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Interleukin-6 as a ...
Interleukin-6 as a Therapeutic Target in Human Ovarian Cancer
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Coward, Jermaine (författare)
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Kulbe, Hagen (författare)
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Chakravarty, Probir (författare)
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Leader, David (författare)
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Vassileva, Vessela (författare)
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Leinster, D. Andrew (författare)
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Thompson, Richard (författare)
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Schioppa, Tiziana (författare)
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Nemeth, Jeffery (författare)
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Vermeulen, Jessica (författare)
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Singh, Naveena (författare)
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Avril, Norbert (författare)
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Cummings, Jeff (författare)
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Rexhepaj, Elton (författare)
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- Jirström, Karin (författare)
- Lund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine
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Gallagher, William M. (författare)
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Brennan, Donal J. (författare)
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McNeish, Iain A. (författare)
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Balkwill, Frances R. (författare)
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(creator_code:org_t)
- 2011
- 2011
- Engelska.
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Ingår i: Clinical Cancer Research. - 1078-0432. ; 17:18, s. 6083-6096
- Relaterad länk:
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http://dx.doi.org/10...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Purpose: We investigated whether inhibition of interleukin 6 (IL-6) has therapeutic activity in ovarian cancer via abrogation of a tumor-promoting cytokine network. Experimental Design: We combined preclinical and in silico experiments with a phase 2 clinical trial of the anti-IL-6 antibody siltuximab in patients with platinum-resistant ovarian cancer. Results: Automated immunohistochemistry on tissue microarrays from 221 ovarian cancer cases showed that intensity of IL-6 staining in malignant cells significantly associated with poor prognosis. Treatment of ovarian cancer cells with siltuximab reduced constitutive cytokine and chemokine production and also inhibited IL-6 signaling, tumor growth, the tumor-associated macrophage infiltrate and angiogenesis in IL-6-producing intraperitoneal ovarian cancer xenografts. In the clinical trial, the primary endpoint was response rate as assessed by combined RECIST and CA125 criteria. One patient of eighteen evaluable had a partial response, while seven others had periods of disease stabilization. In patients treated for 6 months, there was a significant decline in plasma levels of IL-6-regulated CCL2, CXCL12, and VEGF. Gene expression levels of factors that were reduced by siltuximab treatment in the patients significantly correlated with high IL-6 pathway gene expression and macrophage markers in microarray analyses of ovarian cancer biopsies. Conclusion: IL-6 stimulates inflammatory cytokine production, tumor angiogenesis, and the tumor macrophage infiltrate in ovarian cancer and these actions can be inhibited by a neutralizing anti-IL-6 antibody in preclinical and clinical studies. Clin Cancer Res; 17(18); 6083-96. (C) 2011 AACR.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
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Coward, Jermaine
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Kulbe, Hagen
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Chakravarty, Pro ...
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Leader, David
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Vassileva, Vesse ...
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Leinster, D. And ...
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visa fler...
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Thompson, Richar ...
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Schioppa, Tizian ...
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Nemeth, Jeffery
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Vermeulen, Jessi ...
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Singh, Naveena
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Avril, Norbert
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Cummings, Jeff
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Rexhepaj, Elton
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Jirström, Karin
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Gallagher, Willi ...
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Brennan, Donal J ...
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McNeish, Iain A.
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Balkwill, France ...
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