Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1140680 (ovarian cancer)
 28,141 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The histoculture drug sensitivity assay (HDRA) has been demonstrated to have high predictability for resistance, sensitivity, and survival for gastrointestinal cancer (Clin Cancer Res 1: 305-311, 1995; Clin Cancer Res 1: 1537-1543, 1995). In this report, we evaluated the clinical usefulness of the HDRA in ovarian cancer. HDRA was performed on tumors from patients with ovarian cancer. Eighty-five cases (97%) were evaluable. Tumor fragments were cultured on collagen-sponge gels. The cultures were incubated with cisplatin (CDDP) for seven days. Cell viability were assessed with the MTT end point. The optimal cut off concentration of CDDP was determined to be 25 micrograms/ml by correlation with the historical clinical response rate to CDDP. HDRA results were correlated to clinical response of 15 patients who received CDDP-based therapy that included doxorubicin and cyclophosphamide (CAP therapy). The true positive rate was 88%, the true negative rate was 86%, the sensitivity was 88%, the specificity was 86%, and the accurate prediction rate was 87% when HDRA results were compared to the response of the treated patients. The data suggest that the HDRA is capable of predicting the response to antitumor chemotherapy in patients with ovarian cancer and that measuring response to CDDP can be useful for optimization of CAP chemotherapy for patients with this disease.
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PMID:Cisplatin sensitivity of ovarian cancer in the histoculture drug response assay correlates to clinical response to combination chemotherapy with cisplatin, doxorubicin and cyclophosphamide. 1092 50

Forty-seven ovarian cancer cases in which 20 were previously treated with cisplatin (cisPt) based chemotherapy, were checked for in vitro chemosensitivity using MTT assay. The drugs included in the study were cisPt, adriamycin (ADR), epirubicin (EPR) and etoposide (ETO). The logarithemic concentrations (0.1, 1.0, 10.0 and 100.0 micrograms/ml) of these drugs were used in the MTT assay. The IC50 values for these drugs in the above tumor samples were calculated. The effect of pretreatment with cisPt based chemotherapy on the emergence of drug resistance, expression of p53 protein (detected using immunohistochemical method by employing monoclonal antibody to p53) and intracellular glutathione (GSH) levels was also studied. Our results demonstrated the superiority of EPR in terms of its efficacy as compared to the other drugs used in the study. EPR was effective in both, previously cisPt-exposed and cisPt-unexposed ovarian cancer cases indicating its importance as a second line chemotherapy in the refractory ovarian carcinoma cases. Pre-exposure to cisPt based chemotherapy appears to result in the emergence of cisPt resistance, elevated intracellular GSH levels as well as p53 positivity. A statistically significant correlation was also observed between ADR and EPR resistance and p53 positivity (P < 0.01 and 0.05 respectively).
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PMID:Effect of cisplatin-based chemotherapy on emergence of cisplatin resistance, and its correlation with intracellular glutathione levels and accumulation of p53 protein in human ovarian cancer. 1094 37

The topoisomerase I inhibitors are a new class of antineoplastic agents currently under clinical development. Among these compounds there are some camptothecin (CPT) derivatives with improved toxicity profiles and antitumor activity: irinotecan (CPT-11) and topotecan (TPT), particularly active against colon, lung and ovarian cancer. The aim of this study was to evaluate the cytotoxicity of CPT, CPT-11, its metabolite SN38 and TPT in a primary culture system of rat hepatocytes. Cytotoxicity was evaluated by measuring the leakage of lactate dehydrogenase (LDH) into the medium and by assessing cell viability in terms of tetrazolium salts (MTT) reduction by mitochondrial dehydrogenase activity. Our results showed that cytotoxicity was limited in the case of short drug exposure. There was a significant and time-dependent increase in LDH leakage and a significant time- and dose-dependent decrease in MTT reduction after 3 h of incubation (p<0.01). In the treatments with doses related to peak plasma levels, CPT-11 was less responsible for the observed in vitro hepatotoxicity than its metabolite SN38; TPT had lower LDH leakage compared to SN38 and CPT-11 but showed significant and early (3 h) decrease in MTT reduction: this may mean a different mechanism of cellular damage. These results demonstrate that CPT derivatives are directly toxic to liver cells in a distinct time- and dose-related response.
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PMID:Hepatotoxicity of camptothecin derivatives in a primary culture system of rat hepatocytes. 1094 85

Chemosensitivity to the drugs plays a crucial role in the treatment of ovarian cancer. In this study, we evaluate the cytotoxicity of chemotherapeutic agents in six ovarian cancer cell lines; four clear cell adenocarcinoma and two serous papillary adenocarcinoma, using seven single drugs and seven sets of drug combinations with tetrazolium-based semiautomated colorimetric (MTT) assay. The drug concentration which produced 50% growth inhibition (IC50) of cisplatin was within clinically achievable range in five cell lines. The area under the curve (AUC) at IC50 of cyclophosphamide was below the clinically achievable AUC in two serous papillary cell lines. Paclitaxel was more effective in clear cells than serous papillary cells. The intensification of cytotoxicity was observed in the combinations of paclitaxel and cisplatin, and cyclophosphamide and cisplatin or 5-fluorouracil irrespective of histopathological characteristics of the original tumor. Our results indicate that ovarian cancer cell lines respond to chemotherapeutic agents heterogeneously depending upon histopathological features, indicating individualized regimens may improve survival in ovarian cancer patients.
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PMID:Cyclophosphamide and 5-fluorouracil act synergistically in ovarian clear cell adenocarcinoma cells. 1112 61

In a systematic effort to identify a potent anticancer agent against human ovarian cancer, we synthesized 15 oxovanadium(IV) complexes, and examined their cytotoxic activity against human ovarian cancer cell lines PA-1, SKOV-3, ES-2 and OVCAR-3 using a MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyletetrazolium bromide]-based assay. The apoptosis-inducing ability of the oxovanadium compounds was evaluated by the two-color flow cytometric terminal deoxynucleotidyl transferase-based assay that labels 3'-hydroxyl ends of fragmented DNA (TUNEL) assay and confocal laser scanning microscopy. Notably, all eight oxovanadium complexes of 1,10 phenanthroline exhibited significant cytotoxicity and induced apoptosis within 24 h. The mono-chelated, VO(NO2-phen) and bis-chelated, VO(Me2-phen)2, VO(Cl-phen)2 and VO(NO2-phen)2 complexes were the most potent oxovanadium compounds, and killed target cancer cells at low micromolar concentrations. The marked differences in the cytotoxic activity of oxovanadium(IV) complexes containing different heterocyclic ancillary ligands suggest that the cytotoxic activity of these compounds is determined by the identity of the five-member bidentate ligands, as well as the nature of the substituents on the heterocyclic aromatic rings. Our results presented herein provide experimental evidence that oxovanadium compounds induce apoptosis in human ovarian cancer cells. The lead compounds, VO(Me2-phen)2 and VO(NO2-phen)2, may be useful in the treatment of ovarian cancer.
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PMID:Apoptosis-inducing oxovanadium(IV) complexes of 1,10-phenanthroline against human ovarian cancer. 1114 93

VIP/PACAP are autocrine growth factors for lung cancer. VIP and/or PACAP mRNA is present in most lung cancer cell lines examined. Although mRNA for VPAC2-R is not common, VPAC1-R and PAC1-R mRNA is present in many lung cancer cell lines. 125I-VIP binds with high affinity to lung cancer cells and specific 125I-VIP binding is inhibited with high affinity by (Lys15, Arg16, Leu27)VIP1-7 GRF8-27, the VPAC1-R specific agonist, but not by Ro25-1553(18), the VPAC2-R specific agonist. VIP elevates cAMP and increases c-fos gene expression. The increase in cAMP and c-fos mRNA caused by VIP is inhibited by SN(VH). (SH)VH inhibited the proliferation of NCIH1299 cells in the MTT assay, which is based on cytotoxicity. In a recent cell line screen, (SN)VH inhibited the growth of 51 of 56 cancer cell lines including leukemia, lung cancer, colon cancer, CNS cancer, melanoma, ovarian cancer, renal cancer, breast cancer, and prostate cancer (T. Moody, unpublished). It remains to be determined if (SN)VH will be useful for treatment of a wide variety of cancers.
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PMID:VPAC1 receptors and lung cancer. 1119 32

The 3-(4,5 dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay is used successfully to estimate the number of viable cells in drug screening trials. We used the MTT assay to assess the viability of a rodent ovarian carcinoma cell line (DMBA-OC-1R) after exposure to combinations of cisplatin and 5-fluorouracil as free drug and in encapsulated (conjugated and unconjugated) forms. After 48 h of exposure to free drugs, a significant trend towards cell cytotoxicity could be observed and this was well established by 120 h. Cells treated with drug-containing immuno-microspheres showed a similar initial decrease in cell viability after 96 h, and this was maintained for 128 h. These results suggest that immuno-microspheres loaded with chemotherapeutic drugs have the potential to be successfully used in the treatment of ovarian cancer.
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PMID:Assessment of the antitumour activity of targeted immunospecific albumin microspheres loaded with cisplatin and 5-fluorouracil: toxicity against a rodent ovarian carcinoma in vitro. 1123 8

The hollow fiber assay is currently used as an in vivo model for anticancer drug screening in nude mice, but it can also be used as an in vitro model. In the current study, an in vitro hollow fiber model was used to study the effect and mode of induced cell death of a new cyanoguanidine, CHS 828. Human leukemia, adenocarcinoma and lymphoma cell lines as well as primary cultures of human tumor cells from patients with chronic lymphocytic leukemia (CLL) and ovarian cancer (OC) and normal human lymphocytes were cultured in semipermeable hollow fibers. The fibers were incubated for 3 or 14 days prior to CHS 828 exposure for 72 h, followed by determination of living cell density by MTT staining. For cell morphology, using harvested cultures on cytospin slides had technical advantages compared to using paraffin sections of the formalin-fixed fibers. CHS 828 showed higher antitumor activity on CLL and normal human lymphocyte cultures compared to OC cultures, and cell lines cultured 3 days were more sensitive than those cultured 14 days. Morphological examination of CHS 828-treated cultures revealed a mixture of apoptosis and necrosis.
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PMID:A hollow fiber model for in vitro studies of cytotoxic compounds: activity of the cyanoguanidine CHS 828. 1127 84

Progesterone has been used as an ingredient of anticancer drug for patients with ovarian carcinoma. However, the mechanism of anticancer effects by progesterone has not been understood. In this study, the effects of progesterone on ovarian cancer cells, SNU-840, were investigated. After the incubation with progesterone, the viability of the cells was evaluated by MTT assay. As a result, 45% of the cells were viable after 48 h of incubation with 100 microM progesterone. In addition, [(3)H]thymidine incorporation assay showed that the proliferation of the cells was completely inhibited by progesterone after 48 h of incubation at 100 microM concentration. Colorimetric TUNEL assay revealed the fragmentation of the chromosomal DNA, suggesting that the process of the cell death was apoptosis. The level of the p53 mRNA was determined by northern blotting assay, since many apoptosis processes are mediated by up-regulation of the p53 expression. The level of the p53 mRNA reached its maximum at 12 h and decreased after 24 h of incubation with progesterone. In conclusion, progesterone inhibits the proliferation and elicits apoptosis of SNU-840 cells. Also, it up-regulates the p53 mRNA transiently.
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PMID:Apoptosis induced by progesterone in human ovarian cancer cell line SNU-840. 1150 Sep 21

The c-erbB-2 oncogene encodes a tyrosine kinase that constitutes the internal and transmembrane part of the epidermal growth factor receptor (EGFR). ErbB-2 overexpression has been reported in 20% to 30% of human adenocarcinomas of the breast and ovary, and has been linked to an unfavorable prognosis in patients. Hypericin is a protein tyrosine kinase inhibitor that has been exploited in models for anti-tumor and anti-viral activity. In this study, we investigated the effects of hypericin on the activity of the c-erbB-2 oncoprotein and its downstream kinases. We also investigated the effect of hypericin on metastasis. We used ovarian SK-OV-3 cells as a model to determine whether hypericin-induced cell death was associated with inhibition of c-erbB-2 expression and activation. The IC50 of hypericin after 72 hrs exposure was 7.5 microM as determined by the MTT assay. Apoptosis, which was assessed by morphological changes and a flow cytometric assay, was observed at 24 h after continuous exposure to 5 microM hypericin. Inhibition of expression of the c-erbB-2 protein was detected, using a monoclonal anti-erbB-2 antibody after 12-48 hrs of exposure to hypericin. Hypericin was found to inhibit autophosphorylation of the erbB-2 protein and downstream kinases such as MEK and ERK1/2. We also found up-regulation of p21WAF1 expression and down-regulation of Bcl-2 in hypericin treated cells. An invasion assay showed that hypericin inhibited the movement of SK-OV-3 cells into the Matrigel. However, gelatin zymography showed that hypericin had no effect on the secretion of matrix metalloproteinases (MMPs) in SK-OV-3 cells. From these results, we conclude that hypericin inhibits the growth of SK-OV-3 ovarian cancer cells, inhibits the autophosphorylation of c-erbB-2, induces apoptosis, and may inhibit invasion.
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PMID:Inhibition of c-erbB-2 expression an activity in human ovarian carcinoma cells by hypericin. 1172 34


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