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The prognostic valu...
The prognostic value and therapeutic target role of stathmin-1 in urinary bladder cancer
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- Hemdan, Tammer (författare)
- Uppsala universitet,Institutionen för kirurgiska vetenskaper
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- Lindén, Mårten (författare)
- Uppsala universitet,Institutionen för kirurgiska vetenskaper
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- Lind, Sara (författare)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab
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- Namuduri, Arvind (författare)
- Uppsala universitet,Institutionen för kirurgiska vetenskaper
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- Sjöstedt, Evelina (författare)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi
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- D de Ståhl, T (författare)
- Karolinska Institutet
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- Asplund, Anna (författare)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi
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- Malmström, Per-Uno (författare)
- Uppsala universitet,Urologkirurgi
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- Segersten, Ulrika (författare)
- Uppsala universitet,Institutionen för kirurgiska vetenskaper
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(creator_code:org_t)
- 2014-07-29
- 2014
- Engelska.
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 111:6, s. 1180-1187
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Abstract
Ämnesord
Stäng
- Background:The oncoprotein-18/stathmin 1 (STMN1), involved in cell progression and migration, is associated with clinical outcome in breast cancer. Here we aim to investigate its clinical significance in urinary bladder cancer and its possibilities as a therapeutic target.Methods:Immunohistochemical analyses of STMN1 protein expression were performed in three patient cohorts: cohort I (n=115 Ta, n=115 T1, n=112 T2-4 stages), cohort II, based on randomised controlled trials (n=239 T1-T4), and cohort III of primary tumour/matched metastasis (n=90 T1-T4). The effects of STMN1 on cell proliferation and migration were evaluated in the urinary bladder cancer cell line, T24, by inhibiting STMN1-cellular expression using siRNA.Results:In cohort I, high STMN1 expression correlated to shorter disease-specific survival hazard ratio (HR)=2.04 (95% confidence interval (CI) 1.13-3.68; P=0.02), elevated p53- (P<0.001) and Ki67-protein levels (P<0.001). The survival result was validated in cohort II: HR=1.76 (95% CI 1.04-2.99; P=0.03). In the metastatic bladder cancer material, 70% of the patients were STMN1-positive in both the primary tumour and matched metastases. In vitro, the growth and migration of the T24 cells were significantly reduced (P<0.01, P<0.0001, respectively), when transfecting the cells with STMN1-siRNA.Conclusions:STMN1 protein expression has prognostic significance but is primarily a potential treatment target in urinary bladder cancer.
Ämnesord
- NATURVETENSKAP -- Kemi (hsv//swe)
- NATURAL SCIENCES -- Chemical Sciences (hsv//eng)
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- art (ämneskategori)
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