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 of physiological and neoplastic blood vessel growth. Moreover, in vitro studies have demonstrated that VEGF can be up-regulated by conditions associated with the generation of free radicals and reactive oxygen species. In a previous study we reported on strongly increased VEGF concentrations in the bronchoalveolar lavage fluid (BALF) of patients with lung cancer under therapy. In this study we aimed to reveal whether this increase was due to the therapy-associated intrapulmonary oxidative burden.


METHODS
A total of 103 BALF samples from 94 patients with lung cancer (82 patients with non-small-cell lung cancer, 12 patients with small-cell lung cancer) were studied at different times before, during or after cancer treatment. VEGF levels in the lavage fluid and ratios of oxidised methionine in proteins of epithelial lining fluid (ELF) were determined.


RESULTS
As reported previously, strongly increased VEGF levels in the ELF were observed in patients undergoing chemotherapy when radiotherapy had been administered before. Increased levels of oxidised methionine indicated that these patients suffered from severe pulmonary oxidative stress that was significantly less in patients undergoing only chemotherapy. Similarly, VEGF concentrations in the ELF were significantly elevated in cancer patients at the time of diagnosis, but the oxidised methionine levels did not reveal significant oxidant/antioxidant imbalances in these patients.


CONCLUSIONS
Systemic chemotherapy is associated with oxidative stress in vivo, which is more pronounced if patients are additionally treated with radiation. VEGF levels in the ELF are increased by this condition as well as by the activity of the tumour itself.
Beinert
T
T
Charité, Medizinische Klinik m.S. Onkologie und Hämatologie, Berlin, Germany. thomas.beinert@charite.de
Binder
D
D
Oehm
C
C
Ziemer
S
S
Priem
F
F
Stuschke
M
M
Schweigert
M
M
Siebert
G
G
Mergenthaler
H G
HG
Schmid
P
P
Fleischhacker
M
M
Possinger
K
K
D000328:Adult; D000368:Aged; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism* / Q000532:radiotherapy; D018288:Carcinoma, Small Cell / Q000188:drug therapy / Q000378:metabolism* / Q000532:radiotherapy; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects; D016228:Endothelial Growth Factors / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000532:radiotherapy; D008222:Lymphokines / Q000378:metabolism*; D008297:Male; D008715:Methionine / Q000378:metabolism*; D008875:Middle Aged; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects / Q000528:radiation effects; D018714:Radiotherapy, Adjuvant / Q000009:adverse effects; D017382:Reactive Oxygen Species; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D017382:Reactive Oxygen Species; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D008715:Methionine