华　中　科　技　大　学　博　士　学　位　论　文

may be produced by a wide variety of diseases especially malignancies. It is important to elucidate the precise etiology of the pleural effusion especially to discriminate benignfrom malignant effusions. Pleural effusion can present a challenging diagnostic problem which remains unsolved even after clinical and laboratory evaluation. The differential diagnosis is diverse, but most common causes include malignancy, tuberculous, congestive heart failure and empyema-related effusion.

VEGF is the most potent and endothelial specific angiogenic growth factor and it plays a pivotal role in formulation of PE, which has proved to be a useful marker to differentiate malignancy from a benign origin in exudative pleural effusions. Differing VEGF levels were found in malignant and tuberculous pleural effusions, implying a varying degree of influence on the process of fluid accumulation in the pleural space in different disease states. Tumor spreading has been associated with angiogenesis, a process tightly controlled by balance between angiogenesis factor and angiogenesis inhibitor. Pleural angiogenesis, increased vascular permeability, and leakage play a key role in the development of exudative pleural effusions. Although many known angiogenesis-inducing factors including VEGF are present within pleural fluid and these high levels are thought to induce vascular permeability, the relative levels of antiangiogenic factors such as endostatin in PE have been reported only by few studies. Endostatin induces endothelial cell apoptosis and inhibits the proliferation and migration of some types of endothelial cells, and in vivo it has potent anti-angiogenic activity. Although serum levels of endostatin have extensively been studied in patients with malignant diseases, endostatin in pleural effusion has not been fully evaluated. The respective determination of the concentrations of VEGF and endostatin has been proved helpful in differentiating between pleural effusion of malignant and tuberculous or benign origin.

The rel ationship between smoking and lung cancer is well understood, but the mechanism of the close association is not definitely known. However, heavy smoking has been demonstrated to affect serum VEGF levels. Therefore, we intend to implore whether there is an imblance of angiogenesis in sera of heavy smoking subjects.

The present study is divided into three parts as follows.

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