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Enhanced induction of apoptosis of human gastric carcinoma cells after preoperative treatment with 5‐fluorouracil
Author(s) -
Sugamura Kenji,
Makino Masato,
Shirai Hiroyuki,
Kimura Osamu,
Maeta Michio,
Itoh Hisao,
Kaibara Nobuaki
Publication year - 1997
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/(sici)1097-0142(19970101)79:1<12::aid-cncr3>3.0.co;2-o
Subject(s) - medicine , fluorouracil , apoptosis , gastric carcinoma , oncology , carcinoma , cancer research , cancer , gastroenterology , biochemistry , chemistry
BACKGROUND It has been reported that anticancer drugs induce apoptosis, thus it is considered that apoptosis may be important in cancer chemotherapy. The authors examined whether the administration of 5‐fluorouracil (5‐FU) enhanced apoptosis of gastric carcinoma cells, and investigated the relationship between apoptosis and the expression of Ki‐67 and the Bax gene. METHODS Twenty patients with gastric carcinoma were divided into 2 groups. Ten patients received continuous intravenous 5‐FU at 500 mg/body weight/day for 7 days preoperatively whereas the other 10 did not receive any chemotherapy or radiotherapy, and served as controls. For detection of apoptotic cells, apoptotic indices were examined by the terminal deoxynucleotidyl transferase‐mediated deoxyuridine triphosphate biotin nick end labeling (TUNEL) method. The expression of Ki‐67 and the Bax gene were examined by immunohistochemical staining. RESULTS Apoptosis of gastric carcinoma cells increased significantly to 6.1 ± 3.6% in the 5‐FU‐treated group compared with the controls (3.2 ± 1.8%; P < 0.05). The level of expression of Ki‐67, a marker of cell proliferation, was inversely correlated with the extent of TUNEL staining that was specific for apoptosis. The percentage of cells that were immunopositive for Ki‐67 fell to 50.8 ± 7.3% of the apoptotic area in the 5‐FU‐treated group compared with 57.5 ± 6.9% in the controls ( P < 0.05). There was no significant correlation between frequency of apoptotic cells and the level of expression of the Bax gene. CONCLUSIONS The authors demonstrated enhanced apoptosis in gastric tumors after continuous intravenous infusion of 5‐FU for 7 days. This result suggests that it may be possible to evaluate the effects of chemotherapy by detecting apoptotic cells. Cancer 1997; 79:12‐7. © 1997 American Cancer Society.