Document Detail

Synergistic effect of celecoxib on 5-fluorouracil-induced apoptosis in hepatocellular carcinoma patients.
MedLine Citation:
PMID:  21057160     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Cyclooxygenase-2 (COX-2) enzyme over expression is reported in many human HCC cell line studies and is linked to tumor cell resistance to chemotherapy-induced apoptosis. We hypothesized that adding a COX-2 inhibitor would improve the therapeutic benefits in patients with HCC. COX-2 is often increased and involved in drug resistance and poor prognosis.
METHOD: Between January 2001 and December 2007, 15 patients with MDR-positive-HCC from 34 HCC patients based on tissue and serum liver of glypican-3 and fitting the preset eligibility criteria, were treated with a combination regimen with intravenous infusion of (5-FU) 750 mg once per week, 100mg/day cyclophosphamide (Endoxan) and 400 mg/day celecoxib taken orally in divided doses, while the rest of the patients received only 5-FU and Endoxan. Twenty-one patients (62%) had liver disease associated with hepatitis C virus (HCV) and 5 patients with hepatitis B virus (62%).
RESULTS: We found that celecoxib reduced P-glycoprotein with activation of caspase-3 and marked regression of tumor sizes. Sera angiogenic factors (VEGF & bFGF) levels measurement in HCC patients indicated that, the sera levels of both angiogenic factors were reduced significantly (p < 0.05) after treatment. Based on the tumor markers AFP & Glypican-3, 11 of the patients had a PR (11/15), including 3 patients who had normalization of AFP, and four patients had CR (4/15).
CONCLUSIONS: These data suggest that the combination of 5-FU, Endoxan and Celecoxib is highly effective palliative regimen for patients with HCC with good performance status (score ≤ 3). The study suggests a framework for Celecoxib-based combination treatment of HCC.
Ahmad R Bassiouny; Amira Zaky; Hashem M Neenaa
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Annals of hepatology     Volume:  9     ISSN:  1665-2681     ISO Abbreviation:  Ann Hepatol     Publication Date:    2010 Oct-Dec
Date Detail:
Created Date:  2010-11-08     Completed Date:  2011-02-17     Revised Date:  2013-05-16    
Medline Journal Info:
Nlm Unique ID:  101155885     Medline TA:  Ann Hepatol     Country:  Mexico    
Other Details:
Languages:  eng     Pagination:  410-8     Citation Subset:  IM    
Department of Biochemistry, Alexandria University, Egypt.
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MeSH Terms
Antimetabolites, Antineoplastic / pharmacology,  therapeutic use*
Antineoplastic Agents, Alkylating / therapeutic use
Apoptosis / drug effects
Carcinoma, Hepatocellular / drug therapy*,  metabolism,  pathology
Caspase 3 / metabolism
Cyclooxygenase 2 Inhibitors / pharmacology,  therapeutic use*
Cyclophosphamide / therapeutic use
Drug Synergism
Drug Therapy, Combination
Fluorouracil / pharmacology,  therapeutic use*
Glypicans / metabolism
Liver Neoplasms / drug therapy*,  metabolism,  pathology
Middle Aged
P-Glycoprotein / metabolism
Pyrazoles / pharmacology,  therapeutic use*
Retrospective Studies
Sulfonamides / pharmacology,  therapeutic use*
Treatment Outcome
Tumor Markers, Biological / metabolism
Reg. No./Substance:
0/Antimetabolites, Antineoplastic; 0/Antineoplastic Agents, Alkylating; 0/Cyclooxygenase 2 Inhibitors; 0/Glypicans; 0/P-Glycoprotein; 0/Pyrazoles; 0/Sulfonamides; 0/Tumor Markers, Biological; 169590-42-5/celecoxib; 50-18-0/Cyclophosphamide; 51-21-8/Fluorouracil; EC 3.4.22.-/Caspase 3

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