Project description:<p>The Tumor Sequencing Project (TSP) Consortium is a collaboration among participants at the Baylor College of Medicine Human Genome
Sequencing Center, the Broad Institute Genome Sequencing Platform, the Dana Farber Cancer Institute, the Memorial Sloan-Kettering Cancer
Center, the Genome Sequencing Center and Siteman Cancer Center at Washington University, the M.D. Anderson Cancer Center and the
University of Michigan Medical Center. The TSP Part A will pilot approaches to large-scale identification of genomic changes in tumors
by sequencing the exonic regions of 623 genes in 188 specimens of adenocarcinoma of the lung, as well as using high density SNP
genotyping arrays for high resolution identification of changes in chromosomal copy number.</p>
<p>The TSP Part B will pilot approaches to tumor characterization of lung adenocarcinoma samples using next-generation sequencing
technologies and benchmark those results against Part A data generated with ABI3730 instruments.</p>
Project description:Thrombospondin 1 (TSP-1) is an anti-angiogenic matricellular protein with regulatory functions in inflammation and cancer. The type 1 repeats (TSR) domains of TSP-1 have been shown to interact with a wide range of proteins that result in the anti-angiogenic and anti-tumor properties of TSP-1. To evaluate potential therapeutic effects of TSRs in inflammatory bowel disease, we conducted clinical, histological and gene microarray analyses on a mouse model of induced colitis. We used Affymetrix GeneChips to determine the changes in the genetic profile underlying TSR-treatment coincident with induction of colitis using DSS. We identified differentially expressed genes among the treatment groups. Using DSS (dextran sulfate sodium) to induce colitis, wild-type mice were simultaneously injected with either saline or one form of TSP-1 derived peptides, containing either the three domains of the TSR (3TSR), the two last domains (TSR2), or TSR2 with the RFK sequence (TSR2+RFK). Wt mice drinking water only was used as reference.
Project description:<p>The Tumor Sequencing Project (TSP) Consortium is a collaboration among participants at the Baylor College of Medicine Human Genome
Sequencing Center, the Broad Institute Genome Sequencing Platform, the Dana Farber Cancer Institute, the Memorial Sloan-Kettering Cancer
Center, the Genome Sequencing Center and Siteman Cancer Center at Washington University, the M.D. Anderson Cancer Center and the
University of Michigan Medical Center. The TSP Part A will pilot approaches to large-scale identification of genomic changes in tumors
by sequencing the exonic regions of 623 genes in 188 specimens of adenocarcinoma of the lung, as well as using high density SNP
genotyping arrays for high resolution identification of changes in chromosomal copy number.</p>
<p>The TSP Part B will pilot approaches to tumor characterization of lung adenocarcinoma samples using next-generation sequencing
technologies and benchmark those results against Part A data generated with ABI3730 instruments.</p>
Project description:Thrombospondin 1 (TSP-1) is an anti-angiogenic matricellular protein with regulatory functions in inflammation and cancer. The type 1 repeats (TSR) domains of TSP-1 have been shown to interact with a wide range of proteins that result in the anti-angiogenic and anti-tumor properties of TSP-1. To evaluate potential therapeutic effects of TSRs in inflammatory bowel disease, we conducted clinical, histological and gene microarray analyses on a mouse model of induced colitis. We used Affymetrix GeneChips to determine the changes in the genetic profile underlying TSR-treatment coincident with induction of colitis using DSS. We identified differentially expressed genes among the treatment groups.
Project description:Human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is an inflammatory neurodegenerative disease that affects motor, urinary, intestinal, and sensory functions. Typically, HAM/TSP is slowly progressive, but it may vary from limited motor disability after decades (very slow progression) to loss of motor function in a few years from disease onset (rapid). In this study, we aimed to identify prognostic biomarkers for HAM/TSP to support patient management. Thus, proteomic analysis of the cerebrospinal fluid (CSF) was performed with samples from HTLV-1 asymptomatic carriers (AC) (n=13) and HAM/TSP patients (n=21) with rapid, typical, and very slow progression using quantitative label-free liquid chromatography/tandem mass spectrometry. Enrichment analyses were also carried out to identify key biological processes associated with distinct neurological conditions in HTLV-1 infection. Candidate biomarkers were validated by ELISA in paired CSF and serum samples, and samples from HTLV-1-seronegative individuals (n=9) were used as controls. CSF analysis identified 602 proteins. Leukocyte/cell activation, immune response processes and neurodegeneration pathways were enriched in rapid progressors. Conversely, HTLV-1 AC and HAM/TSP patients with typical and very slow progression had enriched processes for nervous system development. Differential expression analysis showed that soluble vascular cell adhesion molecule 1 (sVCAM-1), chitotriosidase 1 (CHIT1), and cathepsin C (CTSC) were upregulated in HAM/TSP. However, only CHIT1 was significantly elevated after validation, particularly in HAM/TSP rapid progressors. In contrast, none of these biomarkers were altered in serum. Additionally, CSF CHIT1 levels in HAM/TSP patients positively correlated with the speed of HAM/TSP progression, defined as points in the IPEC-2 HAM/TSP disability scale per year of disease, and with CSF levels of phosphorylated neurofilament heavy chain, neopterin, CXCL5, CXCL10, and CXCL11. In conclusion, higher CSF levels of CHIT1 were associated with HAM/TSP rapid progression and correlated with other biomarkers of neuroinflammation and neurodegeneration. Therefore, we propose CHIT1 as a surrogate CSF biomarker to identify HAM/TSP patients with a worse prognosis.
Project description:HTLV-1 is the etiologic agent of HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). CD8+ T cells may contribute to the protection or development of HAM/TSP. In this study we used SAGE to assess gene expression profiles of CD8+ T cells isolated from HTLV-1 asymptomatic carriers (HAC) and from HAM/TSP patients, in order to identify genes involved in the HAM/TSP development. Analysis of SAGE was conducted by pooling samples according to clinical status. The comparison of gene expression profiles between controls and HAC or HAM/TSP identified around 900 genes. HAC versus HAM/TSP libraries showed 285 differentially expressed genes. We found that CXCR4 had a lower expression level in the HTLV-1 infected group than in controls. CCL5 had higher expression in HAM/TSP group, as compared to HAC. Our results provide a large-scale perspective of gene expression that may be further tested with functional assays to increase our understanding on the HTLV1-related diseases pathology.
Project description:HTLV-1 is the etiologic agent of HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). CD8+ T cells may contribute to the protection or development of HAM/TSP. In this study we used SAGE to assess gene expression profiles of CD8+ T cells isolated from HTLV-1 asymptomatic carriers (HAC) and from HAM/TSP patients, in order to identify genes involved in the HAM/TSP development. Analysis of SAGE was conducted by pooling samples according to clinical status. The comparison of gene expression profiles between controls and HAC or HAM/TSP identified around 900 genes. HAC versus HAM/TSP libraries showed 285 differentially expressed genes. We found that CXCR4 had a lower expression level in the HTLV-1 infected group than in controls. CCL5 had higher expression in HAM/TSP group, as compared to HAC. Our results provide a large-scale perspective of gene expression that may be further tested with functional assays to increase our understanding on the HTLV1-related diseases pathology. Comparative analysis of gene expression profiles of CD8+ T Lymphocytes isolated from HTLV-1 infected individuals.
Project description:Diabetes is associated with a more aggressive form of atherosclerosis. Thrombospondin-1 (TSP-1), an extracellular matrix protein, is an acute phase reactant that induces vascular smooth muscle (VSMC) migration and proliferation in areas of vascular injury, and is also upregulated in VSMCs exposed to hyperglycemia. We hypothesized that hyperglycemia amplifies the expression of genes induced by TSP-1 in VSMCs. Human aortic VSMCs were cultured in DMEM supplemented with 10 % FBS and 1% antibiotics, cells were used between passages three and five. VSMCs were preincubated in DMEM containing 0.2% FBS with 5 mM glucose (normoglycemia), 25 mM glucose (hyperglycemia), 25 mM mannose (osmotic control), TSP-1 (20µg/mL), 25 mM glucose + TSP-1 (20µg/mL) or 25 mM mannose + TSP-1 (20µg/mL). Data analysis revealed that TSP-1 stimulates gene expression relevant to the pathogenesis of atherosclerosis and diabetic vascular disease.
Project description:In the present study, the eggs of Chinese pond turtles (Mauremys reevesii) were incubated at three temperatures (26℃, 29℃ and 32℃). During the thermosensitive period (TSP) of incubation, the adrenal-kidney-gonad (AKG) complexes were sampled, and a comprehensive investigation for miRNAs was performed using next-generation small RNA sequencing.