Document Detail


The role of P-glycoprotein in human gastric cancer xenografts in response to chemotherapy.
MedLine Citation:
PMID:  11817335     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: To clarify the contribution of P-glycoprotein (P-GP) to drug resistance of gastric cancer, the correlation between chemosensitivity of the tumor and expression of P-GP was examined using human gastric cancer xenografts in nude mice. METHODS: Two strains, P-GP-positive and -negative, were established using primary explants from patients who had not received chemotherapy. Their stable growth was obtained by serial passages as subcutaneous tumors in nude mice. Mitomycin C (MMC, 3.25 mg/kg), adriamycin (ADR, 6mg/kg), or cisplatin (CDDP, 6mg/kg) was administered intraperitoneally once a week for 3 weeks. RESULTS: In the P-GP-negative strain, all three drugs significantly suppressed the tumor growth, while in the P-GP-positive strain, only MMC did so. However, the growth inhibition of MMC was apparently greater in the P-GP-negative strain than in the positive tumor. The expressions of metallothionein (MT), glutathione-S-transferase-pi (GST-pi), and p53 were not different between the strains. Bcl-2 was expressed only in the P-GP-negative strain. Induction of P-GP expression was observed in some specimens after treatment with MMC and with CDDP. CONCLUSIONS: P-GP might affect inherent and acquired resistance against chemotherapeutic agents in gastric cancer.
Authors:
N Monden; S Abe; Y Hishikawa; H Yoshimura; S Kinugasa; D K Dhar; M Tachibana; N Nagasue
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  International journal of surgical investigation     Volume:  1     ISSN:  1028-5229     ISO Abbreviation:  Int. J. Surg. Investig.     Publication Date:  1999  
Date Detail:
Created Date:  2001-12-05     Completed Date:  2002-01-30     Revised Date:  2006-07-25    
Medline Journal Info:
Nlm Unique ID:  100965774     Medline TA:  Int J Surg Investig     Country:  England    
Other Details:
Languages:  eng     Pagination:  3-10     Citation Subset:  IM    
Affiliation:
The Second Department of Surgery, Shimane Medical University, Izumo, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibiotics, Antineoplastic / therapeutic use*
Antineoplastic Agents / therapeutic use*
Cisplatin / therapeutic use*
Doxorubicin / therapeutic use*
Humans
Injections, Intraperitoneal
Mice
Mice, Inbred BALB C
Mice, Nude
Mitomycin / therapeutic use*
Mutation
Neoplasm Transplantation
P-Glycoprotein / physiology*
Stomach Neoplasms / drug therapy*,  physiopathology*
Transplantation, Heterologous
Tumor Suppressor Protein p53 / genetics,  metabolism
Chemical
Reg. No./Substance:
0/Antibiotics, Antineoplastic; 0/Antineoplastic Agents; 0/P-Glycoprotein; 0/Tumor Suppressor Protein p53; 15663-27-1/Cisplatin; 23214-92-8/Doxorubicin; 50-07-7/Mitomycin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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