Rameshwar. Answer Save. The primary objective was to document the efficacy and safety of As2O3. USA.gov. Arsenic pentoxide is the inorganic compound with the formula As 2 O 5. (oxidation = increase in oxidation state, reduction = decrease in oxidation state) (oxidation = increase in oxidation state, reduction = decrease in oxidation state) Subsequent maintenance courses were repeated after intervals of 4 weeks off therapy. Arsenic trioxide’s content is 99.94%, extraction yield can reach to 98.92%. In addition, patients with the AS3MT 14215 (rs3740390) CC genotype had significantly higher plasma iAs% and incidence of hyperleukocytosis, but lower PMI than patients with the CT + TT genotype. The maintenance therapy was to be started 4 weeks after completion of induction therapy at the same daily dose that was used in the induction treatment (0.15 mg/kg); As2O3 was administered for a total of 25 doses per cycle given 5 days per week for 5 weeks. HHS Number of times cited according to CrossRef: Tannic acid ameliorates arsenic trioxide-induced nephrotoxicity, contribution of NF-κB and Nrf2 pathways. Most of the toxicities identified in this study and others using As2O3 have been transient and minor. 1S/As2O3/c3-1-5-2-4 InChI key IKWTVSLWAPBBKU-UHFFFAOYSA-N Show More (10) Description. Long-term outcome of acute promyelocytic leukemia treated with all- 2018 Nov 1;166(1):219-227. doi: 10.1093/toxsci/kfy210. in vitro At present the main method for obtaining arsenic in a free state is sintering its sulfide ores: 2As₂S₃ + 9O₂ = 6SO₂ + 2As₂O₃; As₂O₃ + 3C = 2As + 3CO. Overall survival of 12 patients who were treated with arsenic trioxide for recurrent acute promyelocytic leukemia. Learn more. Relevance. © 2003 American Cancer Society. : Twenty patients with newly diagnosed APL were treated with As2O3 (0.16 mg/kg per day) and ATRA (45 mg/m2 per day) until they achieved a CR. One patient died in CR from sepsis after 3 cycles of As2O3 alone 37 weeks after achieving CR. These therapies may induce remissions in up to 70–80%1 but carry significant morbidity and mortality. … (As=+3). Oxidation number is the property of an element in a chemical form. The other patient developed symptoms at the end of therapy, and he was able to finish therapy after holding the drug for 1 week. Therefore, As (III) has to be oxidized to As (V) prior to its removal. Highlights From: 45th Annual Meeting of the American Society of Hematology December 6-9, 2003 San Diego, California. The results showed that APL patients who developed hyperleukocytosis had a higher plasma iAs%, but a lower MMA% and PMI than those who did not develop hyperleukocytosis during As2O3 treatment. Nine patients had cytogenetic analysis at the time of CR, and 7 of those patients (78%) achieved a cytogenetic remission. Although As2O3 is known to regulate activation of several signaling cascades, the key events, accounting for its antileukemic properties, remain to be defined. Acute promyelocytic leukemia as a paradigm for targeted therapy. The value of achieving molecular remissions was established previously by Lo Coco et al,16 who also established the significance of molecular remission in patients APL. Involvement of PML-I in reformation of PML nuclear bodies in acute promyelocytic leukemia cells by leptomycin B. Only one patient received the full 60 days of therapy before achieving CR. The toxicity profile of As2O3 was favorable. Thermodynamic properties of substances The solubility of the substances Periodic table of elements. The human and African green monkey TRIM5 genes encode Ref1 and Lv1 retroviral restriction factor activities. Polymorphisms in arsenic (+ 3 oxidation state) methyltransferase (AS3MT) have been shown to be related to interindividual variations in arsenic metabolism and to influence adverse health effects in acute promyelocytic leukemia (APL) patients treated with arsenic trioxide (As2O3). International Journal of Hematologic Oncology. Southwest oncology group phase II study of arsenic trioxide in patients with refractory germ cell malignancies. Role of Arsenic Trioxide in Acute Promyelocytic Leukemia. Antonelli R, Shao K, Thomas DJ, Sams R 2nd, Cowden J. Environ Res. Before ATRA was used widely as frontline therapy, Cortes et al. Arsenic (+3 oxidation state) methyltransferase (AS3MT) is a key enzyme responsible for arsenic metabolism in humans, which facilitates conversion of arsenic trioxide to more reactive metabolites such as monomethylarsonous acid (MMAIII) and dimethylarsinous acid (DMAIII). At the time of morphologic CR, 7 of 10 patients who were evaluated by PCR analysis (70% of patients; 95% confidence interval; 0.35–0.93) achieved a molecular remission. Therefore, gallium arsenide oxidation states are +3 for Ga and -3 for As. AS3MT Polymorphisms, Arsenic Metabolism, and the Hematological and Biochemical Values in APL Patients Treated with Arsenic Trioxide. 0 0. coby. Individual variations in inorganic arsenic metabolism associated with AS3MT genetic polymorphisms. Since there are two arsenic atoms and three sulfur atoms with -2 oxidation state: 2 (x)+3 (-2)=0, so 2x-6=0, 2x=6, x=+3. Plasma arsenic methylation metabolism capacity was evaluated by the percentage of inorganic arsenic (iAs), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), primary methylation index (PMI, MMA/iAs), and secondary methylation index (SMI, DMA/MMA). If you do not receive an email within 10 minutes, your email address may not be registered, 9 years ago. A syndrome with clinical characteristics similar to those seen after treatment with ATRA in patients with APL (retinoic acid syndrome) has been reported.30 We observed significant fluid retention in one patient, but it did not meet the criteria for retinoic acid (or differentiation) syndrome. NLM Prior to the start of therapy, all patients had a complete blood cell count (CBCs); coagulation profiles, including prothrombin time, partial thromboplastin time, fibrinogen, fibrin split products, and D‐dimer; blood chemistry, including total protein, albumin, calcium, inorganic phosphorus, blood urea nitrogen, creatinine, glucose, uric acid, total bilirubin, alkaline phosphatase, lactate dehydrogenase, and alanine aminotransferase; electrolytes; urinalysis; electrocardiogram (EKG); chest X‐ray; and bone marrow aspiration with cytogenetic analysis and/or molecular or FISH studies, if indicated. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis. A phase II study of arsenic trioxide in patients with relapsed or refractory malignant lymphoma. Journal of Pediatric Hematology/Oncology. All patients achieved a CR after a mean of 25 days. One of those patients required discontinuation of therapy and had a partial improvement of symptoms after therapy was discontinued. Sixteen patients (84%) achieved a CR, and 6 patients had negative PCR results at the time of hematologic CR; 14 patients had negative PCR results 2–4 months after hematologic CR.15 Thus, because the experience with As2O3 to date relates to patients with recurrent APL, the rate of molecular remissions at the time of CR is very favorable. In compounds, arsenic can display 3 oxidation states - -3, +3 и +5. Polymorphisms in arsenic (+ 3 oxidation state) methyltransferase (AS3MT) have been shown to be related to interindividual variations in arsenic metabolism and to influence adverse health effects in acute promyelocytic leukemia (APL) patients treated with arsenic trioxide (As2O3). Acute promyelocytic leukemia: recent advances in therapy and molecular basis of response to arsenic therapies. American Journal of Health-System Pharmacy. Acute Promyelocytic Leukemia: A History over 60 Years—From the Most Malignant to the most Curable Form of Acute Leukemia. More common, and far more important commercially, is arsenic(III) oxide (As 2 O 3 ). Brief History of Arsenic Discovery History is convoluted Not sure who first discovered Greeks and Romans had slaves mine for arsenic Used in Alchemy Albertus Magnus www.en.wikipedia.com German chemist First to isolate in 1250 AD reported 8 of 11 tested patients in molecular CR after two courses of therapy. What is the oxidation number of arsenic in H2AsO4 -2? Chem., Sect. Agusa T, Fujihara J, Takeshita H, Iwata H. Int J Mol Sci. The data showed that the energy separation (eV) between As2O5 and As2S3 was 5.8, between As2O3 and As2O5 was 3.6, and between As2S3 and As2O3 was 2.1. Therefore, As(III) has to be oxidized to As(V) prior to its removal. Frontline treatment of acute myeloid leukemia in adults. In natural waters arsenic normally occurs in the oxidation states +III (arsenite) and +V (arsenate). The study was an open‐label protocol for patients with recurrent APL. Lu J, Hu S, Wang W, Li J, Dong Z, Zhou J, Hai X. Toxicol Sci. Influence of AS3MT polymorphisms on arsenic metabolism and liver injury in APL patients treated with arsenic trioxide. Basic & Clinical Pharmacology & Toxicology. Please enable it to take advantage of the complete set of features! During maintenance, two patients developed peripheral neuropathy (Grade 2 and Grade 3, respectively). Hepatotoxicity From Arsenic Trioxide for Pediatric Acute Promyelocytic Leukemia. Epub 2019 Jul 19. AS3MT, GSTO, and PNP polymorphisms: impact on arsenic methylation and implications for disease susceptibility. The technology of the acidification is adopted to prepare arsenic trioxide (As2O3). The authors report the experience of The M. D. Anderson Cancer Center with As2O3 in the treatment of patients with recurrent APL. Matrine induces apoptosis in acute myeloid leukemia cells by inhibiting the PI3K/Akt/mTOR signaling pathway. 1.1 Arsenic. That patient had resolution of symptoms after therapy was finished. Nine of their 10 patients (90%) who were treated with As2O3 alone and all 5 of their patients who were treated with As2O3 and low‐dose chemotherapeutic drugs (daunorubicin plus cytarabine; hydroxyurea and harringtonine plus cytarabine) or ATRA achieved a CR.8 Soignet et al.9 reported a CR rate of 92% among 12 patients who had a median CR duration of > 5 months. . 1). Favourite answer. What is the oxidation state of Arsenic in As2S3 (Arsenic Trisulphide)? Patients who maintained a molecular remission in at least two consecutive assessments at least 3 months apart had a very low probability of recurrence.17, The mechanism of action of As2O3 is not understood well. During therapy, patients were monitored with CBCs, SMA‐12, and coagulation profiles until the completion of therapy. Get the latest public health information from CDC: https://www.coronavirus.gov, Get the latest research information from NIH: https://www.nih.gov/coronavirus, Find NCBI SARS-CoV-2 literature, sequence, and clinical content: https://www.ncbi.nlm.nih.gov/sars-cov-2/. Chemotherapy Induced Peripheral Neuropathies (CIPNs): A Biobehavioral Approach. You can sign in to give your opinion on … Chem.. Phase 1 trial and pharmacokinetic study of arsenic trioxide in children and adolescents with refractory or relapsed acute leukemia, including acute promyelocytic leukemia or lymphoma. De Loma J, Skröder H, Raqib R, Vahter M, Broberg K. Toxicol Appl Pharmacol. Treatment of acute promyelocytic leukemia with PETHEMA LPA 99 protocol: a Tunisian single center experience. Non-Coding RNAs as Molecular Targets of Resveratrol Underlying Its Anticancer Effects. It has been reported that arsenic trioxide (As2O3) is effective in patients with APL who develop recurrent disease after treatment with ATRA.8 We conducted a trial to determine the safety and efficacy of As2O3 in patients with recurrent APL, the results of which are presented in this report. These results indicated that AS3MT 14215 (rs3740390) might be used as an indicator for predicting the occurrence of hyperleukocytosis in APL patients treated with As2O3. Arsenic (+3 oxidation state) methyltransferase (AS3MT) is a key enzyme responsible for arsenic metabolism in humans, which facilitates conversion of arsenic trioxide (As2O3) to more reactive metabolites such as monomethylarsonous acid (MMAIII) and dimethylarsinous acid (DMAIII). Investigational strategies in chronic myelogenous leukemia. The patient who was treated in second recurrence received induction originally with ATRA and daunorubicin plus cytarabine; he achieved a CR that lasted for 88 weeks. Among the three patients who did not achieve a molecular remission at the time of hematologic CR, two (Patients 4 and 9) achieved molecular remission after one additional cycle of As2O3, and one patient (Patient 2) achieved molecular remission after two cycles of As2O3. Lv 6. Current first- and second-line treatment options in acute promyelocytic leukemia. The dose was diluted in 250 cc of 5% dextrose and was administered over 2 hours. At the time of CR, 1 of 10 evaluable patients (10%) had achieved a documented molecular remission. Rep. Prog. Journal of Agricultural and Food Chemistry. Treatment concepts of acute promyelocytic leukemia. Efficacy of Transarterial Embolization with Arsenic Trioxide Oil Emulsion in a Rabbit VX2 Liver Tumor Model. Lv 7. Epub 2014 May 8. Molecular remission may be achieved at the time of CR in the majority of patients, and remissions are durable. Shen et al. Eligibility criteria included 1) confirmation of t(15;17) by conventional cytogenetic analysis or positive reverse transcriptase‐polymerase chain reaction (RT‐PCR) assay for PML‐RARα or fluorescence in situ hybridization (FISH) showing evidence of RARα or PML translocation; 2) adequate renal function (creatinine ≤ 2.5 times the upper limit of normal) and liver function (serum bilirubin ≤ 2.5 times the upper limit of normal); 3) negative pregnancy test; and 4) signed informed consent. First-Line Therapy: ATRA-ATO/Reduced Chemotherapy Approach. A: Inorg. With this therapy, > 90% of patients achieve a remission, and 60–70% of patients can be cured.3, 4, 7 However, 20–30% of patients eventually will develop recurrent disease.3 Recently, it was reported that As2O3 was an effective therapy for patients with recurrent APL after they were treated with ATRA. Arsenic trioxide (As2O3) exhibits potent antineoplastic effects and is used extensively in clinical oncology for the treatment of a subset of patients with acute myeloid leukemia (AML). Fourteen patients (82%) achieved a CR with a median follow‐up of 6 months, and 6 patients were still in remission.5 In a different approach, L‐ATRA was used as salvage therapy in six patients who had developed recurrent disease after therapy with ATRA. Search. One patient developed recurrent disease after 29 weeks, and 1 patient died in CR after 37 weeks (Fig. Two patients received no additional As2O3 in maintenance and were consolidated with idarubicin and ATRA for three courses and six courses, respectively (Table 3). Chemotherapy‐Induced Polyneuropathy: Major Agents and Assessment by Questionnaires. Role of arsenic (+3 oxidation state) methyltransferase in arsenic mediated APL treatment: an Obtaining the pure substance and its chemical properties. The current standard therapy for patients with APL includes ATRA plus an anthracycline with or without cytarabine. Sign In Create Free Account. Arsenic(III) oxide react with sodium hydroxide to produce sodium orthoarsenite and water. Long term curative effects of sequential therapy with all-trans retinoic acid, arsenious oxide and chemotherapy on patients with acute promyelocytic leukemia. Treatment was associated with significant toxicity, with elevation of transaminases in 11 patients (55%).20 Other studies have suggested that As2O3 induces apoptosis independent of both PML and PML‐RARα expression in a variety of myeloid leukemia cell lines.21 These finding suggest that As2O3 may be used more widely for the treatment of patients with leukemias other than APL.22 As2O3 has shown activity in vitro against a variety of hematologic cell lines, including plasma23 and lymphoma cell lines,24 and among a variety of solid tumor cell lines.25, 26 There are anecdotal reports of activity in patients with myelodysplastic syndromes,27 and current studies are investigating its activity in other hematologic malignancies, including chronic myeloid leukemia, multiple myeloma,28 and other lymphoproliferative malignancies.29. using L‐ATRA.14 Patients with newly diagnosed, previously untreated APL received L‐ATRA alone until they achieved a CR, and chemotherapy was not added unless there was no molecular remission or if there was a molecular recurrence. Proceedings of the National Academy of Sciences. Novel therapies for patients with chronic myeloid leukemia. Twelve of 18 treated patients (67%) achieved a CR. As an industrial chemical, major uses include in the manufacture of wood preservatives, pesticides, and glass. The most troublesome side effect in our study was Grade ≥ 2 peripheral neuropathy, which was seen in two patients and lead to discontinuation of therapy in one patients. Chemotherapy of acute leukemia in adults. The patient who presented in third recurrence was treated originally with ATRA, achieved a CR, and developed a recurrence after 168 weeks. The protocol was approved by the Institutional Review Board, and all patients signed an informed consent according to institutional guidelines. Working off-campus? From July 1998 to May 2001, adult patients with a confirmed diagnosis of APL in recurrence after initial treatment with ATRA‐based therapy were eligible for this study. -retinoic acid, arsenic trioxide, and gemtuzumab To clarify the causes of this situation, AS3MT polymorphisms 14215 (rs3740390), 14458 (rs11191439), 27215 (rs11191446), and 35991 (rs10748835) and profiles of plasma arsenic metabolites were evaluated in a group of 54 newly diagnosed APL patients treated with single-agent As2O3. With this regimen, the remission rate has improved significantly to 70–95%, and the survival rate has doubled in newly diagnosed patients.2-7. Therapy at the time of initial diagnosis had included liposomal ATRA (L‐ATRA) alone (n = 4 patients) or conventional ATRA in combination with anthracyclines (n = 2 patients), idarubicin (n = 3 patients), idarubicin plus cytarabine, (n = 2 patients), or daunorubicin plus cytarabine (n = 1 patient). 2010 Jul 13;18(1):88-98. doi: 10.1016/j.ccr.2010.06.003. General description Arsenic(III) oxide, also known as arsenic trioxide, is an amphoteric oxide that serves as a raw material for the synthesis of several arsenic-based compounds. Acute promyelocytic leukemia (APL) is characterized by the presence of a translocation, t(15; 17), that fuses the gene encoding for the nuclear receptor for retinoic acid (RARα) to the PML gene (PML‐RARα).1, 2 Patients usually are young, and there is a greater frequency among Hispanic children. Management of acute promyelocytic leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet. The durability of subsequent remissions with As2O3 and the high incidence of molecular remissions in second or subsequent CR make As2O3 particularly attractive for the treatment of patients with early‐stage disease (i.e., newly diagnosed patients with APL). Best Practice & Research Clinical Haematology. 2019 Sep 15;379:114687. doi: 10.1016/j.taap.2019.114687. The occurrence of hyperleukocytosis with As2O3 treatment seriously affects the early survival rate of APL patients, but no definite explanation for such a complication has been clearly established. Survival was measured from the time of treatment until death. As2O3 appears to be a safe and effective agent for the treatment of patients with APL. Epub 2011 Apr 4. treated 17 patients who had failed prior standard acute myelocytic leukemia therapy (idarubicin and cytarabine). Find another reaction. The early studies from China did not describe any molecular analysis.7, 12 Warrell et al.13 reported that the expression of the abnormal RARα species disappeared in some patients. Chemotherapy-Induced Peripheral Neuropathy: A Review and Implications for Oncology Nursing Practice. Environmental Toxicology and Pharmacology. Igf-1 receptor kinase and target therapy toxicities identified in this study and others As2O3. 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J Mol Sci for relapsed or refractory lymphoid malignancies: a Wisconsin Oncology Network study 70–95 %, yield... Compared to all‐trans retinoic acid and arsenic trioxide in the manufacture of wood preservatives, pesticides, 2... Full 60 days of therapy ; 12 ( 4 ):2351-82. doi: 10.1093/toxsci/kfy210 a Tunisian single Center experience effective... Gallium oxidation state in arsenides or intermetallic compounds neuropathy, headache, fatigue, and 7 of those required! Contribution of NF-κB and Nrf2 pathways ( arsenate ) with the rarity of the European LeukemiaNet no of trioxide. Endpoint was the achievement of cytogenetic and molecular remission may be achieved at time. Medical intervention those obtained with ATRA were included ; arsenic methylation metabolism ; arsenic trioxide ’ s content is %... Therapeutic Targets for Cancer Prevention ATRA‐based therapy were treated with liposomal daunorubicin for treatment. Adverse events include peripheral neuropathy: a History over 60 Years—From the most form... Cr that lasted 68 weeks Toxicol Sci it to take advantage of M.! From arsenic trioxide, sold under the brand name Trisenox among others, is important that who.