DF/HCC Program Affiliation

Neuro-Oncology

Research Abstract

The goal of our research is to understand how angiogenesis, and receptor mediated growth mechanisms contribute to nervous system neoplasia. Human malignant gliomas are among the most malignant and most intensely vascularized solid tumors. Tumor angiogenesis is believed to be mediated by soluble factors released from tumor cells which then act on endothelial cells in a paracrine manner. . Vascular endothelial growth factor (VEGF) is a prime regulator of normal and tumor angiogenesis as well as vasculogenesis. VEGF is expressed in glioma cells and its receptors (FLT-1 and KDR) are expressed in the same gliomas. We used a synthetic tyrosine phosphopeptide to raise an antibody that reports the phosphorylation state of tyrosine in the KDR receptor. Immunoblotting and immunostaining of this antibody shows that the KDR receptor is activated in human high grade astrocytomas (71%), but not low grade astrocytomas (0%).

Angiostatin and endostatin are two endogenous inhibitors of tumor-related angiogenesis by selective inhibition of endothelial cell growth. We have demonstrate that systemic administration of angiostatin efficiently suppresses malignant glioma growth in vivo. We are presently examining the effects of endostatin on glioma growth. The findings of the current study strongly support the hypothesis that the onset of angiogenesis is an important event during the disease progression of gliomas.

Publications

• Cargioli TG, Ugur HC, Ramakrishna N, Chan J, Black PM, Carroll RS.Establishment of an in vivo meningioma model with human telomerase reverse transcriptase.Neurosurgery 2007 Apr;60(4):750-9; discussion 759-60.
  17415213
• Yu Y, Jiang X, Schoch BS, Carroll RS, Black PM, Johnson MD.Aberrant splicing of cyclin-dependent kinase-associated protein phosphatase KAP increases proliferation and migration in glioblastoma.Cancer Res 2007 Jan 1;67(1):130-8.
  17210692
• Liu F, Park PJ, Lai W, Maher E, Chakravarti A, Durso L, Jiang X, Yu Y, Brosius A, Thomas M, Chin L, Brennan C, DePinho RA, Kohane I, Carroll RS, Black PM, Johnson MD.A genome-wide screen reveals functional gene clusters in the cancer genome and identifies
  17090523
• Kim SK, Kim SU, Park IH, Bang JH, Aboody KS, Wang KC, Cho BK, Kim M, Menon LG, Black PM, Carroll RS.Human neural stem cells target experimental intracranial medulloblastoma and deliver a therapeutic gene leading to tumor regression.Clin Cancer Res 2006 Se
  17000692
• Ziu M, Schmidt NO, Cargioli TG, Aboody KS, Black PM, Carroll RS.Glioma-produced extracellular matrix influences brain tumor tropism of human neural stem cells.J Neurooncol 2006 Apr 6.
  16598423
• Aboody KS, Najbauer J, Schmidt NO, Yang W, Wu JK, Zhuge Y, Przylecki W, Carroll R, Black PM, Perides G.Targeting of melanoma brain metastases using engineered neural stem/progenitor cells.Neuro-oncol 2006 Apr;8(2):119-26.
  16524944
• Kim SK, Cargioli TG, Machluf M, Yang W, Sun Y, Al-Hashem R, Kim SU, Black PM, Carroll RS.PEX-producing human neural stem cells inhibit tumor growth in a mouse glioma model.Clin Cancer Res 2005 Aug 15;11(16):5965-70.
  16115940
• Schmidt NO, Przylecki W, Yang W, Ziu M, Teng Y, Kim SU, Black PM, Aboody KS, Carroll RS.Brain tumor tropism of transplanted human neural stem cells is induced by vascular endothelial growth factor.Neoplasia 2005 Jun;7(6):623-9.
  16036113
• Benny O, Duvshani-Eshet M, Cargioli T, Bello L, Bikfalvi A, Carroll RS, Machluf M.Continuous delivery of endogenous inhibitors from poly(lactic-co-glycolic acid) polymeric microspheres inhibits glioma tumor growth.Clin Cancer Res 2005 Jan 15;11(2 Pt 1):76
  15701867
• Schmidt KF, Ziu M, Schmidt NO, Vaghasia P, Cargioli TG, Doshi S, Albert MS, Black PM, Carroll RS, Sun Y.Volume reconstruction techniques improve the correlation between histological and in vivo tumor volume measurements in mouse models of human gliomas.J
  15332323
• Schmidt NO, Ziu M, Carrabba G, Giussani C, Bello L, Sun Y, Schmidt K, Albert M, Black PM, Carroll RS.Antiangiogenic therapy by local intracerebral microinfusion improves treatment efficiency and survival in an orthotopic human glioblastoma model.Clin Canc
  14977823
• Carroll RS, Zhang J, Bello L, Melnick MB, Maruyama T, McL Black P.KDR activation in astrocytic neoplasms.Cancer 1999 Oct 1;86(7):1335-41.
  10506722
• Carroll RS, Zhang J, Black PM.Expression of estrogen receptors alpha and beta in human meningiomas.J Neurooncol 1999 Apr;42(2):109-16.
  10421067