Skip to main content
Erschienen in: Child's Nervous System 1/2013

01.01.2013 | Original Paper

Changes in the biological characteristics of glioma cancer stem cells after serial in vivo subtransplantation

verfasst von: Ga-Yeong Shin, Jin-Kyoung Shim, Ji-Hyun Lee, Hye-Jin Shin, Su-Jae Lee, Yong-Min Huh, Eui-Hyun Kim, Eun-Kyung Park, Se-Hoon Kim, Jong Hee Chang, Dong-Seok Kim, Yong-Kil Hong, Sun Ho Kim, Seok-Gu Kang, Frederick F. Lang

Erschienen in: Child's Nervous System | Ausgabe 1/2013

Einloggen, um Zugang zu erhalten

Abstract

Purpose

Currently, the interaction between the niche and glioma cancer stem cells (gCSCs) is gaining attention. However, there are few studies concerned with the effects of repeated exposure to a new microenvironment on gCSCs characteristics. In this study, serial in vivo subtransplantation was performed to create a new microenvironment. We evaluated and compared the biological characteristics of gCSCs after serial in vivo subtransplantation.

Methods

We cultured gCSCs from human glioma specimens according to cultured gliomasphere methods. The isolated gCSCs were termed zero-generation gCSCs (G0-gCSCs). By subsequent serial subtransplantation, we obtained first-generation gCSCs (G1-gCSCs) and second-generation gCSCs (G2-gCSCs). We evaluated and compared the biological characteristics of G0-gCSCs, G1-gCSCs, and G2-gCSCs. The in vitro characteristics included the morphology, surface marker profiles, and neural differentiation capacity and the in vivo characteristics was the survival of mice xenografts. Additionally, brain sections were analyzed using PCNA, TUNEL, and CD31 staining.

Results

We observed no significant differences in the in vitro characteristics of G0-gCSCs, G1-gCSCs, and G2-gCSCs. However, the survival time of mice glioma xenografts was significantly decreased upon serial subtransplantation. In addition, immunohistochemical analyses showed that the number of TUNEL+ cells was significantly decreased while the number of CD31+ cells was significantly increased with serial in vivo subtransplantation.

Conclusions

There were significant in vivo biological changes in gCSCs upon serial in vivo subtransplantation, which were shorter xenograft survival, increased angiogenesis, and decreased apoptosis. This study suggests that the repeated exposure to new microenvironments may affect the biological changes in gCSCs in vivo.
Literatur
1.
Zurück zum Zitat Annabi B, Rojas-Sutterlin S, Laflamme C, Lachambre MP, Rolland Y, Sartelet H, Beliveau R (2008) Tumor environment dictates medulloblastoma cancer stem cell expression and invasive phenotype. Mol Cancer Res 6(6):907–916PubMedCrossRef Annabi B, Rojas-Sutterlin S, Laflamme C, Lachambre MP, Rolland Y, Sartelet H, Beliveau R (2008) Tumor environment dictates medulloblastoma cancer stem cell expression and invasive phenotype. Mol Cancer Res 6(6):907–916PubMedCrossRef
2.
Zurück zum Zitat Dean M, Fojo T, Bates S (2005) Tumour stem cells and drug resistance. Nat Rev Cancer 5(4):275–284PubMedCrossRef Dean M, Fojo T, Bates S (2005) Tumour stem cells and drug resistance. Nat Rev Cancer 5(4):275–284PubMedCrossRef
3.
Zurück zum Zitat Dingli D, Michor F (2006) Successful therapy must eradicate cancer stem cells. Stem Cells 24(12):2603–2610PubMedCrossRef Dingli D, Michor F (2006) Successful therapy must eradicate cancer stem cells. Stem Cells 24(12):2603–2610PubMedCrossRef
4.
Zurück zum Zitat Dirks PB (2008) Brain tumor stem cells: bringing order to the chaos of brain cancer. J Clin Oncol 26(17):2916–2924PubMedCrossRef Dirks PB (2008) Brain tumor stem cells: bringing order to the chaos of brain cancer. J Clin Oncol 26(17):2916–2924PubMedCrossRef
5.
Zurück zum Zitat Folkins C, Man S, Xu P, Shaked Y, Hicklin DJ, Kerbel RS (2007) Anticancer therapies combining antiangiogenic and tumor cell cytotoxic effects reduce the tumor stem-like cell fraction in glioma xenograft tumors. Cancer Res 67(8):3560–3564PubMedCrossRef Folkins C, Man S, Xu P, Shaked Y, Hicklin DJ, Kerbel RS (2007) Anticancer therapies combining antiangiogenic and tumor cell cytotoxic effects reduce the tumor stem-like cell fraction in glioma xenograft tumors. Cancer Res 67(8):3560–3564PubMedCrossRef
6.
Zurück zum Zitat Furnari FB, Fenton T, Bachoo RM, Mukasa A, Stommel JM, Stegh A, Hahn WC, Ligon KL, Louis DN, Brennan C, Chin L, DePinho RA, Cavenee WK (2007) Malignant astrocytic glioma: genetics, biology, and paths to treatment. Genes Dev 21(21):2683–2710PubMedCrossRef Furnari FB, Fenton T, Bachoo RM, Mukasa A, Stommel JM, Stegh A, Hahn WC, Ligon KL, Louis DN, Brennan C, Chin L, DePinho RA, Cavenee WK (2007) Malignant astrocytic glioma: genetics, biology, and paths to treatment. Genes Dev 21(21):2683–2710PubMedCrossRef
7.
Zurück zum Zitat Galli R, Binda E, Orfanelli U, Cipelletti B, Gritti A, De Vitis S, Fiocco R, Foroni C, Dimeco F, Vescovi A (2004) Isolation and characterization of tumorigenic, stem-like neural precursors from human glioblastoma. Cancer Res 64(19):7011–7021PubMedCrossRef Galli R, Binda E, Orfanelli U, Cipelletti B, Gritti A, De Vitis S, Fiocco R, Foroni C, Dimeco F, Vescovi A (2004) Isolation and characterization of tumorigenic, stem-like neural precursors from human glioblastoma. Cancer Res 64(19):7011–7021PubMedCrossRef
8.
Zurück zum Zitat Goplen D, Bougnaud S, Rajcevic U, Boe SO, Skaftnesmo KO, Voges J, Enger PO, Wang J, Tysnes BB, Laerum OD, Niclou S, Bjerkvig R (2010) alphaB-crystallin is elevated in highly infiltrative apoptosis-resistant glioblastoma cells. Am J Pathol 177(4):1618–1628PubMedCrossRef Goplen D, Bougnaud S, Rajcevic U, Boe SO, Skaftnesmo KO, Voges J, Enger PO, Wang J, Tysnes BB, Laerum OD, Niclou S, Bjerkvig R (2010) alphaB-crystallin is elevated in highly infiltrative apoptosis-resistant glioblastoma cells. Am J Pathol 177(4):1618–1628PubMedCrossRef
9.
Zurück zum Zitat Hambardzumyan D, Squatrito M, Holland EC (2006) Radiation resistance and stem-like cells in brain tumors. Cancer Cell 10(6):454–456PubMedCrossRef Hambardzumyan D, Squatrito M, Holland EC (2006) Radiation resistance and stem-like cells in brain tumors. Cancer Cell 10(6):454–456PubMedCrossRef
10.
Zurück zum Zitat Hoelzinger DB, Demuth T, Berens ME (2007) Autocrine factors that sustain glioma invasion and paracrine biology in the brain microenvironment. J Natl Cancer Inst 99(21):1583–1593PubMedCrossRef Hoelzinger DB, Demuth T, Berens ME (2007) Autocrine factors that sustain glioma invasion and paracrine biology in the brain microenvironment. J Natl Cancer Inst 99(21):1583–1593PubMedCrossRef
11.
Zurück zum Zitat Holland EC (2000) Glioblastoma multiforme: the terminator. Proc Natl Acad Sci U S A 97(12):6242–6244PubMedCrossRef Holland EC (2000) Glioblastoma multiforme: the terminator. Proc Natl Acad Sci U S A 97(12):6242–6244PubMedCrossRef
12.
Zurück zum Zitat Hussein D, Punjaruk W, Storer LC, Shaw L, Ottoman R, Peet A, Miller S, Bandopadhyay G, Heath R, Kumari R, Bowman KJ, Braker P, Rahman R, Jones GD, Watson S, Lowe J, Kerr ID, Grundy RG, Coyle B (2011) Pediatric brain tumor cancer stem cells: cell cycle dynamics, DNA repair, and etoposide extrusion. Neuro Oncol 13(1):70–83PubMedCrossRef Hussein D, Punjaruk W, Storer LC, Shaw L, Ottoman R, Peet A, Miller S, Bandopadhyay G, Heath R, Kumari R, Bowman KJ, Braker P, Rahman R, Jones GD, Watson S, Lowe J, Kerr ID, Grundy RG, Coyle B (2011) Pediatric brain tumor cancer stem cells: cell cycle dynamics, DNA repair, and etoposide extrusion. Neuro Oncol 13(1):70–83PubMedCrossRef
13.
Zurück zum Zitat Jin X, Jeon HY, Joo KM, Kim JK, Jin J, Kim SH, Kang BG, Beck S, Lee SJ, Park AK, Park WY, Choi YJ, Nam DH, Kim H (2011) Frizzled 4 regulates stemness and invasiveness of migrating glioma cells established by serial intracranial transplantation. Cancer Res 71(8):3066–3075PubMedCrossRef Jin X, Jeon HY, Joo KM, Kim JK, Jin J, Kim SH, Kang BG, Beck S, Lee SJ, Park AK, Park WY, Choi YJ, Nam DH, Kim H (2011) Frizzled 4 regulates stemness and invasiveness of migrating glioma cells established by serial intracranial transplantation. Cancer Res 71(8):3066–3075PubMedCrossRef
14.
Zurück zum Zitat Johannessen TC, Wang J, Skaftnesmo KO, Sakariassen PO, Enger PO, Petersen K, Oyan AM, Kalland KH, Bjerkvig R, Tysnes BB (2009) Highly infiltrative brain tumours show reduced chemosensitivity associated with a stem cell-like phenotype. Neuropathol Appl Neurobiol 35(4):380–393PubMedCrossRef Johannessen TC, Wang J, Skaftnesmo KO, Sakariassen PO, Enger PO, Petersen K, Oyan AM, Kalland KH, Bjerkvig R, Tysnes BB (2009) Highly infiltrative brain tumours show reduced chemosensitivity associated with a stem cell-like phenotype. Neuropathol Appl Neurobiol 35(4):380–393PubMedCrossRef
15.
Zurück zum Zitat Kang SG, Shinojima N, Hossain A, Gumin J, Yong RL, Colman H, Marini F, Andreeff M, Lang FF (2010) Isolation and perivascular localization of mesenchymal stem cells from mouse brain. Neurosurgery 67(3):711–720PubMedCrossRef Kang SG, Shinojima N, Hossain A, Gumin J, Yong RL, Colman H, Marini F, Andreeff M, Lang FF (2010) Isolation and perivascular localization of mesenchymal stem cells from mouse brain. Neurosurgery 67(3):711–720PubMedCrossRef
16.
Zurück zum Zitat Kievit FM, Florczyk SJ, Leung MC, Veiseh O, Park JO, Disis ML, Zhang M (2010) Chitosan-alginate 3D scaffolds as a mimic of the glioma tumor microenvironment. Biomaterials 31(22):5903–5910PubMedCrossRef Kievit FM, Florczyk SJ, Leung MC, Veiseh O, Park JO, Disis ML, Zhang M (2010) Chitosan-alginate 3D scaffolds as a mimic of the glioma tumor microenvironment. Biomaterials 31(22):5903–5910PubMedCrossRef
17.
Zurück zum Zitat Kim SM, Kang SG, Park NR, Mok HS, Huh YM, Lee SJ, Jeun SS, Hong YK, Park CK, Lang FF (2011) Presence of glioma stroma mesenchymal stem cells in a murine orthotopic glioma model. Childs Nerv Syst 27(6):911–922PubMedCrossRef Kim SM, Kang SG, Park NR, Mok HS, Huh YM, Lee SJ, Jeun SS, Hong YK, Park CK, Lang FF (2011) Presence of glioma stroma mesenchymal stem cells in a murine orthotopic glioma model. Childs Nerv Syst 27(6):911–922PubMedCrossRef
18.
Zurück zum Zitat Lal S, Lacroix M, Tofilon P, Fuller GN, Sawaya R, Lang FF (2000) An implantable guide–screw system for brain tumor studies in small animals. J Neurosurg 92(2):326–333PubMedCrossRef Lal S, Lacroix M, Tofilon P, Fuller GN, Sawaya R, Lang FF (2000) An implantable guide–screw system for brain tumor studies in small animals. J Neurosurg 92(2):326–333PubMedCrossRef
19.
Zurück zum Zitat Lasky JL 3rd, Choe M, Nakano I (2009) Cancer stem cells in pediatric brain tumors. Curr Stem Cell Res Ther 4(4):298–305PubMedCrossRef Lasky JL 3rd, Choe M, Nakano I (2009) Cancer stem cells in pediatric brain tumors. Curr Stem Cell Res Ther 4(4):298–305PubMedCrossRef
20.
Zurück zum Zitat Lee J, Kotliarova S, Kotliarov Y, Li A, Su Q, Donin NM, Pastorino S, Purow BW, Christopher N, Zhang W, Park JK, Fine HA (2006) 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. Cancer Cell 9(5):391–403PubMedCrossRef Lee J, Kotliarova S, Kotliarov Y, Li A, Su Q, Donin NM, Pastorino S, Purow BW, Christopher N, Zhang W, Park JK, Fine HA (2006) 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. Cancer Cell 9(5):391–403PubMedCrossRef
21.
Zurück zum Zitat Li A, Walling J, Kotliarov Y, Center A, Steed ME, Ahn SJ, Rosenblum M, Mikkelsen T, Zenklusen JC, Fine HA (2008) Genomic changes and gene expression profiles reveal that established glioma cell lines are poorly representative of primary human gliomas. Mol Cancer Res 6(1):21–30PubMedCrossRef Li A, Walling J, Kotliarov Y, Center A, Steed ME, Ahn SJ, Rosenblum M, Mikkelsen T, Zenklusen JC, Fine HA (2008) Genomic changes and gene expression profiles reveal that established glioma cell lines are poorly representative of primary human gliomas. Mol Cancer Res 6(1):21–30PubMedCrossRef
22.
Zurück zum Zitat Li L, Neaves WB (2006) Normal stem cells and cancer stem cells: the niche matters. Cancer Res 66(9):4553–4557PubMedCrossRef Li L, Neaves WB (2006) Normal stem cells and cancer stem cells: the niche matters. Cancer Res 66(9):4553–4557PubMedCrossRef
23.
24.
Zurück zum Zitat Liotta LA, Kohn EC (2001) The microenvironment of the tumour–host interface. Nature 411(6835):375–379PubMedCrossRef Liotta LA, Kohn EC (2001) The microenvironment of the tumour–host interface. Nature 411(6835):375–379PubMedCrossRef
25.
Zurück zum Zitat Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, Scheithauer BW, Kleihues P (2007) The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 114(2):97–109PubMedCrossRef Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, Scheithauer BW, Kleihues P (2007) The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 114(2):97–109PubMedCrossRef
26.
Zurück zum Zitat Mangiola A, Anile C, Pompucci A, Capone G, Rigante L, De Bonis P (2010) Glioblastoma therapy: going beyond Hercules Columns. Expert Rev Neurother 10(4):507–514PubMedCrossRef Mangiola A, Anile C, Pompucci A, Capone G, Rigante L, De Bonis P (2010) Glioblastoma therapy: going beyond Hercules Columns. Expert Rev Neurother 10(4):507–514PubMedCrossRef
27.
Zurück zum Zitat Manoranjan B, Venugopal C, McFarlane N, Doble BW, Dunn SE, Scheinemann K, Singh SK (2012) Medulloblastoma stem cells: where development and cancer cross pathways. Pediatr Res 71(4 Pt 2):516–522PubMedCrossRef Manoranjan B, Venugopal C, McFarlane N, Doble BW, Dunn SE, Scheinemann K, Singh SK (2012) Medulloblastoma stem cells: where development and cancer cross pathways. Pediatr Res 71(4 Pt 2):516–522PubMedCrossRef
28.
Zurück zum Zitat Nakamizo A, Marini F, Amano T, Khan A, Studeny M, Gumin J, Chen J, Hentschel S, Vecil G, Dembinski J, Andreeff M, Lang FF (2005) Human bone marrow-derived mesenchymal stem cells in the treatment of gliomas. Cancer Res 65(8):3307–3318PubMed Nakamizo A, Marini F, Amano T, Khan A, Studeny M, Gumin J, Chen J, Hentschel S, Vecil G, Dembinski J, Andreeff M, Lang FF (2005) Human bone marrow-derived mesenchymal stem cells in the treatment of gliomas. Cancer Res 65(8):3307–3318PubMed
29.
Zurück zum Zitat Pietras K, Ostman A (2010) Hallmarks of cancer: interactions with the tumor stroma. Exp Cell Res 316(8):1324–1331PubMedCrossRef Pietras K, Ostman A (2010) Hallmarks of cancer: interactions with the tumor stroma. Exp Cell Res 316(8):1324–1331PubMedCrossRef
30.
Zurück zum Zitat Rahman M, Deleyrolle L, Vedam-Mai V, Azari H, Abd-El-Barr M, Reynolds BA (2011) The cancer stem cell hypothesis: failures and pitfalls. Neurosurgery 68(2):531–545, discussion 545PubMedCrossRef Rahman M, Deleyrolle L, Vedam-Mai V, Azari H, Abd-El-Barr M, Reynolds BA (2011) The cancer stem cell hypothesis: failures and pitfalls. Neurosurgery 68(2):531–545, discussion 545PubMedCrossRef
31.
Zurück zum Zitat Rajcevic U, Petersen K, Knol JC, Loos M, Bougnaud S, Klychnikov O, Li KW, Pham TV, Wang J, Miletic H, Peng Z, Bjerkvig R, Jimenez CR, Niclou SP (2009) iTRAQ-based proteomics profiling reveals increased metabolic activity and cellular cross-talk in angiogenic compared with invasive glioblastoma phenotype. Mol Cell Proteomics 8(11):2595–2612PubMedCrossRef Rajcevic U, Petersen K, Knol JC, Loos M, Bougnaud S, Klychnikov O, Li KW, Pham TV, Wang J, Miletic H, Peng Z, Bjerkvig R, Jimenez CR, Niclou SP (2009) iTRAQ-based proteomics profiling reveals increased metabolic activity and cellular cross-talk in angiogenic compared with invasive glioblastoma phenotype. Mol Cell Proteomics 8(11):2595–2612PubMedCrossRef
32.
Zurück zum Zitat Sakariassen PO, Prestegarden L, Wang J, Skaftnesmo KO, Mahesparan R, Molthoff C, Sminia P, Sundlisaeter E, Misra A, Tysnes BB, Chekenya M, Peters H, Lende G, Kalland KH, Oyan AM, Petersen K, Jonassen I, van der Kogel A, Feuerstein BG, Terzis AJ, Bjerkvig R, Enger PO (2006) Angiogenesis-independent tumor growth mediated by stem-like cancer cells. Proc Natl Acad Sci U S A 103(44):16466–16471PubMedCrossRef Sakariassen PO, Prestegarden L, Wang J, Skaftnesmo KO, Mahesparan R, Molthoff C, Sminia P, Sundlisaeter E, Misra A, Tysnes BB, Chekenya M, Peters H, Lende G, Kalland KH, Oyan AM, Petersen K, Jonassen I, van der Kogel A, Feuerstein BG, Terzis AJ, Bjerkvig R, Enger PO (2006) Angiogenesis-independent tumor growth mediated by stem-like cancer cells. Proc Natl Acad Sci U S A 103(44):16466–16471PubMedCrossRef
33.
Zurück zum Zitat Shu Q, Wong KK, Su JM, Adesina AM, Yu LT, Tsang YT, Antalffy BC, Baxter P, Perlaky L, Yang J, Dauser RC, Chintagumpala M, Blaney SM, Lau CC, Li XN (2008) Direct orthotopic transplantation of fresh surgical specimen preserves CD133+ tumor cells in clinically relevant mouse models of medulloblastoma and glioma. Stem Cells 26(6):1414–1424PubMedCrossRef Shu Q, Wong KK, Su JM, Adesina AM, Yu LT, Tsang YT, Antalffy BC, Baxter P, Perlaky L, Yang J, Dauser RC, Chintagumpala M, Blaney SM, Lau CC, Li XN (2008) Direct orthotopic transplantation of fresh surgical specimen preserves CD133+ tumor cells in clinically relevant mouse models of medulloblastoma and glioma. Stem Cells 26(6):1414–1424PubMedCrossRef
34.
Zurück zum Zitat Singh SK, Clarke ID, Terasaki M, Bonn VE, Hawkins C, Squire J, Dirks PB (2003) Identification of a cancer stem cell in human brain tumors. Cancer Res 63(18):5821–5828PubMed Singh SK, Clarke ID, Terasaki M, Bonn VE, Hawkins C, Squire J, Dirks PB (2003) Identification of a cancer stem cell in human brain tumors. Cancer Res 63(18):5821–5828PubMed
35.
Zurück zum Zitat Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, Henkelman RM, Cusimano MD, Dirks PB (2004) Identification of human brain tumour initiating cells. Nature 432(7015):396–401PubMedCrossRef Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, Henkelman RM, Cusimano MD, Dirks PB (2004) Identification of human brain tumour initiating cells. Nature 432(7015):396–401PubMedCrossRef
36.
Zurück zum Zitat Spradling A, Drummond-Barbosa D, Kai T (2001) Stem cells find their niche. Nature 414(6859):98–104PubMedCrossRef Spradling A, Drummond-Barbosa D, Kai T (2001) Stem cells find their niche. Nature 414(6859):98–104PubMedCrossRef
37.
Zurück zum Zitat Stewart PA, Farrell CL, Del Maestro RF (1991) The effect of cellular microenvironment on vessels in the brain. Part 1: vessel structure in tumour, peritumour and brain from humans with malignant glioma. Int J Radiat Biol 60(1–2):125–130PubMedCrossRef Stewart PA, Farrell CL, Del Maestro RF (1991) The effect of cellular microenvironment on vessels in the brain. Part 1: vessel structure in tumour, peritumour and brain from humans with malignant glioma. Int J Radiat Biol 60(1–2):125–130PubMedCrossRef
38.
Zurück zum Zitat Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352(10):987–996PubMedCrossRef Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352(10):987–996PubMedCrossRef
39.
Zurück zum Zitat Vik-Mo EO, Sandberg C, Olstorn H, Varghese M, Brandal P, Ramm-Pettersen J, Murrell W, Langmoen IA (2010) Brain tumor stem cells maintain overall phenotype and tumorigenicity after in vitro culturing in serum-free conditions. Neuro Oncol 12(12):1220–1230PubMed Vik-Mo EO, Sandberg C, Olstorn H, Varghese M, Brandal P, Ramm-Pettersen J, Murrell W, Langmoen IA (2010) Brain tumor stem cells maintain overall phenotype and tumorigenicity after in vitro culturing in serum-free conditions. Neuro Oncol 12(12):1220–1230PubMed
40.
Zurück zum Zitat Xie X, Hiona A, Lee AS, Cao F, Huang M, Li Z, Cherry A, Pei X, Wu JC (2011) Effects of long-term culture on human embryonic stem cell aging. Stem Cells Dev 20(1):127–138PubMedCrossRef Xie X, Hiona A, Lee AS, Cao F, Huang M, Li Z, Cherry A, Pei X, Wu JC (2011) Effects of long-term culture on human embryonic stem cell aging. Stem Cells Dev 20(1):127–138PubMedCrossRef
41.
Zurück zum Zitat Xouri G, Christian S (2010) Origin and function of tumor stroma fibroblasts. Semin Cell Dev Biol 21(1):40–46PubMedCrossRef Xouri G, Christian S (2010) Origin and function of tumor stroma fibroblasts. Semin Cell Dev Biol 21(1):40–46PubMedCrossRef
42.
Zurück zum Zitat Yu L, Baxter PA, Voicu H, Gurusiddappa S, Zhao Y, Adesina A, Man TK, Shu Q, Zhang YJ, Zhao XM, Su JM, Perlaky L, Dauser R, Chintagumpala M, Lau CC, Blaney SM, Rao PH, Leung HC, Li XN (2010) A clinically relevant orthotopic xenograft model of ependymoma that maintains the genomic signature of the primary tumor and preserves cancer stem cells in vivo. Neuro Oncol 12(6):580–594PubMedCrossRef Yu L, Baxter PA, Voicu H, Gurusiddappa S, Zhao Y, Adesina A, Man TK, Shu Q, Zhang YJ, Zhao XM, Su JM, Perlaky L, Dauser R, Chintagumpala M, Lau CC, Blaney SM, Rao PH, Leung HC, Li XN (2010) A clinically relevant orthotopic xenograft model of ependymoma that maintains the genomic signature of the primary tumor and preserves cancer stem cells in vivo. Neuro Oncol 12(6):580–594PubMedCrossRef
Metadaten
Titel
Changes in the biological characteristics of glioma cancer stem cells after serial in vivo subtransplantation
verfasst von
Ga-Yeong Shin
Jin-Kyoung Shim
Ji-Hyun Lee
Hye-Jin Shin
Su-Jae Lee
Yong-Min Huh
Eui-Hyun Kim
Eun-Kyung Park
Se-Hoon Kim
Jong Hee Chang
Dong-Seok Kim
Yong-Kil Hong
Sun Ho Kim
Seok-Gu Kang
Frederick F. Lang
Publikationsdatum
01.01.2013
Verlag
Springer-Verlag
Erschienen in
Child's Nervous System / Ausgabe 1/2013
Print ISSN: 0256-7040
Elektronische ISSN: 1433-0350
DOI
https://doi.org/10.1007/s00381-012-1963-x

Weitere Artikel der Ausgabe 1/2013

Child's Nervous System 1/2013 Zur Ausgabe

Update Chirurgie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

S3-Leitlinie „Diagnostik und Therapie des Karpaltunnelsyndroms“

Karpaltunnelsyndrom BDC Leitlinien Webinare
CME: 2 Punkte

Das Karpaltunnelsyndrom ist die häufigste Kompressionsneuropathie peripherer Nerven. Obwohl die Anamnese mit dem nächtlichen Einschlafen der Hand (Brachialgia parästhetica nocturna) sehr typisch ist, ist eine klinisch-neurologische Untersuchung und Elektroneurografie in manchen Fällen auch eine Neurosonografie erforderlich. Im Anfangsstadium sind konservative Maßnahmen (Handgelenksschiene, Ergotherapie) empfehlenswert. Bei nicht Ansprechen der konservativen Therapie oder Auftreten von neurologischen Ausfällen ist eine Dekompression des N. medianus am Karpaltunnel indiziert.

Prof. Dr. med. Gregor Antoniadis
Berufsverband der Deutschen Chirurgie e.V.

S2e-Leitlinie „Distale Radiusfraktur“

Radiusfraktur BDC Leitlinien Webinare
CME: 2 Punkte

Das Webinar beschäftigt sich mit Fragen und Antworten zu Diagnostik und Klassifikation sowie Möglichkeiten des Ausschlusses von Zusatzverletzungen. Die Referenten erläutern, welche Frakturen konservativ behandelt werden können und wie. Das Webinar beantwortet die Frage nach aktuellen operativen Therapiekonzepten: Welcher Zugang, welches Osteosynthesematerial? Auf was muss bei der Nachbehandlung der distalen Radiusfraktur geachtet werden?

PD Dr. med. Oliver Pieske
Dr. med. Benjamin Meyknecht
Berufsverband der Deutschen Chirurgie e.V.

S1-Leitlinie „Empfehlungen zur Therapie der akuten Appendizitis bei Erwachsenen“

Appendizitis BDC Leitlinien Webinare
CME: 2 Punkte

Inhalte des Webinars zur S1-Leitlinie „Empfehlungen zur Therapie der akuten Appendizitis bei Erwachsenen“ sind die Darstellung des Projektes und des Erstellungswegs zur S1-Leitlinie, die Erläuterung der klinischen Relevanz der Klassifikation EAES 2015, die wissenschaftliche Begründung der wichtigsten Empfehlungen und die Darstellung stadiengerechter Therapieoptionen.

Dr. med. Mihailo Andric
Berufsverband der Deutschen Chirurgie e.V.