GROWTH OF METASTATIC CACNER CELLS IN THE LYMPH NODES AND ITS REGULATION BY LYMPHOCYTES

淋巴结转移性癌细胞的生长及其受淋巴细胞的调节

• 批准号: 12671828
• 负责人: YAMAMOTO Tetsuya
• 金额: $ 2.5万
• 依托单位: Kochi Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671828/
• 关键词: peplomycin; intranodal injection; surface antigens; reactive oxygen species; lymphocyte subpopulation; cytotoxic activity; cytokine; Mn-SOD; リンパ球亜集団; 細胞傷害能; T細胞; IL-2; IFN-γ; FGF-2; Fas; Fas L; チトクロームC; AIF; ミトコンドリア

To control the metastatic lymph nodes, we examined in and ex vivo and obtained following results.1. The cytotoxic activity of IL-2 activated lymphocytes against cancer cells was increased by pretreatment of cancer cells with anticancer drugs or ^<137>Cs, and a combination of the lymphocytes and anticancer agents brought a strong cytotoxicity.2. Apoptosis induction of cancer cells was inversely associated with Mn-SOD activity of the cancer cells and their apoptosis by IL-2-activated lymphocytes partially depended on reactive oxygen species in the cancer cells. Mn-SOD antisense transfection induced high level apoptosis with an increases of proapoptotic proteins and a decrease of antiapoptotic proteins.3. The intranodal injection of PLM and CDDP brought PR or NO in all patients.4. Concerning lymph node lymphocytes (LNL) ; LNL subpopulations differed from those in peripheral blood lymphocytes (PBL), consisting of a high population of B cells (〜60 %) and low population of T cells (〜10 %). LNL expressed surface antigens similar with those in PBL. The cytotoxic activity of LNL was largely lower than that of PBL. The upregulation of the lowered cytotoxic activity of LNL was not succeeded by IL-2 or INF-γ but in vitro succeeded by the addition of IL-2+IFN-γ/OK-432+peripheral blood monocytes (dendritic cells).

为了控制转移性淋巴结，我们在体内检查并获得了以下结果。1。通过用抗癌药物或 ^<137> CS治疗癌细胞，IL-2激活的针对癌细胞的淋巴细胞的细胞毒性增加，以及淋巴细胞和抗癌药的组合带来了较强的细胞毒性。2。癌细胞的凋亡诱导与癌细胞的Mn-SOD活性成反比，并通过IL-2激活的淋巴细胞的凋亡部分部分取决于癌细胞中的活性氧。 Mn-Sod反义转染诱导高水平凋亡，促凋亡蛋白的增加和抗凋亡蛋白的降低3。 PLM和CDDP的插入室内注射均导致所有患者或没有PR。4。关于淋巴细胞（LNL）； LNL亚群与外周血淋巴细胞（PBL）不同，该细胞由较高的B细胞（〜60％）和T细胞群（〜10％）组成。 LNL表达与PBL中相似的表面抗原。 LNL的细胞毒性活性在很大程度上低于PBL。 IL-2或INF-γ取得了降低的LNL细胞毒性活性的上调，而是通过添加IL-2+IFN-γ/OK-432+外周血单核细胞（树突状细胞）而在体外取得了成功。

项目成果

Tetsuya Yamamoto: "The upregulation by peplomycin of signal transduction in human cells"Japanese Journal of Pharmacology. 87・1. 41-50 (2001)

Tetsuya Yamamoto：“佩普霉素对人体细胞信号转导的上调”日本药理学杂志 87・1（2001）。

木村 剛: "頸部転移リンパ節内への抗癌剤注入療法の試み-^<60>Co外照射との併用による治療効果を中心に-"日本口腔外科学会雑誌. 47. 661-669 (2001)

Tsuyoshi Kimura：“颈转移淋巴结抗癌药物注射疗法的试验-关注与 60 Co外照射组合的治疗效果-”日本口腔颌面外科杂志 47. 661-669（ 2001）

Tokio Osaki: "Peplomycin, a bleomycin derivative, induces myofibroblasts in pulmonary fibrosis"International Journal of Experimental Pathology. 82・4. 231-241 (2001)

大崎东京夫：“博来霉素衍生物培洛霉素诱导肺纤维化中的肌成纤维细胞”，《国际实验病理学杂志》82·4（2001）。

Eisaku Ueta: "Mn-SOD antisense upregulates in vivo apoptosis of squamous cell carcinoma cells by anticancer drugs and γ-rays regulating the expression of Bcl-2 family proteins, COX-2 and p21"International Journal of Cancer. (in press).

Eisaku Ueta：“Mn-SOD 反义通过抗癌药物和 γ 射线调节 Bcl-2 家族蛋白、COX-2 和 p21 的表达来上调鳞状细胞癌细胞的体内凋亡”《国际癌症杂志》（出版中）。

木村 剛: "頸部転移リンパ節内への抗癌剤注入療法の試み-^<60>Co外照射との併用による治療効果を中心に-"日本口腔外科学会雑誌. 47・11. 661-669 (2001)

Tsuyoshi Kimura：“颈部转移淋巴结的抗癌药物注射疗法的试验-关注与60Co外照射的治疗效果”-日本口腔颌面外科杂志47・11-。 669（2001）