Further evidence for oxidant-induced vascular endothelial growth factor up-regulation in the bronchoalveolar lavage fluid of lung cancer patients undergoing radio-chemotherapy

Background: Vascular endothelial growth factor (VEGF) is a potent inducer o f physiological and neoplastic blood vessel growth, Moreover, in vitro stud ies have demonstrated that VEGF can be up-regulated by conditions associate d with the generation of free radicals and reactive oxygen species. In a pr evious study we reported on strongly increased VEGF concentrations in the b ronchoalveolar lavage fluid (BALF) of patients with lung cancer under thera py. In this study we aimed to reveal whether this increase was due to the t herapy-associated intrapulmonary oxidative burden. Patients and methods: A total of 103 BALF samples from 94 patients with lung cancer (82 patients wi th non-small-cell lung cancer, 12 patients with small-cell lung cancer) wer e studied at different times before, during or after cancer treatment. VEGF levels in the lavage fluid and ratios of oxidised methionine in proteins o f epithelial lining fluid (ELF) were determined. Results: As reported previ ously, strongly increased VEGF levels in the ELF were observed in patients undergoing chemotherapy when radiotherapy had been administered before. Inc reased levels of oxidised methionine indicated that these patients suffered from severe pulmonary oxidative stress that was significantly less in pati ents undergoing only chemotherapy, Similarly, VEGF concentrations in the EL F were significantly elevated in cancer patients at the time of diagnosis, but the oxidised methionine levels did not reveal significant oxidant/antio xidant imbalances in these patients. Conclusion: Systemic chemotherapy is a ssociated with oxidative stress in vivo, which is more pronounced if patien ts are additionally treated with radiation. VEGF levels in the ELF are incr eased by this condition as well as by the activity of the tumour itself.