論文 - 詳細
| RRC ID | 39311 |
|---|---|
| 著者 | Suzuki K, Kazui T, Yoshida M, Uno T, Kobayashi T, Kimura T, Yoshida T, Sugimura H. |
| タイトル | Drug-induced apoptosis and p53, BCL-2 and BAX expression in breast cancer tissues in vivo and in fibroblast cells in vitro. |
| ジャーナル | Jpn J Clin Oncol |
| Abstract |
BACKGROUND:Chemotherapeutic management of breast cancers is a difficult task as they show significant differences in chemosensitivity. The present study was undertaken to determine the usefulness of the apoptosis-related factors as indicators of tumor sensitivity to 5'-deoxyfluorouridine (5'-DFUR) in breast cancers. METHODS:(1) Forty-six breast cancer patients were randomly assigned to a group in which oral 5'-DFUR (1200 mg/day) was administered for more than 5 days before operation (24 patients) and a control group who received no preoperative chemotherapy (22 patients). Surgical specimens were examined for the frequency of apoptotic cells [apoptotic index (AI)] by a terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling method and for the expression of p53, BCL-2 and BAX by immunohistochemical staining. (2) Normal human diploid fetal lung fibroblast, IMR90 and SV40 transformed IMR90 were exposed to 5-FU. Apoptotic cells were detected by flow cytometry and BCL-2 and BAX mRNAs by real-time quantitative RT-PCR analysis. RESULTS:(1) No significant difference in the AIs or in BCL-2 and BAX scores was observed between the 5'-DFUR-treated and control groups. However, in the p53 negative subgroup (n = 36), AI and BAX scores were higher and BCL-2 scores lower in the 5'-DFUR group than in the control group (P = 0.006, 0.008 and 0.050, respectively). (2) The sensitivity of IMR90 was significantly decreased by SV40 transformation and the 5-FU-induced cytotoxicity was mainly due to induction of apoptosis. The BCL-2/BAX mRNA ratio was decreased in response to 5-FU in IMR90. These results correlated with our clinical data. CONCLUSIONS:Preoperative treatment with 5'-DFUR induced apoptosis and changes in BCL-2 and BAX expression in p53 negative breast cancers. p53 status, AI and the BCL-2/BAX ratio may be useful information for the choice of postoperative chemotherapy for breast cancer. |
| 巻・号 | 29(7) |
| ページ | 323-31 |
| 公開日 | 1999-7-1 |
| DOI | 10.1093/jjco/29.7.323 |
| PMID | 10470656 |
| MeSH | Antineoplastic Agents / pharmacology Antineoplastic Agents / therapeutic use* Apoptosis* Breast Neoplasms / drug therapy* Breast Neoplasms / metabolism Cell Division / drug effects Drug Screening Assays, Antitumor Female Fibroblasts / metabolism Flow Cytometry Floxuridine / pharmacology Floxuridine / therapeutic use* Humans Immunoenzyme Techniques Immunohistochemistry Middle Aged Prodrugs / therapeutic use Proto-Oncogene Proteins / biosynthesis* Proto-Oncogene Proteins c-bcl-2 / biosynthesis* RNA, Messenger / metabolism Tumor Cells, Cultured Tumor Suppressor Protein p53 / biosynthesis* bcl-2-Associated X Protein |
| IF | 1.914 |
| 引用数 | 23 |
| WOS 分野 | ONCOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | IMR-90-SV(RCB1024) |