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https://www.readbyqxmd.com/read/29781323/targeting-the-b-cell-receptor-pathway-a-review-of-current-and-future-therapies-for-non-hodgkin-s-lymphoma
#1
Thomas D Rodgers, Patrick M Reagan
The B-cell receptor (BCR) pathway is a crucial aspect of mature lymphocytes and is maintained in B-cell neoplasms. Many small module inhibitors targeting kinases within the BCR pathway are approved, with others in development, offering alternative treatment options to standard chemoimmunotherapy. Areas Covered: This review covers both approved inhibitors and investigational inhibitors of spleen tyrosine kinase (SYK), Bruton's tyrosine kinase (BTK), and phosphoinositide-3-kinase (PI3K) in the treatment of B-cell lymphomas...
May 20, 2018: Expert Opinion on Emerging Drugs
https://www.readbyqxmd.com/read/29780814/targeting-chronic-myeloid-leukemia-stem-cells-can-transcriptional-program-be-a-druggable-target-for-cancers
#2
REVIEW
Yosuke Masamoto, Mineo Kurokawa
Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm resulting from acquisition of constitutively active BCR-ABL protein tyrosine kinase in a hematopoietic stem cell (HSC). Though tyrosine kinase inhibitors (TKIs) have changed a fatal disease into manageable disease, most patients cannot discontinue TKI treatment due to persistence of TKI-resistant leukemia stem cells (LSCs). Much effort has been made to find out factors or pathways specifically operating in LSCs to selectively target LSCs, with some promising results at least in preclinical models...
2018: Stem Cell Investigation
https://www.readbyqxmd.com/read/29779329/-mechanisms-of-recombinant-adenovirus-mediated-sd-ha-fusion-protein-proliferation-inhibition-and-induced-apoptosis-of-k562-cells
#3
Y Huang, P Zhang, L Du, M Gui, W L Feng, Z Peng
Objective: To investigate whether fusion protein SD-HA could regulate its downstream signaling molecule activity by competing with the phospho-BCR-ABL Y177 site, and its mechanisms to inhibit proliferation and induce apoptosis of K562 cells. Methods: Co-immunoprecipitation interaction technology analysis of fusion protein SD-HA functioned by potently binding to the phospho-BCR-ABL Y177 site, Ras, MAPK and Akt activities were observed in the Ad5F35-SD-HA-treated cells. Western blot analyses of SD-HA fusion protein on cell membrane receptor pathway to death cascade caspase-8, caspase-3 and PRAP were performed...
April 14, 2018: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/29779140/knee-motion-symmetry-was-not-restored-in-patients-with-unilateral-bi-cruciate-retaining-total-knee-arthroplasty-in-vivo-three-dimensional-kinematic-analysis
#4
Paul Arauz, Yun Peng, Young-Min Kwon
PURPOSE: Although unilateral total knee arthroplasty (TKA) is successful in restoring function, there are concerns in relation to asymmetric gait patterns. Bi-cruciate retaining (BCR) TKA design preserves both anterior and posterior cruciate ligaments with the potential to restore normal joint kinematics. The purpose of this study was to investigate the in vivo three-dimensional (3D) kinematics of the knee in unilateral BCR TKA patients during gait. METHODS: Twenty-nine unilateral BCR TKA patients were evaluated for both knees during treadmill gait using a combined computer tomography and dual fluoroscopic imaging system approach...
May 19, 2018: International Orthopaedics
https://www.readbyqxmd.com/read/29774664/the-lupus-associated-fc%C3%AE-riib-i232t-polymorphism-results-in-impairment-in-the-negative-selection-of-low-affinity-germinal-center-b-cells-via-c-abl
#5
Jyun-Pei Jhou, I-Shing Yu, Haw Hwai, Chih-Shan Chen, Pei-Lung Chen, Shiang-Jong Tzeng
OBJECTIVE: FcγRIIB is an essential negative regulator of B cells to block BCR signaling and to trigger c-Abl-dependent apoptosis of B cells. FcγRIIB-deficient mice display splenomegaly with expansion of B cells, leading to lupus. FcγRIIB-I232T is a hypo-functional polymorphism associated with lupus susceptibility in humans, an autoimmune disease linked to diminished deletion of autoreactive B cells. In the context of FcγRIIB-I232T polymorphism, we investigated the role of FcγRIIB in the deletion of low-affinity germinal center (GC) B cells, an important mechanism for preventing autoimmunity...
May 17, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29774100/differential-proteomic-profile-of-leukemic-cd34-progenitor-cells-from-chronic-myeloid-leukemia-patients
#6
Maria Rosaria Ricciardi, Valentina Salvestrini, Roberto Licchetta, Simone Mirabilii, Mattia Forcato, Gabriele Gugliotta, Simona Salati, Fausto Castagnetti, Gianantonio Rosti, Massimo Breccia, Giuliana Alimena, Rossella Manfredini, Silvio Bicciato, Roberto Massimo Lemoli, Agostino Tafuri
Chronic Myeloid Leukemia (CML) is a stem cell disease sustained by a rare population of quiescent cells which are to some extent resistant to tyrosine kinase inhibitors (TKIs). BCR-ABL oncogene activates multiple cross-talking signal transduction pathways (STP), such as RAS/MEK/ERK, PI3K/Akt, Wnt and STAT5, contributing to abnormal proliferation of clonal cells. From this perspective, the aim of this study was to analyze the expression and activation profile of STP involved in the mechanisms of cell proliferation/quiescence and survival of the progenitor CD34+ cells from chronic phase (CP) CML...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29772458/phenotyping-and-target-expression-profiling-of-cd34-cd38-and-cd34-cd38-stem-and-progenitor-cells-in-acute-lymphoblastic-leukemia
#7
Katharina Blatt, Ingeborg Menzl, Gregor Eisenwort, Sabine Cerny-Reiterer, Harald Herrmann, Susanne Herndlhofer, Gabriele Stefanzl, Irina Sadovnik, Daniela Berger, Alexandra Keller, Alexander Hauswirth, Gregor Hoermann, Michael Willmann, Thomas Rülicke, Heinz Sill, Wolfgang R Sperr, Christine Mannhalter, Junia V Melo, Ulrich Jäger, Veronika Sexl, Peter Valent
Leukemic stem cells (LSCs) are an emerging target of curative anti-leukemia therapy. In acute lymphoblastic leukemia (ALL), LSCs frequently express CD34 and often lack CD38. However, little is known about markers and targets expressed in ALL LSCs. We have examined marker- and target expression profiles in CD34+ /CD38- LSCs in patients with Ph+ ALL (n = 22) and Ph- ALL (n = 27) by multi-color flow cytometry and qPCR. ALL LSCs expressed CD19 (B4), CD44 (Pgp-1), CD123 (IL-3RA), and CD184 (CXCR4) in all patients tested...
May 14, 2018: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29771636/subcellular-topography-modulates-actin-dynamics-and-signaling-in-b-cells
#8
Christina M Ketchum, Xiaoyu Sun, Alexandra Suberi, John T Fourkas, Wenxia Song, Arpita Upadhyaya
B cell signaling activation is most effectively triggered by the binding of B cell receptors (BCRs) to membrane-bound antigens.  In vivo, B cells encounter antigen on antigen presenting cells (APC), which possess complex surfaces with convoluted topographies, a fluid membrane and deformable cell bodies. However, whether and how the physical properties of antigen presentation affect B cell activation is not well understood. Here, we use nanotopographic surfaces that allow systematic variation of geometric parameters to show that surface features on a subcellular scale influence B cell signaling and actin dynamics...
May 17, 2018: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29769313/a-catalytically-versatile-benzoyl-coa-reductase-key-enzyme-in-the-degradation-of-methyl-and-halobenzoates-in-denitrifying-bacteria
#9
Oliver Tiedt, Jonathan Fuchs, Wolfgang Eisenreich, Matthias Boll
Class I benzoyl-coenzyme A (BzCoA) reductases (BCRs) are key enzymes in the anaerobic degradation of aromatic compounds. They catalyze the ATP-dependent reduction of the central BzCoA intermediate and analogues of it to conjugated cyclic 1,5-dienoyl-CoAs probably by a radical-based, Birch-like reduction mechanism. Discovered in 1995, the enzyme from the denitrifying bacterium Thauera aromatica (BCRTar ) has so far remained the only isolated and biochemically accessible BCR, mainly because BCRs are extremely labile and their heterologous production has largely failed, so far...
May 16, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29762238/diagnostic-performance-of-18f-fluciclovine-in-detection-of-prostate-cancer-bone-metastases
#10
Albert Chau, Peter Gardiner, Patrick M Colletti, Hossein Jadvar
PURPOSE: 18F-fluciclovine is a synthetic amino acid radiotracer that has recently been approved in Europe and the United States for PET imaging in men with biochemical recurrence (BCR) of prostate cancer after prior definitive treatment. Accurate identification of the sites of disease in patients presenting with BCR of prostate cancer is important in determining the appropriate treatment. Bone is the most frequent site of metastatic disease in patients with prostate cancer. METHODS: We conducted a comprehensive review of the available preclinical and clinical data on the diagnostic performance of 18F-fluciclovine PET/CT in an attempt to draw practical and general conclusions on the utility and limitations of 18F-fluciclovine PET/CT in localization of osseous metastatic disease in prostate cancer...
May 14, 2018: Clinical Nuclear Medicine
https://www.readbyqxmd.com/read/29755649/evaluation-of-the-primitive-fraction-by-functional-in-vitro-assays-at-the-rna-and-dna-level-represents-a-novel-tool-for-complementing-molecular-monitoring-in-chronic-myeloid-leukemia
#11
María Sol Ruiz, María Belén Sanchez, Leandro Gutiérrez, Daniel Koile, Patricio Yankilevich, Celeste Mosqueira, Santiago Cranco, María Del Rosario Custidiano, Josefina Freitas, Cecilia Foncuberta, Beatriz Moiraghi, Carolina Pavlovsky, Mariel Ana Pérez, Verónica Ventriglia, Julio Sanchez Ávalos, José Mordoh, Irene Larripa, Michele Bianchini
Quantification of BCR-ABL1 mRNA levels in peripheral blood of chronic myeloid leukemia patients is a strong indicator of response to tyrosine-kinase inhibitors (TKI) treatment. However, additional prognostic markers are needed in order to better classify patients. The hypothesis of leukemic stem cells (LSCs) heterogeneity and persistence, suggests that their functional evaluation could be of clinical interest. In this work, we assessed the primitive and progenitor fractions in patients at diagnosis and during TKI treatment using functional in vitro assays, defining a "functional leukemic burden" (FLB)...
April 17, 2018: Oncotarget
https://www.readbyqxmd.com/read/29751004/mutations-affecting-the-actin-regulator-wdr1-lead-to-aberrant-lymphoid-immunity
#12
Laurène Pfajfer, Nina K Mair, Raúl Jiménez-Heredia, Ferah Genel, Nesrin Gulez, Ömür Ardeniz, Birgit Hoeger, Sevgi Köstel Bal, Christoph Madritsch, Artem Kalinichenko, Rico Chandra Ardy, Bengü Gerçeker, Javier Rey-Barroso, Hanna Ijspeert, Stuart G Tangye, Ingrid Simonitsch-Klupp, Johannes B Huppa, Mirjam van der Burg, Loïc Dupré, Kaan Boztug
BACKGROUND: The actin-interacting protein WDR1 promotes cofilin-dependent actin filament turnover. Biallelic WDR1 mutations have recently been identified in an immunodeficiency/autoinflammatory syndrome with aberrant morphology and function of myeloid cells. OBJECTIVE: Given the pleiotropic expression of WDR1, we here investigated to what extent it might control the lymphoid arm of the immune system in humans. METHODS: Histological and detailed immunological analyses were performed to elucidate the role of WDR1 in development and function of B and T lymphocytes...
May 8, 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29746469/cost-benefit-analysis-of-intervention-policies-for-prevention-and-control-of-brucellosis-in-india
#13
Balbir B Singh, Polychronis Kostoulas, Jatinder P S Gill, Navneet K Dhand
BACKGROUND: Brucellosis is endemic in the bovine population in India and causes a loss of US$ 3·4 billion to the livestock industry besides having a significant human health impact. METHODS: We developed a stochastic simulation model to estimate the impact of three alternative vaccination strategies on the prevalence of Brucella infection in the bovine populations in India for the next two decades: (a) annual mass vaccination only for the replacement calves and (b) vaccination of both the adult and young population at the beginning of the program followed by an annual vaccination of the replacement calves and, (c) annual mass vaccination of replacements for a decade followed by a decade of a test and slaughter strategy...
May 10, 2018: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29745343/indazoles-derivatives-promising-anti-tumor-agents
#14
Yichao Wan, Shengzhuo He, Wei Li, Zilong Tang
Currently, cancer continues being a dramatically increasing and serious threat to public health. Although many anti-tumor agents have been developed in recent years, the survival rate of patients is not satisfactory. The poor prognosis of cancer patients is closely related to the occurrence of drug resistance. Therefore, it is urgent to develop new anti-tumor agents to make up for the deficiency. Indazoles is an important class of heterocyclic compounds possessing a variety of biological activities, such as anti-tumor, anti-bacterial, anti-inflammatory, anti-depressant and anti-hypertensive...
May 9, 2018: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/29744600/temporal-and-spatial-distribution-of-trace-metals-in-the-rufiji-delta-mangrove-tanzania
#15
Andrew Minu, Joyanto Routh, Mårten Dario, Mario Bilosnic, Rikard Kalén, J Val Klump, John F Machiwa
Spatial and temporal distribution of trace metals and their cycling is a key issue for understanding the ongoing biogeochemical processes in coastal environments. Sediment cores were collected from six different sampling locations from the Rufiji delta mangrove forests in southeastern coastal Tanzania that are perceived to be impacted by urban development and agricultural activities in the catchment, and pollution in upstream sections of the Rufiji River. The chronology and sediment accumulation rates at these sampling sites were derived based on the distribution of 210 Pbexcess method...
May 9, 2018: Environmental Monitoring and Assessment
https://www.readbyqxmd.com/read/29744080/gaucher-disease-and-chronic-myeloid-leukemia-first-reported-patient-receiving-enzyme-replacement-and-tyrosine-kinase-inhibitor-therapies-simultaneously
#16
MSoledad Noya, Marcio Andrade-Campos, Pilar Irun, Laura López de Frutos, MFernanda López-Fernandez, Pilar Giraldo
Report a female diagnosed as type 1 Gaucher disease after a femoral pathologic fracture when she was 55 years old. Enzyme replacement therapy was started, and she achieved therapeutic goals. In 2015, a Ph' CML with numerous pseudo-Gaucher cells in bone marrow appears. BCR/ABL was not present at GD diagnosis.
May 2018: Clinical Case Reports
https://www.readbyqxmd.com/read/29742077/philadelphia-chromosome-positive-acute-lymphoblastic-leukemia-in-adults-current-treatments-and-future-perspectives
#17
Musa Yilmaz, Hagop Kantarjian, Farhad Ravandi-Kashani, Nicholas J Short, Elias Jabbour
Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) accounts for approximately one-fourth of cases of adult ALL. It typically presents with an aggressive clinical course, responds poorly to standard chemotherapy, and carries a high risk for relapse. The landscape of Ph+ ALL therapy has changed favorably since the development of tyrosine kinase inhibitors (TKIs). With the successful incorporation of TKIs into chemotherapy regimens, remissions occur more frequently and patients live longer...
March 2018: Clinical Advances in Hematology & Oncology: H&O
https://www.readbyqxmd.com/read/29741794/targeting-bruton-s-tyrosine-kinase-for-the-treatment-of-b-cell-associated-malignancies-and-autoimmune-diseases-preclinical-and-clinical-developments-of-small-molecule-inhibitors
#18
Zhen Zhang, Daoguang Zhang, Yang Liu, Dezhi Yang, Fansheng Ran, Michael L Wang, Guisen Zhao
B cell receptor (BCR) signaling plays a key role in B cell development and function. Aberrant BCR signaling has been confirmed as a central driver for the pathogenesis of various B cell malignancies. Bruton's tyrosine kinase (BTK) is a vital component of BCR signaling and exhibits overexpression in various B cell leukemias and lymphomas. Inhibiting BTK has been proved as an efficient way for B cell malignancy intervention. Remarkable achievements have been made in the pursuit of selective BTK inhibitors, represented by the success of the irreversible BTK inhibitors, ibrutinib and acalabrutinib...
May 9, 2018: Archiv der Pharmazie
https://www.readbyqxmd.com/read/29741513/myelofibrosis-clinicopathologic-features-prognosis-and-management
#19
Jennifer M O'Sullivan, Claire N Harrison
Myelofibrosis is one of the BCR-ABL-negative clonal disorders that collectively are known as myeloproliferative neoplasms (MPNs). It is caused by the proliferation of clonal hematopoietic stem cells, which over time leads to characteristic clinical features. The disease presentation is heterogeneous, however, with 30% of patients initially asymptomatic. This variation in clinical phenotype warrants careful risk stratification to guide appropriate management, and prognostic risk scores are continually being refined...
February 2018: Clinical Advances in Hematology & Oncology: H&O
https://www.readbyqxmd.com/read/29740430/multilayer-control-of-b-cell-activation-by-the-b-cell-antigen-receptor-following-themes-initiated-with-bill-paul
#20
REVIEW
Anthony L DeFranco
This article describes the work I did in Bill Paul's lab as a postdoctoral fellow between 1979 and 1983, and to a lesser extent puts that work in the context of other work on B cell activation and antibody responses that was going on in Bill's lab at that time and shortly beforehand, including the discovery of interleukin 4. In addition, this work describes the subsequent and continuing work in my own lab following-up on themes I began during my time working directly with Bill. A particular emphasis was on understanding the biochemical mechanisms of signaling by the B cell antigen receptor (BCR) to the interior of the B cell...
2018: Frontiers in Immunology
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