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Inorganic arsenic is an environmental carcinogen. Arsenic exposure is closely related to diabetes. Obesity is an important risk factor for diabetes, and excess energy is the main cause of obesity. High-fat diet feeding is a common method of modeling obese animals. This paper reviews the research progress of diabetes induced by arsenic and the combined exposure of arsenic and high-fat diet in mice. It is found that the diabetes induced by arsenic in mice is mainly manifested in glucose intolerance, and arsenic can aggravate the glucose intolerance caused by high-fat diet, but the diabetes induced by arsenic and its mechanism are different from the typical type 2 diabetes caused by high-fat diet.
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Background: The presence of toxic metals in human populations is strongly associated with chronic diseases. Aim: To determine levels of lead, chromium, cadmium, mercury and inorganic arsenic (AsIn) in the general population aged over 5 years in Antofagasta, Chile. Material and Methods: People living in Urban Antofagasta for at least five years were considered eligible. Biological samples were obtained to measure heavy metals. Results: One thousand two hundred three participants with a median age of 43 years (656 women) were studied. Their mean time of residence in the city was 30 years, and 52% smoked. Eight percent of the adult population and 12% of children had AsIn values above 35 µg/L, while 75% of the population had levels below 21.9 µg/L. The other metals were below the risk levels defined by the health authority (10 µg/L for chromium, 10 µg/L for mercury, 2 µg/L for cadmium, 5 and 10 μg/dL for blood lead for children and adults, respectively). The factors associated with high levels of AsIn in adults were male sex, living more than 200 meters from monitoring points, and low schooling. In children, the associated variables were high intake of seafood products and having a caregiver with less than 8 years of schooling. Contrary to expectations, the greatest risk of presenting altered levels of the metals occurred in the population living more than 500 meters from the identified risk sources (90% of the population). Conclusions: The findings of this study suggest that all potential sources of exposure to AsIn should be evaluated, and surveillance actions should be established to reduce involuntary exposure to this metalloid.
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Humans , Male , Female , Adult , Metals, Heavy/urine , Lead/blood , Chile/epidemiology , Environmental MonitoringABSTRACT
Objective@#To explore the costs and other information of two different treatment plans for pediatric acute promyelocytic leukemia (APL): one is the traditional intravenous drip arsenic (arsenic trioxide) combined with chemotherapy treatment, and the other is a medication family treatment program based on oral arsenic (Realgar-Indigo naturalis formula), in order to provide a reference for the promotion of pediatric APL family treatment mode and the formulation of medical insurance policies.@*Methods@#The medical record homepage data and drug using of pediatric APL from 2010 to 2018 in Institute of Hematology & Blood Diseases Hospital of Chinese Academy of Medical Sciences & Peking Union Medical College were retrospectively analyzed, and the newly diagnosed pediatric patients (≤14 years old) with APL were included. The hospitalization expenses and hospitalization time of two treatment options were compared. One treatment option was Chinese children APL treatment plan 2010 (CCAPL 2010), which was based on intravenous drip arsenic trioxide. The other was Chinese Children Cancer Group APL treatment plan 2017 (CCCG-APL 2017), which was based on oral Realgar-Indigo naturalis formula.@*Results@#A total of 79 pediatric APL patients were included and grouped according to the treatment plans, 56 patients were treated with CCAPL 2010 plan, and 23 patients were treated with CCCG-APL 2017 plan. The median costs of one single pediatric APL patient in CCAPL 2010 plan was 167 700 yuan (95 800-386 600 yuan), and the median hospital stay time of one single pediatric APL patient was 102 days (14-157 days). The median costs of one single pediatric APL patient in CCCG-APL 2017 plan group was 118 700 yuan(50 800-270 600 yuan), and the median hospital stay time of one single pediatric APL patient was 37 days(5-96 days). The costs and hospital stay time of one single pediatric APL patient with CCCG-APL 2017 plan were remarkably less than those of one single pediatric APL patient with CCAPL 2010 plan (U = 178, P < 0.01; U = 66, P < 0.01).@*Conclusions@#The CCCG-APL 2017 plan simplifies the treatment plan compared with the CCAPL 2010 plan and significantly reduces the patient's medical expenses and shortens the hospitalization days. The CCCG-APL 2017 plan is suitable for family therapy and has good social and economic benefits, which is worthy of clinical promotion.
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Objective To investigate the effects of three mitogen-activated protein kinase (MAPK) inhibitors on the expressions of transforming growth factor-β1 (TGF-β1),α-smooth actin (α-SMA) mRNA and protein in human liver stellate cells (LX-2 cells) activated by sodium arsenite.Methods Cultured in vitro LX-2 cells in the logarithmic growth stage were exposed to sodium arsenite at 0.0 (control),2.5,5.0,10.0,20.0,40.0,80.0 μmol/L for 24 h,respectively,and the cell survival rate was determined by CCK-8 assay.According to the results of the study,LX-2 cells were divided into 5 groups:control group,sodium arsenite group,extracellular signal regulation kinase (ERK) inhibition group,c-Jun amino-terminal kinase (JNK) inhibition group,and p38 inhibition group.LX-2 cells were pre-treated with 10.0 μmol/L ERK,JNK,p38 kinase inhibitors (PD98059,SP600125,SB203580) for 30 min in the 3 inhibition groups,and then 20.0 μmol/L sodium arsenite for 24 h.The control group was not treated with sodium arsenite and inhibitors.Sodium arsenite group was not treated with inhibitors.Then mRNA and protein expression levels of TGF-β1 and α-SMA in LX-2 cells were determined by Western blotting and real-time PCR,respectively.Results The survival rates of LX-2 cells in 5.0,10.0,20.0,40.0,80.0 μmol/L sodium arsenite groups were [(92.35 ± 0.92)％,(84.06 ± 0.84)％,(74.27 ± 0.74)％,(59.57 ± 0.60)％,(27.77 ± 0.23)％],which were significantly lower than that of the control group [(100.00 ± 0.00)％,P ＜ 0.05].It was found that the expressions of TGF-β1,o-SMA mRNA and protein of sodium arsenite group were higher than those of the control group (P ＜ 0.01).The expressions of TGF-β1,α-SMA mRNA and protein of the three inhibition groups were lower than those of the sodium arsenite group (P ＜ 0.05).Conclusions Arsenic exposure can cause abnormally high expressions of TGF-β1,α-SMA mRNA and protein in LX-2 cells.Intervention with three MAPK inhibitors can improve the effects of arsenic induced LX-2 cells activation on the expressions of TGF-β1,α-SMA mRNA and protein.
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Objective To investigate the effects of arsenic trioxide (As2O3) on oxidative stress and apoptosis of neuroblastoma cells (SH-SY5Y) and the protective effect of folic acid (FA).Methods SH-SY5Y cells were cultured in vitro,and were divided into six groups:control group,low arsenic group (2.5 μmol/L As2O3),medium arsenic group (5.0 μmol/L As2O3),high arsenic group (10.0 μmol/L As2O3),FA intervention group (10.0 μmol/L As2O3,0.3 mmol/L FA),and FA control group (0.3 mmol/L FA).Each group of cells was cultured for 24 h or 5 h.Cell chromatin agglutination was observed by fluorescence staining.The ultrastructure of cells was observed by transmission electron microscope.The changes of oxidative stress related indicators of glutathione (GSH),malondialdehyde (MDA),superoxide dismutase (SOD),and reactive oxygen species (ROS) were detected;caspase 3 activity was also detected.Results Under fluorescence microscope,as the dose of arsenic increased,the nucleus became increasingly highlighted and a small number of cells in the medium and high arsenic groups showed chromatin agglutination,and FA intervention reduced chromatin agglutination.Under transmission electron microscope,the mitochondria of low and medium arsenic groups were slightly swollen and the endoplasmic reticulum was expanded;while the mitochondria of high arsenic group were significantly swollen and the nuclear membrane was ruptured,and the apoptotic bodies were observed.Mitochondria were slightly swollen after FA intervention.There were statistically significant differences in GSH content,SOD activity,ROS level and caspase 3 activity between groups (F =14.905,6.120,12.714,36.657,P ＜ 0.05).GSH content and SOD activity in high arsenic group [0.104 ± 0.074,(12.673 ± 5.106) U/mg prot] were lower than those in control group [1.000 ± 0.000,(34.699 ±3.998) U/mg prot,P ＜ 0.05].GSH content in FA intervention group (0.411 ± 0.344) was higher than that in high arsenic group (P ＜ 0.05).The ROS level and caspase 3 activity in high arsenic group were higher than those in control group (P ＜ 0.05),and the ROS level and caspase 3 activity in FA intervention group were lower than those in high arsenic group (P ＜ 0.05).There was no significant difference in MDA content between groups (F =8.207,P ＜ 0.05).Conclusions Arsenic exposure can inhibit the activity of antioxidants,cause oxidative stress injury,and increase the activity of caspase 3,leading to cell apoptosis.FA plays an antagonistic role in arsenicinduced oxidative damage and apoptosis of nerve cells.
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Objective To explore the costs and other information of two different treatment plans for pediatric acute promyelocytic leukemia (APL): one is the traditional intravenous drip arsenic (arsenic trioxide) combined with chemotherapy treatment, and the other is a medication family treatment program based on oral arsenic (Realgar-Indigo naturalis formula), in order to provide a reference for the promotion of pediatric APL family treatment mode and the formulation of medical insurance policies. Methods The medical record homepage data and drug using of pediatric APL from 2010 to 2018 in Institute of Hematology & Blood Diseases Hospital of Chinese Academy of Medical Sciences & Peking Union Medical College were retrospectively analyzed, and the newly diagnosed pediatric patients (≤14 years old) with APL were included. The hospitalization expenses and hospitalization time of two treatment options were compared. One treatment option was Chinese children APL treatment plan 2010 (CCAPL 2010), which was based on intravenous drip arsenic trioxide. The other was Chinese Children Cancer Group APL treatment plan 2017 (CCCG-APL 2017), which was based on oral Realgar-Indigo naturalis formula. Results A total of 79 pediatric APL patients were included and grouped according to the treatment plans, 56 patients were treated with CCAPL 2010 plan, and 23 patients were treated with CCCG-APL 2017 plan. The median costs of one single pediatric APL patient in CCAPL 2010 plan was 167 700 yuan (95 800-386 600 yuan), and the median hospital stay time of one single pediatric APL patient was 102 days (14-157 days). The median costs of one single pediatric APL patient in CCCG-APL 2017 plan group was 118 700 yuan(50 800-270 600 yuan), and the median hospital stay time of one single pediatric APL patient was 37 days (5-96 days). The costs and hospital stay time of one single pediatric APL patient with CCCG-APL 2017 plan were remarkably less than those of one single pediatric APL patient with CCAPL 2010 plan (U ＝ 178, P < 0.01; U ＝ 66, P< 0.01). Conclusions The CCCG-APL 2017 plan simplifies the treatment plan compared with the CCAPL 2010 plan and significantly reduces the patient's medical expenses and shortens the hospitalization days. The CCCG-APL 2017 plan is suitable for family therapy and has good social and economic benefits, which is worthy of clinical promotion.
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Objective To establish an analysis method for the detection of 6 arsenic compounds [AsC, AsB, As(Ⅲ), DMA, MMA and As(V)] in blood and urine by high-performance liquid chromatography-inductively coupled plasma-mass spectrometry(HPLC-ICP-MS), and apply it to real cases. Methods Triton was used to damage cells, and then EDTA·2Na·2H2O was used to complex arsenic compounds in cells, and sonication and protein deposition by acetonitrile were performed for sample pretreatment. With the mobile phase consisted of ammonium carbonate and ultrapure water, gradient elution was per-formed for obtaining the arsenic compounds in samples, which were analysed by ICP-MS with Hamilton PRP-X100 column. Results The limits of detection in blood were 1.66-10 ng/mL, while the lower limits of quantitation in blood ranged from 5 to 30 ng/mL. The limits of detection in urine were 0.5-10 ng/mL, while the lower limits of quantitation in urine were 5-30 ng/mL. The relative standard deviation of inter-day and intra-day precisions was less than 10%. This method had been successfully applied to 3 cases. Conclusion This study has established an analysis method for detecting 6 common arsenic compounds in blood and urine, which can be used to detect the arsenic compounds in the blood and urine from ar-senic poisoning cases as well as the patients under arsenic treatment.
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Objective To screen the suitable sample digestion method for measuring iodine in serum by arsenic cerium catalytic spectrophotometric method , and to carry out the methodology test for the newly developed arsenic cerium catalytic spectrophotometry for determination of iodine in serum .Methods Methodology evaluation.Experimentswere on the sample on the sample digestion method of serum iodine with several common digestive agents . After digestion treatment , the concentration of iodine in serum was determined by arsenic cerium catalytic spectrophotometry .The linearity and linear range of the standard curve, detection limit, precision, recovery rate and anti -interference ability of the newlydeveloped arsenic cerium catalytic spectrophotometry were tested .Results Sample pretreatment method included in the newly developed arsenic cerium catalytic spectrophotometry was selected as follows: perchloric acid -sodium chlorate solution was used as the digestive agent to digest 120 min at 130℃.The calibration relation of C =a+blgA( C: iodine concentration ,A: measuring absorbance ) of the newly developed method existed when arsenic ceriumcatalytic reaction was kept at a certain stable temperature range from 13℃ to 30℃ and in certain stable reacting time .The linear range of the calibration curvewas 0 -300 μg/Land the linear correlative coefficient was -0.9996 --0.9999.The intra assay coefficients of variation ( CVs ) were 0.70%,0.70%and 0.74%(n=6), and the inter assay CVs were 0.57%, 0.51% and 0.57% (n=6) for 3 serum samples.The average recovery was 97.9% with a range from 92.3% to 105.8% for 3 serum samples.Conclusions The newly developed arsenic cerium catalytic spectrophotometry has good precision and accuracy .The sample digestion agent is easy to be prepared and reserved , and the instrument is simple and easy to be operated .The method can be widely used as a reliable technique for measuring iodine in serum.
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Objective To analyze the clinical efficacy and safety of compound Qinghuang powder (compound QHP) for treatment of myelodysplastic syndromes (MDS) and its association with blood arsenic concentration (BAC). Methods 40 patients with MDS were treated with compound QHP, and the clinical efficacy, safety, and its association with BAC were evaluated after treatment for 6, 9 months, respectively. Results After treatment for 6 months, the rate of hematology improvement was 32.5 % (13/40), and the effective rate was 87.5%(35/40). 21 cases depended on the blood transfusion before treatment, after treatment 6 cases completely got rid of blood transfusion and the blood transfusion of another 6 cases was decreased by more than 50 %. The absolute neutrophil count was increased from (0.50±0.13)×109/L to (0.93±0.33)×109/L (t= 4.130, P= 0.0008). The hemoglobin content was increased from (71.06±14.82) g/L to (80.41±27.35) g/L (t= 2.233, P= 0.0321). After treatment for 9 months, 76.2 % (16/40) of the patients got rid of blood transfusion or blood transfusion reduction was more than 50%. The platelet count was increased from (45.04 ± 24.38)×109/L to (60.65±29.46)×109/L (t= 2.241, P= 0.0335). The incidence of abdominal pain and diarrhea after treatment for 1, 3 and 6 months were 12.5 % (5/40), 10.0 % (4/40) and 5.0 % (2/40), respectively, all belonging to mild level . Before treatment , there were 12 patients with abnormal liver function , including 6 cases back to normal after treatment, and 6 cases of significantly relieved, without new case with abnormal liver function. Before treatment, there were 10 cases with abnormal myocardial enzymes, including 1 cases back to normal after treatment and 9 cases significantly relieved, without new case with abnormal myocardial enzymes. No patient with abnormal renal function was observed before and after treatment. The BAC was (7.71±5.65) μg/L before treatment, which was significantly lower than that of 1, 3 and 6 months [(29.27±9.07)μg/L, (27.79 ±10.18) μg/L and (31.98 ±12.55) μg/L respectively, all P 0.05). The BAC in efficacy group [(33.48 ±12.56) μg/L] was significantly higher than that in non-efficacy group [(21.46 ±6.00) μg/L] (t=2.089, P=0.035). 12.5% (5/40) of the patients had mild gastrointestinal side effects after treatment for 1 month, while the BAC of them [(16.93 ±1.80) μg/L] was significantly lower than that in patients without gastrointestinal side effects [(31.78±1.39 ) μg/L, P<0.0001]. The occurrence rate of abdominal pain and diarrhea was decreased after treatment for 3 and 6 months, while the BAC was increased gradually. Conclusions Compound QHP is effective in the treatment of MDS with mild adverse reactions. There is no damage to the heart, liver, and renal function. Besides, it shows that reducing the gastrointestinal adverse reactions and maintaining the effective concentration of BAC play a significant role in the effect of compound QHP in the treatment of MDS.
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Objective To analyze the blood arsenic concentration and the safety of compound Qinghuang powder(compound QHP)in patients with myelodysplastic syndrome(MDS).Methods A total of 45 MDS patients received treatment with compound QHP (the treatment group, n=45). The concentration of blood arsenic in different time was determined by atomic fluorescence spectrometry. The clinical safety of compound QHP was evaluated by analyzing the symptoms of adverse reaction and organ function. The comparison were MDS patients with Qinghuang powder (QHP group, n=47) and healthy people. Results There was no significant difference of the blood arsenic concentration between the treatment group and the healthy control group (P=0.450),while after the treatment for 1 month those concentrations significantly increased (P=0.000). There were no significant difference between the blood arsenic concentration after treatment for 1, 3, and 6 months (P=0.240). The incidence of adverse reaction in the treatment group was significantly lower than that in QHP group(χ2=4.720, P=0.030). The incidence of adverse reactions in the digestive tract was significantly lower in the treatment group than that in QHP group (χ2=4.650, P=0.034). The blood arsenic concentration of patients with abdominal pain diarrhea was significantly lower than those without abdominal pain diarrhea (P=0.020). Before treatment in the compound QHP group, there were 21 cases with increased myocardial enzymes, 10 cases with abnormal liver function and 4 cases with renal dysfunction, respectively. After treatment at 6th month, these indicators returned to normal with 7 cases of myocardial enzymes, 6 cases of liver function and 1 case of renal function, respectively. There was no new case with abnormal myocardial enzymes, liver function and renal dysfunction, respectively. Conclusions Arsenic could be absorbed in the digestive tract into blood in MDS patients after treatment with arsenic-containing compound QHP, and the blood arsenic concentration remained stable during the course of treatment. The adverse reactions were mainly mild gastrointestinal symptoms, but no heart, liver or renal function damage was observed. The incidence of abdominal pain diarrhea in patients treated with compound QHP was significantly lower than that with QHP.
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Objective To explore the preparation and quality control of As2 O3 nanoparticle .Methods PEG‐PLA was used as the vector material to prepare As2 O3 nanoparticle with ultrasonic emulsification method ,and the VEGFR‐2 was coupled to obtain VEGFR‐2/As2 O3‐PEG‐PLA nanoparticle .The particle size distribution ,Zata potential ,loading efficiency (LE) ,encapsulation effi‐ciency(EE) ,drug release in vitro and stability was determined ,and morphological characteristics was observed by transmission elec‐tron microscope(TEM) .Tweety‐four hepatocellular carcinoma nude mices were randomly divided into VEGFR‐2/As2O3‐PEG‐PLA nanoparticles group and As2 O3‐PEG‐PLA nanoparticles group ,by tail vein injection of nanoparticles .High performance liquid chro‐matography was used to determine content of As2 O3 .After 21 d ,six nude mices in each group were killed ,and the immunohisto‐chemistry and western blot method was used to detect the expression of VEGFR‐2 .Results The particle size of VEGFR‐2/As2 O3‐PEG‐PLA was determined to be (141 .9 ± 13 .2)nm ,Zata potential was (10 .2 ± 1 .1)mV .It was found to spherical or oval shape , with uniform size and dispersibility under TEM .LE and EE was (5 .51 ± 1 .83)% and (62 .12 ± 5 .98)% ,respectively .Drug release in vitro showed that VEGFR‐2/As2 O3‐PEG‐PLA exhibited controlled release effect ,with half of the release time as 10 h .Besides , VEGFR‐2/As2 O3‐PEG‐PLA showed a good stability in 3 days .Compared with As2 O3‐PEG‐PLA nanoparticles group ,the concen‐tration of As2 O3 in tumor and liver tissue was high ,the concentration of As2 O3 in blood ,heart ,kidney tissue was low ,the expression of VEGFR‐2 in tumor tissue was low in VEGFR‐2/As2O3‐PEG‐PLA nanoparticles group(P< 0 .05) .Conclusion The prepared As2 O3 nanoparticle using PEG‐PLA as vector and VEGFR‐2 as target showed uniform size ,high EE and LE ,good stability .And it preliminarily proved that VEGFR‐2 could be targeted in nude mice .
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Many studies have proven that arsenic trioxide (As2 O3 )as a single agent is not effective against hepatocellular carcinoma (HCC).Many scholars believe that chemotherapy drug resistance of HCC to As2 O3 is the most important reason.The underlying drug resistance mechanism of HCC cells to As2 O3 remains unclear.Studies show that potential mechanism may be tightly associated with As2 O3 pharmacokinetics and properties of HCC tissues and complex molecular biology.
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ObjectiveTo investigate the effects of Saposhnikovia divaricata extract combined with arsenic trioxide (ATO) on the proliferation and apoptosis in chronic myelogenous leukemia K562 cells. MethodsSaposhnikovia divaricata extract was prepared.Cultured K562 cells were treated with different concentration of Saposhnikovia divaricataextract or/and ATO for 48h. Cell proliferation was determined using the MTT assay. Apoptosis and cell cycle were detected using flow cytometry.ResultsThe MTT assay showed that Saposhnikovia divaricata extract of 750,1 000,1 250,1 500 μg/ml had a significantly proliferation inhibitory effect compared with control group, the inhibitory rates were 23.29% ± 3.31%, 48.30% ± 2.50%, 79.62% ± 3.41% and 88.94% ± 0.06%, respectively (allP<0.05); Saposhnikovia divaricata extract of 500 μg/ml combined with ATO of 1.0, 0.5 μg/ml significantly increased inhibitor rates compared with ATO of 1.0, 0.5 μg/ml (64.99% ± 5.18%vs. 44.48% ± 3.31%,38.59% ± 3.88%vs.26.30% ± 5.03%; allP<0.05). FCM showed that Saposhnikovia divaricata extract of 500 μg/ml combined with ATO of 2.0, 1.0, 0.5 μg/ml significantly increased apoptotic rate compared with ATO group of 2.0, 1.0, 0.5 μg/ml (33.97% ± 0.59%vs.20.97% ± 2.17%, 13.53% ± 0.47%vs.9.77%±0.64%、6.63%±&0.40%vs.4.00%±0.46%; allP<0.05 ). Cell cycle results showed that Saposhnikovia divaricata extract of 500μg/ml combined with ATO of 2.0,1.0, 0.5μg/ml significantly increased the rate of S phase compared with ATO group of 2.0, 1.0, 0.5 μg/ml (60.25 ± 2.59%vs.55.61 ± 1.28%, 60.89 ± 1.53%vs.37.96 ± 1.02%, 47.76 ± 0.87%vs.39.90 ± 0.92%; allP<0.05).ConclusionsSaposhnikovia divaricataextract could obviously inhibit the proliferation of K562 cells and enhance the apoptotic effect of ATO. ATO could induce a G2/M phase arrest, while Saposhnikovia divaricata extract combined with ATO could induce a S phase arrest in K562 cells.
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Objective To investigate the molecular mechanism of As 2 O3 in suppressing metastasis of esophagus carcinoma cells.Methods The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay, adhesion and invasion assay were performed to observe the inhibitory effect of As 2 O3 on proliferation and metastasis of esophagus carcinoma cells .The expressions of matrix metalloproteinases ( MMP)2, MMP9, E-cadherin, and protein tyrosine phosphatase receptor-type O ( PTPRO) were analyzed with Western blot .Results Exposure to As 2 O3 significantly presented suppressive functions on growth and metastasis of esophagus carcinoma cells in a dose-dependent manner ( P <0.01 ) .Additionally , MMP2 and MMP9 expressions were increased after treatment with casticin ( P <0.01 ) , whereas E-cadherin and PTPRO expressions were down-regulated ( P <0.01 ) .Conclusions As2 O3 had a significant function to inhibit proliferation and metastasis of esophagus carcinoma cells .
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Objective To evaluate the effect of arsenic trioxide (As2 O3 ) on the proliferation of human renal carcinoma cell line 786-O ,and to explore the changes of the PI3K-Akt signaling pathway .Methods Human renal cancer cells 786-O was cultured in 96-well plates ,and divided into the control group (n= 45 holes) and the experimental group (n= 45 holes) .After stimulation by 1 μM As2 O3 and saline ,the cells in 15 holes were collected at 0 ,12 ,and 24 h .BrdU assay was performed to quantify DNA synthesis to evaluate the cells proliferation ,the quantitative PCR was used to measure PI3K and Akt relative mRNA expression ,and Western blot was used to quantify the relative expression levels of of intracellular PI 3K and Akt .Results After 12 ,24 h of As2 O3 stimula-tion ,the amount of DNA synthesis in the observation group was gradually lower than that of the DNA synthesis at 0 h(P0 .05) ,and the relative ex-pression levels of PI3K and Akt mRNA and protein in the control group were increased as the proliferation was gradually increased . Conclusion As2 O3 inhibits human renal carcinoma cell line 786-O proliferation through inhibiting the PI3K-Akt transduction path-way ,and has potential clinical value for the treatment of kidney cancer .
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ObjectiveTo investigate the effect of arsenic trioxide (As2O3) on the metastasis capability of Ewing's sarcoma ceils. MethodsMTT assays were performed to choose appropriate concentrations of As2O3 (＜ 2 μmol/L) for the experiments.Migration and invasion assays were performed to assess the effect of As2O3 on the metastasis of Ewing's sarcoma cells. Changes in matrix metalloproteinase(MMP)-9 expressions were detected by gel zymography assay and the phosphoinositide 3-kinase/AKT(PI3K-AKT)pathway was investigated using Western blot. ResultsThe amount of Ewing's sarcoma cells across basal membrane of Transwell in migration and invasion assay decreased gradually with the increase in As2O3 concentration. The average quantities of A-673 across the membrane after treatment by gradual concentrations accounted for 54.3 ％,49.0 ％ and 17.0 ％ of that of untreated group respectively in migration assay (F=112.78,P ＜ 0.01), while 52.7 ％, 32.3 ％ and 10.3 ％ in invasion assay(F =183.76, P ＜ 0.01). Similarly, the percentage of RD-ES was 46.0 ％,39.0 ％ and 8.0 ％ in migration assay (F =408.25,P ＜ 0.01) and 58.7 ％,22.3 ％ and 9.0 ％ in invasion assay (F =373.25, P ＜ 0.01)respectively. The difference had statistics significance.The expression of MMP-9 was suppressed by As2O3 treatment according to gel zymography assay.Western blot assay showed that PI3K-AKT pathway was inhibited and nuclear factor kappa B(NF-κB)was inactivated.ConclusionLow-concentration As2O3 may inhibit metastasis capability of Ewing's sarcoma cells.
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Objective To observe the therapeutic effects of arsenic trioxide combined with transcatheter arterial chemoembolization on treatment of primary liver cancer with pulmonary metastases.Methods Sixty patients were randomly divided into two groups:group A (treatment group,n =30) and group B (control group,n =30).Group A was received periodic transcatheter arterial chemoembolization (TACE) and 10 mg arsenic trioxide by intravenous infusion for 5 hours per day,3 days after TACE.Each cycle consisted of 14 days' administration,and repeated after 2 weeks.Each patient was received 3-4 successive cycles.Group B was received periodic TACE alone.Objective efficiency,benefit rate,quality of life and the correlates with metastatic tumor size and number in the both groups were recorded.Results The objective efficiency was 26.7％ (8/30),and the benefit rate was 60.0％ (18/30) in group A,while they were 0 and 16.7％ (5/30) in group B with significant statistics differences (x2 =7.067,P =0.008;x2 =11.915,P =0.001).The quality of life was improved in 4 patients and stable in 18 of group A,while no patient was improved and 13 were stable in group B (x2 =9.669,P =0.008).There was a significantly positive correlation between the tumor burden and therapeutic effect (Kendall r =-0.765,P ＜ 0.001 ;Spearman r =-0.821,P ＜ 0.001).Conclusion Arsenic trioxide combined TACE is an effective treatment method in treating primary liver cancer with pulmonary metastases.
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Objective To investigate the effect of As2 O3 in combination with cinobufacini on proliferation and apoptosis of the K562 cells and provide theoretical basis for clinical application.Methods Cell proliferation was assayed by analyzing the growth and viability of the cells.Apoptosis was assayed by performing cell morphology,Annexin-V/PI staining,DNA-PI staining,and DNA gel electrophoresis.Results After exposure to As2O3 and cinobufacini,the growth of K562 cells was inhibited and the viability of K562 cells was decreased. After treated with 1.0μmol/L As2O3,0.125μg/ml cinobufacini,0.25μg/ml cinobufacini,1.0μmol/L As2O3 + 0.125 μg/ml cinobufacini,1.0μmol/L As2O3 + 0.25μg/ml cinobufacini for 24 and 48 hours,the proliferation inhibition rate were(24 ± 1.3)%,(21 ± 1.5)%,(38 ± 3.1)%,(57 ±2.7)%,(66 ±3.3)% and(49 ±2.9)%,(48 ±2.7)%,(61 ±2.1)%,(77 ±3.8)%,(82 ±4.2)%,the apoptosis rate of K562 cells were(4.8 ± 0.5)%,(5.6 ± 0.7)%,(9.8 ± 0.6)%,(11.9 ± 1.2)%,(15.2±1.5)% and(11.0 ±0.9)%,(12.9 ±1.1)%,(18.4 ±1.5)%,(21.0 ±2.0)%,(28.0 ±1.9)%.The percentage of apoptotic cells was a time- and dose-dependent manner.Typical DNA ladder was shown by DNA gel electrophoresis.Conclusions As2O3 combined with cinobufacini inhibited the proliferation of K562 cells and induced apoptosis of the K562 cells,the combination of the two drugs had better effect.
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Objective To investigate the therapeutic efficacy and side effects of arsenic trioxide (As2O3) with ATRA on newly-diagnosed patients with acute promyelocytic leukemia (APL). Methods 35 patients of newly-diagnosed APL received As2O3 with ATRA treatment. The therapeutic effects were compared with As2O3 treatment on 33 patients. The dose were adjusted according with As2O3 0.16 mg·kg-2·d-1 and ATRA 25 mg·m-2·d-1 until complete remission (CR). The CR rate, period to CR, the incidence of early death and side effects were observed in two groups. Results There was no significant difference in CR rate, in which 94.3 % for As2O3 with ATRA group and 90.9 % for As2O3 group (P >0.05). Significant difference was observed in the period to CR, in which the medium time to CR was 26.1 days for As2O3 with ATRA group and 30.5 days for As2O3 group (P 0.05). Conclusion The treatment combined with As2O3 and ATRA could lessen the time of reaching CR. The WBC count > 10×l09/L was one of the main causes of therapy associated death and the APL differentiation syndrome should be detected and given attention immediately.
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ObjectiveTo investigate the inhibitory effects and related toxicity of all-trans-retinoic acid(ATRA) combined with arsenic trioxide(As2O3) on transplanted human bladder neoplasms in nude mice.MethodsThe subcutaneously transplanted tumor models of human bladder neoplasms in nude mice were established and then it was randomly divided into four teams: Saline group, ATRA group, As2 O3 group and the combination of ATRA and As2 O3 group.Each group composed of 10 nude mice and received intratumor injection in the following 14 d.The tumor growth inhibitory rate was calculated.The pathological changes of tumor,cardiac, liver, and kidney were observed after H.E.staining.The expression of MVD (Marked with CD43) and VEGF were detected by SP of immunohistochemistry.Blood routine examination and hepatic and nephritic functional examination was carried out to evaluate the side-effects.Results The tumor growth was significantly suppressed in ATRA group(inhibitory rate was 41.82％) and As2O3 group (inhibitory rate was 43.77％) compared with saline group.When ATRA combined with As2O3 ,inhibitory effects were improved(inhibitory rate was 68.55％).The difference of growth inhibitory rate between each group was obviously significant(x2 =26.81, P ＜0.01).There was less expression of MVD (Marked with CD43) and VEGF in ATRA group and As2 O3 group and the combination group compared with saline group (ODVEGF = 19.23 + 2.32,20.72 + 2.01,17.16 ± 1.59,27.33 ± 2.17, respectively; ODMVD = 44.77 + 8.25,43.39 + 7.41, 30.56 + 7.71,141.12 + 8.38, respectively), and the suppressed effect in the combination group was most significant (t = 3.16,3.08,3.37, P ＜ 0.01).WBC inhibition was seen in ATRA group and As2O3 group and the combination group, but no significantly difference among them(P ＞0.05).Hepatic and nephritic toxicity were not found.ConclusionsCombination of ATRA and .As2O3 had obvious synergistic effects on transplantéd tumor of human bladder neoplasm in nude mice, and moderate white blood cell inhibition and no hepatic or nephritic toxicity.