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https://www.readbyqxmd.com/read/28817203/the-combination-of-digoxin-and-gsk2606414-exerts-synergistic-anticancer-activity-against-leukemia-in-vitro-and-in-vivo
#1
Xue-Hong Zhang, Xin-Yu Wang, Zhi-Wei Zhou, Hua Bai, Lin Shi, Yin-Xue Yang, Shu-Feng Zhou, Xiao-Chun Zhang
Digoxin is a member of cardiac glycosides and recent studies show that digoxin plays anticancer role in several types of cancer. However, the anticancer effects and mechanism of digoxin in leukemia is largely unknown. Her, our data show that digoxin treatment significantly inhibits leukemia cell viability. In addition, digoxin treatment significantly induced apoptosis and G2/M cell cycle arrest in leukemia cells. Furthermore, we demonstrated that digoxin treatment inactivate that oncogenic pathway Akt/mTOR signaling in leukemia cells...
August 17, 2017: BioFactors
https://www.readbyqxmd.com/read/28816796/intrathecal-infusion-of-haploidentical-nondonor-lymphocytes-for-central-nervous-system-leukemic-relapse-after-haploidentical-hematopoietic-stem-cell-transplantation
#2
Azusa Mayumi, Akihisa Sawada, Aya Ioi, Kohei Higuchi, Mariko Shimizu, Maho Sato, Masahiro Yasui, Masami Inoue
Leukemic relapse in the central nervous system (CNS) after conventional treatment is associated with a poor prognosis. The effectiveness and safety of IV infusion of human leukocyte antigen (HLA)-mismatched lymphocytes for leukemia, and intrathecal (IT) infusion of HLA-mismatched lymphocytes for cerebrospinal fluid (CSF) dissemination of medulloblastoma have been reported. A 13-year-old girl (HLA-A31) was diagnosed as relapsing from Philadelphia chromosome-positive acute leukemia in the CNS after receiving chemotherapy, tyrosine kinase inhibitors, haploidentical hematopoietic stem cell transplantation (HSCT) from her father (HLA-A31), and craniospinal irradiation...
August 14, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28816792/development-of-secondary-acute-myeloid-leukemia-in-a-pediatric-patient-concurrently-receiving-primary-therapy-for-ewing-sarcoma
#3
Brandon R McNew, Benjamin W Darbro, Deqin Ma, David J Gordon
Ewing sarcoma is a pediatric bone and soft tissue sarcoma that requires intensive therapy, which can cause secondary malignancies. We present a rare case of early, treatment-related AML in a pediatric patient concurrently receiving primary therapy for Ewing sarcoma. Despite AML-directed therapy, our patient died secondary to complications of hyperleukocytosis. Cytogenetic and mutation profiling of the leukemia cells revealed the DNA-topoisomerase-II-inhibitor-associated t(9;11)(p22;q23) translocation and clonal KRAS and BRAF mutations...
August 14, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28816238/acute-myeloid-leukemia-transforms-the-bone-marrow-niche-into-a-leukemia-permissive-microenvironment-through-exosome-secretion
#4
B Kumar, M Garcia, L Weng, X Jung, J L Murakami, X Hu, T McDonald, A Lin, A R Kumar, D L DiGiusto, A S Stein, V A Pullarkat, S K Hui, N Carlesso, Y-H Kuo, R Bhatia, G Marcucci, C-C Chen
Little is known about how leukemia cells alter the bone marrow (BM) niche to facilitate their own growth and evade chemotherapy. Here, we provide evidence that acute myeloid leukemia (AML) blasts remodel the BM niche into a leukemia-growth-permissive and normal-hematopoiesis-suppressive microenvironment through exosome secretion. Either engrafted AML cells or AML-derived exosomes increased mesenchymal stromal progenitors and blocked osteolineage development and bone formation in vivo. Pre-conditioning with AML-derived exosomes 'primed' the animals for accelerated AML growth...
August 17, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28815860/anxieties-felt-by-ccss-after-treatment-and-the-need-for-continued-support
#5
Naoko Iwai, Akira Shimada, Atsushi Iwai, Sonoe Yamaguchi, Hirokazu Tsukahara, Megumi Oda
BACKGROUND: Childhood cancer survivors (CCSs) and their family members continue to live in fear even after treatment is concluded due to concerns about late effects and recurrences. The consequent long-term psychological burden requires long-term follow-up suited to the anxieties and needs of CCSs, which is why we have conducted the present survey. METHODS: We conducted a questionnaire survey at medical facilities in the Chugoku and Shikoku regions of Japan with CCSs who had survived for at least 5 years following treatment, and their family members...
August 16, 2017: Pediatrics International: Official Journal of the Japan Pediatric Society
https://www.readbyqxmd.com/read/28815757/first-line-treatment-selection-and-early-monitoring-patterns-in-chronic-phase-chronic-myeloid-leukemia-in-routine-clinical-practice-simplicity
#6
Stuart L Goldberg, Jorge Cortes, Carlo Gambacorti-Passerini, Rüdiger Hehlmann, H Jean Khoury, Mauricette Michallet, Ron Paquette, Bengt Simonsson, Teresa Zyczynski, Aimee Foreman, Elisabetta Abruzzese, David Andorsky, Aart Beeker, Pascale Cony-Makhoul, Richard Hansen, Elza Lomaia, Eduardo Olavarria, Michael Mauro
Achieving successful outcomes in chronic phase-chronic myeloid leukemia (CP-CML) requires careful monitoring of cytogenetic/molecular responses (CyR/MR). SIMPLICITY (NCT01244750) is an observational study exploring tyrosine kinase inhibitor use and management patterns in patients with CP-CML receiving first-line imatinib (n=416), dasatinib (n=418) or nilotinib (n=408) in the US and 6 European countries in routine clinical practice. Twelve-month follow-up data of 1,242 prospective patients (enrolled October 01 2010-September 02 2015) are reported...
August 17, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28814986/2-deoxy-d-glucose-restore-glucocorticoid-sensitivity-in-acute-lymphoblastic-leukemia-via-modification-of-n-linked-glycosylation-in-an-oxygen-tension-independent-manner
#7
Zaira Leni, Paulina Ćwiek, Valeriya Dimitrova, Andrea S Dulcey, Nicola Zamboni, Cedric Simillion, Geetha Rossi, Kurt Leibundgut, Alexandre Arcaro
In childhood acute lymphoblastic leukemia, treatment failure is associated with resistance to glucocorticoid agents. Resistance to this class of drugs represents one of the strongest indicators of poor clinical outcome. We show that leukemic cells, which are resistant to the glucocorticoid drug methylprednisolone, display a higher demand of glucose associated with a deregulation of metabolic pathways, in comparison to sensitive cells. Interestingly, a combinatorial treatment of glucocorticoid and the glucose analog 2-deoxy-D-glucose displayed a synergistic effect in methylprednisolone-resistant cells, in an oxygen tension-independent manner...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28814980/cooperative-effect-of-chidamide-and-chemotherapeutic-drugs-induce-apoptosis-by-dna-damage-accumulation-and-repair-defects-in-acute-myeloid-leukemia-stem-and-progenitor-cells
#8
Yin Li, Yan Wang, Yong Zhou, Jie Li, Kai Chen, Leisi Zhang, Manman Deng, Suqi Deng, Peng Li, Bing Xu
BACKGROUND: Many conventional chemotherapeutic drugs are known to be involved in DNA damage, thus ultimately leading to apoptosis of leukemic cells. However, they fail to completely eliminate leukemia stem cells (LSCs) due to their higher DNA repair capacity of cancer stem cells than that of bulk cancer cells, which becomes the root of drug resistance and leukemia recurrence. A new strategy to eliminate LSCs in acute myeloid leukemia (AML) is therefore urgently needed. RESULTS: We report that a low-dose chidamide, a novel orally active benzamide-type histone deacetylase (HDAC) inhibitor, which selectively targets HDACs 1, 2, 3, and 10, could enhance the cytotoxicity of DNA-damaging agents (daunorubicin, idarubicin, and cytarabine) in CD34(+)CD38(-) KG1α cells, CD34(+)CD38(-) Kasumi cells, and primary refractory or relapsed AML CD34(+) cells, reflected by the inhibition of cell proliferation, induction of apoptosis, and increase of cell cycle arrest in vitro...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28814571/microrna-15b-deteriorates-hypoxia-reoxygenation-induced-cardiomyocyte-apoptosis-by-downregulating-bcl-2-and-mapk3
#9
Yaling Liu, Liqun Yang, Jiemin Yin, Diansan Su, Zhiying Pan, Peiying Li, Xiaodong Wang
To investigate the role of miRNA-15b in cardiomyocyte apoptosis after ischemia reperfusion injury in acute myocardial infarction (AMI), we conducted the AMI rat model by using left anterior descending ligation and performed hypoxia/reoxygenation experiments in H9c2 cells. MiRNA-15b was measured by quantitative reverse transcription PCR (qRT-PCR). Cardiomyocyte apoptosis was determined by terminal deoxynucleotide transferase dUTP nick end labeling staining. Synthesized miRNA-15b mimic and inhibitor were transfected into H9c2 cells by Lipofectamine regent...
August 16, 2017: Journal of Investigative Medicine: the Official Publication of the American Federation for Clinical Research
https://www.readbyqxmd.com/read/28814164/cpx-351-in-acute-myeloid-leukemia-can-a-new-formulation-maximize-the-efficacy-of-old-compounds
#10
Claudia Brunetti, Luisa Anelli, Antonella Zagaria, Giorgina Specchia, Francesco Albano
The management of Acute Myeloid Leukemia (AML) (with the exception of acute promyelocytic leukemia) has remained largely unchanged over the past 40 years. In particular, patients defined as high-risk, according to the 2017 European Leukemia Net recommendations, represent a subgroup with poor response to current therapies that are frequently associated with high-grade toxicity and potentially fatal complications. Areas covered: Preliminary results from an ongoing phase III clinical trial suggest that CPX-351 could represent an interesting treatment option in both induction and "bridge-to-transplant" settings...
August 17, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28813698/caspase-independent-pathway-is-related-to-nilotinib-cytotoxicity-in-cultured-cardiomyocytes
#11
Qinghui Yang, Chunhui Zhang, Hong Wei, Zenghui Meng, Guangnan Li, Yuanyuan Xu, Yanjun Chen
BACKGROUND/AIMS: Cardiotoxicity is a predominant side-effect of nilotinib during chronic myeloid leukemia treatment. The underlying molecular mechanism remains unclear. The role of autophagy and mitochondrial signaling was investigated in nilotinib-treated cardiac H9C2 cells. METHODS: Cytotoxicity was assessed using Cell Death Detection kit. Immunoblot and immunofluorescence staining was performed, and cathepsin B and caspase3 activity was assessed in nilotinib-treated H9C2 cells with or without distinct pathway inhibitor or specific siRNA...
August 15, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28812970/indole-3-carbinol-induces-g1-cell-cycle-arrest-and-apoptosis-through-aryl-hydrocarbon-receptor-in-thp-1-monocytic-cell-line
#12
Saeed Mohammadi, Fakhri Sadat Seyedhosseini, Nasser Behnampour, Yaghoub Yazdani
OBJECTIVES: The role of aryl hydrocarbon receptor (AhR) in carcinogenesis has been studied recently. Indole-3-carbinol (I3C) is an AhR agonist and a potential anticancer agent. Here, we investigated the effects of I3C on cell cycle progression and apoptosis through activation of AhR on THP-1 acute myeloid leukemia (AML) cell line. METHODS: MTT viability assay was used to measure the cytotoxic effects of I3C on THP-1 cells. Apoptosis and cell cycle assays were investigated using flow cytometry...
October 2017: Journal of Receptor and Signal Transduction Research
https://www.readbyqxmd.com/read/28812191/improved-outcome-of-childhood-acute-myeloid-leukemia-in-an-eastern-european-country-lithuanian-experience
#13
Igne Kairiene, Ramune Pasauliene, Nadezda Lipunova, Goda Vaitkeviciene, Lina Rageliene, Jelena Rascon
The reported treatment outcomes of children treated for cancer in Eastern European countries are inferior to those in Northern/Western Europe. We hypothesized that recent survival rates could be comparable to the current standards and performed a population-based analysis of treatment outcome of childhood acute myeloid leukemia (AML) in Lithuania, a small Eastern European country. Children < 18 years old who were treated for AML from 2000 to 2013 were included (n = 54). Estimates of 5-year event-free (EFS5y) and overall survival (OS5y) rates were analyzed...
August 15, 2017: European Journal of Pediatrics
https://www.readbyqxmd.com/read/28811942/spontaneous-complete-remission-in-a-patient-with-acute-myeloid-leukemia-and-severe-sepsis
#14
Rambod Mozafari, Mahsa Moeinian, Ali Asadollahi-Amin
Without treatment, acute myeloid leukemia (AML) is almost always fatal. Spontaneous remission of AML is a rare phenomenon and usually with a short duration. The exact mechanisms are unknown. However, its association with infection and blood transfusions has been described. We report a 53-year-old male who presented with severe sepsis and who was diagnosed with AML (M4). He has experienced complete spontaneous remission with relatively long duration. To the best of our knowledge, it is the first case of spontaneous remission described in Iran...
2017: Case Reports in Hematology
https://www.readbyqxmd.com/read/28811127/attenuation-of-sunitinib-induced-cardiotoxicity-through-the-a3-adenosine-receptor-activation
#15
Hardip Sandhu, Samantha Cooper, Afthab Hussain, Christopher Mee, Helen Maddock
Sunitinib is an anti-cancer tyrosine kinase inhibitor associated with severe cardiotoxic adverse effects. Using rat Langendorff heart model and human acute myeloid leukemia 60 (HL60) cell line we detected the involvement of protein kinase C (PKC) α during Sunitinib-induced cardiotoxicity and the effect of Sunitinib on cancer progression. The cardioprotective and anti-cancer properties of the A3 adenosine receptor agonist 2-chloro-N6-(3-iodobenzyl)-adenosine-5'-N-methyluronamide (IB-MECA) were investigated...
August 12, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28810819/low-cll-1-expression-is-a-novel-adverse-predictor-in-123-patients-with-de-novo-cd34-acute-myeloid-leukemia
#16
Jin Wang, Yanyu Wang, Wen-Lian Chen, Jie Hao, Zhanyun Liu, Xiangqin Weng, Yan Sheng, Jing Wu, Yongmei Zhu, Bing Chen, Shu-Min Xiong, Yu Chen, Qiusheng Chen, Hui-Ping Sun, Junmin Li
Recent reports state that C-type lectin-like molecule-1 (CLL-1) in acute myeloid leukemia (AML) is expressed primarily on myeloid cells, but there is still no investigation about its prognostic significance on leukemic blast compartment. Hence, this study aimed to evaluate the prognostic value of CLL-1 in 123 patients with de novo CD34+ non-M3 AML. Multiparameter flow cytometry was used to assess the expression of CLL-1 on immature compartment in AML and control groups. We found that CLL-1 expression level on blast compartment was closely linked to clinical characteristics, treatment response and survival outcome of patients...
August 16, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28810803/driving-cars-on-the-highway-to-solid-cancer-some-considerations-on-the-adoptive-therapy-with-car-t-cells
#17
Hinrich Abken
Adoptive therapy with chimeric antigen receptor (CAR) redirected T cells achieved lasting remissions in hematologic malignancies even in terminal stages of the disease; exploring CAR T cell therapy in the treatment of solid tumors has just begun, balancing efficacy versus toxicity in early phase trials. In contrast to leukemia/lymphoma, solid tumors display a tremendously variable biology demanding different strategies to make a T cell attack successful in the long-term. We summarize current developments, discuss the hurdles and consider some modifications to improve the CAR T cell therapy in the treatment of solid tumors...
August 16, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28810632/a-novel-antitumor-compound-nobiliside-d-isolated-from-sea-cucumber-holothuria-nobilis-selenka
#18
Jia-Jia Zhang, Ke-Qi Zhu
An anticancer compound, triterpene glycoside, was isolated from Holothuria nobilis Selenka. Its chemical structure and configuration were determined by two-dimensional nuclear magnetic resonance spectroscopy and electrospray ionization mass spectrometry. The novel active compound was identified as nobiliside D, with the molecular formula C40H61O17SNa and chemical name 3-O-[-β-D-pyranosyl (1-2)-4'-O-sulfon-ate-β-D-xylopyranosyl]-alkoxy-9-ene-3β, 12α, 17α, 25β-4 alcohol. An antitumor test was performed using xCELLigence Real-Time Cell Analysis...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28810561/cytotoxic-t-lymphocytes-promote-cytarabine-induced-acute-myeloid-leukemia-cell-apoptosis-via-inhibiting-bcl-2-expression
#19
Rui Deng, Fang-Yi Fan, Hai Yi, Li Fu, Yan Zeng, Yi Wang, Xiao-Juan Miao, Yan-Rong Shuai, Guang-Cui He, Yi Su
Acute myeloid leukemia (AML) remains difficult to cure due to its drug tolerance and refractoriness. Immunotherapy is a growing area of cancer research, which has been applied for the treatment of numerous types of cancer, including leukemia. The present study generated AML cell-specific cytotoxic T lymphocytes (CTLs) in vitro and investigated the effect of combining CTL treatment with one of the most commonly used drugs for the treatment of hematological malignancies, cytarabine, on AML cell apoptosis. Firstly, it was observed that monocyte-depleted peripheral blood lymphocytes from healthy donors could be used to generate large numbers of CD3(+)CD8(+) CTLs through immune stimulation...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28810515/physcion-blocks-cell-cycle-and-induces-apoptosis-in-human-b-cell-precursor-acute-lymphoblastic-leukemia-cells-by-downregulating-hoxa5
#20
Fei Gao, Wenjun Liu, Qulian Guo, Yongqi Bai, Hong Yang, Hongying Chen
Acute lymphoblastic leukemia (ALL) presents the most common type of malignancy in children and ranks the third most common cancer in adults. This study is aimed to investigate the anti-leukemia activity of physcion in ALL. Our results have showed that physcion could significantly suppress cell growth, induce apoptosis and blocked cell cycle progression in vitro. Mechanistically, we found that physcion downregulated the expression of HOXA5, which is responsible for the anti-leukemia activity of physcion. To verify this finding, siRNA targeting HOXA5 and overexpressing plasmid were used to repress HOXA5 expression and introduce ectopic overexpression of HOXA5 in ALL cell lines, respectively...
August 10, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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