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https://www.readbyqxmd.com/read/29781255/combination-therapy-of-canine-osteosarcoma-with-canine-bone-marrow-stem-cells-bone-morphogenetic-protein-and-carboplatin-in-an-in-vivo-model
#1
R E G Rici, S E A L Will, A C L Luna, L F Melo, A C Santos, R F Rodrigues, R M Leandro, D A Maria
Osteosarcoma (OSA) is the most common malignant bone cancer in children and dogs. The therapeutic protocols adopted for dogs and humans are very similar, involving surgical options such as amputation. Besides surgical options, radiotherapy and chemotherapy also are adopted. However, hematologic, gastrointestinal and renal toxicity may occur because of chemotherapy treatments. Recent study clearly showed that mesenchymal stem cells (MSCs) combined with recombinant human bone morphogenetic protein (rhBMP-2) may be associated with decreases of the tumorigenic potential of canine OSA...
May 20, 2018: Veterinary and Comparative Oncology
https://www.readbyqxmd.com/read/29770255/a-method-for-the-interpretation-of-flow-cytometry-data-using-genetic-algorithms
#2
Cesar Angeletti
Background: Flow cytometry analysis is the method of choice for the differential diagnosis of hematologic disorders. It is typically performed by a trained hematopathologist through visual examination of bidimensional plots, making the analysis time-consuming and sometimes too subjective. Here, a pilot study applying genetic algorithms to flow cytometry data from normal and acute myeloid leukemia subjects is described. Subjects and Methods: Initially, Flow Cytometry Standard files from 316 normal and 43 acute myeloid leukemia subjects were transformed into multidimensional FITS image metafiles...
2018: Journal of Pathology Informatics
https://www.readbyqxmd.com/read/29749441/apoptosis-of-cd19-chimeric-antigen-receptor-t-cells-after-treatment-with-chemotherapeutic-agents
#3
Wenfang Yi, Fuyu Pei, Wen Ding, Mo Yang, Guang Lin, Cheng Zhang, Xuedong Wu, Yuelin He, Xiaoqin Feng, Huanying Liu, Zhiyong Peng, Chunfu Li
The use of chemotherapeutic agents prior to treatment with infusion of cluster of differentiation (CD)19-chimeric antigen receptor (CAR)‑T cells is important for the efficacy of clinical therapies against hematological malignancies. However, the effect of chemotherapeutic agents on CD19‑CAR‑T cells and the associated underlying mechanisms remain unknown. The first aim of the present study was to determine the effect of chemotherapeutic agents on CAR‑T cells using the in vitro Cell Counting kit 8 assay...
May 2, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29747746/justicia-adhatoda-induces-megakaryocyte-differentiation-through-mitochondrial-ros-generation
#4
Usha Gutti, Jaswant Kumar Komati, Aneesh Kotipalli, Raja Gopal Venakata Saladi, Ravi Kumar Gutti
BACKGROUND: Hepatoprotective activity along with improved survival percentage and hematological parameters prior to whole body irradiation were reported with Justicia adhatoda extracts. PURPOSE: To evaluate the thrombopoietic potential of Justicia adhatoda L. leaf extract in megakaryocyte differentiation METHODS: Ethanol extracts were prepared using soxhlet extraction method, and IC50 value was determined. The effect of ethanol extracts obtained from Justicia adhatoda on megakaryocyte maturation and development in megakaryocytic Dami cell lines was tested...
April 1, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/29747685/car-t-cell-therapy-for-breast-cancer-harnessing-the-tumor-milieu-to-drive-t-cell-activation
#5
Pradip Bajgain, Supannikar Tawinwung, Lindsey D'Elia, Sujita Sukumaran, Norihiro Watanabe, Valentina Hoyos, Premal Lulla, Malcolm K Brenner, Ann M Leen, Juan F Vera
BACKGROUND: The adoptive transfer of T cells redirected to tumor via chimeric antigen receptors (CARs) has produced clinical benefits for the treatment of hematologic diseases. To extend this approach to breast cancer, we generated CAR T cells directed against mucin1 (MUC1), an aberrantly glycosylated neoantigen that is overexpressed by malignant cells and whose expression has been correlated with poor prognosis. Furthermore, to protect our tumor-targeted cells from the elevated levels of immune-inhibitory cytokines present in the tumor milieu, we co-expressed an inverted cytokine receptor linking the IL4 receptor exodomain with the IL7 receptor endodomain (4/7ICR) in order to transform the suppressive IL4 signal into one that would enhance the anti-tumor effects of our CAR T cells at the tumor site...
May 10, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29746793/high-throughput-flow-cytometry-identifies-small-molecule-inhibitors-for-drug-repurposing-in-t-all
#6
Dominique R Perez, Christian K Nickl, Anna Waller, Cristina Delgado-Martin, Travis Woods, Nitesh D Sharma, Michelle L Hermiston, Mignon L Loh, Stephen P Hunger, Stuart S Winter, Alexandre Chigaev, Bruce Edwards, Larry A Sklar, Ksenia Matlawska-Wasowska
Kinase inhibitors have dramatically increased patient survival in a multitude of cancers, including hematological malignancies. However, kinase inhibitors have not yet been integrated into current clinical trials for patients with T-cell-lineage acute lymphoblastic leukemia (T-ALL). In this study, we used a high-throughput flow cytometry (HTFC) approach to test a collection of small-molecule inhibitors, including 26 FDA-approved tyrosine kinase inhibitors in a panel of T-ALL cell lines and patient-derived xenografts...
May 1, 2018: SLAS Discovery
https://www.readbyqxmd.com/read/29741257/laboratory-diagnosis-of-clinically-relevant-platelet-function-disorders
#7
REVIEW
P Gresele, E Falcinelli, L Bury
Inherited platelet function disorders (IPFDs) represent a significant fraction of congenital hemorrhagic disorders, and may be associated with bleeding of considerable severity. IPFDs may be difficult to diagnose and a preliminary accurate clinical examination and an objective evaluation of the severity of the bleeding history are mandatory. The laboratory investigation of IPFDs should follow a rational algorithm based on a streamlined panel of laboratory tests with subsequent steps of increasing levels of complexity...
May 2018: International Journal of Laboratory Hematology
https://www.readbyqxmd.com/read/29731869/effects-of-human-umbilical-cord-derived-mesenchymal-stem-cells-on-hematologic-malignancies
#8
Qian Li, Yilin Pang, Tingting Liu, Yongyong Tang, Jing Xie, Bin Zhang, Hu Chen
Mesenchymal stem cells (MSCs) have been used in hematopoietic stem cell transplantation for years. However, the safety of MSCs applied in various types of hematologic malignancy has not been comprehensively explored. In the present study, the effects of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) on six representative hematologic malignancy cell lines were explored, including leukemia, multiple myeloma and lymphoma cells. Direct and indirect co-culture models were established, and cell proliferation was assessed by carboxyfluorescein diacetate succinimidyl ester staining...
May 2018: Oncology Letters
https://www.readbyqxmd.com/read/29729700/fc%C3%AE-receptor-iii-expression-and-morphological-maturity-on-neutrophil-are-associated-with-higher-iron-level-of-major-beta-thalassemia
#9
Mohammad Ghozali, Tiwi Harjanti Cakranita, Adi Imam Tjahjadi, Lelani Reniarti, Reni Ghrahani, Mraa Syamsunarno, Budi Setiabudiawan, Ramdan Panigoro
Lifetime blood transfusion experienced by major β-thalassemia patients complicated with iron overload, therefore, may lead to their tissue injury. Ultimately, free toxic iron may alter immune response via dysregulation of immune cell activity producing prolonged effector reaction. Neutrophil as one of the vital innate immune cell despite serves as the first line of defense resulting acute inflammation has a pivotal role in chronic inflammation while releasing the toxic substance that interferes biological processes...
April 30, 2018: Cellular and Molecular Biology
https://www.readbyqxmd.com/read/29728510/rapid-turnover-and-high-production-rate-of-myeloid-cells-in-adult-rhesus-macaques-with-compensations-during-aging
#10
Ziyuan He, Carolina Allers, Chie Sugimoto, Nursarat Ahmed, Hideki Fujioka, Woong-Ki Kim, Elizabeth S Didier, Marcelo J Kuroda
Neutrophils, basophils, and monocytes are continuously produced in bone marrow via myelopoiesis, circulate in blood, and are eventually removed from circulation to maintain homeostasis. To quantitate the kinetics of myeloid cell movement during homeostasis, we applied 5-bromo-2'-deoxyuridine pulse labeling in healthy rhesus macaques ( Macaca mulatta ) followed by hematology and flow cytometry analyses. Results were applied to a mathematical model, and the blood circulating half-life and daily production, respectively, of each cell type from macaques aged 5-10 y old were calculated for neutrophils (1...
May 4, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29722556/long-term-effect-of-sulfur-mustard-exposure-on-hematologic-and-respiratory-status-a-case-control-study
#11
Mohammad Reza Khazdair, Mohammad Hossein Boskabady
The long term effect of sulfur mustard (SM) exposure including, total and differential white blood cells (WBC), hematological parameters, pulmonary function tests (PFT), and respiratory symptoms (RS) in chemical war victims (CWV) exposed to SM 27-30 years ago were examined. Forty-six CWV and 42 control subjects with similar age from the general population were studied. Hematologic parameters, RS including; chest wheezing, night cough, night wheezing and cough, wheezing due to exercise (by Persian questionnaire), and PFT were assessed in all subjects...
May 3, 2018: Drug and Chemical Toxicology
https://www.readbyqxmd.com/read/29715334/internal-viscosity-dependent-margination-of-red-blood-cells-in-microfluidic-channels
#12
Faisal Ahmed, Marmar Mehrabadi, Zixiang Liu, Gilda A Barabino, Cyrus K Aidun
Cytoplasmic viscosity-dependent margination of red blood cells (RBC) for flow inside microchannels was studied using numerical simulations, and the results were verified with microfluidic experiments. Wide range of suspension volume fractions or hematocrits was considered in this study. Lattice Boltzmann method for fluid-phase coupled with spectrin-link method for RBC membrane deformation was used for accurate analysis of cell margination. RBC margination behavior shows strong dependence on the internal viscosity of the RBCs...
June 1, 2018: Journal of Biomechanical Engineering
https://www.readbyqxmd.com/read/29715056/venetoclax-for-patients-with-chronic-lymphocytic-leukemia-with-17p-deletion-results-from-the-full-population-of-a-phase-ii-pivotal-trial
#13
Stephan Stilgenbauer, Barbara Eichhorst, Johannes Schetelig, Peter Hillmen, John F Seymour, Steven Coutre, Wojciech Jurczak, Stephen P Mulligan, Anna Schuh, Sarit Assouline, Clemens-Martin Wendtner, Andrew W Roberts, Matthew S Davids, Johannes Bloehdorn, Talha Munir, Sebastian Böttcher, Lang Zhou, Ahmed Hamed Salem, Monali Desai, Brenda Chyla, Jennifer Arzt, Su Young Kim, Maria Verdugo, Gary Gordon, Michael Hallek, William G Wierda
Purpose Venetoclax is an orally bioavailable B-cell lymphoma 2 inhibitor. US Food and Drug Administration and European Medicines Agency approval for patients with 17p deleted relapsed/refractory chronic lymphocytic leukemia [del(17p) CLL] was based on results from 107 patients. An additional 51 patients were enrolled in a safety expansion cohort. Extended analysis of all enrolled patients, including the effect of minimal residual disease (MRD) negativity on outcome, is now reported. Patients and Methods Overall, 158 patients with relapsed/refractory or previously untreated (n = 5) del(17p) CLL received venetoclax 400 mg per day after an initial dose ramp up...
May 1, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29707241/kpt-330-inhibition-of-chromosome-region-maintenance-1-is-cytotoxic-and-sensitizes-chronic-myeloid-leukemia-to-imatinib
#14
Danian Nie, Kezhi Huang, Songmei Yin, Yiqing Li, Shuangfeng Xie, Liping Ma, Xiuju Wang, Yudan Wu, Jie Xiao, Jieyu Wang, Wenjuan Yang, Hongyun Liu
As tyrosine kinase inhibitors (e.g., Imatinib, IM) fail to induce long-term response in some chronic myeloid leukemia (CML), novel therapies targeting leukemia-dysregulated pathways are necessary. Nuclear-cytoplasmic trafficking of proteins play a key role in the development of leukemia and drug resistance. KPT-330 (Selinexor), an inhibitor of chromosome region maintenance 1 (CRM1, nuclear receptor exportin 1, XPO1), demonstrated activities against a few hematological malignancies. We examined the anti-leukemic efficacy of KPT-330 in IM-resistant CML...
2018: Cell Death Discovery
https://www.readbyqxmd.com/read/29707107/selective-inhibition-of-bcl-2-is-a-promising-target-in-patients-with-high-risk-myelodysplastic-syndromes-and-adverse-mutational-profile
#15
Veronika Reidel, Johanna Kauschinger, Richard T Hauch, Catharina Müller-Thomas, Niroshan Nadarajah, Rainer Burgkart, Burkhard Schmidt, Dirk Hempel, Anne Jacob, Julia Slotta-Huspenina, Ulrike Höckendorf, Christian Peschel, Wolfgang Kern, Torsten Haferlach, Katharina S Götze, Stefanie Jilg, Philipp J Jost
Somatic mutations in genes such as ASXL1 , RUNX1 , TP53 or EZH2 adversely affect the outcome of patients with myelodysplastic syndromes (MDS). Since selective BCL-2 inhibition is a promising treatment strategy in hematologic malignancies, we tested the therapeutic impact of ABT-199 on MDS patient samples bearing an adverse mutational profile. By gene expression, we found that the level of pro-apoptotic BIM significantly decreased during MDS disease progression in line with an acquired resistance to cell death...
April 3, 2018: Oncotarget
https://www.readbyqxmd.com/read/29705861/the-prognostic-role-of-e2a-pbx1-expression-detected-by-real-time-quantitative-reverse-transcriptase-polymerase-chain-reaction-rq-pcr-in-b-cell-acute-lymphoblastic-leukemia-after-allogeneic-hematopoietic-stem-cell-transplantation
#16
Yan Hong, Xiaosu Zhao, Yazhen Qin, Songhai Zhou, Yingjun Chang, Yu Wang, Xiaohui Zhang, Lanping Xu, Xiaojun Huang
The E2A-PBX1 rearrangement is common in B cell acute lymphoblastic leukemia (B-ALL). However, whether this fusion gene can be used as a reliable marker for minimal residual disease (MRD) following allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains unknown. In this study, clinical data were collected from 28 consecutive B-ALL patients who received allo-HSCT. Their MRD was evaluated by E2A-PBX1 and leukemia-associated immunophenotype (LAIP). The median follow-up was 374 days (55-2342 days)...
April 28, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29698492/evaluation-of-cell-count-and-classification-capabilities-in-body-fluids-using-a-fully-automated-sysmex-xn-equipped-with-high-sensitive-analysis-hsa-mode-and-di-60-hematology-analyzer-system
#17
Hiroyuki Takemura, Tomohiko Ai, Konobu Kimura, Kaori Nagasaka, Toshihiro Takahashi, Koji Tsuchiya, Haeun Yang, Aya Konishi, Kinya Uchihashi, Takashi Horii, Yoko Tabe, Akimichi Ohsaka
The XN series automated hematology analyzer has been equipped with a body fluid (BF) mode to count and differentiate leukocytes in BF samples including cerebrospinal fluid (CSF). However, its diagnostic accuracy is not reliable for CSF samples with low cell concentration at the border between normal and pathologic level. To overcome this limitation, a new flow cytometry-based technology, termed "high sensitive analysis (hsA) mode," has been developed. In addition, the XN series analyzer has been equipped with the automated digital cell imaging analyzer DI-60 to classify cell morphology including normal leukocytes differential and abnormal malignant cells detection...
2018: PloS One
https://www.readbyqxmd.com/read/29695270/distinct-t-helper-cell-responses-to-staphylococcus-aureus-bacteremia-reflect-immunologic-comorbidities-and-correlate-with-mortality
#18
Jared A Greenberg, Cara L Hrusch, Mohammad R Jaffery, Michael Z David, Robert S Daum, Jesse B Hall, John P Kress, Anne I Sperling, Philip A Verhoef
BACKGROUND: The dysregulated host immune response that defines sepsis varies as a function of both the immune status of the host and the distinct nature of the pathogen. The degree to which immunocompromising comorbidities or immunosuppressive medications affect the immune response to infection is poorly understood because these patients are often excluded from studies about septic immunity. The objectives of this study were to determine the immune response to a single pathogen (Staphylococcus aureus) among a diverse case mix of patients and to determine whether comorbidities affect immune and clinical outcomes...
April 25, 2018: Critical Care: the Official Journal of the Critical Care Forum
https://www.readbyqxmd.com/read/29680874/utility-and-proposed-algorithm-of-csf-flow-cytometry-in-hematologic-malignancies
#19
Bernard Tawfik, Larry Brown, Frankling Fuda, Weina Chen, Shuang Niu, Joseph Sailors, Navid Sadeghi
In patients with hematologic malignancies, multiparameter flow cytometry (FCM) offers greater sensitivity than cytology in detecting malignant cells in the initial cerebrospinal fluid (CSF) specimen. However, the role of FCM in assessment of subsequent specimens is unclear. We developed an algorithm to reduce the number of low-yield FCM tests without significant impact on clinically meaningful results. Patients with hematologic malignancies were studied in a derivation cohort, and the following algorithm was developed: (1) cytology and FCM on all initial samples, (2) cytology on all subsequent samples, and (3) FCM on subsequent samples only if previous FCM was positive...
April 21, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29670776/-kit-d816v-positive-acute-mast-cell-leukemia-associated-with-normal-karyotype-acute-myeloid-leukemia
#20
Marta Lopes, Maria Dos Anjos Teixeira, Cláudia Casais, Vanessa Mesquita, Patrícia Seabra, Renata Cabral, José Palla-García, Catarina Lau, João Rodrigues, Maria Jara-Acevedo, Inês Freitas, Jose Ramón Vizcaíno, Jorge Coutinho, Luis Escribano, Alberto Orfao, Margarida Lima
Introduction: Mast cell (MC) leukemia (MCL) is extremely rare. We present a case of MCL diagnosed concomitantly with acute myeloblastic leukemia (AML). Case Report: A 41-year-old woman presented with asthenia, anorexia, fever, epigastralgia, and diarrhea. She had a maculopapular skin rash, hepatosplenomegaly, retroperitoneal adenopathies, pancytopenia, 6% blast cells (BC) and 20% MC in the peripheral blood, elevated lactate dehydrogenase, cholestasis, hypoalbuminemia, hypogammaglobulinemia, and increased serum tryptase (184  μ g/L)...
2018: Case Reports in Hematology
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