title: Nitroglycerin treatment may enhance chemosensitivity to docetaxel and carboplatin in patients with lung adenocarcinoma.
abstract: OBJECTIVE
  Nitroglycerin may improve the response to chemotherapy in advanced non-small cell lung cancer. The effects and mechanisms of nitroglycerin on the enhancement of chemosensitivity to docetaxel and carboplatin regimen (DCb) in patients with lung adenocarcinoma have not been reported.
  
  
  METHODS
  Seventeen patients with operable lung adenocarcinoma and stable angina pectoris were selected to investigate the effects of nitroglycerin on immunoreactivity for hypoxia-inducible factor 1alpha (HIF-1alpha), vascular endothelial growth factor (VEGF), P-glycoprotein (P-gp), the production of which is regulated by HIF-1, and p53 proteins in their resected tumor by semiquantitative immunohistochemical analyses. Eight of 17 patients were treated with nitroglycerin patches before operation, but 9 of 17 patients were not. Furthermore, to study the relationship between changes in plasma VEGF levels by nitroglycerin treatment and response to DCb, 29 patients with advanced lung adenocarcinoma were treated with nitroglycerin for 3 days before chemotherapy using DCb.
  
  
  RESULTS
  The rates of immunoreactive cells for HIF-1alpha, VEGF, and P-gp in tumor tissues treated with nitroglycerin were lower than those without nitroglycerin, but those for p53 were not different between those treated with and without nitroglycerin. Furthermore, the rates of immunoreactive cells for VEGF and P-gp proteins were significantly associated with those for HIF-1alpha in tumor tissue. The magnitude of decrease in plasma VEGF levels after treatment with nitroglycerin was significantly associated with response to DCb in patients with advanced lung adenocarcinoma.
  
  
  CONCLUSIONS
  Nitroglycerin treatment may improve response to DCb in patients with lung adenocarcinoma, partly through decreasing VEGF and P-gp production via reduction of HIF-1alpha.
authors.affiliation: Department of Translational Clinical Oncology, Kyoto University Graduate School of Medicine, Kyoto, and Department of Internal Medicine, Sendai City Hospital, Sendai, Japan. yasuda@kuhp.kyoto-u.ac.jp
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Yasuda
authors.forename: Katsutoshi
authors.initials: K
authors.lastname: Nakayama
authors.forename: Mika
authors.initials: M
authors.lastname: Watanabe
authors.forename: Satoshi
authors.initials: S
authors.lastname: Suzuki
authors.forename: Hiromi
authors.initials: H
authors.lastname: Fuji
authors.forename: Shoji
authors.initials: S
authors.lastname: Okinaga
authors.forename: Akio
authors.initials: A
authors.lastname: Kanda
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Zayasu
authors.forename: Takahiko
authors.initials: T
authors.lastname: Sasaki
authors.forename: Masanori
authors.initials: M
authors.lastname: Asada
authors.forename: Tomoko
authors.initials: T
authors.lastname: Suzuki
authors.forename: Motoki
authors.initials: M
authors.lastname: Yoshida
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Yamanda
authors.forename: Daisuke
authors.initials: D
authors.lastname: Inoue
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kaneta
authors.forename: Takashi
authors.initials: T
authors.lastname: Kondo
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Takai
authors.forename: Hidetada
authors.initials: H
authors.lastname: Sasaki
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yanagihara
authors.forename: Mutsuo
authors.initials: M
authors.lastname: Yamaya
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000601:surgery; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage* / Q000009:adverse effects; D003131:Combined Modality Therapy / Q000009:adverse effects; D018450:Disease Progression; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000601:surgery; D008297:Male; D008875:Middle Aged; D005996:Nitroglycerin / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D012372:ROC Curve; D043823:Taxoids / Q000008:administration & dosage* / Q000009:adverse effects; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000097:blood / Q000378:metabolism
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D043823:Taxoids; D016159:Tumor Suppressor Protein p53; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000077143:Docetaxel; D016190:Carboplatin; D005996:Nitroglycerin