Expression of Bcl‐2 and p53 protein in resectable invasive ductal carcinoma of the pancreas: Effects on clinical outcome and efficacy of adjuvant chemotherapy

Nio, Yoshinori; Dong, Mei; Iguchi, Chikage; Yamasawa, Kunihiro; Toga, Tomoko; Itakura, Masayuki; Tamura, Katsuhiro

doi:10.1002/jso.1033

Cited by 33 publications

(15 citation statements)

References 43 publications

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“…At least 20 Bcl-2 proteins have been identified in mammals, consisting of proapoptotic factors (for example Bax, Bak, Bok and BH3-only proteins) and antiapoptotic factors (such as Bcl-2, Bcl-XL, Bcl-w and Mcl-1). Two studies suggested that Bcl-2 expression was an independent marker of better survival in PDAC 35,36 . The seemingly counterintuitive beneficial prognostic effect of Bcl-2 may be related to non-apoptotic functions, such as cell cycle control, or disturbances in the expression of other Bcl-2 family members 134,135 .…”

Section: Bcl-2mentioning

confidence: 98%

Systematic review of immunohistochemical biomarkers to identify prognostic subgroups of patients with pancreatic cancer

Ansari

Rosendahl

Elebro

et al. 2011

British Journal of Surgery

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None of the molecular markers described can be recommended for routine clinical use as they were identified in small cohorts and there were inconsistencies between studies. Their prognostic and predictive values need to be validated further in prospective multicentre studies in larger patient populations. A panel of molecular markers may become useful in predicting individual patient outcome and directing novel types of intervention.

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Section: Bcl-2mentioning

confidence: 98%

Systematic review of immunohistochemical biomarkers to identify prognostic subgroups of patients with pancreatic cancer

Ansari

Rosendahl

Elebro

et al. 2011

British Journal of Surgery

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“…Although several preclinical and clinical studies have assessed the combination of gemcitabine with radiotherapy or other chemotherapy agents [11], there are no reports dealing with the capacity of reintroduced p53 to recognize gemcitabine-induced genotoxic damage in vivo. Moreover, the prognostic value of p53 expression on the effects of adjuvant chemotherapy in patients with carcinoma of the pancreas is controversial [30, 31]. Our therapeutic schedule consisted of i.p.…”

Section: Discussionmentioning

confidence: 99%

Enhancement of Gemcitabine-Induced Apoptosis by Restoration of p53 Function in Human Pancreatic Tumors

et al. 2005

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Human pancreatic adenocarcinomas are highly resistant to conventional treatment modalities, specially to chemotherapy. Among the genes that modulate apoptosis in response to cytotoxic drugs, the role of p53 has been demonstrated to be of paramount importance. Moreover, p53 is mutated in close to 50% of pancreatic cancer, which renders attractive the reintroduction of this gene as a way to enhance the action of chemotherapeutics. In this paper, gemcitabine, the most effective drug for the treatment of pancreatic tumors, has been selected to develop a new combination approach in vivo based on an administration schedule previously optimized in vitro. In a human xenograft model, the sequential administration of gemcitabine and p53 resulted in potent tumor growth inhibition. Statistical differences were observed with respect to the growth of tumors receiving only gemcitabine or p53. Moreover, the chemosensitization observed in tumors treated with the combination gemcitabine-p53 correlated with differential histological features such as important increases in intratumoral fibrosis and apoptotic levels, when compared with unimodal treatments. Taken together, our data indicate that reintroduction of p53 function in human pancreatic tumors in vivo allows to restore molecular pathways improving the response to gemcitabine. It may constitute a useful step towards a better clinical treatment of patients harboring pancreatic cancer.

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“…Five studies contained data for a marker that were redundant within another study by the same authors (25)(26)(27)(28)(29). Eight studies provided incomplete information on the IHC methodology used (30)(31)(32)(33)(34)(35)(36).…”

Section: Excluded Studiesmentioning

confidence: 99%

Tissue Biomarkers for Prognosis in Pancreatic Ductal Adenocarcinoma: A Systematic Review and Meta-analysis

Jamieson

Carter

McKay

et al. 2011

Clinical Cancer Research

114

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Purpose: The management of pancreatic ductal adenocarcinoma (PDAC) continues to present a great challenge particularly with regard to prediction of outcome following pancreaticoduodenectomy. Molecular markers have been extensively investigated by numerous groups with the aim of enhancing prognostication; however, despite hundreds of studies that have sought to assess the potential prognostic value of molecular markers in predicting the clinical course following resection of PDAC, at this time, no molecular marker assay forms part of recommended clinical practice.Experimental Design: We conducted a systematic review and meta-analysis of the published literature for immunohistochemistry-based biomarkers of PDAC outcome. A dual search strategy was applied to the PubMed database on January 6, 2010, to identify cohort studies that reported associations between immunohistochemical biomarker expression and survival outcomes in PDAC, and conformed to the REMARK (REporting recommendations for tumor MARKer prognostic studies) criteria.Results: A total of 103 distinct proteins met all inclusion criteria. Promising markers that emerged for the prediction of overall survival included BAX (HR ¼ 0.31, 95% CI: 0.71-0.56), Bcl-2 (HR ¼ 0.41, 95% CI: 0.27-0.63), survivin (HR ¼ 0.46, 95% CI: 0.29-0.73), Ki-67: (HR ¼ 2.42, 95% CI: 1.87-3.14), COX-2 (HR ¼ 1.39, 95% CI: 1.13-1.71), E-cadherin (HR ¼ 1.80, 95% CI: 1.33-2.42), and S100 calcium-binding proteins, in particular S100A2 (HR ¼ 3.23, 95% CI: 1.58-6.62).Conclusions: We noted that that there was incomplete adherence to the REMARK guidelines with inadequate methodology reporting as well as failure to perform multivariate analysis. Addressing the persistent incomplete adoption of these criteria may eventually result in the incorporation of molecular marker assessment within PDAC management algorithms. Clin Cancer Res; 17(10); 3316-31. Ó2011 AACR.

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Expression of Bcl‐2 and p53 protein in resectable invasive ductal carcinoma of the pancreas: Effects on clinical outcome and efficacy of adjuvant chemotherapy

Abstract: pBcl-2 expression is a beneficial prognostic factor for patients with IDC, whereas p53 expression may be beneficial in the prediction of the effects of adjuvant chemotherapy on patients with IDC. J. Surg. Oncol. 2001;76:188-196.

Cited by 33 publications

References 43 publications

Systematic review of immunohistochemical biomarkers to identify prognostic subgroups of patients with pancreatic cancer

Systematic review of immunohistochemical biomarkers to identify prognostic subgroups of patients with pancreatic cancer

Enhancement of Gemcitabine-Induced Apoptosis by Restoration of p53 Function in Human Pancreatic Tumors

Tissue Biomarkers for Prognosis in Pancreatic Ductal Adenocarcinoma: A Systematic Review and Meta-analysis

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