title: Expression and prognostic significance of hypoxia-inducible factor 1alpha (HIF-1alpha) in malignant pleural mesothelioma (MPM).
abstract: Malignant pleural mesothelioma (MPM) is a highly chemoresistant cancer with a poor prognosis. Hypoxia is a specific property of solid tumours, contributes to low apoptotic potential, and can be selectively targeted by bioreductive drugs. Hypoxia-inducible factor 1alpha (HIF-1alpha) is a subunit of a heterodimeric transcription complex that regulates several genes associated with tumour progression and anti-apoptosis. In this study, we measured for the first time the expression of HIF-1alpha in MPM. Our results show that HIF-1alpha is commonly expressed in MPM but not in normal mesothelium, consistent with the presence of hypoxia. HIF-1alpha does not appear to predict survival; however, this study suggests that bioreductive drugs should be investigated in clinical trials of MPM.
authors.affiliation: Bart's Mesothelioma Research, Institute of Pathology, Royal London Hospital, Queen Mary School of Medicine and Dentistry, London E1 1BB, UK. a.klabatsa@qmul.ac.uk
authors.forename: A
authors.initials: A
authors.lastname: Klabatsa
authors.forename: M T
authors.initials: MT
authors.lastname: Sheaff
authors.forename: J P C
authors.initials: JP
authors.lastname: Steele
authors.forename: M T
authors.initials: MT
authors.lastname: Evans
authors.forename: R M
authors.initials: RM
authors.lastname: Rudd
authors.forename: D A
authors.initials: DA
authors.lastname: Fennell
mesh_terms: D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D018450:Disease Progression; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis*; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008654:Mesothelioma / Q000378:metabolism* / Q000473:pathology; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000096:biosynthesis; D010997:Pleural Neoplasms / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D019408:Platelet Endothelial Cell Adhesion Molecule-1