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https://www.readbyqxmd.com/read/28210842/uric-acid-as-a-novel-biomarker-for-bone-marrow-function-and-incipient-hematopoietic-reconstitution-after-aplasia-in-patients-with-hematologic-malignancies
#1
Sebastian P Haen, Vicky Eyb, Nora Mirza, Aline Naumann, Andreas Peter, Markus W Löffler, Christoph Faul, Wichard Vogel, Wolfgang A Bethge, Hans-Georg Rammensee, Lothar Kanz, Martin Heni
PURPOSE: Prolonged aplasia and graft failure (GF) represent life-threatening complications after hematopoietic cell transplantation (HCT) requiring suitable biomarkers for early detection and differentiation between GF and poor graft function (PGF). Uric acid (UA) is a strong immunological danger signal. METHODS: Laboratory results were analyzed from patients undergoing either allogeneic or autologous HCT or induction chemotherapy for acute leukemia (n = 50 per group, n = 150 total)...
February 16, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28205194/novel-and-expanded-oncology-drug-approvals-of-2016-part-2-new-options-in-the-management-of-hematologic-malignancies
#2
REVIEW
Todd C Knepper, James Saller, Christine M Walko
The recent past has brought pharmacotherapeutic advances that benefit patients with hematologic malignancies. In 2016, two novel hematology drugs were approved and four previously approved hematology drugs were granted expanded use for the treatment of appropriate patient populations by the US Food and Drug Administration. These new approvals and indications represent significant steps forward in patient management: they include the first-in-class B-cell lymphoma 2 inhibitor, venetoclax, the newest targeted therapy available for the treatment of hematologic malignancies; and nivolumab, the first immune checkpoint inhibitor to be approved for treatment of a hematologic malignancy...
February 15, 2017: Oncology (Williston Park, NY)
https://www.readbyqxmd.com/read/28203342/optimizing-current-and-emerging-therapies-in-multiple-myeloma-a-guide-for-the-hematologist
#3
REVIEW
Shahzad Raza, Rachael A Safyan, Evan Rosenbaum, Alex S Bowman, Suzanne Lentzsch
Multiple myeloma (MM) is the second most common hematologic malignancy. The diagnosis of MM requires ⩾10% clonal plasma cells in the bone marrow or biopsy-proven plasmacytoma, plus evidence of end-organ damage (hypercalcemia, renal failure, anemia, and lytic bone lesions). The definition of MM has recently been expanded to include a ⩾60% clonal plasma cell burden in the bone marrow, serum involved/uninvolved light chain ratio of ⩾100, or more than one focal lesion on magnetic resonance imaging ⩾5 mm in the absence of end-organ damage...
February 2017: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/28203341/new-monoclonal-antibodies-on-the-horizon-in-multiple-myeloma
#4
REVIEW
Elizabeth K O'Donnell, Noopur S Raje
Across all cancers, monoclonal antibodies have emerged as a potential strategy for cancer therapy. Monoclonal antibodies target antigens expressed on the surface of cancer cells and accessory cells. This targeted approach uses the host's immune system to promote the killing of cancer cells. Multiple myeloma (MM) is the second most common hematologic malignancy that remains incurable in the majority of patients. The treatment of MM has evolved dramatically over the past decade and continues to evolve with the approval of four new drugs in 2015...
February 2017: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/28201978/multiple-myeloma-and-the-immune-microenvironment
#5
Yawara Kawano, Aldo M Roccaro, Jamil Azzi, Irene M Ghobrial
One of the great advances in the field of cancer therapy in recent years is the emergence of immune therapies. Immune therapies, especially immune checkpoint inhibitors, have shown promising results in pre-clinical models and clinical trials of solid tumors, such as melanoma, breast cancer and lung cancer. Therapeutic strategies targeting the immune microenvironment have also been applied to hematological malignancies such as multiple myeloma (MM), a plasma cell neoplasia characterized by clonal expansion of malignant plasma cells mainly in the bone marrow (BM)...
February 13, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28194058/l-probe-a-novel-non-anthracycline-combination-chemotherapy-regimen-for-aggressive-b-cell-non-hodgkin-lymphoma-in-elderly-patients
#6
Arjun Datt Law, Gaurav Prakash, Alka Khadwal, Ashim Das, Subhash Varma, Pankaj Malhotra
The management of aggressive B cell lymphomas in elderly patients is associated with poor tolerability of commonly used chemotherapeutic agents. The safety and tolerability of a novel combination chemotherapy regimen utilizing rituximab, lenalidomide, bendamustine, vincristine and prednisolone was assessed in a series of elderly patients with new onset or relapsed/refractory aggressive B cell lymphoma and inability to receive conventional chemotherapy due to poor performance status and/or significant comorbidities...
March 2017: Indian Journal of Hematology & Blood Transfusion
https://www.readbyqxmd.com/read/28167345/osteopetroses-emphasizing-potential-approaches-to-treatment
#7
Anna Teti, Michael J Econs
Osteopetroses are a heterogeneous group of rare genetic bone diseases sharing the common hallmarks of reduced osteoclast activity, increased bone mass and high bone fragility. Osteoclasts are bone resorbing cells that contribute to bone growth and renewal through the erosion of the mineralized matrix. Alongside the bone forming activity by osteoblasts, osteoclasts allow the skeleton to grow harmonically and maintain a healthy balance between bone resorption and formation. Osteoclast impairment in osteopetroses prevents bone renewal and deteriorates bone quality, causing atraumatic fractures...
February 3, 2017: Bone
https://www.readbyqxmd.com/read/28164761/mitogen-activated-protein-kinase-mapk-interacting-kinases-1-and-2-mnk1-and-mnk2-as-targets-for-cancer-therapy-recent-progress-in-the-development-of-mnk-inhibitors
#8
Agnieszka Dreas, Maciej Mikulski, Mariusz Milik, Charles-Henry Fabritius, Krzysztof Brzózka, Tomasz Rzymski
BACKGROUND: MNK1 and MNK2 are MAP kinase-interacting serine/threonine kinases, which are activated by RAS and MAPK signaling pathways and are involved in regulation of protein translation. Both kinases phosphorylate translation initiation factor eIF4E on a conserved serine 209. Overactivated eIF4E can act as an oncogene and contribute to the transformation both in vitro and in vivo and is highly expressed in diverse types of cancer. Interestingly, knockout mice that lack both Mnk1 and Mnk2 do not have any apparent phenotype...
February 3, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28110581/triplet-combinations-in-relapsed-refractory-myeloma-update-on-recent-phase-3-trials
#9
Jean-Samuel Boudreault, Cyrille Touzeau, Philippe Moreau
Multiple myeloma (MM) is a rare hematologic disease of antibody-secreting plasma cells. Our understanding of the pathogenesis of this malignancy has improved greatly, and at the same time, we have access to new and more effective treatments options. Over the last 5 years, a spectrum of novel therapies with different mechanisms of action, including third-generation immunomodulatory drugs (pomalidomide), second generation proteasome inhibitors (carfilzomib and ixazomib), a histone deacetylase inhibitor (panobinostat) and monoclonal antibodies (mAbs) (elotuzumab and daratumumab) has transformed our approach to the treatment of patients with relapsed/refractory MM (RRMM)...
January 21, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28107692/rna-binding-protein-msi2-positively-regulates-flt3-expression-in-myeloid-leukemia
#10
Ayuna Hattori, Daniel McSkimming, Natarajan Kannan, Takahiro Ito
FLT3 is frequently mutated and overexpressed in acute myelogenous leukemia (AML) and other hematologic malignancies. Although signaling events downstream of FLT3 receptor tyrosine kinase has been studied in depth, molecular mechanisms of how FLT3 expression is regulated at the post-transcriptional level in particular remain elusive. In this study, we investigated the roles of an RNA binding protein MSI2 as a regulator of FLT3 expression. MSI2 and FLT3 are significantly co-regulated in human AML and chronic myelogenous leukemia in blast crisis (BC-CML)...
January 11, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28105297/follicular-lymphoma-the-management-of-elderly-patient
#11
REVIEW
Alessia Castellino, Elisa Santambrogio, Maura Nicolosi, Barbara Botto, Carola Boccomini, Umberto Vitolo
Follicular lymphoma (FL) is the most common indolent non-Hodgkin lymphoma, which typically affects mature adults and elderly, whose median age at diagnosis is 65 years. The natural history of FL appears to have been favorably impacted by the introduction of Rituximab. Randomized clinical trials demonstrated that the addition of rituximab to standard chemotherapy induction has improved the overall survival and new strategies of chemo-immunotherapy, such as Bendamustine combined with Rituximab, showed optimal results on response and reduced hematological toxicity, becoming one of the standard treatments, particularly in elderly patients...
2017: Mediterranean Journal of Hematology and Infectious Diseases
https://www.readbyqxmd.com/read/28079976/maresin-1-induces-a-novel-pro-resolving-phenotype-in-human-platelets
#12
Katie L Lannan, Sherry L Spinelli, Neil Blumberg, Richard P Phipps
BACKGROUND: Antiplatelet therapy is a cornerstone of modern medical practice and is routinely employed to reduce the likelihood of myocardial infarction, thrombosis, and stroke. However, current antiplatelet therapies, such as aspirin, often have adverse side effects, including increased risk of bleeding, and some patients are relatively "aspirin-resistant". Platelets are intimately involved in hemostasis and inflammation, and clinical consequences are associated with excessive or insufficient platelet activation...
January 12, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28062906/programmed-cell-death-1-pathway-inhibition-in-myeloid-malignancies-implications-for-myeloproliferative-neoplasms
#13
REVIEW
D C Choi, D Tremblay, C Iancu-Rubin, J Mascarenhas
Myeloproliferative neoplasms (MPNs) are clonal hematopoietic diseases that belong to the spectrum of myeloid malignancies (MyMs), which also include myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), and chronic myelogenous leukemia (CML). While hematopoietic stem cell transplantation (HSCT) is a potentially curative therapeutic approach to many MyMs, the associated morbidity and mortality have necessitated the development of non-HSCT therapeutics for symptom management and disease course modification...
January 6, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28061985/multiple-myeloma-epidemiology-and-survival-a-unique-malignancy
#14
REVIEW
Dickran Kazandjian
Multiple myeloma (MM), although a rare disease, is the second most common hematologic malignancy. It is found in the spectrum of plasma cell dyscrasias, which begins with monoclonal gammopathy of unknown significance (MGUS) to overt plasma cell leukemia and extramedullary myeloma. MM is associated with significant morbidity due to its end-organ destruction. It is a disease of the older population and its incidence in the African American population is twice that of the European American population. Improvements in the treatment of MM in the past couple of decades, beginning with the use of autologous stem cell transplantation followed by availability of novel treatments such as immunomodulatory drugs (ImIDs) and proteasome inhibitors (PIs) has transformed the natural history of the disease leading to longer survival times...
December 2016: Seminars in Oncology
https://www.readbyqxmd.com/read/28060563/efficacy-and-safety-of-elotuzumab-for-the-treatment-of-multiple-myeloma
#15
Maria Gavriatopoulou, Evangelos Terpos, Efstathios Kastritis, Meletios A Dimopoulos
Multiple myeloma (MM) is the second most common hematologic malignancy and despite significant outcome improvements with novel agents, the majority of patients will eventually relapse and develop treatment resistance. Immunotherapy is emerging as a promising therapeutic approach in MM. Areas covered: Elotuzumab is a monoclonal antibody directly targeting the SLAMF7 receptor, expressed on normal and malignant plasma cells. Elotuzumab has no meaningful antimyeloma activity when given as monotherapy to patients with relapsed or refractory MM (RRMM)...
January 11, 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/28053943/novel-oncolytic-viral-therapies-in-patients-with-thoracic-malignancies
#16
REVIEW
Zeeshan Ahmad, Robert A Kratzke
Oncolytic virotherapy is the use of replication-competent viruses to treat malignancies. The potential of oncolytic virotherapy as an approach to cancer therapy is based on historical evidence that certain viral infections can cause spontaneous remission of both hematologic and solid tumor malignancies. Oncolytic virotherapy may eliminate cancer cells through either direct oncolysis of infected tumor cells or indirect immune-mediated oncolysis of uninfected tumor cells. Recent advances in oncolytic virotherapy include the development of a wide variety of genetically attenuated RNA viruses with precise cellular tropism and the identification of cell-surface receptors that facilitate viral transfer to the tissue of interest...
2017: Oncolytic Virotherapy
https://www.readbyqxmd.com/read/28053195/tcr-based-therapy-for-multiple-myeloma-and-other-b-cell-malignancies-targeting-intracellular-transcription-factor-bob1
#17
Lorenz Jahn, Pleun Hombrink, Renate S Hagedoorn, Michel G D Kester, Dirk M van der Steen, Tania Rodriguez, Tsvetelina Pentcheva-Hoang, Arnoud H de Ru, Marjolein P Schoonakker, Miranda H Meeuwsen, Marieke Griffioen, Peter A van Veelen, J H Frederik Falkenburg, Mirjam H M Heemskerk
Immunotherapy of hematological malignancies or solid tumors by administration of monoclonal antibodies or T-cells engineered to express chimeric antigen receptors or T-cell receptors (TCRs) has demonstrated clinical efficacy. However, antigen-loss tumor escape variants and the absence of currently targeted antigens on several malignancies hampers the widespread application of immunotherapy. We have isolated a TCR targeting a peptide of the intracellular B-cell specific transcription factor BOB1 presented in the context of HLA-B*07:02...
January 4, 2017: Blood
https://www.readbyqxmd.com/read/28052693/safety-and-efficacy-of-ex-vivo-donor-lung-adenoviral-il-10-gene-therapy-in-a-large-animal-lung-transplant-survival-model
#18
Tiago Noguchi Machuca, Marcelo Cypel, Riccardo Bonato, Jonathan C Yeung, Yi-Min Chun, Stephen Juvet, Guan Zehong, David M Hwang, Manyin Chen, Tomohito Saito, Constantine Harmantas, Beverly Davidson, Thomas K Waddell, Mingyao Liu, Shaf Keshavjee
OBJECTIVE: Ex vivo normothermic lung perfusion (EVLP) is a novel platform and method developed to facilitate functional assessment and implementation of advanced therapies for donor lungs prior to transplantation. We aimed to determine the safety and immunological and functional benefits of ex vivo adenoviral human IL-10 (AdhIL-10) gene delivery to prevent the development of primary graft dysfunction in a large animal survival model. METHODS: Pig donor lungs were retrieved, preserved for 6 hours at 4oC and then randomly assigned to 4 groups: 1) AdhIL-10 Gene Therapy: 12 hours EVLP + AdhIL-10 intra-bronchial delivery; 2) EVLP-control: 12 hours EVLP; 3) Vector-control: 12 hours EVLP + adenoviral vector intra-bronchial delivery; and 4) Prolonged hypothermic preservation: Additional 12 hours of cold ischemia...
January 4, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28043820/kinase-signaling-and-targeted-therapy-for-primary-myelofibrosis
#19
REVIEW
Qiong Yang, John D Crispino, Qiang Jeremy Wen
The myeloproliferative neoplasms (MPNs) are somatic mutation-driven hematologic malignancies characterized by bone marrow fibrosis and the accumulation of atypical megakaryocytes with reduced polyploidization in the primary myelofibrosis subtype of the MPNs. Increasing evidence points to a dominant role of abnormal megakaryocytes in disease initiation and progression. Here we review the literature related to kinase signaling pathways relevant to megakaryocyte differentiation and proliferation, including Aurora A kinase, RhoA/ROCK, and JAK/STAT, as well as the activities of their targeted inhibitors in models of the disease...
December 30, 2016: Experimental Hematology
https://www.readbyqxmd.com/read/28039364/leptomeningeal-metastases-a-rano-proposal-for-response-criteria
#20
REVIEW
Marc Chamberlain, Larry Junck, Dieta Brandsma, Riccardo Soffietti, Roberta Rudà, Jeffrey Raizer, Willem Boogerd, Sophie Taillibert, Morris D Groves, Emilie Le Rhun, Julie Walker, Martin van den Bent, Patrick Y Wen, Kurt A Jaeckle
Leptomeningeal metastases (LM) currently lack standardization with respect to response assessment. A Response Assessment in Neuro-Oncology (RANO) working group with expertise in LM developed a consensus proposal for evaluating patients treated for this disease. Three basic elements in assessing response in LM are proposed: a standardized neurological examination, cerebral spinal fluid (CSF) cytology or flow cytometry, and radiographic evaluation. The group recommends that all patients enrolling in clinical trials undergo CSF analysis (cytology in all cancers; flow cytometry in hematologic cancers), complete contrast-enhanced neuraxis MRI, and in instances of planned intra-CSF therapy, radioisotope CSF flow studies...
December 29, 2016: Neuro-oncology
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