The Akt and ERK activation by platinum-based chemotherapy in ovarian cancer is associated with favorable patient outcome.

AIM: To investigate the phosphatidylinositol 3-kinase (PI3K)-Akt and extracellular signal regulated protein kinase (ERK) activation by chemotherapy, and the relationship between the activation of them and patient outcomes. The effect of chemotherapy on the cell proliferation and apoptosis markers and their role in the biology of ovarian cancer were also investigated. MATERIALS AND METHODS: This study was carried out in a series of 10 ovarian (or tubal) cancer patients whose specimens were obtained before and after chemotherapy. PI3K-Akt and ERK activation were evaluated by immunohistochemical staining for phosphorylated Akt and ERK. Their correlation with patient outcome was investigated by survival curves using the Kaplan-Meier method. Cell proliferation was evaluated by Ki-67 expression using immunofluorescent staining. Apoptosis was examined by caspase-3 and cleaved Poly ADP ribose polymerase (PARP) using immunofluorescent staining. RESULTS: An increase in Akt and ERK phosphorylation after chemotherapy was observed in 5 and 8 patients, respectively out of 10 patients examined. Akt and ERK activation by chemotherapy were associated with a favorable overall survival. In almost all patients, Ki-67 expression was initially high and largely decreased after chemotherapy. An increase in apoptotic marker expression was observed in almost all patients exposed to chemotherapy. CONCLUSION: Our findings suggest that Akt and ERK activation by chemotherapy may be associated with favorable prognosis.

Complete remission of ovarian small cell carcinoma treated with irinotecan and cisplatin: a case report.

BACKGROUND: Small cell carcinoma of the ovary is a rare type of ovarian carcinoma with a very poor prognosis. CASE REPORT: We report here a case of a 55-year-old woman with small cell carcinoma of the left ovary. The patient underwent cytoreductive surgery with residual tumors of 6 cm at the cul-de-sac and was found to have stage IIIc disease. After six courses of irinotecan (CPT-11) and cisplatin (CDDP) combination therapy, secondary cytoreductive surgery was performed. The patient showed no evidence of residual tumors. After an additional three courses of chemotherapy, the patient is still alive and well without evidence of disease. CONCLUSION: CPT-11 and CDDP combination chemotherapy may be effective and safe for patients with small cell carcinoma of the ovary.

Raloxifene increases proliferation and up-regulates telomerase activity in human umbilical vein endothelial cells.

Vascular endothelial senescence is involved in human atherosclerosis. Telomerase activity is known to be critical in cellular senescence and its level is modulated by regulation of telomerase catalytic subunit (telomerase reverse transcriptase (TERT)) at both the transcriptional and post-transcriptional levels. Since the cardioprotective effect of estrogen itself has not been ruled out, we examined that of raloxifene, which has been classified as a selective estrogen receptor modulator, on the proliferation and telomerase activity of human umbilical vein endothelial cells (HUVECs). Raloxifene, like estrogen, clearly induced the telomerase activity and human TERT (hTERT) expression via estrogen receptor (ER) alpha and ERbeta. Treatment with raloxifene for 5 days significantly induced cell growth, and either cotreatment with a telomerase inhibitor, 3'-azido-3'-deoxythymidine, or transfection with hTERT-specific small interfering RNA significantly attenuated the raloxifene-induced cell growth. Raloxifene also induced the phosphorylation of Akt, and pretreatment with a phosphatidylinositol 3-kinase inhibitor, LY294002, significantly attenuated the raloxifene-induced telomerase activity. In addition, raloxifene induced both the phosphorylation of hTERT and IkappaB. Moreover, cotreatment with an IkappaBalpha phosphorylation inhibitor, BAY-11-7082, or a specific NFkappaB nuclear translocation inhibitor, SN50, significantly attenuated the raloxifene-induced telomerase activity and the association of NFkappaB with hTERT. These results show that raloxifene induced the up-regulation of telomerase activity not only by the transcriptional regulation of hTERT but also by post-translational regulation of the phosphorylation of Akt and hTERT and the association of hTERT with NFkappaB in HUVECs. Thus, the up-regulation of telomerase activity in vascular endothelial cells might be one mechanism contributing to the potential atheroprotective effect of raloxifene.