Grant-in-Aid for Scientific Research (B)
|Allocation Type||Single-year Grants|
|Research Institution||KYUSHU UNIVERSITY(1996-1997)|
University of Occupational and Environmental Health, Japan(1995)
SUGIO Kenji KYUSHU UNIVERSITY Faculty of Medicine, Assistant Professor, 医学部, 助手 (70235927)
USHIJIMA Chie Faculty of Medicine, Research Associate, 医学部, 医員
TSUKAMOTO Shuichi Kyushu Dental Univ.Research Associate, 助手
SAKADA Takashi Kyushu Dental Univ.Research Associate, 助手
大崎 敏弘 産業医科大学, 医学部, 助手 (70248574)
|Project Period (FY)
1995 – 1997
Completed(Fiscal Year 1997)
|Budget Amount *help
¥3,900,000 (Direct Cost : ¥3,900,000)
Fiscal Year 1997 : ¥1,300,000 (Direct Cost : ¥1,300,000)
Fiscal Year 1996 : ¥1,000,000 (Direct Cost : ¥1,000,000)
Fiscal Year 1995 : ¥1,600,000 (Direct Cost : ¥1,600,000)
|Keywords||Lung cancer / Multi-step carcinogenesis / Tumor suppressor gene / Oncogene / Genetic diagnosis / p16 / p53 / p27 / 前癌病変 / 分子生物学 / サイトケラチン|
1) Genetic alteration in precursor lesions of lung cancer
In lung adenocarcinoma, 3p and 9p allele loss occur at the earliest (hyperplasia) stages, and ras mutations occur at the time of non-invasive cancer (carcinoma in situ), which suggested that ras mutations might correlate tumor progression.
2) Genetic alteration in lung cancer and its clinical significance
(1) In non-small cell lung cancer (NSCLC), the frequency of ras mutation was 7%, p53 was 36%, and 3p allelic loss was 46%. The LOH of 3p was a poor prognostic factor in adenocarcinoma. Multivariate analysis showed that ras and p53 mutations were independent unfavorable prognostic factors in early stage of NSCLC.
(2) Immunohistochemical analyzes of p53, p16, Rb, and p27 showed that alternative expression of both p53 and p27 was prognostic factor in adenocarcinoma, and alternative expression of p27 was prognostic factor in squamous cell carcinoma. The accumulation of these alternative gene expressions suggested tumor progression.
3) Early detection of cancer cells for recurrence
(1) The detection of occult micro metastases in the mediastinal lymph nodes with monoclonal antibodies to cytokeratin can be used to predict and early relapse in patients with stage I NSCLC.
(2) Micrometastatic cancer cells were frequently present in bone marrow of patients with operable NSCLC and may be a significant predictor of eqrly recurrence.
Further evaluation of these methods may be useful in identifying patients with NSCLC who are most likely to benefit from adjuvant chemotherapy.