Inhibition of human pancreatic cancer growth in nude mice by boron neutron capture therapy.

Inhibition of human pancreatic cancer growth in nude mice by boron neutron capture therapy.
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DOI:
10.1038/bjc.1997.118
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发表时间:
1997
影响因子:
8.8
通讯作者:
Ono, K
Ono, K
中科院分区:
医学1区
文献类型:
--
作者:
Yanagie, H;Tomita, T;Kobayashi, H;Fujii, Y;Nonaka, Y;Saegusa, Y;Hasumi, K;Eriguchi, M;Kobayashi, T;Ono, K

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将抗癌胚抗原(CEA)单抗与含[10B]化合物的脂质体偶联,制备免疫脂质体。这些免疫脂质体可以选择性地与表面带有CEA的人胰腺癌细胞(ASPC-1)结合。用热中子照射评价了局部注射[10B]化合物、含有[10B]化合物的多层脂质体或[10B]免疫脂质体(抗CEA)对人胰腺癌裸鼠移植瘤的细胞毒作用。注射[10B]溶液、含10B脂质体或免疫脂质体的小鼠经热中子照射后,ASPC-1肿瘤生长受到抑制。体内注射[10B]免疫脂质体热中子照射对肿瘤的抑制作用最强。病理组织学显示,10B组肿瘤组织呈玻璃化、坏死,而注射生理盐水或含生理盐水免疫脂质体的肿瘤组织未见破坏或坏死。这些结果表明,瘤内注射硼化免疫脂质体可以增加肿瘤细胞对10B原子的滞留,从而导致热中子照射对体内肿瘤生长的抑制。瘤内注射免疫脂质体的硼中子俘获疗法(BNCT)能够从4He产生侧摧毁正常组织与癌组织交界处的恶性肿瘤细胞。
Immunoliposomes were prepared by conjugating anti-carcinoembryonic antigen (CEA) monoclonal antibody with liposomes containing [10B]compound. These immunoliposomes were shown to bind selectively to human pancreatic carcinoma cells (AsPC-1) bearing CEA on their surface. The cytotoxic effects of locally injected [10B]compound, multilamellar liposomes containing [10B]compound or [10B]immunoliposomes (anti-CEA) on human pancreatic carcinoma xenografts in nude mice were evaluated with thermal neutron irradiation. After thermal neutron irradiation of mice injected with [10B]solution, 10B-containing liposomes or [10B]immunoliposomes, AsPC-1 tumour growth was suppressed relative to controls. Injection of [10B]immunoliposomes caused the greatest tumour suppression with thermal neutron irradiation in vivo. Histopathologically, hyalinization and necrosis were found in 10B-treated tumours, while tumour tissue injected with saline or saline-containing immunoliposomes showed neither destruction nor necrosis. These results suggest that intratumoral injection of boronated immunoliposomes can increase the retention of 10B atoms by tumour cells, causing tumour growth suppression in vivo upon thermal neutron irradiation. Boron neutron capture therapy (BNCT) with intratumoral injection of immunoliposomes is able to destroy malignant cells in the marginal portion between normal tissues and cancer tissues from the side of 4He generation.
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