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arsenic trioxide

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https://www.readbyqxmd.com/read/28218785/inhibition-of-shh-pathway-mechanisms-by-arsenic-trioxide-in-pediatric-medulloblastomas-a-comprehensive-literature-review
#1
P H S Klinger, A F Andrade, L E A Delsin, R G P Queiroz, C A Scrideli, L G Tone, E T Valera
Recent innovations in the genomic understanding of medulloblastomas have provided new ways to explore this highly invasive malignant brain cancer arising from the cerebellum. Among the four different medulloblastoma subgroups described to date, the sonic hedgehog (SHH) genetic pathway is the pathway activated in the tumorigenesis of medulloblastoma. SHH-related medulloblastomas are usually of nodular/desmoplastic histology and frequently occur in children under the age of three, an age group highly susceptible to the acute and long-term effects of treatment...
February 16, 2017: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/28218039/demethylation-and-alterations-in-the-expression-level-of-the-cell-cycle-related-genes-as-possible-mechanisms-in-arsenic-trioxide-induced-cell-cycle-arrest-in-human-breast-cancer-cells
#2
Farima Moghaddaskho, Haniyeh Eyvani, Mohsen Ghadami, Javad Tavakkoly-Bazzaz, Kamran Alimoghaddam, Ardeshir Ghavamzadeh, Seyed H Ghaffari
Arsenic trioxide (As2O3) has been used clinically as an anti-tumor agent. Its mechanisms are mostly considered to be the induction of apoptosis and cell cycle arrest. However, the detailed molecular mechanisms of its anti-cancer action through cell cycle arrest are poorly known. Furthermore, As2O3 has been shown to be a potential DNA methylation inhibitor, inducing DNA hypomethylation. We hypothesize that As2O3 may affect the expression of cell cycle regulatory genes by interfering with DNA methylation patterns...
February 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28209094/attenuation-of-arsenic-trioxide-induced-cardiotoxicity-through-flaxseed-oil-in-experimental-rats
#3
Mathews V Varghese, M Abhilash, Manju Alex, M V Sauganth Paul, A Prathapan, K G Raghu, R Harikumaran Nair
OBJECTIVES: Arsenic trioxide (As2O3) is a potent drug for acute promyelocytic leukaemia, but its clinical trials are allied with some serious adverse events mainly cardiac functional abnormalities. So the objective of our investigation is to identify the cardioprotective action of flaxseed oil (FSO), a natural compound against As2O3 induced cardiotoxicity. METHODS: Male wistar rats were treated with As2O3 (4 mg/kg) to induce cardiotoxicity. FSO (250 and 500 mg/kg) was given in combination with As2O3 for evaluating its cardioprotective efficacy...
February 17, 2017: Redox Report: Communications in Free Radical Research
https://www.readbyqxmd.com/read/28194055/treatment-of-acute-promyelocytic-leukemia-with-single-agent-arsenic-trioxide-experience-from-a-tertiary-care-center-in-india
#4
Karthik Udupa, Joseph Thomas, Chethana Babu Udupa, V S Binu, Prahlad Sharan
APML is a highly curable hematological malignancy which is treated with differentiation agents and chemotherapy. The morbidity caused by chemotherapy in the treatment of APML is a great cause of concern. We treated 12 patients with newly diagnosed APML with single agent arsenic trioxide between 2010 and 2014 irrespective of risk stratification. Out of 12 patient 2 patients died during induction. All the ten patients who completed induction, completed their consolidation and maintenance without any delays. One out of these ten patients relapsed 10 months after treatment...
March 2017: Indian Journal of Hematology & Blood Transfusion
https://www.readbyqxmd.com/read/28187727/cryptotanshinone-enhances-the-effect-of-arsenic-trioxide-in-treating-liver-cancer-cell-by-inducing-apoptosis-through-downregulating-phosphorylated-stat3-in-vitro-and-in-vivo
#5
Li Shen, Guangshun Zhang, Zhaohuan Lou, Guanhua Xu, Guangji Zhang
BACKGROUND: Arsenic trioxide (ATO) is approved for treating terminal-stage liver cancer in China. Cryptotanshinone (CT), a STAT3 inhibitor, has exhibited certain anti-tumor potency; however, the use of CT enhanced ATO for treating liver cancer has not been reported. Here we try to elucidate how CT could enhance the efficacy of ATO for treating liver cancer and its correlation to STAT3 in vitro and in vivo. METHODS: Cell viability of ATO combined with CT was assessed by (1)MTT assay...
February 10, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28165700/intrinsic-and-stable-conjugation-of-thiolated-mesoporous-silica-nanoparticles-with-radioarsenic
#6
Paul A Ellison, Feng Chen, Shreya Goel, Todd E Barnhart, Robert J Nickles, Onofre T DeJesus, Weibo Cai
The development of new image-guided drug delivery tools to improve the therapeutic efficacy of chemotherapeutics remains an important goal in nanomedicine. Using labeling strategies that involve radioelements that have theranostic pairs of diagnostic positron-emitting isotopes and therapeutic electron-emitting isotopes has promise in achieving this goal and further enhancing drug performance through radiotherapeutic effects. The isotopes of radioarsenic offer such theranostic potential and would allow for the use of positron emission tomography (PET) for image-guided drug delivery studies of the arsenic-based chemotherapeutic arsenic trioxide (ATO)...
February 6, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28143738/manipulating-pml-sumoylation-via-silencing-ubc9-and-rnf4-regulates-cardiac-fibrosis
#7
Yu Liu, Dan Zhao, Fang Qiu, Ling-Ling Zhang, Shang-Kun Liu, Yuan-Yuan Li, Mei-Tong Liu, Di Wu, Jia-Xin Wang, Xiao-Qing Ding, Yan-Xin Liu, Chang-Jiang Dong, Xiao-Qi Shao, Bao-Feng Yang, Wen-Feng Chu
The promyelocytic leukemia protein (PML) is essential in the assembly of dynamic subnuclear structures called PML nuclear bodies (PML-NBs), which are involved in regulating diverse cellular functions. However, the possibility of PML being involved in cardiac disease has not been examined. In mice undergoing transverse aortic constriction (TAC) and arsenic trioxide (ATO) injection, transforming growth factor β1 (TGF-β1) was upregulated along with dynamic alteration of PML SUMOylation. In cultured neonatal mouse cardiac fibroblasts (NMCFs), ATO, angiotensin II (Ang II), and fetal bovine serum (FBS) significantly triggered PML SUMOylation and the assembly of PML-NBs...
January 28, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28129653/rxr%C3%AE-ligand-z-10-induces-pml-rar%C3%AE-cleavage-and-apl-cell-apoptosis-through-disrupting-pml-rar%C3%AE-rxr%C3%AE-complex-in-a-camp-independent-manner
#8
Lin Xu, Zhiping Zeng, Weidong Zhang, Gaoang Ren, Xiaobin Ling, Fengyu Huang, Peizhen Xie, Ying Su, Xiao-Kun Zhang, Hu Zhou
The major oncogenic driver of acute promyelocytic leukemia (APL) is the fusion protein PML-RARα originated from the chromosomal translocation t(15;17). All-trans retinoic acid (ATRA) and arsenic trioxide cure most patients by directly targeting PML-RARα. However, major issues including the resistance of ATRA and arsenic therapy still remain in APL clinical management. Here we showed that compound Z-10, a nitro-ligand of retinoid X receptor α (RXRα), strongly promoted the cAMP-independent apoptosis of both ATRA- sensitive and resistant NB4 cells via the induction of caspase-mediated PML-RARα degradation...
January 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28125133/acute-wt1-positive-promyelocytic-leukemia-with-hypogranular-variant-morphology-bcr-3-isoform-of-pml-rar%C3%AE-and-flt3-itd-mutation-a-rare-case-report
#9
Xi Zhang, Cheng Yang, Xiangui Peng, Xinghua Chen, Yimei Feng
CONTEXT: Acute promyelocytic leukemia (APL) accounts for 8% to 10% of cases of acute myeloid leukemia (AML). Remission in cases of high-risk APL is still difficult to achieve, and relapses occur readily. CASE REPORT: Here, we describe a case of APL with high white blood cell counts in blood tests and hypogranular variant morphology in bone marrow, together with fms-like tyrosine kinase-3 with internal tandem duplication mutations (FLT3-ITD), and bcr-3 isoform of PML-RARα...
January 23, 2017: São Paulo Medical Journal, Revista Paulista de Medicina
https://www.readbyqxmd.com/read/28125064/phenylarsine-oxide-can-induce-the-arsenite-resistance-mutant-pml-protein-solubility-changes
#10
Yu Han Jiang, Ye Jia Chen, Chao Wang, Yong Fei Lan, Chang Yang, Qian Qian Wang, Liaqat Hussain, Yasen Maimaitiying, Khairul Islam, Hua Naranmandura
Arsenic trioxide (As₂O₃) has recently become one of the most effective drugs for treatment of patient with acute promyelocytic leukemia (APL), and its molecular mechanism has also been largely investigated. However, it has been reported that As₂O₃ resistant patients are frequently found in relapsed APL after consolidation therapy, which is due to the point mutations in B-box type 2 motifs of promyelocytic leukemia (PML) gene. In the present study, we for the first time establish whether organic arsenic species phenylarsine oxide (PAO) could induce the mutant PML-IV (A216V) protein solubility changes and degradation...
January 25, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28119236/periostin-contributes-to-arsenic-trioxide-resistance-in-hepatocellular-carcinoma-cells-under-hypoxia
#11
Yujin Liu, Feng Gao, Weixiang Song
Hypoxia has been suggested to induce chemoresistance in tumor cells. In this study, we aimed to test the hypothesis that hypoxia-inducible factor-1alpha (HIF-1α)/periostin axis might promote arsenic trioxide resistance in hepatocellular carcinoma (HCC) cells under hypoxia. HCC cells were exposed to hypoxia and measured for periostin expression. Loss-of-function studies were done to assess the role of periostin in arsenic trioxide resistance. In vivo xenograft mouse studies were performed to determine the effect of periostin silencing on HCC susceptibility to arsenic trioxide...
January 21, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28115242/arsenic-downregulates-tight-junction-claudin-proteins-through-p38-and-nf-%C3%AE%C2%BAb-in-intestinal-epithelial-cell-line-ht-29
#12
Chang Hee Jeong, Jin Sil Seok, Michael C Petriello, Sung Gu Han
Arsenic is a naturally occurring metalloid that often is found in foods and drinking water. Human exposure to arsenic is associated with the development of gastrointestinal problems such as fluid loss, diarrhea and gastritis. Arsenic is also known to induce toxic responses including oxidative stress in cells of the gastrointestinal track. Tight junctions (TJs) regulate paracellular permeability and play a barrier role by inhibiting the movement of water, solutes and microorganisms in the paracellular space...
January 20, 2017: Toxicology
https://www.readbyqxmd.com/read/28111878/first-experience-of-the-aml-berlin-frankfurt-m%C3%A3-nster-group-in-pediatric-patients-with-standard-risk-acute-promyelocytic-leukemia-treated-with-arsenic-trioxide-and-all-trans-retinoid-acid
#13
Ursula Creutzig, Michael N Dworzak, Konrad Bochennek, Jörg Faber, Christian Flotho, Norbert Graf, Udo Kontny, Claudia Rossig, Irene Schmid, Arend von Stackelberg, Jans-Enno Mueller, Christine von Neuhoff, Dirk Reinhardt, Nils von Neuhoff
Recently, studies in adults with acute promyelocytic leukemia (APL) showed high cure rates in low-risk patients treated with all-trans retinoid acid (ATRA) and arsenic trioxide (ATO), while toxicities were significantly reduced compared to the standard treatment with ATRA and chemotherapy. Here we report about first experience with 11 pediatric patients with low-risk APL treated with ATRA and ATO. All patients stayed in molecular remission. All suffered from hyperleukocytosis. Two patients experienced reversible severe side effects...
January 23, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28110321/recent-advances-in-arsenic-trioxide-encapsulated-nanoparticles-as-drug-delivery-agents-to-solid-cancers
#14
Akhtar Anam, Wang Scarlet Xiaoyan, Ghali Lucy, Bell Celia, Wen Xuesong
Since arsenic trioxide was first approved as the front line therapy for acute promyelocytic leukemia 25 years ago, its anti-cancer properties for various malignancies have been under intense investigation. However, the clinical successes of arsenic trioxide in treating hematological cancers have not been translated to solid cancers. This is due to arsenic's rapid clearance by the body's immune system before reaching the tumor site. Several attempts have henceforth been made to increase its bioavailability toward solid cancers without increasing its dosage albeit without much success...
January 19, 2017: Journal of Biomedical Research
https://www.readbyqxmd.com/read/28109899/rgd-conjugated-liposome-hollow-silica-hybrid-nanovehicles-for-targeted-and-controlled-delivery-of-arsenic-trioxide-against-hepatic-carcinoma
#15
Weidong Fei, Yan Zhang, Shunping Han, Jiaoyang Tao, Hongyue Zheng, Yinghui Wei, Jiazhen Zhu, Fanzhu Li, Xuanshen Wang
The aim of our study was to construct an Arg-Gly-Asp (RGD)-conjugated liposome-hollow silica hybrid nanovehicle for targeted delivery and controlled release of arsenic trioxide (ATO), whose anti-solid tumor effect was hampered by poor pharmacokinetics and dose-limited toxicity. Hydrophobic interactions were used to attach intact lipid membrane to the surface of chlorodimethyloctadecylsilane-modified hollow mesoporous silica nanoparticles. The prepared nanovehicles (RGD-LP-CHMSN) were characterized for uniform structure (silica core of ∼140nm in diameter and liposomal shell of ∼6nm), comparable drug loading efficiency (6...
January 18, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28109402/frontline-treatment-of-acute-myeloid-leukemia-in-adults
#16
REVIEW
Gevorg Tamamyan, Tapan Kadia, Farhad Ravandi, Gautam Borthakur, Jorge Cortes, Elias Jabbour, Naval Daver, Maro Ohanian, Hagop Kantarjian, Marina Konopleva
Recent years have highlighted significant progress in understanding the underlying genetic and epigenetic signatures of acute myeloid leukemia(AML). Most importantly, novel chemotherapy and targeted strategies have led to improved outcomes in selected genetic subsets. AML is a remarkably heterogeneous disease, and individualized therapies for disease-specific characteristics (considering patients' age, cytogenetics, and mutations) could yield better outcomes. Compared with the historical 5-to 10-year survival rate of 10%, the survival of patients who undergo modern treatment approaches reaches up to 40-50%, and for specific subsets, the improvements are even more dramatic; for example, in acute promyelocytic leukemia, the use of all-trans retinoic acid and arsenic trioxide improved survival from 30 to 40% up to 80 to 90%...
February 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28108741/metabolism-toxicity-and-anticancer-activities-of-arsenic-compounds
#17
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
#18
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
#19
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
#20
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: In the pharmaceutical industry risk assessments of chronic cardiac safety liabilities are mostly performed during late stages of preclinical 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 the chronic effect (over 72 h) of cardiotoxic drugs on the contractile motion of hiPS-CMs...
January 17, 2017: British Journal of Pharmacology
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