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Hematologic malignancy

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https://www.readbyqxmd.com/read/28813659/the-dna-methylcytosine-dioxygenase-tet2-sustains-immunosuppressive-function-of-tumor-infiltrating-myeloid-cells-to-promote-melanoma-progression
#1
Wen Pan, Shu Zhu, Kun Qu, Katrina Meeth, Jijun Cheng, Kaixin He, Hongdi Ma, Yan Liao, Xizhi Wen, Christine Roden, Zuzana Tobiasova, Zheng Wei, Jun Zhao, Jun Liu, Ji Zheng, Bo Guo, Sajid A Khan, Marcus Bosenberg, Richard A Flavell, Jun Lu
Ten-Eleven-Translocation-2 (Tet2) is a DNA methylcytosine dioxygenase that functions as a tumor suppressor in hematopoietic malignancies. We examined the role of Tet2 in tumor-tissue myeloid cells and found that Tet2 sustains the immunosuppressive function of these cells. We found that Tet2 expression is increased in intratumoral myeloid cells both in mouse models of melanoma and in melanoma patients and that this increased expression is dependent on an IL-1R-MyD88 pathway. Ablation of Tet2 in myeloid cells suppressed melanoma growth in vivo and shifted the immunosuppressive gene expression program in tumor-associated macrophages to a proinflammatory one, with a concomitant reduction of the immunosuppressive function...
August 15, 2017: Immunity
https://www.readbyqxmd.com/read/28811975/chemotherapeutic-agent-mediated-elimination-of-myeloid-derived-suppressor-cells
#2
REVIEW
Zibing Wang, Brian Till, Quanli Gao
Immunotherapy has shown great promise in the fight against cancer, as evidenced by the clinical efficacy of chimeric antigen receptor T cells in hematologic malignancies and checkpoint blockade in certain solid tumors. However, a considerable number of patients fail to respond to these therapies. Induction of myeloid-derived suppressor cells (MDSCs) by growing tumors has been shown to be one important factor limiting the efficacy of cancer immunotherapy. Recently, several chemotherapeutic agents used in conventional cancer chemotherapy have been found to reduce MDSC numbers in tumor tissues as well as in the peripheral lymphoid organs, and combining these agents with immunotherapy improved survival of tumor-bearing hosts...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28810803/driving-cars-on-the-highway-to-solid-cancer-some-considerations-on-the-adoptive-therapy-with-car-t-cells
#3
Hinrich Abken
Adoptive therapy with chimeric antigen receptor (CAR) redirected T cells achieved lasting remissions in hematologic malignancies even in terminal stages of the disease; exploring CAR T cell therapy in the treatment of solid tumors has just begun, balancing efficacy versus toxicity in early phase trials. In contrast to leukemia/lymphoma, solid tumors display a tremendously variable biology demanding different strategies to make a T cell attack successful in the long-term. We summarize current developments, discuss the hurdles and consider some modifications to improve the CAR T cell therapy in the treatment of solid tumors...
August 16, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28810561/cytotoxic-t-lymphocytes-promote-cytarabine-induced-acute-myeloid-leukemia-cell-apoptosis-via-inhibiting-bcl-2-expression
#4
Rui Deng, Fang-Yi Fan, Hai Yi, Li Fu, Yan Zeng, Yi Wang, Xiao-Juan Miao, Yan-Rong Shuai, Guang-Cui He, Yi Su
Acute myeloid leukemia (AML) remains difficult to cure due to its drug tolerance and refractoriness. Immunotherapy is a growing area of cancer research, which has been applied for the treatment of numerous types of cancer, including leukemia. The present study generated AML cell-specific cytotoxic T lymphocytes (CTLs) in vitro and investigated the effect of combining CTL treatment with one of the most commonly used drugs for the treatment of hematological malignancies, cytarabine, on AML cell apoptosis. Firstly, it was observed that monocyte-depleted peripheral blood lymphocytes from healthy donors could be used to generate large numbers of CD3(+)CD8(+) CTLs through immune stimulation...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28809761/the-t-12-21-p13-q22-in-pediatric-b-acute-lymphoblastic-leukemia-an-update
#5
Maximilian Becker, Kristie Liu, Carlos A Tirado
Pediatric B-cell acute lymphoblastic leukemia (B-ALL) is the most common hematological malignancy in children, and the t(12;21)(p13;q22) occurs in approximately 25% of these cases, making it is the most prevalent chromosomal abnormality. The t(12;21) which disrupts hematopoietic differentiation and proliferation, and can be present as a sole abnormality or within the context of a complex karyotype characterized by three or more chromosomal abnormalities. The prognosis of t(12;21) within a complex karyotype is extensively debated...
2017: Journal of the Association of Genetic Technologists
https://www.readbyqxmd.com/read/28808752/return-to-work-and-work-related-disability-among-aml-survivors
#6
Osai Samadi, Henriette Breunis, Joanna Sandoval, Kosalan Akilan, Narhari Timilshina, Shabbir M H Alibhai
Acute myeloid leukemia (AML) is an aggressive, acute-onset hematological malignancy. Greater use of intensive chemotherapy (IC), supportive care, and stem cell transplantation have led to an increasing number of long-term survivors. Few studies have examined employment issues among AML survivors and to our knowledge, no study has examined the long-term effects of treatment on return to work. This study is the first to utilize a validated measure of work-related limitation and productivity (WLQ-16) to assess the long-term effects of AML treatment on employment rates, work-related limitations, and overall productivity...
August 14, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28808609/optimizing-peripheral-blood-stem-cells-transplantation-outcome-through-amend-relapse-and-graft-failure-a-review-of-current-literature
#7
REVIEW
Saeed Mohammadi, Amir Hossein Norooznezhad, Ashraf Malek Mohammadi, Hajar Nasiri, Mohsen Nikbakht, Najmaldin Saki, Mohammad Vaezi, Kamran Alimoghaddam, Ardeshir Ghavamzadeh
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been considered as a valuable approach in treatment of numerous malignant and none malignant hematologic disorders. However, relapse and poor graft function (PGF) after allo-SCT remain to be controversial issues which may affect the transplantation outcome. Relevant articles were searched in MEDLINE database (2000-2016) using keywords and phrases: donor lymphocyte infusions, allogeneic stem cells transplantation, relapsed hematologic malignancies, booster schedules, cell dose, laboratory monitoring protocols and technical aspects of apheresis...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/28808212/recent-advances-in-arsenic-trioxide-encapsulated-nanoparticles-as-drug-delivery-agents-to-solid-cancers
#8
Anam Akhtar, Scarlet Xiaoyan Wang, Lucy Ghali, Celia Bell, Xuesong Wen
Since arsenic trioxide was first approved as the front line therapy for acute promyelocytic leukemia 25 years ago, its anti-cancer properties for various malignancies have been under intense investigation. However, the clinical successes of arsenic trioxide in treating hematological cancers have not been translated to solid cancers. This is due to arsenic's rapid clearance by the body's immune system before reaching the tumor site. Several attempts have henceforth been made to increase its bioavailability toward solid cancers without increasing its dosage albeit without much success...
January 19, 2017: Journal of Biomedical Research
https://www.readbyqxmd.com/read/28807703/is-early-palliative-care-feasible-in-patients-with-multiple-myeloma
#9
Josep Porta-Sales, Maria Guerrero-Torrelles, Deborah Moreno-Alonso, Josep Sarra-Escarre, Victòria Clapés-Puig, Jordi Trelis-Navarro, Anna Sureda-Balarí, Alberto Fernández De Sevilla-Ribosa
CONTEXT: Evidence for the benefits of early palliative care (EPC) in patients with solid tumors is strong, but EPC has received scant attention in hematological malignancies. OBJECTIVE: To assess the benefits of outpatient-based EPC for symptom control in patients with multiple myeloma. METHODS: Retrospective study of patients attending the Multiple Myeloma Palliative Care Clinic (MM-PAL) at our hospital in the year 2013 (February 1 - December 31)...
August 11, 2017: Journal of Pain and Symptom Management
https://www.readbyqxmd.com/read/28807562/targeting-signal-transducers-and-activators-of-transcription-stat-in-human-cancer-by-dietary-polyphenolic-antioxidants
#10
REVIEW
Hamed Amani, Marjan Ajami, Solmaz Nasseri Maleki, Hamidreza Pazoki-Toroudi, Maria Daglia, Arold Jorel Tsetegho Sokeng, Arianna Di Lorenzo, Seyed Fazel Nabavi, Kasi Pandima Devi, Seyed Mohammad Nabavi
Over the course of the last three decades, a large body of evidence has shown that polyphenols, the secondary metabolites occurring in plant foods and beverages, exert protective effects due to their antioxidant activity mediated through different mechanisms ranging from direct radical scavenging and metal chelating activities, to the capacity to inhibit pro-oxidant enzymes and to target specific cell-signalling pathways. In the last decade, dietary components, and polyphenols in particular have gained considerable attention as chemopreventive agents against different types of cancer...
August 11, 2017: Biochimie
https://www.readbyqxmd.com/read/28807405/initiation-of-a-multidisciplinary-rapid-response-team-to-massive-and-submassive-pulmonary-embolism
#11
Brett J Carroll, Heather Pemberton, Kenneth A Bauer, Louis M Chu, Jeffrey L Weinstein, Barbara L Levarge, Duane S Pinto
Pulmonary embolism (PE) can result in rapid clinical decompensation in many patients. With increasing patient complexity and advanced treatment options for PE, multidisciplinary, rapid response teams can optimize risk stratification and expedite management strategies. The Massive And Submassive Clot On-call Team (MASCOT) was created at our institution, which comprised specialists from cardiology, pulmonology, hematology, interventional radiology, and cardiac surgery. MASCOT offers rapid consultation 24 hours a day with a web-based conference call to review patient data and discuss management of patients with high-risk PE...
July 26, 2017: American Journal of Cardiology
https://www.readbyqxmd.com/read/28807337/evaluation-of-cd43-expression-in-non-hematopoietic-malignancies
#12
Bjorn H Batdorf, Steven H Kroft, Paul R Hosking, Alexandra M Harrington, Alexander C Mackinnon, Horatiu Olteanu
OBJECTIVES: CD43 is normally expressed only on the surface of leukocytes, and is considered a sensitive and specific marker for hematologic malignancies. As such, it may have diagnostic utility in confirming hematolymphoid lineage in cases that are negative for CD45. Aberrant CD43 expression has been described in non-hematopoietic tumors, although literature data on this topic is variable and sometimes contradictory. To clarify and expand on existing literature findings, we evaluated CD43 expression by immunohistochemistry (IHC) in a large cohort (307) of non-hematopoietic neoplasms, including poorly differentiated malignancies...
August 2017: Annals of Diagnostic Pathology
https://www.readbyqxmd.com/read/28807048/response-to-single-agent-pd-1-inhibitor-after-progression-on-previous-pd-1-pd-l1-inhibitors-a-case-series
#13
Dylan J Martini, Aly-Khan A Lalani, Dominick Bossé, John A Steinharter, Lauren C Harshman, F Stephen Hodi, Patrick A Ott, Toni K Choueiri
BACKGROUND: Monoclonal antibodies targeting the PD-1/PD-L1 axis have gained increasing attention across many solid tumors and hematologic malignancies due to their efficacy and favorable toxicity profile. With more than 1 agent now FDA-approved in a wide variety of tumor types, and with others in clinical trials, it is becoming more common that patients present to clinic for potential treatment with a second PD-1/PD-L1 inhibitor. CASE PRESENTATION: In this report, we present two patients with renal cell carcinoma and one with melanoma who received PD-1/PD-L1 inhibitors...
August 15, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28806983/profiling-of-metalloprotease-activities-in-cerebrospinal-fluids-of-patients-with-neoplastic-meningitis
#14
Catharina Conrad, Kristina Dorzweiler, Miles A Miller, Douglas A Lauffenburger, Herwig Strik, Jörg W Bartsch
BACKGROUND: Neoplastic invasion into leptomeninges and subarachnoid space, resulting in neoplastic meningitis (NM) is a fatal complication of advanced solid and hematological neoplasms. Identification of malignant involvement of the cerebrospinal fluid (CSF) early in the disease course has crucial prognostic and therapeutic implications, but remains challenging. As indicators of extracellular matrix (ECM) degradation and breakdown of the blood-brain-barrier, Matrix Metalloproteases (MMPs) and A Disintegrin and Metalloproteases (ADAMs) are potential analytes for cerebral pathophysiology and metastatic dissemination of tumor cells into the CSF...
August 14, 2017: Fluids and Barriers of the CNS
https://www.readbyqxmd.com/read/28806110/-anteposition-in-malignant-hematologic-diseases-of-siblings-in-szabolcs-szatm%C3%A3-r-bereg-county-hungary-analysis-of-data-of-a-34-year-period
#15
János Jakó, László Szerafin
INTRODUCTION: In their previous works, the authors reported findings from familial hematologic malignancies in Szabolcs-Szatmár-Bereg county, Hungary. So far there are no other studies on this topic available in Hungary. AIM: Detailed analysis of epidemiologic features of hematologic malignancies of siblings. METHOD: During a 34-year period (between January 1, 1983 and December 31, 2016), 86 families with hematologic malignancies were recorded in Szabolcs-Szatmár-Bereg county...
August 2017: Orvosi Hetilap
https://www.readbyqxmd.com/read/28803919/therapy-related-clonal-hematopoiesis-in-patients-with-non-hematologic-cancers-is-common-and-associated-with-adverse-clinical-outcomes
#16
Catherine C Coombs, Ahmet Zehir, Sean M Devlin, Ashwin Kishtagari, Aijazuddin Syed, Philip Jonsson, David M Hyman, David B Solit, Mark E Robson, José Baselga, Maria E Arcila, Marc Ladanyi, Martin S Tallman, Ross L Levine, Michael F Berger
Clonal hematopoiesis (CH), as evidenced by recurrent somatic mutations in leukemia-associated genes, commonly occurs among aging human hematopoietic stem cells. We analyzed deep-coverage, targeted, next-generation sequencing (NGS) data of paired tumor and blood samples from 8,810 individuals to assess the frequency and clinical relevance of CH in patients with non-hematologic malignancies. We identified CH in 25% of cancer patients, with 4.5% harboring presumptive leukemia driver mutations (CH-PD). CH was associated with increased age, prior radiation therapy, and tobacco use...
August 9, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28803241/gender-specific-aspects-in-patients-with-multiple-myeloma-undergoing-autologous-stem-cell-transplantation-a-single-center-experience
#17
Doris Posch, Werner Rabitsch, Philipp Wohlfarth, Michael Leiner, Edit Porpaczy, Johannes Drach, Markus Raderer, Wolfgang Lamm
OBJECTIVE: Limited data exist on gender-specific aspects in hematologic malignancies and have been obtained mostly in non-Hodgkin lymphomas. The objective of this study was to investigate gender-specific aspects in patients with multiple myeloma (MM) undergoing autologous stem cell transplantation (ASCT). METHODS: A retrospective data analysis of 191 patients with MM who underwent ASCT was performed. Data collected from clinical records included age, sex, stage, induction therapy, outcome of induction, kind of stem cell mobilization, response to induction therapy and ASCT, cytogenetic aberrations, progression-free survival, and overall survival...
August 12, 2017: Oncology
https://www.readbyqxmd.com/read/28803047/puromycin-based-inhibitors-of-aminopeptidases-for-the-potential-treatment-of-hematologic-malignancies
#18
Rohit Singh, Jessica Williams, Robert Vince
Substantial progress has been described in the study of puromycin and its analogs for antibiotic properties. However, the peptidase inhibitory activity of related analogs has not been explored as extensively. Specifically, inhibiting aminopeptidases for achieving antitumor effect has been sparsely investigated. Herein, we address this challenge by reporting the synthesis of a series of analogs based on the structural template of puromycin. We also present exhaustive biochemical and in vitro analyses in support of our thesis...
July 26, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28802908/apoptosis-signaling-and-bcl-2-pathways-provide-opportunities-for-novel-targeted-therapeutic-strategies-in-hematologic-malignances
#19
REVIEW
Huanling Wu, L Jeffrey Medeiros, Ken H Young
Apoptosis is an essential biological process involved in tissue homeostasis and immunity. Aberrations of the two main apoptotic pathways, extrinsic and intrinsic, have been identified in hematological malignancies; many of these aberrations are associated with pathogenesis, prognosis and resistance to standard chemotherapeutic agents. Targeting components of the apoptotic pathways, especially the chief regulatory BCL-2 family in the intrinsic pathway, has proved to be a promising therapeutic approach for patients with hematological malignances, with the expectation of enhanced efficacy and reduced adverse events...
August 8, 2017: Blood Reviews
https://www.readbyqxmd.com/read/28801367/comparison-of-hematological-aspects-between-neuroblastoma-patients-with-and-without-bone-marrow-infiltration
#20
Weida Wang, Xiongwen Peng, Cuirong Liang, Hao Chen, Yingchun Zhang, Xiaofei Sun, Leyuan Shen, Yue Lu
Bone marrow involvement in neuroblastoma indicates an advanced stage of the disease. In this study, we retrospectively analyzed the bone marrow infiltration status and hematological parameters of 111 cases of neuroblastoma. Among the 111 cases, 62 (55.9%) exhibited marrow infiltration. Erythrocytopenia, anemia, and thrombocytopenia were significantly (p<0.05) associated with marrow infiltration of >10% malignant cells. The evaluation of blood cell count parameters with receiver operating characteristic curves indicated that erythrocytopenia can substantially improve the accurate prediction of the risk of bone marrow involvement with a Youden index of 0...
August 2017: Annals of Clinical and Laboratory Science
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