title: Relationship between expression of apoptosis-related proteins and the efficacy of postoperative chemotherapy in patients with T3 gastric cancer.
abstract: OBJECTIVE
  We investigated the relationship between the p53-dependent apoptotic pathway and the survival of patients with gastric cancer, retrospectively, to elucidate new biomarkers of uracil/tegafur (UFT) chemotherapy.
  
  
  METHODS
  We examined the expression of p53, p21, Bax, and myeloid cell leukemia 1 (Mcl-1) proteins immunohistochemically in 105 patients who underwent curative gastrectomy for gastric cancer invading the serosa. Postoperative oral UFT was prescribed for 1 year. Kaplan-Meier survival curves were compared with the two-sided log-rank test.
  
  
  RESULTS
  Positive staining for p53, p21, Bax, and Mcl-1 proteins was found in 63.8, 52.4, 39.0, and 72.4% of the subjects, respectively. Survival time did not differ significantly between the patients with and those without p53, p21, and Bax expression. However, patients with Mcl-1- tumors survived longer than those with Mcl-1+ tumors. Postoperative UFT treatment did not improve survival; however, adjuvant UFT significantly prolonged the survival of patients with p53-, p21-), Bax+, or Mcl-1+ tumors, but not of patients with p53+, p21+, Bax-, or Mcl-1- tumors.
  
  
  CONCLUSIONS
  The efficacy of adjuvant chemotherapy for gastric cancer may be affected by the status of apoptosis-related proteins such as p53, p21, Bax, and Mcl-1. However, because susceptibility to apoptosis did not explain the sensitivity of chemotherapeutic agents, further investigation of the mutual interaction between apoptosis-related proteins is required.
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Science, Kyushu University, Fukuoka, 812-8582, Japan. stsujitani@me.com
authors.forename: Shunichi
authors.initials: S
authors.lastname: Tsujitani
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Saito
authors.forename: Toshiro
authors.initials: T
authors.lastname: Wakatsuki
authors.forename: Masahide
authors.initials: M
authors.lastname: Ikeguchi
authors.forename: Ken
authors.initials: K
authors.lastname: Shirabe
authors.forename: Masaru
authors.initials: M
authors.lastname: Morita
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kakeji
authors.forename: Tokujiro
authors.initials: T
authors.lastname: Yano
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Maehara
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000601:surgery; D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000378:metabolism*; D017024:Chemotherapy, Adjuvant; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D005260:Female; D005743:Gastrectomy; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012189:Retrospective Studies; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000601:surgery; D005641:Tegafur / Q000627:therapeutic use; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014498:Uracil / Q000627:therapeutic use; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000964:Antimetabolites, Antineoplastic; C494826:BAX protein, human; D014408:Biomarkers, Tumor; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D005641:Tegafur; D014498:Uracil