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)

Typically, ovarian cancer remains restricted to the peritoneal cavity. Because of this unique localization, the study of ovarian cancer is particularly suitable for immune analysis and for the development of immunotherapy. Here we report that peritoneal fluid from patients with ovarian or other intra-abdominal cancers contained significantly elevated levels of interleukin 10 (IL-10) (542 +/- 77 pg/ml, N = 35), compared with peritoneal fluid from patients with benign gynecological conditions (34.2 +/- 7.5 pg/ml, N = 63) (P < 0.001). Peritoneal fluid IL-10 levels did not correlate with histology, tumor stage, grade, or prognosis. IL-10 levels were also elevated in the serum of patients with intra-abdominal cancer (1353 +/- 906, N = 8). Established ovarian cancer cell lines (N = 5) did not produce any detectable IL-10. Investigation of the cell surface phenotype of the cells in the peritoneal cavity indicated the presence of significant amounts of activated immune cells. The presence of cytokines such as IL-10 in the peritoneal cavity of ovarian cancer bearing patients could be important in the growth and development of cancer, more specifically, in relation to host immune responsiveness.
Cytokine 1992 Sep
PMID:Presence of interleukin 10 (IL-10) in the ascites of patients with ovarian and other intra-abdominal cancers. 142 Oct

Ascites obtained from human ovarian cancer patients contains material(s) that inhibit the cytolytic activity of tumor necrosis factor (TNF) and lymphotoxin (LT) in vitro. These inhibitor(s) are found in ascites from ovarian cancer patients and are detected in very low amounts in the ascites from patients with nonmalignant hepatic disease. These ascites TNF/LT blocking factors are heat sensitive and heterogeneous with respect to molecular weight. Kinetic studies indicate these factors inhibited cytolysis at the stage of TNF/LT interaction with membrane receptors on L929 cells. Because TNF and LT are key cytokines in host cell-mediated antitumor mechanisms, factor(s) that inhibit these cytokines could have a profound effect on the tumor host interaction and their presence in the ascitic fluid, should be considered before designing clinical trials that employ intraperitoneal administration of TNF or LT for immunotherapy of ovarian cancer.
Lymphokine Cytokine Res 1991 Jun
PMID:Identification of tumor necrosis factor and lymphotoxin blocking factor(s) in the ascites of patients with advanced and recurrent ovarian cancer. 165 48

We have demonstrated the presence of the 55- and 75-kDa receptor for tumor necrosis factor (TNF) and lymphotoxin (LT) (TNF-R) in serum, and ascites from women with ovarian cancer. The present studies were initiated to begin to examine the possible cellular source of these receptors in women with ovarian cancer. Human ovarian tumor cells (PA-1) were cocultured for 24-48 hr with various levels of recombinant human cytokines (IL-1 beta, IL-4, IFN-gamma) and the supernatants were assayed by ELISA for the soluble forms of each receptor. PA-1 cells spontaneously release the 55-kDa TNF-R and low levels of the 75-kDa TNF-R. The release of both 55- and 75-kDa TNF-R was stimulated when PA-1 cells were cultured with IL-1 beta and IFN-gamma but unaffected by IL-4. The level of 55-kDa TNF-R was elevated slightly over spontaneous release but the level of 75-kDa TNF-R increased dramatically. IFN-gamma was the most potent stimulator of receptor release particularly of the 75-kDa TNF-R. IFN-gamma also induced increased expression of cell membrane TNF-R measured by binding of 125I-labeled TNF. Membrane TNF-Rs which were induced by IFN-gamma were the 75-kDa type, because TNF binding was blocked by anti-75-kDa TNF-R antibody. These data suggest that IFN-gamma selectively induced release and expression of 75-kDa TNF-Rs.
Lymphokine Cytokine Res 1993 Aug
PMID:Release of soluble TNF/LT receptors from a human ovarian tumor cell line (PA-1) by stimulation with cytokines in vitro. 821 97

Malignant ascites of epithelial ovarian cancer patients contains high levels of interleukin 6 (IL-6). The present study was conducted to compare the secretion of IL-6 by seven different human ovarian cancer cell lines (OVCA) and cultured human peritoneal mesothelial cells (HPMC) and to examine the regulation of its production by other cytokines. IL-6 was detected in supernatant medium of all mesothelial cell cultures (8/8) and 6/7 ovarian cancer cell lines. Levels of IL-6 secreted by HPMC (median 27,100 pg/1 x 10(5) cells; range 3870-168,200) were 590-fold higher (P < 0.01) than those secreted by OVCA (median 46 pg/1 x 10(5) cells; range 0-16,450). Treatment with TNF-alpha or IL-1 beta (both 10 ng/ml) for both types of cells and both cytokines resulted in a significant (P < 0.05) elevation of IL-6 production. In OVCA IL-6 secretion was increased 7- and 39-fold and in HPMC 6- and 8-fold, respectively. Under TNF-alpha treatment IL-6-levels secreted by HPMC were 149-fold higher (P < 0.01) than those generated by OVCA. Similarly, IL-1 beta-induced IL-6 levels were 102-fold higher in HPMC (median 288,800 pg/1 x 10(5) cells; range 93,125-552,800) than in OVCA. IFN-gamma (10 ng/ml) increased IL-6 generation in OVCA (6-fold) but not HPMC. The proliferation of both cell types however, was significantly (P < 0.05) inhibited by IFN-gamma. Our results suggest that peritoneal mesothelial cells may be a prominent source of IL-6 in ovarian cancer-related ascites.
Cytokine 1995 Aug
PMID:IL-6 secretion by human peritoneal mesothelial and ovarian cancer cells. 858 Mar 70

We defined a cytokine mRNA profile of 12 ovarian cancer biopsies, 10 normal/benign biopsies, six ovarian cancer cell lines and three ovarian cancer xenografts, using RT-PCR. The profile, based on screening for 25 cytokines and 12 receptor mRNAs, was rich in growth factors, pro-inflammatory cytokines and chemokines, but weak in lymphocyte-associated cytokines. The pattern was unique to ovarian tissue, but similar in normal, benign and malignant biopsies, with > 80% samples expressing 16 cytokines in common. Fourteen of these were also expressed by > 65% cell lines, but fewer were detected in xenografts. Potential autocrine loops existed for IL-1, IGF-1, M-CSF, GM-CSF and TNF-alpha. IL-4 and IFN-gamma receptors were expressed in absence of ligand. Chemokines RANTES, MIP-1 alpha and MIP-1 beta were expressed in biopsies, but were rarely detected in cell lines and absent from xenografts. IGF-1 and its receptor was expressed in every sample, as was IFN-gamma receptor. Another 10 cytokine mRNAs and six receptors were expressed in > 80% samples. These may contribute to key survival/growth loops. Similarities between normal and malignant biopsies suggest that analogous processes of remodelling and repair occur. RT-PCR proved a rapid, reproducible screen, but further assays are required to detect quantitative differences between normal and malignant tissues and tumour models.
Cytokine 1996 Jul
PMID:A cytokine profile of normal and malignant ovary. 889 39

The combination of Tumour Necrosis Factor (TNF) and mitoxantrone was evaluated for potential chemotherapeutic effect against a human ovarian cancer cell line A2774 hetero-transplanted in female nude mice. Both antitumour efficacy (relative survival and reduction of ascites) and toxicity (weight loss and liver toxicity) of TNF alone, mitoxantrone alone or TNF + mitoxantrone were evaluated. A significant difference (P < 0.002) was observed only among animals bearing tumours treated with mitoxantrone (0.012 mg/Kg) + TNF (5 x 10(5) U/Kg) and controls. No cytotoxic effects were observed for this combination. These observations provide a rationale for further evaluation of TNF + mitoxantrone based regimes for the treatment of recurrent ovarian cancer.
Cytokine 1996 Apr
PMID:Tumour necrosis factor enhances the therapeutic effect of mitoxantrone in human ovarian cancer xenograft. 916 24

The cytokine tumour necrosis factor alpha (TNF-alpha) is implicated in the regulation of diverse gynaecological cell types, its biological activity being potentially mediated by two distinct cell surface receptors (TNFR) of molecular weight 55 and 75 kDa, respectively. In this study the sensitivity to the growth regulatory properties of TNF-alpha of a panel of human cervical, endometrial and ovarian cancer cell lines was investigated in relation to the expression and biological activity of the 55- and 75-kDa receptor. There was no evidence of expression or function of the 75-kDa receptor in any of the cell lines tested. The expression and biological activity of the 55-kDa receptor was demonstrated in each TNF sensitive cell line, with one exception, the HOG-1 cervical cancer cell line. The data suggest that the 55-kDa receptor mediates the cellular response to TNF-alpha in sensitive gynaecological cancer cell lines but raises the possibility of the presence of a distinct receptor in HOG-1 cells.
Cytokine 1998 Jun
PMID:The growth response to tumour necrosis factor alpha of human gynaecological cancer cell lines. 963 29

A newly described subset of monocytes has been identified in peritoneal exudate cells (PEC) from the malignant ascites from patients with ovarian cancer. These cells were characterized by the production of IL-10 and TGF-beta2, but not IL-12, IL-1alpha, or TNF-alpha, and they expressed CD14, CD16, and CD54, but not HLA-DR, CD80, CD86, CD11a, CD11b, or CD25 cell surface Ags. Since this subset of monocytes could affect the modulation of tumor immune responses in vivo, studies were undertaken to determine their effect on the activation and proliferation of autologous T cells from the peritoneal cavity of patients with ovarian carcinoma. Expression of cytokine-specific transcripts in T cells was determined by RT-PCR. Transcripts for the following cytokines were detected in patient specimens that also contained the IL-10-producing monocytes IL-2 (12 of 17 specimens), GM-CSF (9 of 17 specimens), IFN-gamma (6 of 17 specimens), and TNF-alpha (4 of 17 specimens). Cytokine production by T cells was determined by intracellular flow cytometry and by ELISA. IL-2 and IFN-gamma proteins, unlike their transcripts, were detected only in specimens that lacked IL-10-producing monocytes. IL-10-producing monocytes cocultured with autologous T cells inhibited the proliferation of the T cells in response to PHA. However, T cells cocultured with PEC from which the IL-10-producing monocytes had been removed did not inhibit T cell proliferation. Moreover, the inhibition of T cell proliferation by IL-10-producing monocytes could be reversed by adding neutralizing Abs to both IL-10R and TGF-beta2. These results suggest that this subset of monocytes may modulate immune responses by inhibiting T cell proliferation and cytokine protein production.
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PMID:Identification of an IL-10-producing HLA-DR-negative monocyte subset in the malignant ascites of patients with ovarian carcinoma that inhibits cytokine protein expression and proliferation of autologous T cells. 1057 Mar 18

Adoptive immunotherapy with immune effector cells has proved to be potent for treatment of tumors, however neither the attendant criteria for potential clinical efficacy of the injected cells, nor the method to prepare these cells are presently well established. Our procedure of collecting lymphocytes from biological samples, was based on the use of low IL-2 concentrations (90 to 150 IU/ml) and on the stringent separation of lymphocytes from tumor cells at the very early stages of their outgrowth in culture. When lymphocytes were derived from tumor biopsies (TIL), we observed differences depending on the histological type of tumor. In renal cell carcinoma, natural killer cells were expanded in 4/11 biopsies contrary to what was observed in breast cancer (92 +/- 5% of T lymphocytes from 9 biopsies). The outgrowth of lymphocytes from breast tumors was slower and lower than from renal carcinomas. The autologous tumor cell line was more difficult to obtain from breast carcinoma (23%) than from renal cell carcinoma (61%) biopsies. For ovarian cancer, short-term culture of tumor cells could be obtained for half of the tumor-invaded biological samples. Eight of the 23 tumor-derived cultures contained more than 40% CD8 T. TIL were consistently cytolytic each time they could be evaluated. For ascitic and pleural fluids, data were of similar range. In ascitic-derived cultures, tumor cells and antigen-presenting cells are present and can be supposed to rechallenge T cells with tumor antigens. Lymphocytes derived from lymph nodes could be expanded to a larger number than TIL. However, only 1/18 of these cultures contained more than 40% CD8 T. The presence of few tumor cells in this culture was in favor of significant specific and non-specific cytotoxicity in RCC lymph node cultures and higher percentages of CD8 T in breast cancer lymph nodes. Correlations could not be established between CD8 T percentages and specific in vitro cytotoxicity in our polyclonal populations. Our conclusion is that phenotypic and functional quality of lymphocytes is of interest when the T cells are derived 1) from tumors (RCC, breast or ovarian cancer) and isolated very early to avoid inhibitor factors secreted from tumor cells or 2) from lymph nodes and ascitic and pleural fluids when very few tumor cells are co-cultivated with lymphocytes at initial steps of culture. Final expansion to a number of lymphocytes suitable for therapy (> 109) could be attained in a second step of the procedure by the use of 1,000 IU/ml IL-2 each time it was assayed with 50.106 lymphocytes. In view of these data it appears that phenotypic and functional changes occur during culture depending on the presence of a particular ratio of tumor antigens. This could be artificially reproduced.
Eur Cytokine Netw 2000 Jun
PMID:Interleukin-2 expanded lymphocytes from lymph node and tumor biopsies of human renal cell carcinoma, breast and ovarian cancer. 1090

The 2',5'-oligoadenylate (2-5A) system is an interferon (IFN)-regulated RNA decay pathway that provides innate immunity against viral infections. The biologic action of the 2-5A system is mediated by RNase L, an endoribonuclease that becomes enzymatically active after binding to 2-5A. RNase L is also implicated in mediating apoptosis in response to both viral and nonviral inducers. To study the cellular effects of RNase L activation directly, 2-5A was transfected into the human ovarian cancer cell line, Hey1B. Activation of RNase L by 2-5A resulted in specific 18S rRNA cleavage and induction of apoptosis, as measured by TUNEL and annexin V binding assays. In contrast, the dimeric form of 2-5A, ppA2'p5'A, neither activated RNase L nor caused apoptosis. Treatment with IFN-beta prior to 2-5A transfection enhanced cellular RNase L levels (< or = 2.2-fold) and increased the proportion of cells undergoing apoptosis (by < or =40%). However, rRNA cleavages after 2-5A transfections were not enhanced by IFN-beta pretreatments, indicating that basal levels of RNase L were sufficient for this activity. Apoptosis in response to RNase L activation was accompanied by cytochrome c release from mitochondria. Induction of apoptosis by either 2-5A alone or by the combination of 2-5A and IFN-beta was effectively blocked with either the pancaspase inhibitor, Z-VAD-fmk, or with the caspase 3 inhibitor, DEVD-fmk. Therefore, activation of RNase L by 2-5A leads to cytochrome c release into the cytoplasm and then to caspase activation and apoptosis. These results suggest potential uses for 2-5A in augmenting the anticancer activities of IFN.
J Interferon Cytokine Res 2000 Dec
PMID:Caspase-dependent apoptosis by 2',5'-oligoadenylate activation of RNase L is enhanced by IFN-beta. 1115 76


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