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https://www.readbyqxmd.com/read/28340541/drug-discovery-testing-compounds-in-patients-samples-by-automated-flow-cytometry
#1
Pilar Hernández, Julián Gorrochategui, Daniel Primo, Alicia Robles, José Luis Rojas, Ana Belén Espinosa, Cristina Gómez, Joaquín Martínez-López, Teresa A Bennett, Joan Ballesteros
Functional ex vivo assays that predict a patient's clinical response to anticancer drugs for guiding cancer treatment have long been a goal, but few have yet proved to be reliable. To address this, we have developed an automated flow cytometry platform for drug screening that evaluates multiple endpoints with a robust data analysis system that can capture the complex mechanisms of action across different compounds. This system, called PharmaFlow, is used to test peripheral blood or bone marrow samples from patients diagnosed with hematological malignancies...
March 1, 2017: SLAS Technol
https://www.readbyqxmd.com/read/28340113/gata1-is-a-sensitive-and-specific-nuclear-marker-for-erythroid-and-megakaryocytic-lineages
#2
Winston Y Lee, Olga K Weinberg, Geraldine S Pinkus
Objectives: GATA binding factor 1 (GATA1) is a transcription factor essential for erythromegakaryocytic differentiation. Given its function in lineage specification, we sought to evaluate the immunohistochemical profile of GATA1 in normal marrow and acute leukemia and assess the use of GATA1 as a specific erythromegakaryocytic immunohistochemical marker. Methods: Immunohistochemical studies for GATA1 expression were performed on bone marrow biopsy specimens to define its role in the evaluation of acute leukemia and other hematologic disorders...
March 15, 2017: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28336527/a-phase-i-clinical-trial-of-single-agent-selinexor-in-acute-myeloid-leukemia
#3
Ramiro Garzon, Michael Savona, Rachid Baz, Michael Andreeff, Nashat Gabrail, Martin Gutierrez, Lynn Savoie, Morten Mau-Sorensen, Nina Wagner-Johnston, Karen Yee, T J Unger, Jean Richard Saint-Martin, Robert Carlson, Tami Rashal, Trinayan Kashyap, Boris Klebanov, Sharon Shacham, Michael Kauffman, Richard Stone
Selinexor is a novel, first-in-class, Selective Inhibitor of Nuclear Export (SINE) compound, which blocks XPO1 function, leads to nuclear accumulation of tumor suppressor proteins (TSPs) and induces cancer cell death. A phase I dose-escalation study was initiated to examine the safety and efficacy of selinexor in patients with advanced hematological malignancies. Ninety-five patients with relapsed or refractory acute myeloid leukemia (AML) were enrolled between January 2013 and June 2014 to receive 4, 8 or 10 doses of selinexor in 21- or 28-day cycle...
March 23, 2017: Blood
https://www.readbyqxmd.com/read/28335858/netting-novel-regulators-of-hematopoiesis-and-hematologic-malignancies-in-zebrafish
#4
Wanda Kwan, Trista E North
Zebrafish are one of the preeminent model systems for the study of blood development (hematopoiesis), hematopoietic stem and progenitor cell (HSPC) biology, and hematopathology. The zebrafish hematopoietic system shares strong similarities in functional populations, genetic regulators, and niche interactions with its mammalian counterparts. These evolutionarily conserved characteristics, together with emerging technologies in live imaging, compound screening, and genetic manipulation, have been employed to successfully identify and interrogate novel regulatory mechanisms and molecular pathways that guide hematopoiesis...
2017: Current Topics in Developmental Biology
https://www.readbyqxmd.com/read/28333850/multimodality-ocular-imaging-in-a-case-report-of-hyperviscosity-syndrome-associated-with-lymphoplasmacytic-leukemia-the-images-tell-the-story
#5
Rene Y Choi, Rachel Jacoby, Akbar Shakoor
PURPOSE: To report the clinical course of a patient with ocular manifestations of hyperviscosity syndrome associated with Waldenström macroglobulinemia, and for the first time, video imaging of mobile emboli in the conjunctival and retinal vasculature. METHODS AND PATIENT: A 60-year-old woman with newly diagnosed Waldenström macroglobulinemia, with no visual complaints was evaluated by the Ophthalmology service for a baseline ocular examination. RESULTS: At presentation, ocular examination revealed a visual acuity of 20/25 in each eye...
March 22, 2017: Retinal Cases & Brief Reports
https://www.readbyqxmd.com/read/28333846/prognostic-value-of-fluorine-18-fluorodeoxyglucose-uptake-of-bone-marrow-on-positron-emission-tomography-computed-tomography-for-prediction-of-disease-progression-in-cervical-cancer
#6
Jeong Won Lee, Seob Jeon, Seong Taek Mun, Sang Mi Lee
OBJECTIVE: This study aimed to evaluate the prognostic value of fluorine-18 fluorodeoxyglucose (FDG) uptake of bone marrow (BM) on positron emission tomography (PET)/computed tomography in patients with uterine cervical cancer. METHODS: One hundred forty-five patients with cervical cancer who underwent staging FDG PET/computed tomography and subsequent surgical resection or chemoradiotherapy were retrospectively enrolled in the study. Mean BM FDG uptake (BM standardized uptake value [SUV]) and BM-to-liver uptake ratio of FDG uptake (BLR) were measured...
March 23, 2017: International Journal of Gynecological Cancer
https://www.readbyqxmd.com/read/28331130/cytopenias-and-clonal-expansion-of-gamma-delta-t-cells-in-a-patient-with-anaplasmosis-a-potential-diagnostic-pitfall
#7
Daniel Marko, Anamarija M Perry, Arjuna Ponnampalam, Michel R Nasr
Human granulocytic anaplasmosis is a rare, tick-borne infectious disease caused by Anaplasma phagocytophilum. Herein, we report a rare case of human granulocytic anaplasmosis associated with cytopenias and clonal expansion of gamma/delta T-cells in the bone marrow. A 77-year old man presented multiple times to the emergency department complaining of muscle weakness. Complete blood count detected cytopenias and peripheral blood smear showed pseudo Pelger-Huet neutrophils. These findings prompted bone marrow evaluation with ancillary studies including flow cytometry, karyotyping and T-cell rearrangement studies...
2017: Journal of Clinical and Experimental Hematopathology: JCEH
https://www.readbyqxmd.com/read/28331025/tetraploidy-acute-myeloid-leukaemia-after-chromosome-16-inversion
#8
Alba Sara Vilches, Aranzazu Díaz de Bustamante, Jorge Sanchez-Calero, María Teresa Darnaude
Our patient is a 36-year-old man referred by his general physician to the Department of Hematology because of mild neutropenia in a routine analysis at work. There was no history of previous diseases, and examination was normal. Blood investigations confirmed the neutropenia and showed elongation of prothrombin time. A bone marrow examination was performed revealing about 10% of myeloblasts on the aspirate smears. A cytogenetic study showed chromosome 16 inversion in all of these cells and tetraploidy only in some of them, which were extremely large in size...
March 22, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28327200/a-first-in-human-phase-1-study-of-a-hepcidin-monoclonal-antibody-ly2787106-in-cancer-associated-anemia
#9
Saroj Vadhan-Raj, Rafat Abonour, Jonathan W Goldman, David A Smith, Christopher A Slapak, Robert L Ilaria, Ramon V Tiu, Xuejing Wang, Sophie Callies, Joanne Cox, Jay L Tuttle, Yiu-Keung Lau, Eric J Roeland
BACKGROUND: Hepcidin plays a central role in iron homeostasis and erythropoiesis. Neutralizing hepcidin with a monoclonal antibody (mAb) may prevent ferroportin internalization, restore iron efflux from cells, and allow transferrin-mediated iron transport to the bone marrow. This multicenter, phase 1 study evaluated the safety, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy of a fully humanized mAb (LY2787106) with high affinity for hepcidin in cancer patients with anemia...
March 21, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28326848/autologous-hematopoietic-stem-cells-for-refractory-crohn-s-disease
#10
C A DiNicola, A Zand, D W Hommes
Autologous hematopoietic stem cells are gaining ground as an effective and safe treatment for treating severe refractory Crohn's disease (CD). Autologous hematopoietic stem cell therapy (AHSCT) induces resetting of the immune system by de novo regeneration of T-cell repertoire and repopulation of epithelial cells by bone-marrow derived cells to help patients achieve clinical and endoscopic remission. Areas covered: Herein, the authors discuss the use of AHSCT in treating patients with CD. Improvements in disease activity have been seen in patients with severe autoimmune disease and patients with severe CD who underwent AHSCT for a concomitant malignant hematological disease...
March 22, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28322187/influence-of-genetic-background-on-hematologic-and-histopathologic-alterations-during-acute-granulocytic-anaplasmosis-in-129-svev-and-c57bl-6j-mice-lacking-type-i-and-type-ii-interferon-signaling
#11
Jennifer L Johns Marielle L Discipulo Amanda L Koehne Kaitlin A Moorhead And Claude M Nagamine
The role of host type I IFN signaling and its interaction with other immune pathways during bacterial infections is incompletelyunderstood. Type II IFN signaling plays a key role during numerous bacterial infections including granulocytic anaplasmosis (GA)caused by Anaplasma phagocytophilum infection. The function of combined type I and type II IFN signaling and their potentialsynergism during GA and similar tick-borne diseases is a topic of current research investigation. The goal of this study was toevaluate 2 mouse models of absent type I/type II IFN signaling in experimental A...
March 20, 2017: Comparative Medicine
https://www.readbyqxmd.com/read/28321217/a-vaccine-therapy-for-canine-visceral-leishmaniasis-promoted-significant-improvement-of-clinical-and-immune-status-with-reduction-in-parasite-burden
#12
Bruno Mendes Roatt, Rodrigo Dian de Oliveira Aguiar-Soares, Levi Eduardo Soares Reis, Jamille Mirelle de Oliveira Cardoso, Fernando Augusto Siqueira Mathias, Rory Cristiane Fortes de Brito, Sydnei Magno da Silva, Nelder De Figueiredo Gontijo, Sidney de Almeida Ferreira, Jesus G Valenzuela, Rodrigo Corrêa-Oliveira, Rodolfo Cordeiro Giunchetti, Alexandre Barbosa Reis
Herein, we evaluated the treatment strategy employing a therapeutic heterologous vaccine composed of antigens of Leishmania braziliensis associated with MPL adjuvant (LBMPL vaccine) for visceral leishmaniasis (VL) in symptomatic dogs naturally infected by Leishmania infantum. Sixteen dogs received immunotherapy with MPL adjuvant (n = 6) or with a vaccine composed of antigens of L. braziliensis associated with MPL (LBMPL vaccine therapy, n = 10). Dogs were submitted to an immunotherapeutic scheme consisting of 3 series composed of 10 subcutaneous doses with 10-day interval between each series...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28321122/the-emerging-roles-of-tumor-derived-exosomes-in-hematological-malignancies
#13
REVIEW
M Boyiadzis, T L Whiteside
Exosomes are small (30-150 nm) membranous vesicles of endocytic origin produced by all cells under physiological and pathological conditions. They have recently emerged as vehicles for intercellular transfer of molecular and genetic contents from parent to recipient cells. Exosome-mediated transfer of proteins or genes (RNA, miRNA, DNA) results in reprogramming of recipient cell functions. Exosomes carry and deliver information that is essential for health, and they participate in pathological events, including malignant transformation...
March 21, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28321093/successful-treatment-with-biweekly-chop-for-bone-marrow-relapse-of-blastic-plasmacytoid-dendritic-cell-neoplasm
#14
Keiko Ono, Mikiko Ise, Dai Ikebe, Akiyasu Sato, Xiaofei Wang, Takeaki Sugawara, Hideki Tsujimura, Makiko Itami, Kyoya Kumagai
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematological malignancy derived from precursors of plasmacytoid dendritic cells. The majority of patients initially respond to multi-agent chemotherapy, though most relapse within a year and the prognosis is very poor. We report a 67-year-old man with erythema on the right chest and a nasopharyngeal mass. Histological examination revealed a mass of tumor cells expressing CD4, CD56, and CD123, but neither CD3 nor CD20. He was diagnosed with BPDCN...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28319074/tregs-hype-or-hope-for-allogeneic-hematopoietic-stem-cell-transplantation
#15
REVIEW
F Lussana, M Di Ianni, A Rambaldi
The discovery of T regulatory cells has been one of the most important advances in basic immunology and has opened the door to the development of innovative therapeutic strategies for improving the outcome of solid organ and hematopoietic stem cell transplantation. Basic immunology is rapidly elucidating the complex biology of these cells even though the difficulties in purifying or even expanding them in vitro represent a major limitation to the development of clinical studies. The clinical benefit potentially associated with this therapeutic approach remains to be demonstrated...
March 20, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28319073/ex-vivo-t-cell-depletion-in-allogeneic-hematopoietic-stem-cell-transplant-past-present-and-future
#16
REVIEW
A Saad, L S Lamb
The most common cause of post-transplant mortality in patients with hematological malignancy is relapse, followed by GvHD, infections, organ toxicity and second malignancy. Immune-mediated complications such as GvHD continue to be challenging, yet amenable to control through manipulation of the T-cell compartment of the donor graft with subsequent immunomodulation after transplant. However, risk of both relapse and infection increase concomitantly with T-cell depletion (TCD) strategies that impair immune recovery...
March 20, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28318212/multiple-myeloma-diagnosis-and-treatment
#17
COMPARATIVE STUDY
Thomas C Michels, Keith E Petersen
Multiple myeloma accounts for 1.6% of all cancer cases and approximately 10% of hematologic malignancies in the United States. In 2015, an estimated 28,850 new cases of multiple myeloma were diagnosed in the United States, and the disease caused more than 11,000 deaths. Patients older than 65 years account for 85% of those diagnosed with multiple myeloma, and there is a twofold increased incidence in blacks compared with whites. Patients may present with bone pain or with symptoms that are often nonspecific, such as nausea, vomiting, malaise, weakness, recurrent infections, and weight loss...
March 15, 2017: American Family Physician
https://www.readbyqxmd.com/read/28306669/role-of-shp2-in-hematopoiesis-and-leukemogenesis
#18
Ruchi Pandey, Mallika Saxena, Reuben Kapur
PURPOSE OF REVIEW: SH2 domain-containing tyrosine phosphatase 2 (SHP2), encoded by PTPN11 plays an important role in regulating signaling from cell surface receptor tyrosine kinases during normal development as well as oncogenesis. Herein we review recently discovered roles of SHP2 in normal and aberrant hematopoiesis along with novel strategies to target it. RECENT FINDINGS: Cell autonomous role of SHP2 in normal hematopoiesis and leukemogenesis has long been recognized...
March 16, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28293461/a-rare-cause-of-cytopenia-in-a-patient-with-systemic-lupus-erythematosus-autoimmune-myelofibrosis
#19
Döndü Üsküdar Cansu, Hava Üsküdar Teke, Cengiz Korkmaz
Hematological abnormalities are very common in the course of systemic lupus erythematosus (SLE). Myelofibrosis is a bone marrow disorder in which there is excessive fibrous tissue formation in the bone marrow. Various benign and malignant disorders can cause or be associated with a diffuse increase in the bone marrow reticular tissue. Some diseases such as infections, neoplasms, and autoimmune diseases may also induce bone marrow fibrosis (secondary myelofibrosis). Cytopenia from autoimmune myelofibrosis (AIMF) in SLE is a rare condition...
March 2017: European Journal of Rheumatology
https://www.readbyqxmd.com/read/28293160/hemophagocytic-histiocytosis-a-clinicopathological-correlation
#20
Waseem Iqbal, Abdulaziz Ajlan Alsalloom, Khalid Shehzad, Faisal Mughal, Zafar Rasheed
OBJECTIVES: Histiocytic hyperplasia with hemophagocytosis (HP) is relatively uncommon condition that has often been mistaken in the past for neoplastic disorders. This study was conducted to investigate the possible etiology of HP, its intensity in the bone marrow (BM), and also its effect on hematological parameters with the extent of disease activity. METHODS: Blood samples were collected and BM examination was performed in 250 patients with varied etiology showing HP...
January 2017: International Journal of Health Sciences
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