Compound Danshen Dripping Pill inhibits hypercholesterolemia/atherosclerosis-induced heart failure in ApoE and LDLR dual deficient mice via multiple mechanisms

Heart failure is the leading cause of death worldwide. Compound Danshen Dripping Pill (CDDP) or CDDP combined with simvastatin has been widely used to treat patients with myocardial infarction and other cardiovascular diseases in China. However, the effect of CDDP on hypercholesterolemia/atherosclerosis-induced heart failure is unknown. We constructed a new model of heart failure induced by hypercholesterolemia/atherosclerosis in apolipoprotein E (ApoE) and LDL receptor (LDLR) dual deficient (ApoE-/-LDLR-/-) mice and investigated the effect of CDDP or CDDP plus a low dose of simvastatin on the heart failure. CDDP or CDDP plus a low dose of simvastatin inhibited heart injury by multiple actions including anti-myocardial dysfunction and anti-fibrosis. Mechanistically, both Wnt and lysine-specific demethylase 4A (KDM4A) pathways were significantly activated in mice with heart injury. Conversely, CDDP or CDDP plus a low dose of simvastatin inhibited Wnt pathway by markedly up-regulating expression of Wnt inhibitors. While the anti-inflammation and anti-oxidative stress by CDDP were achieved by inhibiting KDM4A expression and activity. In addition, CDDP attenuated simvastatin-induced myolysis in skeletal muscle. Taken together, our study suggests that CDDP or CDDP plus a low dose of simvastatin can be an effective therapy to reduce hypercholesterolemia/atherosclerosis-induced heart failure.

HLA-B alleles and nasopharyngeal carcinoma in Xinjiang, China：relationship and clinical significance / 中华放射肿瘤学杂志

Objective To explore the relationship between HLA?B allele polymorphisms and nasopharyngeal carcinoma ( NPC) in Xinjiang, China and its clinical significance. Methods A total of 226 patients were assigned to NPC group, while 207 healthy volunteers were assigned to control group. PCR amplification with sequence?specific primers was used to determine HLA?B alleles. Comparison of HLA?B allele frequency between the above two groups, between Han and Uygur populations, and between patients with various clinical characteristics of NPC was made by chi?square test. The Kaplan?Meier method was used to calculate the survival rates and the log?rank univariate analysis was used to explore the relationship between survival rates and HLA?B allele frequency. Results In all the subjects or Han population alone, the allele frequency of HLA?B?46 in the NPC group was significantly higher than that in the control group ( P=0. 000;P=0. 000 ) . In Uygur population, however, there was no significant difference in the allele frequency of HLA?B?46 between the NPC group and the control group (P>0. 05). In the patients with NPC, those less than 30 years old had a significantly higher allele frequency of HLA?B?44 than those no less than 30 years old (P=0. 029);those with differentiated non?keratinizing carcinoma had a significantly higher allele frequency of HLA?B?48 than those with undifferentiated non?keratinizing carcinoma ( P=0. 029);those with stage T1+T2 disease had a significantly higher allele frequency of HLA?B?48 than those with stage T3+T4 disease ( P=0. 029) . The 5?year overall survival, disease?free survival, distant metastasis?free survival, and local relapse?free survival rates had no relationship with the expression of HLA?B?46, HLA?B?44, or HLA?B?48 in NPC patients ( all P>0. 05) . Conclusions HLA?B?46 allele is probably a NPC susceptibility gene in Han population in Xinjiang. HLA?B?44 is probably associated with early age of onset, while HLA?B?48 is probably associated with the pathological type and T stage of NPC. Therefore, HLA?B alleles are probably associated with the development and progression of NPC.

Effect of cetuximab combined with radiation on the expressions of Ku80 and ATM in CNE-2 nude mice xenograft tumor model / 中华放射医学与防护杂志

Objective To investigate the effect of cetuximab (C225) combined with radiation on the expressions of Ku80 and ATM in CNE-2 nude mice xenograft tumor model.Methods The CNE2 nude mice xenograft tumor model was established and divided into control group,conventional radiotherapy (CRT) group,simulated intensity modulated radiation therapy (sIMRT) group,C225 group,CRT + C225 group and sIMRT + C225 group with 8 mice in each group.The dose of radiation was 20 Gy,and 1mg C225 per mice in abdominal cavity was applied for the drug treatment.The transcriptional levels of Ku80 and ATM were assayed by RT-PCR and Western blot.Results Compared with control group,the transcriptional and translational levels of Ku80 and ATM in CRT group,sIMRT group,CRT + C225 group and slMRT + C225 group were decreased (P ＜ 0.05).Compared with CRT group,the down-regulation of transcriptional and translational ATM level in sIMRT group was obvious (P ＜ 0.05),and further strengthened in the CRT + C225 group and sIMRT + C225 groups (P ＜0.05),but there was no significant difference of ATM expression between sIMRT + C225 group and CRT group (P ＞ 0.05).Conclusions C225 alone can restrain the transcriptional and translational level of ATM,and the transcriptional and translational level of Ku80 and ATM are also restrained after megadose.ATM is down-regulated by sIMRT but up-regulated by the combination of C225 and radiation.

Radiosensitizing effect of cisplatin on CNE-1 xenograft in nude mice / 中华放射肿瘤学杂志

Objective To investigate influence of cisplatin (DDP) on the tumor inhibition rate,transcriptional levels of CyclinB1 and CyclinD1 of CNE-1 xenograft in nude mice.Methods Tumor mode of nude mice CNE-1 xenograft was established.Then mice were divided into control arm,DDP arm,high speed irradiation arm,simulated intensity modulated radiation therapy (IMRT) arm and simulated IMRT + DDP arm,with 12 mice in each arm.Irradiation dose was 20 Gy with a single fraction.DDP was 15 μg/g weight.The maximum diameter of tumor base was measured every other day.The growth curve was drawn and tumor inhibition rate werevcalculated after 40 days.The transcriptional level of CyclinB1 and CyclinD1 of xenograft was measured by RT-PCR.The results of different groups were compared with one-factor analysis of variance.Results Tumor inhibition rates of the control arm,DDP arm,high speed irradiation arm,simulated IMRT arm and simulated IMRT + DDP arm were-129.1％,-71.2％,42.5％,35.3％ and 47.1％,respectively.There was significant difference between the high speed irradiation arm and simulated IMRT arm (P =0.034),but not between the high speed irradiation arm and simulated IMRT + DDP arm (P =0.222).The transcriptional levels of CyclinB1 in the arms were 0.429,0.386,0.322,0.354 and 0.268.There were significant differences between the high speed irradiation arm and the simulated IMRT arm or the simulated IMRT + DDP arm (P =0.007 and 0.000).The transcriptional levels of CyclinD1 in the arms were 0.716,0.583,0.348,0.495 and 0.296,respectively.There was significant difference between the acute irradiation arm and the simulated IMRT arm (P =0.000),but there was no significant difference between the high speed irradiation arm and the simulated IMRT + DDP arm (P =0.072).Conclusions Irradiation of 20 Gy single fraction,or combined with DDP are effective on the CNE-1 xenograft in nude mice,but DDP alone can only lower the tumor growth speed.Irradiation of 20 Gy single fraction,or combined with DDP,or DDP alone can reduce the transcriptional levels of CyclinB1 and CyclinD1.As the single therapeutic time is prolonged in IMRT mode,the tumor inhibition rate is reduce,and the reduce of the transcriptional levels of CyclinB1 and CyclinD1 is depressed,while combined DDP can compensate the decline of the biological effect.

Research of anti-tumor effect of PHⅡ-7 to K562/A02 cells / 中国药理学通报

Aim To study the mechanism of anti-tumor effect of PHⅡ-7 to K562 and K562/A02 cells.Methods The effects of individual and combined doxorubicin on K562 and K562/A02 cells were observed by MTT assay.The coefficient of drug interaction was used to analyse the synergistic effect of PHⅡ-7,obtaining the RNA from the cells stimulated by PHⅡ-7 with different doses to analyse the MDR1 gene expression level.Finally,the cumulation of doxorubicin was observed in K562 and K562/A02 cells after being coped with PHⅡ-7.Results PH Ⅱ-7 had anti-tumor effect with IC50 of (1.37?0.37) ?mol?L-1;(1.48?0.34) ?mol?L-1 for K562 and K562/A02,respectively.It could potentiate the anti-tumor effect of dororubicin with CDI of 0.22 and 0.09 for K562 and K562/A02,respectively.PHⅡ-7 could synergistically inhibit the proliferation of K562 and K562/A02 cells.The decrease of MDR1 expression level depended on the increase of dose of PHⅡ-7 acting on cells.PHⅡ-7 could also develop the cumulation of doxorubicin in cells.Conclusion PHⅡ-7 is not only a Cytotoxinic drug but also can synergistically inhibit the proliferation of K562 and K562/A02 cells with the decrease of MDR1 expression level,especially in K562/A02 cells.