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Jingjing Wu, Mingzhi Zhang, Delong Liu
The Bruton tyrosine kinase (BTK) inhibitor, ibrutinib, has been approved for the treatment of chronic lymphocytic leukemia, mantle cell lymphoma, and Waldenstrom's macroglobulinemia. Acquired resistance to ibrutinib due to BTK C481S mutation has been reported. Mutations in PLCγ2 can also mediate resistance to ibrutinib. Untoward effects due to off-target effects are also disadvantages of ibrutinib. More selective and potent BTK inhibitors (ACP-196, ONO/GS-4059, BGB-3111, CC-292) are being investigated. This review summarized the preclinical research and clinical data of ONO/GS-4059...
October 20, 2016: Oncotarget
Lorenz Jahn, Dirk M van der Steen, Renate S Hagedoorn, Pleun Hombrink, Michel G D Kester, Marjolein P Schoonakker, Daniëlle de Ridder, Peter A van Veelen, J H Frederik Falkenburg, Mirjam H M Heemskerk
Immunotherapy of B-cell leukemia and lymphoma with CD20-targeting monoclonal antibodies (mAbs) has demonstrated clinical efficacy. However, the emergence of unresponsive disease due to low or absent cell surface CD20 urges the need to develop additional strategies. In contrast to mAbs, T-cells via their T-cell receptor (TCR) can recognize not only extracellular but also intracellular antigens in the context of HLA molecules. We hypothesized that T-cells equipped with high affinity CD20-targeting TCRs would be able to recognize B-cell malignancies even in the absence of extracellular CD20...
October 20, 2016: Oncotarget
David P Steensma
The term "refractory anemia" was used in 1937 by Cornelius Parker Rhoads to describe patients whose anemia did not improve after treatment with liver extract or iron salts, and this term has been used to denote patients with certain subtypes of myelodysplastic syndromes (MDS) since the 1976 and 1982 French-American-British (FAB) classifications of acute leukemias and MDS. In 2016, the World Health Organization (WHO) proposed elimination of "refractory anemia" in a more general proposal for reclassification of myeloid neoplasia...
October 17, 2016: Leukemia Research
Jing Liu, Dujuan Zhao, Wenxiu He, Huiyuan Zhang, Zhonghao Li, Yuxia Luan
The anti-leukemia effect of cytarabine (Ara-C) is severely restricted by its high hydrophilic properties and rapid plasma degradation. Herein, a novel amphiphilic small molecular prodrug of Ara-C was developed by coupling a short aliphatic chain, hexanoic acid (HA) to 4-NH2 of the parent drug. Based on the amphiphilic nature, the resulting bioconjugate (HA-Ara) could spontaneously self-assemble into stable spherical nanoassemblies (NAs) with an extremely high drug loading (∼71wt%). Moreover, folate receptor (FR)-targeting NAs with high grafting efficient folic acid - bovine serum albumin (FA-BSA) conjugate immobilized on the surface (NAs/FA-BSA) was prepared...
October 19, 2016: Journal of Colloid and Interface Science
Christine Gross, Veit Wiesmann, Sebastian Millen, Martina Kalmer, Thomas Wittenberg, Jan Gettemans, Andrea K Thoma-Kress
The delta-retrovirus Human T-cell leukemia virus type 1 (HTLV-1) preferentially infects CD4+ T-cells via cell-to-cell transmission. Viruses are transmitted by polarized budding and by transfer of viral biofilms at the virological synapse (VS). Formation of the VS requires the viral Tax protein and polarization of the host cytoskeleton, however, molecular mechanisms of HTLV-1 cell-to-cell transmission remain incompletely understood. Recently, we could show Tax-dependent upregulation of the actin-bundling protein Fascin (FSCN-1) in HTLV-1-infected T-cells...
October 2016: PLoS Pathogens
Jinghui Zhang, Kelly McCastlain, Hiroki Yoshihara, Beisi Xu, Yunchao Chang, Michelle L Churchman, Gang Wu, Yongjin Li, Lei Wei, Ilaria Iacobucci, Yu Liu, Chunxu Qu, Ji Wen, Michael Edmonson, Debbie Payne-Turner, Kerstin B Kaufmann, Shin-Ichiro Takayanagi, Erno Wienholds, Esmé Waanders, Panagiotis Ntziachristos, Sofia Bakogianni, Jingjing Wang, Iannis Aifantis, Kathryn G Roberts, Jing Ma, Guangchun Song, John Easton, Heather L Mulder, Xiang Chen, Scott Newman, Xiaotu Ma, Michael Rusch, Pankaj Gupta, Kristy Boggs, Bhavin Vadodaria, James Dalton, Yanling Liu, Marcus L Valentine, Li Ding, Charles Lu, Robert S Fulton, Lucinda Fulton, Yashodhan Tabib, Kerri Ochoa, Meenakshi Devidas, Deqing Pei, Cheng Cheng, Jun Yang, William E Evans, Mary V Relling, Ching-Hon Pui, Sima Jeha, Richard C Harvey, I-Ming L Chen, Cheryl L Willman, Guido Marcucci, Clara D Bloomfield, Jessica Kohlschmidt, Krzysztof Mrózek, Elisabeth Paietta, Martin S Tallman, Wendy Stock, Matthew C Foster, Janis Racevskis, Jacob M Rowe, Selina Luger, Steven M Kornblau, Sheila A Shurtleff, Susana C Raimondi, Elaine R Mardis, Richard K Wilson, John E Dick, Stephen P Hunger, Mignon L Loh, James R Downing, Charles G Mullighan
Chromosomal rearrangements deregulating hematopoietic transcription factors are common in acute lymphoblastic leukemia (ALL). Here we show that deregulation of the homeobox transcription factor gene DUX4 and the ETS transcription factor gene ERG is a hallmark of a subtype of B-progenitor ALL that comprises up to 7% of B-ALL. DUX4 rearrangement and overexpression was present in all cases and was accompanied by transcriptional deregulation of ERG, expression of a novel ERG isoform, ERGalt, and frequent ERG deletion...
October 24, 2016: Nature Genetics
Y-M Feng, X-H Chen, X Zhang
Platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) belongs to immunoglobulin superfamily, which is key factor for adhesion and accumulation of platelets. It is proved that PECAM-1 is closely correlative with cell migration, proliferation, apoptosis, signal transduction and cellular immunity. Meanwhile, PECAM-1 involves in multiple clinical diseases, such as atherosclerosis, thrombosis and leukemia. This paper reviewed the structure and function of PECAM-1, and its roles in cell function and disease generation and progression...
October 2016: European Review for Medical and Pharmacological Sciences
I C Haznedaroglu, U Y Malkan
The existence of a local renin-angiotensin system (RAS) specific to the hematopoietic bone marrow (BM) microenvironment had been proposed two decades ago. Most of the RAS molecules including ACE, ACE2, AGT, AGTR1, AGTR2, AKR1C4, AKR1D1, ANPEP, ATP6AP2, CMA1, CPA3, CTSA, CTSD, CTSG, CYP11A1, CYP11B1, CYP11B2, CYP17A1, CYP21A2, DPP3, EGFR, ENPEP, GPER, HSD11B1, HSD11B2, IGF2R, KLK1, LNPEP, MAS1, MME, NR3C1, NR3C2, PREP, REN, RNPEP, and THOP1 are locally present in the BM microenvironment. Local BM RAS peptides control the hematopoietic niche, myelopoiesis, erythropoiesis, thrombopoiesis and the development of other cellular lineages...
October 2016: European Review for Medical and Pharmacological Sciences
Joannie Lortet-Tieulent, Ann Goding Sauer, Rebecca L Siegel, Kimberly D Miller, Farhad Islami, Stacey A Fedewa, Eric J Jacobs, Ahmedin Jemal
Importance: State-specific information about the health burden of smoking is valuable because state-level initiatives are at the forefront of tobacco control. Smoking-attributable cancer mortality estimates are currently available nationally and by cancer, but not by state. Objective: To calculate the proportion of cancer deaths among adults 35 years and older that were attributable to cigarette smoking in 2014 in each state and the District of Columbia. Design, Setting, and Participants: The population-attributable fraction (PAF) of cancer deaths due to cigarette smoking was computed using relative risks for 12 smoking-related cancers (acute myeloid leukemia and cancers of the oral cavity and pharynx; esophagus; stomach; colorectum; liver; pancreas; larynx; trachea, lung, and bronchus; cervix uteri; kidney and renal pelvis; and urinary bladder) from large US prospective studies and state-specific smoking prevalence data from the Behavioral Risk Factor Surveillance System...
October 24, 2016: JAMA Internal Medicine
Minoru Tanaka, Justin M Roberts, Hyuk-Soo Seo, Amanda Souza, Joshiawa Paulk, Thomas G Scott, Stephen L DeAngelo, Sirano Dhe-Paganon, James E Bradner
Cellular signaling is often propagated by multivalent interactions. Multivalency creates avidity, allowing stable biophysical recognition. Multivalency is an attractive strategy for achieving potent binding to protein targets, as the affinity of bivalent ligands is often greater than the sum of monovalent affinities. The bromodomain and extraterminal domain (BET) family of transcriptional coactivators features tandem bromodomains through which BET proteins bind acetylated histones and transcription factors...
October 24, 2016: Nature Chemical Biology
Chunhao Niu, Xiaoying Sun, Weijing Zhang, Han Li, Liqun Xu, Jun Li, Benke Xu, Yanna Zhang
BACKGROUND: There is an abnormal expression of nuclear receptor subfamily 2 group F member 6 (NR2F6) in human cancers such as breast cancer, colon cancer, and acute myelogenous leukemia. However, its clinical significance in cervical cancer has not been established. We explored NR2F6 expression and its clinicopathological significance in early-stage cervical cancer. METHODS: NR2F6 expression in cervical cancer cell lines and cervical cancer tissues was determined by Western blotting, real-time PCR, and immunochemistry (IHC)...
October 20, 2016: International Journal of Molecular Sciences
Bethany L Mundy-Bosse, Steven D Scoville, Li Chen, Kathleen McConnell, Hsiaoyin C Mao, Elshafa H Ahmed, Nicholas Zorko, Sophia Harvey, Jordan Cole, Xiaoli Zhang, Stefan Costinean, Carlo M Croce, Karilyn Larkin, John C Byrd, Sumithira Vasu, William Blum, Jianhua Yu, Aharon G Freud, Michael A Caligiuri
Natural killer (NK) cells can have potent antileukemic activity following haplo-mismatched, T cell-depleted stem cell transplantations for the treatment of acute myeloid leukemia (AML), but they are not successful in eradicating de novo AML. Here, we have used a mouse model of de novo AML to elucidate the mechanisms by which AML evades NK cell surveillance. NK cells in leukemic mice displayed a marked reduction in the cytolytic granules perforin and granzyme B. Further, as AML progressed, we noted the selective loss of an immature subset of NK cells in leukemic mice and in AML patients...
October 24, 2016: Journal of Clinical Investigation
Jundi Hou, Tao Luo, Ka Lam Ng, Raymond Liang, Anskar Y H Leung, Dong Sun
One of the greatest challenges in acute myeloid leukemia (AML) treatment is preventing relapse. Leukemia cells can hide in bone marrow niche or vascular niche. Hence, many chemical drugs cannot kill these cells. To characterize migration and adhesion properties of leukemia cells in specific niches, CXCR4/SDF-1α signal pathway has been widely used for investigation. AMD3100 is treated as one of the most common chemical drugs that can inhibit this signal. In the current study, we particularly investigate the effect of AMD3100 on the adhesion property of leukemia cells on stromal cells by using engineering tools, namely, optical tweezers (OT) and dielectrophoresis (DEP), to probe single cell property...
October 19, 2016: IEEE Transactions on Nanobioscience
Young Hoon Gong, Seok Jun Yoon, Min Woo Jo, Arim Kim, Young Ae Kim, Jihyun Yoon, Hyeyoung Seo, Dongwoo Kim
Cancer causes a significant deterioration in health and premature death and is a national socioeconomic burden. This study aimed to measure the burden of cancer using the disability-adjusted life year (DALY) metric based on the newly adopted methodology from the Global Burden of Disease Study in 2010. This study was conducted based on data from the Korean National Cancer Registry. The DALYs were calculated using a prevalence-based method instead of the incidence-based method used by previous studies. The total burden of cancer in 2012 was 3,470...
November 2016: Journal of Korean Medical Science
R F Schlenk, F Stegelmann, A Reiter, E Jost, N Gattermann, H Hebart, C Waller, A Hochhaus, U Platzbecker, P Schafhausen, I W Blau, W Verbeek, F H Heidel, M Werner, H Kreipe, V Teleanu, A Benner, H Döhner, M Grießhammer, K Döhner
MPN-associated myelofibrosis is a myeloproliferative neoplasm characterized by bone marrow fibrosis, cytopenias, splenomegaly and constitutional symptoms. Pomalidomide, an immune-modifying drug, is reported to improve anaemia and thrombocytopenia in some patients with MPN-associated myelofibrosis. We designed a phase-2 study of pomalidomide in patients with MPN-associated myelofibrosis and anaemia and/or thrombocytopenia and/or neutropenia. Subjects received pomalidomide 2.0 mg/d in cohort-1 (n=38) or 0.5 mg/d in cohort-2 (n=58)...
October 24, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Çetin Geçmen, Gonca Geçmen, Muzaffer Kahyaoğlu, Çağatay Önal, İbrahim Akın İzgi
No abstract text is available yet for this article.
October 2016: Türk Kardiyoloji Derneği Arşivi: Türk Kardiyoloji Derneğinin Yayın Organıdır
Murat Gül, Naci Babat, Fatih Mehmet Uçar, Mehmet Serdar Kuyumcu, Özcan Özeke
Cardiac mass can be described as an abnormal structure within or directly contiguous to the heart. Tumors and thrombi are the most common types of cardiac masses. Intracardiac thrombi have been encountered in various clinical settings and can result in severe morbidity and mortality due to embolic events. Cardiac neoplasms are extremely rare, and are usually metastatic tumors. The major primary malignancies associated with cardiac metastases include cancers of the lung, breast, stomach, and liver, and lymphoma, leukemia, and melanoma...
October 2016: Türk Kardiyoloji Derneği Arşivi: Türk Kardiyoloji Derneğinin Yayın Organıdır
Wei Yang, Phu Tran, Ziad Khan, Sherif Rezk, Susan O'Brien
No abstract text is available yet for this article.
October 24, 2016: Leukemia & Lymphoma
Pedro Alves Bezerra Morais, Renata Dalmaschio Daltoé, Heberth de Paula
The discovery of the importance of kinase activity and its relationship to the emergence and proliferation of cancer cells, due to changes in normal physiology, opened a remarkable pathway for the treatment of chronic myelogenous leukemia through intense search of drug candidates. Six Abl kinase inhibitors have received the US FDA approval as chronic myelogenous leukemia treatment, and continuous efforts in obtaining new, more effective and selective molecules are being carried out. Herein we discuss the mechanisms of Abl inhibition, structural features and ligand/protein interactions that are important for the design of new Abl kinase inhibitors...
October 24, 2016: Future Medicinal Chemistry
R M Medrano-Juarez, D Sotello, M A Orellana-Barrios, L D'Cuhna, J D Payne, K Nugent
We present a case of acute hemolytic anemia, renal failure, and Clostridium perfringens bacteremia in a patient with acute myelogenous leukemia. The high fatality of C. perfringens bacteremia requires that clinicians recognize and rapidly treat patients at risk for this infection. Although other hemolytic processes are in the differential diagnosis of these events, the presence of high fever, chills, and rapidly positive blood cultures may help narrow the diagnosis. Most cases of C. perfringens bacteremia have a concomitant coinfection, which makes broad spectrum empiric therapy essential...
2016: Case Reports in Infectious Diseases
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