MicroRNA in plasma, Newly diagnosed untreated diabetic cases and healthy controls
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ABSTRACT:
ORGANISM(S): Mus musculus Rattus norvegicus Homo sapiens
PROVIDER: GSE134998 | GEO | 2022/06/22
REPOSITORIES: GEO
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Project description:MicroRNA in plasma, Newly diagnosed untreated diabetic cases and healthy controls
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Project description:The treatment of multiple myeloma has evolved markedly in the last decade, but mortality remains high, emphasizing the need for more effective therapies. Daratumumab, a fully human monoclonal antibody targeting CD38, has shown clinical efficacy in relapsed/refractory multiple myeloma both as monotherapy and in combination with other drugs, including novel agents. More recently, promising results have been reported in patients with untreated newly diagnosed multiple myeloma (NDMM). Clinical trials thus far have shown enhanced efficacy and tolerability of several daratumumab-based combinations in both transplant ineligible and eligible patients, without compromising transplant ability. However, benefit in high-risk subpopulations is still unclear. A subcutaneous formulation of daratumumab has been introduced to decrease the risk of infusion reactions, with preliminary results showing non-inferior efficacy. The antimyeloma activity of daratumumab is achieved through multiple mechanisms including direct, Fc-dependent, and immunomodulatory mechanisms. Enhanced efficacy of daratumumab in combination with immunomodulatory drugs and proteasome inhibitors is supported by preclinical data showing synergism. This review will focus on the role of daratumumab in untreated NDMM patients, highlighting the results of major clinical trials, and listing ongoing trials that are evaluating various daratumumab-based combinations in this setting.
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Project description:Few studies have statistically investigated reduced CD20 expression in B-cell lymphoma after rituximab therapy and genomic mutation of CD20 associated with reduction. We examined CD20-positive rate in follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) by flow cytometry (FCM) and immunohistochemical staining (IHS), comparing 138 cases after rituximab therapy with 360 initial, not yet treated cases. Sequence analysis of exons 3 to 8 of CD20 was performed on 22 cases with low CD20-positive rate after rituximab treatment. The results showed a statistical correlation between CD20-positive rate in FCM and IHS. By FCM, the CD20-positive rate among post-rituximab cases was significantly lower than among initial cases in DLBCL, non-germinal center origin B-cell type (average values [avg] 57.8 and 87.9, respectively) (P < 0.0001), FL2 (avg, 93.9; 103.2) (P = 0.0083), and FL3A (avg, 90.6; 100.7) (P = 0.033). Stratified analyses of post-rituximab cases showed significantly lower CD20-positive rate in cases that were resistant at the start of the treatment and cases with progressive disease during rituximab therapy before biopsy. Sequence analysis showed silent mutation of exon 4 (632 C/T) in seven cases, although this number was not statistically significant. These results suggest the influence of B-lymphoma subtype and a therapeutic effect before biopsy on CD20 expression at relapse and contribute to a better therapeutic approach for relapse cases after rituximab therapy.
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Project description:AimsThe two predominant pathophysiological defects resulting in glucose intolerance are beta-cell dysfunction and insulin insensitivity. This study aimed to re-examine beta-cell function and insulin sensitivity across a continuum from normal glucose tolerance (NGT) to early type 2 diabetes (T2DM) employing highly specific insulin, C-peptide and intact proinsulin assays.Materials and methodsA total of 104 persons with NGT, 85 with impaired glucose tolerance (IGT) and 554 with newly diagnosed T2DM were investigated. Following an overnight fast, all underwent a 4-h standardised mixed meal tolerance test (MTT), and on a second day, a sub-group underwent a frequently sampled insulin-modified intravenous glucose tolerance test (FSIVGTT) over a 3-h period. The participants were stratified according to fasting glucose and BMI for analysis.ResultsThe MTT revealed that increasing FPG was accompanied by progressively elevated and delayed postprandial glucose peaks. In parallel, following an initial compensatory increase in fasting and postprandial insulin responses there followed a progressive demise in overall beta-cell secretory capacity. FSIVGTT demonstrated a major reduction in the early insulin response to IV glucose in persons with IGT accompanied by a dramatic fall in insulin sensitivity. Beyond pre-diabetes, ever-increasing fasting and postprandial hyperglycaemia resulted predominantly from a progressively decreasing beta-cell secretory function.ConclusionThis study utilising improved assay technology re-affirms that beta-cell dysfunction is evident throughout the spectrum of glucose intolerance, whereas the predominant fall in insulin sensitivity occurs early in its evolution.
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Project description:Our knowledge about the microbiota associated with the onset of IBD is limited. The aim of our study was to investigate the correlation between IBD and the fecal microbiota for early diagnosed untreated patients. The fecal samples used were a part of the Inflammatory Bowel South-Eastern Norway II (IBSEN II) study and were collected from CD patients (n = 30), UC patients (n = 33), unclassified IBD (IBDU) patients (n = 3), and from a control group (n = 34). The bacteria associated with the fecal samples were analyzed using a direct 16S rRNA gene-sequencing approach combined with a multivariate curve resolution (MCR) analysis. In addition, a 16S rRNA gene clone library was prepared for the construction of bacteria-specific gene-targeted single nucleotide primer extension (SNuPE) probes. The MCR analysis resulted in the recovery of five pure components of the dominant bacteria present: Escherichia/Shigella, Faecalibacterium, Bacteroides, and two components of unclassified Clostridiales. Escherichia/Shigella was found to be significantly increased in CD patients compared to control subjects, and Faecalibacterium was found to be significantly reduced in CD patients compared to both UC patients and control subjects. Furthermore, a SNuPE probe specific for Escherichia/Shigella showed a significant overrepresentation of Escherichia/Shigella in CD patients compared to control subjects. In conclusion, samples from CD patients exhibited an increase in Escherichia/Shigella and a decrease in Faecalibacterium indicating that the onset of the disease is associated with an increase in proinflammatory and a decrease in anti-inflammatory bacteria.
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Project description:In order to identify relevant, molecularly defined subgroups in Multiple Myeloma (MM), gene expression profiling (GEP) was performed on purified CD138+ plasma cells of 320 newly diagnosed myeloma patients included in the Dutch-Belgian/German HOVON-65/ GMMG-HD4 trial using Affymetrix Gene Chip U133 plus 2.0 arrays. Hierarchical clustering identified 10 distinct subgroups. Bone marrow plasma cell samples were obtained from 320 newly diagnosed multiple myeloma patients included in a large multicenter, prospective, randomized phase III trial (HOVON65/GMMG-HD4). Purified myeloma plasma cells samples with a monoclonal plasma cell purity > 80% were used for analysis.
2010-06-27 | E-GEOD-19784 | biostudies-arrayexpress
Project description:This study aimed to investigate the clinical significance of systemic inflammation markers (SIMs)-including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR)-in patients with newly diagnosed, previously untreated hepatocellular carcinoma (HCC). The present study was performed using prospectively collected registry data of newly diagnosed, previously untreated HCC from a single institution. The training set included 6619 patients from 2005 to 2013 and the validation set included 2084 patients from 2014 to 2016. The SIMs as continuous variables significantly affected the overall survival (OS), and the optimal cut-off value of NLR, PLR, and LMR was 3.0, 100.0, and 3.0, respectively. There were significant correlations between SIMs and the albumin-bilirubin grade/Child-Turcotte-Pugh class (indicative of liver function status) and the staging system/portal vein invasion (indicative of the tumor burden). The OS curves were well stratified according to the prognostic model of SIMs and validated using the bootstrap method (1000 times, C-index 0.6367, 95% confidence interval (CI) 0.6274-0.6459) and validation cohort (C-index 0.6810, 95% CI 0.6570-0.7049). SIMs showed significant prognostic ability for OS, independent of liver function and tumor extent, although these factors were significantly correlated with SIMs in patients with newly diagnosed, previously untreated HCC.
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Project description:Meningiomas are common intracranial tumors in adults. Abnormal miRNA expression plays a role in their pathogenesis. Change in miRNA expression level can be caused by impaired epigenetic regulation of miRNA-encoding genes. We found genomic region covering MIR193B gene as DNA hypermethylated in meningiomas based on analysis of genome-wide methylation (HM450k Illumina arrays). Hypermethylation of MIR193B was as also confirmed by bisulfite pyrosequencing. Both hsa-miR-193b-3p and hsa-miR-193b-5p are downregulated in meningiomas as found with qRT-PCR. Lower expression of hsa-miR-193b-3p and higher MIR193b methylation was observed in WHO GII/GIII as compared to GI meningiomas. 3’UTR of CCND1 mRNA was identified as target of hsa-miR-193b-3p as further validated with luciferase reporter assay in IOMM-Lee meningioma cells. IOMM-Lee cells transfected with hsa-miR-193b-3p mimic showed decreased cyclin D1 level and lower cell viability and proliferation, confirming suppressive nature of this miRNA. Cyclin D1 protein expression (immunoreactivity) was higher in atypical than in benign meningiomas, accordingly to observation of lower hsa-miR-193b-3p level in GII tumors. The commonly observed hypermethylation of MIR193B in meningiomas apparently contributes to downregulation of hsa-miR-193b-3p. Since hsa-miR-193b-3p regulates proliferation of meningioma cells through negative regulation of cyclin D1 expression, it seems to be an important tumor suppressor in meningiomas.
2023-09-04 | GSE241956 | GEO
Project description:The knowledge about correlation patterns between the fecal microbiota and inflammatory bowel diseases (IBD)-comprising the two subforms Crohn's disease (CD) and ulcerative colitis (UC)-for newly diagnosed untreated children is limited. To address this knowledge gap, a selection of faecal specimens (CD, n = 27 and UC, n = 16) and non-IBD controls (n = 30) children (age < 18 years) was analysed utilising bacterial small subunit (SSU) rRNA. We found, surprising age dependence for the fecal microbiota correlating to IBD. The most pronounced patterns were that E. coli was positively (R (2) = 0.16, P = 0.05) and Bacteroidetes, negatively (R (2) = 0.15, P = 0.05) correlated to age for CD patients. For UC, we found an apparent opposite age-related disease correlation for both Bacteroides and Escherichia. In addition, there was an overrepresentation of Haemophilus for the UC children. From our, results we propose a model where the aetiology of IBD is related to an on-going immunological development in children requiring different age-dependent bacterial stimuli. The impact of our findings could be a better age stratification for understanding and treating IBD in children.
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