ROS stress in cancer cells and therapeutic implications.

Use of Arsenic Trioxide (As2O3 ) in the Treatment of Acute Promyelocytic Leukemia (APL): II. Clinical Efficacy and Pharmacokinetics in Relapsed Patients

Multidrug resistance proteins: role of P-glycoprotein, MRP1, MRP2, and BCRP (ABCG2) in tissue defense

Background Two reports from China have suggested that arsenic trioxide can induce complete remissions in patients with acute promyelocytic leukemia (APL). We evaluated this drug in patients with APL in an attempt to elucidate its mechanism of action. Methods Twelve patients with APL who had relapsed after extensive prior therapy were treated with arsenic trioxide at doses ranging from 0.06 to 0.2 mg per kilogram of body weight per day until visible leukemic cells were eliminated from the bone marrow. Bone marrow mononuclear cells were serially monitored by flow cytometry for immunophenotype, fluorescence in situ hybridization, reverse-transcription–polymerase-chain-reaction (RT-PCR) assay for PML–RAR-α fusion transcripts, and Western blot analysis for expression of the apoptosis-associated proteins caspases 1, 2, and 3. Results Of the 12 patients studied, 11 had a complete remission after treatment that lasted from 12 to 39 days (range of cumulative doses, 160 to 515 mg). Adverse effects were relatively m...

https://www.nejm.org/doi/pdf/10.1056/NEJM199811053391901

Complete remission after treatment of acute promyelocytic leukemia with arsenic trioxide

Background All-trans retinoic acid (ATRA) with chemotherapy is the standard of care for acute promyelocytic leukemia (APL), resulting in cure rates exceeding 80%. Pilot studies of treatment with arsenic trioxide with or without ATRA have shown high efficacy and reduced hematologic toxicity. Methods

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Retinoic acid and arsenic trioxide for acute promyelocytic leukemia

In vitro studies on cellular and molecular mechanisms of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia: As2O3 induces NB4 cell apoptosis with downregulation of Bcl-2 expression and modulation of PML-RAR alpha/PML proteins

Introduction: Although retrospective analysis were frequently undertaken, and many prognostic systems for myelodysplastic syndromes (MDS) have been proposed worldwide, few such studies have been performed and the eAectiveness of diAerent scoring systems have not yet been verified in independent patient populations in China. The aim of this single center study was to evaluate the prognostic factors and compare the prognostic scoring systems in Chinese patients with MDS. Materials and methods: One hundred and twenty-eight patients diagnosed as primary MDS in our Institution were studied retrospectively to identify significant prognostic factors and to assess the predictive value of 11 previously described prognostic systems, including French‐ American‐British (FAB) classification, World Health Organization (WHO) classification, Mufti, Sanz, Morra, Aul, Oguma, Toyama, Morel and international prognostic scoring system (IPSS). Results: The median age of the patients was 50 years (range 13‐82). The 2- and 5-year survival rate of the patients were 55.22+4.90% and 26.09+6.36% respectively, with a median survival of 31 months (range 1‐127 months). Fifty patients (39.1%) had progressed to acute leukemia (AL) with a median time of 8 months (range 1‐43 months). Major independent variables indicated by multivariate analysis were the percentage of bone marrow (BM) blast cells and complex karyotype aberrations for survival (P=0.042 and 0.042, respectively) and only the percentage of BM blast cells for AL transformation (P=0.023). All the systems except Mufti scores successfully discriminated risk groups concerning both survival and AL evolution, especially in the high risk group, ranging from 10 to 20 months and from 4 to 7 months, respectively. The FAB and WHO classification, as well as Sanz, Oguma, Morel and IPSS possessed lower P value (P50.0001) than that of the rest scoring systems. Conclusion: The patients in our study were younger than these of the Western population, whereas the survival and AL transformation ratio were comparable to these previous studies. The BM blast proportion and complex chromosomal defects were highly significant for predicting outcome in MDS patients. Most investigated systems eAectively stratified patients into groups with diAerent life expectancies and identified a subset of patients with poor clinical outcome. The FAB, WHO classification, as well as Sanz, Oguma, Morel and IPSS scoring systems were more applicable for predicting survival and leukemia progression. The Hematology Journal (2002) 3, 137‐144. doi:10.1038/sj.thj.6200173

Wei Tang

Papers

Use of Arsenic Trioxide (As2O3 ) in the Treatment of Acute Promyelocytic Leukemia (APL): II. Clinical Efficacy and Pharmacokinetics in Relapsed Patients

In vitro studies on cellular and molecular mechanisms of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia: As2O3 induces NB4 cell apoptosis with downregulation of Bcl-2 expression and modulation of PML-RAR alpha/PML proteins

The myelodysplastic syndromes: analysis of prognostic factors and comparison of prognostic systems in 128 Chinese patients from a single institution.