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BCG-induced cytokin...
BCG-induced cytokine release in bladder cancer cells is regulated by Ca2+ signaling
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- Ibarra, Cristian (author)
- Karolinska Inst, Dept Med Biochem & Biophys, SE-17177 Stockholm, Sweden
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- Karlsson, Marie (author)
- Karolinska Inst, Dept Med Biochem & Biophys, SE-17177 Stockholm, Sweden
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- Codeluppi, Simone (author)
- Karolinska Institutet
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- Varas-Godoy, Manuel (author)
- Karolinska Inst, Dept Med Biochem & Biophys, SE-17177 Stockholm, Sweden;Univ Los Andes, Ctr Invest Biomed, Fac Med, Santiago, Chile
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- Zhang, Songbai (author)
- Karolinska Inst, Dept Med Biochem & Biophys, SE-17177 Stockholm, Sweden
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- Louhivuori, Lauri (author)
- Karolinska Institutet
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- Mangsbo, Sara, 1981- (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för farmaceutisk biovetenskap
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- Hosseini, Arad (author)
- Karolinska Univ Hosp, Dept Mol Med & Surg, Stockholm, Sweden
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- Soltani, Navid (author)
- Karolinska Inst, Dept Med Biochem & Biophys, SE-17177 Stockholm, Sweden
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- Kaba, Rahim (author)
- Karolinska Inst, Dept Med Biochem & Biophys, SE-17177 Stockholm, Sweden
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- Lundgren, T. Kalle (author)
- Karolinska Institutet
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- Hosseini, Abolfazl (author)
- Karolinska Univ Hosp, Dept Mol Med & Surg, Stockholm, Sweden
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- Tanaka, Nobuyuki (author)
- Karolinska Inst, Dept Med Biochem & Biophys, SE-17177 Stockholm, Sweden;Keio Univ, Sch Med, Dept Urol, Tokyo, Japan
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- Oya, Mototsugu (author)
- Keio Univ, Sch Med, Dept Urol, Tokyo, Japan
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- Wiklund, Peter (author)
- Karolinska Institutet
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- Miyakawa, Ayako (author)
- Karolinska Institutet
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- Uhlen, Per (author)
- Karolinska Institutet
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(creator_code:org_t)
- 2018-12-13
- 2019
- English.
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In: Molecular Oncology. - : WILEY. - 1574-7891 .- 1878-0261. ; 13:2, s. 202-211
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Abstract
Subject headings
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- Bacillus Calmette-Guerin (BCG) is widely used in the clinic to effectively treat superficial urinary bladder cancer. However, a significant proportion of patients who fail to respond to BCG risk cystectomy or death. Though more than 3 million cancer treatments with BCG occur annually, surprisingly little is known about the initial signaling cascades activated by BCG. Here, we report that BCG induces a rapid intracellular Ca2+ (calcium ion) signal in bladder cancer cells that is essential for activating the transcription factor nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappa B) and for synthesizing and secreting proinflammatory cytokines, including interleukin 8 (IL-8). A similar Ca2+ response was observed when cells were exposed to the supernatant of BCG. Studying cellular molecular mechanisms involved in the BCG signaling event, we found pivotal roles for phospholipase C and the Toll-like receptor 4. Further assessment revealed that this signaling pathway induces synthesis of IL-8, whereas exocytosis appeared to be controlled by global Ca2+ signaling. These results shed new light on the molecular mechanisms underlying BCG treatment of bladder cancer, which can help in improving therapeutic efficacy and reducing adverse side effects.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Urologi och njurmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Urology and Nephrology (hsv//eng)
Keyword
- BCG
- calcium signaling
- TLR4
- urinary bladder cancer
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Ibarra, Cristian
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Karlsson, Marie
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Codeluppi, Simon ...
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Varas-Godoy, Man ...
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Zhang, Songbai
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Louhivuori, Laur ...
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show more...
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Mangsbo, Sara, 1 ...
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Hosseini, Arad
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Soltani, Navid
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Kaba, Rahim
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Lundgren, T. Kal ...
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Hosseini, Abolfa ...
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Tanaka, Nobuyuki
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Oya, Mototsugu
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Wiklund, Peter
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Miyakawa, Ayako
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Uhlen, Per
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Urology and Neph ...
- Articles in the publication
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Molecular Oncolo ...
- By the university
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Uppsala University
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Karolinska Institutet