title: Molecular Factors Associated with Pemetrexed Sensitivity According to Histological Type in Non-small Cell Lung Cancer.
abstract: This study was designed to investigate potential molecules that predict chemosensitivity to pemetrexed (Alimta®) in surgically resected non-small cell lung cancer (NSCLC).
  
  
  
  Chemosensitivity to ALM and other drugs was assessed by succinate dehydrogenase inhibition (SDI) test in 69 NSCLC samples (55 adenocarcinomas, and 14 squamous cell carcinomas). The mRNA expression levels of Alimta®-target enzymes [thymidylate synthase (TYMS); dihydrofolate reductase (DHFR) and glycinamide ribonucleotide formyltransferase (GARFT)], Alimta®-metabolizing enzymes [γ-glutamyl hydrase (GGH) and folylpolyglutamate synthase] and an Alimta® transporter [reduce folate carrier (RFC)] were measured and examined for potential correlations to chemosensitivity.
  
  
  
  The squamous cell carcinoma samples showed higher TYMS expression and lower RFC expression than did the adenocarcinoma samples. In the adenocarcinoma sample analyses, GGH expression was inversely correlated to sensitivity.
  
  
  
  The histology-dependent differences in chemosensitivity to Alimta® may be attributed to the histology-dependent differences in TYMS and RFC expression. In adenocarcinomas, GGH potentially represents a marker for chemosensitivity to Alimta®.
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Tsukihisa
authors.initials: T
authors.lastname: Yoshida
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Okamoto
authors.affiliation: Clinical Research Institute, National Hospital Organization Beppu Medical Center, Beppu, Japan.
authors.forename: Tokujiro
authors.initials: T
authors.lastname: Yano
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.|Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Takada
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Mikihiro
authors.initials: M
authors.lastname: Kohno
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Suda
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Takenoyama
authors.affiliation: Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Yoshinao
authors.initials: Y
authors.lastname: Oda
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan maehara@surg2.med.kyushu-u.ac.jp.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Maehara
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D000068437:Pemetrexed / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D000068437:Pemetrexed
keywords: Non-small cell lung cancer; adenocarcinoma; biomarker; chemosensitivity; chemotherapy; squamous cell carcinoma