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https://www.readbyqxmd.com/read/28642593/transforming-growth-factor-%C3%AE-1-regulates-the-nascent-hematopoietic-stem-cell-niche-by-promoting-gluconeogenesis
#1
C-Y Zhang, H-M Yin, H Wang, D Su, Y Xia, L-F Yan, B Fang, W Liu, Y-M Wang, A-H Gu, Y Zhou
The understanding of hematopoietic stem cell (HSC) emergence is important to generate HSCs from pluripotent precursors. However, integrated signaling network that regulates the niche of nascent HSCs remains unclear. Herein, we uncovered a novel role of TGF-β1 in the metabolic niche of HSC emergence using the tgf-β1b(-/-) zebrafish. Our findings first showed that Tgf-β1 transcripts were enriched in the nascent HSCs. Loss of tgf-β1b caused a decrease of nascent HSCs within the aorta-gonad-mesonephros. Moreover, tgf-β1b(+) cells were runx1(+) HSCs and underwent an endothelial-to-hematopoietic-transition process...
June 23, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28640953/overview-of-transgenic-mouse-models-of-myeloproliferative-neoplasms-mpns
#2
Andrew Dunbar, Abbas Nazir, Ross Levine
Myeloproliferative neoplasms (MPNs) are a class of hematologic diseases characterized by aberrant proliferation of one or more myeloid lineages and progressive bone marrow fibrosis. In 2005, seminal work by multiple groups identified the JAK2V617F mutation in a significant fraction of MPN patients. Since that time, murine models of JAK2V617F have greatly enhanced the understanding of the role of aberrant JAK-STAT signaling in MPN pathogenesis and have provided an in vivo pre-clinical platform that can be used to develop novel therapies...
June 22, 2017: Current Protocols in Pharmacology
https://www.readbyqxmd.com/read/28630120/selinexor-induced-thrombocytopenia-results-from-inhibition-of-thrombopoietin-signaling-in-early-megakaryopoiesis
#3
Kellie R Machlus, Stephen K Wu, Prakrith Vijey, Thomas S Soussou, Zhi-Jian Liu, Eran Shacham, T J Unger, Trinayan Kashyap, Boris Klebanov, Martha Sola-Visner, Marsha Crochiere, Joseph E Italiano, Yosef Landesman
Selinexor is the first oral Selective Inhibitor of Nuclear Export compound tested for cancer treatment. Selinexor has demonstrated a safety therapy profile with broad antitumor activity against solid and hematological malignancies in phases 2 and 3 clinical trials (NCT03071276, NCT02343042, NCT02227251, NCT03110562, NCT02606461). While selinexor shows promising efficacy, its primary adverse effect is high-grade thrombocytopenia. Therefore, we aimed to identify the mechanism of selinexor-induced thrombocytopenia to relieve it and improve its clinical management...
June 19, 2017: Blood
https://www.readbyqxmd.com/read/28600031/hematopoietic-cell-transplantation-in-myelodysplastic-syndromes-after-treatment-with-hypomethylating-agents
#4
Moreno Festuccia, Kelsey Baker, Theodore A Gooley, Brenda M Sandmaier, H Joachim Deeg, Bart L Scott
The prognosis of patients with myelodysplastic syndromes (MDS) following failure of hypomethylating agent (HMA) therapy is poor. Allogeneic hematopoietic cell transplantation (HCT) can be effective in curing patients who have failed therapy with HMA. However, published results have not addressed the outcomes with HCT in this setting. We identified 125 MDS patients who had been treated with HMA and underwent subsequent HCT. Among these, 68 were considered HMA failures, and 57 responders. Failure was defined as progression to higher grade MDS or acute myeloid leukemia (AML), lack of hematological improvement after at least 4 HMA cycles, or loss of response after initial improvement...
June 6, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28596644/highlights-of-multiple-myeloma-at-the-annual-meeting-of-american-society-of-hematology-2016
#5
REVIEW
Nidhi Tandon, Shaji K Kumar
This review discusses the landmark studies in the field of multiple myeloma (MM) which were presented at American society of hematology annual meeting, 2016. There were contrary results from two large phase III trials (one from US and one from Europe) that evaluated the role of additional interventions like tandem autologous transplant (ASCT) and consolidation after induction therapy followed by ASCT in newly diagnosed MM (NDMM) patients, but there were critical differences between the two studies. Novel agents like carfilzomib and ixazomib proved to be of benefit when used as induction and post ASCT consolidation and maintenance in NDMM...
June 2017: Indian Journal of Hematology & Blood Transfusion
https://www.readbyqxmd.com/read/28594635/epidemiology-of-carbapenem-resistant-klebsiella-pneumoniae-bloodstream-infections-in-a-chinese-children-s-hospital-predominance-of-new-delhi-metallo-%C3%AE-lactamase-1
#6
Fang Dong, Ye Zhang, Kaihu Yao, Jie Lu, Lingyun Guo, Shuang Lyu, Ying Yang, Yan Wang, Hongyan Zheng, Wenqi Song, Gang Liu
The spread of carbapenem-resistant Klebsiella pneumoniae (CRKp) has become a significant problem worldwide; however, relevant data in children are limited. We performed a retrospective study to better understand the epidemiology of CRKp bloodstream infections at Beijing Children's Hospital. A total of 164 K. pneumoniae strains were collected from blood cultures between January 2011 and September 2014, of which 52 (31.7%) were CRKp strains. All 52 CRKp strains were multidrug resistant; 46 (88.5%) and 49 (94...
June 8, 2017: Microbial Drug Resistance: MDR: Mechanisms, Epidemiology, and Disease
https://www.readbyqxmd.com/read/28579115/bleeding-and-thrombosis-associated-with-ventricular-assist-device-therapy
#7
Palak Shah, Udaya S Tantry, Kevin P Bliden, Paul A Gurbel
Over the past decade, continuous-flow rotary pumps have dramatically improved survival for patients with advanced systolic heart failure. Bleeding and thrombosis, however, continue to be the Achilles heel of left ventricular assist device (LVAD) therapy. There is a dynamic and complex interaction between the patient and pump. The net effect of a variety of hematologic derangements, such as hemolysis, high-molecular-weight von Willebrand degradation, platelet activation and diminished pulsatility, is poorly understood...
May 11, 2017: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/28561703/hematologic-malignancies-plasma-cell-disorders
#8
Madhav V Dhodapkar, Ivan Borrello, Adam D Cohen, Edward A Stadtmauer
Multiple myeloma (MM) is a plasma cell malignancy characterized by the growth of tumor cells in the bone marrow. Properties of the tumor microenvironment provide both potential tumor-promoting and tumor-restricting properties. Targeting underlying immune triggers for evolution of tumors as well as direct attack of malignant plasma cells is an emerging focus of therapy for MM. The monoclonal antibodies daratumumab and elotuzumab, which target the plasma cell surface proteins CD38 and SLAMF7/CS1, respectively, particularly when used in combination with immunomodulatory agents and proteasome inhibitors, have resulted in high response rates and improved survival for patients with relapsed and refractory MM...
2017: American Society of Clinical Oncology Educational Book
https://www.readbyqxmd.com/read/28561667/myeloma-in-elderly-patients-when-less-is-more-and-more-is-more
#9
Ashley Rosko, Sergio Giralt, Maria-Victoria Mateos, Angela Dispenzieri
Multiple myeloma is a plasma cell malignancy that occurs among older adults and accounts for 15% of all hematologic malignancies in the United States. Thirty-five percent of patients are diagnosed at age 75 or older. Novel therapeutics and routine use of autologous stem cell transplantation (ASCT) have led to substantial improvements in patient survival, although improvements have been more impressive among patients younger than age 65. Finding the balance between under- and overtreating elderly patients is one of the biggest challenges specific to them as a subgroup of patients with MM...
2017: American Society of Clinical Oncology Educational Book
https://www.readbyqxmd.com/read/28553616/the-oncolytic-virotherapy-era-in-cancer-management-prospects-of-applying-h-1-parvovirus-to-treat-blood-and-solid-cancers
#10
Assia L Angelova, Mathias Witzens-Harig, Angel S Galabov, Jean Rommelaere
Non-Hodgkin lymphoma (NHL) and leukemia are among the most common cancers worldwide. While the treatment of NHL/leukemia of B-cell origin has much progressed with the introduction of targeted therapies, few treatment standards have been established for T-NHL/leukemia. As presentation in both B- and T-NHL/leukemia patients is often aggressive and as prognosis for relapsed disease is especially dismal, this cancer entity poses major challenges and requires innovative therapeutic approaches. In clinical trials, oncolytic viruses (OVs) have been used against refractory multiple myeloma (MM)...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28550043/al-amyloidosis-patients-with-low-amyloidogenic-free-light-chain-levels-at-first-diagnosis-have-an-excellent-prognosis
#11
Tobias Dittrich, Tilmann Bochtler, Christoph Kimmich, Natalia Becker, Anna Jauch, Hartmut Goldschmidt, Anthony D Ho, Ute Hegenbart, Stefan O Schönland
The difference between involved minus uninvolved serum free light chains (dFLC) has been established as invaluable hematologic parameter in systemic light chain amyloidosis (AL). However, patients with initial dFLC below 50mg/L are currently deemed not evaluable for response to therapy. Therefore, we aimed to characterize this subgroup and to define novel hematologic response parameters. We retrospectively analyzed 783 AL patients newly diagnosed at our center between 2002 and 2016. Patients with dFLC<50 showed a smaller bone marrow plasmacytosis (7% vs...
May 26, 2017: Blood
https://www.readbyqxmd.com/read/28536321/-disruption-of-gut-immune-system-caused-by-damage-of-intestinal-stem-cells-and-their-niche-in-graft-versus-host-disease-after-allogeneic-hematopoietic-stem-cell-transplantation
#12
Eiko Hayase, Takanori Teshima
Allogeneic hematopoietic stem cell transplantation(allo-SCT)is curative therapy for various hematological diseases. Graft-versus-host disease(GVHD)and infection remain the main problems in allo-SCT. Gastrointestinal tract is targeted by GVHD. In intestinal GVHD, intestinal stem cells and Paneth cells reside at the base of crypts are damaged by donor T cells. These damage leads to disruption of intestinal mucosal barrier and intestinal dysbiosis, resulting in more exaggerated GVHD. Recently, we and others have reported that R-Spondin1 and interleukin-22 as factors regenerated intestinal tissue homeostasis in murine model of bone marrow transplantation...
2017: Clinical Calcium
https://www.readbyqxmd.com/read/28529898/preclinical-rationale-for-combining-radiation-therapy-and-immunotherapy-beyond-checkpoint-inhibitors-i-e-cart
#13
REVIEW
James P Flynn, Mark H O'Hara, Saumil J Gandhi
An increasing appreciation for the role of the immune system in targeting cancer cells over the last decade has led to the development of several immunomodulatory agents aimed at enhancing the systemic antitumor immune response. One such method is the use of T cells that are genetically engineered to express chimeric antigen receptors (CARs). The remarkable success of this approach in advanced hematologic malignancies has garnered much enthusiasm for using this novel tool in treating other cancers. However, multiple challenges have hampered the application of this therapy to a broader set of solid tumors, most notably lung cancer...
April 2017: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/28528668/trpv1-channels-in-immune-cells-and-hematological-malignancies
#14
Sofia A Omari, Murray J Adams, Dominic P Geraghty
Transient receptor potential vanilloid-1 (TRPV1) is a member of the TRP family of channels that are responsible for nociceptive, thermal, and mechanical sensations. Originally associated exclusively with sensory neurons, TRPV1 is now known to be present in almost all organs, including cells of the immune system, where TRPV1 has been shown to play a pivotal role in inflammation and immunity. Monocytes, macrophages, and dendritic cells express TRPV1, with both mouse and human studies suggesting that TRPV1 activation protects against endotoxin-induced inflammation...
2017: Advances in Pharmacology
https://www.readbyqxmd.com/read/28514768/driving-better-and-safer-her2-specific-cars-for-cancer-therapy
#15
REVIEW
Xianqiang Liu, Nan Zhang, Huan Shi
Given the clinical efficacy of chimeric antigen receptor (CAR)-based therapy in hematological malignancies, CAR T-cell therapy for a number of solid tumors has been actively investigated. Human epidermal growth factor receptor 2 (HER2) is a well-established therapeutic target in breast, as well as other types of cancer. However, HER2 CAR T cells pose a risk of lethal toxicity including cytokine release syndrome from "on-target, off-tumor" recognition of HER2. In this review, we summarize the development of conventional HER2 CAR technology, the alternative selection of CAR hosts, the novel HER2 CAR designs, clinical studies and toxicity...
April 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28507811/adoptive-natural-killer-cell-therapy-is-effective-in-reducing-pulmonary-metastasis-of-ewing-sarcoma
#16
Alexander A Tong, Hasan Hashem, Saada Eid, Frederick Allen, Daniel Kingsley, Alex Y Huang
The survival of patients with metastatic or relapsed Ewing sarcoma (ES) remains dismal despite intensification of combination chemotherapy and radiotherapy, precipitating the need for novel alternative therapies with minimal side effects. Natural killer (NK) cells are promising additions to the field of cellular immunotherapy. Adoptive NK cell therapy has shown encouraging results in hematological malignancies. Despite these initial promising successes, however, NK cell therapy for solid tumors remains to be investigated using in vivo tumor models...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28506131/new-drugs-and-allogeneic-hematopoietic-stem-cell-transplantation-for-hematological-malignancies-do-they-have-a-role-in-bridging-consolidating-or-conditioning-transplantation-treatment
#17
Francesca Patriarca, Luisa Giaccone, Francesco Onida, Luca Castagna, Barbara Sarina, Vittorio Montefusco, Alberto Mussetti, Nicola Mordini, Elena Maino, Raffaella Greco, Jacopo Peccatori, Moreno Festuccia, Francesco Zaja, Stefano Volpetti, Antonio Risitano, Renato Bassan, Paolo Corradini, Fabio Ciceri, Renato Fanin, Michele Baccarani, Alessandro Rambaldi, Francesca Bonifazi, Benedetto Bruno
Novel targeted therapies and monoclonal antibodies can be combined with allogeneic stem cell transplantation (allo-SCT) at different time-points: 1) before the transplant to reduce tumour burden, 2) as part of the conditioning in place of or in addition to conventional agents 3) after the transplant to allow long-term disease control. Areas covered: This review focuses on the current integration of new drugs with allo-SCT for the treatment of major hematological malignancies for which allo-SCT has been a widely-adopted therapy...
July 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28500633/the-novel-role-of-pyrvinium-in-cancer-therapy
#18
REVIEW
Amir Abbas Momtazi-Borojeni, Elham Abdollahi, Faezeh Ghasemi, Michele Caraglia, Amirhossein Sahebkar
Pyrvinium pamoate (PP) is a quinoline-derived cyanine dye which was officially approved by FDA for its anthelmintic properties and therapeutic function against animal-like protists such as Cryp-tosporidium parvum and Plasmodium falciparum in the 1950 s. In the last 10 years, several studies have shown the novel activity of pyrvinium in tumor therapy. Some investigations have indicated that pyrvinium could delay or inhibit tumor cell proliferation in cancer models including colon, breast, lung and prostate cancer and some hematological malignancies...
May 13, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28479419/novel-tumor-suppressor-function-of-klf4-in-pediatric-t-cell-acute-lymphoblastic-leukemia
#19
REVIEW
Ye Shen, Taylor J Chen, H Daniel Lacorazza
Acute lymphoblastic leukemia (ALL) is the most common hematological malignancy in pediatric patients. Despite advances in the treatment of this disease, many children with T-cell ALL (T-ALL) die from disease relapse due to low responses to standard chemotherapy and the lack of a targeted therapy that selectively eradicates the chemoresistant leukemia-initiating cells (LICs) responsible for disease recurrence. We reported recently that the reprogramming factor Krüppel-like factor 4 (KLF4) has a tumor-suppressive function in children with T-ALL...
May 4, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28472843/targeting-multiple-myeloma-cancer-stem-cells-with-natural-products-lessons-from-other-hematological-malignancies
#20
Mark E Issa, Sylvian Cretton, Muriel Cuendet
Multiple myeloma is characterized by the accumulation of malignant plasma cells in the bone marrow. Multiple myeloma is the second most frequently diagnosed hematological malignancy, predominantly affecting the elderly. Despite recent advances in the development of novel therapies, multiple myeloma remains an incurable malignancy where the majority of patients relapse, develop resistance, and eventually die from the disease. This has been attributed to the fact that conventional therapy currently in use targets mainly the bulk of tumor cells, but not the tumor-initiating cancer stem cells...
June 2017: Planta Medica
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