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)

Growth of epithelial ovarian cancer is influenced by several factors including transforming growth factor-alpha and transforming growth factor-beta, macrophage colony stimulating factor, tumor necrosis factor-alpha, interleukin-1 and interleukin-6, c-erb B-2 (HER-2/neu), and mutant p53. Continued expression of the epidermal growth factor receptor, new expression of c-fms, and overexpression of HER-2/neu are associated with a poor prognosis. A number of cytokines have been used to treat patients with ovarian cancer, including interferon-alpha, interferon-gamma, tumor necrosis factor-alpha, and interleukin-2. Judging from preclinical models, interferon-gamma may be more active than interferon-alpha against human ovarian cancer. Although tumor necrosis factor-alpha can stimulate proliferation of some ovarian cancers, the cytotoxic activity of tumor necrosis factor-alpha has been amplified ex vivo by inhibitors of protein synthesis. Similar heterogeneity exists with regard to interleukin-1 where stimulation or inhibition of cell proliferation has been observed. Tumor-infiltrating lymphocytes from ascites fluid contain cells capable of major histocompatibility complex-restricted and major histocompatibility complex-nonrestricted cytotoxicity. Tumor-infiltrating lymphocytes and interleukin-2 have been combined with cytotoxic chemotherapy to treat advanced or recurrent disease. Bispecific monoclonal antibodies that react both with T cells and ovarian tumor cells have produced tumor inhibition in human tumor xenografts. Immunotoxins that contain OVB3 and pseudomonas exotoxin have been evaluated in a phase I clinical trial. Dose-limiting central neurotoxicity has been observed without tumor regression. A monoclonal antibody designated OVX1 has been developed against a high-molecular-weight mucinlike molecule associated with ovarian cancers.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Biology and therapy with biologic agents in gynecologic cancer. 145 11

The discovery of cancer-causing genes has provided us with the exciting opportunity to begin to understand the molecular pathology of ovarian cancer. Activation of several of these genes including HER-2/neu, myc, ras, and p53 has been described in some ovarian cancers (Table 2). In addition, some proto-oncogenes such as the EGF receptor (erbB) and the M-CSF receptor (fms) are expressed along with their respective ligands in some ovarian cancers. Finally, for every oncogene that has been studied in ovarian cancer, there are at least a half-dozen that remain unexplored. In the future, when we have a better understanding of the molecular pathology involved in the development of ovarian cancer, this may allow us to better diagnose and treat, and eventually prevent, ovarian cancer.
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PMID:Oncogenes in ovarian cancer. 150 Mar 87

Ascitic fluid from human ovarian cancer patients often contains a large number of leukocytes along with tumor cells. Some of the recent evidence suggests that the ascitic fluid contains factors capable of inducing the growth of ovarian cancer cells in vitro and in vivo. While these factors have not yet been completely characterized, growth factors secreted by the tumor cells could influence the tumor growth by paracrine and autocrine mechanisms. Earlier, we reported that ovarian epithelial cancer cells produce macrophage colony-stimulating factor. It appears that these tumor cells produce more than one cytokine. Identifying the various products secreted by the tumor cells would provide valuable information needed to understand the biology of ovarian cancer. In the present study, evidence is provided for the first time that five different human ovarian epithelial tumor cell lines and tumor cells isolated from the ascitic fluid of four cancer patients express interleukin (IL) 1 alpha and beta genes constitutively. Production of the lymphokine was determined by analyzing the cellular RNA for IL-1-related transcripts and by immunological assays. Ovarian cancer cells also secrete another pleiotropic cytokine, IL-6, constitutively. In many systems, IL-1 induces the expression of the IL-6 gene. To determine whether the basal levels of IL-6 production are dependent on the endogenous IL-1, neutralization studies were carried out. Addition of antibodies to IL-1 did not decrease the levels of IL-6 secreted by the cancer cell lines. These results suggest that multiple cytokines are produced by ovarian cancer cells and that the endogenous IL-1 may not be directly involved in the regulation of IL-6 gene expression in these cells.
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PMID:Human ovarian epithelial cancer cells cultures in vitro express both interleukin 1 alpha and beta genes. 155 28

Recently, hematopoietic growth factors have been implicated in protean nonhematopoietic processes. In the current study, expression of macrophage colony-stimulating factor (M-CSF) and its receptor (the c-fms proto-oncogene) was investigated in 42 samples of gynecologic tissues. There were 15 samples of normal ovarian and uterine tissue or benign conditions of these organs; 11 samples of primary ovarian cancer tissue; seven samples of metastatic ovarian cancer tissue; and nine samples of primary endometrial cancer tissue. Steady state transcript levels were assessed by Northern Blot analysis. Macrophage colony-stimulating factor (M-CSF) expression was not observed in any of the specimens of benign abnormalities or of normal organs; c-fms expression was detected in two of 15 (13%) of these specimens, albeit at very low levels. In contrast, 14 (78%) of 18 ovarian tumor specimens, and five (55%) of nine endometrial tumor specimens expressed M-CSF. Similarly, 16 (89%) of 18 ovarian tumor specimens and six (67%) of nine endometrial tumor specimens expressed c-fms. Most positive malignant tissues (19 [86%] of 22) showed coexpression of M-CSF and c-fms. Of interest, M-CSF and c-fms mRNA were detected in tumor, but not in adjacent normal tissue. Furthermore, M-CSF and c-fms transcripts were produced by all metastatic tumors, including two cases in which the corresponding primary tumor from the same patient was negative. Because M-CSF mediates its effects by binding to its receptor, the increased levels of both these gene products in gynecologic malignancies suggest that an interaction between M-CSF and c-fms may participate in the development of ovarian and endometrial carcinomas and especially in progression to the metastatic state.
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PMID:Expression of the macrophage colony-stimulating factor and its receptor in gynecologic malignancies. 182 26

Macrophage colony-stimulating factor is a cytokine that stimulates proliferation and differentiation of phagocytic cells. Macrophage colony-stimulating factor is produced by ovarian epithelial cancer cell lines and might provide a useful serum marker for the disease. Among sera from 69 patients with clinically apparent epithelial ovarian cancer, 47 (68%) had at least 2.5 ng/ml macrophage colony-stimulating factor, whereas only two of 80 apparently healthy donors (2.5%) had a comparable elevation of macrophage colony-stimulating factor. Circulating levels of macrophage colony-stimulating factor did not correlate with serum levels of CA 125. Moreover, 14 of 25 ovarian cancer patients (56%) with clinically evident disease and normal levels of CA 125 (less than 35 U/ml) had elevated levels of macrophage colony-stimulating factor. Among 29 patients with serum CA 125 levels less than 35 U/ml before positive surgical surveillance procedures, 9 (31%) had at least 2.5 ng/ml macrophage colony-stimulating factor. Elevated levels of macrophage colony-stimulating factor were also found in patients with carcinomas from other primary sites and in 31% of 134 patients with benign diseases. If intercurrent benign disease can be taken into account, macrophage colony-stimulating factor deserves further evaluation in combination with CA 125 in monitoring ovarian cancer.
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PMID:Increased serum levels of macrophage colony-stimulating factor in ovarian cancer. 195 62

Many nonhematologic tumors produce growth factors that may influence cellular proliferation either by autocrine or by paracrine mechanisms. In the current study, human tumor cell lines were investigated for the constitutive production of macrophage colony-stimulating factor (M-CSF). Culture supernatants obtained from cell lines were analyzed using a radioimmunoassay and a radioreceptor assay specific for M-CSF. Among the various cell types analyzed, all the ovarian cell lines and a majority of the breast cancer cell lines secreted significant amount of an M-CSF-like factor. Treatment of mouse bone marrow cultures with culture supernatants from ovarian cancer cells stimulated the production of macrophage colonies. Analysis of total cellular RNA obtained from the ovarian cell lines by Northern blot showed multiple sizes of M-CSF transcripts with an abundance of a 4.2-kb message. The relative amount of M-CSF transcripts correlated with the level of immunoreactive material seen in the culture supernatants.
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PMID:Constitutive production of macrophage colony-stimulating factor by human ovarian and breast cancer cell lines. 264 21

To determine whether measurement of the levels of multiple tumor markers in the preoperative serum of women presenting with a pelvic mass distinguished benign from malignant disease better than the assay of CA 125 alone, sera from 429 patients, 192 of whom had malignant histology, were assayed for 8 different markers: CA 125, macrophage colony-stimulating factor, OVX1, lipid-associated sialic acid (LASA), CA15-3, CA72-4, CA19-9, and CA54/61. The sensitivity and specificity of CA 125 alone (> 35 U/ml) was 78.1 and 76.8%, respectively. A panel consisting of CA 125, OVX1, LASA, CA15-3, and CA72-4 had a sensitivity of 83.3% and specificity of 84.0% when two or more markers were elevated. Using the concentrations of these five markers, logistic regression analysis had a sensitivity of 85.4% and a specificity of 83.1%. Considering the values of markers in different sequences, classification and regression tree analysis substantially improved the sensitivity to 90.6% and the specificity to 93.2%. When applied in clinical practice this approach could improve the management of women presenting with a pelvic mass and may also have application in screening for ovarian cancer.
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PMID:Combinations of multiple serum markers are superior to individual assays for discriminating malignant from benign pelvic masses. 755 95

Markers supplementing CA 125 are important for monitoring of the disease in patients with mucinous and non-epithelial ovarian cancers. Tumour-associated trypsin inhibitor (TATI) or one of the gastrointestinal mucin markers, CA 19-9 or CA 72.4 are good supplements to CA 125 in mucinous ovarian cancer. Chorionic gonadotrophin (hCG) and alpha fetoprotein (AFP) are the most useful markers for germ cell tumours, and hCG beta may provide additional information. In addition to hCG beta, M-CSF and inhibin show promise of becoming useful supplements to CA 125 in ovarian cancer in general. Markers other than CA 125 may also play a role as prognostic indicators. TATI and procollagen peptides appear useful for this purpose. If these markers prove to provide reliable prognostic information, they could be used to aid selection of optimal treatment regimens.
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PMID:Markers supplementing CA 125 in ovarian cancer. 774 89

We determined the serum levels of macrophage colony-stimulating factor (M-CSF) in 441 women with gynecologic diseases to evaluate its role as a marker for gynecologic malignancy. Serum M-CSF levels were above the normal baseline level of 1,056 U/ml in 64% (56/88) of patients with ovarian cancer, 27% (16/60) of those with cervical cancer, and 25% (15/61) of those with endometrial cancer. M-CSF was significantly elevated in the serum of patients with advanced as compared with early stage cancer (stage I) of the ovary (p < 0.01), cervix (p < 0.05), and endometrium (p < 0.05). Only 5.6% of the patients with benign ovarian tumors and 7.0% of those with endometrial cysts had serum levels of M-CSF that exceeded 1,056 U/ml. M-CSF was localized in the glandular epithelial cells as well as in the stromal macrophages and the endothelial cells of the ovarian cancers. M-CSF thus appeared to be a marker with high specificity for ovarian cancer.
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PMID:Serum level of macrophage colony-stimulating factor as a marker for gynecologic malignancies. 785 72

The macrophage colony-stimulating factor (CSF-1) is best known as a hematopoietic cytokine important to macrophage activation. Recently, the importance of CSF-1 and its receptor (encoded by the c-fms proto-oncogene) in epithelial ovarian cancer has also been recognized, with overexpression of CSF-1 denoting poor prognosis in ovarian cancer patients. During macrophage activation, CSF-1 promotes urokinase-type plasminogen activator (uPA) activity; in macrophages and in malignant cells of lung, breast, colon, and prostatic origin, uPA activity is strongly correlated with the ability to invade and, in the malignant cells, to metastasize. While there is clear evidence of CSF-1 and uPA expression in primary and metastatic ovarian cancer, the significance of their expression to invasion of these cells has not been explored. We find that all of our ovarian cancer cell lines which we have studied co-express CSF-1 and uPA transcripts and protein. Urokinase expression in these ovarian cancer cell lines correlates with the degree of tumorigenicity in nude mice, with the most virulent tumor resulting from Hey cells, a strong expressor of uPA. We studied the invasion of these primary and established ovarian cancer cells through a Matrigel (reconstituted basement membrane matrix) barrier. The ability of ovarian cancer cells to invade is strongly correlated with endogenous CSF-1 expression (Pearson's correlation, r = 0.91; P = 0.01). A total of 0.90 +/- 0.16% of Bix3 cells (very weak expressor of CSF-1) invaded through the barrier, in contrast to 6.95 +/- 0.75% of Hey cells (strong CSF-1 expressor) and 10.44 +/- 2.33% of Bixler cells (the strongest CSF-1 expressor). We studied the ability of two of the cell lines to invade human laminin and type IV collagen (Bix3, a weak invader of Matrigel, and Hey, a strong invader), to determine (a) whether our results on a Matrigel matrix may represent a relevant model for invasion in humans and (b) whether there is a potential confounding effect from the cytokines and proteases in Matrigel. On this human simple matrix, we confirm that Bix3 is a weakly invasive cell line (0.33 +/- 0.04% invasion) which contrasted to the strongly invasive Hey cell line (8.51 +/- 0.47%). Treatment of Bix3 cells with exogenous CSF-1 stimulates percentage of invasion by 2-fold and results in a similar increase in the level of uPA transcripts and cellular associated uPA antigen. Furthermore, cell surface-bound uPA increased from 74% in the absence of CSF-1 to 100% (fully saturated) in the presence of CSF-1.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Macrophage colony-stimulating factor mediates invasion of ovarian cancer cells through urokinase. 788 68


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