Effect of preoperative 5-fluorouracil on apoptosis of advanced gastric cancer.
BACKGROUND
Several studies have reported on apoptosis and the effect of anticancer chemotherapy.


METHODS
We studied apoptosis induced by 5-fluorouracil (5-FU) given preoperatively to 28 patients with advanced gastric cancer and compared the findings with 101 untreated patients. The expression of bcl-2 oncoprotein, cell phase fractions, and histological chemotherapeutic effects were also compared with the apoptotic changes.


RESULTS
The apoptotic and S-phase fractions in 5-FU-treated patients (apoptotic fraction: 10.46 +/- 6.93%, S-phase fraction: 17.49 +/- 11.65%) were significantly greater than those in untreated controls (apoptotic fraction: 6.56 +/- 5.06%, S-phase fraction: 12.17 +/- 6.78%). A positive correlation was observed between 5-FU-induced apoptosis and accumulation of tumor cells in the S-phase fraction. There was an inverse relationship between bcl-2 oncoprotein expression and apoptosis in 5-FU-treated patients, but no significant correlation between histological effect and apoptosis. However, two patients with significant histological effects showed no bcl-2 oncoprotein expression, whereas the histological effects were mild in all the bcl-2-positive patients.


CONCLUSIONS
Apoptosis may be induced by 5-FU administered preoperatively and bcl-2 oncogene expression may suppress 5-FU-induced apoptosis.
Inada
T
T
Department of Surgery, Tochigi Cancer Center, Utsunomiya, Japan.
Ichikawa
A
A
Igarashi
S
S
Kubota
T
T
Ogata
Y
Y
D000230:Adenocarcinoma / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology*; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D005434:Flow Cytometry; D005472:Fluorouracil / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007262:Infusions, Intravenous; D011300:Preoperative Care; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016196:S Phase; D013274:Stomach Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology*
D000964:Antimetabolites, Antineoplastic; D019253:Proto-Oncogene Proteins c-bcl-2; D005472:Fluorouracil