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Anti-tumor Response induced by Autologous Plasma : Basic Studies and Clinical Trials.

自体血浆诱导的抗肿瘤反应：基础研究和临床试验。

基本信息

批准号：
01570757
负责人：
YAMAMOTO Tsuyoshi
金额：
$ 1.34万
依托单位：
Shimane Medical 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：
1989
资助国家：
日本
起止时间：
1989 至 1990
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-01570757/
关键词：
Plasma perfusion Protein A High molar salts Antitumor responses Tumor necrosis Complements

项目摘要

==INTRODUCTION== An enthusiasm, shown during the '80s, towards antitumor host responses observed at plasma perfusion over immobilized protein A seems to have subsided. It so happened possibly because of the toxicity problems, of unestablished working mechanism and of rather limited clinical benefits. The present study was undertaken to conquer the difficulties by developing a non-bacterial methodology, and to carry out clinical trials for improved benefits.==RESULTS== A : Using rabbits and Vx2 carcinoma ; 1. Ex-vivo modulation of serum or plasma with high molar NaCl (1.5 M) or KCl (0.5 M), as well as protein A, have achieved significant prolongations of the survival time. 2. Normal sera (autologous), as well as the supernatant fraction of 3.5% PEG precipitation, did achieve the host response. 3. The response was abrogated when ; a) serum was treated at 56 C for 30 min prior to modulation with 1.5 M NaCl or b) 1.5 M NaCl-treated serum was given at 24th hr of tumor inoculation. 4. Electr … More on microscopy detected increase in cytoplasmic materials in the intercellular space as early as 3 hr after infusion of 25 ml protein A-treated plasma. B : Clinical studies ; 1. An infusion of NaCl or KCl treated serum or plasma attained an acute response in the tumor but without any serious generalized complication. 2. Normal plasma (treated with 0.5 M KCl) was also attained the response in patients with breast adenocarcinoma by gross observation (3/3) and by studies with LM (3/3) and EM (1/1). 3. Combine use of chemotherapy and plasma-therapy attained benefits more than the assumed algebraic sum of each modality alone. 4. In vitro cytotoxicity by protein A- treated serum was not observed unless the tumor cells were suspended in the autologous (tumor bearing) serum. 4. Serum treated with 0.5 M KCl or 1.5 M NaCl for 30 min at room temperature showed elevations of levels of C4a, C3a and C5a.==Conclusions and suggestions== These findings suggest that the response induced by ex-vivo modulated sarum or plasma is beneficial, that infusion of activated C components, especially those of C3, might be the key for the response, though the infused materials themselves are not cytotoxic and the response in the host is antigen dependent. Less

引言：在80年代期间，对在血浆灌注固定化蛋白A时观察到的抗肿瘤宿主反应的热情似乎已经消退。这可能是由于毒性问题，工作机制尚未建立，临床效益有限。本研究旨在通过开发一种非细菌方法来克服这些困难，并进行临床试验以提高疗效。结果：A：采用家兔和大肠癌; 1.用高摩尔NaCl（1.5 M）或KCl（0.5 M）以及蛋白A对血清或血浆进行离体调节已经实现了存活时间的显著缩短。2.正常血清（自体）以及3.5%PEG沉淀的上清液部分确实实现了宿主应答。3.当a）血清在56 ℃处理30分钟，然后用1.5 M NaCl调节或B）在肿瘤接种的第24小时给予1.5 M NaCl处理的血清时，反应被消除。4.电子 ...更多信息在显微镜下检测到早在输注25 ml蛋白A处理的血浆后3小时细胞间隙中细胞质物质的增加。B：临床研究; 1.输注NaCl或KCl处理的血清或血浆在肿瘤中获得急性反应，但没有任何严重的全身并发症。2.乳腺癌患者经大体观察（3/3）和LM（3/3）及EM（1/1）研究，正常血浆（用0.5 M KCl处理）也获得反应。3.联合收割机联合使用化疗和血浆治疗获得的益处超过假设的每种方式单独的代数和。4.除非肿瘤细胞悬浮在自体（携带肿瘤）血清中，否则未观察到蛋白A处理的血清的体外细胞毒性。4.在室温下用0.5 M KCl或1.5 M NaCl处理30分钟的血清显示C4 a、C3 a和C5 a水平升高。结论与建议：这些结果表明，由离体调制的sarum或血浆诱导的应答是有益的，输入活化的C组分，特别是那些C3可能是应答的关键，尽管输入的材料本身没有细胞毒性，并且在宿主中的应答是抗原依赖性的。少