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https://www.readbyqxmd.com/read/28645118/outcome-of-patients-treated-for-myelodysplastic-syndromes-with-5q-deletion-after-failure-of-lenalidomide-therapy
#1
Thomas Prebet, Thomas Cluzeau, Sophie Park, Mikkael A Sekeres, Ulrich Germing, Lionel Ades, Uwe Platzbecker, Katharina Gotze, Norbert Vey, Esther Oliva, Mary M Sugrue, Cecile Bally, Charikleia Kelaidi, Najla Al Ali, Pierre Fenaux, Steven D Gore, Rami Komrokji
While lenalidomide (LEN) is the standard of care for the lower-risk myelodysplastic syndromes (MDS) patients with deletion 5q, 35% will not respond to or do not tolerate the drug. Moreover, most of the patients will lose their response after a few years. Defining the outcome of patients with LEN failure and determining the impact of subsequent therapies is therefore important to develop alternative strategies. Based on an international collaboration, we were able to compile a total of 392 patient cases of lower-risk MDS patients with 5q deletion and to analyze their outcome after failure of lenalidomide...
June 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28643491/association-of-foxp3-polymorphism-with-allograft-outcome-in-kidney-transplantation
#2
Hyewon Park, Nuri Lee, Ji Won In, Eun Youn Roh, Kyoung Un Park, Sue Shin, Jaeseok Yang, Eun Young Song
BACKGROUND: Forkhead box P3 (Foxp3) is the most reliable marker for regulatory T cells, which play an important role in maintaining renal allograft tolerance. Recently, Foxp3 polymorphisms have been reported to be associated with graft outcome in kidney transplantation. We analyzed the association of Foxp3 polymorphisms with renal allograft outcome. METHODS: Foxp3 polymorphisms (rs3761548 A/C, rs2280883 C/T, rs5902434 del/ATT, and rs2232365 A/G) were tested by PCR with sequence-specific primers (PCR-SSP) in 231 adult kidney transplantation recipients from 1996-2004 at Seoul National University Hospital...
September 2017: Annals of Laboratory Medicine
https://www.readbyqxmd.com/read/28643044/pd-1-signaling-and-inhibition-in-aml-and-mds
#3
REVIEW
Faysal Haroun, Sade A Solola, Samah Nassereddine, Imad Tabbara
Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) are clinically and molecularly heterogeneous clonal myeloid disorders with a poor prognosis especially in the relapsed refractory setting and in patients above the age of 60. While allogeneic hematopoietic stem cell transplantation (ASCT) is a potentially curative approach, high relapse, morbidity, and mortality rates necessitate the development of alternative therapies. Immune checkpoint inhibitors unmask tumoral immune tolerance and have demonstrated efficacy in the treatment of chemotherapy-resistant hematologic and solid malignancies...
June 22, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28641654/-efficacy-and-safety-of-posaconazoleon-for-primary-antifungal-prophylaxis-against-invasive-fungal-disease-in-patients-with-stem-cell-transplantation
#4
Ya-Mei Wu, Yong-Bin Cao, Xiao-Hong Li, Li-Xin Xu, Bei Yan, Song-Wei Li, Hai-Tao Wang, Ya-Hui Gao, Tian-Tian Zhang, Ya-Qian Zhang, Li Wang, Xiao-Xiong Wu
OBJECTIVE: To investigate the efficacy and clinical safety of posaconazoleon primary antifungal prophylaxis against invasive fungal disease (IFD) in patients with stem cell transplantation. METHODS: At the start from preconditioning regimen, 45 patients without IFD were administered with posaconazoleon until neutrophils greater than 0.5×10(9)/L, 35 patients treated with micafungin were enrolled in control group. The incidence, risk factors of IFD and side effects of medicines were evaluated...
June 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28639386/development-of-immune-response-to-tissue-restricted-self-antigens-in-simultaneous-kidney-pancreas-transplant-recipients-with-acute-rejection
#5
Muthukumar Gunasekaran, Neeta Vachharajani, Joseph P Gaut, Thin Thin Maw, Rowena Delos Santos, Surendra Shenoy, William C Chapman, Jason Wellen, Thalachallour Mohanakumar
Simultaneous kidney-pancreas transplantation (SKP Tx) is a treatment for end-stage kidney disease secondary to diabetes mellitus. We investigated the role of immune responses to donor human leukocyte antigens (HLA) and tissue-restricted kidney and pancreas self-antigens (KSAgs and PSAgs, respectively) in SKP Tx recipients (SKP TxRs). Sera collected from 39 SKP TxRs were used to determine de novo Abs specific for KSAgs (collagen-IV, Col-IV; fibronectin, FN) and PSAgs (insulin, islet cells, glutamic acid decarboxylase, and pancreas-associated protein-1) by ELISA...
June 21, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/28638096/identification-of-a-flavonoid-isolated-from-plum-prunus-domestica-as-a-potent-inhibitor-of-hepatitis-c-virus-entry
#6
Mihika Bose, Mohini Kamra, Ranajoy Mullick, Santanu Bhattacharya, Saumitra Das, Anjali A Karande
Hepatitis C virus (HCV) infection is a major cause of chronic liver diseases that often requires liver transplantation. The standard therapies are limited by severe side effects, resistance development, high expense and in a substantial proportion of cases, fail to clear the infection which bespeak the need for development of well-tolerated antivirals. Since most of the drug development strategies target the replication stage of viral lifecycle, the identification of entry inhibitors might be crucial especially in case of liver-transplant recipients...
June 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28637347/mechanisms-underlying-the-long-term-survival-of-the-monocot-dracaena-marginata-under-drought-conditions
#7
Radek Jupa, Roman Plichta, Zuzana Paschová, Nadezhda Nadezhdina, Roman Gebauer
Efficient water management is essential for the survival of vascular plants under drought stress. While interrelations among drought stress, plant anatomy and physiological functions have been described in woody dicots, similar research is very limited for non-palm arborescent and shrubby monocots despite their generally high drought tolerance. In this study, potted transplants of Dracaena marginata Lam. in primary growth stage were exposed to several short- and long-term drought periods. Continuous measurements of sap flow and stem diameter, the evaluation of capacitance and leaf conductance, the quantification of non-structural carbohydrates (NSC), and organ-specific anatomical analyses were performed to reveal the mechanisms promoting plant resistance to limited soil moisture...
June 14, 2017: Tree Physiology
https://www.readbyqxmd.com/read/28632754/permissive-hypercapnia-for-severe-acute-respiratory-distress-syndrome-in-immunocompromised-children-a-single-center-experience
#8
Hans Fuchs, Nicola Rossmann, Manuel B Schmid, Manfred Hoenig, Ulrich Thome, Benjamin Mayer, Daniel Klotz, Helmut D Hummler
BACKGROUND: Controlled hypoventilation while accepting hypercapnia has been advocated to reduce ventilator-induced lung injury. The aim of the study was to analyze outcomes of a cohort of immunocompromised children with acute respiratory distress syndrome (ARDS) ventilated with a strategy of stepwise increasing PCO2 targets up to 140 mm Hg. METHODS: Retrospective analysis of outcomes of a cohort of children with oncologic disease or after stem cell transplantation and severe respiratory failure in comparison with a historical control cohort...
2017: PloS One
https://www.readbyqxmd.com/read/28628776/3d-printed-lattices-as-an-activation-and-expansion-platform-for-t-cell-therapy
#9
Bahman Delalat, Frances Harding, Batjargal Gundsambuu, Elena M De-Juan-Pardo, Felix M Wunner, Marie-Luise Wille, Marek Jasieniak, Kristen A L Malatesta, Hans J Griesser, Antonio Simula, Dietmar W Hutmacher, Nicolas H Voelcker, Simon C Barry
One of the most significant hurdles to the affordable, accessible delivery of cell therapy is the cost and difficulty of expanding cells to clinically relevant numbers. Immunotherapy to prevent autoimmune disease, tolerate organ transplants or target cancer critically relies on the expansion of specialized T cell populations. We have designed 3D-printed cell culture lattices with highly organized micron-scale architectures, functionalized via plasma polymerization to bind monoclonal antibodies that trigger cell proliferation...
June 7, 2017: Biomaterials
https://www.readbyqxmd.com/read/28626459/the-immunogenicity-and-immune-tolerance-of-pluripotent-stem-cell-derivatives
#10
REVIEW
Xin Liu, Wenjuan Li, Xuemei Fu, Yang Xu
Human embryonic stem cells (hESCs) can undergo unlimited self-renewal and differentiate into all cell types in human body, and therefore hold great potential for cell therapy of currently incurable diseases including neural degenerative diseases, heart failure, and macular degeneration. This potential is further underscored by the promising safety and efficacy data from the ongoing clinical trials of hESC-based therapy of macular degeneration. However, one main challenge for the clinical application of hESC-based therapy is the allogeneic immune rejection of hESC-derived cells by the recipient...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28622062/novel-zinc-finger-protein-gene-469-znf469-variants-in-advanced-keratoconus
#11
Elvin Yildiz, Handan Bardak, Murat Gunay, Yavuz Bardak, Serhat Imamoglu, Halil Ozbas, Ozkan Bagci
PURPOSE: Common polymorphic variants upstream of Zinc finger protein gene 469 (ZNF469) have been associated with central corneal thickness. Rare ZNF469 variants have been shown in keratoconus patients. The aim of the current study was to investigate the frequency of ZNF 469 gene variants in rapidly progressive advance keratoconus patients who underwent corneal transplant surgery by the age of 30, compared to their frequency in the normal Turkish population. METHODS: A search in a patient database was performed to identify patients with a rapidly progressive keratoconus requiring corneal transplant surgery by the age of 30 in at least one eye...
June 16, 2017: Current Eye Research
https://www.readbyqxmd.com/read/28621766/autologous-haematopoietic-stem-cell-transplantation-for-treatment-of-multiple-sclerosis
#12
REVIEW
Paolo A Muraro, Roland Martin, Giovanni Luigi Mancardi, Richard Nicholas, Maria Pia Sormani, Riccardo Saccardi
Autologous haematopoietic stem cell transplantation (AHSCT) is a multistep procedure that enables destruction of the immune system and its reconstitution from haematopoietic stem cells. Originally developed for the treatment of haematological malignancies, the procedure has been adapted for the treatment of severe immune-mediated disorders. Results from ∼20 years of research make a compelling case for selective use of AHSCT in patients with highly active multiple sclerosis (MS), and for controlled trials...
June 16, 2017: Nature Reviews. Neurology
https://www.readbyqxmd.com/read/28620927/bendamustine-for-relapsed-blastic-plasmacytoid-dendritic-cell-leukaemia
#13
Sarah Bétrian, Sarah Guenounou, Isabelle Luquet, Cécile Demur, Anne Huynh, Loïc Ysebaert, Christian Recher, Françoise Huguet
Optimal treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN), a rare entity of dismal prognosis previously described as CD4+/CD56+ hematodermic malignancies, is not defined. We report five cases of relapsed BPDCN treated with bendamustine hydrochloride, a well-tolerated bifunctional drug acting as an alkylating and antimetabolite agent. All patients were above the age of 50 years and in advanced disease (early first relapse in two, subsequent relapse in three; multi-organ involvement in four; previous intensive chemotherapy in five; and stem cell transplantation in four)...
June 2017: Hematological Oncology
https://www.readbyqxmd.com/read/28620237/lea29y-expression-in-transgenic-neonatal-porcine-islet-like-cluster-promotes-long-lasting-xenograft-survival-in-humanized-mice-without-immunosuppressive-therapy
#14
L Wolf-van Buerck, M Schuster, F S Oduncu, A Baehr, T Mayr, S Guethoff, J Abicht, B Reichart, N Klymiuk, E Wolf, J Seissler
Genetically engineered pigs are a promising source for islet cell transplantation in type 1 diabetes, but the strong human anti-pig immune response prevents its successful clinical application. Here we studied the efficacy of neonatal porcine islet-like cell clusters (NPICCs) overexpressing LEA29Y, a high-affinity variant of the T cell co-stimulation inhibitor CTLA-4Ig, to engraft and restore normoglycemia after transplantation into streptozotocin-diabetic NOD-SCID IL2rγ(-/-) (NSG) mice stably reconstituted with a human immune system...
June 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28619624/fetal-stem-cell-and-gene-therapy
#15
REVIEW
Russell Witt, Tippi C MacKenzie, William H Peranteau
Advances in our understanding of stem cells, gene editing, prenatal imaging and fetal interventions have opened up new opportunities for the treatment of congenital diseases either through in-utero stem cell transplantation or in-utero gene therapy. Improvements in ultrasound-guided access to the fetal vasculature have also enhanced the safety and efficacy of cell delivery. The fetal environment offers accessible stem cell niches, localized cell populations with large proliferative potential, and an immune system that is able to acquire donor-specific tolerance...
June 12, 2017: Seminars in Fetal & Neonatal Medicine
https://www.readbyqxmd.com/read/28611473/apc-targeted-proinsulin-expression-inactivates-insulin-specific-memory-cd8-t-cells-in-nod-mice
#16
Peta Ls Reeves, Rajeev Rudraraju, Xiao Liu, F Susan Wong, Emma E Hamilton-Williams, Raymond J Steptoe
Type 1 diabetes (T1D) results from T-cell mediated autoimmune destruction of pancreatic β cells. Effector T-cell responses emerge early in disease development and expand as disease progresses. Following β cell destruction, a long-lived T-cell memory is generated that represents a barrier to islet transplantation and other cellular insulin-replacement therapies. Development of effective immunotherapies that control or ablate β cell destructive effector and memory T cell responses has the potential to prevent disease progression and recurrence...
June 14, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28610444/midostaurin-for-the-treatment-of-acute-myeloid-leukemia
#17
Mrinal M Patnaik
Midostaurin is a multikinase tyrosine kinase inhibitor acting against targets known to be expressed in hematologic malignancies, especially acute myeloid leukemia. Midostaurin combined with chemotherapy followed by single-agent maintenance therapy elicited statistically significant and clinically meaningful improvement in overall survival versus placebo in patients with newly diagnosed FLT3-mutant acute myeloid leukemia. Although gastrointestinal events were more common with midostaurin, overall the drug was relatively well tolerated...
June 14, 2017: Future Oncology
https://www.readbyqxmd.com/read/28608637/regulatory-t-cell-therapy-in-liver-transplantation
#18
REVIEW
Gavin P Whitehouse, Andrew Hope, Alberto Sanchez-Fueyo
Modern immunosuppression drug regimens have produced excellent short term survival after liver transplantation but it is generally accepted that the side effects of these medications remain a significant contributing factor for less satisfactory long term outcomes. The liver has unique tolerogenic properties as evidenced by the higher rates of operational tolerance seen in liver transplant recipients compared to other solid organ transplants and therefore liver transplantation offers an attractive setting in which to study tolerising therapies...
June 13, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28606879/can-immunosuppression-be-stopped-after-liver-transplantation
#19
REVIEW
Pierre-Alain Clavien, Xavier Muller, Michelle L de Oliveira, Philipp Dutkowski, Alberto Sanchez-Fueyo
Liver transplantation has improved dramatically over the past three decades, mainly as a result of advances in surgical techniques and management of post-transplant complications. The focus has now turned towards rescuing additional organs in the face of scarce organ supply, or prevention of long-term toxicity associated with immunosuppression. The liver appears to be privileged in terms of immune tolerance, with a low incidence of antibody-mediated rejection, which is in sharp contrast to other solid organ transplants, such as kidney, lung, and heart transplants...
July 2017: Lancet. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28604446/evolving-approaches-in-the-identification-of-allograft-reactive-t-and-b-cells-in-mice-and-humans
#20
James S Young, Christine McIntosh, Maria-Luisa Alegre, Anita S Chong
Whether a transplanted allograft is stably accepted, rejected or achieves immunological tolerance is dependent on the frequency and function of alloreactive lymphocytes, making the identification and analysis of alloreactive T and B cells in transplant recipients critical for understanding mechanisms, and the prediction of allograft outcome. In animal models, tracking the fate of graft-reactive T and B cells allows investigators to uncover their biology and develop new therapeutic strategies to protect the graft...
June 8, 2017: Transplantation
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