Basic studies on chemoprevention for head and neck cancer

头颈癌化学预防的基础研究

• 批准号: 08671977
• 负责人: TSUKUDA Mamoru
• 金额: $ 1.22万
• 依托单位: Yokohama City University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08671977/
• 关键词: head and neck carcinoma; squamous cell carcinomas; ATRA; Vitamin D3 derivative; cell growth inhibition; morphological change; 偏平上皮癌; VitD3誘導体; 分化誘導療法; DNA合成

It is well known that all-trans retinoic acid (ATRA) differentiate acute promyelocytic leukemia (APL) cells and ATRA is an efficacious drug for APL.The usefullness of retinoids in chemoprevention for premalignant lesions in the head and neck has been reported. The outcome of cases with advanced head and neck carcinomas is poor in spite of curative treatments, i.e., radiation therapy and/or surgery with chemotherapy and/or immunotherapy. Therefore, a new treatment modality is indispensable for advanced head and neck carcinimas.The inhibitive effects of cell differetiation-related agents, vesnarinone, pamidronate disodium, ATRA and derivatives of Vitamin D3, i.e., 22-oxacalcitriol (OCT) and 1alpha, 25(OH)2D3, on DNA synthesis of human head and neck squamous cell carcinoma cell lines were examined. Futhermore, the sensitivity against chemotherapeutic drugs and morphologocal changes of treated tumor cells was compared to that of non-treated ones. After the treatment with each drug, the cel … More l growth of treated tumor cells was inhibited dependetly on the concentration of each treatment drug. In the derivatives of Vitamin D3, OCT showd a stronger suppression on DNA synthesis than 1alpha, 25(OH)2D3 did. In terms of the comparison of suppressive effects on cell growth between the treatment with OCT and/or ATRA,the combined treatment represented the strongest suppression of DNA synthesis. In cell cycle examination, the treatment resulted in a increase of cells in G0-G1, with an accompanying decrease of cells in S phase. With regard to sensitivity tests using of CDDP or 5-FU,IC50 for CDDP decreased markedly after the treatment with ATRA or vesnarinone. The treated tumor cells showed a less responsiveness to epidermal growth factor. In addition, morphological changes were observed by microscopic analysis after OCT and/or ATRA treatment. The treated cells became bigger and extended the dendrites.These findings suggest the potential usefulness of cell differentiation-related drugs in treatment modality for human squamous cell carcinomas of the head and neck. Less

众所周知，全反式维甲酸(ATRA)可诱导急性早幼粒细胞白血病(APL)细胞分化，ATRA是治疗APL的有效药物。维甲酸对头颈部癌前病变的化学预防作用已有报道。尽管有根治性的治疗，如放射治疗和/或手术配合化疗和/或免疫治疗，但晚期头颈癌患者的预后很差。研究了细胞分化相关药物维司力农、帕米膦酸二钠、全反式维甲酸以及维生素D3的衍生物22-草钙化三醇(OCT)和1α，25(OH)2D3对人头颈部鳞癌细胞株DNA合成的抑制作用。此外，还比较了治疗前后肿瘤细胞对化疗药物的敏感性和细胞形态的变化。在每种药物治疗后，细胞…各处理药物对肿瘤细胞L生长的抑制作用呈浓度依赖性。在维生素D3的衍生物中，OCT对DNA合成的抑制作用强于1α，25(OH)2D3。比较OCT和/或ATRA对细胞生长的抑制作用，OCT和/或ATRA联合处理对DNA合成的抑制作用最强。在细胞周期检查中，G0-G1期细胞增多，S期细胞减少。在CDDP或5-FU的敏感性试验中，经ATRA或维司力农治疗后，CDDP对CDDP的IC50显著降低。经处理的肿瘤细胞对表皮生长因子的反应性较低。此外，通过光镜观察OCT和/或ATRA处理后细胞的形态变化。这些发现表明，细胞分化相关药物在头颈部鳞状细胞癌的治疗方式中具有潜在的应用价值。较少

项目成果

Tsukuda M.: "Chemoradiation-head and neck carcinomas." Jpn.J.Cancer. 24(14). 2049-2057 (1997)

Tsukuda M.：“放化疗-头颈癌。”

Tsukuda M.: "Neuropeptide-containing nerve fibers in the human parotid gland : a semiquantitative analysis using an antibody against protein gene product 9.5." Histoche.J.29. 539-544 (1997)

Tsukuda M.：“人腮腺中含有神经肽的神经纤维：使用针对蛋白质基因产物 9.5 的抗体进行半定量分析。”

佃 守: "頭頸部扁平上皮癌におけるCDDP, 5-FU, MTX, LV併用療法の検討" 耳展. 39(1). 49-55 (1996)

Mamoru Tsukuda：“CDDP、5-FU、MTX 和 LV 联合治疗头颈鳞状细胞癌的研究”Omiten 39(1)。

Tsukuda M.: "Recent chemotherapy for head and neck carcinomas." Otologia. 90(3). 255-267 (1997)

Tsukuda M.：“最近头颈癌的化疗。”

Tsukuda M.: "Influence of epidermal growth factor on head and neck squamous cell lines." Oto-Rhino-Laryngol. 40(2). 156-164 (1997)

Tsukuda M.：“表皮生长因子对头颈鳞状细胞系的影响。”