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ホウ素熱中性子捕捉療法の適応拡大に関する研究副題:単クローン抗体利用の^<10>B集積、即発γ線による癌診断、L体単離による^<10>B-BPAの薬効増強

扩大硼热中子捕获疗法适应症的研究副标题：利用单克隆抗体^<10>B积累、通过即时伽马射线诊断癌症、通过分离L体增强^<10>BPA的药效

基本信息

批准号：
63010045
负责人：
三島豊
金额：
$ 7.55万
依托单位：
Kobe University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Cancer Research
财政年份：
1988
资助国家：
日本
起止时间：
1988 至无数据
项目状态：
已结题

项目摘要

1.a)昨年合成の新化合物3種中の2種はM・^<10>B_<12>H_<11>NH_<3-n>(CH_2CO_2H)_n(n=1,2)と確定。Polysineを先ずCH_3O(C_2H_4O)_mCH_2CO_2Hで、,次にn=2単離品で処理、分子当り^<10>B原子370を含む水溶性ポリマーを得た。これの抗体付加法を研究中。b)分子当り^<10>B原子38を含む水溶性avidinを徳久班員に提供。2.単クローン抗体を用いた黒色腫抗原の生化学的解析により抗原分子は80kdと18kdが非共有結合した糖蛋白であることを解明。3.ヒト黒色腫細胞にビオチン化単クローン抗体、1項記載の^<10>B化avidinを順に反応させ、熱中性子照射。5日間培養してコロニー法(昨年はTrypan Blue法)で高い致死効果を認めた。4.ホウ素化ウラシル化合物のHeLa細胞致死作用を観測、強い毒性を認めず。5.X線感受性が異なる黒色腫細胞でもホウ素熱中性子捕捉処理では同等に殺傷されることを示すための試料4株につき37%生残X線量を測定(4.4、3.7、2.3、1.4Gy)。6.小病巣検出用小型高精度装置の設計は一応終了。京大炉稼働一年間休止のための試作とテストは来年度に繰越し。7.^<10>B-BPA懸濁液を3g/kg用量で雌雄ラット各10匹に経口投与。全例2週間生存(LD_<50>>3g/kg)。投与後の体重、臓器重量は対照ラットと有意差なし。8.a)D,L-BP化をエチルエステルA後α-キモトリプシン処理し、目的のL-BPA数百mgを採取。b)DL-BPAエチルエステルD-酒石酸を加え、生成塩2種の溶解度差を利用する分離法は不成功。原因究明の結果、対策を案出できた。9.マウス同種免疫で得た6種の抗ガングリオシド(GD_2)抗体はヒトメラノーマ移植のヌードマウスに増殖抑制顕著。10.熱中性子照射で生じる^<14>N(n,p)^<14>C、^<10>B(n,α)^7Li反応の皮膚障害に対するRBEは約2.0であると推定。11.メラニン生成活性が低い培養黒色腫細胞を通常medium(tyrosine、phenylalanine含有)で^<10>B-BPA preincubation後熱中性子照射。Do=1.5×10^<12>n/cm^2。同操作をt・p不含mediumで行いDo=1.1×10^<12>n/cm^2。明らかに不含系の方が高致死である。

1. a) Two of the three new compounds synthesized last year <10><12><11><3-n>were identified. Polysine first contains CH_3O(C_2H_4O)_mCH_2CO_2H, then n=2, then n = 3, then n = 4, then n = 3, then n = 4, then n=2, then n = 4, then n = 3, then n = 4, then n = 2, then n = 4, then n = 3, then n = 4, then n=2, then n = 4, then n = 3, then n = 4, then n = 4, then n = 2, then n = 4, then n = 3, then n = 4, then n = 2, then n = 4, then n <10>= This antibody is still under study. b) <10>Molecules containing water-soluble avidin are available for long periods of time. 2. The biochemical analysis of black tumor antigen by using antibody-specific antigen was analyzed. The antigen molecule was 80kd and 18kd, and the non-consensus binding glycoprotein was analyzed. 3. Antibodies against black tumor cells, anti-inflammatory agents <10>against avidin as described in item 1, and hot spot irradiation. 5 Day culture 4. Detection of lethal effect and strong toxicity of the compounds on HeLa cells 5. X-ray sensitivity was different among the black tumor cells, and the amount of residual X-ray was determined (4.4, 3.7, 2.3, 1.4Gy). 6. The design of small high-precision devices for small disease detection has been completed. Beijing University has been working for a year. 7.^ <10>The dosage of B-BPA suspension is 3 g/kg, and the dosage of male and female is 10%. All cases survived within 2 weeks (LD_<50>>3g/kg). The weight after throwing and the weight of the equipment are different from each other. 8.a)D, L-BPA after α-BPA treatment, target L-BPA hundreds of mg taken. b)DL-BPA is not successfully separated by adding DL-BPA and D-tartaric acid to form DL-BPA and using the solubility difference between DL-BPA and D-tartaric acid. The cause of the investigation, the result of the investigation, the strategy of the investigation, the result of the investigation, the result, the result of the investigation, the result of the investigation, the 9. Six kinds of anti-GD2 antibodies were obtained by alloimmunization. 10. The <14><14><10>RBE for skin damage caused by thermal neutral sub-irradiation is estimated to be about 2.0. 11. The production activity of BPA is low. Black cells are usually cultured in medium(containing tyrosine and phenylalanine). <10>BPA is preincubated and then irradiated with hot water. Do=1.5×10^<12>n/cm^2。The same operation t·p does not contain medium line Do=1.1×10^<12>n/cm^2. The light does not contain the system of high death.