Oncology

Laboratory Investigation

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

Cascalló M.a,b · Calbó J.a · Capellà G.b · Fillat C.c · Pastor-Anglada M.a · Mazo A.a

Author affiliations

aDepartment of Biochemistry and Molecular Biology, University of Barcelona, bLaboratori de Recerca Translacional, Institut Català d’Oncologia, cCentre de Regulació Genòmica, Barcelona, Spain

Keywords: GemcitabineApoptosisp53Pancreatic cancer

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Oncology 2005;68:179–189
https://doi.org/10.1159/000086772

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Article / Publication Details

First-Page Preview
Abstract of Laboratory Investigation

Received: December 30, 2003
Accepted: June 25, 2004
Published online: July 29, 2005
Issue release date: July 2005

Number of Print Pages: 11
Number of Figures: 6
Number of Tables: 1

ISSN: 0030-2414 (Print)
eISSN: 1423-0232 (Online)

For additional information: https://www.karger.com/OCL

Abstract

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.

© 2005 S. Karger AG, Basel



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Article / Publication Details

First-Page Preview
Abstract of Laboratory Investigation

Received: December 30, 2003
Accepted: June 25, 2004
Published online: July 29, 2005
Issue release date: July 2005

Number of Print Pages: 11
Number of Figures: 6
Number of Tables: 1

ISSN: 0030-2414 (Print)
eISSN: 1423-0232 (Online)

For additional information: https://www.karger.com/OCL

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Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
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