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)

Interleukin-6 (IL-6) is a multifunctional cytokine which provides multiple signals on various tissues and cells. In addition, IL-6 is produced by some human renal carcinoma cell lines in vitro and is expressed in a majority of primary renal cell carcinoma (RCC). Serum IL-6 influence the response to immunotherapy. IL-6 appears as a target for rational drug design highly promising for development of new cancer therapies. IL-6 effects are mediated by Stat. Stat (Signal transducers and activators of transcription) signaling pathways represent novel molecular targets for therapeutic implications in metastatic renal cell carcinoma. Inhibitors of Stat signaling pathway will not only block tumor growth by inducing apoptosis, but may also increase the sensitivity of tumors to conventional treatment (immunotherapy). The processes involved in tumor associated angiogenesis should lead to compounds able to interfere with angiogenesis. Il-6 has been implicated in the osteoclastic bone resorption and hypercalcemia associated with metastatic RCC. Different agents were shown to be effective in treating lytic bone disease mediated by osteoclast activation: bisphosphonates and osteoprotegerin.
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PMID:[Interleukin-6 and bone metastasis of renal cancer: molecular bases and therapeutic implications]. 1140 May 11

A 59-year-old man who had received chronic hemodialysis developed left occipital pain and hypoglossal nerve palsy. He was diagnosed as having skull base metastasis from renal cell carcinoma related to acquired cystic kidney. Retrospective analysis revealed the patient had had elevated serum C-reactive protein and alkaline phosphatase levels before the symptoms appeared. Radiotherapy to the skull base relieved the pain. Finally he died with generalized metastases. Serum interleukin-6 levels measured during admission had been elevated, and interleukin-6 mRNA was detected in the autopsy specimen of renal cell carcinoma. Interleukin-6 might be involved in the etiology of paraneoplastic signs.
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PMID:Renal cell carcinoma with skull base metastasis preceded by paraneoplastic signs in a chronic hemodialysis patient. 1157 58

Thalidomide is reported to suppress levels of several cytokines, angiogenic and growth factors including TNF-alpha, basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6). The resulting anti-angiogenic, immunomodulatory and growth suppressive effects form the rationale for investigating thalidomide in the treatment of malignancies. We have evaluated the use of high-dose oral thalidomide (600 mg daily) in patients with renal carcinoma. 25 patients (all men; median age, 51 years; range 34-76 years) with advanced measurable renal carcinoma, who had either progressed on or were not suitable for immunotherapy, received thalidomide in an escalating schedule up to a maximum dose of 600 mg daily. Treatment continued until disease progression or unacceptable toxicity were encountered. 22 patients were assessable for response. 2 patients showed partial responses (9%; 95% CI: 1-29), 7 (32%; 95% CI: 14-55) had stable disease for more than 6 months and a further 5 (23%; 95% CI: 8-45) had stable disease for between 3 and 6 months. We also measured levels of TNF-alpha, bFGF, VEGF, IL-6 and IL-12 before and during treatment. In patients with SD > or = 3 months or an objective response, a statistically significant decrease in serum TNF-alpha levels was demonstrated (P = 0.05). The commonest toxicities were lethargy (> or = grade II, 10 patients), constipation (> or = grade II, 11 patients) and neuropathy (> or = grade II, 5 patients). Toxicities were of sufficient clinical significance for use of a lower and well tolerated dose of 400 mg in currently accruing studies.
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PMID:The treatment of advanced renal cell cancer with high-dose oral thalidomide. 1159 64

In local or metastatic cancer, a prognostic tumour marker could be a valuable tool in the selection of different treatments. In renal cell cancer (RCC) no such markers have been available. We therefore evaluated the association between several pretreatment serum markers, tumour classification and short term survival in RCC patients. Serum samples were collected before surgery and three months thereafter from 24 RCC patients. Interleukin-6 (IL-6), IL- 12, soluble IL-2 receptor (sIL-2R) and intercellular adhesion molecule-1 (sICAM-1) were measured in serum samples using specific commercial enzyme immunoassay kits. Serum IL-6, sIL-2R and sICAM-1 levels before nephrectomy were significantly higher in non-local tumours than in local ones (mean IL-6 53 pg/ml versus 6.3 pg/ml, and sICAM-1 443 ng/ml versus 290 ng/ml, sIL-2R 3779 pg/ml versus 1796 pg/ml). In contrast, IL-12 levels were higher in local tumours (148 versus 102 pg/ml) and the levels increased significantly (P < 0.005) after removal of the primary tumour in patients with local disease. All patients with local tumours had normal IL-6 values, while only one with a non-local tumour had IL-6 levels below 10 pg/ml. In addition, IL-6 and sICAM-1 levels before operation were significantly higher in patients with short (less than one year) survival (p=0.007 to IL-6 and p=0.006 to sICAM-1). In contrast, patients with shorter survival had significantly lower IL-12 (p=0.03) levels. Our findings suggest that RCC induces changes in several immunological parameters. These soluble immunological factors, IL-6, IL-12, sIL-2R and sICAM-1, might have a role as prognostic factors in RCC.
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PMID:Soluble immunological parameters and early prognosis of renal cell cancer patients. 1187 46

As regulators of malignant cell behaviour and communication with stroma, cytokines have proved useful in understanding cancer biology and developing novel therapies. In renal cell carcinoma, patients with inflammatory reactions are known to have poor prognosis. In order to elucidate the relation between renal cell carcinoma and the host, serum levels of inflammatory cytokines, interleukin-6, tumour necrosis factor alpha, interleukin-1beta, were measured. One hundred and twenty-two patients with renal cell carcinoma and 21 healthy control subjects were studied, and serum cytokine levels were measured using a highly sensitive ELISA kit. As a result, in the control group, interleukin-6, tumour necrosis factor alpha and interleukin-1beta levels were 1.79+/-2.03, 2.74+/-0.94 and 0.16+/-0.17 pg ml(-1), respectively. In the renal cell carcinoma patients, they were 8.91+/-13.12, 8.44+/-4.15 and 0.53+/-0.57 pg ml(-1), respectively, and significantly higher. In the comparison of stage, interleukin-6 level was significantly higher in the stage IV group compared to the other stage groups including the control group, while tumour necrosis factor alpha level was significantly higher in each stage group compared to the control group. As for grade, interleukin-6 level was significantly higher in the grade 3 group compared to the control, grade 1 and grade 2 groups, while tumour necrosis factor alpha level was significantly higher in each grade group compared to the control group. All cytokines had a positive correlation with tumour size. In regard to the correlation with CRP, all cytokines had a positive correlation with CRP, while interleukin-6 had a particularly strong correlation. In conclusion, interleukin-6 may be one of the factors for the poor prognosis of patients with renal cell carcinoma. In addition, tumour necrosis factor alpha may be useful in the early diagnosis of renal cell carcinoma and post-operative follow-up.
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PMID:Interleukin-6, tumour necrosis factor alpha and interleukin-1beta in patients with renal cell carcinoma. 1198 70

Positive inflammatory reactions in an aggressive phenotype are typical features of renal cell carcinoma (RCC). Although a high blood level of inflammatory cytokines, such as interleukin-6, interleukin-8, and tumor necrosis factor-alpha, has been observed in these patients, the mechanisms underlying this clinical phenomenon remain to be elucidated. CCAAT/enhancer binding protein (C/EBP) family are transcription factors which play a role in cell differentiation and inflammatory reactions. Among these, C/EBP-beta induces a variety of cytokines and thus may play a role in the pathogenesis of RCC. We studied the activation of C/EBP-beta determined by electrophoretic mobility shift assay in nine RCC cell lines and 44 tissue samples. Six cell lines showed an activation of C/EBP-beta, whereas three cell lines did not, and two of these three had no expression at all of C/EBP-beta protein. Of 44 tissue samples, 12 (27.3%) showed a >200% increase in the activity compared with the corresponding normal kidney tissues. Locally advanced cases had a significantly higher rate of increased C/EBP-beta activity (5 of 8 = 62.5% in advanced cases versus 7 of 36 = 19.4% in localized cases). Especially, all four cases with renal vein invasion had an increased C/EBP-beta activity. These data suggest that the increased activation of C/EBP-beta may contribute to promote tumor invasiveness and render a malignant phenotype of RCC, although it needs to be validated in a larger series.
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PMID:Increased activation of CCAAT/enhancer binding protein-beta correlates with the invasiveness of renal cell carcinoma. 1263 1

Although an aggressive phenotype of renal cell carcinoma (RCC) is known to frequently be associated with inflammatory paraneoplastic syndrome including serum C-reactive protein (CRP) elevation, the molecular mechanism underlying this clinical phenomenon as well as what yields the malignant phenotype leading to the progression of RCC has yet to be elucidated. Based on the increased level of inflammatory cytokines such as interleukin-6 in advanced cases of RCC, a cytokine-inducible transcription factor, namely, nuclear factor-kappa B (NF-kappa B), may thus play a role in the progression of RCC. An electrophoretic mobility shift assay (EMSA) was carried out to determine the activity of NF-kappa B. Out of 45 cases of RCC, 15 cases (33%) showed a >200% increase in the NF-kappa B activity in comparison with that seen in normal renal tissue. In locally advanced cases (> or =pT3), 64% (9/14) showed an increased activity whereas it was only observed in 19% (6/31) of localized cases (< or =pT2). All three cases with metastases showed an increased NF-kappa B activity. The NF-kappa B activity determined by EMSA was further confirmed by an immunohistochemical analysis using an antibody recognizing the nuclear localization signal (NLS) in p65 subunit of NF-kappa B. The serum CRP elevation correlated with the increased NF-kappa B activation, and therefore NF-kappa B may be a causative transcription factor of inflammatory paraneoplastic syndrome. A high NF-kappa B activity was associated with an increased expression of both the p65 and p50 subunits of NF-kappa B and a concomitant decreased expression of I kappa B alpha. No functional mutations of the I kappa B alpha gene were detected. The NF-kappa B activity may therefore be a late event in carcinogenesis related to tumor development, thereby representing a possible molecular target in the treatment of RCC.
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PMID:Increased nuclear factor-kappa B activation is related to the tumor development of renal cell carcinoma. 1266 95

We established a new renal carcinoma cell line that produces parathyroid hormone-related protein (PTHrP) and interleukin-6 in culture. The cellular production of PTHrP was confirmed by Northern blot analysis and immunofluorescence examination. Bone and lung metastases occurred simultaneously 3.5 years after surgery. The patient did not show hypercalcemia at this time, despite the presence of multiple osteolytic metastases. About 7 months after bone metastasis was first shown, serum PTHrP was detected by means of an immunoradiometric assay and the calcium level was found to be elevated to 3.29 mmol/l. The hypercalcemia was successfully controlled by i.v. administration of bisphosphonates.
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PMID:Hypercalcemia upon recurrence of renal cell carcinoma producing parathyroid hormone-related protein. 1277 88

Tumor necrosis factor alpha (TNFalpha) and TNFalpha receptor mRNA expression, the effects of TNFalpha on DNA synthesis and cell proliferation as well as its effects on interleukin-6 (IL-6) production and expression in renal cell carcinoma (RCC) were studied using RCC cell lines. The effects of TNFalpha on DNA synthesis and IL-6 production were also studied using short-term established RCC cell lines. A total of 8 cell lines, 4 RCC cell lines (RC-2, RGB, 14T, 4T) and 4 cell lines established at our laboratory (OCUU-1, 2, 4, 5), as well as 10 short-term established RCC cell lines were used. When TNFalpha and TNFalpha receptor mRNA expression was examined by RT-PCR, p55 TNF receptor mRNA expression was observed while TNFalpha and p75 TNF receptor mRNA expression was not observed in all cell lines. When the effects of TNFalpha on DNA synthesis were studied by [3H]-thymidine incorporation assay, DNA synthesis was induced in RGB, 14T, 4T, OCUU-2 and OCUU-4 by adding 10 and 100 pg/ml of TNFalpha while it was not induced in RC-2 and OCUU-5 at all concentrations. When its effects on cell proliferation were evaluated by MTT assay, cell proliferation was observed in RGB, 14T and 4T at TNFalpha concentration of 10 pg/ml and in RGB, 14T, 4T, OCUU-4 and OCUU-5 at TNFalpha concentration of 100 pg/ml. However, cell proliferation was not detected in RC-2 and OCCU-2 at any concentration. When the effects of TNFalpha on IL-6 production were studied by ELISA, IL-6 production was induced in RC-2, RGB, 14T, OCUU-1, OCUU-2 and OCUU-5 while not in 4T and OCUU-4. When its effects on IL-6 expression were examined by Northern blot analysis, the results were similar to those obtained by ELISA. As for the 10 short-term established RCC cell lines, DNA synthesis and IL-6 production were induced with the addition of TNFalpha. These results suggested that TNFalpha induced cell proliferation in RCC.
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PMID:Effects of tumor necrosis factor alpha in renal cell carcinoma. 1453 24

Interleukin-2 (IL-2) has some antitumor activity in patients with renal cell carcinoma. It has been noted that response to IL-2 and prognosis may be adversely affected by elevated serum levels of C-reactive protein (CRP) or interleukin-6 (IL-6). We used thalidomide to treat patients with cancer-induced cachexia and noted that the drug significantly reduced serum levels of CRP and IL-6 to normal or near normal levels in a substantial fraction of patients. We tested whether thalidomide might potentiate the response of patients with renal cell carcinoma to IL-2. Four patients with metastatic renal cell carcinoma and high serum levels of CRP and IL-6 who had experienced disease progression on IL-2 were retreated with the same IL-2 regimen combined with thalidomide 300 mg p.o. daily. Two patients achieved good partial responses and 2 patients had prolonged disease stabilization with the combination of IL-2 plus thalidomide. The regimen was well tolerated without increased IL-2-associated toxicity. Reduction of serum CRP or IL-6 levels with thalidomide may enhance the responsiveness of renal cell carcinoma to IL-2. A Phase II study of the combination is in order. It is possible that the thalidomide-induced normalization of serum acute phase proteins might improve the response of other types of malignancy to IL-2 or other immune-based therapies.
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PMID:Thalidomide reduces serum C-reactive protein and interleukin-6 and induces response to IL-2 in a fraction of metastatic renal cell cancer patients who failed IL-2-based therapy. 1506 91


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