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Apoptosis and Tumor Angiogenesis in Cervical Cancer after Preoperative Chemotherapy

Departments of Obstetrics and Gynecology [M. Ued., K. U., K. K., Y. T., Y. Ok., M. Uek.] and Anatomy and Biology [Y. Ot.], Osaka Medical College, Osaka 569-0801, Japan

The correlation between apoptosis and tumor angiogenesis in uterine cervical cancer treated by preoperative intraarterial infusion chemotherapy (IAC) was investigated. Cervical cancer samples surgically obtained from 12 patients (stages Ib–IIIb) receiving IAC and from 10 patients (stages Ib–IIb) receiving no chemotherapy and biopsy specimens from the 12 patients before IAC were examined. The apoptotic index (AI) was determined with an in situ end-labeling assay. Intratumoral microvessel density (IMVD) and thymidine phosphorylase (dThdPase) expression were evaluated immunohistochemically using anti-CD34 and anti-dThdPase antibodies. AIs were higher in the 8 patients with complete or partial response to IAC than they were in the 4 nonchemoresponsive patients and in the 10 patients who received no chemotherapy (P < 0.01) and were inversely related to IMVDs (r = 0.724; P < 0.01). AIs and IMVDs after IAC were higher and lower than those before IAC (P < 0.01), respectively. The expression of dThdPase, which has angiogenic activity, was markedly decreased after IAC. These results suggest that the antitumor effects of IAC are closely associated with apoptotic cell death, which may be influenced in part by the extent of tumor angiogenesis inhibition.

¹ To whom requests for reprints should be addressed, at Department of Obstetrics and Gynecology, Osaka Medical College, 2-7 Daigaku-cho, Takatsuki-shi, Osaka 569-0801, Japan.

Received 3/ 2/98. Accepted 4/16/98.

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