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  • 2005-2009  (3)
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  • 1
    ISSN: 1365-2559
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Aims : The cellular response to hypoxia includes the hypoxia inducible factor (HIF)-induced transcription of genes involved in diverse processes such as glycolysis, angiogenesis and the growth of experimental tumours. Regulation of the level of hypoxia inducible factors 1α and 2α (HIF-1α and HIF-2α) is a primary determinant of HIF activity. Recent biochemical and candidate gene approach studies have led to the discovery of three HIF-regulatory prolyl hydroxylases, PHD-1, -2 and -3 and an asparaginyl hydroxylase, also known as FIH (factor inhibiting HIF). In this study, we raised and characterized monoclonal antibodies against PHD-1, PHD-2, PHD-3 and FIH.Methods and results : Immunohistochemistry of normal tissues with these monoclonal antibodies demonstrated a wide distribution in epithelial cells, stromal cells and leucocytes, with cytoplasmic staining predominating over nuclear staining. A preliminary study of tumours showed variable staining in tumour, stromal and inflammatory cells. While all tumour types showed some positive staining with each antibody, the overall pattern suggested a slight decrease in the amount of staining seen with PHD-1, -2 and -3 and an increase in FIH staining in neoplasia compared with corresponding normal tissues.Conclusions : These monoclonal antibodies will allow further larger scale studies to determine the significance of PHD and FIH expression in neoplasia.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1365-2559
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Aims : To study the expression of phosphorylated vascular endothelial growth factor receptor 2 (VEGFR2), a membrane-bound tyrosine kinase receptor to vascular endothelial growth factor, in lymphoma and non-neoplastic lymphadenopathy.Methods and results : Archival cases (89 cases of lymphoma and 17 cases of non-neoplastic lymphadenopathy) were studied immunohistochemically with three monoclonal antibodies to the different autophosphorylation sites in the cytoplasmic tail of the receptor. There was increased expression of this receptor in lymphoma and particularly in all cases of peripheral T-cell lymphoma. In this category, there was nuclear re-location of this receptor.Conclusions : This very interesting finding raises the possibility that VEGFR2 may be involved in the transcriptional regulation of this disease. Small molecule inhibitors to this receptor may therefore be a useful adjunct in the therapy of this disease.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1365-2559
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Aims:  To study the expression of hypoxia-regulated markers in pancreatic ductal adenocarcinomas (PA) in relationship to the presence of a fibrotic focus, angiogenesis quantification and clinical outcome.Methods and results:  The expression of hypoxia-inducible factor (HIF)-1α, HIF-2α, carbonic anhydrase 9 (CA9) and vascular endothelial growth factor (VEGF) was immunohistochemically detected in 50 PA and correlated with tumour characteristics, microvascular density (MVD) and survival. HIF-1α was expressed within tumour cells in 68%, HIF-2α in 46%, CA9 in 78% and VEGF in 52% of the cases. Stromal expression was also noted for HIF-2α and CA9 in, respectively, 42% and 48% of the cases. Tumour CA9 expression was associated with that of VEGF (P = 0.004) and that of stromal HIF-2α (P = 0.013), with the presence of a fibrotic focus (P = 0.046) and with an increased MVD (P = 0.034). Tumour VEGF expression correlated with the presence of a fibrotic focus (P = 0.039) and a greater MVD (P = 0.047). Both the presence of a fibrotic focus (P = 0.0002) and high tumour CA9 expression (P = 0.029) were associated with reduced overall survival.Conclusion:  The strong association of the presence of a fibrotic focus with CA9 expression and lower survival demonstrates that hypoxia-driven angiogenesis plays an important role in the progression of PA.
    Type of Medium: Electronic Resource
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