Vascular endothelial growth factor (VEGF) has been suggested to be involved in angiogenesis and microvascular hyperpermeability. We examined immunohistochemically the expression of VEGF in the granulosa and theca cells, along with that of proliferating cell nuclear antigen (PCNA), in the vascular endothelium during the course of follicular development and corpora lutea formation in human ovaries. The immunolocalization of VEGF in these cells was compared with that of another putative angiogenic factor, basic fibroblast growth factor (bFGF). The granulosa cells in the primordial and primary follicles were VEGF negative, but at the preantral stage, the granulosa cells showed weakly positive immunostaining for VEGF. However, the VEGF immunostaining in the granulosa cells was weak throughout the folliculogenesis. In contrast, the theca interna cells of developing follicles showed strong staining for VEGF, which was well correlated with the PCNA positivity in the vascular endothelial cells in the thecal layer. In the atretic follicles, the granulosa and theca cells were VEGF negative. In the corpora lutea, VEGF was strongly expressed in both granulosa and theca lutein cells in the early luteal phase when the PCNA positivity in the endothelium increased, but the VEGF staining in these cells became weak in the mid- and late luteal phases. Accordingly, the PCNA positivity in the vascular endothelium was well correlated with the expression of VEGF in the theca cells during follicular development and atresia, and that in the granulosa and theca lutein cells in corpora lutea formation and regression. In addition, the immunolocalization of VEGF was different from that of bFGF.

No abstract

No abstract

To develop a novel therapeutic strategy for ovarian cancer, we constructed a recombinant adenovirus which highly expresses pro-apoptotic Bax protein and examined its therapeutic effect on a series of ovarian cancer cell lines: A2780, A2780/cDDP, OVCAR-3 and SK-OV-3. A recombinant adenovirus carrying the Bax-alpha gene (AxCALNKYbax) induced high expression of the Bax-alpha protein in all the cell lines. The cytotoxic effect of Bax was observed in three ovarian cancer cell lines: the per cent reduction in the number of cells was 40.0% for cisplatin-sensitive A2780, 50.0% for cisplatin-resistant A2780/cDDP, and 64.8% for marginally cisplatin-resistant OVCAR-3. In contrast, it was only 12.3% for cisplatin-resistant SK-OV-3. Cisplatin-resistant A2780/cDDP had a p53 mutation and exhibited attenuated Bax induction after cisplatin treatment, which may explain why supplementation of Bax was effective in this chemoresistant ovarian cancer. Combination with cisplatin or paclitaxel enhanced the cytotoxic effect of Bax induction in all but one cell line including cisplatin-resistant A2780/cDDP. It appears that adenovirus-mediated Bax induction, with or without combination with conventional chemotherapy, useful strategy for the treatment of ovarian cancer.

ER in the glands of the PMEM was determined to decrease gradually with increased aging. The presence of ER and PR in the gland cells seemed likely to determine the thickness of the PMEM.