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The study of the effect of preoperative heavy-ion irradiation on inhibition of local recurrence in patients with resectable pancreas cancer after curative resection.

术前重粒子线照射对可切除胰腺癌根治性切除术后局部复发抑制作用的研究

基本信息

批准号：
15591315
负责人：
YAMADA Shigeru
金额：
$ 2.18万
依托单位：
National Institute of Radiological Sciences
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15591315/
关键词：
Pnacreas heavy ion angiogenesis hypoxic antibody array cell cycle 低酸素 VEGF VEGFR 重粒子再発 Ras

项目摘要

We measured surviving fractions of MIAPaCa (papillary adenocarcinoma), Bx-Pc and Panc-1 (Invasive ductal carcinoma) treated by heavy-ion therapy. Cell killing effects of heavy ion therapy did not depend on the oxygen concentrations compared to that of X-ray irradiations. Then we measured the protein expressions related angiogenesis. Papillary adenocarcinoma has richer blood flow than invasive ducatal carcinoma. Expressions of VEGF-A and VEGFZR-2 at Panc-1 were higher that at MIAPaCa. Hypoxic concision did not change the expressions of VEGF-A and VEGFR-2. However hypoxic condition enhanced the expression of VEGFR-3 which was related to the lympho node metastasis and local recurrence. Heavy ion therapy reduced the expression of VEGFR-3. So heavy ion therapy reduced the local recurrence after curative resections in patients with pancreas cancer. We measured 736 proteins by Antibody Array System. Heavy ion therapy increased the expressions of cell cycle regulating proteins under oxic condition. However under hypoxic condition the expressions of cell cycle regulating proteins were decreased and cell cycle of damaged cell were delayed. During this delay damaged cell were able to repair DNA breaks.

我们测量了经过重离子治疗的MIAPaCa（乳头状腺癌）、Bx-Pc和Panc-1（浸润性导管癌）的存活分数。与x射线照射相比，重离子治疗的细胞杀伤效果不依赖于氧浓度。然后测量血管生成相关蛋白的表达。乳头状腺癌比浸润性导管癌有更丰富的血流。VEGF-A和VEGFZR-2在Panc-1的表达高于MIAPaCa。低氧浓缩未改变VEGF-A和VEGFR-2的表达。而缺氧条件下VEGFR-3的表达增强，与淋巴结转移和局部复发有关。重离子治疗可降低VEGFR-3的表达。因此，重离子治疗可降低胰腺癌根治性切除术后的局部复发。我们用抗体阵列系统检测了736个蛋白。重离子处理增加了缺氧条件下细胞周期调节蛋白的表达。而在缺氧条件下，细胞周期调节蛋白的表达减少，损伤细胞的细胞周期被延迟。在这一延迟期间，受损细胞能够修复DNA断裂。