制吐剤の動注化学療法に及ぼす影響に関する基礎的研究

止吐药对动脉化疗影响的基础研究

• 批准号: 13672087
• 负责人: SHIKIMORI Michio
• 金额: $ 0.7万
• 依托单位: Hamamatsu University, School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13672087/
• 关键词: VX2 carcinoma; CDDP; THP-ADM; antiemetics; granisetoron; TISSUE LEVEL; VX2vcarcinoma; antiemetics; azasetron; ondansetron; metoclopramide

Background : Intraarterial neoadjuvant chemotherapy with Pirarubicin(THP), Cisplatin (CDDP) and Peplomycin (PEP) (TPP therapy) showed a high primary effect on oral cancers (Hashimoto et al,1993). Mori et al reported that 5 year survival rate of stage IV after TPP therapy were 73.3% in group of intraarterial infusion, and 43.6 % in group of venous infusion, respectively. Experimentally, intraarterially preadministered THP showed a beneficial effect on CDDP con- centrations in the tissue of the lymph nodes. After 5HT receptor antagonists such as granisetron (GRN) became available for clinical use, the clinical response to TPP therapy became lower (Komatsu et al, 1997). In this paper, the influences of antiemetics on the transition of CDDP into tissues was studied. Materials & Methods : VX-2 carcinoma was transplanted to the dorsum pedis of Japanese white rabbits (average body weight 3.0 kg). The tumor was treated intraarterially with CDDP (2mg/kg) via the femoral artery after administrat … More ion of THP 1mg/kg(bolus) via the femoral artery. In experimental groups, GRN (1mg/kg), Azasetron(AZA) (3mg/kg), Ondansetron(OND) (1mg/kg) or Metoclopramide(MCP) (3mg/kg) were administered intravenously via the auricular vein 30 minutes before administration of CDDP, and saline was administered in the control group. The tissue, including the tumor and the popliteal lymph node on the same side, were collected along with the blood 30 minutes after the administration of CDDP.Results : The concentrations of CDDP in the lymph nodes was observed to be significantly higher in the control group (3.39^^+__-3.96 μ g/g) than in the GRN group (1.81^^+__-0.08 μ g/g). From additional experiments, the CDDP levels in lymph nodes were 2.31^^+__-11.50 μ g/g (n=4) in the control group, 2.22^^+__-0.79 μ g/g in the AZA group (n=4), 1.90^^+__-0.43 μ g/g in the OND group (n=4) and 3.39^^+__-5.43 μ g/g in the MCP group (n=4), respectively. There were no significant differences in the CDDP levels in the lymph nodes among the groups. The CDDP levels in the tumors of each groups did not show no specific tendencies. These results were supported by the histological findings that poor vascularlization was observed.Conclusion: It was indicated experimentally that GRN decreases the level of CDDP in the lymph nodes significantly as comparied with the control group. However, it was clarified experimentally that AZA, OND and MCP do not decrease CDDP levels of in the lymph nodes, as compeared with the control group. Less

背景资料：使用吡拉西坦（THP）、顺铂（CDDP）和培洛霉素（PEP）（TPP疗法）的动脉内新辅助化疗显示出对口腔癌的高原发性效应（Hashimoto et al，1993）。Mori等报道TPP治疗后IV期5年生存率动脉灌注组为73.3%，静脉灌注组为43.6%。在实验上，动脉内预给药THP显示对淋巴结组织中CDDP浓度的有益作用。在5 HT受体拮抗剂如格拉司琼（GRN）可用于临床使用后，对TPP治疗的临床反应降低（Komatsu et al，1997）。本文研究了止吐药对顺铂组织转运的影响。材料与方法：将VX-2肿瘤移植于日本白色大白兔（平均体重3.0 kg）的足背。给药后经股动脉给予顺铂（2 mg/kg）治疗。 ...更多信息 经股动脉注入THP 1 mg/kg。实验组在CDDP给药前30 min经耳缘静脉分别给予GRN（1 mg/kg）、阿扎司琼（3 mg/kg）、昂丹司琼（1 mg/kg）或甲氧氯普胺（3 mg/kg），对照组给予生理盐水。结果：对照组淋巴结中CDDP浓度（3.39 ± 3.96 μ g/g）明显高于GRN组（1.81 ± 0.08 μ g/g）;根据附加实验，淋巴结中的CDDP水平在对照组中为2.31^^+__-11.50 μ g/g（n=4），在AZA组中为2.22^^+__-0.79 μ g/g（n=4），在OND组中为1.90^^+__-0.43 μ g/g（n =4），在MCP组中为3.39^^+__-5.43 μ g/g（n=4），分别各组淋巴结中CDDP水平无显著差异。各组肿瘤中CDDP水平无特异性变化趋势。结论：GRN能显著降低淋巴结内CDDP的水平。然而，实验表明，与对照组相比，AZA、OND和MCP不降低淋巴结中的CDDP水平。少