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Erschienen in: Journal of Neuro-Oncology 2/2009

01.04.2009 | Laboratory Investigation - Human/Animal Tissue

Growth factor receptors signaling in glioblastoma cells: therapeutic implications

verfasst von: Mia Carapancea, Oana Alexandru, Ani S. Fetea, Laura Dragutescu, Juan Castro, Ada Georgescu, A. Popa-Wagner, Magnus L. Bäcklund, Rolf Lewensohn, Anica Dricu

Erschienen in: Journal of Neuro-Oncology | Ausgabe 2/2009

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Abstract

In this study, we investigated the protein expression of platelet-derived growth factor receptor (PDGFR), insulin like growth factor-1 receptor (IGF-1R), phosphatidylinositol 3-kinase (PI3-K) and extracellular signal-regulated kinase (ERK1/2) in five primary glioblastoma (GB), with a view to their possible use as therapeutic targets. Our results demonstrated that appreciable levels of these proteins could be detected in the analysed GB cell lines, except for a low level of PDGFR and ERK1/2 expression in one GB cell line. The small molecule inhibitors towards IGF-1R, PDGFR, PI3-K and ERK1/2 respectively, have only modest or no anti-tumour activity on GB cells and therefore their combination with other therapy modalities was analysed. The interaction between small inhibitors and radiation was mostly additive or sub-additive; synergistic interaction was found in five of forty analysed combinations. Our results showed that GB cells are in general resistant to treatment and illustrate the difficulties in predicting the treatment response in malignant gliomas.
Literatur
1.
Zurück zum Zitat Allalunis-Turner MJ, Zia PK, Barron GM, Mirzayans R, Day RSIII (1995) Radiation-induced DNA damage and repair in cells of a radiosensitive human malignant glioma cell line. Radiat Res 144:288–293. doi:10.2307/3578948 PubMedCrossRef Allalunis-Turner MJ, Zia PK, Barron GM, Mirzayans R, Day RSIII (1995) Radiation-induced DNA damage and repair in cells of a radiosensitive human malignant glioma cell line. Radiat Res 144:288–293. doi:10.​2307/​3578948 PubMedCrossRef
3.
Zurück zum Zitat Andrews DW, Resnicoff M, Flanders AE, Kenyon L, Curtis M, Merli G, Baserga R, Iliakis G, Aiken RD (2001) Results of a pilot study involving the use of an antisense oligodeoxynucleotide directed against the insulin-like growth factor type I receptor in malignant astrocytomas. J Clin Oncol 19:2189–2200PubMed Andrews DW, Resnicoff M, Flanders AE, Kenyon L, Curtis M, Merli G, Baserga R, Iliakis G, Aiken RD (2001) Results of a pilot study involving the use of an antisense oligodeoxynucleotide directed against the insulin-like growth factor type I receptor in malignant astrocytomas. J Clin Oncol 19:2189–2200PubMed
4.
Zurück zum Zitat Antoniades HN, Galanopoulos T, Neville-Golden J, Maxwell M (1992) Expression of insulin-like growth factors I and II and their receptor mRNAs in primary human astrocytomas and meningiomas; in vivo studies using in situ hybridization and immunocytochemistry. Int J Cancer 50:215–222. doi:10.1002/ijc.2910500210 PubMedCrossRef Antoniades HN, Galanopoulos T, Neville-Golden J, Maxwell M (1992) Expression of insulin-like growth factors I and II and their receptor mRNAs in primary human astrocytomas and meningiomas; in vivo studies using in situ hybridization and immunocytochemistry. Int J Cancer 50:215–222. doi:10.​1002/​ijc.​2910500210 PubMedCrossRef
5.
Zurück zum Zitat Backlund LM, Nilsson BR, Goike HM, Schmidt EE, Liu L, Ichimura K, Collins VP (2003) Short postoperative survival for glioblastoma patients with a dysfunctional Rb1 pathway in combination with no wild-type PTEN. Clin Cancer Res 9:4151–4158PubMed Backlund LM, Nilsson BR, Goike HM, Schmidt EE, Liu L, Ichimura K, Collins VP (2003) Short postoperative survival for glioblastoma patients with a dysfunctional Rb1 pathway in combination with no wild-type PTEN. Clin Cancer Res 9:4151–4158PubMed
8.
Zurück zum Zitat Bridle KR, Li L, O’Neill R, Britton RS, Bacon BR (2006) Coordinate activation of intracellular signaling pathways by insulin-like growth factor-1 and platelet-derived growth factor in rat hepatic stellate cells. J Lab Clin Med 147:234–241. doi:10.1016/j.lab.2005.12.009 PubMedCrossRef Bridle KR, Li L, O’Neill R, Britton RS, Bacon BR (2006) Coordinate activation of intracellular signaling pathways by insulin-like growth factor-1 and platelet-derived growth factor in rat hepatic stellate cells. J Lab Clin Med 147:234–241. doi:10.​1016/​j.​lab.​2005.​12.​009 PubMedCrossRef
11.
Zurück zum Zitat Chakravarti A, Loeffler JS, Dyson NJ (2002) Insulin-like growth factor receptor I mediates resistance to anti-epidermal growth factor receptor therapy in primary human glioblastoma cells through continued activation of phosphoinositide 3-kinase signaling. Cancer Res 62:200–207PubMed Chakravarti A, Loeffler JS, Dyson NJ (2002) Insulin-like growth factor receptor I mediates resistance to anti-epidermal growth factor receptor therapy in primary human glioblastoma cells through continued activation of phosphoinositide 3-kinase signaling. Cancer Res 62:200–207PubMed
13.
Zurück zum Zitat Cosaceanu D, Budiu RA, Carapancea M, Castro J, Lewensohn R, Dricu A (2007) Ionizing radiation activates IGF-1R triggering a cytoprotective signaling by interfering with Ku-DNA binding and by modulating Ku86 expression via a p38 kinase-dependent mechanism. Oncogene 26:2423–2434. doi:10.1038/sj.onc.1210037 PubMedCrossRef Cosaceanu D, Budiu RA, Carapancea M, Castro J, Lewensohn R, Dricu A (2007) Ionizing radiation activates IGF-1R triggering a cytoprotective signaling by interfering with Ku-DNA binding and by modulating Ku86 expression via a p38 kinase-dependent mechanism. Oncogene 26:2423–2434. doi:10.​1038/​sj.​onc.​1210037 PubMedCrossRef
14.
Zurück zum Zitat Del Valle L, Enam S, Lassak A, Wang JY, Croul S, Khalili K, Reiss K (2002) Insulin-like growth factor I receptor activity in human medulloblastomas. Clin Cancer Res 8:1822–1830PubMed Del Valle L, Enam S, Lassak A, Wang JY, Croul S, Khalili K, Reiss K (2002) Insulin-like growth factor I receptor activity in human medulloblastomas. Clin Cancer Res 8:1822–1830PubMed
15.
Zurück zum Zitat DiBiase SJ, Zeng ZC, Chen R, Hyslop T, Curran WJ Jr, Iliakis G (2000) DNA-dependent protein kinase stimulates an independently active, nonhomologous, end-joining apparatus. Cancer Res 60:1245–1253PubMed DiBiase SJ, Zeng ZC, Chen R, Hyslop T, Curran WJ Jr, Iliakis G (2000) DNA-dependent protein kinase stimulates an independently active, nonhomologous, end-joining apparatus. Cancer Res 60:1245–1253PubMed
16.
Zurück zum Zitat Dimova EY, Moller U, Herzig S, Fink T, Zachar V, Ebbesen P, Kietzmann T (2005) Transcriptional regulation of plasminogen activator inhibitor-1 expression by insulin-like growth factor-1 via MAP kinases and hypoxia-inducible factor-1 in HepG2 cells. Thromb Haemost 93:1176–1184PubMed Dimova EY, Moller U, Herzig S, Fink T, Zachar V, Ebbesen P, Kietzmann T (2005) Transcriptional regulation of plasminogen activator inhibitor-1 expression by insulin-like growth factor-1 via MAP kinases and hypoxia-inducible factor-1 in HepG2 cells. Thromb Haemost 93:1176–1184PubMed
17.
Zurück zum Zitat Dricu A, Carlberg M, Wang M, Larsson O (1997) Inhibition of N-linked glycosylation using tunicamycin causes cell death in malignant cells: role of down-regulation of the insulin-like growth factor 1 receptor in induction of apoptosis. Cancer Res 57:543–548PubMed Dricu A, Carlberg M, Wang M, Larsson O (1997) Inhibition of N-linked glycosylation using tunicamycin causes cell death in malignant cells: role of down-regulation of the insulin-like growth factor 1 receptor in induction of apoptosis. Cancer Res 57:543–548PubMed
18.
Zurück zum Zitat Fleming TP, Saxena A, Clark WC, Robertson JT, Oldfield EH, Aaronson SA, Ali IU (1992) Amplification and/or overexpression of platelet-derived growth factor receptors and epidermal growth factor receptor in human glial tumors. Cancer Res 52:4550–4553PubMed Fleming TP, Saxena A, Clark WC, Robertson JT, Oldfield EH, Aaronson SA, Ali IU (1992) Amplification and/or overexpression of platelet-derived growth factor receptors and epidermal growth factor receptor in human glial tumors. Cancer Res 52:4550–4553PubMed
20.
Zurück zum Zitat Foulstone E, Prince S, Zaccheo O, Burns JL, Harper J, Jacobs C, Church D, Hassan AB (2005) Insulin-like growth factor ligands, receptors, and binding proteins in cancer. J Pathol 205:145–153. doi:10.1002/path.1712 PubMedCrossRef Foulstone E, Prince S, Zaccheo O, Burns JL, Harper J, Jacobs C, Church D, Hassan AB (2005) Insulin-like growth factor ligands, receptors, and binding proteins in cancer. J Pathol 205:145–153. doi:10.​1002/​path.​1712 PubMedCrossRef
23.
Zurück zum Zitat Germano IM, Ito M, Cho KG, Hoshino T, Davis RL, Wilson CB (1989) Correlation of histopathological features and proliferative potential of gliomas. J Neurosurg 70:701–706PubMed Germano IM, Ito M, Cho KG, Hoshino T, Davis RL, Wilson CB (1989) Correlation of histopathological features and proliferative potential of gliomas. J Neurosurg 70:701–706PubMed
25.
Zurück zum Zitat Hagerstrand D, Hesselager G, Achterberg S, Wickenberg Bolin U, Kowanetz M, Kastemar M, Heldin CH, Isaksson A, Nister M, Ostman A (2006) Characterization of an imatinib-sensitive subset of high-grade human glioma cultures. Oncogene 25:4913–4922. doi:10.1038/sj.onc.1209497 PubMedCrossRef Hagerstrand D, Hesselager G, Achterberg S, Wickenberg Bolin U, Kowanetz M, Kastemar M, Heldin CH, Isaksson A, Nister M, Ostman A (2006) Characterization of an imatinib-sensitive subset of high-grade human glioma cultures. Oncogene 25:4913–4922. doi:10.​1038/​sj.​onc.​1209497 PubMedCrossRef
26.
28.
Zurück zum Zitat Hanada M, Feng J, Hemmings BA (2004) Structure, regulation and function of PKB/AKT—a major therapeutic target. Biochim Biophys Acta 1697:3–16PubMed Hanada M, Feng J, Hemmings BA (2004) Structure, regulation and function of PKB/AKT—a major therapeutic target. Biochim Biophys Acta 1697:3–16PubMed
30.
Zurück zum Zitat Jiang R, Mircean C, Shmulevich I, Cogdell D, Jia Y, Tabus I, Aldape K, Sawaya R, Bruner JM, Fuller GN, Zhang W (2006) Pathway alterations during glioma progression revealed by reverse phase protein lysate arrays. Proteomics 6:2964–2971. doi:10.1002/pmic.200500555 PubMedCrossRef Jiang R, Mircean C, Shmulevich I, Cogdell D, Jia Y, Tabus I, Aldape K, Sawaya R, Bruner JM, Fuller GN, Zhang W (2006) Pathway alterations during glioma progression revealed by reverse phase protein lysate arrays. Proteomics 6:2964–2971. doi:10.​1002/​pmic.​200500555 PubMedCrossRef
31.
Zurück zum Zitat Johnson TR, Trojan J, Anthony DD, Rudin SD, Tykocinski ML, Ilan J, Ilan J (1994) Gene therapy of rat brain glioblastoma by an episome-based transcriptional cassette expressing antisense IGF-I cDNA. Indian J Biochem Biophys 31:1–13PubMedCrossRef Johnson TR, Trojan J, Anthony DD, Rudin SD, Tykocinski ML, Ilan J, Ilan J (1994) Gene therapy of rat brain glioblastoma by an episome-based transcriptional cassette expressing antisense IGF-I cDNA. Indian J Biochem Biophys 31:1–13PubMedCrossRef
32.
Zurück zum Zitat Kasprzak HA, Trojan J, Bierwagen M, Kopinski P, Jarocki P, Bartczak K, Czapiewska J (2006) [Usefulness of the antisense and triplex anti-IGF-1 techniques for postoperative cellular gene therapy of malignant gliomas expressing IGF-1]. Neurol Neurochir Pol 40:509–515 (discussion 516) Kasprzak HA, Trojan J, Bierwagen M, Kopinski P, Jarocki P, Bartczak K, Czapiewska J (2006) [Usefulness of the antisense and triplex anti-IGF-1 techniques for postoperative cellular gene therapy of malignant gliomas expressing IGF-1]. Neurol Neurochir Pol 40:509–515 (discussion 516)
34.
Zurück zum Zitat Kiess W, Lee L, Graham DE, Greenstein L, Tseng LY, Rechler MM, Nissley SP (1989) Rat C6 glial cells synthesize insulin-like growth factor I (IGF-I) and express IGF-I receptors and IGF-II/mannose 6-phosphate receptors. Endocrinology 124:1727–1736PubMedCrossRef Kiess W, Lee L, Graham DE, Greenstein L, Tseng LY, Rechler MM, Nissley SP (1989) Rat C6 glial cells synthesize insulin-like growth factor I (IGF-I) and express IGF-I receptors and IGF-II/mannose 6-phosphate receptors. Endocrinology 124:1727–1736PubMedCrossRef
35.
Zurück zum Zitat Kilic T, Alberta JA, Zdunek PR, Acar M, Iannarelli P, O’Reilly T, Buchdunger E, Black PM, Stiles CD (2000) Intracranial inhibition of platelet-derived growth factor-mediated glioblastoma cell growth by an orally active kinase inhibitor of the 2-phenylaminopyrimidine class. Cancer Res 60:5143–5150PubMed Kilic T, Alberta JA, Zdunek PR, Acar M, Iannarelli P, O’Reilly T, Buchdunger E, Black PM, Stiles CD (2000) Intracranial inhibition of platelet-derived growth factor-mediated glioblastoma cell growth by an orally active kinase inhibitor of the 2-phenylaminopyrimidine class. Cancer Res 60:5143–5150PubMed
36.
Zurück zum Zitat Kurmasheva RT, Houghton PJ (2006) IGF-I mediated survival pathways in normal and malignant cells. Biochim Biophys Acta 1766:1–22PubMed Kurmasheva RT, Houghton PJ (2006) IGF-I mediated survival pathways in normal and malignant cells. Biochim Biophys Acta 1766:1–22PubMed
37.
Zurück zum Zitat Lees-Miller SP, Godbout R, Chan DW, Weinfeld M, Day RSIII, Barron GM, Allalunis-Turner J (1995) Absence of p350 subunit of DNA-activated protein kinase from a radiosensitive human cell line. Science 267:1183–1185. doi:10.1126/science.7855602 PubMedCrossRef Lees-Miller SP, Godbout R, Chan DW, Weinfeld M, Day RSIII, Barron GM, Allalunis-Turner J (1995) Absence of p350 subunit of DNA-activated protein kinase from a radiosensitive human cell line. Science 267:1183–1185. doi:10.​1126/​science.​7855602 PubMedCrossRef
38.
Zurück zum Zitat Lokker NA, Sullivan CM, Hollenbach SJ, Israel MA, Giese NA (2002) Platelet-derived growth factor (PDGF) autocrine signaling regulates survival and mitogenic pathways in glioblastoma cells: evidence that the novel PDGF-C and PDGF-D ligands may play a role in the development of brain tumors. Cancer Res 62:3729–3735PubMed Lokker NA, Sullivan CM, Hollenbach SJ, Israel MA, Giese NA (2002) Platelet-derived growth factor (PDGF) autocrine signaling regulates survival and mitogenic pathways in glioblastoma cells: evidence that the novel PDGF-C and PDGF-D ligands may play a role in the development of brain tumors. Cancer Res 62:3729–3735PubMed
40.
Zurück zum Zitat Ly A, Duc HT, Kalamarides M, Trojan LA, Pan Y, Shevelev A, Francois JC, Noel T, Kane A, Henin D, Anthony DD, Trojan J (2001) Human glioma cells transformed by IGF-I triple helix technology show immune and apoptotic characteristics determining cell selection for gene therapy of glioblastoma. Mol Pathol 54:230–239. doi:10.1136/mp.54.4.230 PubMedCrossRef Ly A, Duc HT, Kalamarides M, Trojan LA, Pan Y, Shevelev A, Francois JC, Noel T, Kane A, Henin D, Anthony DD, Trojan J (2001) Human glioma cells transformed by IGF-I triple helix technology show immune and apoptotic characteristics determining cell selection for gene therapy of glioblastoma. Mol Pathol 54:230–239. doi:10.​1136/​mp.​54.​4.​230 PubMedCrossRef
41.
Zurück zum Zitat MacKeigan JP, Taxman DJ, Hunter D, Earp HSIII, Graves LM, Ting JP (2002) Inactivation of the antiapoptotic phosphatidylinositol 3-kinase-Akt pathway by the combined treatment of taxol and mitogen-activated protein kinase inhibition. Clin Cancer Res 8:2091–2099PubMed MacKeigan JP, Taxman DJ, Hunter D, Earp HSIII, Graves LM, Ting JP (2002) Inactivation of the antiapoptotic phosphatidylinositol 3-kinase-Akt pathway by the combined treatment of taxol and mitogen-activated protein kinase inhibition. Clin Cancer Res 8:2091–2099PubMed
49.
Zurück zum Zitat Perer ES, Madan AK, Shurin A, Zakris E, Romeguera K, Pang Y, Beech DJ (2000) Insulin-like growth factor I receptor antagonism augments response to chemoradiation therapy in colon cancer cells. J Surg Res 94:1–5. doi:10.1006/jsre.2000.5923 PubMedCrossRef Perer ES, Madan AK, Shurin A, Zakris E, Romeguera K, Pang Y, Beech DJ (2000) Insulin-like growth factor I receptor antagonism augments response to chemoradiation therapy in colon cancer cells. J Surg Res 94:1–5. doi:10.​1006/​jsre.​2000.​5923 PubMedCrossRef
50.
Zurück zum Zitat Ponten J, Westermark B (1978) Properties of human malignant glioma cells in vitro. Med Biol 56:184–193PubMed Ponten J, Westermark B (1978) Properties of human malignant glioma cells in vitro. Med Biol 56:184–193PubMed
52.
Zurück zum Zitat Resnicoff M, Sell C, Rubini M, Coppola D, Ambrose D, Baserga R, Rubin R (1994) Rat glioblastoma cells expressing an antisense RNA to the insulin-like growth factor-1 (IGF-1) receptor are nontumorigenic and induce regression of wild-type tumors. Cancer Res 54:2218–2222PubMed Resnicoff M, Sell C, Rubini M, Coppola D, Ambrose D, Baserga R, Rubin R (1994) Rat glioblastoma cells expressing an antisense RNA to the insulin-like growth factor-1 (IGF-1) receptor are nontumorigenic and induce regression of wild-type tumors. Cancer Res 54:2218–2222PubMed
53.
Zurück zum Zitat Resnicoff M, Li W, Basak S, Herlyn D, Baserga R, Rubin R (1996) Inhibition of rat C6 glioblastoma tumor growth by expression of insulin-like growth factor I receptor antisense mRNA. Cancer Immunol Immunother 42:64–68. doi:10.1007/s002620050252 PubMedCrossRef Resnicoff M, Li W, Basak S, Herlyn D, Baserga R, Rubin R (1996) Inhibition of rat C6 glioblastoma tumor growth by expression of insulin-like growth factor I receptor antisense mRNA. Cancer Immunol Immunother 42:64–68. doi:10.​1007/​s002620050252 PubMedCrossRef
54.
Zurück zum Zitat Sandberg-Nordqvist AC, Stahlbom PA, Reinecke M, Collins VP, von Holst H, Sara V (1993) Characterization of insulin-like growth factor 1 in human primary brain tumors. Cancer Res 53:2475–2478PubMed Sandberg-Nordqvist AC, Stahlbom PA, Reinecke M, Collins VP, von Holst H, Sara V (1993) Characterization of insulin-like growth factor 1 in human primary brain tumors. Cancer Res 53:2475–2478PubMed
56.
Zurück zum Zitat Schmidberger H, Rave-Frank M, Lehmann JJ, Weiss E, Gerl L, Dettmer N, Glomme S, Hess CF (2003) Lack of interferon beta-induced radiosensitization in four out of five human glioblastoma cell lines. Int J Radiat Oncol Biol Phys 55:1348–1357. doi:10.1016/S0360-3016(02)04575-3 PubMed Schmidberger H, Rave-Frank M, Lehmann JJ, Weiss E, Gerl L, Dettmer N, Glomme S, Hess CF (2003) Lack of interferon beta-induced radiosensitization in four out of five human glioblastoma cell lines. Int J Radiat Oncol Biol Phys 55:1348–1357. doi:10.​1016/​S0360-3016(02)04575-3 PubMed
57.
Zurück zum Zitat Shamah SM, Stiles CD, Guha A (1993) Dominant-negative mutants of platelet-derived growth factor revert the transformed phenotype of human astrocytoma cells. Mol Cell Biol 13:7203–7212PubMed Shamah SM, Stiles CD, Guha A (1993) Dominant-negative mutants of platelet-derived growth factor revert the transformed phenotype of human astrocytoma cells. Mol Cell Biol 13:7203–7212PubMed
58.
Zurück zum Zitat Soroceanu L, Kharbanda S, Chen R, Soriano RH, Aldape K, Misra A, Zha J, Forrest WF, Nigro JM, Modrusan Z, Feuerstein BG, Phillips HS (2007) Identification of IGF2 signaling through phosphoinositide-3-kinase regulatory subunit 3 as a growth-promoting axis in glioblastoma. Proc Natl Acad Sci USA 104:3466–3471. doi:10.1073/pnas.0611271104 PubMedCrossRef Soroceanu L, Kharbanda S, Chen R, Soriano RH, Aldape K, Misra A, Zha J, Forrest WF, Nigro JM, Modrusan Z, Feuerstein BG, Phillips HS (2007) Identification of IGF2 signaling through phosphoinositide-3-kinase regulatory subunit 3 as a growth-promoting axis in glioblastoma. Proc Natl Acad Sci USA 104:3466–3471. doi:10.​1073/​pnas.​0611271104 PubMedCrossRef
59.
Zurück zum Zitat Sourbier C, Lindner V, Lang H, Agouni A, Schordan E, Danilin S, Rothhut S, Jacqmin D, Helwig JJ, Massfelder T (2006) The phosphoinositide 3-kinase/Akt pathway: a new target in human renal cell carcinoma therapy. Cancer Res 66:5130–5142. doi:10.1158/0008-5472.CAN-05-1469 PubMedCrossRef Sourbier C, Lindner V, Lang H, Agouni A, Schordan E, Danilin S, Rothhut S, Jacqmin D, Helwig JJ, Massfelder T (2006) The phosphoinositide 3-kinase/Akt pathway: a new target in human renal cell carcinoma therapy. Cancer Res 66:5130–5142. doi:10.​1158/​0008-5472.​CAN-05-1469 PubMedCrossRef
60.
Zurück zum Zitat Strawn LM, Mann E, Elliger SS, Chu LM, Germain LL, Niederfellner G, Ullrich A, Shawver LK (1994) Inhibition of glioma cell growth by a truncated platelet-derived growth factor-beta receptor. J Biol Chem 269:21215–21222PubMed Strawn LM, Mann E, Elliger SS, Chu LM, Germain LL, Niederfellner G, Ullrich A, Shawver LK (1994) Inhibition of glioma cell growth by a truncated platelet-derived growth factor-beta receptor. J Biol Chem 269:21215–21222PubMed
61.
Zurück zum Zitat Tai YT, Fulciniti M, Hideshima T, Song W, Leiba M, Li XF, Rumizen M, Burger P, Morrison A, Podar K, Chauhan D, Tassone P, Richardson P, Munshi NC, Ghobrial I, Anderson KC (2007) Targeting MEK induces myeloma cell cytotoxicity and inhibits osteoclastogenesis. Blood 110(5):1656–1663 Tai YT, Fulciniti M, Hideshima T, Song W, Leiba M, Li XF, Rumizen M, Burger P, Morrison A, Podar K, Chauhan D, Tassone P, Richardson P, Munshi NC, Ghobrial I, Anderson KC (2007) Targeting MEK induces myeloma cell cytotoxicity and inhibits osteoclastogenesis. Blood 110(5):1656–1663
62.
Zurück zum Zitat Trojan J, Blossey BK, Johnson TR, Rudin SD, Tykocinski M, Ilan J, Ilan J (1992) Loss of tumorigenicity of rat glioblastoma directed by episome-based antisense cDNA transcription of insulin-like growth factor I. Proc Natl Acad Sci USA 89:4874–4878. doi:10.1073/pnas.89.11.4874 PubMedCrossRef Trojan J, Blossey BK, Johnson TR, Rudin SD, Tykocinski M, Ilan J, Ilan J (1992) Loss of tumorigenicity of rat glioblastoma directed by episome-based antisense cDNA transcription of insulin-like growth factor I. Proc Natl Acad Sci USA 89:4874–4878. doi:10.​1073/​pnas.​89.​11.​4874 PubMedCrossRef
63.
Zurück zum Zitat Trojan J, Johnson TR, Rudin SD, Ilan J, Tykocinski ML, Ilan J (1993) Treatment and prevention of rat glioblastoma by immunogenic C6 cells expressing antisense insulin-like growth factor I RNA. Science 259:94–97. doi:10.1126/science.8418502 PubMedCrossRef Trojan J, Johnson TR, Rudin SD, Ilan J, Tykocinski ML, Ilan J (1993) Treatment and prevention of rat glioblastoma by immunogenic C6 cells expressing antisense insulin-like growth factor I RNA. Science 259:94–97. doi:10.​1126/​science.​8418502 PubMedCrossRef
64.
65.
Zurück zum Zitat Trojan LA, Kopinski P, Wei MX, Ly A, Glogowska A, Czarny J, Shevelev A, Przewlocki R, Henin D, Trojan J (2002) IGF-I: from diagnostic to triple-helix gene therapy of solid tumors. Acta Biochim Pol 49:979–990PubMed Trojan LA, Kopinski P, Wei MX, Ly A, Glogowska A, Czarny J, Shevelev A, Przewlocki R, Henin D, Trojan J (2002) IGF-I: from diagnostic to triple-helix gene therapy of solid tumors. Acta Biochim Pol 49:979–990PubMed
66.
Zurück zum Zitat Trojan LA, Kopinski P, Mazurek A, Chyczewski L, Ly A, Jarocki P, Niklinski J, Shevelev A, Trzos R, Pan Y, Gitis DJ, Bierwagen M, Czapiewska JL, Wei MX, Michalkiewicz J, Henin D, Popiela T, Evrard F, Kasprzak H, Anthony D, Trojan J (2003) IGF-I triple helix gene therapy of rat and human gliomas. Rocz Akad Med Bialymst 48:18–27PubMed Trojan LA, Kopinski P, Mazurek A, Chyczewski L, Ly A, Jarocki P, Niklinski J, Shevelev A, Trzos R, Pan Y, Gitis DJ, Bierwagen M, Czapiewska JL, Wei MX, Michalkiewicz J, Henin D, Popiela T, Evrard F, Kasprzak H, Anthony D, Trojan J (2003) IGF-I triple helix gene therapy of rat and human gliomas. Rocz Akad Med Bialymst 48:18–27PubMed
68.
Zurück zum Zitat Vassbotn FS, Andersson M, Westermark B, Heldin CH, Ostman A (1993) Reversion of autocrine transformation by a dominant negative platelet-derived growth factor mutant. Mol Cell Biol 13:4066–4076PubMed Vassbotn FS, Andersson M, Westermark B, Heldin CH, Ostman A (1993) Reversion of autocrine transformation by a dominant negative platelet-derived growth factor mutant. Mol Cell Biol 13:4066–4076PubMed
70.
Zurück zum Zitat Wen B, Deutsch E, Marangoni E, Frascona V, Maggiorella L, Abdulkarim B, Chavaudra N, Bourhis J (2001) Tyrphostin AG 1024 modulates radiosensitivity in human breast cancer cells. Br J Cancer 85:2017–2021. doi:10.1054/bjoc.2001.2171 PubMedCrossRef Wen B, Deutsch E, Marangoni E, Frascona V, Maggiorella L, Abdulkarim B, Chavaudra N, Bourhis J (2001) Tyrphostin AG 1024 modulates radiosensitivity in human breast cancer cells. Br J Cancer 85:2017–2021. doi:10.​1054/​bjoc.​2001.​2171 PubMedCrossRef
72.
Zurück zum Zitat Wu CJ, Chen Z, Ullrich A, Greene MI, O’Rourke DM (2000) Inhibition of EGFR-mediated phosphoinositide-3-OH kinase (PI3-K) signaling and glioblastoma phenotype by signal-regulatory proteins (SIRPs). Oncogene 19:3999–4010. doi:10.1038/sj.onc.1203748 PubMedCrossRef Wu CJ, Chen Z, Ullrich A, Greene MI, O’Rourke DM (2000) Inhibition of EGFR-mediated phosphoinositide-3-OH kinase (PI3-K) signaling and glioblastoma phenotype by signal-regulatory proteins (SIRPs). Oncogene 19:3999–4010. doi:10.​1038/​sj.​onc.​1203748 PubMedCrossRef
73.
Zurück zum Zitat Yin D, Tamaki N, Parent AD, Zhang JH (2005) Insulin-like growth factor-I decreased etoposide-induced apoptosis in glioma cells by increasing bcl-2 expression and decreasing CPP32 activity. Neurol Res 27:27–35. doi:10.1179/016164105X18151 PubMedCrossRef Yin D, Tamaki N, Parent AD, Zhang JH (2005) Insulin-like growth factor-I decreased etoposide-induced apoptosis in glioma cells by increasing bcl-2 expression and decreasing CPP32 activity. Neurol Res 27:27–35. doi:10.​1179/​016164105X18151 PubMedCrossRef
Metadaten
Titel
Growth factor receptors signaling in glioblastoma cells: therapeutic implications
verfasst von
Mia Carapancea
Oana Alexandru
Ani S. Fetea
Laura Dragutescu
Juan Castro
Ada Georgescu
A. Popa-Wagner
Magnus L. Bäcklund
Rolf Lewensohn
Anica Dricu
Publikationsdatum
01.04.2009
Verlag
Springer US
Erschienen in
Journal of Neuro-Oncology / Ausgabe 2/2009
Print ISSN: 0167-594X
Elektronische ISSN: 1573-7373
DOI
https://doi.org/10.1007/s11060-008-9753-8

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Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Frühe Alzheimertherapie lohnt sich

25.04.2024 AAN-Jahrestagung 2024 Nachrichten

Ist die Tau-Last noch gering, scheint der Vorteil von Lecanemab besonders groß zu sein. Und beginnen Erkrankte verzögert mit der Behandlung, erreichen sie nicht mehr die kognitive Leistung wie bei einem früheren Start. Darauf deuten neue Analysen der Phase-3-Studie Clarity AD.

Viel Bewegung in der Parkinsonforschung

25.04.2024 Parkinson-Krankheit Nachrichten

Neue arznei- und zellbasierte Ansätze, Frühdiagnose mit Bewegungssensoren, Rückenmarkstimulation gegen Gehblockaden – in der Parkinsonforschung tut sich einiges. Auf dem Deutschen Parkinsonkongress ging es auch viel um technische Innovationen.

Demenzkranke durch Antipsychotika vielfach gefährdet

23.04.2024 Demenz Nachrichten

Wenn Demenzkranke aufgrund von Symptomen wie Agitation oder Aggressivität mit Antipsychotika behandelt werden, sind damit offenbar noch mehr Risiken verbunden als bislang angenommen.

Update Neurologie

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