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https://www.readbyqxmd.com/read/27906795/factors-determining-the-outcome-of-hematopoietic-stem-cell-transplantation-in-patients-with-acute-lymphoblastic-leukemia-at-king-faisal-specialist-hospital-and-research-center-riyadh-saudi-arabia
#1
Suleimman Al-Sweedan, Amal Al-Seraihy, Ali Al-Ahmari, Abdullah Al-Jefri, Viqaruddin Mohammed, Rafat Jafri, Khawar Siddiqui, Mouhab Ayas
Medical records of 82 patients with acute lymphoblastic leukemia (ALL) who underwent hematopoietic cell transplantation (HCT) at our institution from 2005 to 2011 were reviewed. Forty-five patients were male (54.8%). The median age at HCT was 7.46 years (range, 0.98 to 14.31 y), the median time to HCT after diagnosis was 12.56 months. Ten patients were below the age of 1 year (12%). All patients were in complete remission at the time of HCT. In 83 transplants, 64 patients received HCT from human leukocyte antigen-identical-related donors and 19 from other donors...
November 30, 2016: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/27903673/combining-anti-mir-155-with-chemotherapy-for-the-treatment-of-lung-cancers
#2
Katrien Van Roosbroeck, Francesca Fanini, Tetsuro Setoyama, Cristina Ivan, Cristian Rodriguez-Aguayo, Enrique Fuentes-Mattei, Lianchun Xiao, Ivan Vannini, Roxana Redis, Lucilla D'Abundo, Xinna Zhang, Milena S Nicoloso, Simona Rossi, Vianey Gonzalez-Villasana, Rajesha Rupaimoole, Manuela Ferracin, Fortunato Morabito, Antonino Neri, Peter Ruvolo, Vivian R Ruvolo, Chad V Pecot, Dino Amadori, Lynne Aruzzo, Steliana Calin, Xuemei Wang, M James You, Alessandra Ferrajoli, Robert Z Orlowski, William Plunkett, Tara Lichtenberg, Ramana V Davuluri, Ioana Berindan-Neagoe, Massimo Negrini, Ignacio I Wistuba, Kantarjian Hagop, Anil K Sood, Gabriel Lopez-Berestein, Michael J Keating, Muller Fabbri, George A Calin
Purpose The oncogenic miR-155 is upregulated in many human cancers and its expression is increased in more aggressive and therapy resistant tumors, but the molecular mechanisms underlying miR-155-induced therapy resistance are not fully understood. The main objectives of this study were to determine the role of miR-155 in resistance to chemotherapy and to evaluate anti-miR-155 treatment to chemosensitize tumors. Experimental Design We performed in vitro studies on cell lines to investigate the role of miR-155 in therapy resistance...
November 30, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27899971/the-targetable-role-of-herpes-virus-associated-ubiquitin-specific-protease-hausp-in-p190-bcr-abl-leukemia
#3
Giovanna Carrà, Cristina Panuzzo, Sabrina Crivellaro, Deborah Morena, Riccardo Taulli, Angelo Guerrasio, Giuseppe Saglio, Alessandro Morotti
Philadelphia chromosome-positive (Ph(+)) acute lymphoblastic leukemia (ALL) is driven by the p190 breakpoint cluster region (BCR)-ABL isoform. Although effectively targeted by BCR-ABL tyrosine kinase inhibitors (TKIs), ALL is associated with a less effective response to TKIs compared with chronic myeloid leukemia. Therefore, the identification of additional genes required for ALL maintenance may provide possible therapeutic targets to aid the eradication of this cancer. The present study demonstrated that p190 BCR-ABL is able to interact with the deubiquitinase herpesvirus-associated ubiquitin-specific protease (HAUSP), which in turn affects p53 protein stability...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27899822/mir-150-exerts-antileukemia-activity-in-vitro-and-in-vivo-through-regulating-genes-in-multiple-pathways
#4
Zhi Hong Fang, Si Li Wang, Jin Tao Zhao, Zhi Juan Lin, Lin Yan Chen, Rui Su, Si Ting Xie, Bing Z Carter, Bing Xu
MicroRNAs, a class of small noncoding RNAs, have been implicated to regulate gene expression in virtually all important biological processes. Although accumulating evidence demonstrates that miR-150, an important regulator in hematopoiesis, is deregulated in various types of hematopoietic malignancies, the precise mechanisms of miR-150 action are largely unknown. In this study, we found that miR-150 is downregulated in samples from patients with acute lymphoblastic leukemia, acute myeloid leukemia, and chronic myeloid leukemia, and normalized after patients achieved complete remission...
September 22, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27881582/the-expanding-role-of-the-bcl6-oncoprotein-as-a-cancer-therapeutic-target
#5
Mariano G Cardenas, Erin Oswald, Wenbo Yu, Fengtian Xue, Alexander D MacKerell, Ari M Melnick
BCL6 was initially discovered as an oncogene in B-cell lymphomas, where it drives the malignant phenotype by repressing proliferation and DNA damage checkpoints and blocking B-cell terminal differentiation. BCL6 mediates its effects by binding to hundreds of target genes, and then repressing these genes by recruiting several different chromatin modifying corepressor complexes. Structural characterization of BCL6-corepressor complexes suggested that BCL6 might be a druggable target. Accordingly a number of compounds have been designed to bind to BCL6 and block corepressor recruitment...
November 23, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27880933/immunological-effects-of-nilotinib-prophylaxis-after-allogeneic-stem-cell-transplantation-in-patients-with-advanced-chronic-myeloid-leukemia-or-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia
#6
Nira Varda-Bloom, Ivetta Danylesko, Roni Shouval, Shiran Eldror, Atar Lev, Jacqueline Davidson, Esther Rosenthal, Yulia Volchek, Noga Shem-Tov, Ronit Yerushalmi, Avichai Shimoni, Raz Somech, Arnon Nagler
Allogeneic stem cell transplantation remains the standard treatment for resistant advanced chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia. Relapse is the major cause of treatment failure in both diseases. Post-allo-SCT administration of TKIs could potentially reduce relapse rates, but concerns regarding their effect on immune reconstitution have been raised. We aimed to assess immune functions of 12 advanced CML and Ph+ ALL patients who received post-allo-SCT nilotinib...
November 18, 2016: Oncotarget
https://www.readbyqxmd.com/read/27875673/recent-advances-in-engineered-t-cell-therapies-targeting-b-cell-malignancies
#7
Nathan Singh
Immunotherapy using engineered autologous T cells has been attempted for decades, but clinical trials have only recently demonstrated efficacy. The combination of enhanced manufacturing techniques, highly efficient engineering, appropriate target selection and synthetic receptors with potent T cell activating domains has led to the development of highly-active cellular therapy products. B-cell malignancies have served as the paradigmatic diseases to initially evaluate and subsequently hone engineered T cells targeting cancer...
October 2016: Discovery Medicine
https://www.readbyqxmd.com/read/27870504/chronic-licl-pretreatment-suppresses-thrombin-stimulated-intracellular-calcium-mobilization-through-trpc3-in-astroglioma-cells
#8
Takuji Uemura, Marty Green, Jerry J Warsh
OBJECTIVES: Transient receptor potential canonical type 3 (TRPC3) channels are activated in B lymphoblast cell lines from patients with bipolar disorder (BD), and its expression is reduced by chronic lithium treatment, implicating TRPC3 in the intracellular calcium (Ca(2+) ) dyshomeostasis of BD. Thrombin, via a protease-activated receptor, moderates Ca(2+) signaling and TRPC3 in astrocytes, and also cell proliferation. We examined whether lithium pretreatment attenuates thrombin-stimulated TRPC3 expression and function in astrocytes, and levels of the calcium-binding peptide, S100B, which is expressed mainly in these cells...
November 2016: Bipolar Disorders
https://www.readbyqxmd.com/read/27865176/adoptive-immunotherapy-for-hematological-malignancies-current-status-and-new-insights-in-chimeric-antigen-receptor-t-cells
#9
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/27856368/haploidentical-transplantation-with-post-transplant-cyclophosphamide-for-high-risk-acute-lymphoblastic-leukemia
#10
Samer A Srour, Denái R Milton, Asad Bashey, Amado Karduss-Urueta, Monzr Al Malki, Rizwan Romee, Scott Solomon, Stacey Brown, Michael Slade, Rosendo Perez, Gabriela Rondon, Stephan J Forman, Richard E Champlin, Partow Kebriaei, Stefan O Ciurea
Haploidentical transplantation performed with post-transplantation cyclophosphamide (PTCy)-based graft-versus-host disease (GVHD) prophylaxis has been associated with favorable outcomes for patients with acute myeloid leukemia and lymphomas. However, it remains unclear if such approach is effective for patients with acute lymphoblastic leukemia (ALL). We analyzed outcomes of 109 consecutively treated ALL patients 18 years of age and older at 5 institutions. The median age was 32 years and the median follow-up for survivors was 13 months...
November 14, 2016: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/27846451/sar-study-of-5-alkynyl-substituted-quinazolin-4-3h-ones-as-phosphoinositide-3-kinase-delta-pi3k%C3%AE-inhibitors
#11
Manman Wei, Xi Zhang, Xiang Wang, Zilan Song, Jian Ding, Ling-Hua Meng, Ao Zhang
PI3Kδ is a key component in the aberrant signaling transduction in B cell malignancy, therefore specific targeting PI3Kδ has become an attractive molecularly targeted therapy for chronic lymphocytic leukemia (CLL). Herein, we describe the discovery and optimization of a series of 5-alkynyl substituted PI3Kδ inhibitors based on the first FDA-approved inhibitor idelalisib. Compound 8d bearing the 1-morpholinohex-5-yn-1-one moiety as the C5-substituent was identified to have high potency against PI3Kδ (3.82 nM) and SU-DHL-6 cells (7...
November 9, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27834816/targeting-the-tam-receptors-in-leukemia
#12
REVIEW
Madeline G Huey, Katherine A Minson, H Shelton Earp, Deborah DeRyckere, Douglas K Graham
Targeted inhibition of members of the TAM (TYRO-3, AXL, MERTK) family of receptor tyrosine kinases has recently been investigated as a novel strategy for treatment of hematologic malignancies. The physiologic functions of the TAM receptors in innate immune control, natural killer (NK) cell differentiation, efferocytosis, clearance of apoptotic debris, and hemostasis have previously been described and more recent data implicate TAM kinases as important regulators of erythropoiesis and megakaryopoiesis. The TAM receptors are aberrantly or ectopically expressed in many hematologic malignancies including acute myeloid leukemia, B- and T-cell acute lymphoblastic leukemia, chronic lymphocytic leukemia, and multiple myeloma...
November 8, 2016: Cancers
https://www.readbyqxmd.com/read/27816651/clofarabine-plus-busulfan-is-an-effective-conditioning-regimen-for-allogeneic-hematopoietic-stem-cell-transplantation-in-patients-with-acute-lymphoblastic-leukemia-long-term-study-results
#13
Partow Kebriaei, Roland Bassett, G Lyons, Ben Valdez, Celina Ledesma, Gabriela Rondon, Betul Oran, Stefan Ciurea, Amin Alousi, Uday Popat, Krina Patel, Sairah Ahmed, Amanda Olson, Qaiser Bashir, Nina Shah, Roy Jones, David Marin, Katy Rezvani, Yago Nieto, Issa Khouri, Muzaffar Qazilbash, Chitra Hosing, Elizabeth Shpall, Richard E Champlin, Borje S Andersson
We investigated the long-term safety and disease control data obtained with i.v. busulfan (Bu) combined with clofarabine (Clo) in patients with acute lymphoblastic leukemia (ALL) undergoing allogeneic hematopoietic stem cell transplantation (HSCT). A total of 107 patients, median age 38 years (range, 19 to 64 years) received a matched sibling donor (n = 52) or matched unrelated donor (n = 55) transplant for ALL in first complete remission (n = 62), second complete remission (n = 28), or more advanced disease (n = 17)...
November 2, 2016: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/27803756/dasatinib-induced-pleural-effusion-chylothorax-an-option-to-consider
#14
Lucía Ferreiro, Esther San-José, Juan Suárez-Antelo, Luis Valdés
Dasatinib is a drug for treatment of oncogene fusion protein BCR-ABL-positive chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia resistant/intolerant to imatinib. Pleural effusion (PE) is a common adverse effect, and in this context, we present four cases seen due to this cause. One of them is a chylothorax. The PE grade is variable, and the physiopathology is not well established, although a block in T-lymphocyte function or inhibition of platelet-derived growth factor receptor-β is suggested being involved...
October 2016: Annals of Thoracic Medicine
https://www.readbyqxmd.com/read/27800196/chronic-disseminated-candidiasis-complicated-by-immune-reconstitution-inflammatory-syndrome-in-child-with-acute-lymphoblastic-leukemia
#15
Olga Zając-Spychała, Bogna Ukielska, Katarzyna Jończyk-Potoczna, Benigna Konatkowska, Jacek Wachowiak
Hepatosplenic candidiasis also known as chronic disseminated candidiasis is a rare manifestation of invasive fungal infection typically observed in patients with acute leukemia in prolonged, deep neutropenia. Immune reconstitution inflammatory syndrome (IRIS) is an inflammatory disorder triggered by rapid resolution of neutropenia. Diagnosis and treatment of IRIS are still challenging due to a variety of clinical symptoms, lack of certain diagnostic criteria, and no standards of treatment. The diagnosis of IRIS is even more difficult in patients with hematological malignancies complicated by "probable" invasive fungal infection, when fungal pathogen is still uncertain...
2016: Case Reports in Hematology
https://www.readbyqxmd.com/read/27787922/bone-health-in-patients-with-hematopoietic-disorders-of-bone-marrow-origin-systematic-review-and-meta-analysis
#16
Kieran Steer, Mariya Stavnichuk, Martin Morris, Svetlana V Komarova
Blood cell production and bone homeostasis are physically interlinked systems that exhibit active cross-talk. We examined how bone health is affected in patients with hematopoietic disorders due to abnormal proliferation of bone marrow cells. The electronic databases Medline, Embase, PubMed, BIOSIS Previews, Web of Science, and Cochrane were searched for studies presenting numerical values for trabecular bone volume or bone mineral density in control and patients with hematopoietic disorders. We identified 5 studies for beta-thalassemia, 6 for sickle cell anemia, 2 for polycythemia vera and essential thrombocythemia, 3 for chronic myelogenous leukemia, 6 for myelofibrosis, 5 for multiple myeloma, and 4 studies each for systemic mastocytosis, lymphocytic leukemia, and hemochromatosis...
October 27, 2016: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/27784881/bilineal-extramedullary-blast-crisis-as-an-initial-presentation-of-chronic-myeloid-leukemia-a-case-report-and-literature-review
#17
Xiaoning Gao, Jie Li, Lili Wang, Ji Lin, Hongshi Jin, Yihan Xu, Nan Wang, Yu Zhao, Daihong Liu, Li Yu, Quanshun Wang
BACKGROUND Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder characterized by the Philadelphia chromosome generated by the reciprocal translocation t(9: 22)(q34;q11). CML is usually diagnosed in the chronic phase. Blast crisis represents an advanced phase of CML. Extramedullary blast crisis as the initial presentation of CML with bone marrow remaining in chronic phase is an unusual event. Further, extramedullary blast crisis with T lymphoid/myeloid bilineal phenotype as an initial presentation for CML is extremely unusual...
October 27, 2016: American Journal of Case Reports
https://www.readbyqxmd.com/read/27784344/-value-of-a-panel-fluorescence-in-situ-hybridization-in-three-kinds-of-hematological-malignancies
#18
You-Wen Qin, Xiao-Rui Wang, Yi-Ning Yang, Chun Wang
OBJECTIVE: To evaluate the role of a panel fluorescence in situ hybridization (Panel-FISH) for the detection of common cytogenetic abnormalities in patients with chronic lymphoblastic leukemia (CLL), multiplemyeloma (MM) and myelodysplastic syndrome (MDS). METHODS: Three panels of probes were used to perform FISH assays in 46 patients with CLL, 53 with MM and 93 with MDS. Their results were compared with that obtain by conventional cytogenetic examination. RESULTS: The panel FISH detection in CLL and MM groups showed significantly higher sensitivity in revealing chromosomal abnormalities than that in conventional cytogenetics (73...
October 2016: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/27780981/longitudinal-observation-of-serum-anti-m%C3%A3-llerian-hormone-in-three-girls-after-cancer-treatment
#19
Yoko Miyoshi, Kie Yasuda, Makiko Tachibana, Hisao Yoshida, Emiko Miyashita, Takako Miyamura, Yoshiko Hashii, Kae Hashimoto, Tadashi Kimura, Keiichi Ozono
Gonadal dysfunction and infertility are major endocrinological late effects among childhood cancer survivors. Chemotherapy and radiation have gonadotoxic effects and diminish the ovarian reserve. The serum concentration of anti-Müllerian hormone (AMH) is a useful marker of ovarian reserve in survivors. We conducted a longitudinal study to investigate the variations of AMH in evaluating the acute and chronic effects of cancer therapy on the ovary. Three young female patients with different hematological diseases were registered, and their medical records were reviewed...
October 2016: Clinical Pediatric Endocrinology: Case Reports and Clinical Investigations: Official Journal of the Japanese Society for Pediatric Endocrinology
https://www.readbyqxmd.com/read/27744645/the-promise-of-chimeric-antigen-receptor-t-cell-therapy
#20
Noelle V Frey, David L Porter
Chimeric antigen receptors (CARs) are engineered molecules that can be introduced into T cells to enable them to target specific tumor antigens. CAR T cells targeting CD19 have shown promise in patients with relapsed and refractory B-cell neoplasms, including those with acute lymphoblastic leukemia, chronic lymphocytic leukemia, and non-Hodgkin lymphomas. Notably, durable responses have been observed in patients who had not undergone consolidative stem cell transplant, a finding that correlates with reports of T-cell persistence and B-cell aplasia in studies of anti-CD19 treatment in vivo...
October 15, 2016: Oncology (Williston Park, NY)
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