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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
#1
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
#2
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
#3
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/29792338/molecular-mechanism-for-the-influence-of-gender-dimorphism-on-alcoholic-liver-injury-in-mice
#4
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/29791237/the-future-of-chronic-lymphocytic-leukemia-potential-directions-from-ash-2017
#5
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
#6
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/29789603/vorinostat-and-quinacrine-have-synergistic-effects-in-t-cell-acute-lymphoblastic-leukemia-through-reactive-oxygen-species-increase-and-mitophagy-inhibition
#7
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
#8
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/29789314/inhibition-of-atr-acutely-sensitizes-acute-myeloid-leukemia-cells-to-nucleoside-analogs-that-target-ribonucleotide-reductase
#9
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/29787919/optimal-use-of-novel-agents-in-chronic-lymphocytic-leukemia
#10
Mitchell R Smith, Robert F Weiss
Novel agents are changing therapy for patients with CLL, but their optimal use remains unclear. We model the clinical situation in which CLL responds to therapy, but resistant clones, generally carrying del17p, progress and lead to relapse. Sub-clones of varying growth rates and treatment sensitivity affect predicted therapy outcomes. We explore effects of different approaches to starting novel agent in relation to bendamustine-rituximab induction therapy: at initiation of therapy, at the end of chemo-immunotherapy, at molecular relapse, or at clinical detection of relapse...
May 7, 2018: Leukemia Research
https://www.readbyqxmd.com/read/29787320/gemtuzumab-ozogamicin-for-the-treatment-of-acute-myeloid-leukemia
#11
Jeffrey Baron, Eunice S Wang
Gemtuzumab ozogamicin (GO) is an antibody-drug conjugate consisting of a monoclonal antibody targeting CD33 linked to a cytotoxic derivative of calicheamicin. Despite the known clinical efficacy in relapsed/refractory acute myeloid leukemia (AML), GO was withdrawn from the market in 2010 due to increased early deaths seen in newly diagnosed AML patients receiving GO + intensive chemotherapy. In 2017, new data on the clinical efficacy and safety of GO administered on a fractionated dosing schedule led to re-approval for newly diagnosed and relapsed/refractory AML...
May 22, 2018: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/29786869/rare-labial-ulcer-related-to-the-use-of-all-trans-retinoic-acid-in-a-patient-with-acute-promyelocytic-leukemia
#12
M P Buligon, J C Mielke, K L Ferrazzo, J Chiesa
Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia (AML). All-trans retinoic acid (ATRA) is the first-choice therapy for the treatment of this disease, but has been associated with side effects, the most serious of which is retinoic acid syndrome (RAS). RAS is characterized by unexplained fever, dyspnea, pulmonary infiltrate, leukocytosis and nephropathy. Genital ulcers have been described in some cases, but only two cases of oral ulcers related to this syndrome have been described in the literature...
May 22, 2018: Special Care in Dentistry
https://www.readbyqxmd.com/read/29785718/associations-between-the-smoking-relatedness-of-a-cancer-type-cessation-attitudes-and-beliefs-and-future-abstinence-among-recent-quitters
#13
Úrsula Martínez, Thomas H Brandon, Steven K Sutton, Vani N Simmons
OBJECTIVE: Smoking after a diagnosis of cancer can negatively impact treatment outcomes and quality of life. It is important that patients quit smoking and remain abstinent regardless of cancer type. Some cancer types (e.g., lung) have stronger links to smoking as a cause than do others (e.g., colorectal). The aims of this study were to (1) assess associations between smoking-relatedness of the cancer type with beliefs and attitudes concerning smoking abstinence (e.g., confidence, self-efficacy), and (2) assess these variables as predictors of future abstinence...
May 21, 2018: Psycho-oncology
https://www.readbyqxmd.com/read/29785640/switching-from-high-fat-diet-to-foods-containing-resveratrol-as-a-calorie-restriction-mimetic-changes-the-architecture-of-arcuate-nucleus-to-produce-more-newborn-anorexigenic-neurons
#14
Maryam Safahani, Hadi Aligholi, Farshid Noorbakhsh, Mahmoud Djalali, Hamideh Pishva, Sayed Mostafa Modarres Mousavi, Leila Alizadeh, Ali Gorji, Fariba Koohdani
PURPOSE: These days, obesity threatens the health for which one of the main interventions is calorie restriction (CR). Due to the difficulty of compliance with this treatment, CR mimetics such as resveratrol (RSV) have been considered. The present study compared the effects of RSV and CR on hypothalamic remodeling in a diet-switching experiment. METHODS: C57BL/6 male mice received high-fat diet (HFD) for 4 weeks, subsequently their diet switched to chow diet, HFD + RSV, chow diet + RSV or CR diet for a further 6 weeks...
May 21, 2018: European Journal of Nutrition
https://www.readbyqxmd.com/read/29785506/venetoclax-and-low-dose-cytarabine-induced-complete-remission-in-a-patient-with-high-risk-acute-myeloid-leukemia-a-case-report
#15
Bingshan Liu, Roshni Narurkar, Madhura Hanmantgad, Wahib Zafar, Yongping Song, Delong Liu
Conventional combination therapies have not resulted in considerable progress in the treatment of acute myeloid leukemia (AML). Elderly patients with AML and poor risk factors have grave prognosis. Midostaurin has been recently approved for the treatment of FLT-3-mutated AML. Venetoclax, a BCL-2 inhibitor, has been approved for the treatment of relapsed and/or refractory chronic lymphoid leukemia. Clinical trials on applying venetoclax in combination with cytarabine and other agents to treat various hematological malignancies are currently underway...
May 21, 2018: Frontiers of Medicine
https://www.readbyqxmd.com/read/29785446/digital-droplet-pcr-based-absolute-quantification-of-pre-transplant-npm1-mutation-burden-predicts-relapse-in-acute-myeloid-leukemia-patients
#16
Marius Bill, Juliane Grimm, Madlen Jentzsch, Laura Kloss, Karoline Goldmann, Julia Schulz, Stefanie Beinicke, Janine Häntschel, Michael Cross, Vladan Vucinic, Wolfram Pönisch, Gerhard Behre, Georg-Nikolaus Franke, Thoralf Lange, Dietger Niederwieser, Sebastian Schwind
Allogeneic hematopoietic stem cell transplantation is an established consolidation therapy for patients with acute myeloid leukemia. However, relapse after transplantation remains a major clinical problem resulting in poor prognosis. Thus, detection of measurable ("minimal") residual disease to identify patients at high risk of relapse is essential. A feasible method to determine measurable residual disease may be digital droplet PCR (ddPCR) that allows absolute quantification with high sensitivity and specificity without the necessity of standard curves...
May 22, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29785137/andrographolide-potentiates-the-antitumor-effect-of-topotecan-in-acute-myeloid-leukemia-cells-through-an-intrinsic-apoptotic-pathway
#17
Mohammad Hassan Hodroj, Achraf Jardaly, Sarah Abi Raad, Annalise Zouein, Sandra Rizk
Background: Topotecan (TP) is an anticancer drug acting as topoisomerase I inhibitor that is used in the treatment of many types of cancers including leukemia, but it has significant side effects. Andrographolide, a compound extracted from Andrographis paniculata , was recently proven to inhibit the growth of cancer cells and can induce apoptosis. The aim of this study is to investigate the possible synergism between TP and andrographolide in acute myeloid cells in vitro. Materials and methods: U937 acute myeloid leukemic cells were cultured using Roswell Park Memorial Institute (RPMI) medium and then treated for 24 h with TP and andrographolide prepared through the dilution of dimethyl sulfoxide (DMSO) stocks with RPMI on the day of treatment...
2018: Cancer Management and Research
https://www.readbyqxmd.com/read/29784750/pregnancy-in-patients-with-chronic-myeloid-leukemia
#18
Ellin Berman
Estimates suggest that nearly 30% of patients diagnosed with chronic myeloid leukemia (CML) are aged <49 years, with approximately half being women. For many of these women, childbearing concerns are a major factor as they initiate treatment with tyrosine kinase inhibitors, which are known to be teratogenic. During her presentation at the NCCN 23rd Annual Conference, Dr. Berman identified the challenges in helping women undergoing treatment for CML who want to have children, and emphasized the importance of an individualized and multidisciplinary approach to management...
May 2018: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/29784749/prognostic-significance-of-molecular-markers-and-targeted-regimens-in-the-management-of-acute-myeloid-leukemia
#19
Martin Tallman
The diagnosis, staging, and treatment of acute myeloid leukemia (AML) has evolved based on identification of important genetic alterations and drugs to target those genes. Cytogenetic abnormalities play a major role in managing AML. Achieving minimal residual disease is an increasingly important milestone. Four new targeted therapies are now available for the treatment of AML.
May 2018: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/29784748/emerging-treatment-options-for-acute-lymphoblastic-leukemia-focus-on-car-t-cell-therapy
#20
Patrick A Brown, Bijal Shah
Acute lymphoblastic leukemia (ALL) comprises a heterogeneous group of diseases with different morphologic, cytogenetic, and molecular subgroups, some of which have significant therapeutic implications. It typically presents with an aggressive clinical course, and among adults, responds poorly to standard chemotherapy, and carries a high risk for relapse. Despite the significant progress made in inducing remission, frequent relapses remain a challenge. Novel drugs, such as potent later-generation tyrosine kinase inhibitors, antibody-drug conjugates, bispecific monoclonal antibodies, and chimeric antigen receptor (CAR) T-cell therapies, are being investigated in patients with ALL...
May 2018: Journal of the National Comprehensive Cancer Network: JNCCN
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