Proteomic comparison of oligodendrogliomas with and without 1pLOH

Okamoto, Hiroaki; Li, Jie; Gläsker, Sven; Vortmeyer, Alexander O.; Jaffe, Howard; Robison, R. Aaron; Bögler, Oliver; Mikkelsen, Tom; Lubensky, Irina A.; Oldfield, Edward H.; Zhuang, Zhengping

doi:10.4161/cbt.6.3.3731

Cited by 16 publications

(14 citation statements)

References 40 publications

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“…Silver-stained spots were destained as previously described (Okamoto et al, 2007), then subjected to reduction and alkylation, followed by in situ digestion with trypsin. The resulting peptide mixtures were recovered by sequential extraction as previously described (Stone and Williams, 1993).…”

Section: Rt-pcrmentioning

confidence: 99%

9-Aminoacridine-based anticancer drugs target the PI3K/AKT/mTOR, NF-κB and p53 pathways

et al. 2009

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Acquisition of a transformed phenotype involves deregulation of several signal transduction pathways contributing to unconstrained cell growth. Understanding the interplay of different cancer-related signaling pathways is important for development of efficacious multitargeted anticancer drugs. The small molecule 9-aminoacridine (9AA) and its derivative, the antimalaria drug quinacrine, have selective toxicity for tumor cells and can simultaneously suppress nuclear factor-jB (NF-jB) and activate p53 signaling. To investigate the mechanism underlying these drug activities, we used a combination of twodimensional protein separation by gel electrophoresis and mass spectrometry to identify proteins whose expression is altered in tumor cells by 9AA treatment. We found that 9AA treatment results in selective downregulation of a specific catalytic subunit of the phosphoinositide 3-kinase (PI3K) family, p110c. Further exploration of this observation demonstrated that the mechanism of action of 9AA involves inhibition of the prosurvival AKT/ mammalian target of rapamycin (mTOR) pathway that lies downstream of PI3K. p110c translation appears to be regulated by mTOR and feeds back to further modulate mTOR and AKT, thereby impacting the p53 and NF-jB pathways as well. These results reveal functional interplay among the PI3K/AKT/mTOR, p53 and NF-jB pathways that are frequently deregulated in cancer and suggest that their simultaneous targeting by a single small molecule such as 9AA could result in efficacious and selective killing of transformed cells.

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Section: Rt-pcrmentioning

confidence: 99%

9-Aminoacridine-based anticancer drugs target the PI3K/AKT/mTOR, NF-κB and p53 pathways

et al. 2009

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“…Okamoto et al . compared the proteome of oligodendrogliomas with different chemosensitivities to identify 7 candidate proteins that were over-expressed in chemoresistant oligodendroglioma [23]. Two of these proteins were glyoxalase I and Rho GDP dissociation inhibitor, which have previously been shown to enhance chemoresistance in other tumors.…”

Section: Proteomic Analysis Of Gliomamentioning

confidence: 99%

Proteomic Analysis of Glioma Chemoresistance

Suk¹

2012

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Malignant glioma is the most common and destructive form of primary brain tumor. Along with surgery and radiation, chemotherapy remains as the major treatment modality. The emergence of drug resistance, however, often leads to a therapeutic failure in the treatment of glioma, precluding long-term survival of the patients. A proteomic approach has recently been adapted for the mechanistic analysis of glioma drug resistance. The proteomic analysis of drug-resistant glioma led to the discovery of novel biomarkers that can be used for the prognosis of glioma as well as for monitoring the drug response or resistance of glioma. These proteomics-based biomarkers can also be a druggable target that one can exploit for successful glioma chemotherapy. In this review, recent reports on proteomic analysis of glioma from the perspective of chemoresistance are discussed with a focus on the proteome profiles of glioma cells that are resistant to the alkylating agent, 1, 3-bis (2-chloroethyl)-1-nitrosourea (BCNU), as a prime example. Among numerous proteins that were up- or down-regulated in drug-resistant glioma cells, lipocalin 2 (LCN2) and integrin β3 (ITGB3) were identified as key proteins that determine the survival and death of glioma cells. LCN2, ITGB3, and other proteins identified by proteomic analysis could be utilized to overcome glioma chemoresistance.

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“…Comparison of oligodendroglioma with 1p/19q loss of heterozygosity to those without has been used in an attempt to understand the basis for the different clinical behaviors of tumors with these genotypes. 12 Seven proteins were found to be associated with maintenance of 1p, 2 of which (glyoxalase I and Rho GDP dissociation inhibitor) had previously been associated with chemoresistance in other tumors, and conversely, 12 proteins found exclusively in tumors with 1pLOH had been reported to induce chemosensitivity in other forms of human neoplasia. 12 A more sophisticated approach to finding markers of tumor grade is to compare different tumor samples to a common control.…”

Section: -D Gel and Mass Spectrometrymentioning

confidence: 99%

“…12 Seven proteins were found to be associated with maintenance of 1p, 2 of which (glyoxalase I and Rho GDP dissociation inhibitor) had previously been associated with chemoresistance in other tumors, and conversely, 12 proteins found exclusively in tumors with 1pLOH had been reported to induce chemosensitivity in other forms of human neoplasia. 12 A more sophisticated approach to finding markers of tumor grade is to compare different tumor samples to a common control. A comprehensive study that used this approach chose normal tissue as the comparator and combined both tumor-margin and tumor-epilepsy strategies to look at 27 tumors of different grades.…”

Section: -D Gel and Mass Spectrometrymentioning

confidence: 99%