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)

Cisplatin (DDP) is the most effective drug for the treatment of human ovarian cancer, but the mechanisms that determine sensitivity to the cytotoxic action of DDP are not well understood. Treatment of two human ovarian carcinoma cell lines with epidermal growth factor (EGF) simultaneously increased sensitivity to DDP and caused a persistent change in morphology in the absence of any mitogenic effect. Sensitization to DDP was shown to be dependent on both EGF concentration and EGF receptor number in C127 mouse fibroblasts expressing the human EGF receptor after transfection with a pBPV plasmid construct containing the human EGF receptor gene under control of the transferrin receptor 3'-inducible regulator. Sensitization of human ovarian carcinoma cells to DDP was not blocked by inhibition of protein synthesis. EGF did not enhance sensitivity to DDP or alter morphology in DDP-resistant human ovarian carcinoma cells despite the presence of functional EGF receptors on these cells. These results showed that elements of the signal transduction pathway activated by EGF determined cellular sensitivity to DDP, and that a DDP-resistant phenotype is associated with a defect in this signal transduction pathway.
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PMID:Epidermal growth factor regulates the in vitro sensitivity of human ovarian carcinoma cells to cisplatin. 224 36

Immunohistochemical techniques were used to evaluate the expression of six antigens (CA 125, TAG 72, CA 19-9, OVTL3, DF3, and transferrin receptor) in frozen sections from the primary tumor and metastases of 20 patients with epithelial ovarian cancer. Heterogeneous expression of most antigens was observed within a given tumor nodule, but in each patient the proportion of cells expressing an antigen was similar in the primary tumor and metastases. To explore the stability of the antigenic phenotype of individual cells, we studied CA 125 expression in an ovarian cancer cell line. Cells were separated into CA 125-positive and -negative groups using fluorescence-activated cell sorting. After the two groups of cells were recultured separately, only 38% of cells originally sorted as CA 125 positive still expressed CA 125, whereas 27% of cells sorted as CA 125 negative expressed CA 125. That cells may gain or lose CA 125 expression in culture suggests that expression of CA 125 by ovarian cancer cells is not a stable trait.
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PMID:Heterogeneity of antigen expression in advanced epithelial ovarian cancer. 232 61

Intracavitary instillation of radioantibodies has been proposed as therapy for anatomically confined malignant disease. To evaluate this therapeutic strategy, a monoclonal antibody reactive with human transferrin receptor (7D3) was evaluated for localization in a human malignant mesothelioma transplanted i.p. in athymic nude mice. This antibody was purified and labeled with 131I, 125I, or 111In. Radiolabeled antibody was administered i.p. or i.v. to tumor-bearing mice. Three h after injection, the percentage of injected dose/g (ID/g) of tumor was higher in free-floating ascites tumor cells (31.0%/g tumor cell pellet) after i.p. injection than after i.v. injection (12.0%). However, localization of radiolabel in i.p. solid tumors was similar (5.37% ID/g i.p. versus 4.73% of ID/g i.v.), and by 24 h both routes of administration produced similar localization of radiolabel in both free-floating ascites cells and solid tumors. In contrast, uptake of radiolabel into liver, kidney, and to a lesser extent bone and bone marrow, was less with i.p. than with i.v. administration. In clinical studies with 111In and 90Y antibodies administered i.p. to patients with ovarian cancer, confined biodistribution of the radioantibody was again seen, although interpatient variability of rate of egress of the radiolabel was documented. Therefore, both preclinical and clinical data indicate that i.p. therapy with immunoconjugates may be advantageous for cancer confined to the peritoneal cavity. This advantage stems primarily from reduced localization of isotope in organs of catabolism or toxicity (liver, kidney, bone, and bone marrow), rather than greatly increased levels of isotope in tumor. Unresolved problems include degree of antibody penetration into solid tumors, microdosimetry, and radioantibody effectiveness for tumor killing.
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PMID:Intraperitoneal immunoconjugates. 240 80

An immunotoxin composed of Pseudomonas toxin coupled to an antibody to the human transferrin receptor was evaluated for its effect on ovarian cancer. In the tumor model employed, 60 million human ovarian cancer cells were injected into the peritoneal cavity of an immunodeficient nude mouse. By day 5, cancer cells were implanted and growing in small clusters throughout the peritoneal cavity. On days 5-8, 0.3-2 micrograms of immunotoxin was injected into the peritoneal cavity. Control mice died with malignant ascites at 34-58 days after the implantation of tumor cells, whereas immunotoxin-treated mice lived to 100 days or longer. Irrelevant immunotoxins or antibody alone had no antitumor activity. These findings suggest that intraperitoneal injection of immunotoxins may have a role in the treatment of ovarian cancer.
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PMID:Antitumor effects of an immunotoxin made with Pseudomonas exotoxin in a nude mouse model of human ovarian cancer. 301 39

An immunotoxin composed of an antibody to the human transferrin receptor (454A12) and ricin A chain (RTA) was shown to inhibit the growth of NIH:OVCAR-3 tumors in a nude mouse model of human ovarian cancer. Inhibition of tumor growth by 454A12-RTA was related to the dose administered. The antitumor activity of the immunotoxin was blocked by coinjection of excess antibody with immunotoxin. An immunotoxin made using 454A12 and recombinant ricin A chain (rRTA) had an activity similar to that made with native RTA. The administration of 10 micrograms or greater of the immunotoxin 454A12-RTA/rRTA had significant antitumor activity. The injection of 30 micrograms of an irrelevant immunotoxin, MOPC21-RTA, or 30 to 500 micrograms of the 454A12 antibody had no antitumor activity.
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PMID:Antitumor activity of an immunotoxin in a nude mouse model of human ovarian cancer. 349 65

Using mAb ICO-160, we have studied Fas (APO-1/CD95) antigen expression on blood lymphocytes from healthy women, pregnant women and patients with chronic adnexitis, uterin myoma, ovarian cyst, ovarian and uterin cancer. In peripheral blood from healthy women Fas antigen was detected on 23.42 +/- 2.9% of lymphocytes. The healthy donors were divided in two different subgroups with low and high Fas expression. Expression of Fas antigen on lymphocytes was elevated (high expression subgroup) in all the groups of investigated patients, excepting the ovarian cancer ones with Fas expression similar to that in healthy donors. Comparison of expression of other differentiation antigens between healthy donors and the above groups of patients elucidated in the patients a kind of pronounced imbalance of the immune status and activation of the immune system. Additionally, in patients with ovarian cancer the imbalance of the immune status was reflected as altered ratio between helper and suppressor cells (the ratio was 0.73 in contrast to that 1.08 in group of healthy donors). As follows from the summarized results of all the trials, Fas antigen expression correlated with expression of other activation antigens as CD71 and CD25 (r = 0.05 and r = 0.52, respectively). Consequently, Fas (APO-1/CD95) antigen may be considered as the activation antigen and its expression may be used for assessing the immune status.
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PMID:Fas (APO-1/CD95) Antigen: New Activation Marker for Evaluation of the Immune Status. 1268 65

Iron has been suggested to be a risk factor for colorectal neoplasia. Some individuals who are heterozygous for mutations in the hemochromatosis gene (HFE) have higher than average serologic measures of iron. We therefore investigated whether heterozygosity for HFE mutations was related to risk of advanced distal adenoma and whether the relationship was affected by dietary iron intake. In the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, 679 persons with advanced distal adenoma and 697 control persons were genotyped for the two major HFE mutations (C282Y and H63D), one HFE polymorphism (IVS2+4), and one polymorphism (G142S) in the transferrin receptor gene (TFRC). HFE haplotypes were also created to examine the effect of haplotype on risk. Food frequency questionnaire data were used to estimate daily iron intake. There was no relationship between any HFE genotype or haplotype and advanced adenoma. Stratification of HFE genotype by TFRC genotype did not change the results. In addition, there was no relationship between dietary iron intake and risk of adenoma or between HFE genotype and risk of adenoma, stratified by iron intake. These results do not support a relationship between HFE heterozygosity and risk of advanced distal adenoma.
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PMID:Hemochromatosis gene mutations and distal adenomatous colorectal polyps. 1566 90

The inefficiency of in vivo gene transfer using currently available vectors reflects a major hurdle in cancer gene therapy. Both viral and non-viral approaches that improve gene transfer efficiency have been described, but suffer from a number of limitations. Herein, a fiber-modified adenovirus, carrying the small peptide ligand on the capsid, was tested for the delivery of a transgene to cancer cells. The fiber-modified adenovirus was able to mediate the entry and expression of a beta-galactosidase into cancer cells with increased efficiency compared to the unmodified adenovirus. Particularly, the gene transfer efficiency was improved up to 5 times in OVCAR3 cells, an ovarian cancer cell line. Such transduction systems hold promise for delivering genes to transferrin receptor overexpressing cancer cells, and could be used for future cancer gene therapy.
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PMID:Enhancement of gene delivery to cancer cells by a retargeted adenovirus. 1588 94

The influence of a plant preparation AdMax (Nulab Inc., Clearwater, FL, USA) on immunity in ovarian cancer patients was studied. The preparation is a combination of dried ethanol/water extracts from roots of Leuzea carthamoides, Rhodiola rosea, Eleutherococcus senticosus and fruits of Schizandra chinensis. Twenty eight patients with stage III-IV epithelial ovarian cancer were treated once with 75 mg/m(2) cisplatin and 600 mg/m(2) cyclophosphamide. Peripheral blood was collected 4 weeks after the chemotherapy. Subclasses of T, B and NK lymphocytes were tested for in the blood samples: CD3, CD4, CD5, CD7, CD8, CD11B, CD16, CD20, CD25, CD38, CD45RA, CD50, CD71 and CD95. Immunoglobulin G, A and M concentrations were also determined. Changes were observed in the following T cell subclasses: CD3, CD4, CD5 and CD8. In patients who took AdMax (270 mg a day) for 4 weeks following the chemotherapy, the mean numbers of the four T cell subclasses were increased in comparison with the mean numbers of the T cell subclasses in patients who did not take AdMax. In patients who took AdMax, the mean amounts of IgG and IgM were also increased. The obtained results suggest that the combination of extracts from adaptogenic plants may boost the suppressed immunity in ovarian cancer patients who are subject to chemotherapy.
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PMID:Effect of a combination of extract from several plants on cell-mediated and humoral immunity of patients with advanced ovarian cancer. 1661 74

Different proteins ensure the fine control of iron metabolism at the level of various tissues. Among these proteins, it was discovered a second transferrin receptor (TfR2), that seems to play a key role in the regulation of iron homeostasis. Its mutations are responsible for type 3 hemochromatosis (Type 3 HH). Although TfR2 expression in normal tissues was restricted at the level of liver and intestine, we observed that TfR2 was frequently expressed in tumor cell lines. Particularly frequent was its expression in ovarian cancer, colon cancer and glioblastoma cell lines; less frequent was its expression in leukemic and melanoma cell lines. Interestingly, in these tumor cell lines, TfR2 expression was inversely related to that of receptor 1 for transferrin (TfR1). Experiments of in vitro iron loading or iron deprivation provided evidence that TfR2 is modulated in cancer cell lines according to cellular iron levels following two different mechanisms: (i) in some cells, iron loading caused a downmodulation of total TfR2 levels; (ii) in other cell types, iron loading caused a downmodulation of membrane-bound TfR2, without affecting the levels of total cellular TfR2 content. Iron deprivation caused in both conditions an opposite effect compared to iron loading. These observations suggest that TfR2 expression may be altered in human cancers and warrant further studies in primary tumors. Furthermore, our studies indicate that, at least in tumor cells, TfR2 expression is modulated by iron through different biochemical mechanisms, whose molecular basis remains to be determined.
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PMID:Transferrin receptor 2 is frequently expressed in human cancer cell lines. 1742 3


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