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

02:13 EDT 21st September 2018 | 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+

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...


Prevention of Transfusion-Associated Graft-Versus-Host Disease With Blood Product Irradiation: The Past, Present, and Future.

Transfusion-associated graft-versus-host disease (TA-GVHD) is a disease with a very high mortality rate. In this report, we discuss TA-GVHD from a historical perspective, highlight the pathogenesis of TA-GVHD, and emphasize the importance of blood product irradiation, which is a very effective means to prevent this disease. We summarize the current recommendations in different patient populations from different countries and review recent developments, such as alternatives for the use of radioactive materia...

Inhibition of Vascular Adhesion Protein-1 for Treatment of Graft-Versus-Host Disease in Mice.

Graft-versus-host disease (GVHD) is a potentially lethal complication of hematopoietic stem cell transplantation (HSCT). GVHD comprises acute and chronic forms. To date, several approaches to treat acute GVHD or chronic GVHD have been reported. However, there is no literature precedent regarding all-in-one methods to address the 2 GVHD types. Severe inflammation in organs affected by GVHD is highly problematic, and vascular adhesion protein-1 (VAP-1) is known to be detrimentally involved in various inflamma...


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...

Very Low Numbers of CD4FoxP3 Tregs Expanded in Donors via TL1A-Ig and Low Dose IL-2 Exhibit a Distinct Activation / Functional Profile and Suppress GVHD in a Pre-Clinical Model.

Regulatory T cells (Tregs) are essential for the maintenance of tolerance and immune homeostasis. In allogeneic hematopoietic stem cell transplantation (aHSCT), transfer of appropriate Treg numbers is a promising therapy for the prevention of graft-versus-host disease (GVHD). We have recently reported a novel approach which induces the marked expansion and selective activation of Tregs in vivo by targeting TNF receptor superfamily 25 (TNFRSF25) and CD25. A potential advance to promote clinical application o...

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 ...

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.

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. ...

Posttransplant Cyclophosphamide for HLA-haploidentical Transplantation in Patients With Mucopolysaccharidosis.

We successfully used a haploidentical transplantation protocol with posttransplant cyclophosphamide (CY) (50 mg/kg/d on days +3 and +4) for in vivo T-cell depletion in patients with mucopolysaccharidosis using reduced-intensive conditioning regimens, followed by a busulfan-based conditioning regimen, which included busulfan (12 to 16 mg/kg) and fludarabine(150 to 200 mg/m)+rabbit antihuman thymocyte globulin (7.5 to 10 mg/kg) as a conditioning regimen. Cyclosporine or tacrolimus, methotrexate, mycop...

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...

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 ...

Outcome of gastrointestinal graft-versus-host disease according to the treatment response.

The optimal treatment strategy for gastrointestinal graft-versus-host disease (GI-GVHD) after allogeneic hematopoietic cell transplantation remains to be established. We retrospectively analyzed 68 cases of GI-GVHD at our institution between 2007 and 2017. The survival outcomes were significantly inferior in patients who did not respond to the first-line treatment (1-year overall survival 27.3 vs 69.2%, P = 0.0017; non-relapse mortality 50.0 vs 18.6%, P = 0.026). After subsequent treatments, 18 pati...

HLA-inferred extended haplotype disparity level is more relevant then the level of HLA mismatch alone for the patients survival and GvHD in T cell-replate hematopoietic stem cell transplantation from unrelated donor.

Serious risks in unrelated hematopoietic stem cell transplantation (HSCT) including graft versus host disease (GvHD) and mortality are associated with HLA disparity between donor and recipient. The increased risks might be dependent on disparity in not-routinely-tested multiple polymorphisms in genetically dense MHC region, being organized in combinations of two extended MHC haplotypes (Ehp). We assessed the clinical role of donor-recipient Ehp disparity levels in N=889 patients by the population-based dete...

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...

Corneal fluorescein staining and ocular symptoms but not Schirmer test are useful as indicators of response to treatment in chronic ocular GVHD.

To evaluate long-term ocular surface clinical signs and symptoms response to therapy in patients with chronic ocular GVHD.

TIGIT-Fc alleviates acute graft-versus-host disease by suppressing CTL activation via promoting the generation of immunoregulatory dendritic cells.

Graft-versus-host disease (GVHD) is the most common complication and major limitation of allogeneic hematopoietic stem cell transplantation. The CD226/TIGIT-CD155 signal is critical for the cross-talk between T cells and dendritic cells (DCs). Studies have shown that blockade of the CD226-CD155 interaction, using an anti-CD226 antibody, can significantly ameliorate GVHD. It has also been reported that a TIGIT-Fc fusion protein exerts immunosuppressive effects by binding to CD155 on DCs. Here, we used a mous...

Sequential HLA-haploidentical transplantation utilizing post-transplantation cyclophosphamide for GvHD prophylaxis in high-risk and relapsed/refractory AML/MDS.

This study evaluates the role of sequential therapy in HLA-haploidentical transplantation (haplo-HSCT) of high-risk, relapsed/refractory AML/MDS. We analyzed the course of 33 adults with active disease at time of transplantation (AML n=30; MDS n=3; median age 58 years, range: 32-71). Sequential therapy consisted of cytoreductive chemotherapy (FLAMSA n=21; clofarabine n=12) applied shortly prior to reduced intensity conditioning for T-cell-replete haplo-HSCT using post-transplantation cyclophosphamide as GvH...

Significant Risk of Graft-versus-Host Disease with Exposure to Checkpoint Inhibitors Before and After Allogeneic transplantation.

Investigators are using checkpoint inhibitors (CPI) to treat aggressive hematologic malignancies before patients undergo allogeneic hematopoietic stem cell transplantation (allo-HSCT) and in some patients with relapsed disease after allo-HSCT. CTLA-4 inhibitors and PD-1 inhibitors are two main types of CPI, which work through activation of the immune system. On one hand CPI can achieve graft versus tumor (GVT) effect, and on the other hand there is risk of graft versus host disease (GVHD). After a comprehen...

A Mesenchymal Stromal Cell (MSC)-Derived Combination of CXCL5 and Anti-CCL24 is Synergistic and Superior to MSC and Cyclosporine for the Treatment of Graft-Versus-Host Disease.

The immunosuppressive properties of mesenchymal stromal cells (MSCs) have been clinically proven to be effective in treating graft-versus-host disease (GVHD). However, MSC therapy is limited by the need for laborious and expensive manufacturing processes that are fraught with batch-to-batch variability. Substitution of MSC therapy with key MSC-mediated immunomodulatory factors could be an option for GVHD treatment. Using a simulated in vitro model of the immunosuppressive effects of MSC on allogeneic graft ...

Gastrointestinal graft-versus-host disease is a risk factor for post-engraftment blood stream infection in allogeneic hematopoietic stem cell transplant recipients.

Bloodstream infection (BSI) is a well-known cause of morbidity and mortality in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Here, we conducted a retrospective study to assess the morbidity, etiology, risk factors, and outcomes of BSI in the post-engraftment period (PE-BSI) following allo-HSCT. Forty-three out of 316 patients (13.6%) developed 57 PE-BSI episodes, in which 62 pathogens were isolated: gram-positive bacteria, gram-negative bacteria, and fungi, respectively, accoun...

CD3+ graft cell count influence on chronic GVHD in haploidentical allogeneic transplantation using post-transplant cyclophosphamide.

The effects of graft or donor characteristics in haploidentical hematopoietic cell transplantation (HCT) using post-transplant cyclophosphamide (PT-Cy) are largely unknown. In this multicenter retrospective study we analyzed the correlations between graft cell composition (CD34+, CD3+) and donor features on transplant outcomes in 234 patients who underwent HCT between 2010 and 2016. On multivariate analysis, the use of peripheral blood stem cells (PBSC) was associated with an increased incidence of grade 2-...

Baricitinib-induced blockade of interferon gamma receptor and interleukin-6 receptor for the prevention and treatment of graft-versus-host disease.

The therapeutic benefits of allogeneic hematopoietic stem cell transplantation (allo-HSCT) are derived from the graft-versus-leukemia (GvL) effects of the procedure. There is a strong association between the GvL effects and graft-versus-host disease (GvHD), a major life-threatening complication of allo-HSCT. The limiting of GvHD while maintaining the GvL effect remains the goal of allo-HSCT. Therefore, identifying optimal therapeutic targets to selectively suppress GvHD while maintaining the GvL effects rep...

Design and Patient Characteristics of the Chronic Graft-Versus-Host Disease Response Measures Validation Study.

In 2014, the National Institutes of Health sponsored the second Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-vs-Host (GVHD). The purpose was to update recommendations about key elements of chronic GVHD research, including definitions for diagnosis, severity scoring, and response measures, based on empirical data published since the first 2005 Consensus Conference. The most significant modifications were to the response assessments, since studies demonstrated difficulty with...

Variability of contribution of vitamin D receptor gene polymorphisms to outcome of HLA-matched sibling allogeneic bone marrow transplantation.

Graft-versus-host disease (GVHD) remains one of the major complications of hematopoietic stem cell transplantation (HSCT). Several etiological factors were investigated. Among these, vitamin D and hence its receptor (VDR) gene polymorphisms have gained much interest; however, the results are still controversial. Using PCR-RFLP, we genotyped VDR polymorphisms FokI (rs10735810), ApaI (rs7975232), and Taq1 (rs731236) in 80 patient/donor pairs according to DNA availability. No association was encountered betwee...


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