To determine the effect of chemotherapy on glucose metabolism in patients with malignant ovarian tumor.The blood glucose assay and associated clinical materials of 375 cases with malignant ovarian tumor who received chemotherapy from January 1997 to December 2001 were analyzed retrospectively.Thirty-two cases (8.5%) had elevated fasting blood glucose after chemotherapy. Among them, 14 cases (3.7%) were diagnosed as diabetes mellitus, 9 cases (2.4%) were diagnosed as impaired glucose tolerance. Paclitaxel based chemotherapy seemed to have more opportunity to induce disorders of glucose metabolism than that in cisplatin based chemotherapy (P < 0.05), and this happened most frequently in 1 approximately 3 courses.Chemotherapy may induce disorders of glucose metabolism, which most frequently occurred in 1 approximately 3 courses, including impaired glucose tolerance or diabetes mellitus,especially in patients received paclitaxel chemotherapy.
Objective To investigate the antitumor effects on ovarian cancer using recombinant adenoviruses expressing autocatalytic caspase-3 driven by amplified human telomerase reverse transcriptase promoter (AdHTVP2G5-rev-casp3) combined with flavopiridol. Methods Following the treatment with AdHTVP2G5-rev-casp3 combined with flavopiridol, cell survival rate was measured by cell counting kit 8;cell apoptotic rate and cell cycle distribution were detected by flow cytometry. Western blot was performed to observe the expression of p17, the active subunit of caspase-3, and p85, the cleavage segment of substrate of caspase-3, in AO cells. The mice survival rates were measured for abdominally metastatic tumor models and the volume of tumor nodules were determined for subcutaneous tumor models following the treatments of AdHTVP2G5-rev-casp3 combined with flavopiridol. HE staining was used to detect the histopathological changes of various organs, and the serum level of alanine transaminase (ALT) and aspartate aminotransferase (AST) were measured to monitor liver damages following the intraperitoneal administration of AdHTVP2G5-rev-casp3 and flavopiridol. Results There was no significant cell-killing effects or apoptosis in AO cells following treatments with AdHTVP2G5-rev-casp3 or flavopiridol at low dosage alone (apoptotic rate all ＜ 11% ), whereas significant synergism of their sequential combination was observed in AO cells. This sequential treatment of AdHTVP2G5-rev-casp3 [multiplicity of infection (MOI) was 20]infection for 72 hours, followed by flavopiridol ( 300 nmol/L) for 48 hours, could result in the most substantial cell death, and AO cells survival rate and apoptotic rate were 73. 5% and 11.6%, respectively.Following treatments with AdHTVP2G5-rev-casp3 at low doses ( MOI = 10), there was a significant increase in cell number with S-phase content ( 62. 5% ), which resulted in the most marked apoptosis induced by sequential treatments with flavopiridol. The sequential combination could induce significantly higher levels of p17 and p85 expression than that when their applications alone. Combined AdHTVP2G5-rev-casp3 and flavopiridol treatment prolonged mouse survival [ mean survival time of ( 286 ± 6) days ] and suppressed tumor growth significantly (tumor growth suppression rate of 81% ), when compared with treatment using either alone. The levels of serum ALT and AST were not significantly elevated and no obvious lesions were found in any organs in treatments with AdHTVP2G5-rev-casp3 of low doses combined with flavopiridol.Conclusions AdHTVP2G5-rev-casp3 at low doses results in a significant increase in cell number with Sphase content, which significantly enhanced the sensitivity of cells to flavopiridol. Treatments of autocatalytic caspase-3 combined at low doses with flavopiridol result in significant synergistic antitumor effects,significant tumor growth suppression and prolonged survival of mice. When compared with normal dose flavopiridol alone, the combination could resulted in minimal liver toxicity.
Key words:
Ovarian neoplasms; Caspase 3; Cyclin-dependent kinases; Flavonoids; Piperidines
To identify the potential neoplastic risk in gonadal development abnormality with Y chromosome.Inquiries about the illness history were made. Lymphocyte chromosomal karyotype of peripheral blood was analyzed. Sex determining region Y gene and relative steroids and enzymes were detected. Gonadal site was examined through medical imaging. Gonadal excision was performed by laparotomy or laparoscopy. Pathological examinations were done on all of the specimens.Among 41 cases of androgen insensitive syndrome, spermatogenic cell neoplasm occurred in 1 patient, sertoli cell tumor in 2, and interstitial cell hyperplasia in 5. Among 14 cases of 17 alpha-hydroxylase deficiency (XY) syndrome, one was sertoli cell tumor, and one was sertoli cell hyperplasia. In 4 cases of XY pure gonadal dysgenesis, one was gonadoblastoma with dysgerminoma. One of 16 cases of XO/XY gonadal dysgenesis was spermatogenic cell neoplasm with agenda cell tumor. Four cases of testes degeneration were all with dysgenetic testes. All of the gonadoblastoma and germ-cell tumor were located in the pelvis. Tumors occurred mostly during 15 years of age to 32 years.The gonads of XY pure gonadal dysgenesis has high risks of gonadoblastoma and germ-cell tumor. The older the onset age after puberty, the higher the malignancy risk is. Once diagnosed, bilateral gonads should be excised as soon as possible.
To construct the autocatalytic caspase-3 and investigate its apoptosis-inducing effect in ovarian cancer in vitro and in vivo.PCR recombination technique was used to construct autocatalytic caspase-3 which is named as rev-caspase-3, and Ad-Max system was used to prepare recombinant adenovirus containing rev-caspase-3, which is named as Ad-rev-casp3. Immunohistochemistry was used to detect active caspase-3 expression. Cell counting kit, flow cytometry and western blot were used to measure cell survival rate, apoptotic rate, cell cycle distribution and the expressions of p17, active subunit of caspase-3, and p85, the poly (adenosine diphosphate-ribose) polymerase (PARP) cleavage segment, respectively. Transmission electron microscope was used to detect cell ultrastructure, and real time PCR was used to detect apoptosis-related gene expression. Subcutaneous tumor models and abdominally spread tumor models of human ovarian carcinoma were established using AO cells in BALB/c nude mice. The mouse survival rates were measured for abdominally spread tumor models, and the volume of tumor nodules were determined for subcutaneous tumor models following the treatments of rev-caspase-3.Active caspase-3 protein was significantly expressed, and the expression levels of active subunit of caspase-3, p17, and the PARP cleavage segment, p85, were significantly elevated in cells treated with rev-caspase-3. The decrease of cell survival rate and the increase of cell apoptotic rate were detected following Ad-rev-casp3 treatment. Treatments with Ad-rev-casp3 [multiplicity of infection (MOI) was 70] resulted in survival rate of 30.3% and apoptotic rate of 40.2%. There was a significant increase in cell number of S-phase (56.5%), while there was no significant apoptosis (3.4%) following treatments with Ad-rev-casp3 at a low dosage of MOI=10. Cells treated with rev-caspase-3 displayed significant apoptotic morphology. The levels of active caspase-3 gene expressions (9.44) significantly increased. Rev-caspase-3 treatment significantly prolonged survival, the mean survival duration was (213 +/- 16) days, and suppressed tumor growth (tumor growth suppression rate was 70%), when compared with treatment with phosphate buffered saline (PBS).Recombinant adenovirus containing rev-caspase-3 can significantly induce apoptosis of ovarian carcinoma cells, suppress tumor growth and prolong the mouse survival duration.
Estrogen and progesterone receptor levels (ER and PR) were measured in 21 specimens of cervical carcinoma and in 17 normal cervix by monoclonal enzyme immunoassay (ER-EIA and PR-EIA). In normal cervix, 88.2% of specimens were ER-positive (more than 15 fmol/mg protein), 74.5% were PR-positive (more than 15 fmol/mg protein) and 74.5% were both ER and PR-positive. In cervical cancer, 66.7% of malignancies were ER-positive, 42.9% were PR-positive and 38.1% were both ER and PR-positive. There was no significant difference in ER status between the normal cervix and cervical cancer (P > 0.05), but PR status and levels in normal cervix were significantly higher than those in cervical carcinoma (P < 0.05). ER levels in squamous cell carcinoma was not correlated to the tumor stage, histologic grade and menopausal status. PR levels in premenopausal patients with squamous cell carcinoma were significantly higher than those in postmenopausal patients (P < 0.01). Adenocarcinoma of the cervix contained significantly more ER and PR than squamous cell carcinoma (P < 0.01, P < 0.05). In addition, serum E2 level was also assayed in 21 patients with cervical cancer. There was significant difference in E2 levels between the premenopausal and postmenopausal patients (P < 0.01). Patients were stratified according to E2 levels, a significant difference in PR level and in ratio of PR/ER was noted (P < 0.05, P < 0.01).
Background: Ovarian cancer is the most lethal tumor of the female reproductive system. Establishing a methodology to screen and diagnose ovarian cancer in the early stage is important. Exosomes have been shown to be loaded with tumor-associated molecules. In this study, we compared the proteins loaded in exosomes from the peripheral circulation of epithelial ovarian carcinoma (EOC) patients and controls.
As important cell to cell communicator, exosomes carry a range of bioactive molecules which can significantly influence phenotype of recipient cells. Inhibiting or removing cancer cell-derived exosomes are of therapeutic interest. However, regulation of secretion and release mechanism of exosomes is still unclear. To explore the regulation of exosomes released from normal ovarian epithelial cells and ovarian cancer cells, a normal ovarian epithelial cell line and three ovarian epithelial cancer cell lines were utilized to investigate their exosomes' release and regulation. A cervical cancer cell SiHa was used for identifying tissue specificity. NanoSight NS500 was used to quantify exosome numbers. Exosomes were labeled and observed by confocal microscopy to investigate their interaction with different ovarian cell lines. Exosomes released from normal or ovarian cancer cells were regulated by the extracellular exosomes. Exosome release was inhibited with the extracellular exosome concentration increase. Exosomes from normal ovarian cell and cervical cancer cell also inhibited ovarian cancer cell-derived exosome release, and there was no tissue specificity. PKH26-labeled exosomes from normal ovarian cell and cervical cancer cell were uptaken by ovarian cancer cells. Release of exosomes from ovarian cancer cell is regulated by a feedback mechanism without tissue specificity. This may provide a therapeutic approach to control the release of exosomes from ovarian cancer cells.
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