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https://www.readbyqxmd.com/read/29049036/histone-deacetylase-inhibitor-bg45-mediated-ho-1-expression-induces-apoptosis-of-multiple-myeloma-cells-by-the-jak2-stat3-pathway
#1
Sishi Tang, Bingqing Cheng, Nana Zhe, Dan Ma, Jibing Xu, Xinyao Li, Yongling Guo, Weibing Wu, Jishi Wang
Multiple myeloma (MM) is a hematological malignancy that is characterized by the clonal expansion of plasma cells in the bone marrow. Histone deacetylases (HDACs) represent a new type of molecular targeted therapy for different types of cancers and promising targets for myeloma therapy. We showed that HDAC3 mRNA and protein levels of CD138 mononuclear cells from MM patients were higher than those in healthy donors. Therefore, we investigated the effects of a novel class I HDAC inhibitor BG45 on MM cells in vitro...
October 18, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/29034009/a-multicenter-randomized-study-of-decitabine-as-epigenetic-priming-with-induction-chemotherapy-in-children-with-aml
#2
Lia Gore, Timothy J Triche, Jason E Farrar, Daniel Wai, Christophe Legendre, Gerald C Gooden, Winnie S Liang, John Carpten, David Lee, Frank Alvaro, Margaret E Macy, Carola Arndt, Philip Barnette, Todd Cooper, Laura Martin, Aru Narendran, Jessica Pollard, Soheil Meshinchi, Jessica Boklan, Robert J Arceci, Bodour Salhia
BACKGROUND: Decitabine is a deoxycytidine nucleoside derivative inhibitor of DNA-methyltransferases, which has been studied extensively and is approved for myelodysplastic syndrome in adults but with less focus in children. Accordingly, we conducted a phase 1 multicenter, randomized, open-label study to evaluate decitabine pre-treatment before standard induction therapy in children with newly diagnosed AML to assess safety and tolerability and explore a number of biologic endpoints. RESULTS: Twenty-four patients were fully assessable for all study objectives per protocol (10 in Arm A = epigenetic priming induction, 14 in Arm B = standard induction)...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/29033940/pi3k%C3%AE-inhibition-enhances-the-antitumor-fitness-of-adoptively-transferred-cd8-t-cells
#3
Jacob S Bowers, Kinga Majchrzak, Michelle H Nelson, Bulent Arman Aksoy, Megan M Wyatt, Aubrey S Smith, Stefanie R Bailey, Lillian R Neal, Jeffrey E Hammerbacher, Chrystal M Paulos
Phosphatidylinositol-3-kinase p110δ (PI3Kδ) inhibition by Idelalisib (CAL-101) in hematological malignancies directly induces apoptosis in cancer cells and disrupts immunological tolerance by depleting regulatory T cells. Yet, little is known about the direct impact of PI3Kδ blockade on effector T cells from CAL-101 therapy. Herein, we demonstrate a direct effect of p110δ inactivation via CAL-101 on murine and human CD8(+) T cells that promotes a strong undifferentiated phenotype (elevated CD62L/CCR7, CD127, and Tcf7)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29032274/assessment-of-impact-of-human-leukocyte-antigen-hla-type-on-outcomes-of-allogeneic-hematopoietic-stem-cell-transplant-for-chronic-lymphocytic-leukemia-cll
#4
Brian T Hill, Kwang Woo Ahn, Zhen-Huan Hu, Mahmoud Aljurf, Amer Beitinjaneh, Jean-Yves Cahn, Jan Cerny, Mohamed A Kharfan-Dabaja, Siddhartha Ganguly, Nilanjan Ghosh, Michael R Grunwald, Yoshihiro Inamoto, Tamila Kindwall-Keller, Taiga Nishihori, Richard F Olsson, Ayman Saad, Matthew Seftel, Sachiko Seo, Jeffrey Szer, Martin Tallman, Celalettin Ustun, Peter H Wiernik, Richard T Maziarz, Matt Kalaycio, Edwin Alyea, Uday Popat, Ronald Sobecks, Wael Saber
Chronic lymphocytic leukemia (CLL) is a common hematologic malignancy with many highly effective therapies. Chemorefractory disease, often characterized by deletion of chromosome 17p, has historically been associated with very poor outcomes, leading to the application of allogeneic hematopoietic stem cell transplant (allo-HCT) for medically fit patients. Although the use of allo-HCT has reduced since the introduction of novel targeted therapy for the treatment of CLL, there remains significant interest in understanding factors that may influence the efficacy of allo-HCT as it represents the only known curative treatment for CLL...
October 12, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29025591/identification-of-a-novel-csf3r-sptan1-fusion-gene-in-an-atypical-chronic-myeloid-leukemia-patient-with-t-1-9-p34-q34-by-rna-seq
#5
Guangying Sheng, Jian Zhang, Zhao Zeng, Jinlan Pan, Qinrong Wang, Lijun Wen, Yang Xu, Depei Wu, Suning Chen
Membrane-proximal and truncated mutations of colony-stimulating factor 3 receptor (CSF3R) are frequently found in chronic neutrophilic leukemia (CNL) and atypical chronic myeloid leukemia (aCML). However, rearrangement involving CSF3R in hematological neoplasms has not been reported. Here, we report a case of a 21-year-old female diagnosed as aCML with t(1;9)(p34;q34) who presented a CSF3R rearrangement. First, RNA sequencing identified a novel fusion transcript involving exon 17 of CSF3R and exon 50 of non-erythrocytic-1-spectrin-alpha (SPTAN1)...
October 2017: Cancer Genetics
https://www.readbyqxmd.com/read/29025266/the-abcs-of-immunotherapy-for-adult-patients-with-b-cell-acute-lymphoblastic-leukemia
#6
Troy Z Horvat, Amanda N Seddon, Adebayo Ogunniyi, Amber C King, Larry W Buie, Ryan J Daley
OBJECTIVE: To review the pharmacology, efficacy, and safety of Food and Drug Administration approved and promising immunotherapy agents used in the treatment of acute lymphoblastic leukemia (ALL). DATA SOURCES: A literature search was performed of PubMed and MEDLINE databases (1950 to July 2017) and of abstracts from the American Society of Hematology and the American Society of Clinical Oncology. Searches were performed utilizing the following key terms: rituximab, blinatumomab, inotuzumab, ofatumumab, obinutuzumab, Blincyto, Rituxan, Gazyva, Arzerra, CAR T-cell, and chimeric antigen receptor (CAR)...
October 1, 2017: Annals of Pharmacotherapy
https://www.readbyqxmd.com/read/28991373/novel-enriched-pathways-in-superficial-malignant-peripheral-nerve-sheath-tumors-mpnst-and-spindle-desmoplastic-melanomas-sdm
#7
George Jour, Nicole K Andeen, Rami Al -Rohil, Phyu P Aung, Meenakshi Mehrotra, Dzifa Duose, Benjamin Hoch, Zolt Argenyi, Rajyalakshmi Luthra, Ignacio I Wistuba, Victor G Prieto
Superficial malignant peripheral nerve sheath tumor (MPNST) is a rare, soft tissue neoplasm that shares morphological features and some molecular events with spindle and desmoplastic melanoma (SDM). Herein we sought to identify molecular targets for therapy using targeted RNA/DNA sequencing and gene expression of key immunological players. DNA and RNA from formalin-fixed, paraffin-embedded (FFPE) tissue were extracted and processed. Massive high-throughput deep parallel sequencing was performed using the Oncomine comprehensive panel enabling detection of relevant SNVs, CNVs, gene fusions, and indels from 143 unique genes on the Ion torrent sequencer for clinical trial research programs...
October 9, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28990505/biological-therapy-of-hematologic-malignancies-toward-a-chemotherapy-free-era
#8
Pavel Klener, Tomas Etrych, Pavel Klener
Less than 70 years ago, the vast majority of hematologic malignancies were untreatable diseases with fatal prognoses. The development of modern chemotherapy agents, which had begun after the Second World War, was markedly accelerated by the discovery of the structure of DNA and its role in cancer biology and tumor cell division. The path travelled from the first temporary remissions observed in children with acute lymphoblastic leukemia treated with single-agent antimetabolites until the first cures achieved by multi-agent chemotherapy regimens was incredibly short...
October 6, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28985203/cell-therapy-for-diverse-central-nervous-system-disorders-inherited-metabolic-diseases-and-autism
#9
REVIEW
Jessica M Sun, Joanne Kurtzberg
The concept of utilizing human cells for the treatment of medical conditions is not new. In its simplest form, blood product transfusion as treatment of severe hemorrhage has been practiced since the 1800s. The advent of hematopoietic stem cell transplantation (HSCT) began with the development of bone marrow transplantation for hematologic malignancies in the mid-1900s and is now standard of care for many hematologic disorders. In the past few decades, HSCT has expanded to additional sources of donor cells, a wider range of indications, and the development of novel cell products...
October 6, 2017: Pediatric Research
https://www.readbyqxmd.com/read/28977984/driving-better-and-safer-her2-specific-cars-for-cancer-therapy
#10
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...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28960447/jak1-2-inhibitors-azd1480-and-cyt387-inhibit-canine-b-cell-lymphoma-growth-by-increasing-apoptosis-and-disrupting-cell-proliferation
#11
Z Lu, C C Hong, P C Jark, A L F V Assumpção, N Bollig, G Kong, X Pan
BACKGROUND: Canine diffuse large B-cell lymphoma (DLBCL) is a common and aggressive hematologic malignancy. The lack of conventional therapies with sustainable efficacy warrants further investigation of novel therapeutics. The Janus kinase (JAK) and signal transducer and activator of transcription (STAT) pathways play important roles in the pathogenesis of hematologic malignancies in humans including DLBCLs. AZD1480 and CYT387 are novel JAK1/2 inhibitors that have been used in clinical trials for treating various hematologic cancers in humans...
September 27, 2017: Journal of Veterinary Internal Medicine
https://www.readbyqxmd.com/read/28955654/the-role-of-novel-immunotherapies-in-non-hodgkin-lymphoma
#12
Allyson Pishko, Sunita D Nasta
Immunotherapy is an evolving modality in the treatment of non-Hodgkin lymphoma. Vaccinations with patient-specific tumor-derived antigens have been developed to strengthen immune response to tumor. The success of rituximab, a monoclonal antibody for CD20 on malignant B-cells, fueled further immunotherapy research. The power of the immune system to fight hematologic malignancies is seen in allogeneic stem cell transplant, where donor T cells attack residual malignant cells in the recipient. Now, three innovative therapeutic immunotherapy classes (I) adoptive cellular therapy; (II) immune-checkpoint inhibitors; and (III) novel antibody therapies show promising results in non-Hodgkin lymphoma...
February 2017: Translational Cancer Research
https://www.readbyqxmd.com/read/28948521/contemporary-use-of-interferon-therapy-in-the-myeloproliferative-neoplasms
#13
REVIEW
Charles Elliott Foucar, Brady Lee Stein
PURPOSE OF REVIEW: The purpose of this article is to review the current evidence behind interferon therapy in patients with myeloproliferative neoplasms. RECENT FINDINGS: Preliminary analysis suggests that interferon may be non-inferior to hydroxyurea in patients with polycythemia vera and essential thrombocytosis. Responses have been observed regardless of JAK2 mutational status, but the presence of non-JAK2 somatic mutations may negatively influence response rates...
September 25, 2017: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/28947503/the-dna-repair-inhibitor-dbait-is-specific-for-malignant-hematologic-cells-in-blood
#14
Sylvain Thierry, Wael Jdey, Solana Alculumbre, Vassili Soumelis, Patricia Noguiez-Hellin, Marie Dutreix
Hematologic malignancies are rare cancers that develop refractory disease upon patient relapse, resulting in decreased life expectancy and quality of life. DNA repair inhibitors are promising strategy to treat cancer but are limited by their hematologic toxicity in combination with conventional chemotherapies. Dbait are large molecules targeting the signaling of DNA damage and inhibiting all the double-strand DNA break pathways. Dbait have been shown to sensitize resistant solid tumors to radiotherapy and Platinium salts...
September 25, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28931402/recent-advances-of-bispecific-antibodies-in-solid-tumors
#15
REVIEW
Shengnan Yu, Anping Li, Qian Liu, Xun Yuan, Hanxiao Xu, Dechao Jiao, Richard G Pestell, Xinwei Han, Kongming Wu
Cancer immunotherapy is the most exciting advancement in cancer therapy. Similar to immune checkpoint blockade and chimeric antigen receptor T cell (CAR-T), bispecific antibody (BsAb) is attracting more and more attention as a novel strategy of antitumor immunotherapy. BsAb not only offers an effective linkage between therapeutics (e.g., immune effector cells, radionuclides) and targets (e.g., tumor cells) but also simultaneously blocks two different oncogenic mediators. In recent decades, a variety of BsAb formats have been generated...
September 20, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28927824/cellular-therapy-for-multiple-pathogen-infections-after-hematopoietic-stem-cell-transplant
#16
REVIEW
Gaurav Sutrave, Emily Blyth, David J Gottlieb
Hematopoietic stem cell transplantation (HSCT) represents the only crative treatment option for many hematological conditions but results in a profound T-cell deficiency in the post-HSCT period. Infections account for a significant proportion of non-relapse morbidity and mortality, and infections with multiple organisms either simultaneously or at different times after transplant are common. Adoptive cellular therapy (ACT) with prophylactic or therapeutic infusion of donor derived or third-party, pathogen-specific T-cells represents a novel methodology to rapidly reconstitute T-cell mediated immunity in this context...
September 15, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28918995/cutaneous-adverse-events-of-targeted-therapies-for-hematolymphoid-malignancies
#17
REVIEW
Julia D Ransohoff, Bernice Y Kwong
The identification of oncogenic drivers of liquid tumors has led to the rapid development of targeted agents with distinct cutaneous adverse event (AE) profiles. The diagnosis and management of these skin toxicities has motivated a novel partnership between dermatologists and oncologists in developing supportive oncodermatology clinics. In this article we review the current state of knowledge of clinical presentation, mechanisms, and management of the most common and significant cutaneous AEs observed during treatment with targeted therapies for hematologic and lymphoid malignancies...
July 14, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28915592/targeted-alpha-therapy-using-a-novel-cd70-targeted-thorium-227-conjugate-in-in-vitro-and-in-vivo-models-of-renal-cell-carcinoma
#18
Urs B Hagemann, Dessislava Mihaylova, Steinar R Uran, Joergen Borrebaek, Derek Grant, Roger M Bjerke, Jenny Karlsson, Alan S Cuthbertson
The cell surface receptor CD70 has been previously reported as a promising target for B-cell lymphomas and several solid cancers including renal cell carcinoma. We describe herein the characterization and efficacy of a novel CD70 targeted thorium-227 conjugate (CD70-TTC) comprising the combination of the three components, a CD70 targeting antibody, a chelator moiety and the short-range, high-energy alpha-emitting radionuclide thorium-227 ((227)Th). In vitro analysis demonstrated that the CD70-TTC retained binding affinity to its target and displayed potent and specific cytotoxicity compared to an isotype control-TTC...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915005/a-novel-type-of-aqueous-dispersible-ultrathin-layered-double-hydroxide-nanosheets-for-in-vivo-bioimaging-and-drug-delivery
#19
Li Yan, Mengjiao Zhou, Xiujuan Zhang, Longbiao Huang, Wei Chen, Vellaisamy A L Roy, Wenjun Zhang, Xianfeng Chen
Layered double hydroxide (LDH) nanoparticles have been widely used for various biomedical applications. However, because of the difficulty of surface functionalization of LDH nanoparticles, the systemic administration of these nanomaterials for in vivo therapy remains a bottleneck. In this work, we develop a novel type of aqueous dispersible two-dimensional ultrathin LDH nanosheets with a size of about 50 nm and a thickness of about 1.4 to 4 nm. We are able to covalently attach positively charged rhodamine B fluorescent molecules to the nanosheets, and the nanohybrid retains strong fluorescence in liquid and even dry powder form...
October 4, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28914194/diabetic-retinopathy-recent-updates-on-different-biomarkers-and-some-therapeutic-agents
#20
Amjad Ali Khan, Arshad Husain Rahmani, Yousef Homood Aldebasi
BACKGROUND: Diabetic Retinopathy is a leading cause of sight-threatening complication, which occurs due to a number of physiological and metabolic abnormalities during later stages of diabetes. Many of these abnormal changes are consistent with altered oxidative stress, inflammation, genetic set up, advanced glycation end products, and hematological changes. So the altered levels of different biomolecules related to these changes serve as important biomarkers to assess better evaluation and early treatment of this disease...
September 15, 2017: Current Diabetes Reviews
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