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dc.contributor.authorGriffiths, Ewen A
dc.contributor.authorPritchard, S A
dc.contributor.authorWelch, I M
dc.contributor.authorPrice, Patricia M
dc.contributor.authorWest, Catharine M L
dc.date.accessioned2009-08-06T11:54:47Z
dc.date.available2009-08-06T11:54:47Z
dc.date.issued2005-12
dc.identifier.citationIs the hypoxia-inducible factor pathway important in gastric cancer? 2005, 41 (18):2792-805 Eur. J. Canceren
dc.identifier.issn0959-8049
dc.identifier.pmid16290133
dc.identifier.doi10.1016/j.ejca.2005.09.008
dc.identifier.urihttp://hdl.handle.net/10541/76494
dc.description.abstractTumour hypoxia is well recognised in oncology to be a key factor resulting in treatment resistance and poor prognosis. Hypoxia leads to the expression of a number of gene products that are involved in tumour progression, invasion and metastasis formation. The most important of these proteins is thought to be hypoxia-inducible factor-1alpha (HIF-1alpha), which appears to be a master regulator of the cellular response to hypoxia. HIF-1alpha expression is associated with a poor prognosis and treatment response in a number of tumour sites. There is some evidence that the HIF-1alpha pathway might be involved in gastric carcinogenesis. Studies have shown reactive oxygen species from Helicobacter pylori, associated with the development of gastric cancer, stabilise HIF-1alpha. Non-steroidal anti-inflammatory drugs, shown to reduce the risk of gastric cancer, can decrease HIF-1alpha expression. Although a large study correlating HIF-1alpha expression with prognosis is lacking in gastric cancer, the immunohistochemical expression of HIF-1alpha target genes (Glut-1, VEGF, CA9, iNOS) is associated with a poor prognosis. In addition, the targeted inhibition of HIF-1alpha has been shown to inhibit the growth of gastric tumours in animals. Increased understanding of the importance of hypoxia and the HIF-1alpha pathways may therefore hold the key to prevention strategies, improved selection of patients for adjuvant therapy and new treatments for the disease.
dc.language.isoenen
dc.subjectCancer Proteinsen
dc.subjectStomach Canceren
dc.subjectTumour Markersen
dc.subject.meshAnti-Inflammatory Agents, Non-Steroidal
dc.subject.meshAntigens, Neoplasm
dc.subject.meshCarbonic Anhydrases
dc.subject.meshCell Hypoxia
dc.subject.meshCyclooxygenase 2
dc.subject.meshDrug Resistance, Neoplasm
dc.subject.meshForecasting
dc.subject.meshGenes, Tumor Suppressor
dc.subject.meshGlucose Transporter Type 1
dc.subject.meshHelicobacter Infections
dc.subject.meshHelicobacter pylori
dc.subject.meshHumans
dc.subject.meshHypoxia-Inducible Factor 1, alpha Subunit
dc.subject.meshImmunohistochemistry
dc.subject.meshMicrocirculation
dc.subject.meshNeoplasm Proteins
dc.subject.meshPrognosis
dc.subject.meshStomach Neoplasms
dc.subject.meshTumor Markers, Biological
dc.subject.meshVascular Endothelial Growth Factor A
dc.titleIs the hypoxia-inducible factor pathway important in gastric cancer?en
dc.typeArticleen
dc.contributor.departmentDepartment of Gastrointestinal Surgery, South Manchester University Hospitals NHS Trust, Wythenshawe Hospital, South Moor Road, Wythenshawe, M23 9LT, UK.en
dc.identifier.journalEuropean Journal of Canceren
html.description.abstractTumour hypoxia is well recognised in oncology to be a key factor resulting in treatment resistance and poor prognosis. Hypoxia leads to the expression of a number of gene products that are involved in tumour progression, invasion and metastasis formation. The most important of these proteins is thought to be hypoxia-inducible factor-1alpha (HIF-1alpha), which appears to be a master regulator of the cellular response to hypoxia. HIF-1alpha expression is associated with a poor prognosis and treatment response in a number of tumour sites. There is some evidence that the HIF-1alpha pathway might be involved in gastric carcinogenesis. Studies have shown reactive oxygen species from Helicobacter pylori, associated with the development of gastric cancer, stabilise HIF-1alpha. Non-steroidal anti-inflammatory drugs, shown to reduce the risk of gastric cancer, can decrease HIF-1alpha expression. Although a large study correlating HIF-1alpha expression with prognosis is lacking in gastric cancer, the immunohistochemical expression of HIF-1alpha target genes (Glut-1, VEGF, CA9, iNOS) is associated with a poor prognosis. In addition, the targeted inhibition of HIF-1alpha has been shown to inhibit the growth of gastric tumours in animals. Increased understanding of the importance of hypoxia and the HIF-1alpha pathways may therefore hold the key to prevention strategies, improved selection of patients for adjuvant therapy and new treatments for the disease.


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