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https://www.readbyqxmd.com/read/29793046/validation-of-the-revised-pam-score-in-patients-with-aml-undergoing-allogeneic-hematopoietic-stem-cell-transplantation
#1
Jan M Middeke, Frederike Kollinger, Henning Baldauf, Friedrich Stölzel, Martin Wermke, Malte von Bonin, Katja Sockel, Cornelia S Link, Raphael Teipel, Christoph Röllig, Christian Thiede, Uwe Platzbecker, Gerhard Ehninger, Martin Bornhäuser, Johannes Schetelig
PURPOSE: Despite recent advances, allogeneic hematopoietic stem cell transplantation (alloHSCT) continues to be accompanied by a high rate of morbidity and mortality. Several scores have been developed to predict outcome after HSCT. The PAM score has been recently revised, and utilizes information on patient age, donor type, disease risk, cytomegalovirus (CMV) serostatus of patients and donors, and the forced expiratory volume in one second (FEV1). The aim of this study was to analyze the predictive power of the PAM score in an independent, large cohort of acute myeloid leukemia (AML) patients...
May 21, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29792945/cross-linking-by-epichlorohydrin-and-diepoxybutane-correlates-with-cytotoxicity-and-leads-to-apoptosis-in-human-leukemia-hl-60-cells
#2
Phuong M Le, Vanesa L Silvestri, Samuel C Redstone, Jordanne B Dunn, Julie T Millard
The bifunctional alkylating agents epichlorohydrin (ECH) and diepoxybutane (DEB) have been linked to increased cancer risks in industrial workers. These compounds react with DNA and proteins, leading to genotoxic effects. We used the comet assay to monitor formation of cross-links in HL-60 cells treated with ECH, DEB, and the structurally related anti-cancer drug mechlorethamine (HN2). We report a time- and dose-dependent cytotoxicity that correlated with cross-linking activity, following the order HN2 > DEB > ECH...
May 21, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29792808/eradication-of-established-tumors-by-chemically-self-assembled-nanoring-csan-targeted-t-cells
#3
Jacob Petersburg, Jingjing Shen, Clifford M Csizmar, Katherine A Murphy, Justin Spanier, Kari Gabrielse, Thomas S Griffith, Brian Fife, Carston R Wagner
Our laboratory has developed chemically self-assembled nanorings (CSANs) as prosthetic antigen receptors (PARs) for the non-genetic modification of T-cell surfaces. PARs have been successfully employed in vitro to activate T cells for the selective killing of leukemia cells. However, PAR efficacy has yet to be evaluated in vivo or against solid tumors. Therefore, we developed bispecific PARs that selectively target the human CD3 receptor and human Epithelial Cell Adhesion Molecule (EpCAM), which is overexpressed on multiple carcinomas and cancer stem cells...
May 24, 2018: ACS Nano
https://www.readbyqxmd.com/read/29792762/genetic-profiling-in-acute-myeloid-leukemia-a-path-to-predicting-treatment-outcome
#4
Giuseppe Visani, Federica Loscocco, Alessandro Isidori, Pier Paolo Piccaluga
Despite substantial progresses in acute myeloid leukemia (AML) diagnosis and treatment, at least half of patient will eventually die for the disease. In the last decades, the use of genetic and genomic approaches allowed the identification of patients with higher risk of recurrence after and/or resistance to CHT. However, though many novel drugs have been proposed and tested, only little clinical improvements have been made concerning the treatment of the so called 'high risk' patients. Areas covered: In this article, the authors, based on their own experience and the most updated literature, review the basic knowledge of AML prognostication and treatment prediction developed throughout genetic and genomic profiling, and focus on the use of gene expression profiling as a promising predictive tool...
May 24, 2018: Expert Review of Hematology
https://www.readbyqxmd.com/read/29792669/self-assembling-glutamate-functionalized-cyclodextrin-molecular-tube-for-specific-enrichment-of-n-linked-glycopeptides
#5
Haijiao Zheng, Xiqian Li, Qiong Jia
Cyclodextrin molecular tube (CDMT), a new comer of cyclodextrin family, possesses large and hydrophilic outer area and stable structure. Its development and applications remain highly desired, especially in the field of separation and enrichment. Herein, we developed a CDMT-based enrichment platform focusing on the specific capture of glycopeptides. To enhance the hydrophilicity of CDMT, it was functionalized with glutamate (glu). The prepared gluCDMT exhibited large hydrophilic surface, high stability, and good acidic/alkalic resistance...
May 24, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29792386/disparate-effects-of-shb-gene-deficiency-on-disease-characteristics-in-murine-models-of-myeloid-b-cell-and-t-cell-leukemia
#6
Maria Jamalpour, Xiujuan Li, Karin Gustafsson, Jeffrey W Tyner, Michael Welsh
The Src homology-2 domain protein B is an adaptor protein operating downstream of tyrosine kinases. The Shb gene knockout has been found to accelerate p210 Breakpoint cluster region-cAbl oncogene 1 tyrosine kinase-induced leukemia. In human myeloid leukemia were tumors with high Src homology-2 domain protein B mRNA content, tumors were, however, associated with decreased latency and myeloid leukemia exhibiting immune cell characteristics. Thus, the aim of this study was to investigate the effects of Shb knockout on the development of leukemia in three additional models, that is, colony stimulating factor 3 receptor-T618I-induced neutrophilic leukemia, p190 Breakpoint cluster region-cAbl oncogene 1 tyrosine kinase-induced B-cell leukemia, and G12D-Kras-induced T-cell leukemia/thymic lymphoma...
April 2018: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/29792338/molecular-mechanism-for-the-influence-of-gender-dimorphism-on-alcoholic-liver-injury-in-mice
#7
S-Q Li, P Wang, D-M Wang, H-J Lu, R-F Li, L-X Duan, S Zhu, S-L Wang, Y-Y Zhang, Y-L Wang
It is known that women develop alcoholic liver injury more rapidly and have a lower alcohol toxic threshold than men. However, the detailed molecular mechanisms remain unclear. The precise mechanism responsible for the sex difference needs to be determined. Female and male mice were given ethanol by intragastric infusion every day for 4 weeks. The pathological changes were detected by hematoxylin-eosin, Sirius red, oil red O, periodic acid-Schiff, and Hochest33258 staining in the liver of female and male mice...
January 1, 2018: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/29792154/exploration-of-hetero-aryl-derived-thienylchalcones-for-antiviral-and-anticancer-activities
#8
Vikrant Patil, Siddappa A Patil, Renukadevi Patil, Alejandro Bugarin, Kenneth Beaman, Shivaputra A Patil
BACKGROUND: Search for new antiviral and anticancer agents are essential because of the emergence of drug resistance in recent years. In continuation of our efforts in identifying the new small molecule antiviral and anticancer agents, we identified chalcones as potent antiviral and anticancer agents. OBJECTIVE: With the aim of identifying the broad acting antiviral and anticancer agents, we discovered substituted aryl/heteroaryl derived thienyl chalcones as antiviral and anticancer agents...
May 23, 2018: Medicinal Chemistry
https://www.readbyqxmd.com/read/29791428/-acute-liver-failure-as-presentation-of-adult-t-cell-leukemia-in-an-htlv-1-patient
#9
Julissa Guevara Miranda, Patricia Guzmán Rojas, Fernando Alonso Mejía Cordero
Acute liver failure is the development of severe hepatic injury with deterioration of liver synthesis function and encephalopathy. Among all the variety of causes, neoplastic infiltration represents less than 0.5%. We present the case of a male patient with a past medical history of HTLV-1 infection, who reports symptoms of acute hepatitis, being diagnosed with Adult T-cell leukemia/lymphoma. Unfortunately, the patient had a rapid deterioration and passed away a few days after admission.
January 2018: Revista de Gastroenterología del Perú: órgano Oficial de la Sociedad de Gastroenterología del Perú
https://www.readbyqxmd.com/read/29791237/the-future-of-chronic-lymphocytic-leukemia-potential-directions-from-ash-2017
#10
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 distinct mechanism of action and non-overlapping toxicities is challenging. Area covered: The 2017 American Society Hematology (ASH) 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...
May 23, 2018: Expert Review of Hematology
https://www.readbyqxmd.com/read/29790971/brain-activity-associated-with-attention-deficits-following-chemotherapy-for-childhood-acute-lymphoblastic-leukemia
#11
Slim Fellah, Yin T Cheung, Matthew A Scoggins, Ping Zou, Noah D Sabin, Ching-Hon Pui, Leslie L Robison, Melissa M Hudson, Robert J Ogg, Kevin R Krull
Background: The impact of contemporary chemotherapy treatment for childhood acute lymphoblastic leukemia on central nervous system activity is not fully appreciated. Methods: Neurocognitive testing and functional magnetic resonance imaging (fMRI) were obtained in 165 survivors five or more years postdiagnosis (average age = 14.4 years, 7.7 years from diagnosis, 51.5% males). Chemotherapy exposure was measured as serum concentration of methotrexate following high-dose intravenous injection...
May 21, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29790457/comparison-of-different-conditioning-regimens-of-haploidentical-hematopoietic-stem-cell-transplant-in-patients-with-acute-myeloid-leukemia
#12
Yujie Jiang, Xiaosheng Fang, Xiaohui Sui, Xin Liu, Ying Li, Xianghua Wang, Hongzhi Xu, Lingyan Zhang, Xin Wang
OBJECTIVES: We evaluated the safety and efficacy of 2 conditioning regimens (busulfan/fludarabine vs modified busulfan/cyclophosphamide) in patients with acute myeloid leukemia undergoing haploidentical hematopoietic stem cell transplant. MATERAILS AND METHODS: Twenty patients with primary acute myeloid leukemia had been randomized into busulfan/fludarabine and modified busulfan/cyclophosphamide groups. We retrospectively compared hematopoietic engraftment, regimen-related toxicity, graft-versus-host disease, transplant-related mortality, leukemia-free survival, and overall survival between the groups...
May 23, 2018: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/29790117/regulatory-roles-of-mir-155-and-let-7b-on-the-expression-of-inflammation-related-genes-in-thp-1-cells-effects-of-fatty-acids
#13
J L Marques-Rocha, M Garcia-Lacarte, M Samblas, J Bressan, J A Martínez, F I Milagro
The main aim of this investigation was to study the regulatory roles of let-7b and miR-155-3p on the expression of inflammation-associated genes in monocytes, macrophages, and lipopolysaccharide (LPS)-activated macrophages (AcM). A second goal was to analyze the potential modulatory roles of different fatty acids, including oleic, palmitic, eicosapentaenoic (EPA), and docosahexaenoic (DHA), on the expression of these miRNAs in the three cell types. This hypothesis was tested in human acute monocytic leukemia cells (THP-1), which were differentiated into macrophages with 2-O-tetradecanoylphorbol-13-acetate (TPA) and further activated with LPS for 24 h...
May 22, 2018: Journal of Physiology and Biochemistry
https://www.readbyqxmd.com/read/29789639/fludarabine-and-neurotoxicity-in-engineered-t-cell-therapy
#14
Kate L Lowe, Crystal L Mackall, Elliot Norry, Rafael Amado, Bent K Jakobsen, Gwendolyn Binder
Adoptive T-cell therapy, incorporating engineered T cell receptors (TCRs) or chimeric antigen receptors (CARs), target tumor antigens with high affinity and specificity. To increase the potency of adoptively transferred T cells, patients are conditioned with lymphodepleting chemotherapy regimens prior to adoptive T-cell transfer (ACT), and data suggest that fludarabine is an important component of an effective regimen. In a recent clinical trial using CAR-T cells engineered to target the CD19 B-cell antigen to treat acute lymphoblastic leukemia, JCAR-015 (NCT02535364), two patient deaths due to cerebral edema led to trial suspension...
May 7, 2018: Gene Therapy
https://www.readbyqxmd.com/read/29789603/vorinostat-and-quinacrine-have-synergistic-effects-in-t-cell-acute-lymphoblastic-leukemia-through-reactive-oxygen-species-increase-and-mitophagy-inhibition
#15
Bo Jing, Jin Jin, Rufang Xiang, Meng Liu, Li Yang, Yin Tong, Xinhua Xiao, Hu Lei, Wei Liu, Hanzhang Xu, Jiong Deng, Li Zhou, Yingli Wu
Despite recent progress in the treatment, the outcome of adult acute T-cell lymphoblastic leukemia (T-ALL) is poor. Development of novel approach to combat this disease is urgently required. Vorinostat, a pan-histone deacetylase (HDAC) inhibitor, exerts promising anticancer activity in a variety of solid and hematologic malignancies. However, the efficacy of vorinostat monotherapy is unsatisfactory. Here, we show that quinacrine (QC), an anti-malaria drug with potent autophagy inhibitory activity, could synergistically enhance vorinostat-induced cell death at a non-toxic concentration...
May 22, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29789356/risk-adapted-treatment-of-acute-promyelocytic-leukemia-results-from-international-consortium-for-childhood-apl
#16
Anna Maria Testi, Andrea Pession, Daniela Diverio, David Grimwade, Brenda Gibson, Amilcar Cardoso de Azevedo, Lorena Moran, Guy Leverger, Sarah Elitzur, Henrik Hasle, Jutte van der Werff Ten Bosch, Owen Smith, Marisa De Rosa, Alfonso Piciocchi, Francesco Lo Coco, Robin Foà, Franco Locatelli, Gertjan J L Kaspers
Pediatric acute promyelocytic leukemia (APL), a rare childhood neoplasm, can be cured with all-trans retinoic acid (ATRA) and anthracycline. However, most published trials to date have employed high cumulative doses of anthracyclines. Here, we report the outcome of patients with newly diagnosed APL enrolled into the International Consortium for Childhood APL (ICC-APL-01) trial, which reduced anthracycline exposure but extended that of ATRA. The study recruited 258 children/adolescents with molecularly/cytogenetically-proven APL...
May 22, 2018: Blood
https://www.readbyqxmd.com/read/29789325/genomic-epidemiologic-evidence-that-estrogens-promote-breast-cancer-development
#17
Fritz F Parl, Philip S Crooke, W Dale Plummer, William D Dupont
BACKGROUND: Estrogens are a prime risk factor for breast cancer yet their causal relation to tumor formation remains uncertain. A recent study of 560 breast cancers identified 82 genes with 916 point mutations as drivers in the genesis of this malignancy. Since estrogens play a major role in breast cancer development and are also known to regulate the expression of numerous genes, we hypothesize that the 82 driver genes are likely to be influenced by estrogens, such as 17ß-estradiol (E2), and the estrogen receptor, ESR1 (ERα)...
May 22, 2018: Cancer Epidemiology, Biomarkers & Prevention
https://www.readbyqxmd.com/read/29789314/inhibition-of-atr-acutely-sensitizes-acute-myeloid-leukemia-cells-to-nucleoside-analogs-that-target-ribonucleotide-reductase
#18
Sarah E Fordham, Helen J Blair, Claire J Elstob, Ruth Plummer, Yvette Drew, Nicola J Curtin, Olaf Heidenreich, Deepali Pal, David Jamieson, Catherine Park, John Pollard, Scott Fields, Paul Milne, Graham H Jackson, Helen J Marr, Tobias Menne, Gail L Jones, James M Allan
The ataxia telangiectasia and Rad3-related (ATR) protein kinase promotes cancer cell survival by signaling stalled replication forks generated by replication stress, a common feature of many cancers including acute myeloid leukemia (AML). Here we show that the antileukemic activity of the chemotherapeutic nucleoside analogs hydroxyurea and gemcitabine was significantly potentiated by ATR inhibition via a mechanism involving ribonucleotide reductase (RNR) abrogation and inhibition of replication fork progression...
May 22, 2018: Blood Advances
https://www.readbyqxmd.com/read/29788832/feline-injection-site-sarcoma-immunohistochemical-characteristics
#19
Carolina S Carneiro, Genilson F de Queiroz, Ana Cbcf Pinto, Maria Lz Dagli, Julia M Matera
Objectives Feline injection site sarcoma (FISS) is a rapid growing locally aggressive tumor with a low metastatic rate. Its histologic features are clearly defined, but there are few studies regarding its immunohistochemical characteristics. The present study investigated the immunohistochemical characteristics of 21 cases of FISS. Methods FISSs from 12 male and nine female cats, 20 mixed-breed and one Siamese, were included in the study. After histopathological diagnosis, additional histologic sections were immunostained for vimentin, cytokeratin, desmin, S100 protein, viral feline leukemia virus (FeLV) particles, cyclooxygenase 2 (COX-2) and c-KIT...
May 1, 2018: Journal of Feline Medicine and Surgery
https://www.readbyqxmd.com/read/29788729/three-novel-micrornas-based-on-microrna-signatures-for-gastric-mucosa-associated-lymphoid-tissue-lymphoma
#20
Y Zhang, A Liu, M E, L Quan, Y Qu, A Gu
This study aimed to identify novel microRNAs (miRNAs) that play crucial regulatory roles in the pathogenesis of mucosa-associated lymphoid tissue (MALT) lymphoma by retrieving and analyzing the miRNA expression profile GSE23877. Differentially expressed miRNAs between gastric MALT lymphoma samples and human tonsil tissue samples as well as their target genes were identified. The transcriptional regulatory relationships between miRNAs and target genes were analyzed, and the regulatory network between them was constructed...
March 14, 2018: Neoplasma
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