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https://www.readbyqxmd.com/read/29169144/targeting-the-wnt-beta-catenin-pathway-in-cancer-update-on-effectors-and-inhibitors
#1
REVIEW
Nithya Krishnamurthy, Razelle Kurzrock
The Wnt/beta-catenin pathway is a family of proteins that is implicated in many vital cellular functions like stem cell regeneration and organogenesis. Several intra-cellular signal transduction pathways are induced by Wnt, notably the Wnt/beta-catenin dependent pathway or canonical pathway and the non-canonical or beta-catenin-independent pathway, the latter includes the Wnt/Ca2+ and Planar Cell Polarity pathway (PCP). Wnt activation occurs at the intestinal crypt floor, and is critical to optimal maintenance of stem cells...
November 13, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/29168762/dual-roles-of-fer-kinase-are-required-for-proper-hematopoiesis-and-vascular-endothelium-organization-during-zebrafish-development
#2
Emily M Dunn, Elizabeth J Billquist, Amy L VanderStoep, Phillip G Bax, Laura M Westrate, Lisa K McLellan, Shelby C Peterson, Jeffrey P MacKeigan, Aaron P Putzke
Fer kinase, a protein involved in the regulation of cell-cell adhesion and proliferation, has been shown to be required during invertebrate development and has been implicated in leukemia, gastric cancer, and liver cancer. However, in vivo roles for Fer during vertebrate development have remained elusive. In this study, we bridge the gap between the invertebrate and vertebrate realms by showing that Fer kinase is required during zebrafish embryogenesis for normal hematopoiesis and vascular organization with distinct kinase dependent and independent functions...
November 23, 2017: Biology
https://www.readbyqxmd.com/read/29168461/study-of-stem-cell-homing-self-renewal-marker-gene-profile-of-ex-vivo-expanded-human-cd34-cells-manipulated-with-a-mixture-of-cytokines-stromal-cell-derived-factor-1
#3
Jyoti Kode, Navin Khattry, Ashish Bakshi, Vasanti Amrutkar, Bhausaheb Bagal, Rohini Karandikar, Pallavi Rane, Nobutaka Fujii, Shubhada Chiplunkar
BACKGROUND & OBJECTIVES: Next generation transplantation medicine aims to develop stimulating cocktail for increased ex vivo expansion of primitive hematopoietic stem and progenitor cells (HSPC). The present study was done to evaluate the cocktail GF (Thrombopoietin + Stem Cell factor + Flt3-ligand) and homing-defining molecule Stromal cell-derived factor 1 (SDF1) for HSPC ex vivo expansion. METHODS: Peripheral blood stem cell (n=74) harvests were analysed for CD34hiCD45lo HSPC...
July 2017: Indian Journal of Medical Research
https://www.readbyqxmd.com/read/29168236/a-prospective-multicenter-phase-ii-study-of-intrabone-marrow-transplantation-of-unwashed-cord-blood-using-reduced-intensity-conditioning
#4
Masaya Okada, Taizo Tasaka, Kazuhiro Ikegame, Nobuyuki Aotsuka, Takeshi Kobayashi, Yuho Najima, Yoshiko Matsuhashi, Hideho Wada, Hirotoshi Tokunaga, Shinichi Masuda, Yoshikazu Utsu, Satoshi Yoshihara, Katsuji Kaida, Takashi Daimon, Hiroyasu Ogawa
Cord blood transplantation (CBT) is associated with delayed hematopoietic recovery and graft failure. To overcome these problems, we conducted a prospective, multicenter phase II study of intrabone marrow transplantation in which patients received reduced-intensity conditioning without anti-thymocyte globulin. The primary endpoint was the probability of full donor engraftment. Forty patients with hematologic malignancies were enrolled. CB cells were injected without washing into 4 iliac bone sites (2 at each hemipelvis), at which approximately 6 mL of CB was administered at one site with local anesthesia...
November 23, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/29168234/impact-of-comorbidities-constituting-the-hct-ci-score-on-the-outcome-of-patients-undergoing-allogeneic-hct-for-aml
#5
Manar M I Khalil, Jeffrey H Lipton, Eshetu G Atenafu, Vikas Gupta, Dennis D Kim, John Kuruvilla, Auro Viswabandya, Hans A Messner, Fotios V Michelis
OBJECTIVE: To investigate the prognostic impact of the individual component comorbidities of the hematopoietic cell transplant co-morbidity index (HCT-CI) in patients with acute myeloid leukemia (AML) that underwent allogeneic hematopoietic cell transplant (HCT). METHOD: This single-center study retrospectively investigated the individual comorbidities of the HCT-CI on the outcome of 418 patients that underwent HCT for AML, in CR1 (n=303, 72%) or CR2 (n=115, 28%) at our center between 1999 and 2014...
November 23, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/29168144/a-review-of-chronic-granulomatous-disease
#6
REVIEW
Danielle E Arnold, Jennifer R Heimall
Chronic granulomatous disease (CGD) is a primary immunodeficiency caused by defects in any of the five subunits of the NADPH oxidase complex responsible for the respiratory burst in phagocytic leukocytes. Patients with CGD are at increased risk of life-threatening infections with catalase-positive bacteria and fungi and inflammatory complications such as CGD colitis. The implementation of routine antimicrobial prophylaxis and the advent of azole antifungals has considerably improved overall survival. Nevertheless, life expectancy remains decreased compared to the general population...
November 22, 2017: Advances in Therapy
https://www.readbyqxmd.com/read/29168113/dynamics-of-bone-marrow-vsels-and-hscs-in-response-to-treatment-with-gonadotropin-and-steroid-hormones-during-pregnancy-and-evidence-to-support-their-asymmetric-symmetric-cell-divisions
#7
Ranita Ganguly, Sidhanath Metkari, Deepa Bhartiya
Gender plays an important role in the incidence of hematological malignancies and recently hematopoietic stem cells (HSCs) were found to proliferate more in females that gets further augmented during pregnancy. It was suggested that since basal numbers of HSCs remain the same in both sexes, possibly HSCs in females undergo increased self-renewal and apoptosis. Then how is self-renewal of stem cells regulated in males? More important, do HSCs undergo asymmetric cell divisions (ACD) or a more primitive population of pluripotent, very small embryonic-like stem cells (VSELs) undergo ACD to self-renew and specify into HSCs? Lot more clarity is required on the bone marrow stem cells biology...
November 22, 2017: Stem Cell Reviews
https://www.readbyqxmd.com/read/29167990/histologic-analysis-has-a-prognostical-value-in-colorectal-biopsies-assessed-for-suspicion-of-graft-versus-host-disease
#8
Fanny Sauvestre, Geneviève Belleannée, Claire Bréal, Catherine Mohr, Harold IpKan Fong, Sébastien Cossin, Reza Tabrizi, Noël Milpied, Stéphane Vigouroux, Jean-François Goussot, Marion Marty
Gastrointestinal (GI) graft-versus-host-disease (GVHD) is a common and severe complication of allogeneic hematopoietic stem cell transplantation, but clinical and histological features are unspecific. The aim of this study was to correlate the histological GI GVHD grade with the clinical outcomes. In a retrospective study of 112 patients with clinically suspected GI GVHD, colonic biopsies were reviewed by three pathologists without knowledge of the corresponding clinical data and classified in four scores, according to the NIH Consensus Project recommendations: no GVHD, possible, probable, and unequivocal GVHD...
November 22, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/29167806/aplastic-anemia-is-related-to-alterations-in-t-cell-receptor-signaling
#9
REVIEW
Yankai Xiao, Suwen Zhao, Bo Li
Aplastic anemia (AA) is a disease characterized by bone marrow hematopoietic dysfunction and peripheral blood pancytopenia, which is thought to be mediated by an abnormal T cell-induced immune response. T cell receptor (TCR) signaling is pivotal for T cell development and function. An aberrant TCR signaling leads to an unbalanced immune system that can result in a range of immune-related disorders, including autoimmune diseases, chronic infections, and tumors. In this article, we briefly review the T cell immune pathophysiology of AA, the physiology of normal TCR signaling and its regulatory factors, and clinical and laboratory findings of TCR signaling molecules and their regulatory factors in AA...
2017: Stem Cell Investigation
https://www.readbyqxmd.com/read/29167805/clinical-potential-of-mesenchymal-stem-stromal-cell-derived-extracellular-vesicles
#10
REVIEW
Bernd Giebel, Lambros Kordelas, Verena Börger
Within the last two decades mesenchymal stem/stromal cells (MSCs) emerged after hematopoietic stem cells as the second most investigated and applied somatic stem cell entity so far. MSCs mediate immunosuppressive as well as pro-regenerative activities. Against the initial assumption, MSCs may not primarily exert their therapeutic functions in a cellular but rather in a paracrine manner. Here, extracellular vesicles (EVs), such as exosomes and microvesicles, have been identified as major mediators of these paracrine effects...
2017: Stem Cell Investigation
https://www.readbyqxmd.com/read/29167672/novel-concept-of-cd4-mediated-activation-of-regulatory-t-cells-for-the-treatment-of-graft-versus-host-disease
#11
REVIEW
Janine Schlöder, Carsten Berges, Andrea Tuettenberg, Helmut Jonuleit
Allogeneic hematopoietic stem cell transplantation is the only curative treatment option for several hematological malignancies and immune deficiency syndromes. Nevertheless, the development of a graft-versus-host disease (GvHD) after transplantation is a high risk and a severe complication with high morbidity and mortality causing therapeutic challenges. Current pharmacological therapies of GvHD lead to generalized immunosuppression followed by severe adverse side effects including infections and relapse of leukemia...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29167668/a-practical-approach-to-newborn-screening-for-severe-combined-immunodeficiency-using-the-t-cell-receptor-excision-circle-assay
#12
REVIEW
Monica S Thakar, Mary K Hintermeyer, Miranda G Gries, John M Routes, James W Verbsky
Severe combined immunodeficiency (SCID) is a life-threatening condition of newborns and infants caused by defects in genes involved in T cell development. Newborn screening (NBS) for SCID using the T cell receptor excision circle (TREC) assay began in Wisconsin in 2008 and has been adopted or is being implemented by all states in 2017. It has been established that NBS using the TREC assay is extremely sensitive to detect SCID in the newborn period. Some controversies remain regarding how screening positives are handled by individual states, including when to perform confirmatory flow cytometry, what is the necessary diagnostic workup of patients, what infection prophylaxis measures should be taken, and when hematopoietic stem cell transplantation should occur...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29167177/smoothened-signaling-in-the-mouse-osteoblastoid-lineage-is-required-for-efficient-b-lymphopoiesis
#13
Wenyan Lu, Dominic Dordai, David Huso, Stephen Desiderio
The stromal signals that promote B lymphopoiesis remain poorly understood. Hedgehog (Hh) signaling promotes B lymphopoiesis in a non-cell autonomous fashion in vitro and depletion of the Hh effector smoothened (Smo) from stromal cells is associated with the loss of osteoblastoid markers. These observations suggested that Hh signaling in the osteoblastoid lineage promotes B lymphopoiesis in vivo. To test this we developed a mouse model for conditional ablation of Smo in the osteoblastoid lineage. Depletion of Smo from osteoblastoid cells is associated with profound and selective reductions in the number and proportion of bone marrow B lymphoid progenitors...
November 22, 2017: Blood
https://www.readbyqxmd.com/read/29167174/inherited-bone-marrow-failure-syndromes-considerations-pre-and-post-transplant
#14
Blanche P Alter
Patients with inherited bone marrow failure syndromes are usually identified when they develop hematologic complications such as severe bone marrow failure, myelodysplastic syndrome, or acute myeloid leukemia. They often have specific birth defects or other physical abnormalities that suggest a syndrome, and sequencing of specific genes or next generation sequencing can determine or confirm the particular syndrome. The four most frequent syndromes are Fanconi anemia, dyskeratosis congenita, Diamond Blackfan anemia and Shwachman Diamond syndrome...
November 22, 2017: Blood
https://www.readbyqxmd.com/read/29166742/-allogeneic-hematopoietic-stem-cell-transplantation-for-the-treatment-of-acute-myeloid-leukemia-with-primary-thrombocytosis-three-cases-report-and-literatures-review
#15
X P Zong, L Tang, J N Cen, S N Chen, A N Sun, D P Wu
Objective: To investigate the characteristics of the essential thrombocythemia (ET) cases transformed to the acute myeloid leukemia (AML) and the role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of this disease. Methods: The clinical and laboratory characteristics of 3 ET cases before and after transformation and after allo-HSCT were retrospectively analyzed, meanwhile the related literatures were reviewed and discussed. Results: Case 1 was a male patient of 44 years old, whose PLT was 500×10(9)/L when firstly diagnosed ET...
October 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/29166737/-clinical-analysis-of-patients-with-hemophagocytic-lymphohistiocytosis-complicated-with-gastrointestinal-bleeding
#16
Z L Jin, Y N Wang, Z Wang
Objective: To explore the clinical features of patients with hemophagocytic lymphohistiocytosis (HLH) complicated with gastrointestinal bleeding. Methods: The clinical data of 52 patients with HLH diagnosed from January 2015 to February 2017 were analyzed retrospectively. Results: ①Of the 52 patients[including 36 cases of EBV related (69.2%) , 5 cases of lymphoma related (9.6%) , 3 cases of primary HLH (5.8%) , 3 cases of rheumatism related (5.8%) , 2 cases of tuberculosis related (3.8%) , 3 cases of unknown causes (3...
October 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/29166733/-comparative-study-on-the-efficacy-and-safety-between-pegfilgrastim-peg-rhg-csf-and-recombinant-human-granulocyte-colony-stimulating-factor-in-promoting-hematopoietic-recovery-after-allogeneic-hematopoietic-stem-cell-transplantation-after-hematological-malignancy
#17
F Yang, X D Sun, L Yuan, J C Zhang, J W Hu, N Liu, X Lou, Y F Su, Z Y Yu, J L Chen, Y H Li, L D Hu, H Chen, M Jiang
Objective: To observe the efficacy and safety between Pegfilgrastim (PEG-rhG-CSF) and Recombinant human granulocyte colony stimulating factor (rhG-CSF) in hematological malignancy after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: 157 patients after allo-HSCT were enrolled in this study from June 2015 to November 2016. Two agents of G-CSF were used to stimulate hematopoietic recovery after transplantation. There were 65 cases in PEG-rhG-CSF and 92 cases in rhG-CSF groups. Patients in PEG-rhG-CSF group were given a single subcutaneous dose of 6 mg on the first day and +8 d, while cases in rhG-CSF group were given in dose of 5 μg·kg(-1)·d(-1) by subcutaneous injection from +1 d continuing to neutrophils more than 1...
October 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/29166642/effect-of-calcium-infiltrated-hydroxyapatite-scaffolds-on-the-hematopoietic-fate-of-human-umbilical-vein-endothelial-cells
#18
Qinghao Zhang, Jörg C Gerlach, Eva Schmelzer, Ian Nettleship
Foamed hydroxyapatite offers a three-dimensional scaffold for the development of bone constructs, mimicking perfectly the in vivo bone structure. In vivo, calcium release at the surface is assumed to provide a locally increased gradient supporting the maintenance of the hematopoietic stem cells niche. We fabricated hydroxyapatite scaffolds with high surface calcium concentration by infiltration, and used human umbilical vein endothelial cells (HUVECs) as a model to study the effects on hematopoietic lineage direction...
November 23, 2017: Journal of Vascular Research
https://www.readbyqxmd.com/read/29166614/critical-modulation-of-hematopoietic-lineage-fate-by-hepatic-leukemia-factor
#19
Martin Wahlestedt, Vasileios Ladopoulos, Isabel Hidalgo, Manuel Sanchez Castillo, Rebecca Hannah, Petter Säwén, Haixia Wan, Monika Dudenhöffer-Pfeifer, Mattias Magnusson, Gudmundur L Norddahl, Berthold Göttgens, David Bryder
A gradual restriction in lineage potential of multipotent stem/progenitor cells is a hallmark of adult hematopoiesis, but the underlying molecular events governing these processes remain incompletely understood. Here, we identified robust expression of the leukemia-associated transcription factor hepatic leukemia factor (Hlf) in normal multipotent hematopoietic progenitors, which was rapidly downregulated upon differentiation. Interference with its normal downregulation revealed Hlf as a strong negative regulator of lymphoid development, while remaining compatible with myeloid fates...
November 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/29166611/ccr5-directs-the-mobilization-of-cd11b-gr1-ly6c-low-polymorphonuclear-myeloid-cells-from-the-bone-marrow-to-the-blood-to-support-tumor-development
#20
Elias Hawila, Hila Razon, Gizi Wildbaum, Carolin Blattner, Yair Sapir, Yuval Shaked, Viktor Umansky, Nathan Karin
Cells of hematopoietic origin can be subdivided into cells of the lymphoid lineage and those of the myeloid lineage, among which are myeloid-derived suppressor cells (MDSCs). The MDSCs can be further divided into CD11b(+)Ly6G(-)Ly6C(hi) monocytic (Mo) MDSCs and CD11b(+)Ly6G(+)Ly6C(low) polymorphonuclear (PMN) MDSCs. Both subtypes support tumor growth and suppress anti-tumor immunity. Their accumulation at the tumor site includes mobilization from the bone marrow to the blood followed by colonization at the tumor site...
November 21, 2017: Cell Reports
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