The basic and clinical study on the effective individual oral cancer therapy

口腔癌个体化有效治疗的基础与临床研究

• 批准号: 13307057
• 负责人: SAKASHITA Hideaki
• 金额: $ 27.62万
• 依托单位: Meikai University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13307057/
• 关键词: oral cancer; squamous cell carcinoma; gene alteration; p53; apoptosis; anticancer drug; dendritic cell; VEGF

1. The analysis of cytotoxic effect and its mechanism of apoptosis-induced drug for oral cancer cell lines. : The apoptosis-induced drug does not always reveal high tumor selectivity. Low-molecular-weight polyphenol inhibited NO production from LPS-stimulated macrophage.2. Analysis of p53 gene alterations in primary oral cancer. : At first, immunohistochemistry using MAb p53 antibody was performed, 18 of 33 cases (54.5%) were positive. Then p53 gene alteration was analyzed by PCR-SSCP and direct sequencing. As the results, p53 point mutations were detected in 14 of 33 cases (42.4%). In addition to last year, p53 gene alterations were totally detected in 19 of 54 cases (35.2%).3. Anticancer drug sensitivity test for individual patient. : Case1 : 5-FU : 78.2%, CDDP : 69.2 %, PEP : 0 %, TXL : 60 %, 254-S : 83.5% ; Case 2 : 5-FU : 53.2%, CDDP : 46.3%, PEP : 41.1%, TXL : 73.3%, 254-S : 68.8 % ; Case 3 : CDDP : 48.8%, PEP : 33.2%, TXL : 90.3%, 254-S : 67.9% ; Case 4 : We could not get informed concent ; Case 5 : Assay was failed. ; Case 6 : 5-FU : 37.8, CDDP : 27.1, 254-S : 52.9, TXL : 62, PEP : 3.9(%) ; Case 7 : CDDP : 27.1, PEP : 83(%)4. The basic study on lymphocyte activating therapy. : Immortalization of cancer cells was not succeed yet. VEGF was detected from various oral cancer cell lines. The culture of Dendritic cells (DC) in the medium included VEGF inhibited the maturation of it. To inhibit the action of VEGF is a key way for the success of lymphocyte activating therapy.

1.诱导凋亡药物对口腔癌细胞株的细胞毒作用及其机制分析。：诱导肿瘤生长的药物并不总是表现出高的肿瘤选择性。低分子量多酚抑制LPS刺激的巨噬细胞产生NO.原发性口腔癌p53基因突变分析首先用单克隆抗体p53进行免疫组化，33例中18例阳性（54.5%）。采用PCR-SSCP和直接测序法分析p53基因的改变。结果显示，33例中有14例（42.4%）检测到p53点突变。除去年外，54例患者中有19例（35.2%）检测到p53基因异常.个体患者的抗癌药物敏感性试验。：案例一：5-FU：78.2%，CDDP：69.2%，PEP：0%，TXL：60%，254-S：83.5% ;病例2：5-FU：53.2%，CDDP：46.3%，PEP：41.1%，TXL：73.3%，254-S：68.8%;病例3：CDDP：48.8%，PEP：33.2%，TXL：254-S：67.9% ;病例4：无法获得通知浓度;病例5：检测失败。病例6：5-FU：37.8，CDDP：27.1，254-S：52.9，TXL：62，PEP：3.9（%）;病例7：CDDP：27.1，PEP：83（%）淋巴细胞活化疗法的基础研究。癌细胞永生化尚未成功。从各种口腔癌细胞系中检测到VEGF。树突状细胞（DC）在含有VEGF的培养液中培养，其成熟受到抑制，抑制VEGF的作用是淋巴细胞活化治疗成功的关键。

项目成果

Watanabe K: "Cycloartane glycosides from the Rhizomes of Cimjicifuga racemosa and their cytotoxic activities"Chem Pharm Bull. 50. 121-125 (2002)

Watanabe K：“Cimjicifuga racemosa 根茎中的环阿麻苷及其细胞毒性活性”Chem Pharm Bull。

Fukuda M: "A Patient with Multiple Primary Carcinomas, Including 4 Separate Oral Cancers : Study of p53 Mutations and their Implications for Management"J Oral Maxillofac Surg. (in press). (2004)

Fukuda M：“一名患有多种原发癌（包括 4 种单独口腔癌）的患者：p53 突变及其对治疗的影响的研究”J Oral Maxillofac Surg。

Ide F.: "p53 haploinsufficiency profoundly accelerates the onset of tongue tumors in mice lacking the xeroderma pigmentosum group A gene."Am J Pathol.. 163(5). 1729-1733 (2003)

Ide F.：“p53 单倍体不足极大地加速了缺乏着色性干皮病 A 组基因的小鼠舌肿瘤的发生。”Am J Pathol.. 163(5)。

Fukuda M: "Immunohistochemical detection of cytokeratin 18 and its neo-epitope in Warthin tumor(Adenolymphoma) of the parotid glands"Anticancer Res. 21. 109-112 (2001)

Fukuda M：“腮腺沃辛肿瘤（腺淋巴瘤）中细胞角蛋白 18 及其新表位的免疫组织化学检测”抗癌研究。

Jiang Y: "Inhibition of chlorogenic acid-induced cytotoxicity by CoCl2"Anticancer Res. 21. 3349-3354 (2001)

江Y：“CoCl2抑制绿原酸诱导的细胞毒性”抗癌研究。