Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05231 (interleukin-6)
 23,907 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

Interleukin-6 is a pleiotropic cytokine with a wide range of effects, including induction of B-cell and cytotoxic T-cell differentiation, and induction of acute phase reactant production by hepatocytes. Interleukin-6 also can act as an autocrine growth factor in malignancy. Various cell types produce interleukin-6, including T and B cells, monocytes, fibroblasts, and some solid tumor cells. In previous work we detected the production of substantial amounts of interleukin-6 by human ovarian cancer cells, including the ovarian cancer cell lines CAOV-3, OVCAR-3, and SKOV-3, and several primary ovarian tumor cultures. In this study we retrospectively examined 90 separate serum specimens for interleukin-6 in 36 patients with epithelial ovarian cancer. The mean serum interleukin-6 concentration of those ovarian cancer patients with macroscopic disease (n = 57) was 0.26 +/- 0.04 U/ml (mean +/- SEM). Healthy adult donors have interleukin-6 serum levels of 0.12 +/- 0.03 U/ml. Sixteen of 21 ovarian cancer patients with macroscopic disease (76%) had elevated (greater than 0.20 U/ml) levels of serum interleukin-6, with levels approaching 1 U/ml in some patients (p less than 0.01). Of those nine patients with bulky tumor (residual greater than 2 cm), eight (89%) had an elevated interleukin-6 level (mean, 0.31 +/- 0.05), while eight of 12 (66%) with minimal residual disease (less than 2 cm) had elevated levels. Only two of 15 (13%) patients who were in clinical remission and who had microscopic disease had elevated values. Of the 36 patients, 22 were CA 125 negative (less than 35 U/ml), and of these, four had elevated interleukin-6 levels. Of the 14 patients with an elevated CA 125 level, 12 (86%) had elevated interleukin-6 levels. In those 16 patients in whom serial levels of interleukin-6 were measured, rising levels were found over a 3 to 4 month interval in nine (56%); this correlated with tumor progression. Furthermore, the subsequent survival of patients was shown to correlate with the level of interleukin-6, such that patients whose levels were elevated greater than 0.20 U/ml interleukin-6 survived a mean of 12.5 months, compared with 27.2 months for patients with normal levels (p less than 0.001). These data support the concept that interleukin-6 may be a useful tumor marker in some patients with epithelial ovarian cancer, as it correlates with the tumor burden, clinical disease status, and survival.
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PMID:Serum interleukin-6 levels correlate with disease status in patients with epithelial ovarian cancer. 201 24

The multifunctional cytokine interleukin-6 (IL-6) is produced by epithelial and mononuclear cells as well as by ovarian carcinoma cells. A prospective study was initiated to evaluate the clinical significance of systemic and local measurements of IL-6 concentrations in 67 patients with ovarian tumors. Eighteen patients who underwent laparotomy for ovarian carcinoma showed elevated levels of IL-6 in the serum as well as in the peritoneal cavity in comparison to patients with benign ovarian tumors. Furthermore, patients with advanced ovarian cancer, according to Figo-Stages III/IV, demonstrated higher IL-6 levels in the serum and ascites, respectively, than patients with Figo-Stages I/II reflecting low tumor burden. The results of the study suggest that IL-6 plays a key role in tumor-host interaction, particularly, in the possible facilitated spread of ovarian cancer cells.
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PMID:Concomitant measurements of interleukin-6 (IL-6) in serum and peritoneal fluid of patients with benign and malignant ovarian tumors. 798 16

In previous work, we saw that interleukin-6 (IL-6), a multifunctional cytokine, is produced by epithelial ovarian cancer cells and that ovarian cancer cells express the IL-6 receptor. Here, we examined the possibility that IL-6 acts as an autocrine growth factor for ovarian cancer cells. Inhibition of IL-6 gene expression by exposure to IL-6 antisense oligonucleotides resulted in greatly decreased cellular proliferation. Exposure of ovarian cancer cell lines (CAOV-3, OVCAR-3, and OC-436), to 1-5 microM of a 15-base single-stranded antisense IL-6 oligodeoxynucleotide, specific for a sequence in the second coding exon of the IL-6 gene, resulted in decreased IL-6 production and a > 80-85% inhibition of cellular proliferation. However, the addition of exogenous IL-6 failed to restore the proliferation of the antisense-treated cells. Antibodies to IL-6 did not consistently inhibit cell growth nor did rIL-6 enhance precursor frequency in a limiting dilution analysis. These results suggest that IL-6 does not directly induce the proliferation of ovarian cancer cells although endogenous IL-6 production is needed for optimal cell growth. As the majority of epithelial ovarian cancers produce IL-6, the direct specific inhibition of IL-6 gene expression is of potential therapeutic value.
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PMID:Growth inhibition of ovarian cancer cells induced by antisense IL-6 oligonucleotides. 848 64

The present study was designed to investigate the growth regulatory effects of cytokines in UT-OC-3 ovarian cystadenocarcinoma cells in vitro. The effects of interleukin-6 (IL-6), interferons alpha (IFN-alpha) and gamma (IFN-gamma), granulocyte-macrophage colony-stimulating factor (GM-CSF), tumour necrosis factor alpha (TNF-alpha), and transforming growth factor beta1 (TGF-beta1) were investigated by (125)I-deoxyuridine ((125)IUdR) incorporation assay. In order to understand better the molecular mechanisms of the observed effects, the activation of DNA-binding proteins was studied by electrophoretic mobility shift assay. In addition, cellular DNA was tested by fragmentation analysis to determine if the most growth inhibitory cytokines are able to induce programmed cell death (apoptosis). After 48h in culture, TGF-beta1, TNF-alpha, IFN-alpha and IL-6 showed a clear inhibitory effect on (125)IUdR incorporation (P<0.005), and IFN-gamma and GM-CSF caused even more significant inhibition (P<0.001). IFN-alpha and IFN-gamma were both growth inhibitory after 72h in culture (P<0.005). Similarly, GM-CSF induced a slight inhibition (P<0.05), whereas TGF-beta1 and TNF-alpha almost blocked DNA synthesis (P<0.001) after 72h. IL-6 had no statistically significant effect on cell proliferation after 72h. Transcription factors AP-1 and NF-kappaB were both constitutively expressed in UT-OC-3 cells. The binding activity of AP-1 was found to be stimulated by the growth inhibitory cytokines, TGF-beta1 and TNF-alpha, and the binding of NF-kappaB was stimulated by TNF-alpha. Apoptosis does not seem to be induced by any of these cytokines in the UT-OC-3 ovarian cancer cell model.
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PMID:Regulation of UT-OC-3 ovarian carcinoma cells by cytokines: inhibitory effects on cell proliferation and activation of transcription factors AP-1 and NF-kappaB. 1075 82

Interleukin-6 (IL-6) is a pleiotropic cytokine that has been shown to regulate immune defense mechanisms and hematopoiesis. In addition, IL-6 may also be involved in malignant transformation and tumor progression. A poor prognosis in patients with multiple myeloma, renal cell carcinoma, ovarian cancer, or prostate cancer has been associated consistently with elevated IL-6 serum levels. The aim of this study was, therefore, to assess IL-6 serum levels in 68 advanced gastrointestinal cancer patients and to correlate them with prognosis. IL-6 serum levels were found to be significantly elevated in cancer patients with respect to controls. Moreover, patients with disseminated cancer displayed significantly higher IL-6 serum levels than patients without apparent metastases. On univariate analysis, both overall survival (OS) and time to disease progression (TTP) were shown to be affected by IL-6 serum levels. However, multivariate analysis failed to demonstrate an independent prognostic significance for IL-6 serum levels while confirming the role of previously established variables, such as performance status, carcinoembryonic antigen (CEA) serum levels, and distant metastases. In conclusion, this study showed that IL-6 serum levels were elevated in advanced gastrointestinal cancer patients and correlated with both OS and TTP. However, they were shown not to be an independent prognostic factor.
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PMID:Interleukin-6 serum level correlates with survival in advanced gastrointestinal cancer patients but is not an independent prognostic indicator. 1117 80

In ovarian cancer patients the poor nutritional status and cachexia are caused by the metabolic effects of the enlarging tumor masses and bowel obstruction. These patients may have a high resting energy expenditure due to increase in Cori cycle activity, glucose and triglyceride-fatty acid cycling and gluconeogenesis. Biochemical mediators of cachexia include cytokines, such as tumor necrosis factor and interleukin-6, and tumor-produced catabolic factors, such as lipid-mobilizing factor, proteolysis-inducing factor, and anemia-inducing factor. Mechanisms involved in the pathogenesis of obstruction may include extrinsic occlusion of the bowel due to pelvic, mesenteric omental masses, or intestinal motility disorders due to infilor tration of the mesentery or bowel muscle and nerves. The relief of malnutrition and cachexia may be attempted through nutritional support, pharmacological approach (megestrol acetate, cyclooxygenase inhibitors) and palliative treatment of bowel obstruction. Very few agents have been demonstrated to have true anticachectic activity, so future research should be addressed to the identification of drugs able to block the activity of tumor-produced catabolic factors. The decision regarding optimum management of bowel obstruction should be individualized. Krebs' and Goplerud's score (based on age, nutritional status, tumor status, ascites, previous chemotherapy and irradiation) seems to offer reliable eligibility criteria for those patients who can benefit from surgery.
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PMID:Malnutrition and cachexia in ovarian cancer patients: pathophysiology and management. 1171 91

Incidence rates of ovarian cancer remain lowest in Asian nations, which consume diets rich in soy products, whereas they remain among the highest in the United States and other Western nations, which consume low amounts of soy foods. The hypothesis of this study is that soy-derived isoflavones inhibit the proliferation of ovarian cancer cells in vitro by regulating cytokine synthesis. Cell proliferation was evaluated by bromodeoxyuridine and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. DNA synthesis of Caov-3 and NIH:OVCAR-3, two ovarian cancer cell lines, was significantly inhibited by genistein or daidzein at dietarily relevant concentrations (10(-8)-10(-10) M). Also, the number of viable cells was significantly lower (45-75%) in all isoflavone-treated groups than in the control group (P < 0.01). The addition of ICI-182780, an estrogen antagonist, blocked these inhibitory effects. In addition, interleukin-6 synthesis by these two cell lines was inhibited by genistein or daidzein; production was decreased by approximately 20% compared with the control group (P < 0.05). In contrast, transforming growth factor-beta 1 production in ovarian cancer cells incubated with genistein or daidzein was significantly greater, i.e., by approximately 30%, than in the control group (P < 0.05). Addition of ICI-182780 also neutralized the effects of isoflavones on the production of these two cytokines by ovarian cancer cells. In summary, genistein and daidzein independently modify cytokine production and reduce ovarian cancer cell proliferation via, at least in part, an estrogen receptor-dependent pathway.
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PMID:Isoflavones inhibit proliferation of ovarian cancer cells in vitro via an estrogen receptor-dependent pathway. 1209 20

Interleukin-6 (IL-6) is reportedly increased in serum and CSF from acute stroke patients. However, the cellular origin and possible role of IL-6 in CNS after stroke are unclear. We describe a woman with recurrent stroke, disseminated intravascular coagulation (DIC) and non-bacterial thrombotic endocarditis (NBTE) caused by ovarian cancer (Trousseau syndrome). The patient died 50 days after the final episode of cerebral embolism. The immunohistochemical study revealed IL-6 protein to have been expressed both in cerebral neurons spared from ischemic insult and in epithelial cells of the ovarian tumor. We speculate that IL-6 produced in ovarian cancer may be associated with the hypercoagulable state and the development of NBTE in this patient. In contrast, IL-6 induction in cerebral neurons may contribute to the survival of these neurons after a stroke.
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PMID:Expression of interleukin-6 in cerebral neurons and ovarian cancer tissue in Trousseau syndrome. 1236 26

The polyphenolic compounds curcumin and quercetin increased sensitivity of ovarian cancer cells (CAOV3 and SKOV3) to cisplatin. The effect was obtained when the compounds were added simultaneously with cisplatin, as well as when they were added 24 h before. High serum levels of certain cytokines, for example interleukin-6 (IL-6), have been associated with poor prognosis and cisplatin resistance in various forms of cancer. Furthermore, it has been hypothesized that cytokines may increase proliferation, metastasis, and stimulate production of detoxification enzymes and multi-drug resistant proteins. Curcumin inhibits the production of many cytokines. The two ovarian cell lines differ significantly in IL-6 production, and correspondingly the high producer, CAOV3, was less susceptible to cisplatin. Curcumin inhibited the production of IL-6 in this cell suggesting that one of the mechanisms for synergy between cisplatin and curcumin was by reducing the autologous production of IL-6. However, the synergy was also observed in the low IL-6 producer, SKOV3, indicating that the action was most probably a result of multiple targeting. In sum, this study suggests that the compounds, curcumin and quercetin, potentially may be useful for enhancing drug sensitivity in certain cancer.
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PMID:Inhibition of growth and sensitization to cisplatin-mediated killing of ovarian cancer cells by polyphenolic chemopreventive agents. 1244 90


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