On the other hand, cervical cancer is the leading cancer among women in many resource constrained settings of developing namely countries, where incidence and mortality rate are about five to six times higher. Overall the clinical management of patients with premalignant and malignant cervical disease is a significant burden on the health care system. Although tremendous progress has been made in the diagnosis and treatment of cervical cancer, there is still a need for clinically robust biomarkers to further refine the screening, triage and management of women. Hypoxia is present in a wide range of solid tumors and is often associated with tumor glycolysis, angiogenesis, and poor prognosis, as well as invasion and metastasis by acti vating relevant gene expression through hypoxia inducible factor 1.
In normoxic condition, HIF 1 is degraded within minutes through the interaction of iron and oxygen dependent von Hippel Lindau tumor suppres sor. However, in hypoxic condition or in the ab sence of VHL, HIF 1 is stabilized and binds to DNA on the hypoxia response elements contained within the pro Inhibitors,Modulators,Libraries moter regions of various target genes. HIF 1 synthe sis is increased by various growth factors, cytokines and other signaling molecules responsible for stimulating phos phatidylinositol 3 kinase or mitogen activated pro tein kinase pathways. Increased HIF 1 activates target genes involved in tumor cell growth, angio genesis, metabolism, apoptosis and metastasis. In a hypoxic Inhibitors,Modulators,Libraries cancer microenvironment, Inhibitors,Modulators,Libraries a metabolic shift occurs from an oxidative to glycolytic metabolism.
HIF 1 con verts pyruvate metabolism in mitochondria to cytoplasmic Inhibitors,Modulators,Libraries alteration of pyruvate into lactic acid. In cytoplasmic glucose metabolism, high glucose consumption takes place in tumor cells and glucose transporter type 1 is involved in delivering glucose into these tumor cells. Cyto plasmic glucose metabolism produces Inhibitors,Modulators,Libraries lactic acid that in duces acidosis, but carbonic anhydrase 9 regulates cell pH through Cl HCO3 exchanger uptake of HCO3. c Met, known as hepatocyte growth factor receptor, is acti vated by HIF 1 and it is known for tumor invasion and metastasis. HIF 1 and its regulated markers including c Met, CA9 and GLUT1 were reported to be highly expressed in various cancers and associated with poor prognosis. However, the relationship of these hypoxia markers in the prognosis of cervical cancer is unclear.
Furthermore, hypoxia results in http://www.selleckchem.com/products/Paclitaxel(Taxol).html resistance against radi ation and chemotherapy which are treatment options in cervical cancer, so prognostic significance of hypoxia markers must be clarified. Immunohistochemistry utilizes antigen antibody recognition in detecting spe cific antigens within tissues and its widely used in surgi cal pathology. A variety of markers has been evaluated for their role in the diagnosis, prognosis, and prediction of treatment.