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1.
Journal of Experimental Hematology ; (6): 1504-1509, 2021.
Article in Chinese | WPRIM | ID: wpr-922286

ABSTRACT

OBJECTIVE@#To investigate the effect of arsenic disulfide (AS@*METHODS@#The human DLBCL cell OCI-LY3 was treated with different concentrations of AS@*RESULTS@#The DLBCL cell viability was decreased significantly at 24, 48 or 72 h as cultured with itraconazole. Along with the increasing of itraconazole concentration, the DLBCL cell viability was significantly reduced as compared with that in control group, and the results showed statistically significant(r=-0.690,r=-0.639, r=-0.833, r=-0.808, r=-0.578). The inhibitory and apoptosis rates of the cells were significantly increased as compared with those of the single drug-treated group after treated by the combination of itraconazole and AS@*CONCLUSION@#Itraconazole can inhibit proliferation of DLBCL cells in a concentration-and time-dependent manner. In addition, the combination of AS


Subject(s)
Apoptosis , Arsenicals , Hedgehog Proteins , Humans , Itraconazole/pharmacology , Lymphoma, Large B-Cell, Diffuse/drug therapy , Sulfides
2.
Article in English | WPRIM | ID: wpr-827469

ABSTRACT

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.


Subject(s)
Aged , Aged, 80 and over , Antineoplastic Agents , Therapeutic Uses , Arsenicals , Therapeutic Uses , Drugs, Chinese Herbal , Therapeutic Uses , Female , Humans , Leukemia, Myeloid, Acute , Drug Therapy , Mortality , Male , Middle Aged , Powders , Retrospective Studies
3.
Article in Chinese | WPRIM | ID: wpr-777483

ABSTRACT

Realgar is a mineral traditional medicine with definite efficacy. The function of realgar is detoxicating, insecticiding, eliminating dampness and phlegm, etc. It is widely applied in clinical practice by compatibility medicines. However, the safety and scientificalness of clinical application are questioned because of the toxic effect caused by arsenic compounds. At present, there are still many problems in the research of realgar, which are mainly manifested in three areas: the expression of main components and effective substances are inconsistent; the anti-tumor mechanism is difficult to explain at the molecular level; the mechanism of compatibility is not clear. As a result, realgar and realgar-containing Chinese patent medicines are frequently prohibited from entering the international market, and the reputation of traditional Chinese medicine is also damaged. This paper would analyze the research status of realgar at home and abroad as well as its problems from its main components, effective substances, anti-tumor mechanism and compatibility mechanism. In view of these difficulties, quantum chemical calculation method is proposed to solve them, so as to make up for the shortcomings and limitations of experimental technology and experimental conditions, reduce the cost of realgar research and improve research efficiency. Moreover, it provides inspiration for research of other mineral medicine.


Subject(s)
Arsenicals , Pharmacology , Medicine, Chinese Traditional , Minerals , Sulfides , Pharmacology
4.
Article in English | WPRIM | ID: wpr-771429

ABSTRACT

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.


Subject(s)
Arsenicals , Pharmacology , Therapeutic Uses , Cell Lineage , DNA Methylation , Demethylation , Drugs, Chinese Herbal , Pharmacology , Therapeutic Uses , Female , Gene Ontology , Humans , Leukocyte Disorders , Drug Therapy , Genetics , Male , Middle Aged , Powders , Treatment Outcome
5.
Article in Chinese | WPRIM | ID: wpr-813038

ABSTRACT

To explore the antiviral activity of nano-realgar against herpes simplex virus Type II (HSV-2) in vitro.
 Methods: Acyclovir (ACV) as a positive control, the cytotoxicity of nano-realgar at different concentrations (including 200.00, 150.00, 100.00, 50.00, 25.00, 12.50, 6.25, 3.13, 1.54, 0.78, 0.39 and 0 mg/L) on normal Vero cells were determined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. HSV-2 virus titer was determined by plaque assay, and the Vero cells model of HSV-2 infection was established. Subsequently, the antiviral effects of nano-realgar at different concentrations (including 20.00, 10.00, 5.00, 2.50, 1.25, 0.63, 0.31, 0.15, 0.08, 0.04 and 0 mg/L) on infected cells model were evaluated by the observation of cytopathic effect (CPE) and MTT method under the 3 modes including pre-treatment, treatment and direct inactivation.
 Results: The 50% cytotoxic concentration (CC50) of nano-realgar on Vero cells was 37.15 mg/L. The titer of HSV-2 was 7.30 log PFUs/mL. In the 3 modes, the half-maximal effective concentration (EC50) of nano-realgar on HSV-2 infected Vero cells were 0.13, 1.80 and 0.52 mg/L, and the corresponding therapeutic index (TI) were 285.77, 20.64, 71.44, respectively. The TI value of nano-realgar on pre-treatment mode was higher than that of nano-realgar on treatment and direct inactivation modes.
 Conclusion: Nano-realgar can play a good anti-HSV-2 activity in the 3 modes (pre-treatment, treatment and direct inactivation), and the anti-HSV-2 efficacy of nano-realgar on pre-treatment mode is better than that of nano-realagr on other 2 modes.


Subject(s)
Animals , Antiviral Agents , Arsenicals , Chlorocebus aethiops , Herpesvirus 1, Human , Herpesvirus 2, Human , Sulfides , Vero Cells
6.
Biol. Res ; 51: 18, 2018. tab, graf
Article in English | LILACS | ID: biblio-950904

ABSTRACT

BACKGROUND: Arsenic trioxide (As2O3), a drug that has been used in China for approximately two thousand years, induces cell death in a variety of cancer cell types, including neuroblastoma (NB). The tyrosine kinase receptor (Trk) family comprises three members, namely TrkA, TrkB and TrkC. Various studies have confirmed that TrkA and TrkC expression is associated with a good prognosis in NB, while TrkB overexpression can lead to tumor cell growth and invasive metastasis. Previous studies have shown that As2O3 can inhibit the growth and proliferation of a human NB cell line and can also affect the N-Myc mRNA expression. It remains unclear whether As2O3 regulates Trks for the purposes of treating NB. METHODS: The aim of the present study was to investigate the effect of As2O3 on Trk expression in NB cell lines and its potential therapeutic efficacy. SK-N-SH cells were grown with increasing doses of As2O3 at different time points. We cultured SK-N-SH cells, which were treated with increasing doses of As2O3 at different time points. Trk expression in the NB samples was quantified by immunohistochemistry, and the cell cycle was analyzed by flow cytometry. TrkA, TrkB and TrkC mRNA expression was evaluated by real-time PCR analysis. RESULTS: Immunohistochemical and real-time PCR analyses indicated that TrkA and TrkC were over-expressed in NB, and specifically during stages 1, 2 and 4S of the disease progression. TrkB expression was increased in stage 3 and 4 NB. As2O3significantly arrested SK-N-SH cells in the G2/M phase. In addition, TrkA, TrkB and TrkC expression levels were significantly upregulated by higher concentrations of As2O3 treatment, notably in the 48-h treatment period. Our findings suggested that to achieve the maximum effect and appropriate regulation of Trk expression in NB stages 1, 2 and 4S, As2O3 treatment should be at relatively higher concentrations for longer delivery times;however, for NB stages 3 and 4, an appropriate concentration and infusion time for As2O3 must be carefully determined. CONCLUSION: The present findings suggested that As2O3 induced Trk expression in SK-N-SH cells to varying degrees and may be a promising adjuvant to current treatments for NB due to its apoptotic effects.


Subject(s)
Humans , Oxides/pharmacology , Arsenicals/pharmacology , Membrane Glycoproteins/drug effects , Gene Expression Regulation, Neoplastic/drug effects , Receptor, trkB/drug effects , Cell Proliferation/drug effects , Cell Cycle Checkpoints/drug effects , Neuroblastoma/metabolism , Membrane Glycoproteins/metabolism , Receptor, trkB/metabolism , Cell Line, Tumor/drug effects , Cell Line, Tumor/metabolism , Arsenic Trioxide , Neuroblastoma/pathology
7.
Article in Chinese | WPRIM | ID: wpr-689589

ABSTRACT

<p><b>OBJECTIVE</b>To analyze the correlation of ATO therapeutic dose with the relapse of patients with acute promyelocytic leukemia (APL) and to investigate the optimal dose and courses of ATO.</p><p><b>METHODS</b>The clinical data of 102 patients with APL from January 2008 to June 2015 were analyzed retrospectively. The clinical characteristics of APL patients in relapsed group and maintained remission group were compared. According to ATO dose in 2 years recommended in chinese guideline as criteria of grouping, the patients were divided into ATO high and low dose groups, then the relapse rate in groups was compared. The cut-off value of ATO dose was analyzed by ROC curve.</p><p><b>RESULTS</b>Univariate analysis showed that the relapse rate in high ATO and low ATO groups on 2 year treatment was 2.5% and 17.7% respectively (P<0.05); multiple variate analysis demonstrated that the ATO dose>22.4 mg/kg on 2 year treatment was independent preventive factor for the relapse of APL (OR=0.119, P<0.05). The ROC curve showed that the cut-off value of ATO dose on 2 year treatment was 8.765 mg/kg. The relapse rate of APL in group of ATO dose >8.765 mg/kg group was significantly lower than that in group of ATO dose <8.765 mg/kg.</p><p><b>CONCLUSION</b>The relapse of APL relates with used ATO dose, sufficient use of ATO dose can decrease the relapse rate of APL.</p>


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Arsenic Trioxide , Arsenicals , Humans , Leukemia, Promyelocytic, Acute , Oxides , Recurrence , Retrospective Studies , Tretinoin
8.
Article in Chinese | WPRIM | ID: wpr-689588

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the effects of arsenic trioxide (AsO) on Cdc20 and Mad2 in process of AML HL-60 cell proliferation.</p><p><b>METHODS</b>The proliferation of HL-60 cells was detected by CCK-8 method at different concentrations of arsenic trioxide for 24, 48 and 72 hours. The cell morphological changes were observed by inverted microscopy. The expressions of Mad2 and Cdc20 mRNA and protein in HL-60 cells treated with AsO for 48 h were detected by real-time PCR and Western blot respectively.</p><p><b>RESULTS</b>Arsenic trioxide significantly inhibited the HL-60 cell proliferation and displayed a good time-dose correlation. RT-PCR and Western blot showed that the expression of Mad2 was up-regulated and the expression of Cdc20 was down-regulated in HL-60 cells treated with arsenic trioxide of different concentration (4,8,10 µmol/L).</p><p><b>CONCLUSION</b>Arsenic trioxide can inhibit the human acute myeloid leukemia HL-60 cell proliferation, and its mechanism may be related with up-regulation of Mad2 expression and down-regulation of Cdc20 expression.</p>


Subject(s)
Antineoplastic Agents , Apoptosis , Arsenic Trioxide , Arsenicals , Cdc20 Proteins , HL-60 Cells , Humans , Leukemia, Myeloid, Acute , Oxides
9.
Article in Chinese | WPRIM | ID: wpr-689564

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the effect of ATO on the proportion of Treg in the peripheral blood of patients with severe aplastic anemia (SAA) in vitro.</p><p><b>METHODS</b>The peripheral blood of 20 newlydiagnosed patients were collected, and the peripheral blood monomuclear cells (PBMNC) were extracted. After the PBMNC were treated with ATO of different concentrotions (0, 1, 2.5 and 5 µmol/L) for 96 hours, the proportion of CD44 CD25CD127 regulatatory T cells (Treg) were detected by flow cytometry. The expression levels of Foxp3 mRNA were detected by RT-PCR, and the levels of IFN-γ,IL-4,IL-17 and TGF-β1 were detected by ELTSA to verify the results of flow cytomery.</p><p><b>RESULTS</b>ATO significantly increased the proportion of Treg (P<0.01) at the concentration of 2.5 and 5 µmol/L, and the rising degree of Treg proportion improved with the increasing ATO concentration(r= 0.524). Treg proportion increased at a concentration of 1 µmol/L, but without statistical significance (P>0.05). At 1(P<0.05), 2.5(P<0.01) and 5 µmol/L(P<0.01), ATO significantly up-regulated the expression of Foxp3 mRNA, and the increase of Foxp3 mRNA positively and linearly correlated with the increase of Treg cell-frequency(r=0.523). ATO significantly reduced the levels of IFN-γ (at ATO 1,2.5 and 5 µmol/L, P<0.01), IL-4 (at ATO 2.5 µmol/L, P<0.01; at ATO 5 µmol/L, P<0.01) and IL-17(at ATO 2.5 µmol/L, P<0.05; at ATO 5 µmol/L, P<0.01). ATO had no significant effect on TGF-β1 at 1(P>0.05) and 2.5 µmol/L (P>0.05), but significantly reduced TGF-β1 level at 5 µmol/L (P<0.05).</p><p><b>CONCLUSION</b>ATO can mediate the immune regulation through up-regulating the proportion of Treg in peripheral blood of patients with SAA and reducing the levels of IFN-γ, IL-4 and IL-17.</p>


Subject(s)
Anemia, Aplastic , Arsenic Trioxide , Arsenicals , Forkhead Transcription Factors , Humans , Oxides , RNA, Messenger , T-Lymphocytes, Regulatory
10.
Biol. Res ; 50: 17, 2017. tab, graf
Article in English | LILACS | ID: biblio-838975

ABSTRACT

Realgar is a naturally occurring arsenic sulfide (or Xionghuang, in Chinese). It contains over 90% tetra-arsenic tetrasulfide (As4S4). Currently, realgar has been confirmed the antitumor activities, both in vitro and in vivo, of realgar extracted using Acidithiobacillus ferrooxidans (A. ferrooxidans). Bioleaching, a new technology to greatly improve the use rate of arsenic extraction from realgar using bacteria, is a novel methodology that addressed a limitation of the traditional method for realgar preparation. The present systematic review reports on the research progress in realgar bioleaching and its antitumor mechanism as an anticancer agent. A total of 93 research articles that report on the biological activity of extracts from realgar using bacteria and its preparation were presented in this review. The realgar bioleaching solution (RBS) works by inducing apoptosis when it is used to treat tumor cells in vitro and in vivo. When it is used to treat animal model organisms in vivo, such as mice and Caenorhabditis elegans, tumor tissues grew more slowly, with mass necrosis. Meanwhile, the agent also showed obvious inhibition of tumor cell growth. Bioleaching technology greatly improves the utilization of realgar and is a novel methodology to improve the traditional method.


Subject(s)
Humans , Arsenicals/pharmacology , Sulfides/pharmacology , Acidithiobacillus thiooxidans/metabolism , Antineoplastic Agents/pharmacology , Arsenicals/metabolism , Arsenicals/chemistry , Sulfides/metabolism , Sulfides/chemistry , Apoptosis/drug effects , K562 Cells , Cell Line, Tumor , Cell Proliferation/drug effects , Drug Synergism , Toxicological Phenomena , Antineoplastic Agents/chemistry
11.
IBJ-Iranian Biomedical Journal. 2017; 21 (5): 330-337
in English | IMEMR | ID: emr-188490

ABSTRACT

Background: Arsenic trioxide [ATO] has been reported as an effective anti-cancer and a US Food and Drug Administration [FDA] approved drug for treatment of some cancers. The aim of this study was to determine the underlying apoptosis molecular and cellular mechanisms of ATO in the presence or absence of ionizing radiation [IR] in vitro in the glioblastoma multiforme [GBM] cell line, U87MG


Methods: Cells were treated by different concentrations of ATO either in presence or absence of IR. Viability and apoptosis pathway of both treated and control groups were evaluated using MTT assay and the expression analysis of Box, Bcl-2, and caspase-3 genes, respectively. All treatments were performed on 100-ujm diameter spheroids


Results: Results showed a significant reduction in the survival of the cells in all treated groups. As expected, cell survival was much less in combination treatment than treatment with only ATO. Moreover, combination therapy made Box and caspase-3 up-regulated and Bcl-2 down-regulated


Conclusion: ATO and radiation had a synergistic apoptotic effect on GBM cells by up-regulation of caspase-3 and alteration of the Bax-Bcl-2 balance; therefore, ATO may act as a potential anti-cancer agent against GBM cells through triggering the mitochondria! pathway of apoptosis


Subject(s)
Journal Article , Apoptosis/radiation effects , Arsenicals/therapeutic use , Oxides/therapeutic use , Radiation, Ionizing , In Vitro Techniques , Glioblastoma , Cell Line, Tumor
12.
Salud pública Méx ; 58(2): 220-227, Mar.-Apr. 2016. tab
Article in English | LILACS | ID: lil-793000

ABSTRACT

Abstract Objective: To evaluate whether the presence of polymorphisms of peroxisome proliferator-activated receptor gamma PPARγ (Pro 1 2Ala) and PPARGC1B (Ala203Pro) modifies the association between the inorganic arsenic (iAs) methylation capacity and breast cancer (BC). Materials and methods: Mexican women were interviewed, and blood and urine samples were collected from them (cases/controls= 197/220). The concentration of urinary arsenic species and the polymorphisms of interest were determined by high-performance liquid chromatography with inductively coupled plasma mass spectrometry (HPLC-ICP-MS) and polymerase chain reaction (PCR), respectively. Results: In women with a high %MMA (urinary monomethyl arsenic) and high primary methylation ratio (PM = MMA/iAs), the risk of BC was increased (odds ratio [OR]%MMA T3 vs.T1= 3.60: 95% confidence interval [CI] 2.02-6.41, ORPMI T3 vs.T1= 3.47: 95%CI 1.95-6.17), which was maintained after adjusting for polymorphisms. No significant interactions were observed between the polymorphisms and the arsenic variables on the risk of BC. Conclusion: Pro 12Ala and Ala203Pro polymorphisms did not modify the association between the iAs methylation capacity and BC.


Resumen Objetivo: Evaluar si la presencia de polimorfismos de PPARγ (Pro 1 2Ala) y PPARGC1B (Ala203Pro) modifica la asociación entre la capacidad de metilación del arsénico inorgánico (Asi) y el cáncer de mama (CM). Material y métodos: Se entrevistaron mujeres mexicanas y recolectaron muestras de sangre y orina de (casos/controles=197/220). La concentración de especies de arsénico urinario y los polimorfismos de interés se determinaron mediante cromatografía líquida de alta resolución acoplada a espectrometría de masas (HPLC-ICP-MS) y reacción en cadena de la polimerasa (PCR), respectivamente. Resultados: En mujeres con %MMA (monometilarsénico urinario) y razón de primera metilación altas (PM=MMA/Asi) se incrementó el riesgo de CM (RM%MMAT3vsT1=3.60: intervalo de confianza [IC]95%2.02-6.41, RMPMT3vs.T1=3.47:IC95%1.95-6.17), que se mantuvo, respectivamente, al ajustar por polimorfismos. No se observaron interacciones significativas entre los polimorfismos y las variables arsenicales sobre el riesgo de CM. Conclusión: Los polimorfismos Pro 12Ala y Ala203Pro no modificaron la asociación entre la capacidad de metilación del Asi y el CM.


Subject(s)
Humans , Female , Adult , Middle Aged , Aged , Young Adult , Arsenicals/metabolism , Breast Neoplasms/epidemiology , Carrier Proteins/genetics , Polymorphism, Single Nucleotide , PPAR gamma/genetics , Arsenic/toxicity , Arsenicals/urine , Mass Spectrometry , Breast Neoplasms/genetics , Case-Control Studies , Polymerase Chain Reaction , Risk , Chromatography, High Pressure Liquid , RNA-Binding Proteins , Genetic Predisposition to Disease , Environmental Exposure , Methylation
13.
Article in Chinese | WPRIM | ID: wpr-360084

ABSTRACT

<p><b>OBJECTIVE</b>To study the antiapoptotic effect of leukemia-associated gene MLAA-34 in HeLa cells.</p><p><b>METHODS</b>The MLAA-34 recombinant lentiviral expression vector was constructed, and the stably transfected HeLa cell line with high expression of MLAA-34 was set up; As(2)O(3) was used to induce apoptosis; the MTT assay, colony formation test and flow cytometry were used to detect the ability of cell proliferation, colong formation, apoptosis and cell cycle changes respectively.</p><p><b>RESULTS</b>After treatment with As(2)O(3), the survival rate of HeLa cells with MLAA-34 overexpression was significantly higher than that of the control cells, and the colony formation ability of MLAA-34 significantly increased, and the high expression of MLAA-34 gene significantly decreased the apoptosis rate of HeLa cells, and decreased the proportion of G(2)/M phase cells.</p><p><b>CONCLUSION</b>The leukemia-associated gene MLAA-34 has been comfirmed to show antiapoptotic effect in HeLa cells which are induced by As(2)O(3).</p>


Subject(s)
Antigens, Neoplasm , Genetics , Metabolism , Apoptosis , Apoptosis Regulatory Proteins , Genetics , Metabolism , Arsenicals , Cell Cycle , Cell Proliferation , HeLa Cells , Humans , Lentivirus , Oxides , Transfection
14.
Article in Chinese | WPRIM | ID: wpr-360060

ABSTRACT

<p><b>OBJECTIVE</b>To explore the autophagy of RPMI8226 cells induced by As(2)O(3) and its possible mechanisms.</p><p><b>METHODS</b>RPMI8226 was incubated with different concentration of As(2)O(3) for different time, and the inhibiting rate was calculated by MTT method. The autophagic rate of RPMI8226 cells incubated with different concentration of As(2)O(3) was determined by FACS. The change of cells ultrastructure was observed by transmission electron microsopy (TEM). After incubation with different concentration of As(2)O(3), the expression of Beclin-1 on RPMI8226 was detected by RT-PCR and Western blot.</p><p><b>RESULTS</b>Different concentration of As(2)O(3) could significantly inhibit the proliferation of RPMI8226 cells (P < 0.05), and the inhibitory effect was in dose- and time-dependent way in a certain range. the autophagic rate increased with the increasing of drug concentration and prolonging of action time (P < 0.05). TEM results revealed a typical autophagosome in RPMI-8226 cell treated by As(2)O(3) for 48 hours. Beclin-1 was up-regulated in RPMI 8226 cells when treated with different concentration of As(2)O(3) for 48h (P < 0.05).</p><p><b>CONCLUSION</b>As(2)O(3) can induce autophagy of RPMI8226 cells, and the mechanism may be associated with the upregulation of Beclin-1.</p>


Subject(s)
Apoptosis Regulatory Proteins , Metabolism , Arsenicals , Pharmacology , Autophagy , Beclin-1 , Cell Line, Tumor , Cell Proliferation , Humans , Membrane Proteins , Metabolism , Oxides , Pharmacology , Up-Regulation
15.
Article in Chinese | WPRIM | ID: wpr-815139

ABSTRACT

To observe the effect of high-mobility group box 1 (HMGB1) on autophagy and chemotherapy resistance in human leukemiacell line (K562) cells, and to explore the underlying mechanisms.
 Methods: The K562 cells were cultured in vitro and divided into 6 groups: a chemotherapeutic group, a chemotherapeutic control group, a HMGB1 preconditioning group, a HMGB1 preconditioning control group, a HMGB1 siRNA group and a siRNA control group. The chemotherapeutic group was further divided into a vincristine (VCR) group, an etoposide (VP-16) group, a cytosine arabinoside (Ara-C) group, a adriamycin (ADM) group and a arsenic trioxide (As2O3) group. The cell activity was evaluated by cell counting kit-8. The protein levels of HMGB1, microtubule-associate protein1light chain3 (LC3), AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (m-TOR) were determined by Western blotting. The level of serum HMGB1 was evaluated by enzyme-linked immunosorbent assay (ELISA). The autophagy was examined by monodansylcadaverine staining and observed under transmission electron microscopy.
 Results: Compared with the control group, the cell activity was significantly decreased and the level of serum HMGB1 was significantly increased in the chemotherapeutic (VCR, VP-16, Ara-C, ADM and As2O3) groups (all P<0.05). Compared with the control group, the cell activity and the level of serum HMGB1 were significantly increased in the HMGB1 preconditioning group (both P<0.05). Compared with the siRNA control group, the cell activity and the level of serum HMGB1 were significantly decreased in the HMGB1 siRNA group (both P<0.05). Compared with the control group, the expression of LC3-II and the formation of autophagic bodies were increased in the HMGB1 preconditioning group (both P<0.05), the p-AMPK expression was increased and p-mTOR expression was decreased (both P<0.05).
 Conclusion: HMGB1 can increase the autophagy and promote chemotherapy resistance through the pathway of AMPK/m-TOR in K562 cells.


Subject(s)
AMP-Activated Protein Kinases , Genetics , Physiology , Arsenic Trioxide , Arsenicals , Autophagy , Genetics , Cytarabine , Doxorubicin , Drug Resistance, Neoplasm , Genetics , Physiology , Etoposide , HMGB1 Protein , Genetics , Physiology , Humans , K562 Cells , Physiology , Microtubule-Associated Proteins , Oxides , RNA, Small Interfering , Signal Transduction , TOR Serine-Threonine Kinases , Genetics , Physiology , Vincristine
16.
Ciênc. saúde coletiva ; 20(1): 125-136, 01/2015.
Article in Portuguese | LILACS | ID: lil-733138

ABSTRACT

O conceito de recovery tem sido descrito em artigos como um estado de recuperação ou restabelecimento de funções psíquicas, físicas e sociais no funcionamento cotidiano. O objetivo do artigo é analisar concepções terminológicas em diferentes metodologias investigativas e a evolução paradigmática da noção de recovery. Pesquisa bibliográfica sistemática na base Pubmed com as palavras "recovery + schizophrenia", limitada a dois anos retrospectivos e a artigos completos gratuitos. Dezenove artigos foram analisados. A maioria destes busca associações entre dada característica e recovery, poucos são aqueles que discutem a sua concepção de forma que se distinga de termos comuns como "cura" e "reabilitação". Recovery como um estado em que o portador de transtorno mental grave possa sentir-se criador de seus caminhos tende a estar presente em estudos com metodologia qualitativa e em revisões bibliográficas, em que a medida de recovery deixa de relacionar-se à ausência de sintomas e passa a priorizar o quão participativa pode ser a vida de um indivíduo apesar da doença. Alguns estudos quantitativos vislumbram essa diferença conceitual. Em pesquisas qualitativas ocorre expansão na concepção de recovery e nas formas de promovê-lo.


The concept of recovery has been described in papers as a state of psychic, physical and social recuperation of day-to-day functions. The scope of this article is to analyze the concepts of the term in different research methodologies and the paradigmatic evolution of the recovery concept. Systematic bibliographical research was conducted in the Pubmed database using the words "recovery + schizophrenia" limited to freely available full papers published in the previous two years. Nineteen papers were analyzed. The majority of the papers sought associations between characteristic data and recovery; few papers discussed the concept in a way to distinguish it from other words like cure or rehabilitation. Recovery as a state in which people with severe mental illness can feel like the creators of their own itinerary tend to be found in qualitative studies and in bibliographic reviews in which the meaning of recovery is not related to the lack of symptoms and tends to prioritize how participative the life of an individual can be despite the disease. Some quantitative studies detect this conceptual difference. In qualitative research there is an increase in the concept of recovery and in ways of promoting it.


Subject(s)
Animals , Arsenicals/pharmacology , Heteroptera/drug effects , Leucine/analogs & derivatives , Toxicity Tests/methods , Heteroptera/growth & development , Heteroptera/physiology , Leucine/toxicity , Plants, Genetically Modified , Pollen/chemistry , Time Factors
17.
Chinese Journal of Hematology ; (12): 372-377, 2015.
Article in Chinese | WPRIM | ID: wpr-282029

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the clinical efficacy of all-trans retinoic acid (ATRA) plus arsenic trioxide (ATO) in induction and maintenance therapy in newly diagnosed acute promyelocytic leukemia (APL).</p><p><b>METHODS</b>A retrospective analysis of 298 newly diagnosed APL patients from the department of hematology, First Affiliated Hospital of Zhejiang University since September 2004 to December 2013, including 177 cases with ATRA plus ATO and 116 ATRA plus chemotherapy (CT), was performed to investigate the clinical efficacy between the low-intermediate (WBC≤10×10⁹/L) and high (WBC>10×10⁹/L) risk APL patients, respectively.</p><p><b>RESULTS</b>For the low-intermediate risk patients, the relapse rate in ATRA plus CT and ATRA plus ATO are 22.0% and 6.1% (P=0.004), respectively; the 3 years estimated relapse-free survival (RFS) are 78.0% and 92.9% (P=0.021), respectively. For the high risk patients, the relapse rate in ATRA plus CT and ATRA plus ATO are 25.0% and 5.2% (P=0.035), respectively; the 3 years estimated RFS rate were 80.8% and 93.0% (P=0.021), respectively. But the rate of early death (ED), complete remission (CR) and overall survival (OS) between the two therapy protocols had no statistical difference (P>0.05).</p><p><b>CONCLUSION</b>ATRA plus ATO in induction and maintenance therapy might prolong the RFS time of the low-intermediate risk APL patients and decrease the relapse rate of the low, intermediate and high risk APL patients.</p>


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Arsenicals , Humans , Leukemia, Promyelocytic, Acute , Oxides , Recurrence , Remission Induction , Retrospective Studies , Survival Rate , Tretinoin
18.
Article in Chinese | WPRIM | ID: wpr-259632

ABSTRACT

<p><b>OBJECTIVE</b>This study was to explore the effect of arsenic trioxide (ATO; As(2)O(3)) on differentiation of chronic myeloid leukemia K562 cells and its potential mechanism.</p><p><b>METHODS</b>ATO with different concentration (0.1, 0.5, 1.0, 2.0, 5.0 µmol/L) were used to treat K562 cells, and MTT assay was used to detect the growth level of K562 cells; Benzidine staining was applied to measure the change of hemoglobin content; flow cytometry (FCM) was conducted to detect the expression of CD41 and GPA on K562 cells; RT-PCR and Western blot were used to measure the mRNA expression of BTG1 and TAL1 and the protein expression of BTG1 and TAL1, respectively.</p><p><b>RESULTS</b>ATO significantly inhibited the growth of K562 with dose- and time- dependent manners by benzidine staining, the positive rate of K562 cells induced by ATO reached to 17.63% ± 1.18%, which was significantly higher than that of control (2.87% ± 0.63%) (P < 0.01), and GPA, as the specific marker of erythroid cell differentiation, achieved 68.46% ± 3.67%, while it in control was 3.39% ± 0.84% (P < 0.01), besides, the CD41 expression of megakaryocyte increased but not so obvious as GPA. Meanwhile, the differentiation-related transcriptional factors TAL1 and BTG1 mRNA and the corresponding proteins were expressed more highly.</p><p><b>CONCLUSION</b>ATO can induce the differentiation of K562 cells into erythroid cells and megakaryocyte, which is associated with up-regulation of the related transcription factors TAL1 and BTG1.</p>


Subject(s)
Arsenicals , Cell Differentiation , Humans , K562 Cells , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Megakaryocytes , Oxides , RNA, Messenger , Transcription Factors , Up-Regulation
19.
Article in Chinese | WPRIM | ID: wpr-255154

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the anticancer efficacy and the hepatic and renal toxicity of As2O3-lipiodol emulsion via transarterial embolization in a rabbit VX2 liver tumor model.</p><p><b>METHODS</b>VX2 tumors were implanted in rabbit livers successfully, followed by transarterial embolization with high-dose As2O3(5 mg/kg with 0.2 mL lipiodol, n=10), low-dose As2O3(1 mg/kg with 0.2 mL lipiodol, n=10), and control(0.2 mL lipiodol, n=10). The growth ratios and microvessel densities(MVDs) of the tumors were estimated by multi-row spiral CT and CD34 immunohistochemical staining, respectively. Hepatic and renal function was also evaluated by means of blood biochemical analysis.</p><p><b>RESULTS</b>The growth ratios of the tumors differed significantly among three groups(P<0.01). The high-dose and low dose group showed significantly lower tumor growth ratios[44.05%(-36.40%~64.60%), 95.20%(-11.60%~159.40%)] than control group[145.55%(98.90%~250.30%), all P<0.05]. The MVDs of the tumors were significantly lower in the high-dose(21.4±10.6) and low-dose group(34.1±12.0) than those in control group(57.9±16.1,all P<0.05). The levels of blood ALT and AST obtained 28 days after transarterial embolization were significantly lower in the high-dose[(25.50±12.37)U/L,(24.25±10.89)U/L] and low-dose group[(45.00±14.04)U/L,(35.22±11.86)U/L] than in control group[(79.12±30.52)U/L,(75.25±25.89)U/L, all P<0.05].</p><p><b>CONCLUSION</b>As2O3-lipiodol emulsion via transarterial embolization has anticancer effect without significant hepatic and renal functional damage in rabbit VX2 liver tumors.</p>


Subject(s)
Animals , Antineoplastic Agents , Pharmacology , Arsenicals , Pharmacology , Embolization, Therapeutic , Emulsions , Pharmacology , Ethiodized Oil , Pharmacology , Liver Neoplasms, Experimental , Drug Therapy , Oxides , Pharmacology , Rabbits , Tomography, Spiral Computed
20.
Journal of Experimental Hematology ; (6): 1292-1295, 2015.
Article in Chinese | WPRIM | ID: wpr-274048

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the efficacy of arsenic trioxide combined with all trans retinoic acid (ATRA) for patients with acute promyelocytic leukemia (APL).</p><p><b>METHODS</b>A 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.</p><p><b>RESULTS</b>After 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).</p><p><b>CONCLUSIONS</b>The efficacy of As₂O₃conbined with ATRA for inducing remission is better than that of single drug treatment, moreover the adverse reactions occur less.</p>


Subject(s)
Arsenicals , Therapeutic Uses , Drug Therapy, Combination , Humans , Leukemia, Promyelocytic, Acute , Drug Therapy , Oxides , Therapeutic Uses , Remission Induction , Tretinoin , Therapeutic Uses
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