Studies on immuno-chemotherapy regulating metastatic factors in head and neck carcinomas

免疫化疗调节头颈癌转移因子的研究

• 批准号: 05671437
• 负责人: TSUKUDA Mamoru
• 金额: $ 1.41万
• 依托单位: Yokohama City University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05671437/
• 关键词: Head and Neck Cancer; Cell Attachment Factor; Growth Factor; Metastasis; Immuno-chemotherapy; 頭頸部癌; 転移因子; ICAM-1発現; 血管新生; basic FGF

The past multidisciplnary treatments have not been able to improve the poor prognosis of advanced head and neck carcinomas. The immunological deterioration in patients and, also, the biological activities of tumor cells might cause this poor outcome. Using established cell lines derived from head and neck squamous cell carcinomas, we studied the biological activities of these tumor cells. There were sensitive tumor cells to TNF-alpha, whereas these tumor cells showed a relatively low sensitivity to 5-FU.Otherwhile some head and neck tumor cells secreted G-CSF.From a patient, both a cell line incapable of secreting G-CSF and a cell line capable of secreting G-CSF were established. The effector cells stimulated by the cells incapable of secreting G-CSF did not show a lytic capacity against both autologous tumor cell lines. The supernatant after the stimulation with this tumor cells included TGF-beta1. The half of studied cell lines expressed ICAM-1 antigen which was augmented by the addi … More tion of IFN-gamma. The degree of ICAM-1 expression on tumor cells had a correlation with the clinical response to chemotherapy. On the other hand, the supernatant of tumor cells included fibronectin like-substance and bFGF.The high expression of fibronectin like-substance in the supernatant correlated with the poor response to chemotherapy and that of the latter one showed a relationship with high response to chemotherapy. Using HUVECs, an initial step of hematogenous metastasis was analyzed. The rolling of T cells under flow conditions was dependent on E-selectin as well as P-selectin expressed on endotherial cells, but not on ICAM-1 expression. In contrast, the adhesion of tumor cells was dependent on ICAM-1 expression on endotherial cells as well as expression of selectin family. The biological influence of growth factors, e.g.bFGF and EGF,on the growth and metastasis of tumor cells, and whether the adequate immuno-chemotherapy would modify the biological capacity are under investigation. Less

过去的多学科综合治疗并不能改善晚期头颈癌的不良预后。患者免疫功能的恶化以及肿瘤细胞的生物活性可能是导致这种不良结局的原因。利用已建立的来自头颈部鳞状细胞癌的细胞系，我们研究了这些肿瘤细胞的生物学活性。肿瘤细胞对肿瘤坏死因子-α敏感，而对5-氟尿嘧啶的敏感性较低。此外，还有一些头颈部肿瘤细胞分泌G-CSF。由不能分泌G-CSF的细胞刺激的效应细胞对两种自体肿瘤细胞系均无裂解能力。经该肿瘤细胞刺激后的上清中含有转化生长因子-β1。被研究的细胞株中有一半表达icam-1抗原，该抗原被addi…增强。更多的干扰素-γ。ICAM-1在肿瘤细胞上的表达程度与化疗的临床疗效相关。肿瘤细胞培养上清液中含有纤维连接素样物质和bFGF，其高表达与化疗反应差有关，后者与化疗反应高有关。利用人脐静脉内皮细胞，分析血行转移的起始步骤。在流动条件下T细胞的滚动依赖于内皮细胞上表达的E-选择素和P-选择素，而不是ICAM-1的表达。而肿瘤细胞的黏附能力则依赖于内皮细胞表面ICAM-1的表达和选择素家族的表达。生长因子如碱性成纤维细胞生长因子和表皮生长因子对肿瘤细胞生长和转移的生物学影响，以及适当的免疫化疗是否会改变生物学能力正在研究中。较少

项目成果

佃 守: "頭頸部扁平上皮癌細胞株のICAM-1の発現性" 日耳鼻. 96. 827-832 (1993)

Mamoru Tsukuda：“ICAM-1 在头颈鳞状细胞癌细胞系中的表达”Nippon Otohana 96. 827-832 (1993)。

Mamoru Tsukuda: "A tumor cell line producing granulocyte colony-stimulating factor and an immune suppressive factor" Biotherapy. 6. 217-223 (1993)

Mamoru Tsukuda：“一种产生粒细胞集落刺激因子和免疫抑制因子的肿瘤细胞系”生物疗法。

Izumi Mochimatsu: "Treatments for malignant melanoma in the head and neck." (in press).

望松泉：“头部和颈部恶性黑色素瘤的治疗。”

Tadayuki Yago: "Studies on adhesion of head and neck carcinoma cells to endotherial cells." (in press).

Tadayuki Yago：“头颈癌细胞与内皮细胞粘附的研究。”

Mamoru Tsukuda: "Production of granulocyte colony-stimulating factor by head and neck carcinomas" Biotherapy. 6. 183-187 (1993)

Mamoru Tsukuda：“头颈癌产生粒细胞集落刺激因子”生物疗法。