Ovarian Cancer Research Today is a free monthly online journal that collates and summarizes the latest research about Ovarian Cancer, including details on symptoms, causes, treatment, information. | ||||||||
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Placental leucine aminopeptidase (P-LAP) expression is associated with chemosensitivity in human endometrial carcinoma.Shibata K, Kikkawa F, Kondo C, Mizokami Y, Kajiyama H, Ino K, Nomura S, Mizutani S Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, Japan. shiba@med.nagoya-u.ac.jp <shiba@med.nagoya-u.ac.jp> OBJECTIVE: Although treatment for advanced or recurrent endometrial carcinoma has improved over recent years with the introduction of paclitaxel- and platinum-based chemotherapy, in most, the disease remains incurable because of resistance to chemotherapy. In the previous study, we have shown that placental leucine aminopeptidase (P-LAP) is associated with poor prognosis. The objective of this study was to determine whether P-LAP expression affects the chemosensitivity in endometrial carcinoma patients. METHODS: Here, we investigated the effect of P-LAP to response for paclitaxel and carboplatin in advanced and recurrence endometrial carcinoma. Furthermore, we transfected P-LAP cDNA into endometrial carcinoma cells (AMEC) and investigated cell growth and apoptosis by paclitaxel or carboplatin. RESULTS: In 15 of 17 patients, P-LAP was positive. Twelve of seventeen patients were evaluable for response. Among the eight patients strongly positive for P-LAP, only two patients (25%) showed PR. However, all four patients who were weakly positive for P-LAP showed either complete response (CR) or partial response (PR). P-LAP overexpressor (P-LAP2 and P-LAP8) and a vector control were used to assay chemosensitivity. P-LAP2 clone displayed a 1.7-fold increase in IC(50) against paclitaxel and carboplatin when compared with the vector control, and P-LAP8 clone displayed a 1.6-fold increased in IC(50) against paclitaxel and carboplatin when compared with V1. Compared to vector control cells, apoptotic effect by carboplatin treatment was clearly inhibited in P-LAP2 and P-LAP8 cells. Carboplatin, 10(-6) M, induced the 12.5-fold rate of apoptosis compared to that without treatment at 48 h in vector control cells. However, in P-LAP2 and P-LAP8 clones, 10(-6) M carboplatin induced only 3.2- and 5.1-fold rates of apoptosis, respectively, compared to that of without treatment. CONCLUSIONS: P-LAP was suggested to be involved in reducing chemosensitivity and may be a therapeutic target in endometrial carcinoma. Published 19 October 2004 in Gynecol Oncol, 95(2): 307-13.
© 2004-2008 Ovarian Cancer Research Today. All Rights Reserved. |
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