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      The influence of feeding linoleic, gamma-linolenic and docosahexaenoic acid rich oils on rat brain tumor fatty acids composition and fatty acid binding protein 7 mRNA expression

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          Abstract

          Background

          Experimental studies indicate that gamma linolenic acid (GLA) and docosahexaenoic acid (DHA) may inhibit glioma cells growth but effects of oral consumption of these fatty acids on brain tumor fatty acid composition have not been determined in vivo.

          Methods

          GLA oil (GLAO; 72% GLA), DHA oil (DHAO; 73% DHA) were fed to adult wistar rats (1 mL/rat/day) starting one week prior to C6 glioma cells implantation and continued for two weeks after implantation. Control group were fed same amount of high linoleic acid safflower oil (74–77% linoleic acid). Fatty acid composition of tumor samples was determined in a set of 8–12 animals in each group and serum fatty acid in 6 animals per each group. Gene expression of tumor fatty acid binding protein 7 (FABP7), epidermal growth factor receptor (EGFR), peroxisome proliferator activated receptor γ (PPAR-γ) and retinoid × receptor-α (RXR-α) were determined in a set of 18 animals per group.

          Results

          DHAO feeding increased EPA of brain tumors and decreased ratio of n-6/n-3 fatty acids. Serum levels of EPA were also increased in DHAO group. A similar trend in serum and tumor levels of DHA were observed in DHAO group but it did not achieve statistical significance. GLAO increased serum concentration of GLA but had no significant effect on tumor GLA or dihomo-gamma linolenic acid (DGLA) concentrations. Gene expression of FABP7 was up-regulated in tumors of DHAO group but no other significant effects were observed on EGFR, PPAR-γ or RXR-α expression, and expression of these genes in tumors of GLAO were not different from SFO group.

          Conclusion

          Dietary supplementation of DHA containing oil could be an effective way to increase levels of long chain n-3 fatty acids in brain tumors and this increase may be mediated partly by up-regulation of FABP7 expression.

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          Most cited references52

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          A PCR primer bank for quantitative gene expression analysis.

          X. Wang (2003)
          Although gene expression profiling by microarray analysis is a useful tool for assessing global levels of transcriptional activity, variability associated with the data sets usually requires that observed differences be validated by some other method, such as real-time quantitative polymerase chain reaction (real-time PCR). However, non-specific amplification of non-target genes is frequently observed in the latter, confounding the analysis in approximately 40% of real-time PCR attempts when primer-specific labels are not used. Here we present an experimentally validated algorithm for the identification of transcript-specific PCR primers on a genomic scale that can be applied to real-time PCR with sequence-independent detection methods. An online database, PrimerBank, has been created for researchers to retrieve primer information for their genes of interest. PrimerBank currently contains 147 404 primers encompassing most known human and mouse genes. The primer design algorithm has been tested by conventional and real-time PCR for a subset of 112 primer pairs with a success rate of 98.2%.
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            PerlPrimer: cross-platform, graphical primer design for standard, bisulphite and real-time PCR.

            PerlPrimer is a cross-platform graphical user interface application for the design of primers for standard, bisulphite and real-time PCR, and sequencing. The program incorporates highly accurate melting-temperature and primer-dimer prediction algorithms with powerful tools such as sequence retrieval from Ensembl and the ability to BLAST search primer pairs. It aims to automate and simplify the process of primer design. Open-source and freely available from http://perlprimer.sourceforge.net.
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              Gene expression profiling reveals molecularly and clinically distinct subtypes of glioblastoma multiforme.

              Glioblastoma multiforme (GBM) is the most common form of malignant glioma, characterized by genetic instability, intratumoral histopathological variability, and unpredictable clinical behavior. We investigated global gene expression in surgical samples of brain tumors. Gene expression profiling revealed large differences between normal brain samples and tumor tissues and between GBMs and lower-grade oligodendroglial tumors. Extensive differences in gene expression were found among GBMs, particularly in genes involved in angiogenesis, immune cell infiltration, and extracellular matrix remodeling. We found that the gene expression patterns in paired specimens from the same GBM invariably were more closely related to each other than to any other tumor, even when the paired specimens had strikingly divergent histologies. Survival analyses revealed a set of approximately 70 genes more highly expressed in rapidly progressing tumors that stratified GBMs into two groups that differed by >4-fold in median duration of survival. We further investigated one gene from the group, FABP7, and confirmed its association with survival in two unrelated cohorts totaling 105 patients. Expression of FABP7 enhanced the motility of glioma-derived cells in vitro. Our analyses thus identify and validate a prognostic marker of both biologic and clinical significance and provide a series of putative markers for additional evaluation.
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                Author and article information

                Journal
                Lipids Health Dis
                Lipids in Health and Disease
                BioMed Central
                1476-511X
                2008
                16 November 2008
                : 7
                : 45
                Affiliations
                [1 ]Department of Nutrition and Biochemistry, Tehran University of Medical Sciences, Tehran, Iran
                [2 ]Department of Clinical Biochemistry, Tehran University of Medical Sciences, Tehran, Iran
                [3 ]Department of Biostatistics, Tehran University of Medical Sciences, Tehran, Iran
                [4 ]Department of Immunology, Tehran University of Medical Sciences, Tehran, Iran
                [5 ]Department of Medical Genetics, Tehran University of Medical Sciences, Tehran, Iran
                [6 ]Department of Medicinal Chemistry and Pharmaceutical Sceinces, Tehran University of Medical Sciences, Tehran, Iran
                [7 ]Department of Pathology of Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
                [8 ]Department of Physiology, Tehran University of Medical Sciences, Tehran, Iran
                Article
                1476-511X-7-45
                10.1186/1476-511X-7-45
                2605445
                19014610
                444ebb55-276a-4c8c-beac-518408ea098c
                Copyright © 2008 Nasrollahzadeh et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 24 August 2008
                : 16 November 2008
                Categories
                Research

                Biochemistry
                Biochemistry

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