Cancer Research Cell Death Mechanisms and Cancer Therapy Genetics and Biology of Brain Cancer
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kilic, T.
Right arrow Articles by Stiles, C. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kilic, T.
Right arrow Articles by Stiles, C. D.
[Cancer Research 60, 5143-5150, September 15, 2000]
© 2000 American Association for Cancer Research

Experimental Therapeutics

Intracranial Inhibition of Platelet-derived Growth Factor-mediated Glioblastoma Cell Growth by an Orally Active Kinase Inhibitor of the 2-Phenylaminopyrimidine Class1

Turker Kilic2,3, John A. Alberta2, Pawel R. Zdunek4, Melih Acar5, Palma Iannarelli, Terence O’Reilly, Elisabeth Buchdunger, Peter M. Black and Charles D. Stiles6

Neurosurgical Laboratories and Brain Tumor Center, Brigham and Women’s Hospital, The Children’s Hospital, and Department of Surgery, Harvard Medical School [T. K., P. R. Z., M. A., P. M. B.], and Department of Microbiology and Molecular Genetics, Harvard Medical School and the Dana-Farber Cancer Institute [J. A. A., P. I., C. D. S.], Boston, Massachusetts 02115, and Novartis Pharma AG, Oncology Research, CH-4002 Basel, Switzerland [T. O., E. B.]

Glioblastoma multiforme is the most common primary human brain tumor, and it is, for all practical purposes, incurable in adult patients. The high mortality rates reflect the fact that glioblastomas are resistant to adjuvant therapies (radiation and chemicals), the mode of action of which is cytotoxic. We show here that an p.o.-active small molecule kinase inhibitor of the 2-phenylaminopyrimidine class may have therapeutic potential for glioblastomas. STI571 inhibits the growth of U343 and U87 human glioblastoma cells that have been injected into the brains of nude mice, but it does not inhibit intracranial growth of ras-transformed cells. Studies on a broad panel of genetically validated human and animal cell lines show that STI571 acts by disruption of the ligand:receptor autocrine loops for platelet-derived growth factor that are a pervasive feature of malignant astrocytoma. The cellular response of glioblastoma cells to STI571 does not appear to involve an apoptotic mechanism.




This article has been cited by other articles:


Home page
 Clin. Cancer Res.Home page
E. Razis, P. Selviaridis, S. Labropoulos, J. L. Norris, M.-J. Zhu, D. D. Song, T. Kalebic, M. Torrens, A. Kalogera-Fountzila, G. Karkavelas, et al.
Phase II Study of Neoadjuvant Imatinib in Glioblastoma: Evaluation of Clinical and Molecular Effects of the Treatment
Clin. Cancer Res., October 1, 2009; 15(19): 6258 - 6266.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
J. Paulsson, T. Sjoblom, P. Micke, F. Ponten, G. Landberg, C.-H. Heldin, J. Bergh, D. J. Brennan, K. Jirstrom, and A. Ostman
Prognostic Significance of Stromal Platelet-Derived Growth Factor {beta}-Receptor Expression in Human Breast Cancer
Am. J. Pathol., July 1, 2009; 175(1): 334 - 341.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
J. Mukherjee, D. Kamnasaran, A. Balasubramaniam, I. Radovanovic, G. Zadeh, T.-R. Kiehl, and A. Guha
Human Schwannomas Express Activated Platelet-Derived Growth Factor Receptors and c-kit and Are Growth Inhibited by Gleevec (Imatinib Mesylate)
Cancer Res., June 15, 2009; 69(12): 5099 - 5107.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
T. J. Abouantoun and T. J. MacDonald
Imatinib blocks migration and invasion of medulloblastoma cells by concurrently inhibiting activation of platelet-derived growth factor receptor and transactivation of epidermal growth factor receptor
Mol. Cancer Ther., May 1, 2009; 8(5): 1137 - 1147.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
O. Benny, L. G. Menon, G. Ariel, E. Goren, S.-K. Kim, C. Stewman, P. M. Black, R. S. Carroll, and M. Machluf
Local Delivery of Poly Lactic-co-glycolic Acid Microspheres Containing Imatinib Mesylate Inhibits Intracranial Xenograft Glioma Growth
Clin. Cancer Res., February 15, 2009; 15(4): 1222 - 1231.
[Abstract] [Full Text] [PDF]

Home page
 Reproductive SciencesHome page
R. P. Rocconi, K. S. Matthews, K. J. Kimball, M. G. Conner, A. C. Baker, and M. N. Barnes
Expression of C-kit and Platelet-Derived Growth Factor Receptors in Ovarian Granulosa Cell Tumors
Reproductive Sciences, September 1, 2008; 15(7): 673 - 677.
[Abstract] [PDF]

Home page
 JCOHome page
D. S. Ziegler, A. L. Kung, and M. W. Kieran
Anti-Apoptosis Mechanisms in Malignant Gliomas
J. Clin. Oncol., January 20, 2008; 26(3): 493 - 500.
[Abstract] [Full Text] [PDF]

Home page
 Genes Dev.Home page
S. V. Sharma and J. Settleman
Oncogene addiction: setting the stage for molecularly targeted cancer therapy
Genes & Dev., December 15, 2007; 21(24): 3214 - 3231.
[Abstract] [Full Text] [PDF]

Home page
 Genes Dev.Home page
F. B. Furnari, T. Fenton, R. M. Bachoo, A. Mukasa, J. M. Stommel, A. Stegh, W. C. Hahn, K. L. Ligon, D. N. Louis, C. Brennan, et al.
Malignant astrocytic glioma: genetics, biology, and paths to treatment
Genes & Dev., November 1, 2007; 21(21): 2683 - 2710.
[Abstract] [Full Text] [PDF]

Home page
 The OncologistHome page
S. Marchetti, R. Mazzanti, J. H. Beijnen, and J. H. M. Schellens
Concise Review: Clinical Relevance of Drug Drug and Herb Drug Interactions Mediated by the ABC Transporter ABCB1 (MDR1, P-glycoprotein)
Oncologist, August 1, 2007; 12(8): 927 - 941.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
A. M.P. Omuro, S. Faivre, and E. Raymond
Lessons learned in the development of targeted therapy for malignant gliomas
Mol. Cancer Ther., July 1, 2007; 6(7): 1909 - 1919.
[Abstract] [Full Text] [PDF]

Home page
 Endocr Relat CancerHome page
M. Brama, S. Basciani, S. Cherubini, S. Mariani, S. Migliaccio, M. Arizzi, G. Rosano, G. Spera, and L. Gnessi
Osteoblast-conditioned medium promotes proliferation and sensitizes breast cancer cells to imatinib treatment
Endocr. Relat. Cancer, March 1, 2007; 14(1): 61 - 72.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
L. Yang, E. Jackson, B. M. Woerner, A. Perry, D. Piwnica-Worms, and J. B. Rubin
Blocking CXCR4-Mediated Cyclic AMP Suppression Inhibits Brain Tumor Growth In vivo
Cancer Res., January 15, 2007; 67(2): 651 - 658.
[Abstract] [Full Text] [PDF]

Home page
 Drug Metab. Dispos.Home page
S. Bihorel, G. Camenisch, G. Gross, M. Lemaire, and J.-M. Scherrmann
Influence of Hydroxyurea On Imatinib Mesylate (Gleevec) Transport at the Mouse Blood-Brain Barrier
Drug Metab. Dispos., December 1, 2006; 34(12): 1945 - 1949.
[Abstract] [Full Text] [PDF]

Home page
 Mayo Clin Proc.Home page
R. H. Alvarez, H. M. Kantarjian, and J. E. Cortes
Biology of Platelet-Derived Growth Factor and Its Involvement in Disease
Mayo Clin. Proc., September 1, 2006; 81(9): 1241 - 1257.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
P. Y. Wen, W.K. A. Yung, K. R. Lamborn, P. L. Dahia, Y. Wang, B. Peng, L. E. Abrey, J. Raizer, T. F. Cloughesy, K. Fink, et al.
Phase I/II Study of Imatinib Mesylate for Recurrent Malignant Gliomas: North American Brain Tumor Consortium Study 99-08.
Clin. Cancer Res., August 15, 2006; 12(16): 4899 - 4907.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
S. Jones-Bolin, H. Zhao, K. Hunter, A. Klein-Szanto, and B. Ruggeri
The effects of the oral, pan-VEGF-R kinase inhibitor CEP-7055 and chemotherapy in orthotopic models of glioblastoma and colon carcinoma in mice.
Mol. Cancer Ther., July 1, 2006; 5(7): 1744 - 1753.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
D. A. Reardon, M. J. Egorin, J. A. Quinn, J. N. Rich Sr, I. Gururangan, J. J. Vredenburgh, A. Desjardins, S. Sathornsumetee, J. M. Provenzale, J. E. Herndon II, et al.
Phase II Study of Imatinib Mesylate Plus Hydroxyurea in Adults With Recurrent Glioblastoma Multiforme
J. Clin. Oncol., December 20, 2005; 23(36): 9359 - 9368.
[Abstract] [Full Text] [PDF]

Home page
 NEJMHome page
D. S. Krause and R. A. Van Etten
Tyrosine Kinases as Targets for Cancer Therapy
N. Engl. J. Med., July 14, 2005; 353(2): 172 - 187.
[Full Text] [PDF]

Home page
 Cancer Res.Home page
D. Ma, C. L. Nutt, P. Shanehsaz, X. Peng, D. N. Louis, and D. M. Kaetzel
Autocrine Platelet-Derived Growth Factor-Dependent Gene Expression in Glioblastoma Cells Is Mediated Largely by Activation of the Transcription Factor Sterol Regulatory Element Binding Protein and Is Associated with Altered Genotype and Patient Survival in Human Brain Tumors
Cancer Res., July 1, 2005; 65(13): 5523 - 5534.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
P. Breedveld, D. Pluim, G. Cipriani, P. Wielinga, O. van Tellingen, A. H. Schinkel, and J. H.M. Schellens
The Effect of Bcrp1 (Abcg2) on the In vivo Pharmacokinetics and Brain Penetration of Imatinib Mesylate (Gleevec): Implications for the Use of Breast Cancer Resistance Protein and P-Glycoprotein Inhibitors to Enable the Brain Penetration of Imatinib in Patients
Cancer Res., April 1, 2005; 65(7): 2577 - 2582.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
S. Basciani, M. Brama, S. Mariani, G. De Luca, M. Arizzi, L. Vesci, C. Pisano, S. Dolci, G. Spera, and L. Gnessi
Imatinib Mesylate Inhibits Leydig Cell Tumor Growth: Evidence for In vitro and In vivo Activity
Cancer Res., March 1, 2005; 65(5): 1897 - 1903.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
W. G. Roberts, P. M. Whalen, E. Soderstrom, G. Moraski, J. P. Lyssikatos, H.-F. Wang, B. Cooper, D. A. Baker, D. Savage, D. Dalvie, et al.
Antiangiogenic and Antitumor Activity of a Selective PDGFR Tyrosine Kinase Inhibitor, CP-673,451
Cancer Res., February 1, 2005; 65(3): 957 - 966.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
M. Hagedorn, S. Javerzat, D. Gilges, A. Meyre, B. de Lafarge, A. Eichmann, and A. Bikfalvi
Accessing key steps of human tumor progression in vivo by using an avian embryo model
PNAS, February 1, 2005; 102(5): 1643 - 1648.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
A. H. Shih, C. Dai, X. Hu, M. K. Rosenblum, J. A. Koutcher, and E. C. Holland
Dose-Dependent Effects of Platelet-Derived Growth Factor-B on Glial Tumorigenesis
Cancer Res., July 15, 2004; 64(14): 4783 - 4789.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
M. Furuhashi, T. Sjoblom, A. Abramsson, J. Ellingsen, P. Micke, H. Li, E. Bergsten-Folestad, U. Eriksson, R. Heuchel, C. Betsholtz, et al.
Platelet-Derived Growth Factor Production by B16 Melanoma Cells Leads to Increased Pericyte Abundance in Tumors and an Associated Increase in Tumor Growth Rate
Cancer Res., April 15, 2004; 64(8): 2725 - 2733.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
K. Neville, R. A. Parise, P. Thompson, A. Aleksic, M. J. Egorin, F. M. Balis, L. McGuffey, C. McCully, S. L. Berg, and S. M. Blaney
Plasma and Cerebrospinal Fluid Pharmacokinetics of Imatinib after Administration to Nonhuman Primates
Clin. Cancer Res., April 1, 2004; 10(7): 2525 - 2529.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
D. Matei, D. D. Chang, and M.-H. Jeng
Imatinib Mesylate (Gleevec) Inhibits Ovarian Cancer Cell Growth through a Mechanism Dependent on Platelet-Derived Growth Factor Receptor {alpha} and Akt Inactivation
Clin. Cancer Res., January 15, 2004; 10(2): 681 - 690.
[Abstract] [Full Text] [PDF]

Home page
 JNCI J Natl Cancer InstHome page
K. Beppu, J. Jaboine, M. S. Merchant, C. L. Mackall, and C. J. Thiele
Effect of Imatinib Mesylate on Neuroblastoma Tumorigenesis and Vascular Endothelial Growth Factor Expression
J Natl Cancer Inst, January 7, 2004; 96(1): 46 - 55.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
E. Abruzzese, M. Cantonetti, L. Morino, G. Orlandi, A. Tendas, M.I. Del Principe, M. Masi, S. Amadori, A. Orlandi, L. Anemona, et al.
CNS and Cutaneous Involvement in Patients With Chronic Myeloid Leukemia Treated With Imatinib in Hematologic Complete Remission: Two Case Reports
J. Clin. Oncol., November 15, 2003; 21(22): 4256 - 4258.
[Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
H. Dai, P. Marbach, M. Lemaire, M. Hayes, and W. F. Elmquist
Distribution of STI-571 to the Brain Is Limited by P-Glycoprotein-Mediated Efflux
J. Pharmacol. Exp. Ther., March 1, 2003; 304(3): 1085 - 1092.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
L. Tatton, G. M. Morley, R. Chopra, and A. Khwaja
The Src-selective Kinase Inhibitor PP1 Also Inhibits Kit and Bcr-Abl Tyrosine Kinases
J. Biol. Chem., February 7, 2003; 278(7): 4847 - 4853.
[Abstract] [Full Text] [PDF]

Home page
 Neuro Oncol DukeHome page
F. F. Lang, M. R. Gilbert, V. K. Puduvalli, J. Weinberg, V. A. Levin, W.K. A. Yung, R. Sawaya, G. N. Fuller, and C. A. Conrad
Toward better early-phase brain tumor clinical trials: A reappraisal of current methods and proposals for future strategies
Neuro-oncol, October 1, 2002; 4(4): 268 - 277.
[Abstract] [PDF]

Home page
 Cancer Res.Home page
S. Attoub, C. Rivat, S. Rodrigues, S. Van Bocxlaer, M. Bedin, E. Bruyneel, C. Louvet, M. Kornprobst, T. Andre, M. Mareel, et al.
The c-kit Tyrosine Kinase Inhibitor STI571 for Colorectal Cancer Therapy
Cancer Res., September 1, 2002; 62(17): 4879 - 4883.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
N. A. Lokker, C. M. Sullivan, S. J. Hollenbach, M. A. Israel, and N. A. Giese
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., July 1, 2002; 62(13): 3729 - 3735.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
E. J. Baxter, A. Hochhaus, P. Bolufer, A. Reiter, J. M. Fernandez, L. Senent, J. Cervera, F. Moscardo, M. A. Sanz, and N. C.P. Cross
The t(4;22)(q12;q11) in atypical chronic myeloid leukaemia fuses BCR to PDGFRA
Hum. Mol. Genet., June 1, 2002; 11(12): 1391 - 1397.
[Abstract] [Full Text] [PDF]

Home page
 NEJMHome page
D. G. Savage and K. H. Antman
Imatinib Mesylate -- A New Oral Targeted Therapy
N. Engl. J. Med., February 28, 2002; 346(9): 683 - 693.
[Full Text] [PDF]

Home page
 JCOHome page
M. J. Mauro, M. O'Dwyer, M. C. Heinrich, and B. J. Druker
STI571: A Paradigm of New Agents for Cancer Therapeutics
J. Clin. Oncol., January 1, 2002; 20(1): 325 - 334.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
E. J. Dann, R. Fineman, and J. M. Rowe
Tumor Lysis Syndrome After STI571 in Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia
J. Clin. Oncol., January 1, 2002; 20(1): 354 - 355.
[Full Text] [PDF]

Home page
 The OncologistHome page
Y. A. Elsayed and E. A. Sausville
Selected Novel Anticancer Treatments Targeting Cell Signaling Proteins
Oncologist, December 1, 2001; 6(6): 517 - 537.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
J.-C. Yu, N. A. Lokker, S. Hollenbach, M. Apatira, J. Li, A. Betz, D. Sedlock, S. Oda, Y. Nomoto, K. Matsuno, et al.
Efficacy of the Novel Selective Platelet-Derived Growth Factor Receptor Antagonist CT52923 on Cellular Proliferation, Migration, and Suppression of Neointima following Vascular Injury
J. Pharmacol. Exp. Ther., September 1, 2001; 298(3): 1172 - 1178.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
T. Sjoblom, A. Shimizu, K. P. O'Brien, K. Pietras, P. Dal Cin, E. Buchdunger, J. P. Dumanski, A. Ostman, and C.-H. Heldin
Growth Inhibition of Dermatofibrosarcoma Protuberans Tumors by the Platelet-derived Growth Factor Receptor Antagonist STI571 through Induction of Apoptosis
Cancer Res., August 1, 2001; 61(15): 5778 - 5783.
[Abstract] [Full Text] [PDF]

Home page
 The OncologistHome page
B. A. Chabner
The Oncologic Four-Minute Mile
Oncologist, June 1, 2001; 6(3): 230 - 232.
[Full Text] [PDF]

Home page
 The OncologistHome page
M. J. Mauro and B. J. Druker
STI571: Targeting BCR-ABL as Therapy for CML
Oncologist, June 1, 2001; 6(3): 233 - 238.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 2000 by the American Association for Cancer Research.