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Enhancer of zeste homolog 2 (EZH2) is a catalytic subunit of polycomb repressive complex 2 (PRC2). It acts as a histone methylation transferase and plays a key role in oncogenesis, development, metastasis, and drug tolerance. Studies have found that the expression of EZH2 is regulated by a variety of carcinogenic transcription factors, anti-cancer microRNA, tumor-related non-coding RNA and post-translational modifications. Moreover, the effect of EZH2 in silencing target genes is mainly through trimethylation of histone H3 at lysine 27 (H3K27me3). This article summarizes the main regulatory roles and functions of EZH2 in tumorigenesis, and reviews the progress of target therapies based on EZH2.
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We studied the effect of celastrol on the proliferation and apoptosis of adult T-cell leukemia (ATL) cells. After treating adult T-cell leukemia cell lines with different concentrations of celastrol, we analyzed the cell proliferation by MTT and colony formation assays. Flow cytometry was conducted to detect cell apoptosis by Annexin V-FITC/PI staining. Western blotting and dual-luciferase reporter assay were done to study the mechanism how celastrol suppressed the growth of adult T-cell leukemia cells. Celastrol could significantly inhibit the proliferation of adult T-cell leukemia cells, and induce apoptosis of ATL cells. With the increase of the concentration of celastrol, the ratio of Bax/Bcl-2 protein was up-regulated. The Caspase-3/7 protein was cleaved and activated after treatment with celastrol. Moreover, the expression of HTLV-1-encoded viral protein Tax was significantly inhibited in the celastrol treated cells. Taken together, these results indicated that celastrol effectively inhibited the proliferation of adult T-cell leukemia cells by regulating the expression of Bcl-2 family protein, and induced cell apoptosis by activating Caspase dependent pathway. In addition, celastrol could inhibit the expression of viral protein Tax. This study will provide an experimental basis for the clinical application of celastrol in the treatment of adult T-cell leukemia.
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Objective To explore the role of Yes-associated protein 1 (YAP1) in the proliferation,cell cycle,migration and invasion of human non-small cell lung cancer (NSCLC) cells.Methods A lenti-siRNA targeting YAP1 (si-YAP1) was used to inhibit the expression of YAP1 gene of human NSCLC cell line A549 cells.CCK-8 assay and flow cytometry were used to determine the effects of silencing of YAP1 expression on A549 cells proliferation and cell cycle,respectively;Transwell assay was used to observe the effect of silencing of YAP1 expression on A549 cell migration and invasion.Results After infection with si-YAP1,the expressions of YAP1 mRNA and protein in A549 cells were significantly down-regulated (P<0.01).YAP1 silencing significantly inhibited A549 cell proliferation,increased the percentage of cells in G0/G1 phase (P<0.01),and significantly decreased the migration and invasion of A549 cells (P<0.01).Conclusion YAP1 silencing can inhibit malignant biological characteristics of NSCLC,which suggests that YAP 1 gene may serve as an important target in the gene therapy of lung cancer.
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Objective To investigate the outcome of a new designed extramedullary femoral osteotomy module and to compare with conventional intramedullary system in clinical study.Methods The extramedullary femoral osteotomy module was designed with the extramedullary alignment rod connecting with the T type rod at right angle,and it had a 5°-7° adjustable valgus design.The positioning module fixation screw was parallel with the epicondylar axis.The coronal plane of the distal femur bone cut was orientated by the extramedullary alignment rod pointing to the inguinal midpoint,and the sagittal plane was orientated by the extramedullary alignment rod keeping parallel with the distal femoral medullary cavity.The terminal distal femoral bone cut was conducted with suitable osteotomy after the orientation.Sixty patients who underwent unilateral total knee arthroplasty (TKA) from October 2015 to March 2016 were randomly divided into intramedullary and extramedullary group for prospective controlled study.Blood loss,drainage and the incidence of deep vein thrombosis (DVT) were evaluated at one week postoperatively.Knee valgus angle and femoral prosthesis flexion angle were analyzed at two weeks postoperatively.Moreover,the extramedullary femoral osteotomy module was used in 273 patients (78 males and 195 females) with an average age of 68.7 (range,57-82 years old) who underwent unilateral TKA from April 2016 to January 2017.Blood loss,operation duration and lower limb ultrasonography preoperatively and at one week postoperatively were recorded.Knee valgus angle and femoral prosthesis flexion angle were measured at 2 weeks postoperatively.Range of knee motion and Hospital for Special Surgery (HSS) knee score at six weeks postoperatively were also reported.Results In the randomized controlled trial,blood loss and drainage in extramedullary group was less than that in intramedullary group (t=-3.330,P=0.004).There was no significant difference in the incidence of DVT at 1 week postoperatively (x2=2.269,P=0.132) and the knee valgus angle and femoral prosthesis flexion angle at 2 weeks postoperatively within the two groups.In the clinical application,operation time was 60.13± 13.69 min,and blood loss and drainage was 109.11±70.73 ml.There were four cases of popliteal vein thrombosis,nine cases of posterior tibial vein thrombosis,and seventeen cases of muscular venous thrombosis at one week postoperatively.The incidence rate of DVT was 11.0%.There was no symptomatic pulmonary embolism at three months postoperatively.Knee valgus angle was 7.34°±0.69°,and 211 knees accounting for 77.3% were in the range of ±3° error.Femoral prosthesis flexion angle was 6.43°±1.59°,and 273 knees were all in the range of ±10° error.Range of knee motion improved from 54.52±5.96 preoperative to 86.20±4.92 at six weeks postoperative.HSS knee score improved from 100.88°±7.51° preoperative to 110.42°±7.08° at six weeks postoperative.Conclusion The new designed extramedullary femoral osteotomy module used in distal femoral osteotomy during TKA can significantly reduce the risk of bleeding and the incidence rate of DVT postoperatively.Furthermore,patients can obtain as excellent prosthesis position and limb alignment as conventional intramedullary system.
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Objective To explore the characteristics of gait and surface electromyography (sEMG) of underwater treadmill training (UWTT). Methods From January to September, 2015, gait and sEMG parameters of ten healthy adults were synchronously collected using three-dimensional gait analysis system and sEMG systems on land and UWTT. Results When walking in self comfortable speed, compared with walk on land, there was significant increase in gait cycle (t=-11.411, P0.05). The integral electromyography of biceps femoris, gastrocnemius, tibialis anterior muscle were significant less than iEMG on land (t>3.984, P0.05). Conclusion There are signifi-cant differences in gait and muscle contraction intensity between land walking and UWTT. The dynamic physiology and neural control of UWTT need further study.
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Human T-cell leukemia virus type 1 (HTLV-1) is a retrovirus demonstrated to be associated with human disease. Infection by the HTLV-1 can cause T-cell leukemia (ATL) in adults. HTLV-1 bZIP factor (HBZ) is a viral protein encoded by the minus strand of the HTLV-1 provirus. Among the regulatory and accessory genes of HTLV-1, HBZ is the only gene that remains intact and which is expressed consistently in all patients with ATL. Moreover, HBZ has a critical role in the leukemogenesis of ATL. Here, we review the function of HBZ in the oncogenesis of HTLV-1 and its molecular mechanism of action.
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Animais , Humanos , Fatores de Transcrição de Zíper de Leucina Básica , Genética , Metabolismo , Carcinogênese , Infecções por HTLV-I , Patologia , Virologia , Vírus Linfotrópico T Tipo 1 Humano , Genética , Metabolismo , Leucemia de Células T , Patologia , Virologia , Proteínas dos Retroviridae , Genética , MetabolismoRESUMO
Chemotherapy as a routine method for clinical treatment of cancer has disadvantages such as significant toxicity and strong resistance. In order to improve the efficacy of the drugs and reduce the by-effects, we tried to combine static magnetic field (SMF) with cisplatin or adriamycin. The growth of Hepa1-6 cells treated with the static magnetic field (SMF) combined with cisplatin or adriamycin was significantly inhibited, as detected with MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide) test. Combined treatment group cells underwent significant morphological changes as observed by HE (Hematoxylin and eosin) staining under optical microscope. Cell cycle analysis indicated that SMF increased the ratio of cells arrested in G2/M phase caused by cisplatin, and when treated with SMF combined with adriamycin, cells were almost arrested in G1 and G2/M phase. SCGE test showed that SMF can enhance the ability of cisplatin or adriamycin to promote cell DNA damage. Atomic force microscope observation found that the combination of antitumor drugs and magnetic field treatment induced larger and deeper holes on the cell membrane, and surface structure damage is serious. The combination of antitumor drugs and magnetic field technology effectively inhibits the growth of tumor cells, and reduces drug doses. The results implicate this method as potential cancer therapy.
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Humanos , Antineoplásicos , Farmacologia , Ciclo Celular , Linhagem Celular Tumoral , Cisplatino , Farmacologia , Dano ao DNA , Doxorrubicina , Farmacologia , Campos MagnéticosRESUMO
Objective To evaluate ascending venography in the diagnosis of iliac vein compression syndrome.Methods From April 2011 to April 2013,we have had 556 patients with varicose veins suspected of Cockett syndrome.The degree of varicose veins by the International Union of Venous Clinical Classification (CEAP classification) was as following[1]:shallow varicose veins of lower limb (C2) in 190;varicose veins with limb swelling (C3) in 149 cases ; with body skin changes,such as pigmentation,eczema or lipid hard skin disease (C4) in 130; with healed ulcers (C5) in 17; with active ulcer(C6) in 70.Deep vein anterograde contrast and femoral venous cannula angiography were performed on 760 times.Results Iliac vein compression syndrome (Cockett) was detected by ascending venography in 154 patients,the diagnosis was established by following femoral venous cannula angiography.In the other 48 patients in whom Cockett syndrome was suspected by ascending venography,final diagnosis was reached by femoral venous cannula angiography.Altogether there were 202 iliac vein compression syndrome cases,with a positive rate 38.19% (202/529).The narrowness was larger than 50% in 173 cases.In 145 cases there were visible collateral vessels.Conclusions Deep vein ascending angiography is a useful screening method in the diagnosis and treatment of Cockett syndrome.
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Objective To explore the effect of lymph node metastases in gastric cancer on vagniae vasorum of gastric vessels,in order to provide evidence for the surgical treatment of gastric cancer.Methods The study included 90 specimens of left and right gastric arteries from 47 patients who underwent radical gastrectomy for carcinoma from January 2004 to 2006.All specimens were dealt with frozen section method,then they were stained with HE and immunohistochemical method respectively.Results Metastatic cancer cells were not found inside vagina vasorum in stage Ⅰ specimens.Cytokeratiu positive of tumor cens in or on vagina vasorum was showed on 25 slices from 10 tumors.Among them,2 slices from 1 tumor belonged to stage Ⅱ.8 slices from 3 tumors belonged to stage Ⅲ and 15 slices from 6 tumors belonged to stage Ⅳ.There was significant differences among cytokeratin positive rate in different stages of gastric cancer(P<0.01).Conclusion Vaginae vasorum dissection is recommended when clearing lymph node around arteries in radical gastrectomy for carcinomas in stage Ⅱ above.
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BACKGROUND:The majority of people do not believe that the femoral component flexion in total knee arthroplasty affect or affect little postoperative function and it is the only that the radiographic films is not satisfactory.So it has not caused people's enollgh attention.But the femoral component flexion affects the results of total knee arthroplasty obviously.OnJECTIVE:To investigate the curative effects of femoral component installed in the position of flexion during the operative procedure of total knee arthroplasty(123 knees)on the follow up results in 78 patients.DESIGN:Grouping contrast observation.SETTlNG:First Department of Bone and Joint,Wangjing Hospital of China Academy of Traditional Cllinese Medicine.PARTlCIPANTS:123 knees(78 patients)were given total knee arthroplasty in the First Department of Bone and Joint,Wangjing Hospital of China Academy of Traditional Chinese Medicine from October 2001 to June 2004.Seventeen(13.8%,15 patients)knees were found with femoral component flexion(FCF),in which there were 5 male cases and 10 female cases,aged from 47 to 81 years old.106(63 patients)knees were found without FCF,in which there were 22 male cases and 41 female cases,aged from 47 to 79 years old.METHODS:Total knee arthroplasties about their HSS rating scores,ranges of motion and flexion contractures werecompared in the two groups before operation and after operation,and the degrees of the FCF angle and the distances of femoral component flexion were measured.MAIN OUTCOME MEASURES:①Femoral Drostllesis flexion measurement;②HSS scores and activity:③femoral prosthesis flexion angle and distance buckling;④adverse events and side effects.RESULTS:Follow up lasted for one year above.①The degrees of flexion of femoral components were from 7°to 19°(average 11.3°)and the distance of flexion was from 2 mm to 4 mm(average 2.6 mln)in those 17 knees of total knee arthroplasty.②Differences in HSS rating scores and range of motion were not statistically significant(P>0.05)before operations between the group of femoral component flexion and the group of femoral component plane.However,after operations the above aspects in the group of femoral component flexion were less than that in the group of femoral component plane significantly(P=0.01,P<0.01),and were statistically significant(P=0.02,P<0.01)between post-operations and pre-operations in HSS rating scores and range of motion respectively in the two groups.③The statistic differences in cases and angles of flexion contractures of postperations between the group of femoral component flexion and the group of femoral component plane were significant(P<0.01),the situation in the group of femornl component flexion were more bad than that in the group of femoral component plane,but were all improved significantly in cases and angles of flexion contractures after operations in the two groups(P<0.05,P<0.01).④There was one case with the right deep venous thrombosis and one case with myositis ossifican in non-FCF group,and there was one case in FCF group with impingement sign between patellar and component.CONCLUSION:The findings show that femoral component flexion will increase the incidence of knee flexion contracture and result in knee extension dysfunction after total knee arthroplasty surgery.
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Objective:To study the relationshop between cell adhesion molecules CD 62 P expression and biological behavior of rectal cancer.Methods:The levels of CD 62 P expression was observed in 40 cases of rectal cancer using SP immunohistochemistry staining.Rusults:The rate of CD 62 P expression was 65%(26/40) in rectal cancer.CD 62 P expression was more intensive in rectal cancer with infiltrated serosa and lymph node metastasis ( P
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Objective To examine the expression of p16 protein in malignant tumor of bile duct and itsrelationship with tumor behavior. Methods pl6 protein was studied by immunohistochemical method.Results The positive expression rate of MTS,/p16 in malignant tumor was lower than that in benign ones,and had close correlationship with the invasiveness and lymph nodes metastasis (P0.01 ). Conclusion The investigation of MTS1/p16 is of .great importance in evaluating the invasiveness of tumor, meta-potential of lymph node and clinicalprognosis.
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Objective: To explore the application experiences and effects of emergency damage contro(lDC)treatment for severe abdomen trauma. Methods: The clinical data of 192 patients with severe abdomen trauma were selected as the object of this study. A retrospective analysis was done on therapy condition and effects of emergency damage control treatments. Results: Pre-hospital emergency care was performed in all 192 patients, damage control operations (DCO)were done in 186 cases, 184 cases entered surgical intensive care unit (SICU)for resuscitation, and 177 cases were adopted corresponding reoperations after SICU resuscitation. The abnomal DCO indices recovered gradually in the 72 hours after DCO. The cure rate was 90.7% with 174 cases, and the incidence of complication was as low as 2.3% with 4 cases after reoperations, and the 4 cases all healed by conservative treatments. Mortality rate was 6.2% with 12 cases, and it caused by associated organs injuries, severe primary disease and secondary infection of other organs. Conclusion: Emergency damage control treatment modus should be chosen positively and eligibly under indication to severe abdomen trauma patients. According to the difference of location and degree of injury, eligible therapies by stages are the key managements.
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Objectives:In order to study the immune function after postoperative parenteral nutrition enriched with arginine in patients with gastrointestinal carcinoma. Methods:Forty patients who underwent radical operation of gastrointestinal carcinoma were randomly divided into experimental group( n= 20),in which patients received TPN enriched with arginine,and control group (TPN, n =20).At day 1 before operation,day 1 and day 8 after operation,IgG,IgA,IgM,T cell subgroups.NK cell activity and IL 2 were dectected. Results:The immune function of patients with gastrointestinal carcinoma was depressed at different levels.At day 1 after operation,IgG,IgM,IgA,CD4 +,CD4 +/CD8 +,Nk cell activity and IL 2 decreased more significantly than those before operation.The immunefunction recovered rapidly and exceeded the level before preoperation in experimental group.The difference was significant( P
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Objective: To investigate the inhibitory effect of survivin antisense oligonucleotide (ASODN) on the expression of survivin gene and proliferation of human hepatocellular carcinoma cell line SMMC-7721. Methods: The 20 mer antisense oligonucleotide (ASODN) targeted to the promoter region of survivin mRNA was designed and synthesized. The expression of survivin gene in hepatocellular carcinoma cell line SMMC-7721 was blocked by means of ASODN transfection mediated by DOTAP liposomal reagent. The changes of survivin protein and mRNA expression after transfection were as-sessd by Western blot and in situ hybridization, respectively. The apoptotic rate was detected by flow cytometer. The changes of cell adherent rate, cell growth activity, and the inhibitory rate of cell growth were also studied. Results: The expression of survivin protein and mRNA were decreased markedly after survivin ASODN transfection. Meanwhile, the cell adherent rate also decreased markedly while the apoptotic rate increased markedly. Conclusions: Transfection of ASODN targeted to the promotor region of survivin mRNA by DOTAP liposomal transfection reagent could down-regulated the expression of survivin protein and mRNA significantly in 7721 cell line and inhibit the proliferation of cancer cells. Survivin could be an important target in the therapy of hepatocellular carcinoma.