Pharmacologic and toxicologic evaluation of C-novyi-NT spores
Pharmacologic and toxicologic evaluation of C-novyi-NT spores
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DOI：
10.1093/toxsci/kfi316
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发表时间：
2005-12-01
影响因子：
3.8
通讯作者：
Huso, DL
中科院分区：
文献类型：
--
作者：
Diaz, LA;Cheong, I;Huso, DL
诺氏梭菌（Clostridium novyi）-NT（C.诺氏-NT）孢子已显示在小鼠和兔的实验性肿瘤中是有效的治疗剂。在本研究中，进行了药理学和毒理学研究，以更好地了解影响这种治疗形式的疗效和毒性的因素。我们发现孢子被网状内皮系统迅速从循环中清除。即使在给予大剂量后，在健康小鼠或家兔中也未观察到临床毒性。孢子对血管化不良的非肿瘤性病变（包括心肌梗死）小鼠也没有毒性。在荷瘤小鼠中，毒性似乎与肿瘤大小和孢子剂量相关，与任何细菌感染的预期一致。然而，没有败血症的实验室或组织病理学证据，并且毒性可以通过简单的水化得到有效控制。
Clostridium novyi-NT (C. novyi-NT) spores have been shown to be potent therapeutic agents in experimental tumors of mice and rabbits. In the present study, pharmacologic and toxicologic studies were performed to better understand the factors influencing the efficacy and toxicity of this form of therapy. We found that spores were rapidly cleared from the circulation by the reticuloendothelial system. Even after large doses were administered, no clinical toxicity was observed in healthy mice or rabbits. The spores were also not toxic in mice harboring poorly vascularized non-neoplastic lesions, including myocardial infarcts. In tumor-bearing mice, toxicity appeared related to tumor size and spore dose, as expected with any bacterial infection. However, there was no laboratory or histopathologic evidence of sepsis, and the toxicity could be effectively controlled by simple hydration.