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- S" K0 C; J7 ^( B) X加州大学洛杉矶分校的研究组首次确认了祖细胞而不是神经干细胞构成一组称为少突胶质细胞瘤的神经胶质瘤。这种差异解释了少突胶质细胞瘤比其他的脑肿瘤，如多形性胶质母细胞瘤，对于治疗更加敏感的原因。研究者认为该发现意义重大，因为它为癌症医生和研究者提供了新的细胞治疗途径，并且颠覆了目前认为脑肿瘤来自于神经干细胞的概念，因为少突胶质细胞瘤来自于祖细胞，针对性的干细胞疗法可能对于治疗此类脑肿瘤疾病作用不大。患有少突胶质细胞瘤的病患比患有多形性胶质母细胞瘤的病患寿命更长。这两类肿瘤看起来很相似，但结果却如此不同。神经内科、小儿科及神经外科系的William A. Weiss博士说我们对此颇感兴趣，并且对于神经胶质瘤的分子基础研究还有大量的工作要做，但是目前的治疗方法并没有得到改善。绝大多数的病人死于此种疾病。我们现在必须具备对肿瘤进行细分，以及辨别不同细胞来源的神经胶质瘤的能力，这将有益于更有效的治疗。- W: N, S6 {7 `1 a8 T/ J' {
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该研究12月14日发表在Cancer cell上。国家脑肿瘤协会认为，胶质母细胞瘤来自于大脑的神经胶质细胞，具有高度的活跃性，患有此疾病的患者寿命约为诊断后的6到12个月。神经胶质细胞和神经细胞都来源于祖细胞，进而也来自于神经干细胞。Oligodendrglial细胞是一种神经胶质细胞，支持神经细胞，通过产生髓鞘使其免受影响，髓鞘是一种促进神经元间交流的物质。) {9 y( R1 p7 ^3 t5 ^" Z1 H8 \
& {9 { f; C# j; F4 k5 D& X/ _- P2 V对人类和老鼠肿瘤进行MRI和详细分分析，研究组发现肿瘤细胞在脑中分化的两种关键方法，分化模式对肿瘤是否对治疗敏感产生影响。来源于神经干细胞的肿瘤，如星形细胞瘤，对于治疗的敏感度不那么强烈，因为休眠状态的干细胞肿瘤细胞不会分化，除非受到某种因素的刺激。来自于祖细胞的肿瘤，例如少突神经胶质瘤，对于治疗更加敏感，因为祖细胞可进行积极地分裂。. s6 W& E/ V s
+ x+ j( C' D; k. A4 K加州大学旧金山分校Helen Diller家庭综合癌症中心的神经学副教授Anders I. Persson博士认为，这些结果表明，少突胶质细胞瘤的肿瘤细胞来自于普通的少突胶质前体细胞，即祖细胞而不是神经干细胞的来源，可改善肿瘤患者的病情。
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由于少突胶质细胞瘤对于治疗更加敏感，研究组假设这种敏感度可能是神经祖细胞的一个特性。为了对此进行测试，他们对干细胞、星形细胞瘤、祖细胞及少突胶质细胞瘤采取神经胶质瘤治疗的化学治疗方法。他们发现干细胞与星形细胞瘤很大程度上依赖于药物，但是少突细胞和神经祖细胞的生长极大地停滞。- L5 B8 x9 F* k C* Q& ]+ {" F
% T" {% c% `1 w* g/ h9 z原文：( r& z2 H; C* {0 }
Cell of Origin for Brain Tumors May Predict Response to Therapy" Y3 U5 B* V6 |# W; G; g
The finding is significant, the researchers say, because it gives cancer doctors and researchers new cellular pathways to target in developing therapies. It also updates current beliefs -- that brain tumors derive from neural stem cells -- with the indication that, since oligodendroglioma derives from progenitor cells, stem cell-specific therapies may not hold promise for treating those types of brain tumors.
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7 O# [4 O/ K# k( p* J. a# h& K. M ^- kDifferent life expectancies for two types of brain tumors were what first piqued the scientists' interest.: I" ^( u$ ^6 K1 P, }1 w9 C" v
$ \2 k* I8 U/ ?2 m6 c+ E$ m"With treatment, patients with oligodendroglioma can live many years longer than patients with gliobastoma multiforme. For two types of tumor that appear similar, the outcome is so different. We were interested in understanding this," said William A. Weiss, MD, PhD, corresponding author and professor in the Departments of Neurology, Pediatrics and Neurological Surgery.( |( x$ ^7 h/ z+ v
. y' w9 P1 F2 J7 q/ |"There has been a great deal of research into the molecular basis of glial tumors, but current therapies have not advanced much. Many remain ineffective and the majority of patients die from the disease, so fresh strategies are desperately needed. The ability we now have to sub-classify tumors and differentiate gliomas based on differences in cell of origin will be helpful in the search for more effective treatments," Weiss added.- l5 r3 t# T+ Q, ]% y/ \
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Findings are described in the December 14 issue of the journal Cancer Cell.
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Glioblastomas arise from the glial cells in the brain and are known to be highly aggressive, resulting in a life expectancy of just six to 12 months after diagnosis, according to the National Brain Tumor Society. Glial and neuronal cells both arise from progenitor cells, which in turn arise from neural stem cells. Oligodendrglial cells are a type of glial cell that supports neuronal cells, insulating them by producing myelin, a substance that promotes communication between neurons.0 C% q- t4 g m6 N5 O5 @6 R' x* {0 ^
5 Y1 o. @& f8 F# D2 L# P/ m+ m2 A"Our study shows that tumors can arise from either neural stem cells or progenitor cells, which produce different types of brain cancers that exhibit different responses to therapy," Weiss said.; V4 \9 W! F- q; Z9 Y+ |! x
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Using MRI and detailed analyses of both human and mouse tumors, the team discovered that tumor cells differentiate in the brain in two key ways, and the mode of differentiation impacts whether the tumor will be sensitive to therapy. Tumors that arise from neural stem cells such as astrocytomas (of which glioblastoma is the most common) are less sensitive to therapy because dormant stem cell-like tumor cells do not divide unless provoked by certain factors. Tumors that arise from progenitor cells, such as oligodendroglioma, are more sensitive to therapy because progenitor cells are actively dividing.
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"These results suggest that oligodendroglioma tumor cells arise from normal oligodendrocyte progenitor cells, and that a progenitor rather than a neural stem cell origin underlies improved prognosis in patients with this tumor," said lead author Anders I. Persson, PhD, assistant professor of Neurology in UCSF's Helen Diller Family Comprehensive Cancer Center.
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L0 ~- G3 R$ N. Y- h7 a+ l$ aSince oligodendrogliomas are more sensitive to therapy, the team hypothesized that this sensitivity might be a property of the glial progenitors from which they arise. To test this, they treated stem cells, astrocytomas, progenitors and oligodendrogliomas with the chemotherapeutic used for glioma treatment, temozolomide. They found that stem cells and astrocytoma cells were largely resistant to the drug, but the growth of oligodendroglioma cells and of glial progenitors was vastly stalled.
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" [0 A) V/ ?0 t2 R+ D3 B! V"By studying the properties and behavior of the precursor cells, we have better clues about which cellular pathways could be effective for therapy, depending on the type of tumor," Persson said. "So for instance, now that we know to determine whether a brain tumor is a progenitor disease or stem cell disease, we could use MRI to make these diagnoses, resulting in faster, more effective treatment for glioma patients."
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The study was supported by the Swedish Society for Medical Research, Swedish Medical Research Council, Hjarnfonden (the Swedish Brain Foundation), Sandler Postdoctoral Fellowship and the Joel A. Gingras Jr/American Brain Tumor Association Fellowship. Funding was also provided by a Sandler Opportunity Award in Basic Science, National Institutes of Health, Brain Tumor Society, UCSF Academic Senate, Accelerate Brain Cancer Cure and the Burroughs Wellcome Fund.
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! ?# G0 ]3 L' J2 Y8 T5 x$ PAdditional UCSF authors include Claudia Petritsch, PhD; Fredrik J. Swartling, PhD; Melissa Itsara; David D. Goldenberg; Scott Vandenberg, MD, PhD; Kim N. Nguyen; Stanislava Yakovenko; Jennifer Ayers-Ringler; Mitchel S. Berger, MD; Gabriele Bergers, PhD; and Tracy R. McKnight, PhD.
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7 D5 Y/ M/ J) v: ?Authors not affiliated with UCSF include Steven Goldman, MD, PhD, Frasier Sim, PhD and Romane Auvergne, PhD, from the University of Rochester; Akiko Nishiyama from the University of Connecticut; and William B. Stallcup, PhD, from Burnham Institute for Medical Research.
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' f, `6 M0 R# |7 oUCSF is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care.1 A+ S0 A) X* n
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链接：http://www.sciencedaily.com/releases/2010/12/101214141943.htm |
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发表于 2010-12-25 08:39
