Kegg Pathway: Pancreatic cancer

Int J Oncol. 2008 Aug; 33(2): 415-9
Chan C, Lin HJ, Lin J

In current literature there is evidence that psychological factors can affect the incidence and progression of some cancers. Data obtained from animal models support the hypothesis that stress can be a cofactor. The underlying mechanisms for the association between psychological factors and Pancreatic cancer are very poorly understood. In this study, we examined the possible growth promoting effects of the stress-associated hormone, norepinephrine, on immortalized human Pancreatic duct epithelial cells. Our results suggest that norepinephrine can increase cell proliferation of human Pancreatic duct epithelial cells. We also evaluated the ability of norepinephrine to induce interleukin-6 (IL-6), interleukin-10 (IL-10), and vascular endothelial growth factor (VEGF). All of which may promote oncogenesis of immortalized human Pancreatic duct epithelial cells. We found that norepinephrine can increase the IL-6 and VEGF but not IL-10 levels secreted by human Pancreatic duct epithelial cells. Since norepinephrine can increase cell proliferation of human Pancreatic duct epithelial cells, we performed further testing to see if dietary agents, sulforaphane and resveratrol, can inhibit norepinephrine-mediated increases in cell proliferation in human Pancreatic duct epithelial cells. Interestingly, our results demonstrated that sulforaphane but not resveratrol inhibits norepinephrine-mediated increases in cell viability in human Pancreatic duct epithelial cells. Furthermore, sulforaphane also inhibits norepinephrine-mediated increase of the IL-6 levels but not VEGF levels. Our study is the first to demonstrate that stress-associated hormone, norepinephrine, can increase the cell proliferation and IL-6 levels of human Pancreatic duct epithelial cells, which can be inhibited by sulforaphane, a chemopreventive agent and a natural compound from the Cruciferous vegetables.

Int J Oncol. 2008 Aug; 33(2): 317-23
Zagon IS, Kreiner S, Heslop JJ, Conway AB, Morgan CR, McLaughlin PJ

This study examined overexpression of the opioid growth factor receptor (OGFr) in Pancreatic cancer cells and phenotypic changes in tumorigenicity. Tumors of MIA PaCa-2 cells transfected with OGFr cDNA (OGFr-1) had 3.3 times more OGFr than empty vector (EV) neoplasias, and 4.3 times more OGFr than tumors from wild-type (WT) mice. No differences in OGFr binding were detected between tumors of EV and WT animals. Tumor incidence in OGFr-1 animals was reduced by up to 50% from EV mice. Latency times for OGFr-1 tumor expression were increased 30%, tumor volume was decreased 70%, and DNA synthesis was reduced 24% relative to EV mice. Exogenous OGF reduced OGFr-1 tumor volume up to 55% compared to OGFr-1 mice given vehicle. These data support OGFr gene function as a regulator of cell proliferation that impacts on tumorigenic expression, and suggest that molecular and pharmacological manipulation of OGFr may prevent or delay human Pancreatic cancer.

Int J Oncol. 2008 Aug; 33(2): 297-308
Wente MN, Gaida MM, Mayer C, Michalski CW, Haag N, Giese T, Felix K, Bergmann F, Giese NA, Friess H

CXC chemokines have a major influence on the angiogenesis, growth and metastatic potential of Pancreatic ductal adenocarcinoma. CXCL16 is a unique transmembrane CXC chemokine, which is shed by members of the disintegrins and metalloproteases (ADAMs), in particular by ADAM10 and ADAM17. In our study, we evaluated expression and potential function of CXCL16 and its receptor CXCR6. CXCL16 and the receptor CXCR6 are upregulated in Pancreatic ductal adenocarcinoma (PDAC) and chronic pancreatitis tissues in contrast to normal Pancreatic tissues at the mRNA and protein levels. In 85 and 100% of the investigated samples, tumor cells showed positive immuno-staining for CXCL16 and CXCR6, respectively; furthermore, tubular complexes of chronic pancreatitis and the invasive front of PDAC were immunopositive for CXCL16 and CXCR6. Stimulation of PDAC cells with proinflammatory cytokines increased CXCL16 protein levels, whereas silencing of ADAM10 with siRNA transfection led to a decrease in CXCL16 protein levels in cell culture supernatants. No effects on cell viability were notable after incubation of cancer cells with CXCL16. However, CXCL16 markedly increased invasiveness of PDAC cells. Clinically, 82.5% of PDAC patients had higher CXCL16 serum values than the highest value seen in healthy donors. SELDI-TOF-MS analysis confirmed the upregulation of CXCL16 in sera of PDAC patients. In conclusion, CXCL16 in both transmembrane and soluble forms, and its receptor CXCR6, seem to play an important role in the pathobiology of Pancreatic cancer and might be potential markers for Pancreatic cancer diagnosis and a target for multimodal therapy concepts in the future.

Dig Surg. 2008 Jul 17; 25(4): 278-292
Kuhlmann KF, Gouma DJ, Wesseling JG

Background: The prognosis of patients with Pancreatic cancer is poor. This is mainly caused by the late diagnosis, the aggressive biology and the lack of effective treatment modalities. Adenoviral gene therapy has the potential to selectively treat both primary tumor and (micro)metastatic tissue. Methods: This review provides an overview of what has been achieved so far in the field of adenoviral gene therapy for Pancreatic cancer. Results: Transductional targeting allows decreased toxicity due to vector dissemination to non-target cells and permits delivery with a lower viral dose. It can evade or diminish the immune response, which remains a major problem. Transcriptional targeting evolves quickly but essential drawbacks such as the lack of an efficient animal model delay clinical application. Few clinical trials utilizing adenoviruses have been performed in patients with Pancreatic cancer today. Worldwide, only seven phase III trials are being performed investigating adenoviral vectors in cancer patients. Conclusion: A clear therapeutic effect of adenoviral gene therapy in Pancreatic cancer has not yet been achieved, because the step from bench to bedside has encountered drawbacks. Combinations of the different targeting strategies and techniques to evade the immune system harbor the future for adenoviral gene therapy in patients with Pancreatic cancer.

Kaohsiung J Med Sci. 2008 Jun; 24(6): 324-7
Lin HL, Kuo LC, Chen CW, Lin YK, Lee WC

Pancreatic cancer is sometimes called a "silent disease" because it often causes no symptoms in the early stage. The symptoms can be quite vague and various depending on the location of cancer in the pancreas. The anatomic site distribution is 78% in the head of the pancreas, 11% in the body, and 11% in the tail. Pancreatic cancer is rarely detected in the early stage, and it is very uncommon to diagnose Pancreatic tail cancer during an emergency department visit. The manifestation of Pancreatic tail cancer as left flank pain is very rare and has seldom been identified in the literature. We present a case of Pancreatic tail cancer with the sole manifestation of dull left flank pain. Having negative findings on an ultrasound study initially, this female patient was misdiagnosed as having possible acute gastritis, urolithiasis or muscle strain after she received gastroendoscopy and colonofiberscopy. Her symptoms persisted for several months and she visited our emergency department due to an acute exacerbation of a persistent dull pain in the left flank area. Radiographic evaluation with computed tomography was performed, and Pancreatic tail tumor with multiple metastases was found unexpectedly. We review the literature and discuss this rare presentation of Pancreatic tail cancer.