Search results for "TYR"
showing 10 items of 2017 documents
The effects of prebiotics on microbial dysbiosis, butyrate production and immunity in HIV-infected subjects
2017
Altered interactions between the gut mucosa and bacteria during HIV infection seem to contribute to chronic immune dysfunction. A deeper understanding of how nutritional interventions could ameliorate gut dysbiosis is needed. Forty-four subjects, including 12 HIV+ viremic untreated (VU) patients, 23 antiretroviral therapy-treated (ART(+)) virally suppressed patients (15 immunological responders and 8 non-responders) and 9 HIV- controls (HIV-), were blindly randomized to receive either prebiotics (scGOS/lcFOS/glutamine) or placebo (34/10) over 6 weeks in this pilot study. We assessed fecal microbiota composition using deep 16S rRNA gene sequencing and several immunological and genetic marker…
Metabolic adaptation in the human gut microbiota during pregnancy and the first year of life
2018
Abstract Background The relationship between the gut microbiome and the human host is dynamic and we may expect adjustments in microbiome function if host physiology changes. Metatranscriptomic approaches should be key in unraveling how such adjustments occur. Methods We employ metatranscriptomic sequencing analyses to study gene expression in the gut microbiota of infants through their first year of life, and of their mothers days before delivery and one year afterwards. Findings In infants, hallmarks of aerobic metabolism disappear from the microbial metatranscriptome as development proceeds, while the expression of functions related to carbohydrate transport and metabolism increases and …
PTPN22 and CTLA-4 Polymorphisms Are Associated With Polyglandular Autoimmunity
2017
Context Single nucleotide polymorphisms (SNPs) of various genes increase susceptibility to monoglandular autoimmunity. Data on autoimmune polyglandular syndromes (APSs) are scarce. Objective Evaluate potential associations of eight SNPs with APSs. Setting Academic referral endocrine clinic. Patients A total of 543 patients with APS and monoglandular autoimmunity and controls. Intervention The SNP protein tyrosine phosphatase nonreceptor type 22 (PTPN22) rs2476601 (+1858); cytotoxic T-lymphocyte‒associated antigen 4 (CTLA-4) rs3087243 (CT60) and rs231775 (AG49); vitamin D receptor (VDR) rs1544410 (Bsm I), rs7975232 (Apa I), rs731236 (Taq I); tumor necrosis factor α rs1800630 (-863); and inte…
Quizartinib versus salvage chemotherapy in relapsed or refractory FLT3-ITD acute myeloid leukaemia (QuANTUM-R): a multicentre, randomised, controlled…
2019
Background Patients with relapsed or refractory FLT3 internal tandem duplication (FLT3-ITD)-positive acute myeloid leukaemia have a poor prognosis, including high frequency of relapse, poorer response to salvage therapy, and shorter overall survival than those with FLT3 wild-type disease. We aimed to assess whether single-agent quizartinib, an oral, highly potent and selective type II FLT3 inhibitor, improves overall survival versus salvage chemotherapy. Methods QuANTUM-R is a randomised, controlled, phase 3 trial done at 152 hospitals and cancer centres in 19 countries. Eligible patients aged 18 years or older with ECOG performance status 0-2 with relapsed or refractory (duration of first …
Autoimmune associations and autoantibody screening show focused recognition in patient subgroups with generalized myasthenia gravis
2013
Autoimmune associations in myasthenia gravis (MG)-patients and their relatives have not been re-assessed since their separation into early- or late-onset MG (EOMG, LOMG), or thymoma-associated MG. Here, we analysed 226 EOMG-, 97 LOMG-, and 150 thymoma-patients for autoimmune disorders in themselves and their relatives. From 283 of them sera were tested for different organ- and non-organ-specific autoantibodies (autoAbs) by immunofluorescence test (IFT) and ELISA; genotyping was performed in 213 patients. Relatives with autoimmune disorders were reported by more patients with EOMG (40% of 210) than LOMG (20% of 89; p0.01) than thymomas (8% of 150; p0.001). In 150 genotyped EOMG-females, the …
Identification of Differentially Expressed Genes in Papillary Thyroid Carcinomas With and Without Rearrangements of the Tyrosine Kinase Receptors RET…
2005
Background The transforming capacities of RET and/or NTRK1 chimeric oncogenes as well as the molecular background of non-rearranged papillary thyroid carcinomas (PTCs) remain to be elucidated. To assess altered gene expression, we examined PTCs with and without tyrosine kinase receptor rearrangements by mRNA differential display (DD). Materials and methods Six of 13 PTCs examined harbored RET chimeras (3× RET/PTC1, 1× RET/PTC3) and/or NTRK1 chimeras (2× trk, 1× TRK-T3, 2 unknown TRK hybrids). The method of DD analysis was refined by a novel fragment-recovery technique using a high-performance fluorescence scanner. Results Of 500 up- or down-regulated mRNA transcripts, 19 selected fragments …
The kinase inhibitor LS104 induces apoptosis, enhances cytotoxic effects of chemotherapeutic drugs and is targeting the receptor tyrosine kinase FLT3…
2008
Activating mutations of FLT3 are found in approximately one-third of acute myeloid leukemia (AML)-cases and are considered to represent an attractive therapeutic target. In this study, we report that the hydroxystyryl-acrylonitrile compound LS104 inhibits proliferation and induces potent cytotoxic effects in FLT3 expressing leukemic cells in vitro. Immunoblot and phosphoprotein-FACS analysis demonstrated inhibiton of phosphorylation of FLT3-ITD and of its downstream targets. In pharmacokinetic studies, a rapid and dose dependent cellular uptake of LS104 lasting up to 11h could be demonstrated. Combination of LS104 with chemotherapeutic agents markedly enhanced cytotoxic effects. Recently, a…
miR-155 regulative network in FLT3 mutated acute myeloid leukemia
2015
Abstract Background Acute myeloid leukemia (AML) represents a heterogeneous disorder with recurrent chromosomal alterations and molecular abnormalities. Among AML with normal karyotype (NK-AML) FLT3 activating mutation, internal tandem duplication (FLT3-ITD), is present in about 30% of patients, conferring unfavorable outcome. Our previous data demonstrated specific up-regulation of miR-155 in FLT3-ITD+ AML. miR-155 is known to be directly implicated in normal hematopoiesis and in some pathologies such as myeloid hyperplasia and acute lymphoblastic leukemia. Methods and results To investigate about the potential influence of miR-155 de-regulation in FLT3-mutated AML we generated a transcrip…
Downregulation of organic cation transporters OCT1 (SLC22A1) and OCT3 (SLC22A3) in human hepatocellular carcinoma and their prognostic significance
2012
Abstract Background Organic cation transporters (OCT) are responsible for the uptake and intracellular inactivation of a broad spectrum of endogenous substrates and detoxification of xenobiotics and chemotherapeutics. The transporters became pharmaceutically interesting, because OCTs are determinants of the cytotoxicity of platin derivates and the transport activity has been shown to correlate with the sensitivity of tumors towards tyrosine kinase inhibitors. No data exist about the relevance of OCTs in hepatocellular carcinoma (HCC). Methods OCT1 (SLC22A1) and OCT3 (SLC22A3) mRNA expression was measured in primary human HCC and corresponding non neoplastic tumor surrounding tissue (TST) by…
Prevalence and Clinical Outcomes for Patients With ALK-Positive Resected Stage I to III Adenocarcinoma: Results From the European Thoracic Oncology P…
2014
Purpose The prevalence of anaplastic lymphoma kinase (ALK) gene fusion (ALK positivity) in early-stage non–small-cell lung cancer (NSCLC) varies by population examined and detection method used. The Lungscape ALK project was designed to address the prevalence and prognostic impact of ALK positivity in resected lung adenocarcinoma in a primarily European population. Methods Analysis of ALK status was performed by immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) in tissue sections of 1,281 patients with adenocarcinoma in the European Thoracic Oncology Platform Lungscape iBiobank. Positive patients were matched with negative patients in a 1:2 ratio, both for IHC and for …