Surgical and medical therapy for pancreatic carcinoma

Magee, Conor; Ghaneh, Paula; Neoptolemos, John P.

doi:10.1053/bega.2002.0317

Cited by 38 publications

(48 citation statements)

References 93 publications

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“…Only patients with pancreatic ductal adenocarcinoma were included since the survival rate of other less common types of pancreatic or 'periampullary' cancer such as ampullary carcinoma and intrapancreatic bile duct cancer have much more favourable prognoses (Magee et al, 2002). Patients were grouped according to the type of randomised adjuvant treatment (chemoradiation or chemotherapy).…”

Section: Data Collectionmentioning

confidence: 99%

Meta-analysis of randomised adjuvant therapy trials for pancreatic cancer

et al. 2005

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The aim of this study was to investigate the worldwide evidence of the roles of adjuvant chemoradiation and adjuvant chemotherapy on survival in potentially curative resected pancreatic cancer. Five randomised controlled trials of adjuvant treatment in patients with histologically proven pancreatic ductal adenocarcinoma were identified, of which the four most recent trials provided individual patient data (875 patients). This meta-analysis includes previously unpublished follow-up data on 261 patients. The pooled estimate of the hazard ratio (HR) indicated a 25% significant reduction in the risk of death with chemotherapy (HR ¼ 0.75, 95% confidence interval (CI): 0.64, 0.90, P-values stratified (P strat ) ¼ 0.001) with median survival estimated at 19.0 (95% CI: 16.4, 21.1) months with chemotherapy and 13.5 (95% CI: 12.2, 15.8) without. The 2-and 5-year survival rates were estimated at 38 and 19%, respectively, with chemotherapy and 28 and 12% without. The pooled estimate of the HR indicated no significant difference in the risk of death with chemoradiation (HR ¼ 1.09, 95% CI: 0.89, 1.32, P strat ¼ 0.43) with median survivals estimated at 15.8 (95% CI: 13.9, 18.1) months with chemoradiation and 15.2 (95% CI: 13.1, 18.2) without. The 2-and 5-year survival rates were estimated at 30 and 12%, respectively, with chemoradiation and 34 and 17% without. Subgroup analyses estimated that chemoradiation was more effective and chemotherapy less effective in patients with positive resection margins. These results show that chemotherapy is effective adjuvant treatment in pancreatic cancer but not chemoradiation. Further studies with chemoradiation are warranted in patients with positive resection margins, as chemotherapy appeared relatively ineffective in this patient subgroup.

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Section: Data Collectionmentioning

confidence: 99%

Meta-analysis of randomised adjuvant therapy trials for pancreatic cancer

et al. 2005

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“…In addition, there are limited treatment options available. Chemotherapies and radiotherapies are largely ineffective, and metastatic disease frequently recurs even after surgical resection of primary lesions (2)(3)(4). Recently, a number of risk factors have been identified, including age, cigarette smoking, high dietary intake of meat and fat, low serum folate levels, obesity, long-standing diabetes mellitus, chronic pancreatitis and family history (5), but exactly how these risk factors contribute to carcinogenesis remains largely unknown.…”

Section: Introductionmentioning

confidence: 99%

Hedgehog signaling pathway regulates human pancreatic cancer cell proliferation and metastasis

et al. 2012

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Abstract. Pancreatic cancer is one of the most aggressive and devastating malignancies. The Hedgehog (Hh) pathway has been reported to play an important role in pancreatic cancer development and progression. The aim of this study was to examine the activation of the Hh pathway in human pancreatic cancer tissue samples and pancreatic cancer cell lines, and the molecular mechanisms involved in the Hh pathway mediated effects on pancreatic cancer cell proliferation and invasion. The expression levels of Hh molecules in human pancreatic cancer tissue samples and pancreatic cancer cell lines were evaluated using RT-PCR. The role of the Hh pathway in cell proliferation and invasion was evaluated using flow cytometry, MTT, colony formation assays and Transwell invasion assays, and the expression of cancer stem cell markers and epithelial-mesenchymal transition (EMT) were evaluated using flow cytometry and RT-PCR. Tumorigenicity assays were used to further investigate the role of the Hh pathway in vivo. Hh molecules were highly expressed in human pancreatic cancer tissue samples and pancreatic cancer cell lines. Inhibition of the Hh pathway notably decreased cell proliferation and induced apoptosis through inhibition of the PI3K/AKT pathway and cancer stem cells. Furthermore, inhibition of the Hh signaling pathway significantly inhibited EMT by suppressing the activation of transcription factors Snail and Slug, which are correlated with significantly reduced pancreatic cancer cell invasion, suggesting that the Hh signaling pathway is involved in early metastasis. These results indicate that activation of the Hh pathway is a common event. Inhibition of the Hh pathway may be a potential molecular target of new therapeutic strategies for pancreatic cancer.

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“…With an overall 5-year survival rate of 3% (1), pancreatic cancer has one of the poorest prognoses among all cancers (2). Aside from its silent nature and tendency for late discovery, pancreatic cancer also shows unusual resistance to chemotherapy and radiation therapy.…”

Section: Introductionmentioning

confidence: 99%

In vitro Modeling of Human Pancreatic Duct Epithelial Cell Transformation Defines Gene Expression Changes Induced by K-ras Oncogenic Activation in Pancreatic Carcinogenesis

et al. 2005

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Genetic analysis of pancreatic ductal adenocarcinomas and their putative precursor lesions, pancreatic intraepithelial neoplasias (PanIN), has shown a multistep molecular paradigm for duct cell carcinogenesis. Mutational activation or inactivation of the K-ras, p16INK4A , Smad4, and p53 genes occur at progressive and high frequencies in these lesions. Oncogenic activation of the K-ras gene occurs in >90% of pancreatic ductal carcinoma and is found early in the PanINcarcinoma sequence, but its functional roles remain poorly understood. We show here that the expression of K-ras G12V oncogene in a near diploid HPV16-E6E7 gene immortalized human pancreatic duct epithelial cell line originally derived from normal pancreas induced the formation of carcinoma in 50% of severe combined immunodeficient mice implanted with these cells. A tumor cell line established from one of these tumors formed ductal cancer when implanted orthotopically. These cells also showed increased activation of the mitogenactivated protein kinase, AKT, and nuclear factor-KB pathways. Microarray expression profiling studies identified 584 genes whose expression seemed specifically up-regulated by the K-ras oncogene expression. Forty-two of these genes have been reported previously as differentially overexpressed in pancreatic cancer cell lines or primary tumors. Real-time PCR confirmed the overexpression of a large number of these genes. Immunohistochemistry done on tissue microarrays constructed from PanIN and pancreatic cancer samples showed laminin B3 overexpression starting in high-grade PanINs and occurring in >90% of pancreatic ductal carcinoma. The in vitro modeling of human pancreatic duct epithelial cell transformation may provide mechanistic insights on gene expression changes that occur during multistage pancreatic duct cell carcinogenesis. (Cancer Res 2005; 65(12): 5045-53)

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Surgical and medical therapy for pancreatic carcinoma

Cited by 38 publications

References 93 publications

Meta-analysis of randomised adjuvant therapy trials for pancreatic cancer

Meta-analysis of randomised adjuvant therapy trials for pancreatic cancer

Hedgehog signaling pathway regulates human pancreatic cancer cell proliferation and metastasis

In vitro Modeling of Human Pancreatic Duct Epithelial Cell Transformation Defines Gene Expression Changes Induced by K-ras Oncogenic Activation in Pancreatic Carcinogenesis

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