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PubMed Journals Articles About "Targeting DOT1L DUSP6 Prevent GvHD" RSS

20:57 EST 15th January 2019 | BioPortfolio

Targeting DOT1L DUSP6 Prevent GvHD PubMed articles on BioPortfolio. Our PubMed references draw on over 21 million records from the medical literature. Here you can see the latest Targeting DOT1L DUSP6 Prevent GvHD articles that have been published worldwide.

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Showing "Targeting DOT1L DUSP6 prevent GvHD" PubMed Articles 1–25 of 7,000+

Increased susceptibility to develop spontaneous and post-traumatic osteoarthritis in Dot1l-deficient mice.

We earlier identified that the histone methyltransferase DOT1L is as a master protector of cartilage health via limiting excessive activation of the Wnt pathway. However, cartilage-specific homozygous Dot1l knockout mice exhibited a severe growth phenotype and perinatal death, which hampered their use in induced or ageing models of osteoarthritis (OA). The aim of this study was to generate and examine haploinsufficient and inducible conditional Dot1l-deficient mouse models to evaluate the importance of DOT1...


Selective targeting of histone modification fails to prevent graft versus host disease after hematopoietic cell transplantation.

Allogeneic hematopoietic cell transplantation is often complicated by graft versus host disease (GvHD), primarily mediated through allo-reactive donor T cells in the donor stem cell graft. Enhancer of Zeste Homolog 2 (EZH2), a histone-lysine N-methyltransferase and a component of the Polycomb Repressive Complex 2, has been shown to play a role in GvHD pathology. Although not yet clear, one proposed mechanism is through selective tri-methylation of lysine 27 in histone 3 (H3K27me3) that marks the promoter re...

Dusp6 is a genetic modifier of growth through enhanced ERK activity.

Like other single gene disorders, muscular dystrophy displays a range of phenotypic heterogeneity even with the same primary mutation. Identifying genetic modifiers capable of altering the course of muscular dystrophy is one approach to deciphering gene-gene interactions that can be exploited for therapy development. To this end, we used an intercross strategy in mice to map modifiers of muscular dystrophy. We interrogated genes of interest in an interval on mouse chromosome 10 associated with body mass in ...


The testosterone metabolite 3α-androstanediol inhibits oxidative stress-induced ERK phosphorylation and neurotoxicity in SH-SY5Y cells through an MKP3/DUSP6-dependent mechanism.

Testosterone exerts neuroprotective effects on the brain, but the mechanisms by which these effects are exerted appear to be different in males and females. While in females they involve local conversion to estradiol, in males they may be androgen receptor-dependent, or mediated through metabolism to neurosteroids such as 5α-androstane-3α,17β-diol (3α-diol), which acts through different mechanisms than testosterone itself. Recently, we demonstrated that 3α-diol can protect neurons and neuronal-like cel...

Dual-specificity phosphatase 6 deletion protects the colonic epithelium against inflammation and promotes both proliferation and tumorigenesis.

The Ras/mitogen-activated protein kinase (MAPK) pathway controls fundamental cellular processes such as proliferation, differentiation, and apoptosis. The dual-specificity phosphatase 6 (DUSP6) regulates cytoplasmic MAPK signaling by dephosphorylating and inactivating extracellular signal-regulated kinase (ERK1/2) MAPK. To determine the role of DUSP6 in the maintenance of intestinal homeostasis, we characterized the intestinal epithelial phenotype of Dusp6 knockout (KO) mice under normal, oncogenic, and pro...

Design, synthesis and anti leukemia cells proliferation activities of pyrimidylaminoquinoline derivatives as DOT1L inhibitors.

A series of novel pyrimidylaminoquinoline derivatives 8(a-i) and 9(a-i) containing amino side chain, and the bisaminoquinoline analogs 3(b-e) have been designed and synthesized by structural modifications on a lead DOT1L inhibitor, 3a. All the compounds have been evaluated for their DOT1L inhibitory activities. The results showed that most of the compounds have strong anti DOT1L activities. Compounds 3e, 8h and 9e are the most potential ones from each category with the IC values of 1.06 ± 0.35 μM, 5...

DOT1L promotes progenitor proliferation and primes neuronal layer identity in the developing cerebral cortex.

Cortical development is controlled by transcriptional programs, which are orchestrated by transcription factors. Yet, stable inheritance of spatio-temporal activity of factors influencing cell fate and localization in different layers is only partly understood. Here we find that deletion of Dot1l in the murine telencephalon leads to cortical layering defects, indicating DOT1L activity and chromatin methylation at H3K79 impact on the cell cycle, and influence transcriptional programs conferring upper layer i...

Vitamin D-modulated dendritic cells delay lethal graft-versus-host disease through induction of regulatory T cells.

Graft-versus-host disease (GVHD) is the most lethal complication after allogeneic bone marrow transplantation (allo-BMT). Current approaches to prevent GVHD rely on donor lymphocyte/T cell depletion or general immunosuppression, leading to opportunistic infections and cancer relapse. Tolerogenic dendritic cells can induce regulatory T cells (Tregs) with the ability to suppress inflammation and prevent transplant rejection, making them an attractive cellular therapy to control GVHD. Active vitamin D (1α,25-...

Graft-versus-host disease (GvHD) of the tongue and of the oral cavity: a large retrospective study.

Graft-versus-host disease (GvHD) causes severe mucositis, impairs feeding and favors infection. The objective of this study was to identify the impact of GvHD in the oral cavity. We reviewed all consecutive patients who developed oral GvHD after HSCT. The study period was over 14 years. 53 patients were identified. M/F = 1.4; median age was 48.6 years; the median follow-up was for up to 3 years and 6 months. Conditioning regimens included several drugs (e.g., busulfan, cyclophosphamide and fludarabin...

Characterization of late acute and chronic graft-versus-host disease according to the 2014 NIH consensus criteria in Japanese patients.

To characterize the incidences and outcomes of late acute (LA) and chronic GVHD in East Asians according to the 2014 NIH criteria, we retrospectively analyzed 506 consecutive Japanese patients who had a first allogeneic hematopoietic cell transplantation (HCT) at our center between 2006 and 2013. According to manifestations at onset, 91 patients (60%) had LA GVHD and 60 (40%) had chronic GVHD. The cumulative incidences of LA and chronic GVHD were 20% and 17%, respectively, at 48 months after HCT. The involv...

Graft Versus Host Disease of the Central Nervous System after Liver Transplantation: A Rare Complication.

Graft versus host disease (GVHD) of the central nervous system (CNS) following solid organ transplantation is a rare but serious complication and has been previously reported after bone marrow transplantation. GVHD after liver transplantation is a rare entity with a high mortality rate. We report the case of a patient who developed GVHD and subsequently had seizures and altered mental status after deceased donor liver transplantation. The diagnosis of GVHD of the CNS was established by Short Tandem Repeat (...

Tear Film Proteomics Reveal Important Differences Between Patients With and Without Ocular GvHD After Allogeneic Hematopoietic Cell Transplantation.

To date, no biomarkers for ocular graft versus host disease (GvHD), a frequent complication following allogeneic hematopoietic cell transplantation (HCT), exist. In this prospective study, we evaluated the potential of human tear proteins as biomarkers for ocular GvHD.

Selective DOT1L, LSD1, and HDAC class I inhibitors reduce HOXA9 expression in MLL-AF9 rearranged leukemia cells, but dysregulate the expression of many histone-modifying enzymes.

Mixed lineage leukemia results from chromosomal rearrangements of the gene mixed lineage leukemia (MLL). MLL-AF9 is one such rearrangement that recruits the lysine methyltransferase, human disruptor of telomere silencing 1-like (DOT1L) and lysine specific demethylase 1 (LSD1), resulting in elevated expression of the Homeobox protein A9 (HOXA9), and leukemia. Inhibitors of LSD1 or DOT1L reduce HOXA9 expression, kill MLL-rearranged cells, and may treat leukemia. To quantify their effects on histone modifying ...

Clinicopathological comparison between acute gastrointestinal-graft-versus-host disease and infectious colitis in patients after hematopoietic stem cell transplantation.

The aim of this study is to elucidate the differences of the clinicopathological characteristics between acute gastrointestinal (GI)-graft-versus-host disease (GVHD) and infectious colitis (IC) after hematopoietic stem cell transplantation (HSCT). Of the 282 patients who underwent HSCT at our institution between January 1991 and December 2015, we could investigate 182 patients in detail. Of the 182 patients, we selected those who underwent colonoscopy and were diagnosed with acute GI-GVHD or IC after HSCT. ...

Differences of Immune Reconstitution of Dendritic Cells in Pediatric GvHD Patients After Allogenic Stem Cell Transplantation.

Hematopoietic stem cell transplantation (HSCT) is a life-saving procedure for children with a variety of (non) malignant conditions. GvHD is a severe complication with high morbidity and mortality. The pathogenesis remains unclear. We studied dendritic cell (DC) reconstitution to detect potential differences, which may improve our knowledge in the development of chronic GvHD (cGvHD).

The association between the incidence of intestinal graft-versus-host disease and antibiotic use after allogeneic hematopoietic stem cell transplantation.

Intestinal microbiota plays an important role in the regulation of allogeneic immune reaction after allogeneic hematopoietic stem cell transplantation (allo-SCT). Intestinal graft-versus-host disease (GVHD) is one of the major causes of mortality after allo-SCT and often complicated with intestinal dysbiosis. Recent studies suggest that antibiotic-induced dysbiosis is a risk factor for intestinal GVHD. We retrospectively evaluated the impacts of antibiotic use on the incidence of intestinal GVHD occurring b...

Extended CCR5 Blockade for Graft-Versus-Host Disease Prophylaxis Improves Outcomes of Reduced Intensity Unrelated Donor Hematopoietic Cell Transplantation: A Phase II Clinical Trial.

Graft-versus-host disease (GVHD) remains the most common treatment-related complication after allogeneic hematopoietic cell transplantation (allo-HCT). Lymphocyte migration plays a critical role in the pathogenesis of GVHD. A previous phase I/II trial demonstrated that CCR5 blockade with maraviroc in the first 30 days after transplant resulted in a low incidence of early acute GVHD, primarily in visceral organs, but without impact on late acute and chronic GVHD. We conducted a phase II trial to examine the ...

Quantity and Quality Reconstitution of NKG2A NK cells Are Associated with Graft-Versus-Host Disease after Allogeneic Hematopoietic Cell Transplantation.

The immune mechanism underlying graft-versus-host disease (GVHD) following allogeneic stem cell transplantation (HSCT) remains unclear. Natural killer (NK) cells play a crucial role in mediating pathogen-specific immunity and are the first donor-derived lymphocytes reconstituted post-HSCT. However, NK cells vary at different stages after HSCT. Here, we found that the absolute NKG2A subset cell counts and the percentages of NKG2A among NK cells were significantly reduced in GVHD patients after HSCT compared ...

Quantitative assessment of T cell clonotypes in human acute graft-versus-host disease tissues.

Due to difficulty in isolating T cells from human biopsy samples, the characteristics of T cells that are infiltrating human acute graft-versus-host disease (GVHD) tissues remain largely uninvestigated. In the present study, T cell receptor-β deep sequencing of various GVHD tissue samples and concurrent peripheral blood obtained from post-transplant patients was performed in combination with functional assays of tissue-infiltrating T cell clones. The T cell repertoire was more skewed in GVHD tissues than i...

Higher peak tacrolimus concentrations after allogeneic hematopoietic stem cell transplantation increase the risk of endothelial cell damage complications.

Noninfectious transplantation-related complications (TRC) such as graft-versus-host disease (GVHD) and endothelial cell damage (TRC-EC) are critical after allogeneic hematopoietic stem cell transplantation. Tacrolimus (TAC) is used to control GVHD. Hypertension and renal failure are common adverse events following TAC treatment. Higher blood concentrations of TAC would be expected to reduce the risk of GVHD, but may increase TRC-EC. TRC-EC often develops in patients with GVHD, thus it is difficult to clinic...

Helminth-Induced Production of TGF-β and Suppression of Graft-versus-Host Disease Is Dependent on IL-4 Production by Host Cells.

Helminths stimulate the secretion of Th2 cytokines, like IL-4, and suppress lethal graft-versus-host disease (GVHD) after bone marrow transplantation. This suppression depends on the production of immune-modulatory TGF-β and is associated with TGF-β-dependent in vivo expansion of Foxp3 regulatory T cells (Treg). In vivo expansion of Tregs is under investigation for its potential as a therapy for GVHD. Nonetheless, the mechanism of induced and TGF-β-dependent in vivo expansion of Tregs, in a Th2 polarized...

Host MyD88 signaling protects against acute graft-versus-host disease after allogeneic bone marrow transplantation.

Recent experimental strategies to reduce graft-versus-host disease (GVHD) have focused largely on modifying innate immunity. Toll-like receptor (TLR)-driven myeloid differentiation primary response 88 (MyD88)-dependent signalling pathways that initiate adaptive immune function are also critical for the pathogenesis of GVHD. This study aimed to delineate the role of host MyD88 in the development of acute GVHD following fully major histocompatibility complex-mismatched allogeneic bone marrow transplantation (...

Sjögren's Syndrome, Non-Sjögren's Syndrome, and Graft-Versus-Host Disease Related Dry Eye.

I have reviewed available literature on dry eye related to Sjögren's syndrome (SS), non-Sjögren's syndrome (non-SS), and graft-versus-host disease (GVHD) to examine aqueous tear deficient dry eye as a subtype of dry eye. This section will focus on clinical studies regarding those subtypes of dry eye. I searched the PubMed database from 1990-2017 for discussion of clinical features, diagnostic criteria, and risk factors of SS, non-SS, and GVHD-related dry eye. In addition, therapeutic options for each subt...

Topical Cyclosporine Pretreatment of Ocular Surface in Allogeneic Hematopoietic Stem Cell Transplant Recipients.

Dry eye disease (DED) of ocular graft-versus-host disease (GVHD) is a common complication after allogeneic hematopoietic stem cell transplantation (HSCT). Ongoing inflammation and irreversible fibrotic changes of the ocular surface and adnexa are obstacles for effective treatment of ocular GVHD. We hypothesized that topical cyclosporine A (CsA) pretreatment might be effective in preventing ocular GVHD.

Subconjunctival injection of mesenchymal stromal cells protects the cornea in an experimental model of GVHD.

To evaluate the therapeutic effect of subconjunctival injection of human mesenchymal stromal cells (hMSCs) in the cornea of mice with graft versus host disease (GVHD).


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