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arsenic trioxide

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https://www.readbyqxmd.com/read/28108741/metabolism-toxicity-and-anticancer-activities-of-arsenic-compounds
#1
Islam Khairul, Qian Qian Wang, Yu Han Jiang, Chao Wang, Hua Naranmandura
A variety of studies indicated that inorganic arsenic and its methylated metabolites have paradoxical effects, namely, carcinogenic and anticancer effects. Epidemiological studies have shown that long term exposure to arsenic can increase the risk of cancers of lung, skin or bladder in man, which is probably associated with the arsenic metabolism. In fact, the enzymatic conversion of inorganic arsenic by Arsenic (+3 oxidation state) methyltransferase (AS3MT) to mono- and dimethylated arsenic species has long been considered as a major route for detoxification...
January 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28108472/relapsed-acute-promyelocytic-leukemia-lacks-classic-leukemic-promyelocyte-morphology-and-can-create-diagnostic-challenges
#2
Vanessa J Dayton, Robert W McKenna, Sophia L Yohe, Michelle M Dolan, Elizabeth Courville, Harold Alvarez, Michael A Linden
OBJECTIVES: Although current therapies for acute promyelocytic leukemia (APL), such as all-trans retinoic acid and arsenic trioxide, usually result in remission, some patients relapse. Early recognition of relapse is critical for prompt intervention. In this study, we systematically reviewed morphologic, immunophenotypic, and cytogenetic findings in paired diagnostic and relapsed APL cases and describe and quantify the changes in blast morphology at relapse. METHODS: By electronic database search, we identified eight paired diagnostic and relapsed APL cases for which peripheral blood or bone marrow smears were available for review...
January 20, 2017: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28101221/a-complex-translocation-3-17-15-in-acute-promyelocytic-leukemia-confirmed-by-fluorescence-in-situ-hybridization
#3
Yanming Wang, Junjie Ma, Xinguang Liu, Riming Liu, Lingling Xu, Li Wang, Jiannong Cen, Xiaoxia Chu
Acute promyelocytic leukemia (APL) is typified by t(15;17)(q22;q21), generating the promyelocytic leukemia (PML) gene at 15q22 with the retinoic acid α-receptor (RARA) gene at 17q21. The PML-RARA fusion gene is believed to play a vital role in leukemogenesis. A sizeable minority of patients with complex variants of APL have been reported. The present study reports the case of a 33-year-old male with APL carrying a potential complex translocation. The initial symptom was bleeding gums. Chromosomal analysis of the bone marrow cells revealed an atypical 17q aberration...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28094846/chronic-drug-induced-effects-on-contractile-motion-properties-and-cardiac-biomarkers-in-human-induced-pluripotent-stem-cell-derived-cardiomyocytes
#4
Ivan Kopljar, An De Bondt, Petra Vinken, Ard Teisman, Bruce Damiano, Nick Goeminne, Ilse Van den Wyngaert, David J Gallacher, Hua Rong Lu
BACKGROUND AND PURPOSE: Risk assessment of chronic cardiac safety liabilities within the pharmaceutical industry is mostly performed during late stages of pre-clinical drug development using in vivo animal models. Here, we explored the potential of human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs) to detect chronic cardiac risks such as drug-induced cardiomyocyte toxicity. EXPERIMENTAL APPROACH: Video microscopy-based motion field imaging was applied to evaluate chronic effect (over 72 h) of cardiotoxic drugs on the contractile motion of hiPS-CMs...
January 17, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28092839/effect-and-mechanism-of-sorbus-pohuashanensis-hante-hedl-flavonoids-protect-against-arsenic-trioxide-induced-cardiotoxicity
#5
Xiaojin Yu, Zhenyu Wang, Zunpeng Shu, Zhengqing Li, Yuan Ning, Keli Yun, Haina Bai, Ruihai Liu, Wenli Liu
The cardiotoxicity of arsenic trioxide (ATO) limits its clinical application in cancer treatment. Evidences suggest that sorbus has antioxidant activity and its consumption has been linked with improved cardioprotection. In this study, we investigated the cardio-protective effect and mechanisms of Sorbus pohuashanensis (Hante) Hedl. flavonoids (SPF) against ATO in BALB/c mice and H9c2 cells. Eleven major flavonoids were confirmed by ultra-performance liquid chromatography electrospray ionization quadrupole time of flight mass spectrometry (UPLC-ESI-Q-TOF-MS)...
January 13, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28071820/response-profiling-using-shotgun-proteomics-enables-global-metallodrug-mechanisms-of-action-to-be-established
#6
Dominique Kreutz, Andrea Bileck, Kerstin Plessl, Denise Wolrab, Michael Groessl, Bernhard K Keppler, Samuel M Meier, Christopher Gerner
Response profiling using shotgun proteomics for establishing global metallodrug mechanisms of action in two colon carcinoma cell lines, HCT116 and SW480, has been applied and evaluated with the clinically approved arsenic trioxide. Surprisingly, the complete established mechanism of action of arsenic trioxide was observed by protein regulations in SW480, but not HCT116 cells. Comparing the basal protein expression in the two cell lines revealed an 80 % convergence of protein identification, but with significant expression differences, which in turn seem to affect the extent of protein regulation...
November 7, 2016: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28061438/combination-of-arsenic-trioxide-and-everolimus-rad001-synergistically-induces-both-autophagy-and-apoptosis-in-prostate-cancer-cells
#7
Sheng Tai, Lingfan Xu, Ming Xu, Ligang Zhang, Yangyang Zhang, Kaipin Zhang, Li Zhang, Chaozhao Liang
The inhibitor of PI3K-AKT-mTOR pathway, such as Rad001, has not shown therapeutic efficacy as a single agent in prostate cancer. Arsenic trioxide induces the autophagic pathway in prostate cancer cells. We identified Arsenic trioxide can synergize with Rad001 to induce cytotoxicity of prostate cancer cells. Moreover, we identified synergistic induction of autophagy and apoptosis as the underlying mechanism. This enhanced autophagic cell death is accompanied by increased Beclin1 mRNA stability as well as upregulation of ATG5-ATG12 conjugate, Beclin1, and LC3-2...
January 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28054265/assessment-of-arsenic-trioxide-in-the-heart-of-gallus-gallus-alterations-of-oxidative-damage-parameters-inflammatory-cytokines-and-cardiac-enzymes
#8
Si-Wen Li, Xiao Sun, Ying He, Ying Guo, Hong-Jing Zhao, Zhi-Jun Hou, Ming-Wei Xing
The aim of this study was to assess the effects of arsenic trioxide (As2O3) in the chicken heart, and 72 1-day-old male Hy-line chickens were fed either a commercial diet (C group) or an arsenic supplement diet containing 7.5 mg/kg (L group), 15 mg/kg (M group), or 30 mg/kg (H group) As2O3 for 90 days. The results showed that exposure to As2O3 merely lowered (P < 0.05) the activities of catalase (CAT) and glutathione peroxidase (GSH-Px) in M and H groups at 90 days, significantly downregulated the inhibition ability of hydroxyl radicals (OH·), and upregulated (P < 0...
January 4, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28043121/anthropogenic-cycles-of-arsenic-in-mainland-china-1990-2010
#9
Ya-Lan Shi, Wei-Qiang Chen, Shi-Liang Wu, Yong-Guan Zhu
Arsenic (As) is a trace element in the global environment with toxicity to both humans and ecosystem. This study characterizes China's historical anthropogenic arsenic cycles (AACs) from 1990 to 2010. Key findings include the following: (1) the scale of China's AACs grew significantly during the studied period, making China the biggest miner, producer, and user of arsenic today; (2) the majority of arsenic flows into China's anthroposphere are the impurity of domestically mined nonferrous metal ores, which far exceeds domestic intentional demands; (3) China has been a net exporter of arsenic trioxide and arsenic metalloid, thus suffering from the environmental burdens of producing arsenic products for other economies; (4) the growth of arsenic use in China is driven by simultaneous increases in many applications including glass making, wood preservatives, batteries, semiconductors, and alloys, implying the challenge for regulating arsenic uses in multiple applications/industries at the same time; (5) the dissipative arsenic emissions resulting from intentional applications are at the same order of magnitude as atmospheric emissions from coal combustion, and their threats to human and ecosystem health can spread widely and last years to decades...
January 18, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/28024484/-effects-of-arsenic-trioxide-on-k562-cell-proliferation-and-its-mechanisms
#10
Fan-Ping Wang, Jing-Jing Zhang, Li-Min Fang, Ya-Li Zhang, Lu-Lu Chen, Yue-Yuan Zhang, Jun-Peng Li, Ming-Yong Wang
OBJECTIVE: To investigate the effects of arsenic trioxide (As2O3) on K562 cell proliferation by regulating cell cycle protein D1 and cyclin-dependent kinase inhibitor p27kip1. METHODS: MTT was used to detect the effect of As2O3 on K562 cell proliferation, so as to screen out the appropriate drug concentration. Furthermore, the K562 cell apoptosis was observed by microscopy. The expression of CyclinD1 and p27kip1 in K562 cells treated with As2O3 was analyzed by reverse transcription-polymerase chain reaction(RT-PCR), immunohistochemistry and Western blot...
December 2016: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28024471/-combination-of-homoharringtonine-with-arsenic-trioxide-induces-apoptosis-of-human-acute-myeloid-leukemia-cell-line-u937
#11
Ping Chen, Xi Jiang, Pei-Dong You, Qing Jin, Qin Yuan, Hui-Fang Huang
OBJECTIVE: To investigate the effects and mechanisms of the combination of homoharringtonine (HHT) with arsenic trioxide(As2O3) on human myeloid cell line U937 in vitro. METHODS: MTT method was used to determine the antiproliferating effect of different concentrations of HHT, As2O3 and their combination on U937 cells; the flow cytometry with Annexin-V-FITC/PI double staining was used to determine the apoptosis-induced effect of HHT and As2O3 alone or their combination; Western blot method was used to detect the protein expression of P-Akt(Ser473),P-Akt(Thr308),BCL-XL, BID,MCL-1,P-MCL-1 and so on...
December 2016: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28013460/arsenic-trioxide-induces-ros-activity-and-dna-damage-leading-to-g0-g1-extension-in-skin-fibroblasts-through-the-atm-atr-associated-chk-pathway
#12
Jutapon Chayapong, Harishkumar Madhyastha, Radha Madhyastha, Queen Intan Nurrahmah, Yuichi Nakajima, Narantsog Choijookhuu, Yoshitaka Hishikawa, Masugi Maruyama
Arsenic (As) toxicity is a global health problem, affecting millions of people. Exposure to arsenic, mostly via drinking water, has been associated with cancer of skin, lungs, and blood, in addition to several kinds of skin lesions. The present study focused on the effect of arsenic trioxide (As2O3) on normal skin fibroblast cells. Specifically, the effect of As2O3 on ROS generation and oxidative stress was investigated. Proteins involved in the DNA damage signaling pathway and cell cycle were also studied...
December 24, 2016: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28007179/cellular-arsenic-transport-pathways-in-mammals
#13
REVIEW
Barbara A Roggenbeck, Mayukh Banerjee, Elaine M Leslie
Natural contamination of drinking water with arsenic results in the exposure of millions of people world-wide to unacceptable levels of this metalloid. This is a serious global health problem because arsenic is a Group 1 (proven) human carcinogen and chronic exposure is known to cause skin, lung, and bladder tumors. Furthermore, arsenic exposure can result in a myriad of other adverse health effects including diseases of the cardiovascular, respiratory, neurological, reproductive, and endocrine systems. In addition to chronic environmental exposure to arsenic, arsenic trioxide is approved for the clinical treatment of acute promyelocytic leukemia, and is in clinical trials for other hematological malignancies as well as solid tumors...
November 2016: Journal of Environmental Sciences (China)
https://www.readbyqxmd.com/read/28003274/long-term-outcome-of-acute-promyelocytic-leukemia-treated-with-all-trans-retinoic-acid-arsenic-trioxide-and-gemtuzumab
#14
Yasmin Abaza, Hagop M Kantarjian, Guillermo Garcia-Manero, Elihu Estey, Gautam Borthakur, Elias Jabbour, Stefan Faderl, Susan O'Brien, William Wierda, Sherry Pierce, Mark Brandt, Deborah McCue, Rajyalakshmi Luthra, Keyur Patel, Steven Kornblau, Tapan Kadia, Naval Daver, Courtney DiNardo, Nitin Jain, Srdan Verstovsek, Alessandra Ferrajoli, Michael Andreeff, Marina Konopleva, Zeev Estrov, Maria Foudray, David McCue, Jorge Cortes, Farhad Ravandi
The combination of all-trans retinoic acid (ATRA) plus arsenic trioxide (ATO) has been shown to be superior to ATRA plus chemotherapy in the treatment of standard risk newly diagnosed patients with acute promyelocytic leukemia (APL). A recent study demonstrated the efficacy of this regimen with added gemtuzumab ozogamycin (GO) in high-risk patients. We examined the long-term outcome of newly diagnosed APL patients treated at our institution on three consecutive prospective clinical trials using the combination of ATRA, ATO, with or without GO...
December 21, 2016: Blood
https://www.readbyqxmd.com/read/27980225/melatonin-protects-against-arsenic-trioxide-induced-liver-injury-by-the-upregulation-of-nrf2-expression-through-the-activation-of-pi3k-akt-pathway
#15
Yue Zhang, Zhengkai Wei, Weijian Liu, Jingjing Wang, Xuexiu He, Hailong Huang, Jiali Zhang, Zhengtao Yang
Melatonin has been demonstrated to have anti-inflammatory and antioxidant effects. The aim of this study was to investigate the protective effects of melatonin on arsenic trioxide (As2O3)-induced toxicity in liver and oxidative stress in rats. The rats were injected with 3mg/kg As2O3 on alternate days and melatonin was given with an intraperitoneal injection (i.p.) 1 h before As2O3 treatment. On the 8th days, the rats were killed to determine liver histological injury, antioxidant activities and accumulation of arsenic in liver tissues...
December 14, 2016: Oncotarget
https://www.readbyqxmd.com/read/27965050/the-optimal-dose-of-arsenic-trioxide-induced-opposite-efficacy-in-autophagy-between-k562-cells-and-their-initiating-cells-to-eradicate-human-myelogenous-leukemia
#16
Zhenzhen Guo, Mingjing Meng, Shengnan Geng, Zhenhua Du, Yaqiu Zheng, Jingjing Yao, Zibo Li, Guang Han, Haihong Lin, Gangjun Du
ETHNOPHARMACOLOGICAL RELEVANCE: Arsenic trioxide (As2O3), a main component of arsenolite which is a common traditional Chinese medicine (TCM) wildly used as a therapeutic agent for more than 2400 years in china, has been accepted as a standard treatment for the patients with acute promyelocytic leukemia (APL) based on the principle in TCM of "using a poison to fight against other poisons or malignancy illnesses". However, it remains unknown that which mechanism is actually responsible for the therapeutic effects against these blood malignancies...
January 20, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/27940255/arsenic-trioxide-is-an-immune-adjuvant-in-liver-cancer-treatment
#17
Lei Wang, Ren Wang, Lin Fan, Wentao Liang, Kai Liang, Yingxin Xu, Guizhu Peng, Qifa Ye
Tumor cells are inhibited effectively by As2O3in vitro and in vivo, although the underlying immune regulatory mechanisms remain unknown. Regulatory T cells play a key role in tumor immune escape. In the present study, we aimed to assess the in vivo effects of As2O3 on the immune status in hepatic cancer and its in vitro regulatory role in cytokine-induced killers(CIKs)cytotoxicity. In a tumor H22 xenograft model of hepatic cancer, we demonstrated that As2O3 treatment decreased tumor volumes and weights, and improved survival by reducing Tregs infiltration into the tumor...
January 2017: Molecular Immunology
https://www.readbyqxmd.com/read/27920692/effects-of-arsenic-trioxide-on-minor-progressive-high-grade-osteosarcoma-of-the-extremities-metastatic-to-the-lung-results-of-39-patients-treated-in-a-single-institution
#18
Lu Xie, Wei Guo, Xiaodong Tang, Yi Yang, Jie Xu
Patients who mildly progressed after first-line chemotherapy were administered arsenic trioxide (ATO) 5-10 mg intravenously daily. Thirty-nine patients were finally enrolled in the study, of whom 19 patients received first-line chemotherapy with ATO infusion while 20 patients did not. Progression-free survival at 4 months was 89.2 and 62.7% (p = 0.043) for the ATO group and the control group, respectively, while the 2-year overall survival was 61 and 16.4% (p = 0.032).
September 2016: Case Reports in Oncology
https://www.readbyqxmd.com/read/27913456/acute-promyelocytic-leukemia-preventing-early-complications-and-late-toxicities
#19
Sameem Abedin, Jessica K Altman
Acute promyelocytic leukemia (APL) is a unique subtype of acute myeloid leukemia (AML), which presents with a distinct coagulopathy. Therapeutic advances have made APL one of the true success stories in oncology, transforming this once lethal disease into the most curable form of AML. For many patients, cure will now be achieved without the use of chemotherapy. It is hoped that limiting chemotherapy will reduce mortality even further, particularly among more vulnerable older adults whose survival lagged behind that of younger patients...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27895727/deficiency-of-sumo-specific-protease-1-induces-arsenic-trioxide-mediated-apoptosis-by-regulating-xbp1-activity-in-human-acute-promyelocytic-leukemia
#20
Fei-Fei Wang, Ming-Zhu Liu, Yi Sui, Qing Cao, Bo Yan, Mei-Ling Jin, Xi Mo
Small ubiquitin-like modifier (SUMO)/sentrin-specific protease 1 (SENP1), a member of the SENP family, is highly expressed in several neoplastic tissues. However, the effect of SENP1 in acute promyelocytic leukemia (APL) has not been elucidated. In the present study, it was observed that SENP1 deficiency had no effect on the spontaneous apoptosis or differentiation of NB4 cells. Arsenic trioxide (As2O3) could induce the upregulation of endoplasmic reticulum (ER) stress, resulting in the apoptosis of NB4 cells...
November 2016: Oncology Letters
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