title: SMO expression level correlates with overall survival in patients with malignant pleural mesothelioma.
abstract: BACKGROUND
  Malignant mesothelioma is an aggressive, treatment-resistant tumor arising from mesothelium of pleura, peritoneum and pericardium. Despite current combined regimen, its prognosis remains dismal, calling for more effective targeted therapies. We investigated whether aberrant Hh activation may play a role in mesothelioma.
  
  
  METHODS
  SMO and SHH expression levels were analyzed in 46 mesothelioma tissue specimens with real-time RT-PCR, and correlation with survival was analyzed with univariate and multivariate Cox proportional hazards models, Kaplan-Meier survival curves, and the log-rank test. We also examined multiple mesothelioma cell lines for SMO expression and the effect of Hh inhibition by a specific SMO antagonist on cell proliferation by MTS assay.
  
  
  RESULTS
  We observed strong correlation between higher SMO and SHH expression levels with poorer overall survival. Remarkably, Hh inhibition by a specific SMO inhibitor significantly suppressed cell proliferation in the mesothelioma cell lines examined.
  
  
  CONCLUSIONS
  Our data strongly support that Hh signaling deregulation plays critical roles in proliferation of mesothelioma, and consistently exerts significant impact on prognosis of the disease. Therefore our findings revealed the hitherto unappreciated role of Hh activation in mesothelioma, and pinpointed Hh signaling antagonist as a potential new therapy against this devastating disease.
authors: Department of Surgery, University of California, San Francisco, CA, USA.
authors: Yi
authors: Y
authors: Zhang
authors: Jianxing
authors: J
authors: He
authors: Fang
authors: F
authors: Zhang
authors: Hui
authors: H
authors: Li
authors: Dongsheng
authors: D
authors: Yue
authors: Changli
authors: C
authors: Wang
authors: David M
authors: DM
authors: Jablons
authors: Biao
authors: B
authors: He
authors: Natalie
authors: N
authors: Lui
mesh_terms: D000368:Aged; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D005260:Female; D053823:Hedgehog Proteins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008654:Mesothelioma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010997:Pleural Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D060888:Real-Time Polymerase Chain Reaction; D043562:Receptors, G-Protein-Coupled / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction; D000072086:Smoothened Receptor; D016019:Survival Analysis
chemical_list: D053823:Hedgehog Proteins; D043562:Receptors, G-Protein-Coupled; C509239:SHH protein, human; C491023:SMO protein, human; D000072086:Smoothened Receptor
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