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Expressionand Regulation of Autocrineand Angiogenic Factors produced by Oral Cancer

口腔癌自分泌和血管生成因子的表达及调控

基本信息

批准号：
09470455
负责人：
OKAMOTO Tetsuji
金额：
$ 7.42万
依托单位：
HIROSHIMA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09470455/
关键词：
Oral Cancer Salivary Gland Tumor Gene Therapy Differentiation Apoptosis FGF FGF Receptor Caspase 扁平上皮癌 VEGF FGFR KGF 遺伝子診断

项目摘要

Malignant salivary gland adenocarcinoma is devastating neoplasm that is associated with a poor prognosis in the head and neck regions. Although the reasons for aggressiveness of these disorder are not well known, some alternations of oncogenic molecules and the overexpression of growth factors which may give neoplastic cells a growth advantage have been demonstrated. The normal salivary gland is composed of well-defined epithelial and stromal cell components which communicate to maintain normal gland structure, function and differentiation. The epithelial compartment of benign salivary gland tumors usually exhibits some degree of morphological differentiation that distinguishes it from the stromal compartment. In contrast, malignant tumors are undifferentiated and exhibit no apparent relationship between epithelial and stromal cells.Our previous studies indicated that FGF receptors. underwent parallel changes during malignant progression. FGFR1-IIIc and FGFR4 were overexpressed in malignant salivary gland adenocarcinoma, but absent in normal salivary gland and benign salivary gland tumors which overexpressed FGFR2IIIb (KGFR).In present study, full-length of wild type KGFR/wtFGFR2-IIIb cDNA was ligated into pcDNA 3.l/zeo mammalian expression vector ; and transfected into malignant salivary gland adenocarcinoma HSY cell. The results clarified that wtFGFR2IIIb inhibit populational growth rate, induce cell differentiation and programmed cell death of malignant salivary gland adenocarcinoma in vitro and in vivo.Base on present study, FGFR2-IIIb gene transfer ex vivo with gene gun would be available and may be quite efficent for malignant salivary gland adenocarcinoma. FGFR2-IIIb gene transfer ex vivo is expected to .be a brand new gene therapy for malignant salivary gland adenocarcinoma.In summary, the introduction of wtFGFR2-IIIb into malignant salivary gland adenocarcinoma cells can suppress the growth of the cancer cells and induce apoptosis in vitro and in vivo.

恶性唾液腺腺癌是一种毁灭性的肿瘤，与头颈部预后不良有关。虽然这些疾病的侵袭性的原因还不是很清楚，一些致癌分子的改变和生长因子的过度表达，这可能会给肿瘤细胞的生长优势已被证明。正常的唾液腺由明确的上皮细胞和基质细胞组成，它们相互沟通以维持正常的腺体结构、功能和分化。良性唾液腺肿瘤的上皮区室通常表现出一定程度的形态分化，使其与间质区室区分开来。相反，恶性肿瘤是未分化的，上皮细胞和间质细胞之间没有明显的关系。在恶性进展期间发生平行变化。本研究将野生型KGFR/wtFGFR 2-IIIb（KGFR）全长cDNA连接到pcDNA 3.1/zeo哺乳动物表达载体中，转染恶性涎腺腺癌HSY细胞，观察KGFR/wtFGFR 2-IIIb的表达情况。结果表明，wtFGFR 2-IIIb在体外和体内均能抑制恶性涎腺腺癌的群体生长速率，诱导细胞分化和程序性细胞死亡，因此，本研究为应用基因枪体外转FGFR 2-IIIb基因治疗恶性涎腺腺癌提供了可能。体外转FGFR 2-IIIb基因有望成为一种全新的基因治疗恶性涎腺腺癌的方法，总之，在体外和体内将wtFGFR 2-IIIb基因导入恶性涎腺腺癌细胞中可以抑制癌细胞的生长并诱导其凋亡。