Paradoxical effects by preoperative oral low-dose tegafur administration in human gastric carcinomas: enhanced apoptosis and increased intratumoral microvessel density.
This study examined the effect of preoperative low-dose tegafur treatment in human gastric carcinomas. Among 55 patients with gastric carcinoma, 33 received an oral administration of tegafur 600 mg/body/day for 7 days before. Formalin-fixed, paraffin-embedded specimens were immunostained for Ki-67, P53, P21, CD34, Bax, VEGF, and dThdPase and also examined by the terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling procedure. The apoptotic index (AI), Ki-67 labeling index (KI) and intratumoral microvessel density (IMVD) were counted. Mean AI and IMVD were 3.4+/-1.60 and 126.1+/-36.56 in the treated carcinomas, and 2.3+/-0.88 and 98.0+/-44.40 in the non-treated carcinomas, both values being significantly higher in the former (P<0.05). The treatment resulted in a significant increase of mean AI in the intestinal type, in the early, and in the P53-positive carcinomas (P<0.05), while the treatment brought a significant increase of IMVD in the diffuse type, in the early and in the P53-negative carcinomas (P<0.05, respectively). No significant difference was noted on the frequency of P53, P21, BAX, VEGF and dThdPase expressions between the two groups. Ki-67 expression did not correlate with any factors. Preoperative low-dose tegafur treatment resulted in a paradoxical effect; enhanced apoptosis and increased IMVD in human gastric carcinomas.
Goto
Eizo
E
Division of Organ Pathology, Department of Microbiology and Pathology, Faculty of Medicine, Tottori University, 86 Nishi-cho, Yonago 683-8503, Japan. gotoe@grape.med.tottori-u.ac.jp
Okamoto
Eiji
E
Adachi
Hironobu
H
Fukuda
Yasuhiko
Y
Ito
Hisao
H
D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D017209:Apoptosis; D002277:Carcinoma / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology* / Q000601:surgery; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D019394:Ki-67 Antigen / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D011300:Preoperative Care; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2; D013274:Stomach Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology* / Q000601:surgery; D005641:Tegafur / Q000627:therapeutic use*; D013939:Thymidine Phosphorylase / Q000096:biosynthesis; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis; D051028:bcl-2-Associated X Protein
D000964:Antimetabolites, Antineoplastic; C494826:BAX protein, human; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D019394:Ki-67 Antigen; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D005641:Tegafur; D013939:Thymidine Phosphorylase