Molecular mechanisms of pancreatic cancer and potential targets of treatment

Aho, Ursula; Zhao, Xia; Löhr, Matthias; Andersson, Roland

doi:10.1080/00365520601106384

Cited by 9 publications

(2 citation statements)

References 169 publications

(203 reference statements)

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“…Central mechanisms include nuclear factor kappaB (NF-kB) which promotes cancer growth via inhibition of apoptosis and increased expression of cyclooxygenase-2 in human pancreatic cancer tissue; this leads to increased vascular endothelial growth factor expression and metastatic potential [33]. The synergistic effects with anti-inflammatory agents combined with gemcitabine treatment are of interest in this context.…”

Section: Potential Ways Of Improving Intracellular Gemcitabine Uptakementioning

confidence: 99%

Gemcitabine chemoresistance in pancreatic cancer: Molecular mechanisms and potential solutions

Andersson

Aho

Nilsson³

et al. 2009

Scandinavian Journal of Gastroenterology

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121

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Ductal pancreatic adenocarcinoma is associated with a very poor prognosis and most patients are given palliative care. Chemotherapy in the form of gemcitabine has been found to reduce disease-related pain, and the otherwise frequently occurring weight changes, to increase Karnofsky performance status and quality of life and has also resulted in a modest improvement in survival time. The intracellular uptake of gemcitabine is dependent on nucleoside transporters, predominantly human equilibrative nucleoside transporter-1 (hENT-1), which is over-expressed in human pancreatic adenocarcinoma cells. Cellular resistance to gemcitabine can be intrinsic or acquired during gemcitabine treatment. One of the mechanisms is a decrease in hENT-1 expression. Modifications of gemcitabine not rendering it dependent on the nucleoside transporter may be a successful future mode of chemotherapy treatment, and determination of the nucleoside receptor status at the time of diagnosis could potentially also contribute to a more targeted therapy in the future.

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Section: Potential Ways Of Improving Intracellular Gemcitabine Uptakementioning

confidence: 99%

Gemcitabine chemoresistance in pancreatic cancer: Molecular mechanisms and potential solutions

Andersson

Aho

Nilsson³

et al. 2009

Scandinavian Journal of Gastroenterology

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121

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“…Pancreatic ductal adenocarcinoma (PDAC) is a devastating disorder for most people who are afflicted, with a reported 5-year survival of less than 1% [1]. In Western countries, pancreatic adenocarcinoma comprises the fourth most common cause of malignancy-related death, and the annual incidence has been estimated to be approximately 10 cases per 100,000 population [2].…”

Section: Introductionmentioning

confidence: 99%

Pancreatic Cancer: The Role of Pancreatic Stellate Cells in Tumor Progression

et al. 2011

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Pancreatic ductal adenocarcinoma is an aggressive and highly lethal disease frequently characterized by a dense stromal or desmoplastic response. Accumulating evidence exists that tumor desmoplasia plays a central role in disease progression and that e.g. activated pancreatic stellate cells (PSCs) are responsible for the excess matrix production. The mechanisms underlying the tumor versus stroma interplay are complex. Pancreatic cancer cells release mitogenic and fibrogenic stimulants, such as transforming growth factor β₁, platelet-derived growth factor (PDGF), sonic hedgehog, galectin 3, endothelin 1 and serine protease inhibitor nexin 2, all of which may promote the activated PSC phenotype. Stellate cells in turn secrete various factors, including PDGF, stromal-derived factor 1, epidermal growth factor, insulin-like growth factor 1, fibroblast growth factor, secreted protein acidic and rich in cysteine, matrix metalloproteinases, small leucine-rich proteoglycans, periostin and collagen type I that mediate effects on tumor growth, invasion, metastasis and resistance to chemotherapy. This review intends to shed light on the mechanisms by which PSCs in the stroma influence pancreatic cancer development. The increased understanding of this interaction will be of potential value in designing new modalities of targeted therapy.

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