1.Research advances in diagnosis and treatment of hepatocellular carcinoma complicated by arterioportal shunt
Journal of Clinical Hepatology 2017;33(2):364-368
Hepatocellular carcinoma (HCC) complicated by arterioportal shunt (APS) is commonly seen in clinical practice,with an incidence rate of 28.8%-63.2%.It is manifested as abdominal pain,diarrhea,and ascites and can also lead to serious complications of portal hypertension including gastrointestinal bleeding.Although there are various therapeutic methods,they tend to have poor clinical effects.APS is one of the most important causes of death in patients with HCC.This article introduces the etiology,typing,clinical manifestation,and therapies of HCC complicated by APS and points out that although there are various therapeutic methods for HCC complicated by APS,interventional treatment remains the most important method.The exploration of interventional treatment helps to improve patients' prognosis.
2.Effects and mechanism of UBC9 in liver fibrosis
The Journal of Practical Medicine 2017;33(13):2079-2082
Objective To investigate the roles of ubiquitin-conjugating enzyme(UBC9)in HSCs activa-tion and liver fibrosis. Methods Western blot was used to analyze the expression of UBC9 under the stimulus of different concentrations of TGF-β1. The effective shRNA-targeting UBC9 gene was synthesized and HCSs were in-stantaneously transfected using lipofectamine method. Non-specific shRNA-transfected group cells and shRNA-tar-geting UBC9-transfected group cells were set up. The mRNA and protein levels of UBC9 were determined with Quantitative Real-Time PCR and Western blot. Western blot also used to examine the expression level of collagenⅠ,α-SMA and P-smad3 after transfection of UBC9 shRNA into HCSs and CCK-8 assay was used to detect cell proliferative capacity after transfection. Results UBC9 expression was significantly up-regulated in TGF-β1-treat-ed HSCs. Knockdown of UBC9 significantly inhibited TGF-β1-induced HSCs proliferation,as well as decreased the expression levels of a-SMA and collagen I. Furthermore ,knockdown of UBC9 attenuated the phosphorylation of Smad3 in the presence of TGF-β1. Conclusions UBC9 may function as a novel regulator to modulate HSC activa-tion,potentially by inhibiting the TGF-β1/Smad3 signaling pathway,which reveals novel mechanistic insights into the anti-fibrotic effect of UBC9.
3.Effect of SUMOylation on maintenance of telomere
Chinese Journal of Pathophysiology 2000;0(10):-
Telomeres are the unique structure at the end of chromosomes,which pose two special challenges for the cellular DNA replication and repair machinery.Because of the inability of lagging strand synthesis to fully replicate a linear template,the chromosome ends is progressively shortening at each replication cycle.The tandem DNA repeats must maintain enough length to allow the cell dividing and mitosing,otherwise the cells would lose the dividing ability and undergo replicative senescence.There are two special pathways to regulate telomere length,which consist of telomerase and alternative lengthening of telomeres(ALT).SUMO is an evolutionarily conserved protein,which is covalently attached to target proteins and alters their conformation,stability,interaction and localization.Currently,a lot of proteins have been proved to be the substrates of SUMOylation.A growing body of evidence implicate that SUMOylation plays a very important role to elongate telomeres in both telomerase and ALT.The Rad5 and Rad52,as well as BLM have been showed either to be modified by SUMO or to interact with SUMO.SUMOylation positively modifies the activity of telomere.
4.Research progress in FTO gene and obesity
Zhihua XIAO ; Wuhua GUO ; Jixiang ZHANG
Chinese Journal of Pathophysiology 1989;0(05):-
Obesity is a rapidly growing international health problem. The association of fat mass and obesity associated(FTO) gene and obesity is becoming the hot topic in the gene research. FTO is a member of the nonheme dioxygenase [Fe(Ⅱ) and 2-oxoglutarate-dependent dioxygenases]superfamily. FTO levels in the brain,especially in the hypothalamus,participate in the central control of food intake. The mutation of FTO gene accentuates body mass index,hip circumference and total weight,leading to obesity.
5.The Growth Inhibition Induced by SUMO-1 siRNA in Hepatocellular Carcinoma Cell Line SMMC-7721
Wuhua GUO ; Lihua YUAN ; Zhihua XIAO ; Liangping LUO ; Jixiang ZHANG
Tianjin Medical Journal 2010;38(1):4-6,后插1
Objective: To study the efficiency of silencing small ubiquitin-like modifier-1(SUMO-1) induced by siRNA in hepatocellular carcinoma cell line SMMC-7721 and the growth inhibition of SMMC-7721 thereof. Methods: The SUMO-1 siRNA was transfected into SMMC-7721 by means of lipofectamine~(TM) 2000. The silencing efficiency of SUMO-1 was examined by RT-PCR and western blot. The cell growth and cell cycle were examined by MTT and flow cytometry(FCM). The cell apoptosis was detected by DeadEnd~(TM) Colorimetric TUNEL System. Results: The siRNA could significantly silence the expression of SUMO-1 in SMMC-7721.The maximal silencing rate was utmost 73.43% at 48 hours after being transfected SUMO-1 siRNA. MTT assay revealed that the cell line grew more slowly. FCM result showed that the number of G_2 stage cells was increased significantly. But apoptosis cells were not found by TUNNEL assay. Conclusion: SiRNA is a good manner to silence the expression of SUMO-1 in SMMC-7721 in vitro. Owing to the growth inhibition induced by SUMO-1 siRNA, SUMO-1 plays an important role in development of SMMC-7721.
6.Expression of GTPBP4 in hepatocelluar carcinoma (HCC) tissues and preliminary study on the functions of the GTPBP4 gene
Maosheng LIU ; Yan ZHENG ; Shuimei WU ; Tengzheng LI ; Sisi ZHONG ; Wuhua GUO ; Zhengyuan XIE
Chinese Journal of Clinical Oncology 2016;43(24):1083-1087
Objective:To investigate the protein expression of GTPBP4 in human hepatocelluar carcinoma (HCC) tissues and the influ-ence of GTPBP4 silencing by siRNA on the proliferation and cell cycle of HCC cell line Hep G2. Methods:Western blot analysis was per-formed to observe the protein expression of GTPBP4 in 24 cases of HCC tissues compared with their adjacent noncancerous liver tis-sues. Lentivirus-mediated RNA interference (RNAi) was used to silence GTPBP4 expression in Hep G2, and the infection efficiency was observed under a fluorescence microscope. The silencing effect was tested by Western blot and real-time PCR. After silencing the GT-PBP4 gene, cell proliferation was detected using CCK-8 assay, and the cell cycle was observed using flow cytometry. Results:(1) GT-PBP4 was overexpressed in 21 cases (87.5%) of HCC tissues (P<0.000 1). (2) After the lentivirus with GFP reporter infected the Hep G2 cells, 90%of the cells showed green fluorescence. LV-GTPBP4-RNAi effectively inhibited the expression of GTPBP4 at both mRNA (70%) and protein (67%) levels. (3) The proliferation ability of the LV-GTPBP4-RNAi group significantly decreased after 96 h (inhibition rate:54.51%). Flow cytometry showed that the LV-GTPBP4-RNAi group significantly increased at the G0/G1 phase, whereas the S phase de-creased and arrested at the G0/G1 phase. Conclusion:GTPBP4 overexpression in HCC tissues was associated with hepatocarcinogenesis and promoted tumor cell proliferation, but the specific molecular mechanisms remain to be investigated.
7.Superior rectal artery chemoembolization for rectal cancer associated with hepatic metastasis:preliminary results in 17 patients
Fangtian ZUO ; Qing SHI ; Tiantian XU ; Sufen FANG ; Yang YANG ; Wuhua GUO
Journal of Interventional Radiology 2017;26(10):912-914
Objective To discuss the safety and curative effect of superior rectal artery chemoembolization in treating rectal cancer complicated by hepatic metastasis.Methods A total of 17 patients with rectal cancer complicated by hepatic metastases were treated with hepatic arterial chemoembolization together with subsequent superior rectal artery chemoembolization.Super-selective catheterization of superior rectal artery with a 3-F microcatheter was performed first,which was followed by perfusion of 5-Fu and oxaliplatin through the microcatheter,and then irinotecan and Lipiodol emulsion was injected.Results Technical success was obtained in all 17 patients.In 2-7 days after the treatment,the amount of faeces containing mucus,blood and pus was significantly increased,besides,obvious necrotic tissues could be observed in the faeces in some patients.Among the 3 patients who had complained of abdominal pain,the pain disappeared in 3 days (n=2) or in 5 days (n=1) after the treatment.One week after the treatment,anal pain disappeared in 5 patients and was remarkably improved in 2 patients;tenesmus feeling was significantly relieved in 7 patients although the improvement of tenesmus feeling was not obvious in other 4 patients.During the long period following-up,no intestinal perforation or local infection was observed.Conclusion For the treatment of rectal cancer associated with hepatic metastasis,superior rectal artery chemoembolization is safe and effective.It can quickly cause rectal tumor necrosis,which is an important therapeutic response in treating rectal cancer with comprehensive therapy.
8.Clinical progress of noninvasive assessment of portal vein pressure using doppler ultrasound
China Modern Doctor 2015;(12):154-156,160
Portal hypertension (PHT) is a common clinical syndrome, the measurement methods of portal vein pressure mainly include two types: direct and indirect measurement methods. Direct methods including classic portal vein catheter technique, direct puncturing portal venous in the abdominal operation, ultrasound guided percutaneous tran-shepatic portal catheterization, etc. Indirect methods including color ultrasonic doppler observations in the portal hemo-dynamic changes, rectal vein-portal vein radionuclide imaging method, magnetic resonance angiography, spiral CT por-tal vein imaging (SCTP), etc. All kinds of invasive operations are not clinical routine, and ultrasound has been widely used in clinical, this article focuses on present situation and progress of ultrasonic noninvasive assessment of PHT.
9.Clinicial efficacy and prognosis of bevacizumab combined with chemotherapy in retreated advanced non-squamous non-small cell lung cancer
Hong TAO ; Lili GUO ; Hongbo WU ; Wei WU ; Wuhua WEI ; Li TONG ; Hongxia LI ; Zhe LIU
Chinese Journal of Clinical Oncology 2018;45(10):503-507
Objective:To investigate the efficacy and safety of bevacizumab combined with chemotherapy in patients with retreated advanced non-squamous non-small cell lung cancer (NSNSCLC) and analyze its prognostic factors. Methods:Forty-one patients with previously treated advanced NSNSCLC in Beijing Chest Hospital from February 2013 to June 2017 were recruited. Clinical data of the patients were retrospectively analyzed. There were 38 cases of adenocarcinoma and 3 cases of other pathological types. Bevacizumab combined with chemotherapy served as second-line treatment for 19 patients, and it served as beyond second-line therapy for 22 pa-tients. Eighteen patients harbored epidermal growth factor receptor (EGFR) gene mutations, while the other 23 patients harbored wild-type EGFR gene. The efficacy and safety of bevacizumab combined with chemotherapy were evaluated. To evaluate the prognos-tic factors, single and multiple factor analyses were conducted. Results:All patients received bevacizumab combined with chemothera-py and could be evaluated for response. The mean number of cycles of chemotherapy and chemotherapy combined with bevacizumab were 3.1 and 5.0, respectively. The objective response rate (ORR) of all recruited patients was 12.2%. The disease control rate (DCR) was 82.9%. Regarding the effect of second-line and beyond second-line therapy in patients, data were similar. The ORRs were 10.5%and 13.6%, respectively (P=0.572), and DCRs were 89.5%and 77.3%, respectively, without significantly statistical difference (P=0.271). The median progression-free survival (PFS) and overall survival (OS) were 4.6 months [95%confidence interval (CI) 3.619-5.581] and 11.9 months (95%CI 9.797-14.003), respectively. In the single factor analysis, patients with EGFR mutations, those who received>4 cy-cles of bevacizumab administration, and women had longer OS (χ2=19.673, P=0.000;χ2=6.820, P=0.009;andχ2=6.374, P=0.012;respec-tively). The Cox regression analysis showed that EGFR mutation status and number of cycles of bevacizumab administration were inde-pendent prognostic factors [hazard ratio (HR)=0.129, P=0.001 and HR=0.336, P=0.012;respectively]. The common adverse reactions in-clude bone marrow suppression, bleeding, hypertension, and proteinuria. Most of them were grade 1-2. Conclusions:Bevacizumab combined with chemotherapy provides good efficacy and controllable safety in patients with retreated advanced NSNSCLC. Patients with EGFR mutations and>4 cycles of bevacizumab administration have superior prognosis.