Antineoplastic Agents ; therapeutic use ; Arsenicals ; therapeutic use ; Humans ; Myelodysplastic Syndromes ; drug therapy ; Oxides ; therapeutic use

Aged ; Arsenicals ; therapeutic use ; Female ; Humans ; Leukemia, Basophilic, Acute ; drug therapy ; Oxides ; therapeutic use

Arsenicals ; therapeutic use ; Humans ; Leukemia, Promyelocytic, Acute ; drug therapy ; Medicine, Chinese Traditional ; Oxides ; therapeutic use

Chinese arsenic drugs have been applied in Chinese medicine for several centuries. Beginning from 1970s, arsenic containing drugs have been generally used for the treatment of malignant hematologic diseases including acute promyelocytic leukemia, myelodysplastic syndrome, and multiple myeloma. No matter what ingredients of arsenic drugs were applied, either arsenic trioxide, arsenic disulfide, or arsenic containing Chinese herbal compositions including Qinghuang Powder and Realgar-Indigo naturalis formula, they all provided the distinct approaches for the management of malignant hematologic diseases, and good clinical efficacy was obtained with mild adverse reactions. Moreover, the mechanisms of action have been continually elucidated.
Arsenicals ; therapeutic use ; China ; Drugs, Chinese Herbal ; therapeutic use ; Hematologic Neoplasms ; drug therapy ; Humans ; Oxides ; therapeutic use

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

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

Arsenic trioxide has been used to treat lymphoma experimentally since it was used to treat acute promyelocytic leukemia successfully. Massive works in this field have been done throughout the world. It was found that arsenic trioxide exerted an anti-lymphomatic effect via many pathways, and many substances could increase or reduce this effect. Arsenic trioxide can be used to treat relapsed and refractory lymphomas resistant to other chemotherapies with some therapeutic effects and limited side effects, which indicates that arsenic trioxide is a new potential drug for lymphoma. This article is an overview about these foundational and clinical studies.
Angiogenesis Inhibitors ; therapeutic use ; Antineoplastic Agents ; therapeutic use ; Apoptosis ; drug effects ; Arsenicals ; therapeutic use ; Humans ; Lymphoma ; drug therapy ; Oxides ; therapeutic use

OBJECTIVETo investigate the cardiac effect of QT interval prolongation in the treatment of acute promyelocytic leukemia (APL) with arsenic trioxide (As(2)O(3)), and the relationship between QT and serum arsenic concentration.

METHODSBlood serum arsenic concentrations of thirty APL patients were determined at 2 hours, 4 hours, 8 hours, and 24 hours after As(2)O(3) injection using atomic fluorophotometry. Cardiac functions were measured simultaneously using a 12-lead body-surface electrocardiogram (ECG). Q-T intervals were manually measured, and then corrected using Bazett's formula (QTc). QT dispersion (QTd) was also calculated. In order to assess the effects of arsenic on the symptoms of anemia, twenty-four anemia patients were divided into two groups on the basis hemoglobin concentration: Group 1 (Hb > or = 90 g/L), and Group 2 (60 g/L < or = Hb < 90 g/L). QTc and QTd of these patients were also manually measured.

RESULTSAll QT intervals of APL patients treated with As(2)O(3) injection were prolonged [32.2 ms (27, 41 ms); P < 0.05], but the changes of QTd were not prominent [3 ms (-8, 7 ms), P > 0.05]. There was a delay of 2 hours in maximum QTc following peaks in serum arsenic concentration. Changes in QTc and QTd of the two anemic groups were not prominent.

CONCLUSIONSAs(2)O(3) can prolong QTc intervals in APL patients, but the effects are delayed compared to peak serum arsenic concentrations. As(2)O(3) has no prolongation effect on QTd. Mild and moderate anemia do not effect QTc and QTd.

Arsenicals ; pharmacology ; therapeutic use ; Electrocardiography ; drug effects ; Humans ; Leukemia, Promyelocytic, Acute ; drug therapy ; Oxides ; pharmacology ; therapeutic use

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*

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