Effect of low dose arsenious acid combined with total particulate matter of cigarette smoke on oxidative stress in human lung cancer cell line A549 / 公共卫生与预防医学

Objective To investigate the effect of low-dose arsenious acid solution (As(III)) combined with total particulate matter (TPM) from cigarette smoke on cellular oxidative stress in human lung cancer cell line A549 cells. Methods A549 cells were divided into four groups: negative control group (0.75% DMSO), low dose As(III) group (0.88% μg/mL, 75% DMSO), cigarette smoke TPM group (75 μg/mL), and combined exposure group (75 μg/mL TPM, 0.88 μg/mL As (III)). After 24 hours' exposure, the superoxide dismutase (SOD) level in cell culture medium and intracellular 8-hydroxy-2-deoxyguanosine (8-OHdG) content were detected by ELISA, and intracellular reactive oxygen species (ROS) level was detected by fluorescent probe DCFH-DA. 2×2 factorial design was used to evaluate the interaction. Results Compared with the control group, the level of SOD in the combined exposure group was significantly increased (P<0.05). In addition, the ROS content in the combined exposure group and TPM alone group was significantly increased (P<0.05). The levels of 8-OHdG in the combined exposure group and low-dose As(III) treated group were significantly higher than those in the control group(P<0.05). The results of the factorial analysis showed that low-dose As(III) and TPM had interaction on SOD levels, ROS and 8-OHdG contents in A549 cells. The effects on SOD and ROS were synergistic, while the effect on 8-OHdG was antagonistic. Conclusion Low-dose arsenious acid solution As(III) and TPM in cigarette smoke have interaction on oxidative stress in A549 cells.

Decitabine combined with arsenious acid in the treatment of patients with higher-risk myelodysplastic syndromes and chronic myelomonocytic leukemia / 中国实用内科杂志

OBJECTIVE: To evaluate the clinical efficacy of decitabine combined with arsenious acid in the treatment of patients with higher-risk myelodysplastic syndromes(MDS) and chronic myelomonocytic leukemia(CMML). METHODS: Totally 39 patients with MDS and 8 patients with CMML received the treatment of decitabine and arsenious acid from April 2016 to December 2018. Decitabine [20 mg/(m~2·d)] and arsenious acid [0.15 mg/(m~2·d)] were administered intravenously for 5 consecutive days every 4-6 weeks. Patients who achieved complete or partial remission entered into the consolidation cycle. Efficacy and influencing factor were analyzed. RESULTS: Clinical response were observed in 31 patients after a median of 2 courses(ranging 1-12) of treatment. The overall response rate(ORR) was 66.0%. The median duration of response was 16 weeks(ranging 2-52 weeks). There were 8 cases(17.0%) of complete remission(CR), 10 cases(21.3%) of partial remission(PR),12 cases(25.5%) of hematological improvement(HI), 1 case(2.1%) of marrow complete remission(mCR), 8 cases(17.0%) of stable disease(SD), and 1 case(2.1%) of progressive disease(PD). By next generation sequencing, 25 genes mutated with 70 times in 33 cases. The mutation frequency of epigenetic regulators(57.6%) was higher than splicing factors(33.5%), transcription factors and kinase signaling(54.5%),and TP53(21.2%)(P<0.01). There was no significant difference in response rates among these patients(47.4%, 54.5%, 50.0% and85.7%, P=0.977). Gene mutation frequency(VAF) of patients who responded to the regimen declined significantly(16.67% vs. 10.26%,P=0.014). CONCLUSION: Decitabine combined with arsenious acid has significant effect in the treatment of patients with higher-risk MDS and CMML and is well-tolerated. Gene mutation test results by next generation sequencing might be related to clinical response.

All-transretinoic acid combined with arsenious acid and chemotherapy in the treatment of acute promyelocytic leukemia patients with 10 years for survival / 中国基层医药

Objective To study the curative effect and characteristics of all -transretinoic acid (ATRA) and arsenic acid (As2 O3 )combination chemotherapy for acute promyelocytic leukemia (APL).Methods ATRA (30 -60mg/d),As2 O3 (0.1%As2 O3 d1 -28),chemotherapy(anthracycline -based chemotherapy regimens and homoharringtonine -based chemotherapy regimens or high -doses of cytosine arabinoside and small -doses of metho-trexate)were used alternately 4 -5 cycles.Results 12 cases had complete response(CR),CR rate was 100%,first cases and relapse cases all got CR,the median time needed 30 days to get CR.Follow -up deadline,all cases 10 year disease -free survival (DFS )rate was 100%,all reexamination minimal residual disease (MRD)was negative. Conclusion Using this method to treat adult APL,the CR rate is high,has less adverse reaction,and did not produce resistance phenomenon.It can be used for APL consolidation and maintenance therapy.This is one of the ways that can be recommended in the treatment.

Bortezomib combined with homoharringtonine or arsenious acid induced apoptosis in HL-60 cells and its mechanism / 白血病·淋巴瘤

Objective To explore the apoptosis effect induced by bortezomib combined with homoharringtonine or arsenious acid in HL-60 cell line and the mechanism.Methods Cell' s apoptosis was demonstrated by MTT assay and Hoechst33342 staining.Expression of bcl-2,Caspase-9,Caspase-3 and PARP protein was detected by Western blot.Results HL-60 cells' apoptosis could be induced by bortezomib,homoharringtonine and arsenious acid respectively.Proliferation inhibition of HL-60 cells could be enhanced significantly when treated by bortezomib combined with homoharringtonine or arsenious acid compared with treated by any of the three drugs alone (P ＜ 0.05).At the same time morphology shows the apoptosis induced by drugs combined is more obviously than by one drug.Western blot showed bcl-2 protein was down-regulated and Caspase-9,Caspase-3 and PARP proteins were all cleaved activation when cells were treated by 15 μmol/ L arsenious acid alone,but only cleaved activation of PARP and down-regulation of bcl-2 protein be detected when cells were treated with 30 nmol/L homoharringtonine alone,expression of Caspase-9 and Caspase-3 had no change compared with the control.The changes of associated proteins were paralleled with the cell' s apoptosis when treated with combined drugs.Conclusion HL-60 cells' apoptosis effect is inhanced significantly when bortezomib combined with homoharringtonine or arsenious acid.Arsenious acid and bortezomib can inhibit caspase signaling pathway and down-regulate the expression of bcl-2 protein together,but homoharringtonine and bortezomib can only down-regulate the expression of bcl-2 protein and induce cleaved activation of PARP together.

The Changes in Myeloid Derived Suppressor Cells in Mice with Hepatic Transplanted Tumor and the Regulatory Effects of Arsenious Acid / 中国肿瘤临床

Objective: To discuss the correlation between myeloid derived suppressor cells (MDSCs) and hepatic trans-planted tumor and to explore new ways to inhibit the development of hepatic cancer. Methods: We established the animal models with H_(22) hepatic carcinoma cells transplanted to the anterior right limb. Then the MDSCs morphology was observed with confocal microscopy and the proportion of MDSCs in blood and spleen was measured with flow cytometry. The 36 mice were divided into three groups: the control group, the low-dose group (2mg/kg) and the high-dose group (4mg/kg). Then As_2O_3 was injected twice a week to the mice before repeating the aforementioned measures. The direct effects of As_2O_3 on MDSCs cultured with H_(22)-ascites supernatant was observed. Results: At 25 days after transplantion, the tumor weight was increased to 5.67g, and the proportion of MDSCs in blood and spleen was increased to 20.46% and 9.50%, re-spectively. There was a positive correlation between hepatic transplanted tumor and MDSCs in blood and spleen and the relative factors were 0.95 and 0.96, respectively (t=-5.270 and 5.939, P<0.05). With the effect of As_2O_3, the proportion of MD-SCs in blood in low-dose group and high-dose group was 11.31% and 10.00% at 28 days after treatment, lower than that in the control group (t=3.193 and 5.486, P<0.05), and there was also a statistical difference between the high-dose group and low-dose group (t=3.066, P<0.05). The proportion of MDSCs in the spleen in low-dose group and high-dose group was 10.90% and 9.04% at 28 days, lower than that in the control group (t=3.586.and 5.279, P<0.05), but there was no statistical difference between the high-dose group and low-dose group (1=1.298, P>0.05). In vitro, the proportion of MDSCs in nutrient fluid was increased to 12.67% at 12 days after treatment with H_(22)-ascites supematant, and was decreased to 7.44% at 18 days after treatment with As_2O_3. Conclusion: The proportion of MDSCs in H_(22) tumor-bearing mice is increased because of tu-mor development. There is a positive correlation between MDSCs and hepatic transplanted tumor. As_2O_3 can decrease MD-SCs and inhibit tumor growth.

Therapeutic Effect Evaluation of Arsenious Acid-FOLFOX4 Combined Chemotherapy in Metastatic Liver Cancer / 中国普外基础与临床杂志

0.05),but the benefit was significantly different (P

The mechanisms of As_2O_3 in treating rheumatoid arthritis / 中华风湿病学杂志

Objective To explore the possible mechanisms of Arsenic Trioxide in treating rheumatoid arthritis(RA)by observing the changes of HE staining and NF-KB expression as well as the apoptosis of syn- oviocytes in adjuvant-induced arthritis rats.Methods After the animal model was set up on Wistar rats sue- cessfully,they were randomly divided into AA model group and arsenic trioxide treatment group.The treat- ment group were injected with 4 mg'kg~(-1)9?d~(-1)arsenic trioxid fluid for 7 days.All of the rats were killed 3 days after the complete of injections.The joint specimens were exposed,fixed,decalcified,wrapped and cut into slices.All slices were examined by HE stain and immunohistological evaluation.Results HE staining showed that when compared with the normal control group,the layers of synoviocytes of the AA group were increased to 6-8,and the arrangement of synoviocytes was disordered and heavy inflammatory cell infiltration were found in the AA group.In the arsenic trioxide treatment group,the layers of synoviocytes increased to 3～4,and medi- um amount of inflammatory cell infiltration were found.The intensity of synovial NF-kB(p65)positive stain in AA model group was significantly higher than that in the normal control group.The synovial expression and ac- tivation of NF-kB in the treatment group were decreased markedly,and did not return to normal level.The average gray scale calculation showed that there were significant differences between the three groups(P

Experimental study of radiofrequency ablation combined with arsenious acid therapy on liver VX2 tumors in rabbits / 中国普通外科杂志

Objective To evaluate the safety and efficacy of combining radiofrequency ablation(RFA) with arsenious acid(AA) locally to treat liver VX2 tumor in rabbits,and to explore its mechanism.Methods Twenty-eight New Zealand White rabbits with implanted liver VX2 tumors were randomly divided into four groups: control group(n= 7),AA group(n=7),RFA group(n=7),and combination(RFA+AA) group(n=7).ALT was measured before treatment and on the day 0,day 3,day 7 and day 14 after treatment,meanwhile ultrasonic(US) examination was performed.All rabbits were killed 14 days after treatment.Vascular endothelial growth factor(VEGF) was examined by immunohistochemistry,and the relationship of VEGF and gross tumor volume was analyzed.Results Combination(RAF+AA) therapy caused little damage to hepatic function but had better inhibited tumor growth.The level of VEGF in AA,RFA and RAF+AA group was lower than that of the control group(P