1.Silencing MTA1 by RNAi reverses adhesion, migration and invasiveness of cervical cancer cells (SiHa) via altered expression of p53, and E-cadherin/β-catenin complex.
Yumei, RAO ; Hongyan, WANG ; Liangsheng, FAN ; Gang, CHEN
Journal of Huazhong University of Science and Technology (Medical Sciences) 2011;31(1):1-9
It has been reported that metastasis-associated gene 1 (Mta1) is overexpressed in many malignant tumors with high metastatic potential. In addition, some studies indicated that MTA1 participated in invasion, metastasis, and survival of cancer cells by regulating cell migration, adhesion and proliferation. But the role of MTA1 is unclear in vitro in the development of cervical cancer cells. This study investigated whether and how MTA1 mediated cell proliferation, migration, invasion and adhesion in cervical cancer. MTA1 expression level was detected by Western blot in two cervical cancer cell lines of different invasion potentials. The effects of MTA1 expression on SiHa cell apoptosis, cycle, proliferation, migration, invasion and adhesion were tested by flow cytometry, MTT, wound-healing assay, Transwell assay and adhesion assay, respectively. The expression levels of p53, E-cadherin, and β-catenin activity were evaluated in untreated and treated cells. The results showed that MTA1 protein expression was significantly higher in SiHa than in HeLa, which was correlated well with the potential of migration and invasion in both cell lines. Furthermore, the cell invasion, migration and adhesion capabilities were decreased after inhibition of MTA1 expression mediated by Mta1-siRNA transfection in SiHa. However, no significant differences were found in cell apoptosis, cycle, and proliferation. In addition, E-cadherin and p53 protein levels were significantly up-regulated, while β-catenin was significantly down-regulated in SiHa transfected with the siRNA. These results demonstrated that MTA1 played an important role in the migration and invasion of cervical cancer cells. It was speculated that the decreased migration and invasion capability by inhibiting the MTA1 expression in the SiHa cell line may be mediated through the altered expression of p53, and E-cadherin/β-catenin complex. MTA1 could serve as a potential therapeutic target in cervical cancer.
2.Treatment of transplanted renal artery stenosis with percutaneous transluminal angioplastly
Ming ZHAO ; Jianmin HU ; Ying GUO ; Liangsheng YUE ; Lipei FAN ; Hua CHEN ; Min LI
Chinese Journal of Organ Transplantation 2010;31(5):276-279
Objective To evaluate the efficacy of percutaneous transluminal angioplasty (PTA) in the treatment of transplanted renal artery stenosis (TRAS)-induced renal dysfunction and hypertension. Methods Between July 1998 and January 2007, PTA was performed on 16 patients with RTAS. Color Doppler uhrasonography preceded the intra-arterial angiographic investigation,with false-negative results in 18. 75 % of patients. Sixteen cases of TRAS were examined at 1 st week,6th month and 13 years after PTA. Hypertension improvement was defined as mean arterial pressure decrease of at least 15 % from the pre-PTA value. Graft function was evaluated by SCr levels, and the improvement was defined as a 20% change. Results Angioplasty was technically feasible in 100 %.Sixteen patients with RTAS were cured clinically. During the follow-up period, graft function was improved in 81.25 %, 68. 75 %, 62. 5 %, 56. 25 %, 50 % of patients respectively at 1st week, 6th month and 1-3 years after PTA. The blood pressure was decreased in 62. 5%, 75 %, 75 %,56. 25 %, 50 % of patients respectively, but no patient remained hypotensor medication free.Conclusion PTA improved renal dysfunction and hypertension induced by TRAS, and it is a safe and effective treatment for TRAS.
3.Expression and prognosis significance of P16 in cervical cancer
Yue CHEN ; Xiaowei ZHANG ; Zhixiao DENG ; Weijian TAN ; Xiaojun HUANG ; Liangsheng FAN
The Journal of Practical Medicine 2014;(15):2417-2420
Objective To access the expression of germ P16 in cervical cancer patients , find out the connection between with the expression in germ of P16 and the prognosis of cervical cancer , and discuss whether P16 can role as an indicator to predict the prognosis. Methods The pathological sections of all 74 cases were tested for the presence of P16 germ , using an immunohistochemistry technique. And the results were analyzed to investigate the value of P16 on the prediction of prognosis of cervical cancer. Results Of all 74 cervical cancer cases, there are 63 cases show positive expression of P16, with the positive expression rate of 85% (63/74). The positive expression of gene P16 is associated with the prognosis of cervical cancer (P = 0.041). The cumulative survival rate for two years of the positive expression set is 85.2%, and the negative set 100%, which is statistically significant (P = 0.043). Positiveexpression of P16 is closely related (P < 0.05) with clinical stages LVSI and interstitial infiltrates, but is irrelevant (P > 0.05) with TNM and histological differentiation. Conclusions We suggest that the expression of germ P16 is closely connected prognosis in cervical cancer , and it might be used as one of indicator to predict the prognosis of cervical cancer.
4.Correlation of human leucocyte antigen matching to acute rejection and allograft survival after renal allograft
Liuyang LI ; Jianrong CHEN ; Jun QIAN ; Min LI ; Erwei SUN ; Ying GUO ; Liangsheng YUE ; Lipei FAN ; Hua CHEN ; Ming ZHAO
Chinese Journal of Tissue Engineering Research 2008;12(31):6165-6168
BACKGROUND: Panel reactive antibody (PRA) can mediate hyperacute rejection, and lead to decrease in success rate of transplantation and survival rate of renal graft in highly sensitized recipients compared to non-sensitized recipients.OBJECTIVE: According to human leucocyte antigen (HLA) cross-matching standards to select suitable donors for sensitized recipients and to evaluate the incidence of acute rejection and survival rate of renal allografts.DESIGN: Case observation.SETTING: Zhujiang Hospital of Southern Medical University.PARTICIPANTS: 136 sensitized recipients with positive PRA underwent renal transplantation in Department of Organ Transplantation, Zhujiang Hospital of Southern Medical University between January 1997 and December 2003 were selected, including 41 males and 95 females, aged (45±9) years. Recipients of first, second, third, and fourth transplant were 115, 18, 2 and 1 case, respectively. The informed consent was obtained from all patients. The protocol was approved by Hospital Ethics Committee. Lambda antigen tray (LAT) and LAT-Mix were purchased from One Lambda, Inc, USA. Special monoclonal tray -Asian HLA class Ⅰ (SMT72R) and Micro SSP Generic HLA Class Ⅱ (DRB/DQB) were also purchased from One Lambda, Inc, USA.METHODS: Pre-operative PRA levels and specificity of recipients were detected by ELISA test with Lambda antigen tray (LAT). Donor and recipient HLA class Ⅰ typing was performed with special tray - Asian HLA class Ⅰ (SMT72R), and HLA class Ⅱ gene typing with Micro SSP Generic HLA Class Ⅱ (DRB/DQB) (Micro-SSP). HLA-matching between donor and recipient was performed according to HLA cross-reactive group (CREG) standards by UNOS and class Ⅱ antigen permissible mismatch. The incidence of acute rejection and survival rate of renal allografts were evaluated within 1, 3 and 5 years.MAIN OUTCOME MEASURES: ①PRA levels and specificity of sensitized recipients before and after transplantation; ②HLA-matching between donor and recipient; ③Incidence of acute rejection and survival rate of renal allografts after transplantation.RESULTS: 136 PRA positive sensitized recipients were all included in final analysis. ① There were 104 recipients with anti-HLA class Ⅰ IgG antibody, 76 with anti-HLA class Ⅱ IgG antibody, and 44 with both anti-HLA class Ⅰ and Ⅱ IgG antibodies in 136 recipients. ②The number of cases of 0, 1, 2, 3, and 4 mismatch (MM) was 7, 26, 47, 39 and 17, respectively by the standard of conventional HLA antigen matching; However, the number of the recipients with 0, 1, 2, 3, and 4MM was 31, 53, 36, 16, and 0, respectively according to the principle of HLA CREG matching. ③By the principle of HLA CREG matching, rates of acute rejection in sensitized recipients with 2MM and 3MM HLA-CREG were significantly higher than those with 0MM (P < 0.05). Renal allograft survival rate in sensitized recipients with 0MM was significantly higher than those with 2MM and 3MM (P < 0.05).CONCLUSION: ①HLA CREG matching can significantly improve the ratio of well-matched. ② Good HLA matching can reduce the incidence of acute rejection in sensitized recipients and increase the survival rate of renal grafts.
5.Proteasome inhibitors sensitize ovarian cancer cells to paclitaxel induced apoptosis
Danhui WENG ; Yan LI ; Yanfei KONG ; Liangsheng FAN ; Yi HU ; Xiaohong SONG ; Hui XING ; Shixuan WANG ; Ding MA
Chinese Journal of Obstetrics and Gynecology 2008;43(10):770-773
Objective To explore the semitivity of ovarian cancer cell line SKOV3 to paclitaxel,oroteasome inhibitors,bortezomib,and their combination.Methods The methyl thiazolyl tetrazolitim (MTT)assay was applied to examine the cell viability after treatment.The annexin V-propidium iodide apoptosis detection kit was used to determine the apoptosis rate of different groups.Western blot assay was used to evaluate the expression levels of phosphorylated protein kinase B(AKT)and glycogen synthase kinase-3 beta(GSK-3β).Results In MTT assay,the cell viability ratios of the combination group at serial time points from 12,24,36,48 and 72 hours Were(65.2±5.8)%,(58.3±14.4)%,(35.3±5.0)%,(19.2±1.5)%,and(11.4 ±2.5)%,which were significantly lower than those of the paclitaxel group (P<0.05).After arug treatments,apoptosis rates of paclitaxel group,bortezomib group and the combination group were (14.7±0.5)%,(15.1±0.8)%and(20.5±0.7)%respectively.The rate of the combination group was significantly higher than that of non-treated group and paclitaxel group(P<0.05).Western blot assay showed the changes in expression levels of phosphorylated AKT and GSK-3β,which were decreased significantly after paclitaxd and bortezomib combination treatment [(3.2±0.8)%,(19.3±0.4)%;P<0.05].Conclusions The lethal effect of paclitaxel on tumor cells could be increased significantly by its combination with proteasome inhibitors,bertezomib.The AKT/GSK-3β signaling pathway plays an important role in the molecular mechanism of the combination treatment.
6.Proteasome inhibitors sensitize ovarian cancer cells to cisplatin
Yan LI ; Danhui WENG ; Fanfei KONG ; Liangsheng FAN ; Yi HU ; Xiaohong SONG ; Hui XING ; Wei WANG ; Ding MA ; Shixuan WANG
Chinese Journal of Obstetrics and Gynecology 2010;45(6):445-448
Objective To explore the sensitivity and the molecular mechanism of cisplatinresistance ovarian cancer cell line C13 to proteasome inhibitors and the combination with cisplatin. Methods After different treatments, methyl thiazolyl tetrazolium (MTT) assay was applied to examine the cell viability, annexin-V/propidium iodide(PI) apoptosis detection kit was used to determine the apoptosis rate of different groups, western blot assay was introduced to evaluate the expression levels of Fas-associated death domain-like interleukin-1 beta converting enzyme inhibitory protein (cFLIPs), and the activity of caspase-8 was examined. Results MTT assay shown that the cell viability ratios of combination group at serial time points from 12, 24, 36, 48, 60, 72 hours were ( 56.0 ± 8.4 ) %, (44.7 ± 7.3 ) %, ( 33.7 ±11.2) %, (27.6 ± 8.0) %, (27. 6 ± 7.6) % and (28.1 ± 2.4) %, which were much lower than those of cisplatin group (P <0.05). After treated for 24 hours, apoptosis rates of cisplatin group, bortezomib group and combination group were ( 16.7 ± 1.7) %, (23.4 ± 2.1 ) % and (26.9 ± 1.6) %, respectively. The rate of combination group was much higher than that of non-treated group and that of cisplatin group or bortezomib group ( P < 0.05 ). Western blot assay showed the changes of expression levels of cFLIPs, which were downregulated seriously after cisplatin, bortezomib or combination treatment [ (43.2 ± 2.3 )% vs( 75.7 ± 3.0)%vs (67.9 ± 2.1 ) %, P < 0.05 ]. The caspase-8 activity of combination group was (5.6 ± 1.6) folds than that of non-treated group, which was higher than those of other two groups [ ( 2.3 ± 1.0) and (4.2 ± 0.9 ) folds,P < 0.05 ]. Conclusions The tumor cell lethal effect of cisplatin could be increase significantly by the combination application of proteasome inhibitors, bortezomib. And the cFLIPs/caspase-8 signaling pathway may be play an important role in the molecular mechanism of the combination treatment.
7.Application of Rituxnab in antibody-mediated rejection among renal transplantation recipients
Yongguang LIU ; Tianlai LIU ; Min LI ; Ying GUO ; Hua CHEN ; Jianmin HU ; Lipei FAN ; Liangsheng YUE ; Liuyang LI ; Ming ZHAO
Chinese Journal of Organ Transplantation 2011;32(9):531-533
Objective Toobservetheindication, safetyandefficacyofanew immunosuppressant Rituximab in kidney transplantation. MethodsFive patients, who were diagnosed as antibody mediated rejection (AMR) from December 2010 to June 2011, were treated with single dose of Rituximab (500 mg) and followed up for 6 months. The clinical data, such as age, gender, onset of illness, induction therapy, maintaining therapy, allograft function, change of PRA, opportunistic infection and other complications were collected and retrospectively analyzed to evaluate the safety and efficacy of Rituximab used in AMR patients. ResultsAfter Rituximab therapy, all the patients had improved renal function measured by sera creatinine level: 4 cases retumed to normal, and 1 keep stable. Series of allograft biopsy demonstrated obviously reduced C4d deposition in nephridial tissue after treatment. One patient developed CMV viremia, another had urinary infection, but no one had lifethreatening infection during the follow-up period. The survival rate of human and allograft was both 100 %. Conclusion Rituximab has a good efficacy and safety in treatment of AMR after renal transplantation.
8.A comparison study on venous anastomosis for right donor kidney transplantation in rats
Xinjun DENG ; Yongguang LIU ; Ying GUO ; Min LI ; Liangsheng YUE ; Lipei FAN ; Hua CHEN ; Jianqiang ZHANG ; Yafei WEI ; Minyi HE ; Ming ZHAO
Chinese Journal of Organ Transplantation 2012;(12):746-749
Objective To explore the optimized method of venous anastomosis for right donor kidney transplantation in rats.Methods Sprague Dawley (SD) rats were used as donors and recipients for homologous rat kidney transplantation.Both bilateral kidneys were harvested from the donor rats (n =45).Ninety rats were used as recipients and divided into 4 groups according to randomly digital table:In groups AC (n =15 each),the right donor kidneys were transplanted into the left nephridial pit of recipients,and endto-side,venous bypass and modified end-toend (donor's proximal end of vena cava was anastomosed to recipients renal Vein followed by ligation of its distal end) venous anastomosis was done,respectively; In the control group (n =45),the left donor kidneys were transplanted into the same side of the recipients,and the conventional end-to-end venous anastomosis was used.Then the intra-operative findings,successful operation rate and postoperative complications were compared between two groups.Results The venous anastomosis time in group B was longer than in groups A,C and control group (P<0.05),which significantly increased warm ischemia time of donor kidneys and operative time of recipients (P<0.05).The venous anastomosis time,warm ischemia time of donor kidneys and operative time of recipients showed no significant difference between groups A or C and control group (P>0.05).The successful operation rate in group C (93.3%)was similar to that in control group (86.7%) (P>0.05),but higher than in group A (53.3%) and group B (53.3%) (P<0.05).There was no significant difference in postoperative complications between group A and group C.Conclusion For right donor kidney transplantation,the method of harvesting the right donor kidney with a part of vena cava,and then anastomosing the proximal end to recipients renal vein and ligating the distal end,is highly feasible,efficient and economic.
9.Silencing MTA1 by RNAi Reverses Adhesion, Migration and Invasiveness of Cervical Cancer Cells (SiHa) via Altered Expression of p53, and E-cadherin/β-catenin Complex
RAO YUMEI ; WANG HONGYAN ; FAN LIANGSHENG ; CHEN GANG
Journal of Huazhong University of Science and Technology (Medical Sciences) 2011;31(1):1-9
It has been reported that metastasis-associated gene 1 (Mtal) is overexpressed in many malignant tumors with high metastatic potential.In addition,some studies indicated that MTA1 participated in invasion,metastasis,and survival of cancer cells by regulating cell migration,adhesion and proliferation.But the role of MTA 1 is unclear in vitro in the development of cervical cancer cells.This study investigated whether and how MTA1 mediated cell proliferation,migration,invasion and adhesion in cervical cancer.MTA1 expression level was detected by Western blot in two cervical cancer cell lines of different invasion potentials.The effects of MTA1 expression on SiHa cell apoptosis,cycle,proliferation,migration,invasion and adhesion were tested by flow cytometry,MTT,wound-healing assay,Transwell assay and adhesion assay,respectively.The expression levels of p53,E-cadherin,and β-catenin activity were evaluated in untreated and treated cells.The results showed that MTA1 protein expression was significantly higher in SiHa than in HeLa,which was correlated well with the potential of migration and invasion in both cell lines.Furthermore,the cell invasion,migration and adhesion capabilities were decreased after inhibition of MTA1 expression mediated by Mtal-siRNA transfection in SiHa.However,no significant differences were found in cell apoptosis,cycle,and proliferation.In addition,E-cadherin and p53 protein levels were significantly up-regulated,while β-catenin was significantly down-regulated in SiHa transfected with the siRNA.These results demonstrated that MTA1 played an important role in the migration and invasion of cervical cancer cells.It was speculated that the decreased migration and invasion capability by inhibiting the MTA1 expression in the SiHa cell line may be mediated through the altered expression of p53,and E-cadherin/β-catenin complex.MTA1 could serve as a potential therapeutic target in cervical cancer.
10.Adjuvant chemotherapy versus adjuvant concurrent chemoradiotherapy after radical surgery for early-stage cervical cancer: a randomized, non-inferiority, multicenter trial.
Danhui WENG ; Huihua XIONG ; Changkun ZHU ; Xiaoyun WAN ; Yaxia CHEN ; Xinyu WANG ; Youzhong ZHANG ; Jie JIANG ; Xi ZHANG ; Qinglei GAO ; Gang CHEN ; Hui XING ; Changyu WANG ; Kezhen LI ; Yaheng CHEN ; Yuyan MAO ; Dongxiao HU ; Zimin PAN ; Qingqin CHEN ; Baoxia CUI ; Kun SONG ; Cunjian YI ; Guangcai PENG ; Xiaobing HAN ; Ruifang AN ; Liangsheng FAN ; Wei WANG ; Tingchuan XIONG ; Yile CHEN ; Zhenzi TANG ; Lin LI ; Xingsheng YANG ; Xiaodong CHENG ; Weiguo LU ; Hui WANG ; Beihua KONG ; Xing XIE ; Ding MA
Frontiers of Medicine 2023;17(1):93-104
We conducted a prospective study to assess the non-inferiority of adjuvant chemotherapy alone versus adjuvant concurrent chemoradiotherapy (CCRT) as an alternative strategy for patients with early-stage (FIGO 2009 stage IB-IIA) cervical cancer having risk factors after surgery. The condition was assessed in terms of prognosis, adverse effects, and quality of life. This randomized trial involved nine centers across China. Eligible patients were randomized to receive adjuvant chemotherapy or CCRT after surgery. The primary end-point was progression-free survival (PFS). From December 2012 to December 2014, 337 patients were subjected to randomization. Final analysis included 329 patients, including 165 in the adjuvant chemotherapy group and 164 in the adjuvant CCRT group. The median follow-up was 72.1 months. The three-year PFS rates were both 91.9%, and the five-year OS was 90.6% versus 90.0% in adjuvant chemotherapy and CCRT groups, respectively. No significant differences were observed in the PFS or OS between groups. The adjusted HR for PFS was 0.854 (95% confidence interval 0.415-1.757; P = 0.667) favoring adjuvant chemotherapy, excluding the predefined non-inferiority boundary of 1.9. The chemotherapy group showed a tendency toward good quality of life. In comparison with post-operative adjuvant CCRT, adjuvant chemotherapy treatment showed non-inferior efficacy in patients with early-stage cervical cancer having pathological risk factors. Adjuvant chemotherapy alone is a favorable alternative post-operative treatment.
Female
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Humans
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Uterine Cervical Neoplasms/drug therapy*
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Prospective Studies
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Quality of Life
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Neoplasm Staging
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Chemoradiotherapy
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Chemotherapy, Adjuvant/adverse effects*
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Adjuvants, Immunologic
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Antineoplastic Combined Chemotherapy Protocols/therapeutic use*
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Retrospective Studies