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Transcriptomics analysis of Colon tumor xenograft model in streptozotocin-induced diabetic mice

ABSTRACT: This is a transcriptomics analysis contributing to a bigger project that tries to shed light on the role of type 2 diabetes mellitus (T2DM) as a risk factor for colon cancer (CC). Here we present a gene expression screening of 7 colon tumor xenograft samples, 2 with diabetic mice and 5 with normal blood glucose levels. For xenograft model details see: Prieto I, et al. (2017) Colon cancer modulation by a diabetic environment: A single institutional experience. PLoS One 12(3):e0172300

ORGANISM(S): Homo sapiens

PROVIDER: GSE115329 | GEO | 2019/01/16

REPOSITORIES: GEO

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Transcriptomics analysis of paired tumor and normal mucosa samples in a cohort of patients with colon cancer, with and without T2DM.

Project description:This is a transcriptomics analysis contributing to a bigger project that tries to shed light on the role of type 2 diabetes mellitus (T2DM) as a risk factor for colon cancer (CC). Here we present a gene expression screening of paired tumor and normal colon mucosa samples in a cohort of 42 CC patients, 23 of them with T2DM. Using gene set enrichment, we identified an unexpected overlap of pathways over-represented in diabetics compared to non-diabetics, both in tumor and normal mucosa, including diabetes-related metabolic and signaling processes. An integration with other -omic studies suggests that in diabetics, the local micro-environment in normal colon mucosa may be a factor driving field cancerization which may promote carcinogenesis. Several of these pathways converged on the tumor initiation axis TEAD/YAP-TAZ. Cell culture studies confirmed that high glucose concentrations upregulate this pathway in non-tumor colon cells. In conclusion, diabetes is associated to deregulation of cancer-related processes in normal colon mucosa adjacent to tissue which has undergone a malignant transformation. These data support the existence of the field of cancerization paradigm in diabetes and set a new framework to study link between diabetes and cancer.

2019-01-16 | GSE115313 | GEO

Transcriptomics analysis of Colon tumor xenograft model in streptozotocin-induced diabetic mice

Project description:Transcriptomics analysis of Colon tumor xenograft model in streptozotocin-induced diabetic mice

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Transcriptome analysis of xenograft tumors treated with vehicle control or CBL0137

Project description:RNAseq was used to identify host and viral transcriptome changes in xenograft tumors treated with DMSO or CBL0137. Mouse xenograft experiments were regulated by Institutional Animal Care & Use Committee (IACUC# 2017-0035) of Weill Cornell Medical Center(WCMC). Non-obese diabetic/severe combined immunodeficiency (NOD-SCID) mice were obtained from Jackson Laboratories. Six to eight-week-old male and female mice (10 male/18 female) were injected in the flank with 1 x 107 BL cells in PBS with Matrigel eleven days before the treatment. Once the mice developed tumors with the size greater than 300 mm^3, they were grouped randomly and injected with vehicle (5% dextrose), 10mg/kg, or 60mg/kg of CBL0137. One week later, mice were injected with second dose of vehicle or CBL0137. Mice were humanely sacrificed at set experimental timepoints or when tumors reached the institutional cutoff. Tumors were harvested and snap frozen in liquid nitrogen for RNA, DNA, and sectioning for immunohistochemistry. RNAseq experiments were performed with tumor samples from 3 control and 3 60mg/kg CBL0137 treated mice.

2020-04-20 | GSE140652 | GEO

Streptozotocin-induced Type 1 and 2 Diabetes Mellitus Mouse Models Show Different Functional, Cellular and Molecular Patterns of Diabetic Cardiomyopathy

Project description:The main cause of morbidity and mortality in diabetes mellitus (DM) are cardiovascular complications. Diabetic cardiomyopathy (DCM) remains incompletely understood. Animal models have been crucial in exploring DCM pathophysiology while identifying potential therapeutic targets. Streptozotocin (STZ) has been widely used to produce experimental models of both type 1 and type 2 DM (T1DM and T2DM). Here we compared these two models for their effects on cardiac structure, function, and transcriptome. Different doses of STZ and different diet chows were used to generate T1DM and T2DM in C57BL/6J mice. Normal euglycemic and non-obese sex and age-matched mice served as controls (CTRL). Immunohistochemistry, RT-PCR, and RNA-Seq were employed to compare hearts from the three animal groups. STZ-induced T1DM and T2DM differently affect left ventricular function and myocardial performance. T1DM displays an exaggerated apoptotic cardiomyocyte (CM) death and reactive hypertrophy and fibrosis along with increased cardiac oxidative stress, CM DNA damage and senescence when compared to T2DM mice. T1DM and T2DM differently affect whole cardiac transcriptome. In conclusion, STZ-induced T1DM and T2DM mouse models show significant differences in cardiac remodeling, function and whole transcriptome. These differences could be of key relevance when choosing an animal model to study specific features of DCM.

2023-02-20 | E-MTAB-12558 | biostudies-arrayexpress

Transcriptome analysis of diabetic and non diabetic patients affected by post-ischemic heart failure

Project description:Increased morbidity and mortality associated with post-ischemic heart failure (HF) in diabetic patients underscore the need for a better understanding of the underlying molecular events. Indeed, effective HF therapy in diabetic patients requires a complex strategy encompassing the development of improved diagnostic and prognostic markers and innovative pharmacological approaches. Whole mRNAs expression was measured in the heart of patients with heart failure (HF) with or without concomitant Type 2 diabetes mellitus (T2DM) and compared it to control non-failing hearts. We identified distinct genes modulated in HF patients compared to controls, as well as to T2DM HF patients compared to not diabetic HF patients. Our study included left ventricle (LV) cardiac biopsies taken from the vital, non-infarcted zone (remote zone) derived from patients affected by dilated hypokinetic post-ischemic cardiomyopathy, undergoing surgical ventricular restoration procedure. Inclusion criteria for diabetic were: GLICEMIA: >=126 mg/dl, previous T2DM diagnosis or anti-diabetic therapy, while for non diabetic: GLICEMIA: <100 mg/dl and HbA1c: n.v. 4.8-6.0%. Moreover, HF patients were matched for End Systolic Volume (ESV), Ejection fraction (LVEF), Age, Sex, Ethnic distribution, Smoke habits, Hypertension, Glomerular filtration rate (GFR), Body Mass Index (BMI). Genes expression was assessed by Affymetrix GeneChips Human Gene 1.0 ST array, using total RNA extracted from 7 T2DM HF patients, 12 non-T2DM HF patients and 5 controls.

2012-03-21 | E-GEOD-26887 | biostudies-arrayexpress

RNA-seq profiling of colon and ileum tissues from the UC Davis Type 2 Diabetes Mellitus Rat Model

Project description:The RNA-seq analysis continues our work profiling the the gastrointestinal tract of the UC Davis Type 2 Diabetes Mellitus (UCD-T2DM) Rat. Male UCD-T2DM rats (age ~170 days) were included in this study if either recently diagnosed as diabetic (n=6, RD, nonfasting glucose > 300 mg/dl) or 3-month post-onset of diabetes (n=6, D3M). A set of younger non-diabetic UCD-T2DM rats were also studied as a non-diabetic comparison (n=6, ND, age ~70 days).

2022-07-29 | GSE181275 | GEO

Expression analysis of wild-type Streptococcus pneumoniae PN4595-T23 and TprA2 deletion mutant

Project description:Investigation of differentially regulated gene in deletion of TprA2 compared to the wild-type. TprA2 is a transcriptional regulator. Its characterization is described in Kadam et al 2017 Promiscuous signaling by a regulatory system unique to the pandemic PMEN1 pneumococcal lineage. PLoS Pathog. 2017 May; 13(5): e1006339.

2017-11-10 | GSE106753 | GEO

Label-Free LC-MS/MS Proteomic Analysis of Urinary Identification in Diabetic Vascular Dementia

Project description:Objective: The aim of this study was to identify novel diagnostic biomarkers of diabetic vascular dementia (DVD) and unraveling the underlying mechanisms using mass spectrometry (MS). Methods: Label-Free LC-MS/MS proteomics analysis was applied to urine samples from four groups including 14 vascular dementia CC(VD), 22 type 2 diabetes mellitus (T2DM), 12 DVD, 21 Normal Control (NC). Searching the MS data by Proteome Discoverer software, protein abundances were analyzed qualitatively and quantitatively and compared between these groups. Combining bioinformatics analysis using GO, pathway crosstalk analysis using KEGG, PPI network analysis using STRING and literature searching, the differentially expressed proteins (DEPs) of DVD can be comprehensively judged and were further quantified by receiver operating characteristic (ROC) curve methods. Results: The proteomic findings showed quantitative changes in DVD was compared to NC, T2DM, and VD groups; among 7,527 identified urine proteins, 1222, 1152, and 1180 of the proteins displayed quantitative changes unique to DVD vs NC, T2DM, and VD, respectively, including 481 overlapped common DEPs. Then 9 unique proteins and 2 composite markers (CM) were confirmed by a ROC curve method. Conclusion: This study provided a novel insight into the potential pathogenesis of DVD and elucidated a method for the earlier detection.

2021-01-14 | PXD022189 | Pride

mCRPC LuCaP PDXs ChIP-seq

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2022-04-06 | GSE163220 | GEO

A potential study model seeking for proteins related to dental implant failure of type 2 diabetic patients estabilished by proteomics.

Project description:Type 2 diabetes mellitus(T2DM)patients are a concern for dentists due to the lower success rate of healing period implant treatment. Here, we firstly calculated the success rate of in the healing period of diabetic and non-diabetic patients in the implant center of our hospital.Then we investigated the potential risk factors by proteomics analysis of 5 T2DM implant faliure patients in our implant center and compared the difference between high glucose induction study model and mesenchymal stem cell model from diabetic patients. The results suggested that the significantly higher implant failure rates in the T2DM group and the cell models derived from patients can be more comprehensive and accurate in reflecting the exact situation of BMSCs in patients with diabetes.

2021-11-02 | PXD016489 | Pride

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