreatic cancer being the fifth highest cause of cancer death in developed regions, there is a paucity of population-based management details for patients with pancreatic cancer. The objective of this study was to reflect on current practice and outcomes to facilitate future improvement. METHODS: A comprehensive population-based patterns-of-care study in 2 Australian states was conducted. Patients diagnosed with pancreatic adenocarcinoma between July 2009 and June 2011 were identified by cancer registries, and detailed clinical data were collected from medical records. RESULTS: Data were collected for 1863 patients, 96% of those eligible. The majority resided in major cities; their median age was 72 years, and 54% were men. Over half of the cases (58%) had metastatic disease at diagnosis. Resection was attempted for 20% of patients but only completed in 15%. The uptake of adjuvant chemotherapy (76%) and the proportion alive at 1-year (22%) were higher than reported in previous population-based reports. Of those with no complete surgical resection, 43% received palliative chemotherapy. CONCLUSIONS: This population-based overview of the management of patients with pancreatic cancer suggests that, despite evidence that the proportion surviving and the use of adjuvant chemotherapy has increased, there may still be underutilization of cancer-directed therapies.

33 Article βIII-tubulin: a novel mediator of chemoresistance and metastases in pancreatic cancer. 2015

McCarroll, Joshua A / Sharbeen, George / Liu, Jie / Youkhana, Janet / Goldstein, David / McCarthy, Nigel / Limbri, Lydia F / Dischl, Dominic / Ceyhan, Güralp O / Erkan, Mert / Johns, Amber L / Biankin, Andrew V / Kavallaris, Maria / Phillips, Phoebe A. ·Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Australia, Sydney, Australia. · ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Australian Centre for NanoMedicine, UNSW, Australia. · Pancreatic Cancer Translational Research Group, Lowy Cancer Research Centre, Prince of Wales Clinical School, University of New South Wales (UNSW Australia), Sydney, Australia. · Prince of Wales Hospital, Prince of Wales Clinical School, Sydney, NSW, Australia. · Department of Surgery, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany. · Department of Surgery Koc University School of Medicine, Istanbul, Turkey. · The Kinghorn Cancer Centre, Cancer Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, Australia. · Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Bearsden, Glasgow, Scotland G61 1BD, United Kingdom. ·Oncotarget · Pubmed #25544769.

ABSTRACT: Pancreatic cancer is a leading cause of cancer-related deaths in Western societies. This poor prognosis is due to chemotherapeutic drug resistance and metastatic spread. Evidence suggests that microtubule proteins namely, β-tubulins are dysregulated in tumor cells and are involved in regulating chemosensitivity. However, the role of β-tubulins in pancreatic cancer are unknown. We measured the expression of different β-tubulin isotypes in pancreatic adenocarcinoma tissue and pancreatic cancer cells. Next, we used RNAi to silence βIII-tubulin expression in pancreatic cancer cells, and measured cell growth in the absence and presence of chemotherapeutic drugs. Finally, we assessed the role of βIII-tubulin in regulating tumor growth and metastases using an orthotopic pancreatic cancer mouse model. We found that βIII-tubulin is highly expressed in pancreatic adenocarcinoma tissue and pancreatic cancer cells. Further, we demonstrated that silencing βIII-tubulin expression reduced pancreatic cancer cell growth and tumorigenic potential in the absence and presence of chemotherapeutic drugs. Finally, we demonstrated that suppression of βIII-tubulin reduced tumor growth and metastases in vivo. Our novel data demonstrate that βIII-tubulin is a key player in promoting pancreatic cancer growth and survival, and silencing its expression may be a potential therapeutic strategy to increase the long-term survival of pancreatic cancer patients.

34 Article The role of the hepatocyte growth factor/c-MET pathway in pancreatic stellate cell-endothelial cell interactions: antiangiogenic implications in pancreatic cancer. 2014

Patel, Mishaal B / Pothula, Srinivasa P / Xu, Zhihong / Lee, Alexandra K / Goldstein, David / Pirola, Romano C / Apte, Minoti V / Wilson, Jeremy S. ·Pancreatic Research Group, South Western Sydney Clinical School, Ingham Institute for Applied Medical Research and the School of Medical Sciences, University of New South Wales, Sydney, New South Wales 2170, Australia. · Pancreatic Research Group, South Western Sydney Clinical School, Ingham Institute for Applied Medical Research and the School of Medical Sciences, University of New South Wales, Sydney, New South Wales 2170, Australia. m.apte@unsw.edu.au. ·Carcinogenesis · Pubmed #24876152.

ABSTRACT: Activated cancer-associated human pancreatic stellate cells (CAhPSCs, which produce the collagenous stroma of pancreatic cancer [PC]) are known to play a major role in PC progression. Apart from inducing cancer cell proliferation and migration, CAhPSCs have also been implicated in neoangiogenesis in PC. However, the mechanisms mediating the observed angiogenic effects of CAhPSCs are unknown. A candidate pathway that may be involved in this process is the hepatocyte growth factor (HGF)/c-MET pathway and its helper molecule, urokinase-type plasminogen activator (uPA). This study investigated the effects of CAhPSC secretions on endothelial cell function in the presence and absence of HGF, c-MET and uPA inhibitors. HGF levels in CAhPSC secretions were quantified using ELISA. CAhPSC secretions were then incubated with human microvascular endothelial cells (HMEC-1) and angiogenesis assessed by quantifying HMEC-1 tube formation and proliferation. CAhPSC-secreted HGF significantly increased HMEC-1 tube formation and proliferation; notably, these effects were downregulated by inhibition of HGF, its receptor c-MET and uPA. Phosphorylation of p38 mitogen-activated protein kinase was downregulated during inhibition of the HGF/c-MET pathway, whereas phosphatidylinositol-3 kinase and ERK1/2 remained unaffected. Our studies have shown for the first time that CAhPSCs induce proliferation and tube formation of HMEC-1 and that the HGF/c-MET pathway plays a major role in this induction. Given that standard antiangiogenic treatment targeting vascular endothelial growth factor has had limited success in the clinical setting, the findings of the current study provide strong support for a novel, alternative antiangiogenic approach targeting the HGF/c-MET and uPA pathways in PC.

35 Article Pancreatic cancer hENT1 expression and survival from gemcitabine in patients from the ESPAC-3 trial. 2014

Greenhalf, William / Ghaneh, Paula / Neoptolemos, John P / Palmer, Daniel H / Cox, Trevor F / Lamb, Richard F / Garner, Elizabeth / Campbell, Fiona / Mackey, John R / Costello, Eithne / Moore, Malcolm J / Valle, Juan W / McDonald, Alexander C / Carter, Ross / Tebbutt, Niall C / Goldstein, David / Shannon, Jennifer / Dervenis, Christos / Glimelius, Bengt / Deakin, Mark / Charnley, Richard M / Lacaine, François / Scarfe, Andrew G / Middleton, Mark R / Anthoney, Alan / Halloran, Christopher M / Mayerle, Julia / Oláh, Attila / Jackson, Richard / Rawcliffe, Charlotte L / Scarpa, Aldo / Bassi, Claudio / Büchler, Markus W / Anonymous5150777. ·Affiliations of authors: Liverpool Cancer Research UK Cancer Trials Unit, Liverpool Cancer Research UK Centre, University of Liverpool, Liverpool, UK (WG, JPN, EG, TFC, PG, EC, CMH, CLR, FC, RJ) · the Princess Margaret Hospital, Toronto, Canada (MJM) · Manchester Academic Health Sciences Centre, Christie NHS Foundation Trust, School of Cancer and Enabling Sciences, University of Manchester, UK (JWV) · Queen Elizabeth Hospital, University Hospital Birmingham NHS Foundation Trust, Birmingham, UK (DHP) · Beatson West of Scotland Cancer Centre, Glasgow, UK (ACM) · Glasgow Royal Infirmary, Glasgow, UK (RC) · Hôpital Tenon, Université, Pierre et Marie Curie, Paris, France (FL) · Austin Health, Melbourne, Australia (NCT) · Prince of Wales Hospital and Clinical School University of New South Wales, New South Wales, Australia (DG) · Nepean Cancer Centre and University of Sydney, Sydney, Australia (JS) · Agia Olga Hospital, Athens, Greece (CD) · Medical Oncology, Clatterbridge Centre for Oncology, Bebington, Merseyside, UK (DS) · Department of Oncology, Akademiska Sjukhuset, Uppsala University, Uppsala, Sweden (BG) · University Hospital, North Staffordshire, UK (MD) · Freeman Hospital, Newcastle upon Tyne, UK (RMC) · Service de Chirurgie Digestive et Viscérale, Hôpital Tenon, Paris, France (FL) · Cross Cancer Institute and University of Alberta, Alberta, Canada (JRM, AGS) · Churchill Hospital, Oxford University Hospitals NHS Trust, Oxford, UK (MRM) · St James's University Hospital, Leeds, UK (AA) · Department of Medicine A, University Medicine Greifswald, Greifswald, Germany (JM) · Petz Aladar Hospital, Gyor, Hungary (AO) · Departments of Surgery and Pathology and ARC-NET Research Center, University of Verona, Italy (AS, CB) · Department of Surgery, University of Heidelberg, Heidelberg, Germany (MWB). ·J Natl Cancer Inst · Pubmed #24301456.

ABSTRACT: BACKGROUND: Human equilibrative nucleoside transporter 1 (hENT1) levels in pancreatic adenocarcinoma may predict survival in patients who receive adjuvant gemcitabine after resection. METHODS: Microarrays from 434 patients randomized to chemotherapy in the ESPAC-3 trial (plus controls from ESPAC-1/3) were stained with the 10D7G2 anti-hENT1 antibody. Patients were classified as having high hENT1 expression if the mean H score for their cores was above the overall median H score (48). High and low hENT1-expressing groups were compared using Kaplan-Meier curves, log-rank tests, and Cox proportional hazards models. All statistical tests were two-sided. RESULTS: Three hundred eighty patients (87.6%) and 1808 cores were suitable and included in the final analysis. Median overall survival for gemcitabine-treated patients (n = 176) was 23.4 (95% confidence interval [CI] = 18.3 to 26.0) months vs 23.5 (95% CI = 19.8 to 27.3) months for 176 patients treated with 5-fluorouracil/folinic acid (χ(2) 1=0.24; P = .62). Median survival for patients treated with gemcitabine was 17.1 (95% CI = 14.3 to 23.8) months for those with low hENT1 expression vs 26.2 (95% CI = 21.2 to 31.4) months for those with high hENT1 expression (χ(2)₁= 9.87; P = .002). For the 5-fluorouracil group, median survival was 25.6 (95% CI = 20.1 to 27.9) and 21.9 (95% CI = 16.0 to 28.3) months for those with low and high hENT1 expression, respectively (χ(2)₁ = 0.83; P = .36). hENT1 levels were not predictive of survival for the 28 patients of the observation group (χ(2)₁ = 0.37; P = .54). Multivariable analysis confirmed hENT1 expression as a predictive marker in gemcitabine-treated (Wald χ(2) = 9.16; P = .003) but not 5-fluorouracil-treated (Wald χ(2) = 1.22; P = .27) patients. CONCLUSIONS: Subject to prospective validation, gemcitabine should not be used for patients with low tumor hENT1 expression.

36 Article Role of pancreatic stellate cells in pancreatic cancer metastasis. 2010

Xu, Zhihong / Vonlaufen, Alain / Phillips, Phoebe A / Fiala-Beer, Eva / Zhang, Xuguo / Yang, Lu / Biankin, Andrew V / Goldstein, David / Pirola, Romano C / Wilson, Jeremy S / Apte, Minoti V. ·Pancreatic Research Group, South Western Sydney Clinical School, School of Medical Sciences, Faculty of Medicine, Room 505, Level 5, Wallace Wurth Building, The University of New South Wales, Sydney, NSW 2052, Australia. ·Am J Pathol · Pubmed #20934972.

ABSTRACT: Pancreatic stellate cells (PSCs) produce the stromal reaction in pancreatic cancer (PC), and their interaction with cancer cells facilitates cancer progression. This study investigated the role of human PSCs (hPSCs) in the metastatic process and tumor angiogenesis using both in vivo (orthotopic model) and in vitro (cultured PSC and PC cells) approaches. A sex mismatch study (injection of male hPSCs plus female PC cells into the pancreas of female mice) was conducted to determine whether hPSCs accompany cancer cells to metastatic sites. Metastatic nodules were examined by fluorescent in situ hybridization for the presence of the Y chromosome. Angiogenesis was assessed by i) immunostaining tumors for CD31, an endothelial cell marker; and ii) quantifying human microvascular endothelial cell (HMEC-1) tube formation in vitro on exposure to conditioned media from hPSCs. Transendothelial migration was assessed in vitro by examining the movement of fluorescently labeled hPSCs through an endothelial cell monolayer. Human PSCs i) were found in multiple metastatic sites in each mouse injected with male hPSCs plus female PC cells; ii) increased CD31 expression in primary tumors from mice injected with MiaPaCa-2 and hPSCs and stimulated tube formation by HMEC-1 in vitro; and iii) exhibited transendothelial migration that was stimulated by cancer cells. Human PSCs accompany cancer cells to metastatic sites, stimulate angiogenesis, and are able to intravasate/extravasate to and from blood vessels.

37 Minor Response. 2015

Goldstein, David / Von Hoff, Daniel. ·: Department of Medical Oncology, Prince of Wales Hospital, NSW, Australia (DG);HonorHealth and The Translational Genomics Research Institute (TGen), Scottsdale, AZ (DVH). ·J Natl Cancer Inst · Pubmed #26251330.

ABSTRACT: -- No abstract --

38 Minor Albumin-bound paclitaxel plus gemcitabine in pancreatic cancer. 2014

Von Hoff, Daniel D / Goldstein, David / Renschler, Markus F. · ·N Engl J Med · Pubmed #24476438.

ABSTRACT: -- No abstract --

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