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This study showed that the concept of platinum sensitivity could be applied to recurrent cervical cancer and PFI could be one of the independent prognostic factors for patients with recurrent cervical cancer who have previously been treated with platinum-based chemotherapy.

Tumor debulking surgery with DS resulted in controllable blood loss, and OS was successful in all patients without severe complications or postoperative treatment delay. Currently, OS is considered to have very few benefits over CS; thus, the success rate of CS rate should be improved while maintaining safety.

Abstract. Paclitaxel (PX) binds to and stabilizes tubulin, preventing depolymerization, and resulting in cell death. Based on a previous report showing the activity of phosphatidylinositol kinase (PIK) on tubulin, we investigated the effect of the PI4K inhibitor orobol and the PI3K activator platelet derived growth factor (PDGF) on PX sensitivity. Drug sensitivity was examined by classical colony forming assay. Tubulin isotype expression was determined by semiquantitative RT-PCR. Microtubule texture was observed by laser confocal microscope using anti-ß-tubulin antibody. Apoptotic activity was estimated by frequency of condensed nuclear chromatin with Hoechst 33342 stain. Orobol enhanced PX sensitivity of human ovarian carcinoma 2008 cells by 18.9±1.2-fold (N=3; P<0.01). In contrast, pretreatment with PDGF rendered cells resistant to PX by 2.3±0.4-fold (N=3; P<0.01). Neither orobol nor PDGF showed any effect on cell growth. Orobol produced a 2.5-fold sensitization in cisplatinresistant 2008/C13 * 5.25 (C13) cells, and PDGF rendered the cells 2.3-fold resistant to PX. Orobol suppressed the ß4a-tubulin isotype expression by 85% and other isotypes by 20%. In contrast, PDGF induced ß4a-tubulin isotype expression by 1.3-fold, while it supressed all the other isotypes by 20-40%. Orobol produced thick microtubules and PDGF generated ring condensed microtubules. Orobol promoted PX-induced apoptosis, while PDGF caused 50% reduction of apoptosis. These results indicate that orobol and PDGF regulate PX sensitivity by reciprocally altering the proportion of tubulin isotype expression and PX-induced apoptotic signaling. IntroductionThe antimicrotubule agent paclitaxel (PX) has shown some efficacy in the treatment of ovarian and metastatic breast cancers, and particularly encouraging is its utility in advanced ovarian cancers that are refractory to DNA damage-based chemotherapy (1). In contrast to tubulin depolymerizing toxins such as nocodazole or colcemid, PX stabilizes microtubule formation and, in continuous treatment, it prevents completion of mitosis, resulting in cell-cycle blockage in mitosis and activation of apoptosis. PX reversibly binds to microtubules in vitro and apparently does not bind to free tubulin (2,3). PX strongly stimulates the rate and extent of microtubule polymerization and reduces the concentration of soluble tubulin (4). Additionally, PX also inhibits tubulin exchange at microtubule ends and reduces the fluxral rigidity of them (5). At subnanomolar concentrations, PX suppresses microtubule dynamics by affecting shortening of microtubules (6). At higher concentrations, PX suppresses dynamics by inhibiting the growing and shortening of microtubules (7). Little is known about how microtubule dynamics are regulated in cells. In vitro and in cells, microtubule ends switch between states of growing and shortening, a process known as 'dynamic instability', apparently due to the gain and loss of a stabilizing GTP-or GDP-Pi-liganded tubulin cap at the microtubule ends. Net growing of microtubules can occur ...