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 therapeutic efficacy of gemcitabine, a new nucleoside analogue, was assessed in a variety of well-established human soft tissue sarcoma and ovarian cancer xenografts grown s.c. in nude mice. Tumour lines selected had different histological subtypes, growth rates and sensitivities to conventional cytostatic agents. The three different doses and schedules designed on the basis of a mean weight loss between 5% and 15% were i.p. injections of daily 3.5 mg kg-1 x 4, every 3 days 120 mg kg-1 x 4, and weekly 240 mg kg-1 x 2, which ultimately resulted in 19%, 10% and 4% toxic deaths, respectively. The weekly schedule induced > or = 50% growth inhibition in 2/4 soft tissue sarcoma and 4/6 ovarian cancer lines, while in three ovarian cancer lines > or = 75% growth inhibition was obtained. The anti-tumour effects of gemcitabine appeared to be similar or even better than previous data with conventional drugs tested in the same tumour lines. In comparison with the every 3 days schedule, the weekly and the daily schedule were less effective in 5/7 and 3/3 tumour lines (P < 0.001), respectively. In another experiment in three human tumour lines selected for their differential sensitivity to gemcitabine, weekly injections of 240 mg kg-1 x 6 did not result in a significant increase in the percentages of growth inhibition when compared to lower doses of 120 mg kg-1 or 60 mg kg-1 in the same schedule. However, the 240 mg kg-1 weekly x 6 schedule showed superior effects in 2/3 tumour lines in comparison with the same dose given every 2 weeks x 3 (P < 0.05). The preclinical activity of gemcitabine suggests that the drug can induce responses in soft tissue sarcoma and ovarian cancer patients. Our results further indicate that clinical trials of gemcitabine in solid tumour types should be designed on the basis of a schedule rather than a dose dependence.
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PMID:The influence of the schedule and the dose of gemcitabine on the anti-tumour efficacy in experimental human cancer. 831 20

CDDP-microcapsule (CDDP-mc) was prepared in the search for method for administering anti-cancer agents and has been examined for its properties, vital reaction and antitumor effect. In the present study, the results of the examination and possibility of application of CDDP-mc are reported. 1) It took 48 hours for CDDP to be released from the microcapsule into saline. 2) CDDP-mc size is 80-200 microns, and it contains 0.645mg of CDDP per mg of microcapsule. It was available as a drug enabling us to introduce a high concentration of CDDP into tumor tissue. 3) The side effects of CDDP-mc on animals (rabbit and rat) were more limited than those of ordinary CDDP solution and slight, especially for intraperitoneal or local injection. Intraarterial infusion of CDDP-mc, however, causes transitory palsy of the treated lower extremity probably due to embolism. 4) Its intraperitoneal administration was much more effective than the ordinary CDDP solution against Yoshida's sarcoma implanted in rats. 5) The subcutaneous administration of CDDP-mc was more effective compared to ordinary solution of CDDP. 6) The above results suggested that CDDP-mc is clinically applicable to the treatment of ovarian cancer and uterine cancer when administered intraperitoneally and locally (intra-tumor).
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PMID:[Experimental study on antitumor effect of cisplatin-microcapsule]. 849 8

With improvement in survival after cancer treatment, it is becoming increasingly important to examine treatment-related morbidity and mortality. Sarcomas can develop within the irradiated field after radiation therapy (RT) for gynecologic malignancies. We undertook a study to assess the outcome after treatment of postirradiation sarcoma (PIS) of the gynecologic tract. In reviewing our data and the literature, we compare the absolute risk of PIS and other radiation-associated second malignant neoplasms (SMNs) with the mortality risk of surgery and general anesthesia. Between 1955 and 1987, 114 patients with uterine sarcomas were seen at the University of California, Los Angeles (UCLA), Medical Center. Thirteen had a prior history of RT. Conditions for which these patients received RT included choriocarcinoma (one), menorraghia (four), cervical cancer (six), and ovarian cancer (two). RT doses were known in six cases and ranged from 4,000 to 8,000 cGy. Latency time from RT to the development of PIS ranged from 3 to 30 years, with a median of 17 years. Twelve patients were treated with surgery or additional RT. Two patients remain alive 5 months and 57 months, respectively, following salvage therapy. Five-year disease-specific survival for all patients is 17%. From our data and a review of the literature, we estimate that the absolute risk of PIS with long-term follow-up ranges from 0.03 to 0.8%. Postirradiation sarcoma of the gynecologic tract is a relatively rate event associated with a poor prognosis. Mortality risks of radiation-associated SMN are similar to mortality risks of surgery and general anesthesia. Given the large number of patients with gynecologic malignancies who can be cured or palliated with RT, concern regarding radiation sarcomagenesis should not be a major factor influencing treatment decisions.
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PMID:Postirradiation sarcoma of the gynecologic tract. A report of 13 cases and a discussion of the risk of radiation-induced gynecologic malignancies. 855 38

Germline mutations in the p53 tumor suppressor gene are associated with the Li-Fraumeni syndrome, characterized by childhood sarcoma, leukemia and early onset breast cancer and has occasionally been found also in familial breast-ovarian cancer. Most mutations found are of missense type and located in the central region of the gene (exons 5 to 8). In the present study, a germline p53 alteration was identified in a late onset breast cancer family (kindred Lund 5; mean age 58 years) using single stranded conformation polymorphism and sequence analysis. The mutation (a CCG to CTG transition) at codon 82 in exon 4, resulting in a proline to leucine substitution, has not previously been reported and was not present in a control set of 60 healthy individuals. Three of five woman with breast cancer (45, 57 and 65 years) were carriers of the alteration. Loss of heterozygosity at the p53 locus was not seen in the primary tumors of these women, but appeared as a partial loss of the wildtype allele in subsequent recurrent lesions of two gene carriers. The family manifested no linkage to the p53 gene (a two-point LOD-score of -0.41), and has previously also been excluded for linkage to the BRCA1 and BRCA2 loci, as well as being carrier of a BRCA1 germline mutation. Although it seems unlikely that the p53 germline mutation is the major cause of disease predisposition in Lund 5, the data suggest that some p53 alteration may confer a subtle influence on breast cancer development and progression.
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PMID:A novel p53 germline alteration identified in a late onset breast cancer kindred. 871 Mar 80

The objective in this paper is to describe the severity and outcome of arterial occlusion complicating treatment of women with gynecologic cancer. A series of six patients who underwent amputation were identified. Acute arterial occlusions were seen in three patients. One patient suffered extensive thrombosis of the hand and wrist resulting in amputation 3 weeks after cytoreductive surgery and chemotherapy for Fallopian tube cancer. She had a history of pulmonary embolism and deep-vein thrombosis. This patient was thought to have thrombophilia. One elderly patient with known arteriosclerosis developed sepsis following radical deep excision and groin dissection for vulvar cancer and lost two digits presumably due to microemboli. One patient developed thrombosis of the femoral artery on the second day following cytoreductive surgery for ovarian cancer. She responded to anticoagulation therapy; however, necrosis remained in portions of the heel and toes. Three patients underwent amputation of a lower extremity when they developed chronic arterial insufficiency after pelvic radiotherapy. The patients were irradiated at the ages of 28, 30, and 35 years for cervix cancer in two patients and a low-grade retroperitoneal sarcoma in one patient. Two received neutron beam therapy and one received conventional photon beam therapy. All three had extensive late radiation morbidity to the bladder and rectum and had multiple prior surgeries. The amputations occurred at the ages of 48, 48, and 55 due to accelerated arteriosclerosis. Two patients died as a result of this complication. Acute and chronic arterial occlusions are rare yet dramatic complications of therapy for gynecologic cancer. This series illustrates the predisposing factors, presentation, and management of these unusual events.
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PMID:Arterial occlusion complicating treatment of gynecologic cancer: a case series. 889 66

We have examined the use of the LDH (lactate dehydrogenase) assay for chemosensitivity testing in established and primary cultures of sarcoma, leukaemia and ovarian cancer in parallel with the MTT assay. The method we describe is rapid, sensitive and ideal for 96-well plate assays using adherent or suspension cultures. Excellent agreement between the two methods was observed (r = 0.936) using a variety of antitumour agents, with some notable exceptions. In the Bax (human synovial sarcoma) cell line MTT colour production by control cells was very low, thus MTT-->formazan production could not be relied upon as a definitive end point equating with cell number. In contrast, colour production of control cells using the LDH assay was significantly greater and all cultures tested were suitable for titration of chemosensitivity. There was a discrepancy between IC50 values obtained either by cell counting or MTT in the HTB88 (human leiomyosarcoma) line treated with 5-FU (59.9 microM vs > 200 microM, respectively). However, cell counting agreed well with the LDH assay (IC50 47.3 microM). Whilst the MTT assay remains a reliable method for chemosensitivity testing, the LDH assay may prove more appropriate in certain experimental settings.
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PMID:Chemosensitivity testing of fresh and continuous tumor cell cultures using lactate dehydrogenase. 906 57

The relevance of continuous cell line cultures to the problem of clinical anticancer drug resistance is unclear. There is also mounting scepticism regarding the use of tumour cell lines with in vitro acquired drug resistance, possessing high levels of resistance unlikely to be seen in the clinical setting. To overcome some of these problems we have initiated a study of drug resistance using fresh tumour material obtained from patients suffering from ovarian cancer and soft tissue sarcoma (STS). Studies involving ovarian cancer have involved over 30 specimens of stage III-IV disease. For these samples we have specifically focused on the multidrug-resistant (MDR) phenotype, examining the role of proteins P-glycoprotein (Pgp), multidrug resistance-protein (MRP) and lung-resistance-associated protein (LRP). Techniques have involved chemosensitivity testing, immunocytochemistry and flow cytometry, to measure Pgp function (drug efflux capacity with modulator reversal). Pgp was the most commonly expressed marker and its expression correlated with survival. MDR modulation using cyclosporins was shown to chemosensitise a proportion of the samples. Hence, in vitro screening can help to identify patients likely to benefit from resistance reversal strategies. Studies involving STS have looked at a combination of MDR and p53 disruption (commonly seen in this disease). Data have been examined alongside clinical data and the course of disease has been closely monitored. Although our studies are ongoing, we have identified a group of patients with aggressive disease showing marked drug resistance in vitro. All patients have relapsed with persistent disease following chemotherapy or radiotherapy. A number of chemoresistant patients showed a combination of p53 disruption in the presence of an MDR phenotype. Feedback from these translational studies should be used to guide the selection of patients for clinical trials using resistance reversal strategies and may suggest new targets for drug development.
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PMID:Drug resistance studies using fresh human ovarian carcinoma and soft tissue sarcoma samples. 933 43

We evaluated epidemiologic evidence pertaining to the human carcinogenic potential of triazine herbicides in general and of atrazine, the most common triazine. Cancers for which data are available included non-Hodgkin's lymphoma, Hodgkin's disease, leukemia, multiple myeloma, soft tissue sarcoma, colon cancer, and ovarian cancer. The investigations had methodologic limitations, including lack of in-depth exposure measurements and small numbers of subjects with heavy exposure and/or with many years since starting exposure, possibly required for the induction of cancer. The relation between triazines and non-Hodgkin's lymphoma has been assessed in four independent population-based case-control studies, reporting odds ratios ranging from 1.2 to 2.5. However, chance and/or confounding by other agricultural exposures may have produced these weak statistical associations. Furthermore, a pooled analysis of three of the case-control studies and the combined analysis of two retrospective follow-up studies did not demonstrate the types of dose-response or induction time patterns that would be expected if triazines were causal factors. The epidemiologic data pertaining to Hodgkin's disease, leukemia, multiple myeloma, soft tissue sarcoma, colon cancer, and ovarian cancer were inadequate for determining whether associations with atrazine or triazines exist in humans. For each of these cancers, only one or two studies evaluating the relationship were available, and the results of the studies typically were imprecise.
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PMID:A review of epidemiologic studies of triazine herbicides and cancer. 940 33

The feasibility of combined studies on a cell-line panel and primary cultures of patient tumor cells in the preclinical evaluation of new anticancer drugs was evaluated in a study of the activity and cross-resistance pattern in vitro of the new semi-synthetic vinca alkaloid vinorelbine (Vrb). The activity of Vrb was investigated in ten cell lines representing different resistance mechanisms and in a total of 256 fresh human tumor samples, using the fluorometric microculture cytotoxicity assay (FMCA). Resistance to Vrb in the cell lines was associated with expression of the multidrug resistance-mediating P-glycoprotein and the multidrug resistance-associated protein (MRP) and by a recently described tubulin-associated mechanism, while the cell lines with topoisomerase II- and glutathion-associated resistance did not show decreased sensitivity to the drug. Cross-resistance to vincristine (Vcr) and other tubulin-active agents was high in cell lines as well as in patient cells. As with most commonly used anti-cancer drugs, Vrb was more active in hematological than in solid tumor samples. Among the solid tumors investigated, the highest in vitro response rates were observed in ovarian cancer (27%), sarcoma (25%), non-small cell lung cancer (21%) and bladder cancer (20%), while no response was observed in renal or colorectal cancer. Compared to Vcr, Vrb appeared to be slightly more active in solid tumors and slightly less active in hematological tumors. The results show that although Vrb displays a high degree of cross-resistance to Vcr and other tubulin-active drugs, some difference in the activity spectrum could be detected and that the drug is sensitive to multiple mechanisms of resistance. The results also suggest that leukemias, ovarian cancer, sarcoma and bladder cancer are possible further targets for Vrb. The combination of studies on a cell-line panel and patient tumor cells from a broad spectrum of diagnoses to evaluate a new drug seems feasible and may give information on the mechanism of action and target diagnoses for phase II trials.
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PMID:In vitro evaluation of new anticancer drugs, exemplified by vinorelbine, using the fluorometric microculture cytotoxicity assay on human tumor cell lines and patient biopsy cells. 941 16

The efficacy and safety of docetaxel in clinical trials in patients with a variety of malignancies are reviewed. The overall response rate for docetaxel as a first-line treatment for metastatic breast cancer is 59%. Docetaxel in combination with doxorubicin or vinorelbine has proved particularly effective in the first-line treatment of metastatic breast cancer. Docetaxel is also one of the most active single agents in the treatment of non-small-cell lung cancer (NSCLC), producing an overall response rate of 27% when used as a first-line agent. Docetaxel plus cisplatin was more effective against NSCLC than either drug used alone, yielding response rates of 33-48%. Docetaxel has shown activity against a variety of other tumors, including ovarian cancer (response rate in second-line therapy, 34%), head-and-neck cancer (response rate in first-line therapy, 35%), and soft-tissue sarcoma (response rate in first-line therapy, 32%). The main toxic effect is grade 3-4 neutropenia, which occurs in 57% of treatment cycles but is brief and manageable. The dosage of docetaxel should be reduced from 100 mg/m2 to 75 mg/m2 if patients have neutropenia lasting more than one week, febrile neutropenia, or impaired liver function. Other adverse effects include severe fluid retention and asthenia. Some adverse effects can be avoided by administering corticosteroid premedication. Docetaxel has shown efficacy against a wide range of cancers in clinical trials and has a manageable adverse-effect profile.
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PMID:Efficacy and safety of docetaxel in clinical trials. 943 29


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