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Search Results: 1 - 10 of 920 matches for " APL. ARSENIC TRIOXIDE "
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Vikram Mathews,Ezhilarasi Chendamarai,Biju George,Auro Viswabandya
Mediterranean Journal of Hematology and Infectious Diseases , 2011, DOI: 10.4084/mjhid.2011.
Abstract: It is well recognized that arsenic trioxide (ATO) is an efficacious agent for the treatment of acute promyelocytic leukemia (APL). Use of single agent ATO in the treatment of APL leads to remissions which are durable in the majority. ATO is probably the most effective single agent in the treatment of APL and there have been very few reports of primary resistance. It has been used both as a single agent and in combination with other conventional drugs to treat APL. Use of ATO is the accepted standard of care in the management of relapsed APL, where it is often used effectively as a bridge to a stem cell transplant. However, its role in newly diagnosed APL remains controversial. ATO probably has multiple mechanisms of action. Better understanding of its mechanisms of action/s is likely to lead to more rationale use of this agent or its derivatives either alone or in combination with other drugs. There is limited data on the kinetics of leukemia clearance and normal haematopoietic recovery after the administration of single agent ATO for the treatment of APL, preliminary data suggests that it is likely to be different from conventional therapy. There have been a number of concerns of the potential short and long term toxicity of this agent. Most such concerns arise from the toxicity profile noted in people exposed to long term arsenic exposure in the environment. With the therapeutic doses and schedules of administration of ATO in the treatment of malignancies the overall toxicity profile has been favorable. In a resource constrained environments the use of a single agent ATO based regimen is a realistic and acceptable option to treat almost all patients. In the developed world it has the potential in combination with other agents to improve the clinical outcome with reduction of dose intensity of chemotherapy and remains an option for patients who would not tolerate conventional therapy. In this review we focus on the use of single agent ATO for the treatment of APL and summarize our experience and review the literature.
The Role of Arsenic Treatment after Induction in Alternative and Long-Term Cases for the Prevention of Acute Promyelocytic Leukemia Recurrence
Mozaffar Aznab,Kamran Alimoghadam,Ardeshir Ghavamzadeh,Ghobad Salimi
International Journal of Hematology-Oncology and Stem Cell Research , 2010,
Abstract: "nIntroduction: Arsenic has been used as an effective medicine in the treatment of severe promyelocytic leukemia in recurrence and resistance cases toward ATRA. In this study, it has been used as induction and maintenance therapy after remission. "nMethod & Material: We studied 31 patients diagnosed by APL. Arsenic was started at a dose of 0.15 mg/kg (daily) until patient’s bone marrow remission.(1) We started Arsenic as a consolidation therapy after 28 days rest and then we continued the treatment with Arsenic each 3-4 months during 2 years for 14 days. "nResults: 4 patients died (12.9%) during the first 15 days of treatment. 27 patients (87%) went into remission. 2 patients refused the continuation of treatment regardless the remission. 25 patients received a long term treatment. The disease of 3 out of 25 patients recurred during follow -up period. "n1 patient died during the treatment after recurrence and 3 others given ATRA & Arsenic went into remission. Now, It has been past 2 months since the end of their remission. "nThe recurrence appeared in the form of full involvement of thoraco-lumbar which was observed as an extensive tumor on MRI and was found to cover the mentioned area. "n1 patient faced CNS fungal infection during neutropenia period and then recovered after operation and proper treatment; however his vision was severely damaged. "nAs 4 patients faced leukocytosis over 1000/000ml, we were obliged to discontinue arsenic for 3-4 days and chemotherapy by Danurobicine was prescribed for 2 days. "nThe patient’s follow-up and the median survival time were 54 and 48 months, respectively. The overall survival was 80.6%. "nDiscussion: Arsenic as the first line therapy for APL is an effective treatment .Consistent long- term therapy with intervals will reduce the risk of disease recurrence. "n "nKey word: APL, Arsenic Trioxide,
Pharmacokinetic of Arsenic Trioxide in Newly Diagnosed Acute Promyelocytic Leukemia Patients
R. Hosseini,A. Mandegary,K. Alimoghaddam,A. Ghavamzadeh
Journal of Applied Sciences , 2008,
Abstract: The high complete remission rate with arsenic trioxide (ATO) in relapsed Acute Promyelocytic Leukemia (APL) patients has been led to its use in newly diagnosed patients. Twenty newly diagnosed APL patients between January 2006 and 2007 received 2 h intravenous infusion of 10 mg day-1 arsenic trioxide for induction therapy until achieving complete remission. Plasma arsenic concentration was analyzed by graphite furnace atomic absorption method by dilution of plasma with a suitable matrix modifier. The concentration of arsenic in 24 h urine of patients was measured by using a valid standard addition method and a suitable matrix modifier. The Limits of Detection (LOD) were 1.2 and 1.5 μg L-1 for arsenic in plasma and urine, respectively. Pharmacokinetic parameters of 20 patients were as following: Cmax: 43.6 ±19.5 μg L-1, tmax: 2.15±0.7 h, AUC0-24: 683±317 μg h L-1, AUC0-∞: 2027±958 μg h L-1, t1/2: 41±10 h, kel: 0.02±0.01 h-1, Vd: 5.6±3.6 L kg-1 and Cltotal: 0.1±0.05 L kg-1 h-1. During the first day of induction, 1.4±0.2% of administrated arsenic excreted into urine. Renal clearance was 5.1±4.1 mL kg-1 h-1. However, the results showed that the pharmacokinetic of ATO in newly diagnosed APL patients weren`t dependent to the sex of patients.
Activation of ERK and P38 by the Addition of Arsenic Trioxide in Flt3-ITD Cells  [PDF]
Sawami Suzuki, Hiroko Inaba, Takashi Satoh, Toshio Okazaki, Shinichiro Takahashi
Open Journal of Blood Diseases (OJBD) , 2011, DOI: 10.4236/ojbd.2011.12003
Abstract: Flt3-internal tandem duplications (Flt3-ITD) is a prevalent mutation in acute myeloid leukemia (AML). We recently reported arsenic trioxide (ATO) and Flt3 inhibition synergize to induce apoptosis in Flt3-ITD cells. However, the signaling effect of ATO in these cells has not been elucidated. Here, we demonstrate that the treatment of ATO potently induces the activation of extracellular regulated kinase (ERK)- mitogen activated protein kinase (MAPK), and modestly activates p38-MAPK in BaF3-Flt3-ITD cells, among other major (PI3-kinase-Akt, c-jun N-terminal kinase [JNK]) signaling pathways examined. In contrast, in BaF3-Flt3-wild type (WT) cells, slight activation of p38, but none for others, was observed. As MAPK kinase (MEK), as well as p38 inhibition is reported to enhance ATO-induced apoptosis in AML and various hematological malignancies, our results suggest that Flt3 mutation status is important for the effect of these combinations.
Lenalidomide and Arsenic Trioxide Have Independent Non-Interfering Effects When Used in Combination on Myeloma Cell Lines in Vitro  [PDF]
Huaquan Wang, Xianghong Chen, Erika A. Eksioglu, Junmin Zhou, Nicole R. Fortenbery, Julie Djeu, Alan List, Sheng Wei
Journal of Cancer Therapy (JCT) , 2013, DOI: 10.4236/jct.2013.43095

Multiple myeloma (MM) is a plasma cell neoplasm characterized for its fast evolution and for being practically incurable, presenting a strong need for the development of therapies to target it. Among those under study are lenalidomide and arsenic trioxide (ATO) which show individual clinical promise, although never tested together. However, the combination of ATO with thalidomide, another immunomodulatory drug and lenalidomide’s structural albeit less potent analog, have been tried clinically with some success. Therefore, we investigated the effect the combination of lenalidomide and ATO have on the MM-derived U266 and RPMI 8226 cell lines. We observed that both compounds have separate, non-interfering, anti-myeloma mechanisms with ATO demonstrating strong cytotoxic effects while lenalidomide’s role remains cytostatic and immunomodulatory. However, ATO decreases cdc25c, which helps sensitize cells to lenalidomide effects enhancing the efficacy of their interaction. Mechanistically the combination of these two agents decreased the expression of MDM2, without affecting p53 activation or its expression. Therefore, this short study provides the foundation to continue mechanistic studies of the combination of lenalidomide and ATO as a foundation for future clinical application.

The Effect of Decitabine Combined with Arsenic Trioxide on DAPK Gene and HL-60 Cell Proliferation and Apoptosis  [PDF]
Jinhai Ren, Jingjing Yao, Xiaonan Guo, Xiaoling Guo, Shengxin Cai
Journal of Cancer Therapy (JCT) , 2015, DOI: 10.4236/jct.2015.615134
Abstract: Purpose: Our study was to detect the effect of Decitabine (DAC) combined with arsenic trioxide (AS2O3) on DAPK gene and HL-60 cell proliferation and apoptosis. Methods: DAC and AS2O3 monotherapy, combination treatment and DAC pretreatment were used in this study after incubating with HL-60 cell for 24 h, 48 h, 72 h. CCK8 was used to detect the cell proliferation of HL-60 cell. Flow cytometry was used to detect the cell apoptosis. Then, we used RT-PCR to obtain the gene expression level of DAPK. Results: HL-60 cells were treated with different concentrations of DAC (20 μmol/L, 40 μmol/L, 80 μmol/L), AS2O3 (1 μmol/L, 2.5 μmol/L, 5 μmol/L) monotherapy for 24 h, 48 h, 72 h; along with the extension of the drug concentration and time, proliferation inhibition rate had gradually increased. Monotherapy of DAC, AS2O3 could inhibit the proliferation and induce apoptosis of HL-60 cells, and was time- and dose-dependent. DAC (80 μmol/L) was firstly used for pretreatment, and then, different concentrations of AS2O3 (1 μmol/L, 2.5 μmol/L, 5 μmol/L) were used for 24 h, 48 h, 72 h. It was found that cell proliferation inhibition rate and apoptosis rate had increased significantly. When the two drugs were used together, the increasing proliferation inhibition rate, apoptosis rate and DAPK had become more obvious. Conclusion: DAC and AS2
Efecto en la Estructura Histológica del Timo de Ratas Sprague-Dawley Tratadas con Trióxido de Arsénico
Alfaro-Burgos,S; Valenzuela-Estrada,M;
International Journal of Morphology , 2012, DOI: 10.4067/S0717-95022012000200068
Abstract: in coastal areas of northern chile medium or high levels of arsenic are commonly found in drinking water. arsenic exposure may be associated with acute or chronic effects. the objective of this investigation was to determine the histological damage caused by arsenic trioxide level of the compartments of the thymus of sprague-dawley rats. we used 24 rats of both sexes of 55 days of life. the rats were weighed and divided into 3 groups (4 females and 4 males). in the treated groups were administered 5 mg and 10 mg of as2o3 respectively, in a single daily dose for 15 days intraperitoneally. the control group was administered distilled water without arsenic. after treatment the animals were sacrificed and the thymus removed, washed, weighed and divided into two, then fixed in 10% buffered formalin. by conventional histology samples were obtained serially every 4 thymus, 5 microns thick and separated by 100 microns each, then were stained with he. we analyzed 30 fields (120 fields per organ). the results showed that as2o3 causes loss of cellularity in both compartments of the thymus, both in the cortex and in the bone, medullary compartment was more affected (near the corticomedullary junction). there was a significant reduction in the size of the medulla in both groups (5 and 10 mg as2o3 respectively), probably the decrease of the tissue responsible for thymic atrophy. we observed an increase in the size of the cortex in female rats treated with 10 mg of as2o3. the corticomedullary junction of the treated rats showed diffuse or difficult to distinguish.
Evaluation of response to arsenic trioxide in patients with refractory multiple myeloma
Zohreh Sanaat,Mahtab Rezazadeh,Jalil Vaez Gharamaleki,Jamal Eivazi Ziae
Tehran University Medical Journal , 2010,
Abstract: "n Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Background: Multiple myeloma is a plasma cell dyscrasia characterized by proliferation of plasma cells in bone marrow associated with the production of monoclonal immunoglobulins. In recent years, the use of arsenic trioxide, formerly approved for treatment of acute promyelocytic leukemia has been considered for refractory myeloma treatment. This study was designed and carried out to evaluate the efficacy and possible side effects of ATO on patients with refractory multiple myeloma."n"nMethods: This study carried out on myeloma patients whose diseases were at least refractory to two standard treatment regimens conducted in Ghazi Tabatabaei Hospital in Tabriz- Iran. Arsenic trioxide was administered as an intravenous infusion at a dose of 0.25 mg/kg/d for 5 d/week during the first two consecutive weeks of each 4-week cycle with two week rest. Patients who completed one 4-weak cycle were evaluated for response to treatment."n"nResults: Twelve patients with refractory disease to conventional treatment regimens received arsenic trioxide. The response to the treatment assessed based on the amount of serum proteins electrophoresis of the 10 patients. Stable disease observed in four patients (33%), progressive disease in five patients (41.6%), complete response in one (3.8%) and the remaning two patients could not be assessed for response (because of increased liver enzymes after the first week). One patient completed six cycles. Some adverse events such as: increase liver enzymes and serum creatinine, neutropenia, pruritus, nausea, vomiting, lower extremities edema, and noninfectious diarrhea were observed."n"nConclusions: The use of arsenic trioxide is promising in treatment of refractory multiple myeloma.
Arsenic Trioxide Compound Modulates Multiple Myeloma Phenotypes: Assessment on Cell Line Models
MR Khorramizadeh,F Saadat,H Allahyary,S Sadeghian
Iranian Journal of Public Health , 2006,
Abstract: Recent evidences suggest that multiple myeloma phenotypes (MMPs) are involved in the infiltration of multiple myeloma-affected marrow foci. In this study, the effects of arsenic trioxide on the invasive and angiogenic phenotypes of multiple myeloma (MM) cell line were assessed on a dose-response and time-course basis. Multiple myeloma cell line, Karpas 707, was treated with step-wise elevated concentrations of arsenic trioxide compound at 24, 48, and 72 h intervals. Cytotoxicity was assessed with a colorimetric assay. Potential antiinvasive phenotype was analyzed with MMP-2 zymography. To verify directly the anti angiogenic effect, F1 endothelial cell line was also treated with arsenic and the dose-dependent cytotoxicity was assessed with a colorimetric assay. Apoptotic properties of arsenic trioxide compound were investigated using TUNEL assay. The significant dose-dependent inhibitory effects of arsenic trioxide on MMP-2 were seen at given concentrations. Cytotoxicity analysis revealed much higher cell death than untreated cells (P< 0.01), both in Karpas 707 and F1 endothelial cell lines. Colectively, this study showed that arsenic trioxide might potentially elicit anti-invasive anti-angiogenesis properties in the treatment of myeloma dissemination process. In addition, the concurrent inhibition of MMPs activity and endothelial cell proliferation could compose the scenario of neoangiogenesis inhibition in the marrow-infiltrated foci.
Phytopathological and nutraceutical evaluation of cauliflower plants treated with high dilutions of arsenic trioxide
Grazia Trebbi,Giovanni Dinelli,Ilaria Marotti,Valeria Bregola
International Journal of High Dilution Research , 2012,
Abstract: Introduction: This research aimed at verifying the effects of highly diluted (HD) treatments on cauliflower (Brassica oleracea L.) plants both healthy and inoculated by the fungus Alternaria brassicicola, causing the dark leaf spot disease. In vitro spore germination assays (A), growth chamber experiments (B) and field trials (C) were performed. Material and Methods: (A): spore suspensions were prepared in HD treatments and their inhibiting effect on germination was recorded microscopically after incubation at 25 °C for 5 h. (B): the same treatments were tested in plants artificially inoculated with the fungus. The infection level on leaves was blindly evaluated by a previously defined infection scale. (C): the field was divided into plots according to a complete randomized block design. In the first trial (i), plants were artificially inoculated and weekly treated; the infection level was evaluated on cauliflower heads. The second trial (ii) was performed on the same field with the aim to induce a natural infection, mediated by infected crop residues. Measurement endpoints concerned the evaluation of some physiological parameters along with the glucosinolate content on cauliflower heads. Results: (A): arsenic trioxide (As 35x and 35x diluted 1:5000) and Cuprum 5x induced highly significant inhibition of germination rate (-60%) vs. control. (B): As 35x and Cu 3 g/l induced a significant decrease of mean infection level (-50%). (C): in (i), a significant reduction of disease symptoms on heads was recorded for As 35x and Cu 3 g/l (-45%). In (ii) natural fungal infection did not occur due to dry weather conditions; physiological and nutraceutical analyses of healthy heads demonstrated that As 35x induced a significant increase of both head size and glucosinolate content. Discussion: Some evidences on the efficacy of arsenic, at different decimal and centesimal HD, in fungal and viral disease control were previously reported [1]. In the present study the efficacy of HD arsenic in dark leaf spot control in field has been shown for the first time: since fungal inoculation was performed on the leaves before flowering, we can hypothesize that this treatment induced an increase of plant resistance to fungal infection. Conclusions: This research showed the possibility of using HD arsenic in agriculture ( ¢a “agrohomeopathy ¢a ), as it increased both plant resistance to fungal infection and the content of glucosinolates, ie secondary metabolites involved in plant resistance mechanisms [2] and considered as ¢a “plant food protection agents ¢a [3]. Ackn
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