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 over-expression of the proto-oncogene HER-2 (c-erbB-2/neu) in ovarian, endometrial and mammary carcinoma is an important indicator for poor prognosis. We have previously shown in 3 out of 4 ovarian carcinoma cell lines an interferon-gamma (IFN-gamma)-mediated reduction in HER-2 specific protein and RNA levels. The oncogene expression was lowered only in the ovarian carcinoma cell lines but not in 3 IFN-gamma-sensitive human breast cancer cell lines. We extended our observations also to IFN type I, alpha and omega. The expression of the oncogene was measured by both the p185HER-2 ELISA and in selected cases by a living cell radioimmunoassay using the monoclonal antibody (MAb) 4D5 against the extracellular domain. Both IFN types reduced the expression of HER-2 in the ovarian carcinoma cell lines OVCAR-3, HTB-77, 2774 and SKOV-6, and in the SKUT-2 endometrial carcinoma cells. In contrast, SKOV-8 human ovarian carcinoma cells were sensitive for both IFN types regarding proliferation, but only IFN-gamma reduced proto-oncogene expression. In the SKBR-3 human mammary carcinoma cells, neither IFN type had an effect on HER-2 expression. The antibodies 4D5, 7C2, 3E8, and 3H4 which bind to the extracellular domain of p185HER-2 protein specifically inhibited anchorage-independent growth of SKBR-3 and HTB-77 cells. Expression of the oncogene HER-2 is the leading prognostic factor in ovarian cancer. Its modulation might represent a mechanism by which IFNs inhibit cell proliferation.
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PMID:Effects of interferons on the expression of the proto-oncogene HER-2 in human ovarian carcinoma cells. 137 Feb 27

The human ovarian carcinoma cell line, NIH:OVCAR-3, possesses high affinity receptors for interleukin-1 (IL-1). Binding experiments with 125I-IL-1 alpha indicate a dissociation constant of approximately 55 pM and the presence of approximately 7800 receptors/cell. These receptors bind both IL-1 alpha and IL-1 beta and internalize IL-1. Proliferation is NIH:OVCAR-3 cells is inhibited by IL-1. Half-maximal inhibition is observed with 2-3 units/ml of IL-1 alpha or IL-1 beta. A maximal effect (80% inhibition of cell proliferation) is achieved by treatment of cells with greater than or equal to 10 units/ml of IL-1 for 3 days. The antiproliferative effect of IL-1 is blocked by IL-1 receptor antagonist. Light and electron microscopy studies show that IL-1 treatment causes cytopathological changes and a reduction in the number of mitotic figures in NIH:OVCAR-3. IL-1 stimulates prostaglandin E2 release by NIH:OVCAR-3 cells, but this response is unrelated to the antiproliferative effect of IL-1. Interferon-alpha A (IFN-alpha A) also inhibits growth of NIH:OVCAR-3 cells in a concentration-dependent manner. Combination of IFN-alpha A and IL-1 gives synergistic inhibition of NIH:OVCAR-3 cell proliferation. IL-1 alone or in combination with IFN-alpha A or other agents may be useful for treatment of human ovarian cancer.
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PMID:Antiproliferative effect of interleukin-1 on human ovarian carcinoma cell line (NIH:OVCAR-3). 182 35

The circulating levels of a 90-kilodalton (KD) tumor-associated antigen were measured in the blood of 26 patients with ovarian cancer in clinical remission who received a short course of recombinant alpha-2b-interferon (rIFN-alpha-2b, 3 million U/m2/d intramuscularly for 3 days) before second-look procedures. The administration of rIFN-alpha-2b to 90-KD antigen-positive patients produced a slight increase of the marker. However, in patients without the marker but with evidence of disease, a remarkable increase above the cutoff level was observed. Less pronounced modifications of 90-KD antigen serum levels were found in patients with no disease at second look. Moreover, considering the 90-KD antigen mean percentage increase, the dynamic test with rIFN-alpha-2b was able to eliminate five of six false-negative results obtained with the 90-KD antigen basal assay alone. The sensitivity of the assay increased to 92% after IFN compared with 54% for the 90-KD antigen assay alone. An increase (greater than 100% above pretreatment titer) of 90-KD antigen levels during the test also was observed in four patients with no evidence of disease at second look. In two of these false-positive cases, recurrence of disease was observed 13 and 24 months later. At the time of this analysis, none of the patients with a negative second look and negative dynamic test had relapsed. These results suggest that the dynamic test with rIFN-alpha-2b might be a new tool to assess disease status in patients with ovarian cancer before second-look procedures.
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PMID:Recombinant alpha-2b-interferon dynamic test as a potential tool in predicting disease status during second look in ovarian cancer. A preliminary report. 193 6

Thirty-nine patients with epithelial ovarian cancer admitted to the Division of Medical Oncology of the Medical School II of Naples were given 159 courses of alpha 2b interferon (30 Mil./sqm IU) intraperitoneally from October 1986 to November 1989. IFN was generally administered every three weeks, but six patients received the drug weekly at the same dose, for an additional period. In 15 patients IFN was added to standard systemic chemotherapy as first line treatment; the remaining patients, all pretreated (22 with minimal and 2 with no residual disease), received an intraperitoneal multidrug treatment combining IFN, cisplatin and mitoxantrone. Peritoneal access was achieved through a temporarily implanted 18 gauge catheter and the drug was instilled in a large fluid volume (2,000 ml) to ensure wide spread and uniform distribution. IFN was well tolerated: only one patient had to discontinue treatment because of severe fatigue. No major complication related to catheter implantation or function occurred. 3/15 untreated and 11/20 pretreated patients, evaluable for response, achieved a pathological complete response (pCR). In view of IFN's lack of significant toxicity and the safety and tolerability of a temporary small gauge catheter for peritoneal access, intraperitoneal chemotherapy including IFN should be useful in ovarian cancer patients with minimal or absent disease after first-line systemic treatment.
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PMID:Alpha 2b interferon (IFN) by intraperitoneal administration via temporary catheter in ovarian cancer. Preliminary data. 205 Jan 63

In 78 patients with breast and 37 patients with ovarian cancer the effect of combined chemo- and immunotherapy with thymopentin (Timunox, Cilag) on different parameters of cell-mediated immunity (leukocyte migration inhibition test, serum level of TNF-alpha, IL-1, interferon-alpha, distribution of lymphocyte subsets) and the clinical course of disease was evaluated and compared to patients receiving only chemotherapy. In cancer patients additionally treated with thymopentin an increase in reactivity in the LMI test and an increase of IFN-alpha serum levels could be observed, whereas serum levels of TNF-alpha and IL-2 and the distribution of T-helper, T-suppressor, total T and natural killer cells did not change. Concerning the clinical course of disease, no significant differences could be observed in patients with disseminated spread of disease, whereas in patients receiving combined chemo-immunotherapy in the course of an adjuvant treatment a benefit was found compared to those receiving only chemotherapy. Thus, it seems that the additional administration of thymopentin in breast and ovarian cancer patients under chemotherapy results in a reduction of immunosuppressive side effects of chemotherapy and a positive effect of the survival time in patients with limited spread of disease.
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PMID:Investigations on cell-mediated immunity in patients with breast and ovarian carcinomas receiving a combination of chemotherapy and immunotherapy with thymopentin. 223 66

Mouse mAb M111 identifies a cell surface glycoprotein of 115,000 to 135,000 Da. M111 was expressed constitutively in subsets of cells of multiple lineages at discrete stages of cell maturation, suggesting that M111 is a differentiation Ag of the three germ layers. Ag expression could be induced by IFN-gamma but not by IFN-alpha, IFN-beta, or TNF. Induction of M111 expression was maximal at 48 h of culture in 200 U/ml of IFN-gamma and was independent of induction of class II MHC Ag. Induction was dependent on the cell type used. Nine colon cancer cell lines of undifferentiated phenotype were constitutively M111-; IFN-gamma induced M111 expression in seven of them. In contrast, IFN-gamma failed to induce M111 expression in six of six M111- ovarian cancer cell lines. Eight normal fibroblast cultures tested were M111-; they could not be induced to express M111. Three of five sarcoma cell lines were M111+; culture in IFN-gamma induced an increase in M111 expression in all of them. Constitutive and IFN-gamma-induced expression of M111 was independent of constitutive and induced expression of HLA class I and II molecules. IFN-gamma-mediated induction of M111 expression was not accompanied by coordinate changes in the expression of other differentiation traits. These results suggest that expression of the M111 gene is controlled by two mechanisms, one related to differentiation and the other activated by IFN-gamma.
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PMID:IFN-gamma-regulated expression of a differentiation antigen of human cells. 312 30

Fourteen patients with relapsing ovarian cancer were treated with a regimen of intravenous interferon gamma (IFN gamma). During an initial induction phase, patients received 2 mg/m2 IFN gamma intravenously over 2 h daily for 5 days, repeated every 2 weeks for six courses. Patients who responded were continued on a maintenance phase, receiving 3 mg/m2 intravenously over 2 h, twice weekly every 2 weeks for 2 to 6 months. All patients had received prior cisplatin containing chemotherapy regimens. Of the 14 patients entered, 7 completed the six courses of the induction treatment. Four patients were clinical responders and continued on maintenance therapy. The most commonly reported toxicities included malaise, fever, and deteriorating performance status. There appears to be some clinically apparent antitumor activity demonstrated by this dosing schedule of interferon gamma in ovarian cancers.
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PMID:A phase II study of the efficacy of recombinant interferon gamma in relapsing ovarian adenocarcinoma. 313 45

Effects of combination treatment with human recombinant alpha-2b interferon (IFN-alpha 2b) and gamma interferon (IFN-gamma) and sequencing of the combination on colony formation of human tumor cells were studied in a human tumor clonogenic assay (HTCA) with or without ascites-associated macrophages (AAM). Five different human tumor cell lines were studied. Three of the five cell lines (ovarian cancer cell line BG-1, cervical cancer cell line ME-180, and melanoma cell line SK-MEL 28) were sensitive to both IFNs. Cervical cancer cell line CaSki was sensitive to IFN-alpha 2b but resistant to IFN-gamma. Endometrial cancer cell line HEC-1A was resistant to both IFNs. Synergistic interaction was observed in BG-1 and SK-MEL 28 with a combination of the IFNs. ME-180 did not exhibit a positive interaction, in spite of its sensitivity to each IFN. CaSki and HEC-1A also did not exhibit a positive combined interaction at clinically achievable concentrations. One sequential combination method (method 1: IFN-alpha 2b----IFN gamma with a 24-h interval) resulted in a similar antitumor effect as the simultaneous combination. A reversed sequential method (method 2: IFN-gamma----IFN-alpha 2b with a 24-h interval) was less effective in three of the five cell lines. In BG-1, AAM enclosed in the lower layer markedly enhanced the antitumor effect of combined IFNs as well as each IFN alone. The antitumor effect with method 1 was significantly greater than that achieved with simultaneous combination or combination according to method 2 in the presence of AAM (P less than 0.01). These results suggest that (1) a synergistic antitumor effect of IFN-alpha 2b and IFN gamma is demonstrable in selected types of tumors, depending upon the sensitivity of each tumor cell line to both IFNs; (2) optimal scheduling for the direct antitumor effect of combined IFNs seems to be long-term exposure of cells to the IFN, the cells being treated with both IFNs either simultaneously or sequentially (IFN-alpha 2b preceding IFN-gamma); and (3) AAM potentiate the antitumor effect of IFNs either alone or in combination. Finally, IFN-alpha 2b may have some priming effects for the indirect effect of IFN gamma mediated through AAM in certain tumor cells.
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PMID:Effects of scheduling and ascites-associated macrophages on combined antiproliferative activity of alpha-2b interferon and gamma-interferon in a clonogenic assay. 313 42

Fresh biopsies from 14 of 22 (64%) ovarian carcinomas cultivated in the human tumor stem cell assay (HTSCA) were sensitive (greater than 70% inhibition in cell growth) to human interferons (HuIFNs). To achieve 70% inhibition of colony growth, 500 units/ml of a naturally produced IFN-alpha or IFN-alpha A were required in 71% of the sensitive specimens. The antiproliferative potencies of five IFNs were evaluated including two native alpha IFNs, two highly purified cloned subtypes of IFN-alpha, IFN-alpha D and IFN-alpha A, and one native fibroblast-derived beta interferon (IFN-beta). The antiviral activity of the IFN-alpha as determined by a human cell target correlated with their relative antiproliferative action. IFN-alpha D had minimal inhibitory effect at the highest concentration tested, while three IFN-alpha with high antiviral activities were equivalent with respect to growth inhibition in the HTSCA. Although instability could not be eliminated as a contributing factor, IFN-beta had significantly less growth inhibitory potency for cells from ovarian cancers when compared simultaneously with native IFN-alpha in the human tumor stem cell assay (HTSCA). Assuming direct antiproliferative effects are primary, future clinical trials evaluating IFN-alpha in ovarian cancer may require high titers of IFN.
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PMID:Antiproliferative activity of human interferons against ovarian cancer cells grown in human tumor stem cell assay. 650 40

Clonogenic tumor cells from fresh biopsies of human cancers were cultivated in vitro and tested for sensitivity by continuous exposure to pharmacologically achievable concentrations of either of two highly purified human leukocyte interferon subtypes (IFN-alpha A and IFN-alpha D) prepared by recombinant DNA methods. The interferons were compared on a weight basis at concentrations of 0.4 and 4.0 ng/ml (equivalent to 80 and 800 units of interferon activity for IFN-alpha A and 2.0 and 20 units for IFN-alpha D). Inhibition of tumor colony-forming units (50% of control or less) was observed in 38.1% of the 273 tumors tested against IFN-alpha A, and in 16% of the 71 tumors tested against IFN-alpha D. Of the tumor types with at least ten samples tested against IFN-alpha A, the percentage of cases exhibiting inhibition was as follows: melanoma (51.7%), lung cancer (50%), myeloma (33.4%), ovarian cancer (33.9%), sarcoma (33.3%), adenocarcinoma of unknown primary (30.4%), breast cancer (28%), acute leukemia (30.8%), and renal cancer (23%). More marked inhibition (30% of control or less) was observed in 18.7% of all tumors tested against IFN-alpha A. Of 60 melanomas tested, 18 (30%) exhibited marked in vitro inhibition of growth with IFN-alpha A. Although a smaller number of tumors (71) were tested against IFN-alpha D on a weight basis, it appeared, in general, to be slightly less active than IFN-alpha A (p less than 0.01), and only 8% of tumors tested exhibited marked inhibition over the same dosage range of interferon. Comparison of the dose-response curves for the 68 tumors tested simultaneously against both interferons did not reveal marked interpatient differences in the inhibition curves, although IFN-alpha D was slightly less active overall. Tumors exhibiting at least 50% inhibition of tumor colony formation also proved to be sensitive to a significantly larger number of cytotoxic drugs (tested simultaneously) than the tumors not inhibited with interferon (p less than 0.0001 for IFN-alpha A). We conclude that the in vitro clonogenic assay may aid in targeting tumor types most likely to exhibit interferon sensitivity and assist in case selection for entry into clinical trials with cloned interferons.
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PMID:Effects of cloned human leukocyte interferons in the human tumor stem cell assay. 668 47


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