AntiCancer, Inc., San Diego, CA, USA.
Cell Cycle. 2012 Feb 1;11(3):628-32. doi: 10.4161/cc.11.3.19116.
Malignant glioma tumors are the most common primary central nervous system tumors. Despite the multidisciplinary approach to treatment, prognosis remains poor. In this study, we demonstrated that the Salmonella typhimurium A1-R tumor-targeting strain can inhibit and eradicate human glioma in an orthotopic nude-mouse model. S. typhimurium A1-R was administered by injection through a craniotomy open-window or intravenously in nude mice. To establish the model, 2x10(5) U87-RFP human glioma cells were injected stereotactically into the mouse brain through the craniotomy open window. Two weeks after glioma-cell implantation, mice were treated with S. typhimurium A1-R [2x10(7) CFU/200 μl intravenous injection (i.v.) or 1x10(6) CFU/1 μl intracranial injection (i.c.)] once a week for 3 weeks. Brain tumors were observed by fluorescence imaging through the craniotomy open window over time. S. typhimurium A1-R, administered i.c., inhibited brain tumor growth 7.6-fold compared with untreated mice (p=0.009) and improved survival 73% (p=0.001). Two of ten mice appeared to have their tumors eradicated. Intravenous administration of S. typhimurium A1-R was not effective. The craniotomy open window enabled observation of tumor growth in the brain in real time in both treated and untreated mice. The results of the present study demonstrate that bacterial therapy of brain cancer is a novel, effective and safe treatment strategy in a highly treatment-resistance cancer.
恶性神经胶质瘤是最常见的原发性中枢神经系统肿瘤。尽管采用了多学科治疗方法，但预后仍然很差。在这项研究中，我们证明了鼠伤寒沙门氏菌 A1-R 肿瘤靶向株可以在原位裸鼠模型中抑制和根除人类神经胶质瘤。通过开颅术窗口或静脉内注射将鼠伤寒沙门氏菌 A1-R 施用于裸鼠。为了建立模型，通过开颅术窗口将 2x10(5)个 U87-RFP 人类神经胶质瘤细胞立体定向注射到小鼠脑中。在神经胶质瘤细胞植入 2 周后，用鼠伤寒沙门氏菌 A1-R [2x10(7)CFU/200 μl 静脉内注射 (i.v.) 或 1x10(6)CFU/1 μl 颅内注射 (i.c.)] 每周一次治疗 3 周。通过开颅术窗口随时间观察荧光成像中的脑肿瘤。与未治疗的小鼠相比，经 i.c.给予的鼠伤寒沙门氏菌 A1-R 抑制脑肿瘤生长 7.6 倍（p=0.009），并提高存活率 73%（p=0.001）。十只老鼠中有两只似乎已经消除了肿瘤。鼠伤寒沙门氏菌 A1-R 的静脉内给药无效。开颅术窗口使我们能够实时观察治疗和未治疗小鼠的脑内肿瘤生长情况。本研究的结果表明，细菌性脑癌治疗是一种针对高度耐药性癌症的新型、有效和安全的治疗策略。
