Antiangiogenic Strategies for Treatment of Malignant Gliomas

Andrew, S.; Norden, Andrew D.; Wen, Patrick Y.

doi:10.1016/j.nurt.2009.04.010

Cited by 32 publications

(26 citation statements)

References 123 publications

(137 reference statements)

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“…Using SAM, we identified GBM-specific serum markers and subsequently validated many of them. Some of the genes identified in this screen, such as CHI3L, IGFBP2, and VEGFA, have been previously reported as GBMspecific serum markers with prognostic value (15)(16)(17)(18). In our study, we could also show the GBM-specific expression of the transcripts of these genes by RT-qPCR (data not shown).…”

Section: Discussionsupporting

confidence: 59%

Identification of Potential Serum Biomarkers of Glioblastoma: Serum Osteopontin Levels Correlate with Poor Prognosis

Sreekanthreddy

Srinivasan

Kumar

et al. 2010

Cancer Epidemiology, Biomarkers &Amp; Prevention

121

110

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Background: The aim of this study is to identify serum biomarkers with classification and prognosis utility for astrocytoma, in particular glioblastoma (GBM).Methods: Our previous glioma microarray database was mined to identify genes that encode secreted or membrane-localized proteins. Subsequent analysis was done using significant analysis of microarrays, followed by reverse transcription-quantitative PCR (RT-qPCR) and immunohistochemical validation in tumor tissues, ELISA and Western blot validation in sera, and correlation with survival of GBM patients.Results: Significant analysis of microarrays identified 31 upregulated and 3 downregulated genes specifically in GBMs. RT-qPCR validation on an independent set of samples confirmed the GBM-specific differential expression of several genes, including three upregulated (CALU, CXCL9, and TIMP1) and two downregulated (GPX3 and TIMP3) novel genes. With respect to osteopontin (OPN), we show the GBM-specific upregulation by RT-qPCR and immunohistochemical staining of tumor tissues. Elevated serum OPN levels in GBM patients were also shown by ELISA and Western blot. GBM patients with high serum OPN levels had poorer survival than those with low serum OPN levels (median survival 9 versus 22 months respectively; P = 0.0001). Further, we also show high serum TIMP1 levels in GBM patients compared with grade II/III patients by ELISA and downregulation of serum GPX3 and TIMP3 proteins in GBMs compared with normal control by Western blot analysis.Conclusions: Several novel potential serum biomarkers of GBM are identified and validated. High serum OPN level is found as a poor prognostic indicator in GBMs.Impact: Identified serum biomarkers may have potential utility in astrocytoma classification and GBM prognosis. Cancer Epidemiol Biomarkers Prev; 19(6); 1409-22. ©2010 AACR.

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Section: Discussionsupporting

confidence: 59%

Identification of Potential Serum Biomarkers of Glioblastoma: Serum Osteopontin Levels Correlate with Poor Prognosis

Sreekanthreddy

Srinivasan

Kumar

et al. 2010

Cancer Epidemiology, Biomarkers &Amp; Prevention

121

110

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“…A hallmark of current cancer treatment is inhibition of tumor angiogenesis (2,3). Antiangiogenic inhibitors of VEGF receptors and VEGF-independent inhibitors combined with chemotherapy have shown some promise, but the patients' survival in clinical trials was not significantly changed (4). We documented overexpression of tumor-specific vascular basement membrane protein laminin-411 in glioblastoma and its association with tumor recurrence and decreased patients' survival time (5,6).…”

Section: Inhibition Of Brain Tumor Growth By Intravenous Poly (β-L-mamentioning

confidence: 85%

Inhibition of brain tumor growth by intravenous poly(β- l -malic acid) nanobioconjugate with pH-dependent drug release

Inoue

Ljubimov

Patil

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

160

180

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Effective treatment of brain neurological disorders such as Alzheimer's disease, multiple sclerosis, or tumors should be possible with drug delivery through blood–brain barrier (BBB) or blood–brain tumor barrier (BTB) and targeting specific types of brain cells with drug release into the cell cytoplasm. A polymeric nanobioconjugate drug based on biodegradable, nontoxic, and nonimmunogenic polymalic acid as a universal delivery nanoplatform was used for design and synthesis of nanomedicine drug for i.v. treatment of brain tumors. The polymeric drug passes through the BTB and tumor cell membrane using tandem monoclonal antibodies targeting the BTB and tumor cells. The next step for polymeric drug action was inhibition of tumor angiogenesis by specifically blocking the synthesis of a tumor neovascular trimer protein, laminin-411, by attached antisense oligonucleotides (AONs). The AONs were released into the target cell cytoplasm via pH-activated trileucine, an endosomal escape moiety. Drug delivery to the brain tumor and the release mechanism were both studied for this nanobiopolymer. Introduction of a trileucine endosome escape unit resulted in significantly increased AON delivery to tumor cells, inhibition of laminin-411 synthesis in vitro and in vivo, specific accumulation in brain tumors, and suppression of intracranial glioma growth compared with pH-independent leucine ester. The availability of a systemically active polymeric drug delivery system that passes through the BTB, targets tumor cells, and inhibits glioma growth gives hope for a successful strategy of glioma treatment. This delivery system with drug release into the brain-specific cell type could be useful for treatment of various brain pathologies.

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“…There are three major strategies to antiangiogenesis therapy in patients with glioblastoma ( Fig 6) (10,11). The first is to inhibit the VEGF pathway by targeting the VEGF molecules either with antibodies to VEGF (bevacizumab) or with a decoy VEGF (aflibercept).…”

Section: Antiangiogenesis Therapymentioning

confidence: 99%

“…Another approach is direct inhibition of the receptor, VEGFR. Several drugs that inhibit VEGFR have been developed, including cediranib, sunitinib, and sorafenib (10). Antiangiogenesis therapy with bevacizumab is now approved for recurrent glioblastomas, with modest improvement in survival reported (11).…”

Section: Antiangiogenesis Therapymentioning

confidence: 99%

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Genetics of Glioblastoma: A Window into Its Imaging and Histopathologic Variability

Belden¹,

Valdés²,

Ran³

et al. 2011

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Antiangiogenic Strategies for Treatment of Malignant Gliomas

Cited by 32 publications

References 123 publications

Identification of Potential Serum Biomarkers of Glioblastoma: Serum Osteopontin Levels Correlate with Poor Prognosis

Identification of Potential Serum Biomarkers of Glioblastoma: Serum Osteopontin Levels Correlate with Poor Prognosis

Inhibition of brain tumor growth by intravenous poly(β- l -malic acid) nanobioconjugate with pH-dependent drug release

Genetics of Glioblastoma: A Window into Its Imaging and Histopathologic Variability

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