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Pancreatic Neoplasms: HELP
Articles by George Sharbeen
Based on 4 articles published since 2008
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Between 2008 and 2019, G. Sharbeen wrote the following 4 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Article MutY-Homolog (MYH) inhibition reduces pancreatic cancer cell growth and increases chemosensitivity. 2017

Sharbeen, George / Youkhana, Janet / Mawson, Amanda / McCarroll, Joshua / Nunez, Andrea / Biankin, Andrew / Johns, Amber / Goldstein, David / Phillips, Phoebe. ·Pancreatic Cancer Translational Research Group, Lowy Cancer Research Centre, Prince of Wales Clinical School, University of New South Wales, Sydney, Australia. · Children's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales, Sydney, Australia. · Australian Centre for NanoMedicine, University of New South Wales, Sydney, Australia. · Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Bearsden, Glasgow, Scotland, United Kingdom. · The Kinghorn Cancer Centre, Cancer Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, Australia. ·Oncotarget · Pubmed #27999205.

ABSTRACT: Patients with pancreatic ductal adenocarcinoma (PC) have a poor prognosis due to metastases and chemoresistance. PC is characterized by extensive fibrosis, which creates a hypoxic microenvironment, and leads to increased chemoresistance and intracellular oxidative stress. Thus, proteins that protect against oxidative stress are potential therapeutic targets for PC. A key protein that maintains genomic integrity against oxidative damage is MutY-Homolog (MYH). No prior studies have investigated the function of MYH in PC cells. Using siRNA, we showed that knockdown of MYH in PC cells 1) reduced PC cell proliferation and increased apoptosis; 2) further decreased PC cell growth in the presence of oxidative stress and chemotherapy agents (gemcitabine, paclitaxel and vincristine); 3) reduced PC cell metastatic potential; and 4) decreased PC tumor growth in a subcutaneous mouse model in vivo. The results from this study suggest MYH may be a novel therapeutic target for PC that could potentially improve patient outcome by reducing PC cell survival, increasing the efficacy of existing drugs and reducing metastatic spread.

2 Article Delineating the Role of βIV-Tubulins in Pancreatic Cancer: βIVb-Tubulin Inhibition Sensitizes Pancreatic Cancer Cells to Vinca Alkaloids. 2016

Sharbeen, G / McCarroll, J / Liu, J / Youkhana, J / Limbri, L F / Biankin, A V / Johns, A / Kavallaris, M / Goldstein, D / Phillips, P A. ·Pancreatic Cancer Translational Research Group, Lowy Cancer Research Centre, Prince of Wales Clinical School, University of New South Wales (UNSW), Sydney, Australia, 2052. · Children's Cancer Institute, Lowy Cancer Research Centre, UNSW, Sydney, Australia, 2031; Australian Centre for NanoMedicine, ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, UNSW, Australia. · 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. · The Kinghorn Cancer Centre, Cancer Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, Australia. · Pancreatic Cancer Translational Research Group, Lowy Cancer Research Centre, Prince of Wales Clinical School, University of New South Wales (UNSW), Sydney, Australia, 2052; Australian Centre for NanoMedicine, ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, UNSW, Australia. Electronic address: p.phillips@unsw.edu.au. ·Neoplasia · Pubmed #27889644.

ABSTRACT: Pancreatic cancer (PC) is a lethal disease which is characterized by chemoresistance. Components of the cell cytoskeleton are therapeutic targets in cancer. βIV-tubulin is one such component that has two isotypes-βIVa and βIVb. βIVa and βIVb isotypes only differ in two amino acids at their C-terminus. Studies have implicated βIVa-tubulin or βIVb-tubulin expression with chemoresistance in prostate, breast, ovarian and lung cancer. However, no studies have examined the role of βIV-tubulin in PC or attempted to identify isotype specific roles in regulating cancer cell growth and chemosensitivity. We aimed to determine the role of βIVa- or βIVb-tubulin on PC growth and chemosensitivity. PC cells (MiaPaCa-2, HPAF-II, AsPC1) were treated with siRNA (control, βIVa-tubulin or βIVb-tubulin). The ability of PC cells to form colonies in the presence or absence of chemotherapy was measured by clonogenic assays. Inhibition of βIVa-tubulin in PC cells had no effect chemosensitivity. In contrast, inhibition of βIVb-tubulin in PC cells sensitized to vinca alkaloids (Vincristine, Vinorelbine and Vinblastine), which was accompanied by increased apoptosis and enhanced cell cycle arrest. We show for the first time that βIVb-tubulin, but not βIVa-tubulin, plays a role in regulating vinca alkaloid chemosensitivity in PC cells. The results from this study suggest βIVb-tubulin may be a novel therapeutic target and predictor of vinca alkaloid sensitivity for PC and warrants further investigation.

3 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.

4 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.