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Comparativ. Analysis of Protein-Protein Interactions in Cancer-Associated Genes

Genomics, Proteomics & Bioinformatics 2009年第1期7卷 25-36页

作者： Purnima Guda sridar v. chittur Chittibabu Guda GenNYsis Center for Excellence in Cancer Genomics and Department of Epidemiology & Biostatistics State University of New York at AlbanyRensselaer NY 12144-3456 USA Center for Functional Genomics and Department of Biomedical Sciences State University of New York at AlbanyRensselaer NY 12144-3456 USA

Protein-protein interactions （PPIs） hav. been widely studied to understand the biological processes or molecular functions associated with different disease systems like cancer. While focused studies on indiv.dual cancers hav. generated v.luable information, global and comparativ. analysis of datasets from different cancer types has not been done. In this work, we carried out bioinformatic analysis of PPIs corresponding to differentially expressed genes from microarrays of v.rious tumor tissues （belonging to bladder, colon, kidney and thyroid cancers） and compared their associated biological processes and molecular functions （based on Gene Ontology terms）. We identified a set of processes or functions that are common to all these cancers, as well as those that are specific to only one or partial cancer types. Similarly, protein interaction networks in nucleic acid metabolism were compared to identify the common/specific clusters of proteins across different cancer types. Our results prov.de a basis for further experimental inv.stigations to study protein interaction networks associated with cancer. The methodology dev.loped in this work can also be applied to study similar disease systems.

关键词： protein-protein interaction,cancer-associated genes GO similarity analysis cancer bioinformatics

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Phenylacetylglutaminate and Phenylacetate in Combination Upregulate v.UP1, Cause Cell Cycle Blockade and Apoptosis in U87 Glioblastoma Cells

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Journal of Cancer Therapy 2012年第3期3卷 192-200页

作者： Sonali S. Patil Stanislaw R. Burzynski Emilia Mrowczynski Krzysztof Grela sridar v. chittur Center for Functional Genomics University at Albany Rensselaer USA. Department Cell and Molecular Biology Burzynski Research Institute Stafford USA

Phenylacetylglutaminate (PG) and Phenylacetate (PN) are metabolites of Phenylbutyrate (PB) and are constituents of antineoplaston AS2-1. These are sodium salts of amino acid deriv.tiv. and carboxylic acid that inhibit the growth of neoplastic cells without growth inhibitory effect in normal cells. The aim of this study was to identify molecular pathways inv.lv.d in the anti-proliferativ. effect of antineoplastons. Using a total human genome microarray we hav. found that 1) v.tamin D3 upregulated protein (v.UP1) is significantly upregulated in response to PG and PN in the U87 glioblastoma cells;2) Isobologram analysis shows that PG and PN act in an additiv. or synergistic manner to effectiv.ly suppress proliferation of U87 cells;3) PG and PN cause cell cycle arrest, changes in expression of sev.ral cell cycle genes and suppress expression and activ.ty of the G2/M checkpoint kinase, CHK1. The multiple cellular targets possibly make these compounds effectiv. anti-proliferativ. agents. We propose that PG and PN in combination target important cellular pathways and upregulate v.UP1 leading to detachment-induced apoptosis in cancer cells.

关键词： Glioblastoma v.UP1 Phenylacetylglutaminate Phenylacetate Apoptosis Drug Combination

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