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arsenic trioxide

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https://www.readbyqxmd.com/read/28533572/%C3%AE-lipoic-acid-mitigates-arsenic-induced-hematological-abnormalities-in-adult-male-rats
#1
Sonali Ghosh, Raghwendra Mishra, Sagnik Biswas, Rupak K Bhadra, Prabir K Mukhopadhyay
BACKGROUND: Arsenic toxicity is a major global health problem and exposure via contaminated drinking water has been associated with hematological and other systemic disorders. The present investigation has been conducted in adult male rats to evaluate the protective ability of α-lipoic acid (ALA) against such hematological disorders. METHODS: Twenty-four adult male Wister rats (b.wt.130±10g) were grouped and accordingly group I (control) received the normal diet, group II (treated) was given arsenic orally for 28 consecutive days as arsenic trioxide (3 mg/kgbw/rat/day) whereas group III (supplemented) received the same dose of arsenic along with ALA (25 mg/kgbw/rat/day) as oral supplement...
May 2017: Iranian Journal of Medical Sciences
https://www.readbyqxmd.com/read/28525371/arsenic-trioxide-and-angiotensin-ii-have-inhibitory-effects-on-herg-protein-expression-evidence-for-the-role-of-pml-sumoylation
#2
Yu Liu, Duo Li, Dan Nie, Shang-Kun Liu, Fang Qiu, Mei-Tong Liu, Yuan-Yuan Li, Jia-Xin Wang, Yan-Xin Liu, Chang-Jiang Dong, Di Wu, Wei Tian, Jia Yang, Wei Mu, Jia-Tong Li, Dan Zhao, Xiao-Feng Wang, Wen-Feng Chu, Bao-Feng Yang
The human ether-a-go-go-related gene (HERG) channel is a novel target for the treatment of drug-induced long QT syndrome, which causes lethal cardiotoxicity. This study is designed to explore the possible role of PML SUMOylation and its associated nuclear bodies (NBs) in the regulation of HERG protein expression. Both arsenic trioxide (ATO) and angiotensin II (Ang II) were able to significantly reduce HERG protein expression, while also increasing PML SUMOylation and accelerating the formation of PML-NBs. Pre-exposure of cardiomyocytes to a SUMOylation chemical inhibitor, ginkgolic acid, or the silencing of UBC9 suppressed PML SUMOylation, subsequently preventing the downregulation of HERG induced by ATO or Ang II...
May 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28521962/the-functional-roles-of-pml-nuclear-bodies-in-genome-maintenance
#3
REVIEW
Hae Ryung Chang, Anudari Munkhjargal, Myung-Jin Kim, Seon Young Park, Eunyoung Jung, Jae-Ha Ryu, Young Yang, Jong-Seok Lim, Yonghwan Kim
In the nucleus, there are several membraneless structures called nuclear bodies. Among them, promyelocytic leukemia nuclear bodies (PML-NBs) are involved in multiple genome maintenance pathways including the DNA damage response, DNA repair, telomere homeostasis, and p53-associated apoptosis. In response to DNA damage, PML-NBs are coalesced and divided by a fission mechanism, thus increasing their number. PML-NBs also play a role in repairing DNA double-strand breaks (DSBs) by homologous recombination (HR). Clinically, the dominant negative PML-RARα fusion protein expressed in acute promyelocytic leukemia (APL) inhibits the transactivation of downstream factors and disrupts PML function, revealing the tumor suppressor role of PML-NBs...
May 5, 2017: Mutation Research
https://www.readbyqxmd.com/read/28521025/mechanism-of-as2o3-induced-action-potential-prolongation-and-using-hips-cms-to-evaluate-the-rescue-efficacy-of-drugs-with-different-rescue-mechanism
#4
Meng Yan, Lifang Feng, Yanhui Shi, Junnan Wang, Yan Liu, Fengmei Li, Baoxin Li
Arsenic trioxide (As2O3) has been verified as a breakthrough in the management of acute promyelocytic leukemia in recent decades. However, cardiotoxicity, especially long QT syndrome (LQTS) has become the most important issue during As2O3 treatment. The characterized mechanisms behind this adverse effect are inhibition of cardiac hERG channel trafficking and increase of cardiac calcium currents. In our study, we found a new pathway underlying As2O3-induced cardiotoxicity that As2O3 accelerates lysosomal degradation of hERG on plasma membrane after using brefeldin A (BFA) to block protein trafficking...
May 17, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28516389/microenvironmental-scenario-of-the-bone-marrow-of-inorganic-arsenic-exposed-experimental-mice
#5
Jacintha Archana Pereira, Sujata Law
Exposure to arsenic on a regular basis, mainly through drinking water, agricultural pesticide, and sometimes therapeutic dose, results in various diseases of different tissues including the bone marrow hematopoietic system. Hematopoiesis is a dynamic process by which bone marrow (BM) hematopoietic stem/progenitor cells (HSPCs) generate a relatively constant pool of functionally mature blood cells by the support of microenvironmental components. The present study has been aimed to understand stem cell microenvironmental status during arsenic toxicity and the consequent reflection of dysregulation involving the hematopoietic machinery in experimental mice...
May 17, 2017: Biological Trace Element Research
https://www.readbyqxmd.com/read/28510787/a-phase-ii-trial-of-arsenic-trioxide-and-temozolomide-in-combination-with-radiation-therapy-for-patients-with-malignant-gliomas
#6
Priya Kumthekar, Sean Grimm, James Chandler, Minesh Mehta, Maryanne Marymont, Robert Levy, Kenji Muro, Irene Helenowski, Katie McCarthy, Leanne Fountas, Jeffrey Raizer
Standard treatment for GBM is radiation (RT) and temozolomide (TMZ). Arsenic trioxide (ATO) is synergistic with RT based on several mechanisms of action previously identified, however not tested herein. The MTD of ATO, RT and TMZ was determined in a Phase I trial. We now present the combined Phase I/II data. Patients with newly diagnosed malignant gliomas were eligible for treatment. Patients were treated with RT (60 GY), TMZ (75 mg/m(2) daily × 42 days) and ATO 0.20 mg/kg daily in week 1 then twice a week ×5 weeks, after completing RT they were treated with TMZ 5/28 for up to 12 months...
May 16, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28507443/erratum-retinoic-acid-and-arsenic-trioxide-in-the-treatment-of-acute-promyelocytic-leukemia-current-perspectives-corrigendum
#7
(no author information available yet)
[This corrects the article on p. 1585 in vol. 10, PMID: 28352191.].
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28501332/inhibition-of-nicotinamide-phosphoribosyltransferase-and-depletion-of-nicotinamide-adenine-dinucleotide-contribute-to-arsenic-trioxide-suppression-of-oral-squamous-cell-carcinoma
#8
Xin Yue Wang, Jin Zhi Wang, Lu Gao, Fu Yin Zhang, Qi Wang, Ke Jian Liu, Bin Xiang
Emerging evidence suggests that increased nicotinamide phosphoribosyltransferase (NAMPT) expression is associated with the development and prognosis of many cancers, but it remains unknown regarding its role in oral squamous cell carcinoma (OSCC). In the present study, the results from tissue microarray showed that NAMPT was overexpressed in OSCC patients and its expression level was directly correlated with differential grades of cancer. Interestingly, treatment of OSCC cells with chemotherapy agent arsenic trioxide (ATO) decreased the levels of NAMPT protein and increased cellular death in an ATO dose- and time-dependent manner...
May 10, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28494415/studies-on-curative-efficacy-of-monoterpene-eugenol-on-anti-leukemic-drug-arsenic-trioxide-induced-cardiotoxicity
#9
Prakash Binu, Nellikunnath Priya, Surendran Abhilash, Radhakrishnan Chandraprabha Vineetha, Raveendran Harikumaran Nair
BACKGROUND: Arsenic trioxide (As2O3) is emerging as a frontline agent for the treatment of acute promyelocytic leukemia (APL) but the therapeutic application is limited by its toxicity. QT prolongation, torsades de pointes and sudden cardiac death have been implicated in the As2O3 therapy. So eugenol is a monoterpene compound is well known for its antioxidant properties and protective effect on the cardiovascular system. OBJECTIVE: In this study, the cardioprotective effect of eugenol on cardiac electrical conductivity, tissue electrolytes, myocardial markers, antioxidant system, lipid peroxidation and nitric oxide production was investigated in male Wistar rats treated with arsenic trioxide...
May 7, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28492552/all-trans-retinoic-acid-and-arsenic-trioxide-fail-to-derepress-the-monocytic-differentiation-driver-irf8-in-acute-promyelocytic-leukemia-cells
#10
XiangZhen Liu, Juan Chen, ShanHe Yu, Li Yan, HeZhou Guo, JianMin Dai, Wu Zhang, Jiang Zhu
All-trans retinoic acid (ATRA) and/or arsenic trioxide (ATO) administration leads to granulocytic maturation and/or apoptosis of acute promyelocytic leukemia (APL) cells mainly by targeting promyelocytic leukemia/retinoic acid receptor alpha (PML/RARα). Yet, ~10-15% of APL patients are not cured by ATRA- and ATO-based therapies, and a potential failure of ATRA and ATO in completely reversing PML/RARα-driven oncogenic alterations has not been comprehensively examined. Here we characterized the in vivo primary responses of dysregulated genes in APL cells treated with ATRA and ATO using a GFP-labeled APL model...
May 11, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28490888/maintenance-therapy-with-all-trans-retinoic-acid-and-arsenic-trioxide-improves-relapse-free-survival-in-adults-with-low-to-intermediate-risk-acute-promyelocytic-leukemia-who-have-achieved-complete-remission-after-consolidation-therapy
#11
Bin Liang, Zhouyi Zheng, Yifen Shi, Jingjing Chen, Xudong Hu, Honglan Qian, Zhijian Shen, Songfu Jiang, Kang Yu, Jianhua Feng
BACKGROUND: Currently, the optimal maintenance therapy for patients with acute promyelocytic leukemia (APL) who have achieved complete remission (CR) after completing consolidation chemotherapy remains controversial. The comparative effectiveness of the all-trans retinoic acid (ATRA) plus arsenic trioxide (As2O3) maintenance strategy with classic ATRA plus chemotherapy has not been evaluated. In this study, we compared the efficacy and toxicity of maintenance therapy with ATRA plus As2O3 and classic ATRA plus chemotherapy in low- to intermediate-risk APL patients reaching the first CR after induction and consolidation therapy...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28486108/trib3-promotes-apl-progression-through-stabilization-of-the-oncoprotein-pml-rar%C3%AE-and-inhibition-of-p53-mediated-senescence
#12
Ke Li, Feng Wang, Wen-Bin Cao, Xiao-Xi Lv, Fang Hua, Bing Cui, Jiao-Jiao Yu, Xiao-Wei Zhang, Shuang Shang, Shan-Shan Liu, Jin-Mei Yu, Ming-Zhe Han, Bo Huang, Ting-Ting Zhang, Xia Li, Jian-Dong Jiang, Zhuo-Wei Hu
Acute promyelocytic leukemia (APL) is driven by the oncoprotein PML-RARα, which antagonizes myeloid differentiation and promotes APL-initiating cell self-renewal. Combined all-trans retinoic acid (ATRA) with arsenic trioxide (As2O3) or chemotherapy dramatically improves the prognosis of APL patients. Here we report that expression of pseudokinase Tribble 3 (TRIB3) associates positively with APL progression and therapeutic resistance. The elevated TRIB3 expression promotes APL by interacting with PML-RARα and suppressing its sumoylation, ubiquitylation, and degradation...
May 8, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28480800/combined-chemotherapy-for-acute-promyelocytic-leukemia-a-meta-analysis
#13
Xueliang Li, Chao Wang, Guanglong Chen, Buqiang Ji, Yongchang Xu
BACKGROUND: This study evaluates the efficacy of combined chemotherapy for the management of acute promyelocytic leukemia (APL). METHOD: Literature search was carried out in several electronic databases. Meta-analyses were performed to achieve weighted effect sizes of overall survival (OS), disease-free survival (DFS), complete remission (CR) rate, and relapse rate. Metaregression analyses were performed to evaluate the factors affecting CR and relapse rates. RESULTS: Data from 37 studies (7566 patients) were used for meta-analysis...
May 7, 2017: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/28474970/ellagic-acid-protects-against-arsenic-trioxide-induced-cardiotoxicity-in-rat
#14
A A Hemmati, S Olapour, H Najafzadeh Varzi, M J Khodayar, M Dianat, B Mohammadian, H Yaghooti
Arsenic trioxide (As2O3) is utilized for treating patients suffering from hematological malignancies particularly acute promyelocytic leukemia. Unfortunately, the extensive application of this chemotherapeutic agent has been limited due to its adverse effects such as cardiotoxicity. Ellagic acid, as a phenolic compound, has shown to exert antioxidant, anti-inflammatory, antifibrotic, and antiatherogenic properties. It is also capable of protecting against drug toxicity. In this study, we evaluated whether ellagic acid can protect against As2O3-induced heart injury in rats...
January 1, 2017: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/28467781/extracellular-signal-regulated-kinase-8-mediated-nf-%C3%AE%C2%BAb-activation-increases-sensitivity-of-human-lung-cancer-cells-to-arsenic-trioxide
#15
Dan-Dan Wu, Andy T Y Lau, Fei-Yuan Yu, Na-Li Cai, Li-Juan Dai, Myoung Ok Kim, Dong-Yan Jin, Yan-Ming Xu
Extracellular signal-regulated kinase 8 (ERK8), also known as mitogen-activated protein kinase 15 (MAPK15), is the most recently identified protein kinase of the ERK family members and yet the least has been studied so far. Here, we report that ERK8 is highly expressed in several human lung cancer cell lines and is positively correlated with their sensitivities to the anti-cancer drug arsenic trioxide (As2O3). As2O3 at physiologically relevant concentrations (5-20 μM) potently stimulates the phosphorylation of ERK8 at Thr175 and Tyr177 within the TEY motif in the kinase domain, leading to its activation...
April 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28466809/a-proteomics-research-of-apoptosis-of-leukemia-cells-induced-by-arsenic-trioxide
#16
L Wang, Q Guo, W Liu, Y Bai
Leukemia is a malignant hyperplasia disease of hematopoietic system caused by a kind of hematopoietic cells detaining at a certain stage. In this study, we used HL-60 cell line to detect the effect of apoptosis induction by various concentrations of As2O3. Percentage of apoptotic cells was increased in the presence of As2O3, detected through flow cytometry. Mass spectrometric identification indicated that there were 102 differential proteins before and after intervention. Among them, expression of CH60, AT1A1, ANXA6, and EF2 increased and expression of ATPA, MYO1G, RS3 decreased...
March 31, 2017: Cellular and Molecular Biology
https://www.readbyqxmd.com/read/28462082/on-arsenic-trioxide-in-the-clinical-treatment-of-acute-promyelocytic-leukemia
#17
REVIEW
Peng Zhang
Arsenic is generally considered hypertoxic. However, it has been used in traditional Chinese medicine since ancient times, to treat serious illnesses. Recently, a single dose of arsenic trioxide (As2O3) has been found especially effective in treating acute promyelocytic leukemia (APL). Generally speaking, As2O3 is a more effective treatment of APL than other, newer medications and has less severe adverse reactions and greater safety.
2017: Leukemia Research Reports
https://www.readbyqxmd.com/read/28459147/synergistic-effects-of-arsenic-trioxide-and-radiation-triggering-of-intrinsic-pathway-of-apoptosis
#18
Kave Moloudi, Ali Neshasteriz, Arshad Hosseini, Nazila Eyvazzadeh, Mehdi Shomali, Samira Eynali, Elahe Mirzaei, Asaad Azarnezhad
Background: Arsenic trioxide (ATO) has been reported as an effective anti-cancer and a US Food and Drug Administration (FDA) approved drug for treatment of some cancers. The aim of this study is to determine the underlying apoptosis molecular and cellular mechanisms of ATO in the presence or absence of ionizing radiation (IR) in vitro in the glioblastoma multiforme (GBM) cell line, U87MG. Methods: Cells were treated by different concentrations of ATO either in presence or absence of IR...
May 1, 2017: Iranian Biomedical Journal
https://www.readbyqxmd.com/read/28458011/chrysin-and-silibinin-sensitize-human-glioblastoma-cells-for-arsenic-trioxide
#19
Michael Gülden, Daniel Appel, Malin Syska, Stephanie Uecker, Franziska Wages, Hasso Seibert
Arsenic trioxide (ATO) is highly efficient in treating acute promyelocytic leukemia. Other malignancies, however, are often less sensitive. Searching for compounds sensitizing arsenic resistant tumours for ATO the plant polyphenols, chrysin and silibinin, and the ATP binding cassette (ABC) transporter inhibitor MK-571, respectively, were investigated in human glioblastoma A-172 cells. The sensitivity of A-172 cells to ATO was characterized by a median cytotoxic concentration of 6 μM ATO. Subcytotoxic concentrations of chrysin, silibinin and MK-571, respectively, remarkably increased the sensitivity of the cells to ATO by factors of 4-6...
April 27, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28454374/arsenic-trioxide-inhibits-tumor-induced-myeloid-derived-suppressor-cells-and-enhances-t-cell-activity
#20
Qingmin Gao, Jingwei Jiang, Zhaohui Chu, Hao Lin, Xinli Zhou, Xiaohua Liang
Myeloid-derived suppressor cells (MDSCs), one of the major orchestrators of the immunosuppressive network, are associated with immune suppression and considered a prime target for cancer immunotherapy. At present, various strategies have been explored to deplete and/or inactivate MDSCs in vivo. In this study, we investigated the effect of arsenic trioxide (ATO) on MDSCs derived from tumor-bearing mice. This study examined the in vitro and in vivo effects of ATO administration on MDSCs from C57/j mice bearing either the B16 or H22 tumor...
April 2017: Oncology Letters
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