DNA hypermethylation is an epigenetic modification that plays a critical role in the oncogenesis of myelodysplastic syndromes (MDS). Aberrant DNA methylation represses the transcription of promotors of tumor suppressor genes, inducing gene silencing. Realgar (α-As₄S₄) is a traditional medicine used for the treatment of various diseases in the ancient time. Realgar was reported to have efficacy for acute promyelocytic leukemia (APL). It has been demonstrated that realgar could efficiently reduce DNA hypermethylation of MDS. This review discusses the mechanisms of realgar on inhibiting DNA hypermethylation of MDS, as well as the species and metabolisms of arsenic in vivo.
Arsenicals/therapeutic use* ; DNA ; DNA Methylation/genetics* ; Humans ; Myelodysplastic Syndromes/genetics* ; Sulfides

Qinghuang Powder (QHP), an oral arsenic, has become an effective drug in the treatment of myelodysplastic syndromes (MDS) in Xiyuan Hospital, China Academy of Chinese Medical Sciences for many years, and the action mechanism of the compound or active ingredient As₂S₂ of QHP has been elucidated. Considering the relatively safety, chemotherapy-free and convenient oral profile, QHP is widely used in the clinical treatment for MDS patients, especially for elderly patients. In this review, the authors document the efficacy and safety of oral arsenic-containing compound QHP in the treatment of MDS, with a special focus on the association of efficacy of QHP with the cytogenetics, prognostic risk, DNA methylation, gene mutation, blood arsenic concentration, mechanism of action of As₂S₂ and the countermeasures against adverse reactions of gastrointestinal tract.
Aged ; Arsenic/therapeutic use* ; Arsenicals/adverse effects* ; Drugs, Chinese Herbal ; Humans ; Myelodysplastic Syndromes/genetics* ; Powders/therapeutic use*

OBJECTIVE: To analyze the overall survival (OS) of elderly acute myeloid leukemia (AML) patients treated with oral arsenic-containing Qinghuang Powder (, QHP) or low-intensity chemotherapy (LIC). METHODS: Forty-two elderly AML patients treated with intravenous or subcutaneous LIC (1 month for each course, at least 3 courses) or oral QHP (3 months for each course, at least 2 courses) were retrospectively analyzed from January 2015 to December 2017. The main endpoints of analysis were OS and 1-, 2-, 3-year OS rates of patients, respectively. And the adverse reactions induding bone marrow suppression, digestive tract discomfort and myocardia injury were observed. RESULTS: Out of 42 elderly AML patients, 22 received LIC treatment and 20 received QHP treatment, according to patients' preference. There was no significant difference on OS between LIC and QHP patients (13.0 months vs. 13.5 months, >0.05). There was no significant difference on OS rates between LIC and QHP groups at 1 year (59.1% vs. 70.0%), 2 years (13.6% vs. 15%), and 3 years (4.6% vs. 5.0%, all >0.05). Furthermore, there was no significant difference of OS on prognosis stratification of performance status > 2 (12 months vs. 12 months), age> 75 year-old (12.0 months vs. 12.5 months), hematopoietic stem cell transplant comorbidity index >2 (12 months vs. 13 months), poor cytogenetics (12 months vs. 8 months), and diagnosis of secondary AML (10 months vs. 14 months) between LIC and QHP patients (>0.05). CONCLUSION QHP may be an alternative treatment for elderly AML patients refusing LIC therapy.
Aged ; Aged, 80 and over ; Antineoplastic Agents ; therapeutic use ; Arsenicals ; therapeutic use ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Leukemia, Myeloid, Acute ; drug therapy ; mortality ; Male ; Middle Aged ; Powders ; Retrospective Studies

OBJECTIVE: To explore the effect of Qinghuang Powder (QHP,()combined with Bupi Yishen Decoction (BPYS, ) on myelodysplastic syndromes (MDS) patients with refractory cytopenia with multilineage dysplasia (RCMD) and determine the change of DNA methylation in MDS-RCMD patients after the treatment of Chinese medicine formula. METHODS: All 308 MDS-RCMD patients were treated with QHP combined with BPYS for 2 months at least, absolute neutrophil count (ANC), hemoglobin (Hb), platelets (PLT), primitive bone marrow cells and chromosome karyotype were chosen as the main evaluation indexes to analyze the treatment effect according to criteria from the MDS International Working Group. Then 43 bone marrow samples from 15 MDS-RCMD patients and 28 healthy donors were obtained for the examination of DNA methylation. Gene Ontology (GO) and Pathway analysis were applied to analyze the methylation data. RESULTS: The overall MDS response rate to QHP was 61.68% (190/360) including hematologic improvement-neutrophil (HI-N) or hematologic improvement-erythroid (HI-E) or hematologic improvement-platelet (HI-P). Patients with anemia had a better response rate than patients with neutropenia or thrombocypenia (55.88% vs 31.54% or 55.88% vs. 36.9%). The DNA methylation microarray analysis disclosed that 4,257 hypermethylated genes were demethylated upon the treatment with QHP and BPYS. GO analysis and Pathway analysis showed that these demethylated genes were involved in a lot of tumor-related pathways and functions. CONCLUSIONS QHP combined with BPYS could effectively treat MDS-RCMD patients through hematologic improvement (HI-N, HI-P or HI-E) and PLT and RBC transfusion independence due to the demethylation, thereby providing another choice for the treatment of patients with MDS-RCMD.
Arsenicals ; administration & dosage ; pharmacology ; therapeutic use ; Cell Lineage ; drug effects ; DNA Methylation ; drug effects ; Demethylation ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; therapeutic use ; Female ; Gene Ontology ; Humans ; Leukocyte Disorders ; drug therapy ; genetics ; Male ; Middle Aged ; Powders ; Treatment Outcome

BACKGROUNDDespite great reduction of in-stent restenosis, first-generation drug-eluting stents (DESs) have increased the risk of late stent thrombosis due to delayed endothelialization. Arsenic trioxide, a natural substance that could inhibit cell proliferation and induce cell apoptosis, seems to be a promising surrogate of sirolimus to improve DES performance. This randomized controlled trial was to evaluate the efficacy and safety of a novel arsenic trioxide-eluting stent (AES), compared with traditional sirolimus-eluting stent (SES).

METHODSPatients with symptoms of angina pectoris were enrolled and randomized to AES or SES group. The primary endpoint was target vessel failure (TVF), and the second endpoint includes rates of all-cause death, cardiac death or myocardial infarction, target lesion revascularization (TLR) by telephone visit and late luminal loss (LLL) at 9-month by angiographic follow-up.

RESULTSFrom July 2007 to 2009, 212 patients were enrolled and randomized 1:1 to receive either AES or SES. At 2 years of follow-up, TVF rate was similar between AES and SES group (6.67% vs. 5.83%, P = 0.980). Frequency of all-cause death was significantly lower in AES group (0 vs. 4.85%, P = 0.028). There was no significant difference between AES and SES in frequency of TLR and in-stent restenosis, but greater in-stent LLL was observed for AES group (0.29 ± 0.52 mm vs. 0.10 ± 0.25 mm, P = 0.008).

CONCLUSIONSAfter 2 years of follow-up, AES demonstrated comparable efficacy and safety to SES for the treatment of de novo coronary artery lesions.

Aged ; Arsenicals ; administration & dosage ; therapeutic use ; Coronary Angiography ; Coronary Artery Disease ; diagnostic imaging ; surgery ; Drug-Eluting Stents ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Oxides ; administration & dosage ; therapeutic use ; Percutaneous Coronary Intervention ; methods ; Polymers ; chemistry ; Sirolimus ; administration & dosage ; therapeutic use

OBJECTIVETo investigate the efficacy of arsenic trioxide combined with all trans retinoic acid (ATRA) for patients with acute promyelocytic leukemia (APL).

METHODSA total of 159 cases of APL were selected from January 2011 to December 2014 in our hospital, among them 75 cases were treated by As₂O₃combined with ATRA, 43 cases were treated with As₂O₃alone, 41 cases were treated with ATRA alone. The cardiac enzymes level, lever function index change, death rate, complate remission (CR) rate, time of reaching CR and complicatiens were compared in 3 groups.

RESULTSAfter treatment of 8 courses, ALT and AST levels in As₂O₃+ ATRA group were significantly higher than those in As₂O₃and ATRA alone groups; the CK-MB and TnI-UI index increased in As₂O₃group (P < 0.05); as compared with As₂O₃group, the mortality and CR rate in As₂O₃+ ATRA group were no significant different, but the time of reaching CR was significantly shortened. For relapsed patients, the CR rate in As₂O₃+ ATRA group was no significantly different from that in As₂O₃group, while was significantly higher than that in ATRA group. The ratio of liver function damage in As₂O₃+ ATRA group was increased, moreover the incidence of leukocytosis and headache in ATRA group was significantly higher than that in As₂O₃+ ATRA and As₂O₃group (P < 0.05).

CONCLUSIONSThe efficacy of As₂O₃conbined with ATRA for inducing remission is better than that of single drug treatment, moreover the adverse reactions occur less.

Arsenicals ; therapeutic use ; Drug Therapy, Combination ; Humans ; Leukemia, Promyelocytic, Acute ; drug therapy ; Oxides ; therapeutic use ; Remission Induction ; Tretinoin ; therapeutic use

OBJECTIVETo study the effect of Qinghuang Powder (QHP) combined Chinese herbs for Pi-strengthening and Shen-reinforcing (CHPSSR) on hypoxia-inducible factor 1alpha (HIF-1alpha) in bone marrow mononuclear cells of myelodysplastic syndrome (MDS) patients.

METHODSChanges of HIF-1alpha in bone marrow mononuclear cells of MDS patients were detected in 25 MDS patients treated by QHP combined CHPSSR using flow cytometry. Meanwhile, 13 healthy subjects were recruited as the control group. Changes HIF-1alpha levels in various serial bone marrow mononuclear cells were detected.

RESULTS(1) Among the 25 patients in the treatment group, there were 19 patients effective and 6 patients ineffective, with the total effective rate being 76%. (2) Compared with before treatment, levels of peripheral blood WBC, Hb, PLT, and ANC significantly increased in the treatment group after treatment, showing statistical difference (P < 0.05, P < 0.01). (3) Compared with before treatment, the HIF-1alpha mean fluorescence intensity was enhanced in bone marrow lymphocytes, monocytes, granulocytes, and nucleated red blood cells of the treatment group after treatment (P < 0.05, P < 0.01). Compared with the control group, the HIF-1alpha mean fluorescence intensity was weakened in bone marrow lymphocytes, monocytes, and nucleated red blood cells of the treatment group before treatment; while it was obviously enhanced in granulocytes (P < 0.01). But after treatment the HIF-1alpha mean fluorescence intensity increased more in the granulocytes of the treatment group than in those of the control group (P < 0.01), but there was no statistical difference in bone marrow lymphocytes, monocytes, or nucleated red blood cells.

CONCLUSIONQHP combined CHPSSR could improve HIF-1alpha levels in bone marrow lymphocytes, monocytes, granulocytes, and nucleated red blood cells of MDS patients, thus improving Hb levels of MDS patients, and improving their anemia and correlated symptoms.

Adolescent ; Adult ; Aged ; Arsenicals ; therapeutic use ; Bone Marrow ; Bone Marrow Cells ; drug effects ; metabolism ; Case-Control Studies ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; metabolism ; Male ; Middle Aged ; Monocytes ; drug effects ; metabolism ; Myelodysplastic Syndromes ; drug therapy ; metabolism ; Phytotherapy ; Young Adult

OBJECTIVETo observe the clinical efficacy of a low dose Qinghuang Powder (QP) combined with Chinese drugs for Shen supplementing and Pi invigorating (CDSSPI) in treatment of hypocellular myelodysplastic syndromes (hypo-MDS).

METHODSTotally 33 hypo-MDS patients enrolled in this study came from outpatient clinics between November 2011 and December 2012. A self-control method was used in this study. Patients took QP (0.4 g per day) combined with CDSSPI (one dose per day), and Stanozolol Tablet (2 mg each time, three times per day), 3 months as one therapeutic course, a total of 2 courses. The clinical efficacy was evaluated timely at the end of each therapeutic course. The venous blood was withdrawn before treatment, at month 3 and 6 after treatment. Changes of neutrophils (ANC), hemoglobin (Hb), and platelet (PLT) were mainly observed.

RESULTSTotally 31 patients in this study finished the treatment. Three months after treatment ANC, Hb, and PLT increased more than before treatment (P < 0.05). Six months after treatment Hb and PLT increased (P < 0.01, P < 0.05), but with no statistical difference in ANC (P > 0.05). Hb increased higher at month 6 after treatment than at month 3 after treatment (P < 0.01), but with no statistical difference in ANC or PLT (P > 0.05). After 3-month treatment the number of hematologic progress, stability, disease progression were: 13 cases (41.9%), 15 cases (48.4%), and 3 cases (9.7%), respectively; after 6-month treatment the number of hematologic improvement, stability, and disease progression were: 18 cases (58.1%), 7 cases (22.6%), 6 cases (19.3%), respectively. There was no significant difference between 3-month efficacy and 6-month efficacy (P > 0.05). There was no correlation between the efficacy and ages of hypo-MDS patients or the efficacy and courses of hypo-MDS patients (P > 0.05).

CONCLUSIONSA low dose QP combined with CDSSPI showed confirmative efficacy in treatment of hypo-MDS. But the efficacy had little correlation with ages and courses of hypo-MDS patients.

Arsenicals ; administration & dosage ; pharmacology ; therapeutic use ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; therapeutic use ; Hemoglobins ; Humans ; Medicine, Chinese Traditional ; methods ; Myelodysplastic Syndromes ; drug therapy ; Neutrophils ; Phytotherapy ; methods

Adult ; Aged ; Arsenicals ; pharmacology ; therapeutic use ; Bone Marrow Cells ; drug effects ; metabolism ; DNA Methylation ; drug effects ; Female ; Humans ; Inhibitor of Differentiation Proteins ; metabolism ; Male ; Middle Aged ; Myelodysplastic Syndromes ; metabolism ; therapy ; Oxides ; pharmacology ; therapeutic use ; Treatment Outcome ; Young Adult

OBJECTIVETo summarize limitations involved in arsenic trioxide therapeutic effects in acute promyelocytic leukemia, because current studies show that some individuals of acute promyelocytic leukemia have relatively poor outcomes during treatment with arsenic trioxide.

DATA SOURCESMost relevant articles were included in the PubMed database between 2000 and 2013 with the keywords "acute promyelocytic leukemia," "arsenic trioxide," "thiol" or "methylation." In addition, a few older articles were also reviewed.

STUDY SELECTIONData and articles related to arsenic trioxide effect in acute promyelocytic leukemia treatment were selected and reviewed. We developed an overview of limitations associated with arsenic trioxide therapeutic effect.

RESULTSThis review focuses on the researches about the arsenic trioxide therapeutic effect in acute promyelocytic leukemia and summarizes three mainly limitations which can influence the arsenic trioxide therapeutic effect to different degrees. First, with the combination of arsenic and glutathione the therapeutic effect and cytotoxicity decrease when glutathione concentration increases; second, arsenic methylation, stable arsenic methylation products weaken the apoptosis effect of arsenic trioxide in leukemia cells; third, gene mutations affect the sensitivity of tumor cells to arsenic trioxide and increase the resistance of leukemia cells to arsenic trioxide.

CONCLUSIONSThe chief limitations are listed in the review. If we can exclude all of them, we can obtain a better therapeutic effect of arsenic trioxide in patients with acute promyelocytic leukemia.

Antineoplastic Agents ; therapeutic use ; Arsenicals ; therapeutic use ; Humans ; Leukemia, Promyelocytic, Acute ; drug therapy ; genetics ; Mutation ; Oxides ; therapeutic use