腦干膠質瘤的干細胞研究進展_《華西醫學》

作者：

楊翔 ,  張躍康

四川大學華西醫院神經外科（成都, 610041）;

關鍵詞：

腦干膠質瘤神經腫瘤干細胞信號通路靶向治療

DOI：

10.7507/1002-0179.20130198

視頻：

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腦干膠質瘤是威脅人類健康的重要疾病，尤其是彌漫內生性橋腦膠質瘤，對兒童的影響更是致命性的。腦干膠質瘤占兒童后顱窩腫瘤的30%，而彌漫內生性橋腦膠質瘤占兒童腦腫瘤15%左右。后者其中位生存時間幾乎不超過1年。由于過去在其生物學特性等方面研究欠缺導致此類腫瘤的治療幾乎無實質性進展。但隨著近年腦干膠質瘤干細胞及其相關信號通路、細胞因子等方面的基礎研究興起，治療方面取得了一定的成績。在此，我們將就近幾年在彌漫內生性橋腦膠質瘤基礎方面的研究進展作相關綜述及討論。

引用本文： 楊翔,張躍康. 腦干膠質瘤的干細胞研究進展. 華西醫學, 2013, 28(4): 627-630. doi: 10.7507/1002-0179.20130198 復制

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18.	Zarghooni M, Bartels U, Lee E, et al.Whole-genome profiling of pediatric diffuse intrinsic pontine gliomas highlights platelet-derived growth factor receptor and poly (ADP-ribose) polymerase as potential therapeutic targets[J]. J Clin Oncol, 2010, 28(8): 1337-1344.
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21.	Clement V, Sanchez P, de Tribolet N, et al. HEDGEHOG-GLI1 signaling regulates human glioma growth, cancer stem cell self-renewal, and tumorigenicity[J]. Curr Biol, 2007, 17(2): 165-172.
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26.	Kim SK, Kim SU, Park IH, et al. Human neural stem cellstarget experimental intracranial medulloblastoma and deliver atherapeutic gene leading totumor regression[J]. Clin Cancer Res, 2006, 12(18): 5550-5556.
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28.	Li G, Mitra SS, Monje M, et al. Expression of epidermal growth factor variantⅢ(EGFRvⅢ) in pediatric diffuse intrinsic pontine gliomas[J]. J Neurooncol , 2012, 108(3): 395-402.

1. 　Reya T, Morrison SJ, Clarke MF, et al. Stem cells, cancer, and cancer stem cells[J]. Nature, 2001, 414(6859) : 105-111.
2. 　Lapidot T, Sirard C, Vormoor J, et al. A cell initiating human acute myeloid leukaemia after transplantation into SCID mice[J]. Nature, 1994, 367(6464): 645-648.
3. 　Singh SK, Hawkins C, Clarke ID, et al. Identification of human brain tumour initiating cells[J]. Nature, 2004, 432(7015): 396-401.
4. 　Lee J, Kotliarova S, Kotliarov Y, et al. Tumor stem cells derived from glioblastomas cultured in bFGF and EGF more closely mirror the phenotype and genotype of primary tumors than do serum-cultured cell lines[J]. Cancer Cell, 2006, 9(5): 391-403.
5. 　Nicolis SK. Cancer stem cells and “stemness” genes in neuro-oncology[J]. Neurobiol Dis, 2007, 25(2): 217-229.
6. 　Zhang XP, Zheng G, Zou L, et al. Notch activation promotes cell proliferation and the formation of neural stem cell-like colonies in human glioma cells[J]. Mol Cell Biochem, 2008, 307(1-2): 101-108.
7. 　Fan X, Matsui W, Khaki L, et al. Notch Pathway Inhibition Depletes Stem-like Cells and Blocks Engraftment in Embryonal Brain Tumors[J]. Cancer Res , 2006, 66(15): 7445-7452 .
8. 　Diamandis P, Wildenhain J, Clarke ID, et al. Chemical genetics reveals a complex functional ground state of neural stem cells[J]. Nat Chem Biol, 2007, 3(5): 268-273.
9. 　Singh SK, Clarke ID, Hide T, et al. Cancer stem cells in nervous system tumors[J]. Oncogene, 2004, 23(43): 7267-7273.
10. 　Yang ZJ, Ellis T, Markant SL, et al. Medulloblastoma can be initiated by deletion of Patched in lineage-restricted progenitors or stem cells[J]. Cancer Cell, 2008, 14(2): 135-145.
11. 　Masui K, Suzuki SO, Torisu R,et al. Glial progenitors in the brainstem give rise to malignant gliomas by platelet-derived growth factor stimulation[J]. Glia , 2010, 58(9): 1050-1065.
12. 　Monje M, Mitra SS, Freret ME, et al. Hedgehog-responsive candidate cell of origin for diffuse intrinsic pontine glioma[J]. Proc Natl Acad Sci USA, 2011, 108 (11): 4453-4458.
13. 　Mazur MD, Couldwell WT. Investigating a candidate cell of origin for diffuse intrinsic pontine glioma[J]. World Neurosurg, 2011, 76(5): 368-369.
14. 　Sharpless NE, DePinho RA. The INK4A/ARF locus and its two gene products[J]. Curr Opin Genet Dev, 1999, 9(1) 1: 22-30.
15. 　Marino S. Medulloblastoma: developmental mechanisms out of control[J]. Trends Mol Med, 2005, 11(1): 17-22.
16. 　Bar EE, Chaudhry A, Lin A, et al. Cyclopamine-mediated hedgehog pathway inhibition depletes stem-like cancer cells in glioblastoma[J].Stem cells, 2007, 25(10): 2524-2533.
17. 　Ehtesham M, Sarangi A, Valadez JG, et al. Ligand-dependent activation of the hedgehog pathway in glioma progenitor cells[J].Oncogene, 2007, 26 (39): 5752-5761.
18. 　Zarghooni M, Bartels U, Lee E, et al.Whole-genome profiling of pediatric diffuse intrinsic pontine gliomas highlights platelet-derived growth factor receptor and poly (ADP-ribose) polymerase as potential therapeutic targets[J]. J Clin Oncol, 2010, 28(8): 1337-1344.
19. 　Grill J, Puget S, Andreiuolo F, et al. Critical oncogenic mutations in newly diagnosed pediatric diffuse intrinsic pontine glioma[J]. Pediatr Blood Cancer, 2012, 58(4): 489-491.
20. 　Masui K, Suzuki SO, Torisu R, et al. Glial progenitors in the brainstem give rise to malignant gliomas by platelet-derived growth factor stimulation[J]. Glia , 2010, 58(9): 1050-1065.
21. 　Clement V, Sanchez P, de Tribolet N, et al. HEDGEHOG-GLI1 signaling regulates human glioma growth, cancer stem cell self-renewal, and tumorigenicity[J]. Curr Biol, 2007, 17(2): 165-172.
22. 　Kondo T, Raff M. Chromatin remodeling and histone modification in the conversion of oligodendrocyte precursors to neural stem cells[J]. Genes Dev, 2004, 18(23): 2963-2972.
23. 　Wu G, Broniscer A, McEachron TA, et al. Somatic histone H3 alterations in pediatric diffuse intrinsic pontine gliomas and non-brainstem glioblastomas[J]. Nat Genet, 2012, 44(3): 251-253.
24. 　Schmidt NO, Przylecki W, Yang W, et al. Brain tumor tropism of transplanted human neural stem cells is induced by vascular endothelial growth factor[J]. Neoplasia, 2005, 7(6): 623-629.
25. 　Schmidt NO, Koeder D, Messing M, et al. Vascular endothelial growth factor-stimulated cerebral microvascular endothelial cells mediate the recruitment of neural stem cells to the neurovascular niche[J]. Brain Res, 2009, 1268: 24-37.
26. 　Kim SK, Kim SU, Park IH, et al. Human neural stem cellstarget experimental intracranial medulloblastoma and deliver atherapeutic gene leading totumor regression[J]. Clin Cancer Res, 2006, 12(18): 5550-5556.
27. 　Choi SA, Lee JY, Wang KC, et al. Human adipose tissue-derived mesenchymal stem cells:Characteristics and therapeutic potential as cellular vehicles for prodrug gene therapy against brainstem gliomas[J]. Eur J Cancer, 2012, 48(1): 129-137.
28. 　Li G, Mitra SS, Monje M, et al. Expression of epidermal growth factor variantⅢ(EGFRvⅢ) in pediatric diffuse intrinsic pontine gliomas[J]. J Neurooncol , 2012, 108(3): 395-402.

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