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Journal ArticleDOI

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

01 May 1997-Blood (American Society of Hematology)-Vol. 89, Iss: 9, pp 3354-3360
TL;DR: As2O3 treatment is an effective and relatively safe drug in APL patients refractory to ATRA and conventional chemotherapy, and Pharmacokinetic studies showed that after a peak level of 5.54 micromol/L, plasma arsenic was rapidly eliminated, and the continuous administration of As2O2 did not alter its pharmacokinetic behaviors.
About: This article is published in Blood.The article was published on 1997-05-01 and is currently open access. It has received 1398 citations till now. The article focuses on the topics: Arsenic trioxide & Acute promyelocytic leukemia.
Citations
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Journal ArticleDOI
TL;DR: ROS stress in cancer cells is reviewed, its underlying mechanisms and relationship with mitochondrial malfunction and alteration in drug sensitivity are reviewed, and new therapeutic strategies that take advantage of increased ROS in cancer Cells to enhance therapeutic activity and selectivity are suggested.

1,823 citations

Journal ArticleDOI
TL;DR: The role of these four ABC transporter proteins in protecting tissues from a variety of toxicants is discussed and species variations in substrate specificity and tissue distribution of these transporters are addressed since these properties have implications for in vivo models of toxicity used for drug discovery and development.

1,327 citations

Journal ArticleDOI
TL;DR: Low doses of arsenic trioxide can induce complete remissions in patients with APL who have relapsed and the clinical response is associated with incomplete cytodifferentiation and the induction of apoptosis with caspase activation in leukemic cells.
Abstract: 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...

1,210 citations

Journal ArticleDOI
TL;DR: ATRA plus arsenic trioxide is at least not inferior and may be superior to ATRA plus chemotherapy in the treatment of patients with low-to-intermediate-risk APL.
Abstract: 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

1,184 citations

Journal ArticleDOI
01 Mar 2008-Blood
TL;DR: The history of introduction of ATRA and ATO into clinical use and the mechanistic studies in understanding this model of cancer targeted therapy are reviewed.

1,121 citations

References
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Journal ArticleDOI
01 Aug 1996-Blood
TL;DR: In this paper, As2O3 was shown to trigger NB4 cell apoptosis at micromolar concentration, as proved by morphology, histogramic related nuclear DNA contents, and DNA gel eletrophoresis.

811 citations

Journal ArticleDOI
TL;DR: Cell transformation and cytogenetic effects, including endoreduplication, chromosome aberrations, and sister chromatid exchanges were induced by the arsenicals with similar dose-responses, which support a possible role for chromosomal changes in arsenic-induced transformation.
Abstract: Sodium arsenite and sodium arsenate were observed to induce morphological transformation of Syrian hamster embryo cells in a dose-dependent manner. A linear dose-dependence with a slope of approximately 1 was observed with both compounds when the data were plotted on a log-log graph. The trivalent sodium arsenite was greater than 10-fold more potent than the pentavalent sodium arsenate. The compounds also exhibited toxicity; however, transformation was observed at non-toxic as well as toxic doses. At low doses, enhanced colony-forming efficiency of the cells was observed. To understand the mechanism of arsenic-induced transformation, the genetic effects of the two arsenicals were examined over the same doses that induced transformation. No arsenic-induced gene mutations were detected at two genetic loci. However, cell transformation and cytogenetic effects, including endoreduplication, chromosome aberrations, and sister chromatid exchanges were induced by the arsenicals with similar dose-responses. These results support a possible role for chromosomal changes in arsenic-induced transformation.

183 citations

Journal ArticleDOI
W Huang1, GL Sun1, XS Li1, Q Cao1, Y Lu1, GS Jang1, FQ Zhang1, Jr Chai1, ZY Wang1, S Waxman1 
15 Aug 1993-Blood
TL;DR: Results show that a positive RT/PCR of PML-RAR alpha is a sensitive predictor of relapse in APL.

180 citations

Journal Article
TL;DR: There seems no question that long-term arsenic ingestion can cause palmar and plantar keratoses and skin cancer, particularly basal cell carcinoma of the superficial multicentric type, usually on the torso.
Abstract: Palmar and plantar keratoses developed in seven patients many years after ingeston of trivalent inorganic arsenic. Six had basal cell carcinoma (superficial multicentric type in five), carcinoma "in situ" or squamous cell carcinoma of the skin. Two had systemic carcinoma--one, bilateral breast adenocarcinoma and one, carcinoma of the colon. From these observations and from the findings of a review of the literature, there seems no question that long-term arsenic ingestion can cause palmar and plantar keratoses and skin cancer, particularly basal cell carcinoma of the superficial multicentric type, usually on the torso. It is suspected but not proved to cause other cancers. Although over the last 50 years general exposure to arsenic has greatly decreased, particularly that from insecticides, this element is still found occasionally in drinking water (naturally or as a smelter byproduct), in certain foods and in cigarette smoke.

132 citations

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