Neuro-Oncology Research Laboratory, Center for Neuroscience and Stem Cell Research, CHOC Children's Hospital, 455 S. Main Street, Orange, CA 92868-3874, USA.
Curr Stem Cell Res Ther. 2010 Dec;5(4):297-3.
In children, cancers are the deadliest of diseases and second only to accidents as the leading cause of death. The deadliest of the brain cancers are the malignant gliomas. Approximately two-thirds of children can survive less malignant types of brain cancers, however, in ~67% of these survivors recurs under the current regimes of surgery followed by administration of high doses toxic drugs and exposure to high doses of radiation. Even more distressing is that fortunate survivors are generally left with life-long cognitive disabilities. A new medical approach is desperately needed. Stem cells, with their natural ability to seek out brain tumors, could be used to accurately deliver therapy directly to the cancer sparing normal tissues for suppression of tumor growth. Despite exciting initial reports, clinical potency of stem cell therapy in animal brain tumor models has to date proven disappointing. Attempts to extrapolate the animal study results to humans are stymied by the fact that stem cells are heterogeneous, resulting in differences in their efficacy. Indeed, therapeutic success relies on an effective strategy to select for a stem cell sub-population within some particular stage of the development at which they are competitive and capable of targeting brain tumors. To improve this during developmental path, concept of a 'therapeutic window' is proposed. The "therapeutic window" for stem cells or more specifically a "biochemical therapeutic window" can be determined from biochemical assays and a "biological therapeutic window" from biological assays or even a molecular window for genetic description. Taken together, we can use selective processes to generate more effective stem cells to treat cancers as is clearly needed today.
在儿童中,癌症是最致命的疾病,仅次于事故,是导致死亡的主要原因。最致命的脑癌是恶性神经胶质瘤。大约三分之二的儿童可以存活下来,恶性程度较低的脑癌,但在目前的手术治疗后,接受高剂量有毒药物治疗并接受高剂量辐射的情况下,约有 67%的患者会复发。更令人痛苦的是,幸运的幸存者通常会留下终身的认知障碍。非常需要一种新的医疗方法。干细胞具有寻找脑肿瘤的天然能力,可以用来将治疗剂直接精确地递送到肿瘤部位,同时保护正常组织免受肿瘤生长的影响。尽管有令人兴奋的初步报告,但干细胞疗法在动物脑肿瘤模型中的临床疗效迄今为止一直令人失望。试图将动物研究结果外推到人类,受到干细胞异质性的事实的阻碍,这导致它们的疗效存在差异。事实上,治疗的成功依赖于一种有效的策略,即在它们具有竞争力并能够靶向脑肿瘤的特定发育阶段,选择干细胞亚群。为了在发育过程中提高这一点,提出了“治疗窗口”的概念。干细胞的“治疗窗口”或更具体地说是“生化治疗窗口”可以从生化测定中确定,而“生物治疗窗口”可以从生物测定中确定,甚至可以从遗传描述的分子窗口中确定。总之,我们可以使用选择性过程来产生更有效的干细胞来治疗癌症,这是当今非常需要的。