华　中　科　技　大　学　博　士　学　位　论　文

The study of tumor hypoxia and angiogenesis in lung cancer

Candidate for Ph.D: Zhou Wenbin

Supervisor: Prof. Bai Ming

Abstract

Background： Lung cancer is one of the highest incidence and mortality in all kinds of caner in the world，and it is the most common cause of death due to cancer. Recently，the incidence of lung cancer is rising step by step，especially in China. Non-small cell lung cancer (NSCLC) accounts for more than 75% of pulmonary carcinomas. Treatment of patients with NSCLC is a particular challenge in oncology, because more than one third of patients have distant metastases at diagnosis, allowing only palliative treatment. Tumor growth, invasion and metastasis are infuenced by a variety of factors, and most important of these factors are tumor hypoxia and angiogenesis. Carbonic anhydrases IX(CAIX) is considered as an reliable marker of tumor hypoxia. Considerable interest has been focused on angiogenic factors in the field of lung cancer. Angiogenesis represents the formation of new blood vessels from existing vasculature. Neovascularisation is a requirement for growth of solid tumours beyond 1~2 mm in diameter. The angiogenic process is a balance between stimulatory and inhibitory factors. The pro-angiogenic stimuli may be released by the tumour, stromal and inflammatory cells, by the extracellular matrix, or by the endothelial cells themselves. Tumour cells secrete or induce the release of growth factors which stimulate migration and proliferation of endothelial cells. Furthermore, these factors may be involved in capillary morphogenesis or release of proteolytic enzymes.

Vascular endothelial growth factor (VEGF) and endostatin are two of the most potent factors involved in angiogenesis. Clinical and experimental studies demonstrated significantly elevated serum and tissue levels of VEGF in patients with lung cancer, implicating VEGF in the pathogenesis of this disease.

Pleural effusion often remains a diagnostic problem after the biochemical and cytological analysis of the pleural fluid. In most series, malignancy is the most common cause of pleural exudates. Pleural effusions are common and important complications that

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