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https://www.readbyqxmd.com/read/27910858/immunosuppression-in-liver-tumors-opening-the-portal-to-effective-immunotherapy
#1
REVIEW
P Guha, J Reha, S C Katz
We have recently witnessed substantial progress with immunotherapy for selected diseases. Checkpoint inhibitors and chimeric antigen receptor T (CAR-T) cells are among the most promising agents. Whereas much of the early success with CAR-T cells has been demonstrated with hematological malignancies, important barriers remain for the application of CAR-T cell therapies for the management of metastatic solid tumors. The challenges are particularly apparent when considering primary and metastatic tumors in the liver...
December 2, 2016: Cancer Gene Therapy
https://www.readbyqxmd.com/read/27899804/casein-kinase-2-controls-the-survival-of-normal-thymic-and-leukemic-%C3%AE-%C3%AE-t-cells-via-promotion-of-akt-signaling
#2
S T Ribeiro, M Tesio, J C Ribot, E Macintyre, J T Barata, B Silva-Santos
The thymus is the major site for normal and leukemic T-cell development. The dissection of the molecular determinants of T-cell survival and differentiation is paramount for the manipulation of healthy or transformed T cells in cancer (immuno)therapy. Casein Kinase 2 (CK2) is a serine-threonine protein kinase whose anti-apoptotic functions have been described in various hematological and solid tumors. Here we disclose an unanticipated role of CK2 in healthy human thymocytes that is selective to the γδ T-cell lineage...
November 30, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27894203/management-of-adverse-events-induced-by-next-generation-immunomodulatory-drug-and-proteasome-inhibitors-in-multiple-myeloma
#3
Marco Salvini, Francesca Bonello, Mario Boccadoro, Alessandra Larocca
In the last decade the introduction of novel agents has strongly improved multiple myeloma prognosis by doubling median overall survival. Unfortunately disease relapse is very common and patients may become refractory to previous drugs. Therefore, new therapeutic strategies are urgently needed. Areas covered. We have reviewed the available data on next generation novel agents, particularly immunomodulatory drug pomalidomide and proteasome inhibitors carfilzomib and ixazomib, the latter being the first-in-class orally available...
November 29, 2016: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/27890933/preclinical-activity-of-cpi-0610-a-novel-small-molecule-bromodomain-and-extra-terminal-protein-inhibitor-in-the-therapy-of-multiple-myeloma
#4
K T Siu, J Ramachandran, A J Yee, H Eda, L Santo, C Panaroni, J A Mertz, R J Sims, M R Cooper, N Raje
Inhibition of the bromodomain and extra-terminal (BET) proteins is a promising therapeutic strategy for various hematologic cancers. Previous studies suggest that BET inhibitors constrain tumor cell proliferation and survival mainly through suppression of MYC transcription and activity. However, suppression of the transcription of additional genes also contributes to the anti-tumor activity of BET inhibitors but is less well understood. Here we examined the therapeutic potential of CPI-0610, a potent BET inhibitor currently undergoing Phase I clinical testing, in multiple myeloma (MM)...
November 28, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27873264/current-trends-and-alternative-scenarios-in-ebv-research
#5
Janos Minarovits, Hans Helmut Niller
Epstein-Barr virus (EBV) infection is associated with several distinct hematological and epithelial malignancies, e.g., Burkitt lymphoma, Hodgkin lymphoma, nasopharyngeal carcinoma, gastric carcinoma, and others. The association with several malignant tumors of local and worldwide distribution makes EBV one of the most important tumor viruses. Furthermore, because EBV can cause posttransplant lymphoproliferative disease, transplant medicine has to deal with EBV as a major pathogenic virus second only to cytomegalovirus...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27872496/inactivation-of-klf4-promotes-t-cell-acute-lymphoblastic-leukemia-and-activates-the-map2k7-pathway
#6
Y Shen, C S Park, K Suppipat, T-A Mistretta, M Puppi, T Horton, K Rabin, N S Gray, J P P Meijerink, H D Lacorazza
T cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy with a high incidence of relapse in pediatric ALL. Although most T-ALL patients exhibit activating mutations in NOTCH1, the cooperating genetic events required to accelerate the onset of leukemia and worsen disease progression are largely unknown. Here, we show that the gene encoding the transcription factor KLF4 is inactivated by DNA methylation in children with T-ALL. In mice, loss of KLF4 accelerated the development of NOTCH1-induced T-ALL by enhancing the G1-to-S transition in leukemic cells and promoting the expansion of leukemia-initiating cells...
November 22, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27865176/adoptive-immunotherapy-for-hematological-malignancies-current-status-and-new-insights-in-chimeric-antigen-receptor-t-cells
#7
REVIEW
Alessandro Allegra, Vanessa Innao, Demetrio Gerace, Doriana Vaddinelli, Caterina Musolino
Hematological malignancies frequently express cancer-associated antigens that are shared with normal cells. Such tumor cells elude the host immune system because several T cells targeted against self-antigens are removed during thymic development, and those that persist are eliminated by a regulatory population of T cells. Chimeric antigen receptor-modified T cells (CAR-Ts) have emerged as a novel modality for tumor immunotherapy due to their powerful efficacy against tumor cells. These cells are created by transducing genes-coding fusion proteins of tumor antigen-recognition single-chain Fv connected to the intracellular signaling domains of T cell receptors, and are classed as first-, second- and third-generation, differing on the intracellular signaling domain number of T cell receptors...
November 2016: Blood Cells, Molecules & Diseases
https://www.readbyqxmd.com/read/27859015/hla-e-allelic-genotype-correlates-with-hla-e-plasma-levels-and-predicts-early-progression-in-chronic-lymphocytic-leukemia
#8
Bettina Wagner, Fabiola da Silva Nardi, Sabine Schramm, Thomas Kraemer, Alexander A Celik, Jan Dürig, Peter A Horn, Ulrich Dührsen, Holger Nückel, Vera Rebmann
BACKGROUND: Human leukocyte antigen-E (HLA-E) is a nonclassical major histocompatibility complex class I molecule that recently came into sharper focus as a putative marker of advanced tumor stages and disease progression. In solid tumors, increased HLA-E expression as well as elevated soluble HLA-E (sHLA-E) plasma levels are associated with a poor prognosis; however, a role for HLA-E in hematologic malignancies remains to be established. METHODS: The authors analyzed HLA-E alleles and sHLA-E levels in a cohort of 110 individuals with chronic lymphocytic leukemia (CLL)...
November 2, 2016: Cancer
https://www.readbyqxmd.com/read/27843137/pi3k%C3%AE-inhibition-elicits-anti-leukemic-effects-through-bim-dependent-apoptosis
#9
M J Carter, K L Cox, S J Blakemore, A H Turaj, R J Oldham, L N Dahal, S Tannheimer, F Forconi, G Packham, M S Cragg
PI3Kδ plays pivotal roles in the maintenance, proliferation, and survival of malignant B-lymphocytes. Although not curative, PI3Kδ inhibitors (PI3Kδi) demonstrate impressive clinical efficacy and, alongside other signaling inhibitors, are revolutionizing the treatment of hematological malignancies. However, only limited in vivo data are available regarding their mechanism of action. With the rising number of novel treatments, the challenge is to identify combinations that deliver curative regimes. A deeper understanding of the molecular mechanism is required to guide these selections...
November 15, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27842666/simplified-response-monitoring-criteria-for-multiple-myeloma-in-patients-undergoing-therapy-with-novel-agents-using-computed-tomography
#10
Christoph Schabel, Marius Horger, Sara Kum, Katja Weisel, Jan Fritz, Sorin D Ioanoviciu, Georg Bier
INTRODUCTION: Multiple myeloma is a malignant hematological disorder of the mature B-cell lymphocytes originating in the bone marrow. While therapy monitoring is still mainly based on laboratory biomarkers, the additional use of imaging has been advocated due to inaccuracies of serological biomarkers or in a-secretory myelomas. Non-enhanced CT and MRI have similar sensitivities for lesions in yellow marrow-rich bone marrow cavities with a favourable risk and cost-effectiveness profile of CT...
December 2016: European Journal of Radiology
https://www.readbyqxmd.com/read/27830572/inflammation-associated-co-morbidity-between-depression-and-cardiovascular-disease
#11
Angelos Halaris
Morbidity and mortality of cardiovascular disease (CVD) is exceedingly high worldwide. Depressive illness is a serious psychiatric illness that afflicts a significant portion of the world population. Epidemiological studies have confirmed the high co-morbidity between these two disease entities. The co-morbidity is bidirectional and the mechanisms responsible for it are complex and multifaceted. In addition to genetic, biological systems, psychosocial, and behavioral factors that are involved include the central and autonomic nervous systems, the neuroendocrine, immune, and the vascular and hematologic systems...
November 10, 2016: Current Topics in Behavioral Neurosciences
https://www.readbyqxmd.com/read/27830540/multifaceted-role-of-the-polycomb-group-gene-ezh2-in-hematological-malignancies
#12
REVIEW
Goro Sashida, Atsushi Iwama
Polycomb repressive complex (PRC) is a critical regulator of normal tissue homeostasis as well as tumorigenesis. EZH2, an enzymatic subunit of PRC2, is a histone H3K27 methyltransferase that functions in the regulation of gene silencing. EZH2 overexpression was first identified in prostate and breast cancers and is associated with poor clinical outcome. Subsequently, gain- and loss-of-function mutations of EZH2 have been identified in various tumors, including hematological malignancies, implicating EZH2 as either an oncogene or a tumor suppressor gene, depending on the cancer type...
November 9, 2016: International Journal of Hematology
https://www.readbyqxmd.com/read/27822872/constitutive-expression-of-inducible-cyclic-adenosine-monophosphate-early-repressor-icer-in-cycling-quiescent-hematopoietic-cells-implications-for-aging-hematopoietic-stem-cells
#13
Steven J Greco, Ghassan Yehia, Julius A Potian, Carlos A Molina, Pranela Rameshwar
Despite extensive insights on the interaction between hematopoietic stem cells (HSCs) and the supporting bone marrow (BM) stroma in hematopoietic homeostasis there remains unanswered questions on HSC regulation. We report on the mechanism by which HSCs attain cycling quiescence by addressing a role for inducible cyclic AMP early repressor (ICER). ICER negatively transcriptional regulators of cAMP activators such as CREM and CREB. These activators can be induced by hematopoietic stimulators such as cytokines...
November 8, 2016: Stem Cell Reviews
https://www.readbyqxmd.com/read/27807492/novel-brentuximab-vedotin-combination-therapies-show-promising-activity-in-highly-refractory-cd30-non-hodgkin-lymphoma-a-case-series-and-review-of-the-literature
#14
Wilfred Delacruz, Robert Setlik, Arash Hassantoufighi, Shyam Daya, Susannah Cooper, Dale Selby, Alexander Brown
Non-Hodgkin lymphomas (NHLs) are a heterogeneous group of hematologic malignancies which typically respond to standard first-line chemoimmunotherapy regimens. Unfortunately, patients with refractory NHL face a poor prognosis and represent an unmet need for improved therapeutics. We present two cases of refractory CD30+ NHL who responded to novel brentuximab vedotin- (BV-) based regimens. The first is a patient with stage IV anaplastic large cell lymphoma (ALCL) with cranial nerve involvement who failed front-line treatment with cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone (CHOEP) and second line cyclophosphamide, vincristine, doxorubicin, dexamethasone alternating with high-dose methotrexate (MTX), and cytarabine (hyperCVAD) with intrathecal- (IT-) MTX and IT-cytarabine, but responded when BV was substituted for vincristine (hyperCBAD)...
2016: Case Reports in Oncological Medicine
https://www.readbyqxmd.com/read/27806947/the-chromatin-associated-sin3b-protein-is-required-for-hematopoietic-stem-cell-functions-in-mice
#15
David J Cantor, Gregory David
Hematopoietic stem cells (HSCs) reside at the top of the hematopoietic hierarchy and are the origin of all blood cells produced throughout an individual's life. The balance between HSC self-renewal and differentiation is maintained by various intrinsic and extrinsic mechanisms. Among these, the molecular pathways that restrict cell cycle progression are critical to the maintenance of functional HSCs. Alterations in the regulation of cell cycle progression in HSCs invariably lead to the development of hematologic malignancies or bone marrow failure syndromes...
November 2, 2016: Blood
https://www.readbyqxmd.com/read/27798847/epigenetics-of-hematopoiesis-and-hematological-malignancies
#16
REVIEW
Deqing Hu, Ali Shilatifard
Hematological malignancies comprise a diverse set of lymphoid and myeloid neoplasms in which normal hematopoiesis has gone awry and together account for ∼10% of all new cancer cases diagnosed in the United States in 2016. Recent intensive genomic sequencing of hematopoietic malignancies has identified recurrent mutations in genes that encode regulators of chromatin structure and function, highlighting the central role that aberrant epigenetic regulation plays in the pathogenesis of these neoplasms. Deciphering the molecular mechanisms for how alterations in epigenetic modifiers, specifically histone and DNA methylases and demethylases, drive hematopoietic cancer could provide new avenues for developing novel targeted epigenetic therapies for treating hematological malignancies...
September 15, 2016: Genes & Development
https://www.readbyqxmd.com/read/27795512/how-has-the-management-of-ph-acute-lymphoblastic-leukemia-all-changed-over-the-years
#17
Sabina Chiaretti, Robin Foà
For decades, Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL) has been considered the ALL subgroup with the worse outcome. It represents the most frequent genetic subtype of adult ALL and, in the elderly, it accounts for approximately 50% of cases. The introduction of tyrosine kinase inhibitors (TKIs) has led to obtain complete hematologic remissions (CHR) in virtually all patients, to improve disease-free survival and overall survival, and to increase the percentage of patients who can undergo an allogeneic stem cell transplant (allo-SCT)...
2016: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/27793034/therapeutic-efficacy-of-the-bromodomain-inhibitor-otx015-mk-8628-in-alk-positive-anaplastic-large-cell-lymphoma-an-alternative-modality-to-overcome-resistant-phenotypes
#18
Michela Boi, Maria Todaro, Valentina Vurchio, Shao Ning Yang, John Moon, Ivo Kwee, Andrea Rinaldi, Heng Pan, Ramona Crescenzo, Mangeng Cheng, Leandro Cerchietti, Olivier Elemento, Maria E Riveiro, Esteban Cvitkovic, Francesco Bertoni, Giorgio Inghirami
Anaplastic large cell lymphomas (ALCL) represent a peripheral T-cell lymphoma subgroup, stratified based on the presence or absence of anaplastic lymphoma kinase (ALK) chimeras. Although ALK-positive ALCLs have a more favorable outcome than ALK-negative ALCL, refractory and/or relapsed forms are common and novel treatments are needed. Here we investigated the therapeutic potential of a novel bromodomain inhibitor, OTX015/MK-8628 in ALK-positive ALCLs.The effects of OTX015 on a panel of ALK+ ALCL cell lines was evaluated in terms of proliferation, cell cycle and downstream signaling, including gene expression profiling analyses...
October 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27767376/pharmacogenomics-and-histone-deacetylase-inhibitors
#19
Andrew Kl Goey, Tristan M Sissung, Cody J Peer, William D Figg
The histone deacetylase inhibitor valproic acid (VPA) has been used for many decades in neurology and psychiatry. The more recent introduction of the histone deacetylase inhibitors (HDIs) belinostat, romidepsin and vorinostat for treatment of hematological malignancies indicates the increasing popularity of these agents. Belinostat, romidepsin and vorinostat are metabolized or transported by polymorphic enzymes or drug transporters. Thus, genotype-directed dosing could improve pharmacotherapy by reducing the risk of toxicities or preventing suboptimal treatment...
October 21, 2016: Pharmacogenomics
https://www.readbyqxmd.com/read/27766226/nf-k%C3%AE-activation-in-u266-cells-on-mesenchymal-stem-cells
#20
Sara Zahedi, Karim Shamsasenjan, Aliakbar Movassaghpour, Parvin Akbarzadehlaleh
Purpose: Mesenchymal Stem Cells (MSCs) are one of the essential members of Bone Marrow (BM) microenvironment and the cells affect normal and malignant cells in BM milieu. One of the most important hematological malignancies is Multiple Myeloma (MM). Numerous studies reported various effects of MSCs on myeloma cells. MSCs initiate various signaling pathways in myeloma cells, particularly NF-kβ. NF-kβ signaling pathway plays pivotal role in the survival, proliferation and resistance of myeloma cells to the anticancer drugs, therefore this pathway can be said to be a vital target for cancer therapy...
September 2016: Advanced Pharmaceutical Bulletin
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