author={Shinya Yamada and Xingyao Bu and Vazgen Khankaldyyan and Ignacio Gonzales-Gomez and J. Gordon McComb and Walter E. Laug},
OBJECTIVETo determine the effect of the angiogenesis inhibitor Cilengitide (EMD 121974) on glioblastoma growth and associated angiogenesis in the brains of nude mice. METHODSHuman glioblastoma cells (105 U87MG cells) in 1 μl of medium were stereotactically injected during a 20-minute period into the caudate/putamen of nude mice. The mice were intraperitoneally treated daily with Cilengitide or solvent (control) beginning 5 days after tumor injection. The mice were sacrificed from 1 hour to 63… 

Figures from this paper

Combination therapy of cilengitide with belotecan against experimental glioblastoma

In vitro and in vivo the antitumor effects of combination therapy of cilengitide with belotecan, a camptothecin derivate, to treat experimental glioblastoma presented more cytotoxic effects compared to the monotherapy of either drug in vitro andIn vivo.

The Integrin Inhibitor Cilengitide Affects Meningioma Cell Motility and Invasion

Data show that a monotherapy with cilengitide is not likely to achieve major responses in rapidly growing malignant meningiomas, although brain invasion may be reduced because of the strong antimigratory properties of the drug.

Integrin αvβ3-Targeted Radioimmunotherapy of Glioblastoma Multiforme

Radioimmunotherapy with 90Y-labeled Abegrin may prove promising in the treatment of highly vascular, invasive, and heterogeneous malignant brain tumors.

Integrin AvB3-Targeted Radioimmunotherapy of Glioblastoma

Radioimmunotherapy with 90 Y-labeled Abegrin may prove promising in the treat- ment of highly vascular, invasive, and heterogeneous malignant brain tumors.

Differential growth inhibition of cerebral metastases by anti-angiogenic compounds.

The combination of endogenous IL-12 production with integrin blockade resulted in additive effects for murine hematogenous head metastases but not for focal brain metastases.

The integrin antagonist cilengitide increases the antitumor activity of temozolomide against malignant melanoma.

Cilengitide was tested in combination with the methylating agent temozolomide (TMZ), a well-tolerated anticancer drug with favourable pharmacokinetic properties currently used for the therapy of metastatic melanoma, and exerted synergistic antiproliferative effects against melanoma and endothelial cells in vitro and induced a statistically significant reduction of in vivo melanoma growth.

TNF and manipulation of the tumor cell-stromal interface: "ways to make chemotherapy effective".

Tumor necrosis factor alpha (TNF) is a very promising vaso-active agent because of its anti-tumor effects but its severe systemic toxicity is a major drawback, therefore a new setting, in which the optimal therapeutic benefit of TNF could be exploited, needed to be found.

Bimodal anti‐glioma mechanisms of cilengitide demonstrated by novel invasive glioma models

  • M. OnishiT. Ichikawa I. Date
  • Biology, Medicine
    Neuropathology : official journal of the Japanese Society of Neuropathology
  • 2013
The results indicate that cilengitide exerts a phenotypic anti‐tumor effect by inhibiting angiogenesis and glioma cell invasion, clearly shown by the experimental treatment of two different animal invasiveglioma models.

Integrin inhibitor cilengitide for the treatment of glioblastoma: a brief overview of current clinical results.

Cilengitide, a cyclized Arg-Gly-Glu(RGD)-containing pentapeptide that selectively blocks activation of the αvβ3 and αv β5 integrins has shown encouraging activity in patients with glioblastoma as single agent, and in association with standard RT and temozolomide.

Effect of tumor microenvironment modulation on the efficacy of oncolytic virus therapy.

Oncolytic virus treatment of experimental rat gliomas increased tumor vascular permeability, host leukocyte infiltration into tumors, and intratumoral expression of inflammatory cytokine genes, including interferon gamma (IFN-gamma).



Preferential Susceptibility of Brain Tumors to the Antiangiogenic Effects of an &agr;v Integrin Antagonist

The cyclic pentapeptide EMD 121974 may become a treatment option specific to brain tumors because of its antiangiogenic effect, and its use may be especially indicated after tumors are removed surgically.

Activity of irofulven (6-hydroxymethylacylfulvene) in the treatment of glioblastoma multiforme-derived xenografts in athymic mice

Irofulven is active in a spectrum of human glioblastoma multiforme-derived xenografts and evaluation in patients with this neoplasm is warranted.

Angiostatin suppresses malignant glioma growth in vivo.

It is demonstrated that systemic administration of angiostatin efficiently suppresses malignant glioma growth in vivo, and the tumoristatic activity against intracranial tumors independent of the blood brain barrier suggests that targeting the vascular compartment may offer novel therapeutic strategies against malignantgliomas.

Vascular Apoptosis and Involution in Gliomas Precede Neovascularization: A Novel Concept for Glioma Growth and Angiogenesis

It is suggested that vascular cell apoptosis and involution preceded tumor necrosis and that angiogenesis is a later event in tumor progression in experimental gliomas and could be linked to vascular involution.

αv‐Integrin antagonist EMD 121974 induces apoptosis in brain tumor cells growing on vitronectin and tenascin

The αv‐antagonist EMD 121974 suppresses brain tumor growth through induction of apoptosis in both brain capillary and brain tumor cells by preventing their interaction with the matrix proteins vitronectin and tenascin.

Species-specific urokinase receptor ligands reduce glioma growth and increase survival primarily by an antiangiogenesis mechanism

The results suggest that the major role of the uPAR system in brain tumor progression is in the stromal compartment and particularly in neovascularization, a hallmark of invasive brain tumors.

Activity of temozolomide in the treatment of central nervous system tumor xenografts.

It is suggested that temozolomide may be active in the treatment of a broad spectrum of central nervous system cancers, including Mer+ tumors resistant to 1,3-bis(2-chloroethyl)-1-nitrosourea.

Intracranial injection of human meningioma cells in athymic mice: an orthotopic model for meningioma growth.

The three types of human meningiomas grown intracranially in athymic mice maintained their relative positions in the spectrum of malignancy, however, atypical mening iomas became more aggressive after xenografting and acquired malignant features, implying that there had been immune constraint in the original host.

GM3 as a Novel Growth Regulator for Human Gliomas

GM3 treatment dramatically reduces cell numbers in primary cultures of high-grade human glioblastoma multiforme (GBM) tumors and the rat 9L cell gliosarcoma cell line, suggesting that GM3 may have considerable value as a selectively toxic chemotherapeutic agent for human high- grade gliomas.