Establishment of melecular-based diagnositics for esophageal cancer

食管癌分子诊断学的建立

• 批准号: 15390398
• 负责人: MORI Masaki
• 金额: $ 9.47万
• 依托单位: KYUSHU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15390398/
• 关键词: micrometastasis; esohageal cancer; chemical carcinogenesis; radiation sensitivity; MAL; MMP2; FHIT; CKS2; CEA; cytokeratin7; Lyn B tyrosine kinase

Esophageal cancer is considered to be one of the most aggressive malignacy in the Eastern countries, including Japan. Early detection of the tumor development as well as tumor recurences has been a key subject of the disease. The purpose of our current study is to establish molecular-based diagnositics for esophageal cancer and we have conveyed 4 major researches for this purpose : 1) the detection of the tumor cells (micrometastasis) in either blood or bone marrow of the patient for the postoperative disease surveillance, 2) the establishment of rat esophageal chemical-induced carcinoma model for the elucidation of the genes associated with esophageal carcinogenesis, 3) the detection of the genes responsible for radiation sensitivities, 4) the detection of tumor associated genes using DNA microarray methodology applied for the human esophageal tumor specimens. Results : 1) The blood and bone marrow samples were obtained from 150 patients with esophageal cancer. No significant differences were currently observed between the cases with early recurrence or metastasis of the tumor. More detailed-studies are needed for longer period of the postoperative observation. 2) Genes such as rat gelatinase A (MMP2), keratin 6a, Lyn B tyrosine kinase were found to be highly expressed in development of carcinoma. Genes such as ALDH. SLP were repressed along the tumor development. 3) Genes such as SPP1, CKS2 were found to be associated with tumor radio sensitivity. 4) Transfection of MAL and FHIT genes induce dramatic changes in tumor cell biology. For the gene FHIT, the mechanism of apoptotic activity by Ad-FHIT is to identify the candidate cancer associated targets affected by Ad-FHIT treatment. Those molecules may consider to be both tumor markers for the early detection of tumor development, and also a fine molecular target for the treatments of esophagel cancer.

食道癌被认为是包括日本在内的东方国家最具侵袭性的恶性肿瘤之一。早期发现肿瘤的发展以及肿瘤的复发一直是该病的关键课题。本研究的目的是建立基于分子的食管癌诊断方法，主要包括四个方面的研究：1)检测患者血液或骨髓中的肿瘤细胞(微转移)，用于术后疾病监测；2)建立大鼠食道化学诱癌模型，以阐明与食管癌发生相关的基因；3)检测与辐射敏感有关的基因；4)应用DNA微阵列技术检测肿瘤相关基因。结果：1)采集150例食道癌患者的血液和骨髓标本。在肿瘤早期复发或转移的病例中，目前没有发现明显的差异。更详细的研究需要更长时间的术后观察。2)大鼠明胶酶A(MMP2)、角蛋白6a、Lyn B酪氨酸激酶等基因在肿瘤的发生发展过程中呈高表达。ALDH等基因。SLP在肿瘤发生发展过程中受到抑制。3)SPP1、CKS2等基因与肿瘤放射敏感性相关。4)转导MAL和FHIT基因可引起肿瘤细胞生物学发生显著变化。对于FHIT基因，Ad-FHIT诱导细胞凋亡的机制是确定受Ad-FHIT治疗影响的候选肿瘤相关靶点。这些分子可能被认为既是早期发现肿瘤发展的肿瘤标志物，也是治疗食道癌的良好分子靶点。

项目成果

Yamashita K, Sunil, et al.: "MAL gene expression in esophageal cancer suppresses motility, invasion and tumoril genicity and enhances apoptosis through the Fas pathway"Oncogene. 22. 3463-3471 (2003)

Yamashita K、Sunil 等人：“食管癌中的 MAL 基因表达抑制运动、侵袭和致瘤性，并通过 Fas 途径增强细胞凋亡”癌基因。

Clinical significance of the overexpression of the candidate oncogene CYP24 in esophageal cancer

• DOI: 10.1093/annonc/mdh056
• 发表时间: 2004-02-01
• 期刊: ANNALS OF ONCOLOGY
• 影响因子: 50.5
• 作者: Mimori, K;Tanaka, Y;Mori, M
• 通讯作者: Mori, M

Global analysis of altered gene expressions during the process of esophageal squamous cell carcinogenesis in the rat: a study combined with a laser microdissection and a cDNA microarray.

• DOI: 10.1158/0008-5472.401.65.2
• 发表时间: 2005-01
• 期刊: Cancer research
• 影响因子: 11.2
• 作者: K. Nishida;S. Mine;T. Utsunomiya;H. Inoue;M. Okamoto;H. Udagawa;T. Hanai;M. Mori

黒木 保, 井上 裕, 森 正樹: "消化器外科 レビュー:発癌機構(分担執筆)"総合医学社. 268 (2003)

Tamotsu Kuroki、Yutaka Inoue、Masaki Mori：“胃肠外科评论：癌发生机制（合著者）”Sogo Igakusha 268（2003）。

Differential expression of MMP and uPA systems and prognostic relevance of thier expression in esophageal squamous cell carcinoma

食管鳞癌中MMP和uPA系统的差异表达及其表达的预后相关性

• 发表时间: 2004
• 期刊: Int J Cancer 110
• 作者: Sueda T;Ymashita K et al.
• 通讯作者: Ymashita K et al.