1.BRCA1 microsatellite instability in endometrial carcinoma and its relationship with clinical pathology
Dan SUN ; Yujuan FAN ; Hong XU ; Jiangtao FAN
The Journal of Practical Medicine 2015;31(22):3717-3719
Objective To study the occurrence of BRCA1 MSI in endometrial cancer and its relationship with clinic pathologic features; to explore the correlation between MSI and protein expression in BRCA1 gene. Methods Application of PCR-SSCP and DNA sequence analysis method was used to study D17S579 and D17S1349 in 49 sporadic endometrial cancer tissues, 20 cases with endometrial atypical hyperplasia and 28 cases with normal endometrial tissues. Results In the total samples of D17S579 and D17S1349, the three groups were significantly different: 34.69%(17/49) in the endometrial cancer group, 10%(2/20) in the endometrial atypical hyperplasia group and 7.14%(2/28) in the normal endometrium group (χ2= 11.208, P = 0.004). BRCA1 MSI positive rate related to the pathology grade and clinical stage, but no relationship was found in muscular infiltration depth, lymph node metastasis and histopathology types. In the endometrial cancer group, BRCA1 MSI positive rate and BRCA1 protein expression were in moderate correlated negatively (r = -0.779, P = 0.000). Conclusion BRCA1 MSI might play a role in the development of endometrial cancer, and low expression of BRCA1 protein. BRCA1 MSI might be associated with pathology grade and clinical stages in EC.
2.Combined use of telmisartan and pyridoxamine improved aortic remodeling in spontaneously hyperten-sive rats
Fan LIN ; Pengli ZHU ; Chengai SUN ; Hong LIN ; Huizhen YU
Chinese Journal of cardiovascular Rehabilitation Medicine 2014;23(4):415-419
Objective:To explore influence of monotherapy or combined use of telmisartan and pyridoxamine on aor-tic remodeling in spontaneously hypertensive rats (SHR)and its possible mechanism.Methods:A total of 48 male SHE were randomly and equally divided into hypertension control group,telmisartan group,group,and telmisartan+ group (combined treatment group). Kyoto Wistar rats of the same age and gender were regarded as normal blood pressure control group (normal control group). Thoracic aortic section were examined by related staining af-ter 16 weeks intervention to calculate the ratio of aortic wall thickness to radius of lumen (Tw/Rl),the ratio of wall area to lumen area (W/L),and the area ratio of media elastic fiber/collagen fiber. Concentrations of related en-zymes and receptor etc. of abdominal aortic were measured.Results:Compared with hypertension control group, there was significant rise in ratio of media elastic fiber/collagen fiber area and significant reduction in media collagen fiber/media area ratio in telmisartan group,pyridoxamine monotherapy group and combined treatment group,and there were significant decrease in Tw/Rl [(0.17±0.02)vs. (0.12±0.01)]and W/L [(0.29±0.03)vs. (0.22± 0.02)]ratios in combined treatment group,P <0.05 or <0.01;immunohistochemistry indicated that there were significant reductions in thoracic aortic receptor of advanced glycation end products (RAGE) [(0.24±0.03)vs.(0.17±0.03)]and extracellular signal-regulated kinase 1/2 (p-ERK1/2 )expression [(0.63 ± 0.06)vs. (0.37± 0.04)]in combined treatment group,P <0.05,<0.01. Fluorescence quantitative PCR indicated that medication can significantly reduce nicotinamide adenine dinucleotide phosphate (NADPH)oxidase subunit p47phox mRNA ex-pression (P <0.01 all),especially in combined treatment group (P =0.001).Conclusion:Combined use of telmis-artan and pyridoxamine is superior to the single use of either drug on improving thoracic aortic remodeling in SHR, the mechanism may be related to it reduces local expression of RAGE and p-ERK1/2 ,and inhibits oxidase subunit p47 of NADPH.
3.Effect of pyridoxamine and telmisartan on kidneys oxidative stress in spontaneously hypertensive rats
Pengli ZHU ; Hong LIN ; Huizhen YU ; Fan LIN ; Chengai SUN
Chinese Journal of Geriatrics 2012;(12):1108-1111
Objective To investigate the effects and the mechanism of telmisartan and pyridoxamine on oxidative stress in spontaneously hypertensive rats(SHR).Methods SHRs(male,20 weeks of age) were randomly divided into four groups (n= 12 for each):hypertension control (HC) group (2 ml of distilled water),telmisartan group[T,6 mg/(kg · d)],pyridoxamine group[P,200 mg/(kg · d)]and combined group(TP,6 mg/kg telmisartan and 200 mg/kg pyridoxamine per day).Treatments were continued for 16 weeks.The normal control group included 13 WKY rats and received gastric lavage with distilled water.SBP of tail artery was measured during the intervention ervey 2 weeks.The levels of AGEs,SOD and MDA were measured by ELISA,xanthine oxidase and thiobarbituric acid methods after the intervention.Expressiones of NF-κBp65,ERK1 and ERK2 in renal tissue were detected by immunohistochemistry.Expression of RAGE in the renal cortex was investigated by Western blot.Results SOD activity was decreased in the HC group.The levels of AGEs,MDA,RAGE and the activations of NF-κBp65 and ERK1/2 were increased in the HC group (t=4.53,5.52,2.93,al1 P<0.05).After the 16 weeks' intervention,SOD activity was elevated in T,P and TP groups compared to that in HC group (P<0.05).The positive expressiones of NF-κBp65,ERK1 and ERK2 were significantly reduced in T,P and TP groups compared to those in HC group (F=20.13、148.82、18.70,all P<0.05).All the positive expressiones of NF-κBp65,ERK 1and ERK2 were lowest in the TP group versus T and P groups (t = 3.58、2.84,P < 0.05).Conclusions Telmisartan and pyridoxamine can alleviate the oxidative stress in spontaneously hypertensive rats,which may result from the blocking effect of Ang Ⅱ,the reduction of AGEs-RAGE and inhibiting the signal pathways of ROS,NF-κBp65 and ROS-ERK1/2.
4.Time-series Analysis in Imatinib-resistant Chronic Myeloid Leukemia K562-cells under Different Drug Treatments
ZHAO YAN-HONG ; ZHANG XUE-FANG ; ZHAO YAN-QIU ; BAI FAN ; QIN FAN ; SUN JING ; DONG YING
Journal of Huazhong University of Science and Technology (Medical Sciences) 2017;37(4):621-627
Chronic myeloid leukemia (CML) is characterized by the accumulation of active BCR-ABL protein.Imatinib is the first-line treatment of CML;however,many patients are resistant to this drug.In this study,we aimed to compare the differences in expression patterns and functions of time-series genes in imatinib-resistant CML cells under different drug treatments.GSE24946 was downloaded from the GEO database,which included 17 samples of K562-r cells with (n=12) or without drug administration (n=5).Three drug treatment groups were considered for this study:arsenic trioxide (ATO),AMN107,and ATO+AMN107.Each group had one sample at each time point (3,12,24,and 48 h).Time-series genes with a ratio of standard deviation/average (coefficient of variation) >0.15 were screened,and their expression patterns were revealed based on Short Time-series Expression Miner (STEM).Then,the functional enrichment analysis of time-series genes in each group was performed using DAVID,and the genes enriched in the top ten functional categories were extracted to detect their expression patterns.Different time-series genes were identified in the three groups,and most of them were enriched in the ribosome and oxidative phosphorylation pathways.Time-series genes in the three treatment groups had different expression patterns and functions.Time-series genes in the ATO group (e.g.CCNA2 and DAB2)were significantly associated with cell adhesion,those in the AMN107 group were related to cellular carbohydrate metabolic process,while those in the ATO+AMN107 group (e.g.AP2M1) were significantly related to cell proliferation and antigen processing.In imatinib-resistant CML cells,ATO could influence genes related to cell adhesion,AMN107 might affect genes involved in cellular carbohydrate metabolism,and the combination therapy might regulate genes involved in cell proliferation.
5.C6 oral glucose metabolism and differentially expressed genes in livers of 1 type diabetic mice.
Xin-Ran WANG ; Chao ZHANG ; Rong XU ; Li-Na TANG ; Hong-Fan SUN
Chinese Journal of Applied Physiology 2011;27(4):406-408
Animals
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Carbon Radioisotopes
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Diabetes Mellitus, Experimental
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genetics
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metabolism
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Diabetes Mellitus, Type 1
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genetics
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metabolism
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Gene Expression Regulation
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Glucose
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administration & dosage
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metabolism
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Lipid Metabolism
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Liver
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metabolism
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Male
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Mice
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Mice, Inbred C57BL
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Transcriptome
6.External application of Algoplaque can control phlebitis caused by peripheral indwelling needle invein
Jingbo HU ; Yanqing ZHU ; Peilong SUN ; Zhongming FAN ; Zan WU ; Peihua DONG ; Hong CHEN ; Huiqin ZHANG
Chinese Journal of Practical Nursing 2009;25(5):12-14
Objective To explore the effect of prevention and treatment of external application of Algoplaque for controlling phlebitis caused by peripheral indewelling needle in vein for patients. Methods This research was divided into two parts,prevention and treatment. As for prevention research,patients were randomly divided into the experimental and the control groups,each group included 30 patients. In the experimental group,we applied directly external application of Algoplaque at the upper of needle puncture site of the vein and nearby the eye. In the control group,we applied the film directly to fix the indwelling needle. As for the treatment research, it was carried out in patients with occurred phlebitis, who were randomly divided into two groups,the experimental group included 30 cases of patients and the control group included 28 cases of patients. Observation time was one to five days. Results The incidence of phlebitis in the experimental group of prevention research was 23%, in the control group it was 90%. The incidence of phlebitis in the experimental group was significantly lower than that of the control group. The effective rate in the experimental group of treatment research was 96.7% and it was 67.9% in the control group. The difference was very significant. Conclusions External application of Algoplaque can effectively control phlebitis caused by peripheral indewelling needle in vein.
7.Assessment of antiangiogenic therapy in a nude murine hepatocellular carcinoma model with real-time gray-scale contrast-enhanced ultrasonography
Peili FAN ; Hong DING ; Xiaodong ZHU ; Xiyuan LIN ; Jubo ZHANG ; Wenping WANG ; Huichuan SUN
Chinese Journal of Ultrasonography 2009;18(8):708-712
ular perfusion in tumors objectively, which is potential in monitoring tumor vascular response to antiangiogenic therapy.
8.Production and mechanism of CCL5 by macrophages in U14 cervical cancer-bearing mice during infection
Hong REN ; Guoli REN ; Limin SUN ; Xiuhua FAN ; Yuran WANG ; Xiaoxi LI
Chinese Journal of Obstetrics and Gynecology 2015;(5):367-373
Objective To investigate the production and mechanism of chemokine (C-C motif) ligand 5 (CCL5) by macrophages in U14 cervical cancer-bearing mice during infection. Methods The U14 cervical cancer cells were injected in C57BL/6 mice to induce tumor-bearing condition. Lipopolysaccharide (LPS) was injected into C57BL/6 mice to induce infection. The protein expression of CCL5 in the serum and the CCL5 mRNA expression in inflammatory cells were measured by ELISA and fluorescence quantitative-PCR in four groups. Macrophages were induced in the tumor conditioned medium (TCM) which extracted from mice serum. The protein expression levels of CCL5, prostaglandin E2 (PGE2) and cyclic adenosine monophosphate (cAMP) in the medium and CCL5, PGE2 and cAMP mRNA expression in the macrophages were detected in different groups. In order to determine whether the inhibition was related to PGE2, selective cyclooxygenase 2(COX-2) inhibitor NS398 was used to reverse this phenomenon and protein kinase A (PKA) inhibitor H89 demonstrated the mechanism through blocking cAMP/PKA signaling pathway. Results (1) The protein and mRNA level of CCL5 in tumor-bearing mice were respectively (151±35) pg/ml and 1.0, which were lower than those in the tumor-free mice (691 ± 85) pg/ml and 4.5 ± 0.8, there were significant difference between them (all P<0.05). The protein and mRNA level of PGE2 in tumor-bearing mice were (1 198±83) pg/ml and 5.8±0.8, which were higher than those in the tumor-free mice (187±25) pg/ml and 1.0, the difference were significant (all P<0.05). The protein and mRNA level of CCL5 in tumor-free+LPS mice were (4 049±141) pg/ml and 31.5±2.0, which were higher than those in the tumor-bearing+LPS mice (1 951±71) pg/ml and 12.1±2.8, the difference were also significant (P<0.05). The protein and mRNA level of PGE2 in tumor-free+LPS mice were (676±70) pg/ml and 3.4±0.4, which were lower than those in tumor-bearing+LPS mice (2 550±382) pg/ml and 11.6±0.9, the difference were also significant (all P<0.05). (2) Macrophages were cultured in vitro using TCM derived from mice. The protein and mRNA level of CCL5 in tumor-bearing mice TCM were respectively (1 626 ± 177) pg/ml and 28.6 ± 1.2, which were higher than those in the tumor-free mice TCM [(27 ± 3) pg/ml and 1.0], there were significant difference (P<0.05). The protein and mRNA level of PGE2 in tumor-bearing mice TCM were (790 ± 156) pg/ml and 1.7 ± 0.3, which were higher than those in the tumor-free mice TCM [(448 ± 115) pg/ml, 1.0], the difference were significant (all P<0.05). The protein and mRNA level of cAMP in tumor-bearing mice TCM were (164 ± 30) pg/ml and 1.6 ± 0.3, which weres higher than those in the tumor-free mice TCM [(118 ± 25) pg/ml,1.0], the difference were significant (all P<0.05). The protein and mRNA level of CCL5 in tumor-free + LPS mice TCM were (10 475 ± 742) pg/ml and 212.0 ± 5.7, which were higher than those in the tumor-bearing+LPS mice TCM [(6 375±530) pg/ml, 142.3±2.5], the difference were significant (all P<0.05). The protein and mRNA level of PGE2 in tumor-free+LPS mice TCM were (2 438±95) pg/ml and 4.3±0.7, which weres lower than those in the tumor-bearing + LPS mice TCM [(3 441 ± 163) pg/ml, 5.9 ± 0.3], the difference were significant (all P<0.05). The protein and mRNA level of cAMP in tumor-free+LPS mice TCM were (340 ± 13) pg/ml and 4.1 ± 0.4, which were lower than those in the tumor-bearing + LPS mice TCM [(542 ± 42) pg/ml, 5.4 ± 0.5], the difference were significant (all P<0.05). (3) Using COX-2 inhibitor NS398 in the tumor-bearing+LPS mice, the protein and mRNA level of CCL5, PGE2 and cAMP were (7 691±269) pg/ml and 159.0±8.9, (2 820±152) pg/ml and 4.9 ± 0.3, (465 ± 8) pg/ml and 4.3 ± 0.4, respectively, and there were significant difference (all P<0.05), compared to before treatment. Using PKA inhibitor H89 in the tumor-bearing+LPS mice, the protein and mRNA level of CCL5, PGE2 and cAMP were (8 375±520) pg/ml and 177.0±8.8, (2 650±35) pg/ml and 4.7 ± 0.4, (368 ± 13) pg/ml and 3.1 ± 0.7, respectively, and there were significant difference (all P<0.05), compared to before treatment. Conclusion TCM of U14 cells activated macrophages to release PGE2 could inhibit the expression of CCL5 levels by cAMP/PKA signaling pathway.
9.Effects of interventional therapy with norcantharidin microsphere on hepatoma in rats and its mechanism
Qi LI ; Zhongze FAN ; Xianqian LI ; Xiaohua LIU ; Jue SUN ; Wei GU ; Paul HENG ; Hong GAO
Journal of Integrative Medicine 2006;4(4):378-83
OBJECTIVE: To investigate the effects of interventional therapy with norcantharidin-alginic acid/poly acid anhydride microspheres (N-MS) infusion via hepatic artery on hepatoma in rats. METHODS: N-MS was prepared by emulsion-chemical crosslink technique. Eighty-nine hepatoma-bearing rats were randomly divided into five groups, which were normal saline group, norcantharidin (NCTD) group, blank microsphere (B-MS) group, NCTD-lipiodol group and N-MS group. Normal saline, NCTD, B-MS, NCTD-lipiodol and N-MS were injected via hepatic artery accordingly. After the interventional therapy, eight rats from each group were observed for survival time, and the rest rats were killed on the 8th day after intervention to measure the tumor volume and necrostic degree. The apoptotic index of liver tumor cells was detected by TUNEL staining, and the expression of ki-67 was assayed by immuno-histochemical streptavidin-biotin peroxidase method. RESULTS: The survival time of the rats in the N-MS group was prolonged as compared with those in the other four groups, and the tumor volume of the rats in the N-MS group was smaller than those in the other four groups. The tumor growth rate and the expression level of ki-67 in the N-MS group were both significantly lower than those in the other four groups. The tumor necrotic degree and the apoptotic index in the N-MS group were significantly higher than those in the other four groups. CONCLUSION: Interventional therapy with N-MS could yield preferable therapeutic effects on hepatomas in rats. This anti-tumor efficacy may be associated with microvessel embolization in liver tumor and the sustained releasing of NCTD. Its inhibiting effect on tumor cell proliferation maybe result from decreasing the expression of Ki-67 and inducing the tumor cell apoptosis.
10.Quantitative analysis of contrast-enhanced ultrasonography on hepatocellular carcinoma: Correlation with tumor differentiated grades
Peili FAN ; Hong DING ; Jiakai GUO ; Xiyuan LIN ; Yuan JI ; Huichuan SUN ; Wenping WANG
Chinese Journal of Medical Imaging Technology 2009;25(12):2243-2245
Objective To investigate the relationship between hemodynamic parameters from quantitative analysis of contrast-enhanced ultrasonography (CEUS) on hepatocellular carcinoma (HCC) and pathological tumor differentiated grades. Methods Seventy-seven HCC lesions were examinated and off-line analyzed with dynamic images. Quantitative parameters such as slope of decrease to half of peak (SD), increased signal intensity (ISI), area under the curve (AUC) and blood flow coefficient (BF) were acquired, and the standardized values (sISI, sAUC and sBF) included the ratio of parameters from tumor to those from hepatic parenchyma. These quantitative parameters were correlated with tumor grades according to Edmonson criteria. Results There was significant difference (P<0.05) of SD, AUC and BF, as well as standardized values (sISI, sAUC and sBF) between different grades of HCC. AUC, BF, sISI, sAUC and sBF were negative correlated with differentiated grades, respectively (P<0.05). Well-differentiated HCC had significantly higher perfusion values than HCC of other grades (P<0.05). Conclusion Quantitative analysis of CEUS can assess differentiation of HCC indirectly, and might reveal biological behavior of malignant tumors.