Basic study on chemoresistance and thermoresistance of head and neck cancer

1995年应用ATP法对139例头颈部恶性肿瘤进行药物敏感试验。化疗敏感性依次为5-FU（27%）>CDDP=CBDCA>MTX>PEP（23%）。这一结果表明，其余约25%显示出天然抗性。P-糖蛋白的表达是化疗耐药的原因之一，约60%的肿瘤表达P-糖蛋白，并与阿霉素耐药密切相关。当鳞癌组织中谷胱甘肽（GSH）含量增加时，对顺铂的敏感性降低。1996年：研究了细胞内GSH含量与顺铂敏感性的关系。结果表明，GSH水平降低引起细胞坏死性死亡，GSH水平升高引起细胞凋亡。本研究采用多项临床试验，对顺铂敏感性的4个主要耐药因素，即药物内流、外流、DNA-Pt加合物和DNA修复进行了研究。 ...更多信息 ncer细胞系结果显示了细胞系间的异质性。凋亡诱导基因Fas（+）、Bcl-2（-）阳性者，化疗敏感性良好。具有G-CSF受体的癌细胞系通过rG-CSF刺激增加细胞侵袭。1997年：应用免疫组化方法检测了115例头颈部恶性肿瘤中多药耐药相关蛋白（MRP）的表达，30%的头颈部恶性肿瘤MRP表达阳性，但与临床无相关性，与肿瘤的耐药无关。研究了蛋白激酶抑制剂H-7对顺铂（CDDP）杀伤人鼻咽癌细胞株KB细胞的增效作用。H-7处理KB细胞后，PKC活性明显降低，细胞对CDDP敏感，细胞内GSH水平呈剂量依赖性下降。40 ℃的低温可增加顺铂的铂在癌细胞中的积累。因此，即使在低的高温下，CDDP敏感性在CDDP耐药变体中也是高温化学增强的。联合顺铂和bcl-2反义治疗可增加顺铂的敏感性，从而为基因化疗提供了可能。免疫组化检测凋亡诱导基因bax的表达。Ⅰ期和Ⅱ期早期的阳性表达率明显高于晚期。少

1995 : The chemosensitivity test by ATP method was applied to 139 cases of head and neck cancer. The evaluated rate was 95%, and the chemosensitive rate was in the order of 5-FU (27%) >CDDP=CBDCA>MTX>PEP (23%). This results indicate that the rest of about 25% show the natural resistance. The expression of P-glycoprotein as one of the cause of chemoresistance appeared in about 60% of them, and showed significant correlation with ADM-resistance. When the content of glutathione (GSH) in squamous cell carcinoma increased, the sensitivity to CDDP decreased. It was proved that the LAK activity increased with hyperthermic condition.1996 : The relationship between the intracellular GSH content and CDDP sensitivity was investigated. The result showed that the decreased level of GSH induced necrotic cell death, while the increased GSH induced apoptosis. The 4 main resistant factors, drug influx, efflux, DNA-Pt adducts and DNA repair, were investigated concerning CDDP sensitivity using several ca … More ncer cell lines. The result showed the heterogeneity among the cell lines. The cases stained with apoptosis-inducing genes, Fas (+) and Bcl-2 (-), showed good chemosensitivity. The cancer cell lines having G-CSF receptors increased the cell invasion by rG-CSF stimulation. This fact should be bore in mind for clinical use.1997 : The expression of multidrug resistance-associated protein (MRP) in 115 cases of head and neck carcinomas was investigated by immunohistochemistry, and 30% of them showed positive staining without any clinical correlation and anticancer drug resistance. The synergistic effects of H-7, a protein kinase inhibitor (PKC), on CDDP cytotoxicity to KB cells, a human pharyngeal carcinoma cell line, was investigated. The treatment with H-7 markedly decreased PKC activity and significantly sensitized the cells to CDDP.The treatment of KB cells with H-7 induced a dose-dependent depletion of intracellular GSH levels. A low hyperthermia at 40ﾟC increased accumulation of platinum of CDDP into cancer cells. As a result, CDDP sensitivity was hyperthermically chemopotentiated in CDDP-resistant variants even at low hyperthermia. A combination with CDDP and bcl-2 antisense therapy increased CDDP sensitivity, and thus a possibility of gene chemotherapy was introduced. The expression of bax, a gene inducing apoptosis, was immunohistchemically examined. The positive expression was significantly more observed in the early stage I and II than the late stage. Less