[Clinical significance of P-glycoprotein expression and multidrug resistance assessed by in vitro thymidine incorporation assay in patients with gastric carcinoma].
Drug resistance in chemotherapy is a significant problem in the treatment of gastric carcinomas as well as other malignant tumors. Multidrug resistant cells frequently overexpress the 170 kDa P-glycoprotein (P-gp). Twenty-four fresh tumor specimens of gastric carcinoma were assessed by flow cytometric detection of P-gp using monoclonal antibody C219. Eight patients were P-gp positive. Differentiated gastric carcinomas contained significantly higher concentrations of P-gp positive. Incidence of P-gp positive case was high in advanced stage. Sixteen cases received in vitro chemosensitivity test assessed by thymidine incorporation assay (TIA). Seven of 9 multidrug resistant cases by TIA were P-gp positive, and all of 7 non-multidrug resistance were negative. Expression of P-gp and multidrug resistance were closely correlated (p < 0.01). Also, in 89 patients with operable gastric carcinoma, the relationship between multidrug resistance by TIA and their clinicopathologic features as well as their survival lengths were examined. Thirty-one of 89 specimens from gastric carcinoma patients were multidrug resistant by TIA. Patients with multidrug resistant group had a significantly poorer cumulative survival rate than non-multidrug resistant cases (p < 0.01). The multivariated analyses showed that multidrug resistance analyzed is useful indicator for prognosis (p < 0.1). We suggest that multidrug resistance cases or P-gp-positive cases of gastric carcinoma are highly malignant, and these determinations are clinically useful.
Fujii
H
H
Second Dept. of Surgery, Fukui Medical School.
Tanigawa
N
N
Muraoka
R
R
Masuda
Y
Y
Shimomatsuya
T
T
Kato
Y
Y
Aotake
T
T
Kitaoka
A
A
Yamakawa
M
M
Tanaka
T
T
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004317:Doxorubicin / Q000494:pharmacology*; D018432:Drug Resistance, Multiple; D004354:Drug Screening Assays, Antitumor; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011379:Prognosis; D013274:Stomach Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D015996:Survival Rate; D013936:Thymidine; D014407:Tumor Cells, Cultured / Q000187:drug effects
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004317:Doxorubicin; D013936:Thymidine