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Pancreatic Neoplasms: HELP
Articles by Srinivasa P. Pothula
Based on 6 articles published since 2009
(Why 6 articles?)
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Between 2009 and 2019, S. Pothula wrote the following 6 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Review Circulating pancreatic stellate (stromal) cells in pancreatic cancer-a fertile area for novel research. 2017

Pang, Tony C Y / Xu, Zhihong / Pothula, Srinivasa / Becker, Therese / Goldstein, David / Pirola, Romano C / Wilson, Jeremy S / Apte, Minoti V. ·Pancreatic Research Group, South Western Sydney Clinical School,University of New South Wales, and Ingham Institute of Applied Medical Research, Australia and. · Centre for Circulating Tumour Cell Diagnostics and Research, InghamInstitute for Applied Medical Research, South Western Sydney Clinical School, University of New South Wales, and School ofMedicine, Western Sydney University, Australia. ·Carcinogenesis · Pubmed #28379317.

ABSTRACT: Pancreatic stellate cells (PSCs) are known to play an important role in facilitating pancreatic cancer progression-both in terms of local tumour growth as well as the establishment of metastases. We have previously demonstrated that PSCs from the primary cancer seed to distant metastatic sites. We therefore hypothesise that PSCs circulate along with pancreatic cancer cells (circulating tumour cells-CTCs) to help create a growth permissive microenvironment at distant metastatic sites. This review aims to explore the concept of circulating PSCs in pancreatic cancer and suggests future directions for research in this area.

2 Review Key role of pancreatic stellate cells in pancreatic cancer. 2016

Pothula, Srinivasa P / Xu, Zhihong / Goldstein, David / Pirola, Romano C / Wilson, Jeremy S / Apte, Minoti V. ·Pancreatic Research Group, South Western Sydney Clinical School, Faculty of Medicine, The University of New South Wales, Sydney, Australia; Ingham Institute for Applied Medical Research, Liverpool, NSW, Australia. · Pancreatic Research Group, South Western Sydney Clinical School, Faculty of Medicine, The University of New South Wales, Sydney, Australia. · Pancreatic Research Group, South Western Sydney Clinical School, Faculty of Medicine, The University of New South Wales, Sydney, Australia; Ingham Institute for Applied Medical Research, Liverpool, NSW, Australia. Electronic address: m.apte@unsw.edu.au. ·Cancer Lett · Pubmed #26571462.

ABSTRACT: Pancreatic stellate cells (PSCs) are responsible for producing the collagenous stroma in pancreatic cancer. Findings from the majority of in vitro and in vivo studies to date indicate that PSCs interact with cancer cells as well as with other cellular elements in the stroma including immune cells, endothelial cells and neuronal cells to set up a growth permissive microenvironment for pancreatic tumours. However, two recent studies reporting a protective effect of myofibroblasts in pancreatic cancer have served to remind researchers of the possibility that the role of PSCs in this disease may be context and time-dependent, such that any possible early protective role of PSCs is subverted in later stages by the ability of cancer cells to turn PSCs into cancer-promoting aides. This concept is supported by the development in recent years of several novel therapeutic approaches targeting the stroma that have been successfully applied in pre-clinical settings to inhibit disease progression. A multi-pronged approach aimed at tumour cells as well as stromal elements may be the key to achieving better clinical outcomes in patients with pancreatic cancer.

3 Review Pancreatic cancer: The microenvironment needs attention too! 2015

Apte, M V / Xu, Z / Pothula, S / Goldstein, D / Pirola, R C / Wilson, J S. ·Pancreatic Research Group, South Western Sydney Clinical School, Faculty of Medicine, University of New South Wales, Sydney, Australia; Ingham Institute for Applied Medical Research, Sydney, Australia. Electronic address: m.apte@unsw.edu.au. · Pancreatic Research Group, South Western Sydney Clinical School, Faculty of Medicine, University of New South Wales, Sydney, Australia; Ingham Institute for Applied Medical Research, Sydney, Australia. · Pancreatic Research Group, South Western Sydney Clinical School, Faculty of Medicine, University of New South Wales, Sydney, Australia; Department of Medical Oncology, Prince of Wales Hospital, Sydney, and Faculty of Medicine, University of New South Wales, Sydney, Australia. ·Pancreatology · Pubmed #25845856.

ABSTRACT: The abundant stromal/desmoplastic reaction, a characteristic feature of a majority of pancreatic adenocarcinomas (PDAC), has only recently been receiving some attention regarding its possible role in the pathobiology of pancreatic cancer. It is now well established that the cells predominantly responsible for producing the collagenous stroma are pancreatic stellate cells (PSCs). In addition to extracellular matrix proteins, the stroma also exhibits cellular elements including, immune cells, endothelial cells and neural cells. Evidence is accumulating to indicate the presence of significant interactions between PSCs and cancer cells as well as between PSCs and other cell types in the stroma. The majority of research reports to date, using in vitro and in vivo approaches, suggest that these interactions facilitate local growth as well as distant metastasis of pancreatic cancer, although a recent study using animals depleted of myofibroblasts has raised some questions regarding the central role of myofibroblasts in cancer progression. Nonetheless, novel therapeutic strategies have been assessed, mainly in the pre-clinical setting, in a bid to interrupt stromal-tumour interactions and inhibit disease progression. The next important challenge is for the translation of such pre-clinical strategies to the clinical situation so as to improve the outcome of patients with pancreatic cancer.

4 Review Pancreatic cancer and its stroma: a conspiracy theory. 2014

Xu, Zhihong / Pothula, Srinivasa P / Wilson, Jeremy S / Apte, Minoti V. ·Zhihong Xu, Srinivasa P Pothula, Jeremy S Wilson, Minoti V Apte, Pancreatic Research Group, South Western Sydney Clinical School, Faculty of Medicine, The University of New South Wales, Sydney, NSW 2170, Australia. ·World J Gastroenterol · Pubmed #25170206.

ABSTRACT: Pancreatic cancer is characterised by a prominent desmoplastic/stromal reaction that has received little attention until recent times. Given that treatments focusing on pancreatic cancer cells alone have failed to significantly improve patient outcome over many decades, research efforts have now moved to understanding the pathophysiology of the stromal reaction and its role in cancer progression. In this regard, our Group was the first to identify the cells (pancreatic stellate cells, PSCs) that produced the collagenous stroma of pancreatic cancer and to demonstrate that these cells interacted closely with cancer cells to facilitate local tumour growth and distant metastasis. Evidence is accumulating to indicate that stromal PSCs may also mediate angiogenesis, immune evasion and the well known resistance of pancreatic cancer to chemotherapy and radiotherapy. This review will summarise current knowledge regarding the critical role of pancreatic stellate cells and the stroma in pancreatic cancer biology and the therapeutic approaches being developed to target the stroma in a bid to improve the outcome of this devastating disease.

5 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.

6 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.