Project description:Food safety evaluation of new, genetically modified (GM) plant varieties has led to basic questions regarding the safety assessment of new plant varieties and whole foods derived thereof. An important part of the hazard identification in the European approach is a targeted compositional analysis of new GM plant varieties compared to one or more conventional reference varieties. Comparative analysis will become much more informative with unbiased analytical approaches, such as omics profiling. Analysis tools that estimate the similarity of new varieties to the reference would in turn greatly facilitate hazard identification. Further in-depth biological, functional and eventually toxicological analysis of the data would then only be necessary for varieties that fall outside the scale of those with a history of safe human consumption. For this purpose, the use of a one-class classifier tool was explored in this study to assess and classify transcriptome profiles of potato varieties. Five potato varieties were grown in the Netherlands during the same year (NL samples) and included four biological replicates for four varieties or two biological replicates for the fifth one. They were all analysed in 2011. A sixth variety was grown in the UK in a previous study and a previous year, for which the data are submitted in E-MTAB-605. The two UK samples were analysed in the original study in 2008 and again together with the NL samples in the present study, resulting in four profiles for two samples.
Project description:Although patients of colorectal cancer use Traditional Chinese Medicine (TCM) herbal therapy extensively in China, no strong evidence exists to demonstrate the safety and survival outcomes of TCM herbal therapy combined with conventional western medicine for treatment of this disease. The purpose of this multi-center perspective cohort study is to evaluate the relationship between TCM herbal therapy and survival outcomes in patients with advanced colorectal cancer.
Project description:The advent of human induced pluripotent stem (iPS) cells enables for the first time the derivation of unlimited numbers of patient-specific stem cells and holds great promise for regenerative medicine. However, realizing the full potential of iPS cells requires robust, precise and safe strategies for their genetic modification. Safe human iPS cell engineering is especially needed for therapeutic applications, as stem cell-based therapies that rely on randomly integrated transgenes pose oncogenic risks. Here we describe a strategy to genetically modify iPS cells from patients with beta-thalassemia in a potentially clinically relevant manner. Our approach is based on the identification and selection of âsafe harborâ sites for transgene expression in the human genome. We show that thalassemia patient iPS cell clones harboring a transgene can be isolated and screened according to chromosomal position. We next demonstrate that iPS cell clones that meet our âsafe harborâ criteria resist silencing and allow for therapeutic levels of beta-globin expression upon erythroid differentiation without perturbation of neighboring gene expression. Combined bioinformatics and functional analyses thus provide a robust and dependable approach for achieving desirable levels of transgene expression from selected chromosomal loci. This approach may be broadly applicable to introducing therapeutic or suicide genes into patient specific iPS cells for use in cell therapy. iPS cell clones were derived from beta-thalassemia patients. A single copy of beta-globin transgene cis-linked to locus control region (LCR) elements and an excisable Neo-eGFP transcription unit were inserted into these cell clones. beta-globin expression was induced by erythroid differentiation.
Project description:Ginkgo biloba leaf extract (GBE) has been used for centuries in traditional Chinese medicine and today is used as an herbal supplement for various indications such as improving neural function, anti-oxidant and anti-cancer effects. As part of the herbal supplement industry, these compounds are largely unregulated, and may be consumed in large concentrations over extended periods of time. This is of particular concern, because the long-term effects in terms of toxicity and carcinogenicity data is lacking for many herbal products, including GBE. The 2-year B6C3F1 mouse carcinogenicity bioassay indicated a marked dose-related increase in hepatocellular carcinoma (HCC) development associated with exposure to GBE. We have shown that the mechanism of this increase in tumorigenesis is related to a marked increase in the incidence of β-catenin mutation, and report a novel mechanism of constitutive β-catenin activation through post-translational modification leading to constitutive Wnt signaling and unregulated growth signaling and oncogenesis. Furthermore, using global gene expression profiling, we show that GBE-induced HCC exhibit overrepresentation of gene categories associated with human cancer and HCC signaling including upregulation of relevant oncogenes and suppression of critical tumor suppressor genes, as well as chronic oxidative stress, a known inducer of calpain-mediated degradation and promoter of hepatocarcinogenesis in humans. These data provide a molecular mechanism to GBE-induced HCC in B6C3F1 mice that is relevant to human cancer, and provides relevant molecular data that will provide the groundwork for further risk assessment of unregulated compounds, including herbal supplements. Six hepatocellular carcinomas induced by GBE, six spontaneous hepatocellular carcinomas, and six normal liver samples, three technical replicates each.
Project description:Human induced pluripotent stem cells (hIPSCs) represent a unique opportunity for regenerative medicine since they offer the prospect of generating unlimited quantities of cells for autologous transplantation as a novel treatment for a broad range of disorders. However, the use of hIPSCs in the context of genetically inherited human disease will require correction of disease-causing mutations in a manner that is fully compatible with clinical applications. Genomic instability induced by reprogramming or genetic modification would be a main issue for the safe use of these cells. We analyzed primary hIPSC lines and genetically modified derivatives by array-based comparative genomic hybridization.
Project description:Digital transformation of herbal medicine: Conversion to biological entity data using tonifying herbal medicine-induced transcriptome sequencing_HT29_batchE
Project description:Digital transformation of herbal medicine: Conversion to biological entity data using tonifying herbal medicine-induced transcriptome sequencing_A549_batchA
Project description:Digital transformation of herbal medicine: Conversion to biological entity data using tonifying herbal medicine-induced transcriptome sequencing_Tonifying_HT29
Project description:Digital transformation of herbal medicine: Conversion to biological entity data using tonifying herbal medicine-induced transcriptome sequencing_HT29_batchD
Project description:Digital transformation of herbal medicine: Conversion to biological entity data using tonifying herbal medicine-induced transcriptome sequencing_HT29_batchB
