1.MicroRNA-related pathways and tumorigenesis and tumor development
Journal of International Oncology 2012;39(8):566-569
Aberrant microRNA(miRNA) expression has been found in most of human cancers.miRNA-related regulation pathways,including the interaction between miRNA and protein-coding gene and the interaction between miRNA and IncRNA,have been shown correlated with the initiation and progression of human cancers.miRNA might be a therapeutic target in the treatment of malignancies.
2.Potential role of ezrin and its related microRNA in ovarian cancer invasion and metastasis
Jun LI ; Shanhui LIANG ; Xin LU
Chinese Journal of Obstetrics and Gynecology 2010;45(10):787-792
Objective To screen microRNA (miRNA) that inhibit expression of the metastasisrelated gene ezrin in ovarian cancer cells and explore their correlation to the invasion and metastasis of ovarian cancer. Methods The differential expression of ezrin in two paired high-metastatic and lowmetastatic cell lines were examined by real time reverse transcription (RT)-PCR and western blot. A functional screen with microarray was employed to identify miRNA that were differentially expressed between SKOV3 and SKOV3ip cell lines. Three programs, TARGETSCAN ( http://www. targetscan. org ),MICROCOSM ( http ://www. ebi. ac. uk/enright-srv/microcosm/htdocs/targets/v5/) and PICTAR (http://www. pictar. mdc-berlin. de), were employed to identify all miRNA, which may inhibit the expression of ezrin and were differentially expressed between SKOV3 and SKOV3ip cells. To test the repressive potential of these miRNA, synthetic mimetics were transfected individually into SKOV3ip cells and endogenous ezrin expression levels monitored by western blot and real-time RT-PCR. Results ( 1 ) The mRNA average level of ezrin were (81.74 ± 5.34) -fold higher expression level in SKOV3ip versus SKOV3 cells ( P < 0. 01 ), while (2. 61 ±0. 14)-fold in HO-8910PM versus HO-8910 cells (P <0. 01 ). Elevated protein level of ezrin were observed in SKOV3ip cells compared with that in SKOV3 cells, and the same that in HO-8910PM cells compared with HO-8910 cells. Paired SKOV3 and SKOV3ip cells were employed to study the more significant difference in ezrin expression between them. (2) By a functional screen using miRNA microarray combined with bioinformatics analysis,the miR-183 and miR-22 were indentified as two candidate miRNA,which may have the potential regulatory role in ezrin expression. Real time RT-PCR assays revealed that miR-183 and miR-22 were, respectively, an average of (5.84 ± 0.66)-fold and(6.67 ± 0.67)-fold higher expression level in SKOV3ip versus SKOV3 cells (P <0. 01 ), which were in agreement with the microarray data. A subsequent validation by western blot and real time RT-PCR revealed that over-expression of miR-183 and miR-22 could both lead to an obvious decrease in ezrin protein level,while there were not signicant difference in the level of ezrin mRNA( P >0. 05 ). Conclusion Increased expression of miR-183 and miR-22 may both repress the protein level of ezrin,indicating that miR-183 and miR-22 may bear a potential role in inhibiting ovarian cancer metastasis in a ezrin-mediated way.
3.Differential expression of Ezrin in cervical cancer tissues and the relationship between Ezrin and PCNA, MMP-2, MMP-9, HPV
China Oncology 2013;(11):904-909
Background and purpose:Previous studies have revealed potential roles for Ezrin in a variety of cancers. Ezrin participates in several functions including cell adhesion, motility and cell survival, and there is increasing evidence that it regulates tumour progression. This study aimed to determine the differential expression of Ezrin between cervical cancer tissues and normal controls and to explore the association of Ezrin expression with clinical pathological characteristics and with the expression of PCNA, MMP-2, MMP-9 and HPV E6 protein. Methods:Retrospective study was performed among 30 cervical cancer tissue samples which were diagnosed in our hospital from Jan. 2002 to Dec. 2006. Ten normal cervixes from uterine myomas were employed as normal controls. Semi-quantitative immunohistochemisty analysis was performed to detect the association of Ezrin expression with clinical pathological characteristics, and with expression of PCNA, MMP-2 and MMP-9, HPV E6 protein in cervical cancer tissue and normal controls. Analyze the association of Ezrin expression with the clinical characteristics. Results:The expression of Ezrin was strong and the distribution was diffuse mainly in the cytoplasm and membrane in cervical cancer tissues, while the normal cervical tissues was weak and mainly in the membrane. However, there was no signiifcant association between the expression of Ezrin and the clinical characteristics including tumor stage, histology and grade. Ezrin expression was positively correlated with the expression of MMP-2, MMP-9 and HPV E6 protein in cervical cancer tissues, except PCNA. Conclusion:Ezrin was over-expressed in cervical cancer tissues and may be involved in the progress of invasion and metastasis in cervical cancer.
4.Thoracic endovascular aortic repair in 58 patients with Stanford type B aortic dissection
Jun LU ; Jun XIN ; Wei ZHOU ; Weiyang LI
Chinese Journal of Postgraduates of Medicine 2015;38(1):32-34
Objective To assess the efficacy and clinical resuhs of thoracic endovascular aortic repair (TEVAR) in Stanford type B aortic dissection,and to explore the therapentic strategy and prevention of complication.Methods Fifty-eight patients with Stanford type B aortic dissection underwent TEVAR were enrolled,and were followed up regularly.Results The technical feasibility and success with deployment proximal to the entry tear was 100.0%(58/58),requiring partial coverage of the left subclavian artery in 20 patients and total coverage in 4 patients,and 2 patients used chimney stents.Hospital mortality was 5.2% (3/58).Type Ⅰ endoleak was found in 11 patients (19.0%,11/58).In 55 survival patients,48 patients occurred thrombosis in pseudocoele and 2 patients' endoleak disappeared.Seven patients' endoleak appeared blood flow.Forty-eight patients(87.3 %,48/55) were followed up for 3-68 months.Two patients died,and 2 patients' endoleak disappeared,with total suberization in pseudocoele.Other 5 patients' endoleak relieved,with partial suberization in pseudocoele.One patient had new intimal tear at the distal end of the stent-graft and required a second stent implantation.Conclusion TEVAR is safe and effective for the treatment of Stanford type B aortic dissection.
5.Evaluation and management of high-risk gestational trophoblastic neoplasm
Hailin YU ; Meili XI ; Jun LI ; Xin LU
China Oncology 2015;(7):529-534
Background and purpose:Gestational trophoblastic neoplasm (GTN) is a spectrum of disease arising from trophoblastic cells, and the majority of patients with GTN have favorable outcome because of the sensi-tivity to chemotherapy. While the cure rate for high-risk patients is still 70% to 80% as a result of drug resistance and disease recurrence. This study aimed to evaluate the clinical characteristics and outcome of patients with high-risk GTN.Methods:The clinical records of patients with high-risk GTN treated in Obstetrics and Gynecology Hospital of Fudan University from Jan. 2003 to Jan. 2013 were analyzed and reviewed retrospectively from the aspect of different treatment.Results:Fifty-one patients with high-risk GTN were admitted to this hospital. Among 51 high-risk GTN patients, 46 patients were evaluated retrospectively and 5 patients were excluded for incomplete treatments. Of the 46 patients with high-risk GTN, 27 patients were treated by chemotherapy alone, 19 patients received chemotherapy and adjuvant surgical therapy. Forty-four patients received EMA-CO (VP-16+Act-D+MTX/VCR+CTX) as a ifrst-line chemotherapy, 81.82% (36/44) had complete remission and 8 patients developed resistance to EMA-CO. EMA-EP (VP-16+Act-D+MTX/VP-16+cisplatin) was used as second-line chemotherapy for the 8 patients resistant to EMA-CO, 6 patients (2 underwent adjuvant surgical therapy) achieved remission and 2 patients died as a result of drug-resistance and disease progression. For the remaining 2 patients, one was treated by 5-FU+KSM and pulmonary resection, and the other was treated by MTX for misdiagnosis as ectopic pregnancy and then converted to EMA-CO for the pathological diagnosis of choriocarcinoma after surgery. Both of them achieved complete remission. Ultimately, 95.65% (44/46)patients achieved complete remission. Among the 19 patients who underwent adjuvant surgical therapy, 94.70% (18/19) patients achieved complete remission after chemotherapy and adjuvant surgery, and the remaining one patient died of disease progression.Conclusion:Standard combination chemotherapy is crucial in the treatment of high-risk GTN. The role of adjuvant surgery in the management of high-risk GTN should not be underestimated.
6.Effects of enriched environment and impoverished environment on brain function of premature rats after hypoxic-ischemic brain damage
Liqun LU ; Jun JIANG ; Xin YANG ; Songmei LIU
Journal of Third Military Medical University 2003;0(22):-
Objective To investigate the effects of enriched environment and impoverished environment on brain function after hypoxic-ischemic brain damage(HIBD).Methods Three-day-old SD rats,which were divided into enriched environment group(EE),standard environment group(SE) and impoverished environment group(IE) by random digits table were used to establish HIBD model.The sham-operation rats served as control group.Different environment stimulations were administrated to the rats respectively since the 2nd day after HIBD.On the 32nd day,hanging test and incline plane test were carried out to evaluate the sensorimotor function.Morris water maze was used to evaluate the learning and memory ability.The expression of GFAP in the cortex and hippocampus was measured by the method of immunohistochemistry.Results The brain function of IE group was much worse than that of SE group(P0.05).Immunohistochemical analysis showed the expression of GFAP in the cortex and hippocampus of Sham group was significantly lower than that of other groups(P
7.Effect of angiotensin II on insulin secretion function of RIN-m cell and its mechanism
Xin LU ; Hua ZHANG ; Jun Lü ; Hong CHEN ; Dehong CAI
Chinese Journal of Endocrinology and Metabolism 2010;26(3):221-224
Objective To investigate the effect of angiotenisn ⅡI (Ang Ⅱ) on RIN-m β-cell,and to explore the mechanism of β-cell function impairment caused by Ang Ⅱ.Methods RIN-m cells were cultured with various concentrations of AngⅡ (0.1,1,10,100 nmol/L).After incubation for 24 hours,the basal(3.3 mmol/L) and glucose-stimulated(16.7 mmol/L) insulin secretion(GSIS)were detected by radioimmunoassay,mRNA and protein expressions of uncoupling protein 2(UCP2)were determined by RT-PCR and Western blot,respectively.The intracellular ATP content was measured by luciferase bioluminescence.The mitochondrial membrane potential and cellular Ca~(2+) concentration were detected by flow cytometry.Results (1) Various concentrations of Ang Ⅱ had no significant influence on the basal insulin secrection of RIN-m cell(F=0.644,P = 0.634).Except for 0.1 nmol/L AngⅡ,the other concentrations of Ang Ⅱ markedly reduced GSIS of RIN-m cells(F= 118.528,P = 0.000).(2) Compared with the control group,Ang Ⅱ significantly increased mRNA and protein expression of UCP2(F= 1 370,P = 0.000;F=675.175,P = 0.000).(3)Except for 0.1 nmol/L Ang Ⅱ,the other concentrations of Ang Ⅱ significantly decreased the mitochondrial membrane potential,cellular ATP content,and cellular Ca2+ concentration of RIN-m cell(F=4.035,P=0.008;F=3.353,P = 0.013;F=5.867,P = 0.001).Conclusion Ang Ⅱ impairs GSIS of p-cell,the mechanism of impairment may be interpreted that Ang Ⅱ can increase the expression of UCP2,furthermore,it can reduce mitochondrial membrane potential,decrease the content of cellular ATP and the concentration of cellular Ca~(2+),can finally impair the function of β-cell.
9.Discussion on Therapy of Resolving Phlegm and Promoting Diuresis in Treatment of Gastric Cancer Ascites:Experience from Professor WEI Pin-kang
Li HUA ; Cangcang LU ; Xin LV ; Jun SHI
Chinese Journal of Information on Traditional Chinese Medicine 2017;24(1):114-115
Professor WEI Pin-kang believes that, as a complication of gastric cancer, malignant ascites and gastric cancer have the same pathogenesis: water and dampness retention is the external performance and phlegm resistance is the inner essence. Hence therapy of resolving phlegm and promoting diuresis is suggested for the fundamental treatment of gastric ascites. Using the method of the combination of internal and external treatment, this therapy includes resolving phlegm and draining water medicine both to dispel pathogen and to improve symptoms. Xiaotan LishuiDecoction based on this therapy is composed of Arisacma Cum Bile, processed Pinelliae Rhizome, Cremastrae Pseudobulbus Pleiones Pseudobulbus, old pericarp of bottle gourd, Polyporus, Natriee Sulfas, Phytolaccae Radix and Poria.
10.siRNA targeting survivin induces sensitization of hepatocarcinoma cells to tumor necrosis factor related apoptosis-inducing ligand
Xin LU ; Qichang ZHENG ; Xiaogang SHU ; Jun XIONG ; Tao QIN
Chinese Journal of General Surgery 2001;0(07):-
Objective To study the effect of siRNA targeting survivin and tumor necrosis factor related apoptosis-inducing ligand on the proliferation and apoptosis of hepatocellular carcinoma ( HCC) cells. Methods siRNA eukaryotic expression vector was constructed and the effects of soluble tumor necrosis factor related apoptosis-inducing ligand ( sTRAIL) on HCC cells were observed. Results The recombinant plasmid Psilence ( + )-survivin was successfully constructed. Survivin mRNA expression inhibition ratio reached 73% by RT-PCR. Observed by MTT method sTRAIL failed to inhibit the survival rate of HepG2、HepG2/Silence( - ) cells at 12 h、24 h、48 h when compared to control groups. With the survivin gene being inhibited, the survival rate of HepG2/Silence( + ) cells(0. 518?0. 017) decreased in 12 h compared to control groups (0. 741?0. 005 ) and reached the lowest level in 48 h ( P