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)

In a European joint project carried out in 6 laboratories a disease-oriented program was set up consisting of a panel of 7 tumor types, each represented by 4 to 8 different human tumor lines, for secondary screening of promising anticancer drugs. Human tumor lines were selected on the basis of differences in histology, growth rate, and sensitivity to conventional cytostatic agents. Xenografts were grown s.c. in nude mice, and treatment was started when tumors reached a mean diameter of 6 mm in groups of mice where at least 6 tumors were evaluable. Drugs were given at the maximum tolerated dose. For evaluation of drug efficacy, median tumor growth curves were drawn, and specific growth delay and treated/control x 100% were calculated. Doxorubicin (8 mg/kg i.v. days 1 and 8) was effective (treated/control < 50%, and specific growth delay > 1.0) in 0 of 2 breast cancers, 1 of 3 colorectal cancers, 2 of 5 head and neck cancers, 3 of 6 non-small cell lung cancers, 4 of 6 small cell lung cancers, 0 of 3 melanomas, and 3 of 6 ovarian cancer lines. Amsacrine (8 mg/kg i.v. days 1 and 8) was not effective, while datelliptium (35 mg/kg i.p. days 1 and 8) was active against 2 of 6 small cell lung cancer lines. Brequinar sodium (50 mg/kg i.p. days 1-5) showed efficacy in 4 of 5 head and neck cancers, 5 of 8 non-small cell lung cancers, and 4 of 5 small cell lung cancer lines. The project has been shown to be a feasible approach. Clinical activity for doxorubicin and inactivity for amsacrine against solid tumor types was confirmed in the human tumor xenograft panel. Additional anticancer drugs will be studied in the European joint project to further define the reliability of this novel, promising screening approach.
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PMID:Phase II preclinical drug screening in human tumor xenografts: a first European multicenter collaborative study. 139 20

A patient with liver metastasis from ovarian cancer was treated by intra-arterial infusion chemotherapy (well differentiated adenocarcinoma--CDDP 50 mg/body, ADR 30 mg/body, CPA 500 mg/body (iv)). After the chemotherapy, the metastatic tumor appeared remarkably smaller and could be resected successfully at the second reduction surgery. This patient is active 30 months after the first appearance and enjoying a favorable quality of life.
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PMID:[A case of stage IVb ovarian carcinoma successfully treated with intra-arterial infusion chemotherapy using implantable reservoir system]. 153 Mar 35

The antitumor activity of delta 7-prostaglandin A1 (delta 7-PGA1) or delta 12-prostaglandin J2 (delta 12-PGJ2) on human ovarian cancer cell lines resistant to cisplatin (CDDP), doxorubicin (ADR), and L-phenylalanine mustard (l-PAM) was studied in vitro. A2780AD, A2780 (parent cells of A2780AD), 2008DDP, and 2008 cells (parent cells of 2008DDP) were used. The antitumor activities of the drugs were defined with 50% inhibitory concentration (IC50) estimated from growth inhibition curves, which were obtained by an indirect colorimetric method. Drug-resistance ratios obtained from IC50 values, by comparing A2780AD and A2780 cells, were 62.5 for ADR, 4.6 for CDDP, 4.9 for l-PAM, 1.5 for delta 7-PGA1, and 1.8 for delta 12-PGJ2. Those obtained by comparing 2008DDP and 2008 cells were 1.1 for ADR, 16.0 for CDDP, 2.9 for l-PAM, 2.3 for delta 7-PGA1, and 3.2 for delta 12-PGJ2. Thus some human ovarian cancer cells resistant to ADR, CDDP, and l-PAM remain sensitive to antitumor PGs.
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PMID:Human ovarian cancer cell lines resistant to cisplatin, doxorubicin, and L-phenylalanine mustard are sensitive to delta 7-prostaglandin A1 and delta 12-prostaglandin J2. 202 57

The dissatisfying results achieved in the therapy of ovarian carcinoma with an unchanging low rate (between 10% and 30%) of five-year-survival were the reason for efforts to develop a new treatment scheme combining chemotherapy with hormone therapy for epithelial ovarian carcinoma in FIGO stages III and IV. Basic theoretical and experimental reflections: Although in many cases patients may show good response to standard chemotherapy containing cisplatin, a large percentage (70% to 90%) suffers a relapse due to the fact that single tumour cells are resistant to chemotherapy. In order to counteract this resistance we developed a method of therapy (in accordance with the ideas of Coldman and Goldie) based on the sequential application of various non cross-resistant cytostatic agents. This new regimen, comprised of Doxorubicin, Cisplatin, Vincristine, Cyclophosphamide and Methotrexate (AP-VC-MTX), was compared to two standard types of chemotherapy (Doxorubicin/Cyclophosphamide or Doxorubicin/Cisplatin) in a prospective, randomised study. The AP-VC-MTX regimen showed equal therapeutical results but had a significantly lower level of nephrotoxicity and gastrointestinal toxicity than the combined Doxorubicin/Cisplatin therapy. As a result of these studies we chose the AP-VC-MTX method as standard therapy for patients suffering from advanced stage ovarian carcinoma. Hormone therapy was tested in numerous phase II studies on patients who had previously received cytostatics and was found to be an effective alternative. One of the substances that was most closely studied was Medroxyprogesterone acetate (MPA). Its therapeutic value was established in in vitro tests which showed direct cytotoxicity in ovarian carcinoma and is based on the theory that, on the one hand, the MPA is attached to the progesterone receptor and impairs growth in a similar way to endometrium and breast carcinoma and, on the other hand, the MPA reduces the level of gonadotropin and estrogen, which may be factors, which stimulate tumour growth in ovarian cancer. Furthermore, the myeloprotective effect and the corticoid-like effect of the MPA usually result in lower bone marrow toxicity and an increase in weight. 81 in vitro chemosensitivity tests carried out on tumour-cell cultures of 25 patients suffering from ovarian carcinoma, showed sensitivity to Cisplatin in 38%, Doxorubicin in 44%, 4-OOH-Cyclophosphamide (the in vitro active metabolite of Cyclophosphamide) in 50%, Vincristine in 53%, MTX in 19% and MPA in 36%.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Combined chemo- and hormone-therapy in advanced ovarian carcinoma--theoretical, experimental foundations and clinical results]. 214 2

Doxorubicin, cisplatin, and cyclophosphamide are the three drugs most commonly used in the treatment of ovarian cancer, but no effect greater than additivity was observed for any combination of these drugs in the present study. Only a few studies have been reported concerning the degree of their additivity or their best order of sequencing. In our in vitro studies, cisplatin in combination with doxorubicin or 4-hydroperoxycyclophosphamide (4HC) was tested against seven human gynecologic tumor-cell lines in different sequences, using a double-agar layer tissue-culture system. Drug interactions with respect to inhibition of tumor clonogenicity were evaluated by isobologram and fractional survival methods. Doxorubicin and 4HC were sequenced simultaneously and at 1, 6 and 24 h after cisplatin, and cisplatin was sequenced at 1, 6 and 24 h after 4HC. The isobolograms constructed for doxorubicin or 4HC plus cisplatin revealed strict additivity between these agents against ovarian cancer clonogenicity. Both doxorubicin and 4HC showed the greatest additivity when used simultaneously and at 1 h vs 6 or 24 h after cisplatin. Although the mechanisms by which these sequencing effects occur are unknown, these studies provide new leads for the design of clinical trials with combinations of these three agents.
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PMID:In vitro evaluation of cisplatin interaction with doxorubicin or 4-hydroperoxycyclophosphamide against human gynecologic cancer cell lines. 259 4

The ability of the Tiapamil analog N-(3,4 Dimethoxyphenyl)-N-methyl-2-(naphthyl)-m-dithiane-2-propylamine hydrocloride (RO11-2933) to influence the cytotoxic activity of Doxorubicin (DX) and seven other antitumor agents was evaluated in sensitive and treatment-induced multidrug resistant human ovarian cancer cells. In vitro treatment of A2780 sensitive cells with 1 microM RO11-2933 for 72hr potentiated by less than 3-fold the cytotoxic effects of each antitumor drug tested, with the exception of Cisplatin and Fluorouracil, which were potentiated by 7.2- and 5.0-fold, respectively. In A2780-DX3 resistant cells, RO11-2933 increased by a mean of 50-fold the cytotoxic effects of the anthracyclines and the Vinka alkaloids analyzed. A potentiation of Cisplatin activity was also observed (6.5-fold), whereas the Tiapamil analog did not significantly modify the antiproliferative activity of Bleomycin, Fluorouracil or Ara-C. Analysis of DX uptake and retention showed that in resistant cells RO11-2933 restored the intracellular DX content to levels comparable to those of sensitive A2780 cells, suggesting that the cytoplasmic membrane might represent a possible site of action of this compound. The results obtained indicate that RO11-2933 might represent an effective agent in combination with several anticancer drugs for the treatment of drug resistant ovarian carcinomas.
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PMID:Effect of the tiapamil analog RO11-2933 on cellular sensitivity to antitumor drugs in sensitive and multidrug resistant human ovarian cancer cells. 275 Dec 61

The development of acquired resistance has limited the effectiveness of chemotherapy in the treatment of ovarian cancer. Experimental model systems were developed to study the mechanisms associated with primary resistance to chemotherapeutic agents and broad cross-resistance (multidrug resistance) which is characteristic of human ovarian cancer. Doxorubicin-resistant cell lines developed in vitro by exposure of a sensitive cell line to increasing concentrations of doxorubicin develop resistance on the basis of a decrease in drug accumulation and have increased expression of the mdr-1 gene. This gene encodes for a membrane glycoprotein and leads to a decreased drug accumulation in drug resistant cell lines. Cell lines established from patients refractory to doxorubicin-containing combinations, however, do not demonstrate a decrease in drug accumulation. Studies are in progress on the measurement of mdr-1 levels in tumors of patients undergoing treatment to determine whether agents, such as verapamil may be useful in the treatment of drug resistant gynecologic cancers. Human ovarian cancer cell lines from drug resistant patients also has been demonstrated to increase levels of glutathione. Lowering of glutathione levels with buthionine sulfoximine (BSO), which irreversibly inhibits the enzyme gamma-glutamyl cysteine synthetase, leads to a marked potentiation of the cytotoxicity of melphalan both in vitro and in vivo in a nude mouse model of human ovarian cancer. Based on those studies, BSO is undergoing toxicologic evaluation before initiation of clinical trials in drug resistant patients. Our studies demonstrate that drug resistance in human ovarian cancer is likely due to interaction of multiple factors. However, biochemical intervention in some of the key steps leading to drug resistance has been demonstrated experimentally feasible and indicates that pharmacologic reversal of drug resistance is a clinical possibility.
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PMID:Multidrug resistance in ovarian cancer. 330 67

Mitoxantrone is similar to Adriblastin in its mechanism of action and antitumor activity. Objective remissions were obtained in 20-30% pretreated patients and in 23-44% of untreated patients by single-drug treatment of patients suffering from metastatic breast cancer. The objective response rates to Mitoxantrone in combination with CTX, 5-FU, MTX, VCR, MMC. Prednimustine or Vindesine were 16-46% in treatment and 38-89% in primary treatment. Randomized studies comparing Mitoxantrone with Adriblastin in single-drug and combination treatment did not show any significant differences in efficacy. However, Mitoxantrone was significantly less toxic. Remission rates of between 24 and 54% were achieved by single-drug treatment in pretreated patients suffering from non-Hodgkin lymphoma. Mitoxantrone appears to be active in ovarian cancer, lung cancer and hepatocellular carcinoma.
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PMID:Mitoxantrone: mechanism of action, antitumor activity, pharmacokinetics, efficacy in the treatment of solid tumors and lymphomas, and toxicity. 332 53

Thirty-one patients with refractory ovarian cancer and other malignancies principally confined to the abdominal cavity were treated with an intraperitoneal combination-chemotherapy regimen consisting of cisplatin (100 to 200 mg/m2), cytosine arabinoside (10(-4) to 10(-3) mol/L) and doxorubicin (2 to 18 mumol/L). Sodium thiosulfate was simultaneously administered intravenously to prevent cisplatin-induced nephrotoxicity. Eight of 26 evaluable patients demonstrated clinical response including seven of 17 (41%) with ovarian cancer refractory to frontline chemotherapy. Systemic toxicity was mild except for nausea and vomiting. Abdominal pain secondary to doxorubicin was the major complication of therapy. We conclude that combination intraperitoneal therapy with cisplatin, cytosine arabinoside, and doxorubicin can be safely administered with objective tumor responses observed in patients with ovarian cancer heavily pretreated and in individuals with other malignancies involving the peritoneal cavity. Doxorubicin-induced local pain limits the ability to administer multiple courses of this treatment regimen.
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PMID:Combination intraperitoneal chemotherapy with cisplatin, cytarabine, and doxorubicin for refractory ovarian carcinoma and other malignancies principally confined to the peritoneal cavity. 654 84

Doxorubicin, ellipticine and etoposide are antineoplastic drugs with topoisomerase II inhibitory activity. The relationship between drug-induced sister-chromatid exchanges (SCEs) or chromosomal aberrations (CAs) and cytotoxicity, or drug-induced DNA double-strand breaks (DSBs) and cytotoxicity, or drug-induced SCEs and DSBs was investigated in human ovarian cancer cells sensitive (A2780) and resistant (A2780-DX3) to topoisomerase II inhibitors. 30-min drug treatments produced SCEs, CAs and DSBs in sensitive cells, doxorubicin being more potent than etoposide at equimolar concentrations. The same treatments of resistant (A2780-DX3) cells did not produce chromosomal damage (SCEs, CAs, DSBs) and no cytotoxicity was observed. A plot of cytotoxicity versus SCEs indicated a good correlation between these two parameters for topoisomerase II inhibitors and not for mytomicin C. The plot of DSBs versus SCEs also showed a very good correlation.
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PMID:Sister-chromatid exchanges, chromosomal aberrations and cytotoxicity produced by topoisomerase II-targeted drugs in sensitive (A2780) and resistant (A2780-DX3) human ovarian cancer cells: correlations with the formation of DNA double-strand breaks. 752 71


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