Is the hypoxia-inducible factor pathway important in gastric cancer?

被引:94
作者
Griffiths, EA
Pritchard, SA
Welch, IM
Price, PM
West, CM
机构
[1] Univ Manchester, Acad Dept Radiat Oncol, Christie Hosp NHS Trust, Manchester M20 4BX, Lancs, England
[2] S Manchester Univ Hosp NHS Trust, Dept Gastrointestinal Surg, Wythenshawe Hosp, Manchester M23 9LT, Lancs, England
[3] S Manchester Univ Hosp NHS Trust, Dept Histopathol, Wythenshawe Hosp, Manchester M23 9LT, Lancs, England
关键词
tumour hypoxia; HIF-1; alpha; gastric adenocarcinoma;
D O I
10.1016/j.ejca.2005.09.008
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Tumour 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-1 alpha (HIF-1 alpha), which appears to be a master regulator of the cellular response to hypoxia. HIF-1 alpha expression is associated with a poor prognosis and treatment response in a number of tumour sites. There is some evidence that the HIF-1 alpha 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-1 alpha. Non-steroidal anti-inflammatory drugs, shown to reduce the risk of gastric cancer, can decrease HIF-1 alpha expression. Although a large study correlating HIF-1 alpha expression with prognosis is lacking in gastric cancer, the immunohistochemical expression of HIF-1 alpha target genes (Glut-1, VEGF CA9, iNOS) is associated with a poor prognosis. In addition, the targeted inhibition of HIF-1 alpha has been shown to inhibit the growth of gastric tumours in animals. Increased understanding of the importance of hypoxia and the HIF-1 alpha pathways may therefore hold the key to prevention strategies, improved selection of patients for adjuvant therapy and new treatments for the disease. (c) 2005 Elsevier Ltd. All rights reserved.
引用
收藏
页码:2792 / 2805
页数:14
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