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https://www.readbyqxmd.com/read/29916761/a-phase-2-study-of-ofatumumab-arzerra-%C3%A2-in-combination-with-a-pan-akt-inhibitor-afuresertib-in-previously-treated-patients-with-chronic-lymphocytic-leukemia-cll
#1
Christine I Chen, Harminder Paul, Lisa W Le, Ellen N Wei, Susi Snitzler, Trina Wang, Olga Levina, Sumeet Kakar, Anthea Lau, Michelle Queau, James B Johnston, Deborah A Smith, Suzanne Trudel
AKT plays a centralized role in tumor proliferation and survival and is aberrantly activated in chronic lymphocytic leukemia (CLL). In this phase 2 trial, 30 relapsed/refractory CLL patients were treated with combination afuresertib, a novel oral AKT inhibitor, and ofatumumab for 6 months, followed by afuresertib maintenance for 12 months. We aimed to achieve deeper and more durable responses, without requiring long-term continuous treatment. Treatment was generally well tolerated but respiratory infections were common, with 18% severe requiring hospitalization...
June 19, 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29900054/large-scale-database-mining-reveals-hidden-trends-and-future-directions-for-cancer-immunotherapy
#2
Jakob Nikolas Kather, Anna Sophie Berghoff, Dyke Ferber, Meggy Suarez-Carmona, Constantino Carlos Reyes-Aldasoro, Nektarios A Valous, Rodrigo Rojas-Moraleda, Dirk Jäger, Niels Halama
Cancer immunotherapy has fundamentally changed the landscape of oncology in recent years and significant resources are invested into immunotherapy research. It is in the interests of researchers and clinicians to identify promising and less promising trends in this field in order to rationally allocate resources. This requires a quantitative large-scale analysis of cancer immunotherapy related databases. We developed a novel tool for text mining, statistical analysis and data visualization of scientific literature data...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29896298/cancer-radiotheranostics-targeting-carbonic-anhydrase-ix-with-111-in-and-90-y-labeled-ureidosulfonamide-scaffold-for-spect-imaging-and-radionuclide-based-therapy
#3
Shimpei Iikuni, Masahiro Ono, Hiroyuki Watanabe, Yoichi Shimizu, Kohei Sano, Hideo Saji
Hypoxic cells dynamically translocate during tumor growth and after radiotherapy. The most desirable direction for therapy targeting hypoxic cells is combining imaging and therapy (theranostics), which may help realize personalized medicine. Here, we conducted cancer radiotheranostics targeting carbonic anhydrase-IX (CA-IX), which is overexpressed in many kinds of hypoxic cancer cells, using low-molecular-weight 111 In and 90 Y complexes with a bivalent ureidosulfonamide scaffold as the CA-IX-binding moiety ([111 In/90 Y]US2)...
2018: Theranostics
https://www.readbyqxmd.com/read/29895903/integrated-dna-rna-targeted-genomic-profiling-of-diffuse-large-b-cell-lymphoma-using-a-clinical-assay
#4
Andrew M Intlekofer, Erel Joffe, Connie L Batlevi, Patrick Hilden, Jie He, Venkatraman E Seshan, Andrew D Zelenetz, M Lia Palomba, Craig H Moskowitz, Carol Portlock, David J Straus, Ariela Noy, Steven M Horwitz, John F Gerecitano, Alison Moskowitz, Paul Hamlin, Matthew J Matasar, Anita Kumar, Marcel R van den Brink, Kristina M Knapp, Janine D Pichardo, Michelle K Nahas, Sally E Trabucco, Tariq Mughal, Amanda R Copeland, Elli Papaemmanuil, Mathai Moarii, Ross L Levine, Ahmet Dogan, Vincent A Miller, Anas Younes
We sought to define the genomic landscape of diffuse large B-cell lymphoma (DLBCL) by using formalin-fixed paraffin-embedded (FFPE) biopsy specimens. We used targeted sequencing of genes altered in hematologic malignancies, including DNA coding sequence for 405 genes, noncoding sequence for 31 genes, and RNA coding sequence for 265 genes (FoundationOne-Heme). Short variants, rearrangements, and copy number alterations were determined. We studied 198 samples (114 de novo, 58 previously treated, and 26 large-cell transformation from follicular lymphoma)...
June 12, 2018: Blood Cancer Journal
https://www.readbyqxmd.com/read/29891120/evolving-understanding-of-chronic-myelomonocytic-leukemia-implications-for-future-treatment-paradigms
#5
REVIEW
Anita Geevarghese, John Mascarenhas
Chronic myelomonocytic leukemia (CMML) is a relatively uncommon hematologic malignancy that manifests as peripheral monocytosis, has varying degrees of bone marrow dysplasia, and is associated with poor outcomes. Despite a growing appreciation of the pathobiologic mechanisms driving CMML, current therapies have not clearly demonstrated any survival benefit. The complex pathobiology of CMML highlights the intricate aberrantly activated cellular pathways that influence disease phenotype and limit current treatment options...
May 23, 2018: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29890129/microrna-199a-b-5p-enhance-imatinib-efficacy-via-repressing-wnt2-signaling-mediated-protective-autophagy-in-imatinib-resistant-chronic-myeloid-leukemia-cells
#6
Peng-Hsu Chen, Ann-Jeng Liu, Kuo-Hao Ho, Ya-Ting Chiu, Zhe-Harn Anne Lin, Yi-Ting Lee, Chwen-Ming Shih, Ku-Chung Chen
Imatinib (IM) is a first-line therapeutic drug for chronic myeloid leukemia (CML), a hematological disease. Mutations in the BCR-ABL domain increase formation of IM resistance in CML. However, not all patients are BCR-ABL domain-mutant dependent. Investigating non-mutant mechanisms in the development of acquired IM resistance is a critical issue. We explored the mechanisms which influence IM efficacy and resistance in CML. Higher protective autophagy was identified in IM-resistant K562 (K562R) cells. Inhibition of autophagy by the inhibitors, chloroquine and 3-methyladenine, enhanced IM's efficacy in K562R cells...
June 8, 2018: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29881883/red-blood-cells-metabolome-changes-upon-treatment-with-different-x-ray-irradiation-doses
#7
Fabio Baroni, Chiara Marraccini, Lucia Merolle, Vando Piccagli, Daniele Lambertini, Mauro Iori, Tommaso Fasano, Emanuela Casali, Alberto Spisni, Roberto Baricchi, Thelma A Pertinhez
The upholding of red blood cells (RBC) quality and the removal of leukocytes are two essential issues in transfusion therapy. Leukodepletion provides optimum results, nonetheless there are cases where irradiation is recommended for some groups of hematological patients such as the ones with chronic graft-vs-host disease, congenital cellular immunodeficiency, and hematopoietic stem cell transplant recipients. The European guidelines suggest irradiation doses from 25 to 50 Gray (Gγ). We evaluated the effect of different prescribed doses (15 to 50 Gγ) of X-ray irradiation on fresh leukodepleted RBCs bags using a novel protocol that provides a controlled irradiation...
June 7, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29877241/-chronic-lymphocytic-leukemia-update-on-pathophysiology-and-management
#8
Junji Suzumiya
Chronic lymphocytic leukemia (CLL) is the most common hematological malignancy in the Western countries. Although a multi-step model has been proposed for the pathogenesis of CLL as well as other malignancies, the precise mechanism underlying the development of CLL remains complicated and unclear. In addition, several studies have investigated adverse prognostic factors, including gene abnormalities and the evolution of clones with the disease progression. FCR (fludarabine, cyclophosphamide, and rituximab) has been the standard first-line therapy for "fit" younger patients without TP53 abnormality/17p deletion...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/29876013/combined-hat-ezh2-modulation-leads-to-cancer-selective-cell-death
#9
Francesca Petraglia, Abhishek A Singh, Vincenzo Carafa, Angela Nebbioso, Mariarosaria Conte, Lucia Scisciola, Sergio Valente, Alfonso Baldi, Amit Mandoli, Valeria Belsito Petrizzi, Concetta Ingenito, Sandro De Falco, Valeria Cicatiello, Ivana Apicella, Eva M Janssen-Megens, Bowon Kim, Guoqiang Yi, Colin Logie, Simon Heath, Menotti Ruvo, Albertus T J Wierenga, Paul Flicek, Marie Laure Yaspo, Veronique Della Valle, Olivier Bernard, Stefano Tomassi, Ettore Novellino, Alessandra Feoli, Gianluca Sbardella, Ivo Gut, Edo Vellenga, Hendrik G Stunnenberg, Antonello Mai, Joost H A Martens, Lucia Altucci
Epigenetic alterations have been associated with both pathogenesis and progression of cancer. By screening of library compounds, we identified a novel hybrid epi-drug MC2884, a HAT/EZH2 inhibitor, able to induce bona fide cancer-selective cell death in both solid and hematological cancers in vitro , ex vivo and in vivo xenograft models. Anticancer action was due to an epigenome modulation by H3K27me3, H3K27ac, H3K9/14ac decrease, and to caspase-dependent apoptosis induction. MC2884 triggered mitochondrial pathway apoptosis by up-regulation of cleaved-BID, and strong down-regulation of BCL2...
May 22, 2018: Oncotarget
https://www.readbyqxmd.com/read/29872437/perspectives-on-chimeric-antigen-receptor-t-cell-immunotherapy-for-solid-tumors
#10
REVIEW
Paris Kosti, John Maher, James N Arnold
Chimeric antigen receptor (CAR) T-cell therapy entails the genetic engineering of a patient's T-cells to express membrane spanning fusion receptors with defined specificities for tumor-associated antigens. These CARs are capable of eliciting robust T-cell activation to initiate killing of the target tumor cells. This therapeutic approach has produced unprecedented clinical outcomes in the treatment of "liquid" hematologic cancers, but to date has not produced comparable responses in targeting solid malignancies...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29867836/future-perspectives-on-drug-targeting-in-adult-t-cell-leukemia-lymphoma
#11
REVIEW
Francesca Marino-Merlo, Antonio Mastino, Sandro Grelli, Olivier Hermine, Ali Bazarbachi, Beatrice Macchi
Human T cell leukemia virus type 1 (HTLV-1) is the etiological agent of adult T cell leukemia/lymphoma (ATL), HTLV-1 associated myelopathy (HAM/TSP), and of a number of inflammatory diseases with an estimated 10-20 million infected individuals worldwide. Despite a number of therapeutic approaches, a cure for ATL is still in its infancy. Conventional chemotherapy has short-term efficacy, particularly in the acute subtype. Allogeneic stem cell transplantation offers long-term disease control to around one third of transplanted patients, but few can reach to transplant...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29844860/phase-i-dose-escalation-study-of-f50067-a-humanized-anti-cxcr4-monoclonal-antibody-alone-and-in-combination-with-lenalidomide-and-low-dose-dexamethasone-in-relapsed-or-refractory-multiple-myeloma
#12
Guillemette Fouquet, Stéphanie Guidez, Valentine Richez, Anne-Marie Stoppa, Christophe Le Tourneau, Margaret Macro, Cécile Gruchet, Arthur Bobin, Niels Moya, Thomas Syshenko, Florence Sabirou, Anthony Levy, Paul Franques, Hélène Gardeney, Lionel Karlin, Lotfi Benboubker, Monia Ouali, Jean-Claude Vedovato, Pierre Ferre, Mariya Pavlyuk, Michel Attal, Thierry Facon, Xavier Leleu
Purpose: Multiple myeloma (MM) remains an incurable disease as tumor cells ultimately resist to all available drugs. Homing of tumor cells to the bone marrow microenvironment, involving especially the CXCR4/SDF-1 axis, allows them to survive, proliferate and resist to therapy. F50067, a humanized anti-CXCR4 IgG1 antibody, has promising preclinical activity in MM.We present a phase I multicenter escalation study in relapsed/refractory MM (RRMM) to determine the maximum tolerated dose (MTD) for F50067 alone and in combination with lenalidomide and low dose dexamethasone (Len-Dex)...
May 8, 2018: Oncotarget
https://www.readbyqxmd.com/read/29801808/management-of-the-elderly-patient-with-al-amyloidosis
#13
Mario Nuvolone, Paolo Milani, Giovanni Palladini, Giampaolo Merlini
Systemic immunoglobulin light chain (AL) amyloidosis is an aging-associated protein misfolding and deposition disease. This condition is caused by a small and otherwise indolent plasma cell (or B cell) clone secreting an unstable circulating light chain, which misfolds and deposits as amyloid fibrils possibly leading to progressive dysfunction of affected organs. AL amyloidosis can occur in the typical setting of other, rarer forms of systemic amyloidosis and can mimic other more prevalent conditions of the elderly...
May 22, 2018: European Journal of Internal Medicine
https://www.readbyqxmd.com/read/29791237/the-future-of-chronic-lymphocytic-leukemia-potential-directions-from-ash-2017
#14
Stefano Molica
Novel targeted therapies - including ibrutinib, venetoclax, and idelalisib - have revolutionized the treatment landscape of chronic lymphocytic leukemia (CLL). Therefore, studying combinations of novel agents (NAs) with a distinct mechanism of action and nonoverlapping toxicities is challenging. Area covered: The 2017 American Society Hematology Annual Meeting has represented a showcase for several trials combining NAs. These studies are currently evaluating the efficacy NA plus anti-CD20 monoclonal antibody, NA plus NA (with or without anti-CD20 monoclonal antibody), and NA plus chemo-immunotherapy...
June 2018: Expert Review of Hematology
https://www.readbyqxmd.com/read/29783691/old-and-young-actors-playing-novel-roles-in-the-drama-of-multiple-myeloma-bone-marrow-microenvironment-dependent-drug-resistance
#15
REVIEW
Sabrina Manni, Marilena Carrino, Gianpietro Semenzato, Francesco Piazza
Multiple myeloma (MM) is the second most frequent hematologic cancer. In addition to the deleterious effects of neoplastic plasma cell growth and spreading during the disease evolution, this tumor is characterized by the serious pathological consequences due to the massive secretion of monoclonal immunoglobulins and by the derangement of bone physiology with progressive weakening of the skeleton. Despite significant progresses having been made in the last two decades in the therapeutic management of this plasma cell tumor, MM remains invariably lethal, due to its extremely complex genetic architecture and to the constant protection it receives from the tumor niche, which is represented by the bone marrow microenvironment...
May 18, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29770997/gemcitabine-nab-paclitaxel-for-pediatric-relapsed-refractory-sarcomas
#16
Jonathan L Metts, Adina L Alazraki, Dana Clark, Ernest K Amankwah, Karen J Wasilewski-Masker, Bradley A George, Thomas A Olson, Thomas Cash
BACKGROUND: Pediatric patients with relapsed/refractory sarcomas have poor outcomes and need novel therapies that provide disease control while maintaining an acceptable quality of life. The activity and toxicity of gemcitabine and nab-paclitaxel in combination has not been reported in pediatrics. PROCEDURE: We reviewed the records of fifteen relapsed/refractory patients and one treatment-naïve patient who received gemcitabine/nab-paclitaxel at our institution...
May 17, 2018: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/29751067/clonal-expansion-and-myeloid-leukemia-progression-modeled-by-multiplex-gene-editing-of-murine-hematopoietic-progenitor-cells
#17
Xiangguo Shi, Ayumi Kitano, Yajian Jiang, Victor Luu, Kevin A Hoegenauer, Daisuke Nakada
Recent advances in next-generation sequencing have identified novel mutations and revealed complex genetic architectures in human hematological malignancies. Moving forward, new methods to quickly generate animal models that recapitulate the complex genetics of human hematological disorders are needed to transform the genetic information to new therapies. Here, we used a ribonucleoprotein-based CRISPR/Cas9 system to model human clonal hematopoiesis of indeterminate potential and acute myeloid leukemia (AML)...
May 8, 2018: Experimental Hematology
https://www.readbyqxmd.com/read/29747654/bcl-2-as-therapeutic-target-for-hematological-malignancies
#18
REVIEW
Guilherme Fleury Perini, Glaciano Nogueira Ribeiro, Jorge Vaz Pinto Neto, Laura Tojeiro Campos, Nelson Hamerschlak
Disruption of the physiologic balance between cell proliferation and cell death is an important step of cancer development. Increased resistance to apoptosis is a key oncogenic mechanism in several hematological malignancies and, in many cases, especially in lymphoid neoplasias, has been attributed to the upregulation of BCL-2. The BCL-2 protein is the founding member of the BCL-2 family of apoptosis regulators and was the first apoptosis modulator to be associated with cancer. The recognition of the important role played by BCL-2 for cancer development and resistance to treatment made it a relevant target for therapy for many diseases, including solid tumors and hematological neoplasias...
May 11, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29743205/preclinical-development-of-a-bispecific-antibody-that-safely-and-effectively-targets-cd19-and-cd47-for-the-treatment-of-b-cell-lymphoma-and-leukemia
#19
Vanessa Buatois, Zoë Johnson, Susana Salgado-Pires, Anne Papaïoannou, Eric Hatterer, Xavier Chauchet, Françoise Richard, Leticia Barba, Bruno Daubeuf, Laura Cons, Lucile Broyer, Matilde D'Asaro, Thomas Matthes, Simon LeGallou, Thierry Fest, Karin Tarte, Robert K Clarke Hinojosa, Eulàlia Genescà Ferrer, José María Ribera, Aditi Dey, Katharine Bailey, Adele K Fielding, Linda Eissenberg, Julie Ritchey, Michael Rettig, John F DiPersio, Marie H Kosco-Vilbois, Krzysztof Masternak, Nicolas Fischer, Limin Shang, Walter G Ferlin
CD47, a ubiquitously expressed innate immune checkpoint receptor that serves as a universal "don't eat me" signal of phagocytosis, is often up-regulated by hematological and solid cancers to evade immune surveillance. Development of CD47-targeted modalities is hindered by the ubiquitous expression of the target, often leading to rapid drug elimination and hemotoxicity including anemia. To overcome such liabilities, we have developed a fully human bispecific antibody, NI-1701, designed to co-engage CD47 and CD19 selectively on B cells...
May 9, 2018: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29731877/outcome-of-patient-with-high-risk-chronic-myelomonocytic-leukemia-treated-with-decitabine-prior-to-transformation-to-acute-myeloid-leukemia-a-case-report
#20
Huan Liu, Juan Cheng, Long Zhao, Qian Xu, Mingming Xue, Shuling Zhang, Bei Liu
The present study describes a patient with high-risk chronic myelomonocytic leukemia (CMML), for whom decitabine therapy achieved partial remission, prior to a sudden transformation to acute myeloid leukemia (AML) and an inferior outcome. The 53-year-old male reported easily bruising for 5 months. Examination indicated a diagnosis of CMML. Chromosome analysis identified a 48, XY, +8, +21 karyotype, classifying the patient as high-risk, according to a clinical/molecular CPSS (CPSS-Mol) model. Gene sequencing detected a mutation in DNA methyltransferase 3α, which is relatively rarely identified in CMML and has recently been reported to have an independent prognostic impact on overall survival time...
May 2018: Oncology Letters
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