Gene expression abnormalities in human glial tumors identified by gene array

Ljubimova, Julia Y.; Khazenzon, Natasha M.; Chen, Zutang; Neyman, Yulia I.; Turner, Lauré; Riedinger, Mary S.; Black, Keith L.

doi:10.3892/ijo.18.2.287

Cited by 75 publications

(97 citation statements)

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“…Many of the identified genes have known or suspected relevance to cancer, while some of them have no known functions. In accordance with previous findings, we found Osteonectin and Vimentin to be upregulated in the majority of all grades of astrocytoma (Sallinen et al, 2000;Ljubimova et al, 2001;Fathallah-Shaykh et al, 2002). Although differential regulation of b2-microglobulin has been reported in diffuse large-B-cell lymphoma (Jordanova et al, 2003) and multidrug resistance phenotype in tumor cells (Scheffer et al, 2002), we found b2-microglobulin to be upregulated in GBM.…”

Section: Discussionsupporting

confidence: 79%

“…A more global, systematic understanding of expression patterns of various genes and their downstream gene products in astrocytoma will hopefully provide new diagnostic and therapeutic targets. Towards this, a number of studies have reported the gene expression profile of astrocytoma (Liau et al, 2000;Sallinen et al, 2000;Ljubimova et al, 2001;Rickman et al, 2001;Watson et al, 2001;Fathallah-Shaykh et al, 2002;Tanwar et al, 2002;Godard et al, 2003;Nutt et al, 2003;Wang et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

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Upregulation of ASCL1 and inhibition of Notch signaling pathway characterize progressive astrocytoma

et al. 2005

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Section: Discussionsupporting

confidence: 79%

Section: Introductionmentioning

confidence: 99%

Upregulation of ASCL1 and inhibition of Notch signaling pathway characterize progressive astrocytoma

et al. 2005

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“…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). Laminin-411 consists of three different polypeptide chains, and it was hitherto impossible to efficiently block its synthesis in vivo by existing technologies.…”

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

confidence: 98%

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.

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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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“…19 Each cycle consisted of 30 sec of denaturation at 94°C, 60 sec of annealing at 60°C and 60 sec of elongation at 72°C, with 32 cycles performed. 14 GAPDH was used as the endogenous control. RT-PCR products were analyzed by electrophoresis on 2% agarose gels.…”

Section: Rt-pcrmentioning

confidence: 99%

Downregulation of laminin α4 chain expression inhibits glioma invasionin vitro andin vivo

et al. 2005

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The laminin family is a structural constituent of the extracellular matrix that plays an essential role in promoting the motility of infiltrative tumor cells. We investigated the role of laminin a4 chain, a subset of laminin-8, -9 and -14, in the motile and invasive activities of human glioma cells. All malignant glioma cell lines examined expressed more mRNA for the laminin a4 and b1 chains than for the b2 chain, indicating that these cells predominantly express the laminin-8 isoform. Introducing an antisense oligonucleotide for laminin a4 chain (AS-Ln-a4) into the glioma cells resulted in downregulation of laminin a4 expression. AS-Ln-a4 also significantly suppressed glioma cell adhesion and migration. Furthermore, invasiveness was significantly reduced in cells transfected with AS-Ln-a4 compared to those transfected with the sense oligonucleotide (S-Ln-a4). Indeed, when glioma spheroids were implanted into rat brain slices, AS-Ln-a4-transfected cells failed to invade surrounding normal brain tissues. In addition, intracerebral injection of glioma cells transfected with AS-Ln-a4 into nude mice resulted in the formation of a noninvasive tumor, whereas injection of cells transfected with S-Ln-a4 resulted in diffuse invasion of brain tissue. These results suggest that mainly laminin-8 is essential for the invasive activity of human glioma cells; thus, a novel therapeutic strategy could target this molecule to treat patients with malignant glioma. ' 2005 Wiley-Liss, Inc.

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Gene expression abnormalities in human glial tumors identified by gene array

Cited by 75 publications

References 0 publications

Upregulation of ASCL1 and inhibition of Notch signaling pathway characterize progressive astrocytoma

Upregulation of ASCL1 and inhibition of Notch signaling pathway characterize progressive astrocytoma

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

Downregulation of laminin α4 chain expression inhibits glioma invasionin vitro andin vivo

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