Objective To identify G?quadruplex structures in the promoter region of MET. Methods CD spectroscopy,UV spectroscopy,non?denatured electrophoresis and PCR stop assay were applied to indicate the G?quadruplex structure and its function. Results The Pu23WT se?quence in the promoter of MET adopted an intramolecular parallel G?quadruplex structure under physiological conditions in vitro,which can stop the extension of Pmet. Conclusion G?quadruplex structure in the promoter might inhibit MET gene expression in vivo.

Objective To compare clinical efficacy and complications of three operation methods for treating the localized and high risk prostate cancer.Methods From July 2006 to July 2010,102 cases with localized and high risk prostate cancer were included in the study.Among them,51 cases received open radical prostatectomy (Group A).Their characters included aged (63.7±7.9),PSA (31.8±6.6) μg/L,Gleason scores (8.5±0.5).In this group,T2c stage was diagnosed in 38 cases and T3a stage in 13 cases.32 cases received laparoscopic radical prostatectomy(Group B).Their characters included aged (64.4± 8.3),PSA (29.9±5.2) μg/L,Glcason scores (8.7±0.4).In this group,T2c stage was diagnosed in 21 cases and T3a stage in 11 cases.19 cases received 125I implantation (Group C).Their characters included aged (61.4± 7.4),PSA (30.6±.5.7)μg/L,Gleason scores (8.6±0.6).T2v stage was found in 8 cases and T3a stage in 11 cases.Operation time,amount of bleeding,hospitalization time,drainage time,gastrointestinal function recovery time,medical expenses and survival and recurrence rate in 1 year,3 years,5 years were compared within those groups.Results Operation time in three group were (232.6±38.4) min,(186.3±31.4) min,(35.4±14.6) min,respectively.Amount of bleeding in three group were (413.6±132.4) ml,(273.9± 77.4) ml,(19.4±4.4) ml,respectively.Hospitalization time in three group were (20.9±3.7) d,(15.6± 2.2) d,(6.4±2.6) d respectively.Drainage time in three group were (8.3±1.8) d,(7.5±0.9) d,(3.2± 0.8) d,respectively.Gastrointestinal function recovery time in three group were (4.1 ±0.6) d,(3.2± 0.4) d,(0.4±0.1) d,respectively.Medical expenses in three group were (23±4) thousand yuan,(32±3) thousand yuan,(45t3) thousand yuan respectively.All those items exhibited the significantly statistical difference (P＜0.05).The survival and recurrence rates had no significant difference during the follow-up in three groups.Conciusions Compared to the open radical prostectomy and laparoscopic radical prostectomy,particle implantation for prostate cancer had advantages in minimally invasive,less bleeding,short operation time,fast recovery and protection for Intestinal function.

Objective To detect the infection of human papillomavirus (HPV)in patients with non-small cell lung cancer (NSCLC)and explore the relationship between HPV infection and clinicopathological features.Methods HPV detection and genotyping in 156 cases of NSCLC were performed using a new liquid chip based on Luminex.Patient clinical characteristics were also recorded,and the relationship between HPV infection and clinicopathological features was studied.Results Of the 156 tumor-DNA samples tested,40 (25.6%)cases showed presence of HPV-DNA,of which 37 cases were of a high-risk HPV type (16,18,33, 58).The differences were statistically significant between the HPV-positive and HPV-negative groups in gender (χ2 =4.387,P =0.036),smoking (χ2 =8.130,P =0.004),histologic type (χ2 =4.075,P =0.044)and lymph node metastasis (χ2 =7.082,P =0.008).The differences were not statistically significant between the HPV-positive and HPV-negative groups in age (χ2 =0.013,P =0.910),differentiated degree (χ2 =1.727, P =0.189),clinical stages (χ2 =0.179,P =0.672),distant metastasis (χ2 =3.012,P =0.083).Logistic regression analysis revealed that lymph node metastasis alone was an independent predictive factor of HPV infection in NSCLC (OR =0.384,95%CI:0.153-0.967,P =0.042),and gender (OR =1.402,95%CI:0.522-3.769,P =0.503),smoking (OR =0.506,95%CI:0.194-1.322,P =0.506),histologic type (OR =0.393,95%CI:0.133-0.161,P =0.091)were not independent predictive factors of HPV infection. Conclusion The infection of HPV presents in part of Chinese NSCLC patients,and HPV infection may be connected with occurrence and development of lung cancer.

Objective To evaluate thedifferential diagnosis of specially cystic masses located at the area of the left adrenal gland,and to improve the understanding of the clinical symptoms and pathological features,diagnosis and treatment of gastric duplicated cyst.Methods A retrospective study,with literature review,of clinical characteristics and imaging findings of pathologically proved gastric duplicated cyst in 2 adults (2 males,28 years and 42 years)was conducted.Two patients presented no clinical manifestation.Abdominal ultrasonography and CT scan revealed a cystic lesion,in the area of the left adrenal gland,with a thickness wall,measuring 5 cm ×6 cm× 7 cm and 8 cm × 12 cm × 13 cm,attached to the greater curvature of the stomach.The lesion had septums,and the walls and septums could not be enhanced.Preoperative diagnosis of patients was misdiagnosed as a cyst of the left adrenal gland,with inflection or bleeding.Results Complete excision was performed by laparoscopic surgery in all cases.The lesion located in the area of left adrenal gland and no communication between the duplicated cyst and the lumen of stomach was detected.Postoperatively,the lesions were pathologically proved to be gastric duplicated cyst.There was no recurrence during the follow-up of 8 months and 2 years.Conclusions Preoperative definite diagnosis of adult gastric duplication cyst is very difficult.Ultrasonography and Computed Tomography are valuable imaging modality for locating the site and determining the nature of adult gastric duplicated cyst.Preoperative definite diagnosis could be made by EUS (endoscopic ultrasonography) and EUS-guided fine needle aspiration biopsy in gastric duplicated cyst.Although adult gastric duplicated cyst is an extremely rare disease entity,but this unusual developmental abnormality should be include in the differential diagnosis of cystic masses located the area of the left adrenal gland.Because of the possibility of malignancy of the cyst,laparoscopic excision is the first choice as the minimally invasive treatment.

Objective To discuss the diagnosis,therapy and prognosis of primary ureter transitional cell carcinoma with low stage and grade.Methods Retrospective review of 18 cases surgery to treat the primary ureter carcinoma of G1-2 Ta-2 was carried out.There were 12 males and 6 females with the mean age of 67 years.Of the 18 cases with the size of tumor were from 0.5 to 1.5 cm.13 cases had the tumors on the left and 5 cases on the right.The tumors were located at middle parts of the ureter in 3 cases,and at the lower part in 15 cases.The course of the disease was from 5 days to 3 months.10 cases had gross hematuria and 8 cases renal hydronephrosis were found incidentally by B-ultrasound.B-ultrasound was performed in all cases.15 cases were indicated pyelic separation from 1.0-1.5 cm and ureteral separation from 0.8-1.0 cm.8 cases were indicated the low-echo space-occupying disease of ureter.IVU indicated mild hydronephrosis in 12 cases of 15 cases,of whom 5 cases were demonstrated a filling defect.CT indicated the mass of ureter in 10 cases of 15 cases.Cystoscope were performed in 18 cases,of whom 5 cases were found the tumor in the ureter-bladder cuff.Retrograde pyelogram showed filling defect of the diseased ureter in 10 of 11 cases(2 cases had failure of intubation).4 cases ureteroscopy with biopsy were used and demonstrated the diagnosis.Results 8 cases were treated surgically of radical nephroureterectomy with a bladder cuff excision.7 cases were performed ureteral segmental resection,of which 2 cases anastomosis and 5 cases ureterocystostomy with bladder cuff excision.3 cases tumors were resected by ureteroscopy postoperative pathological findings confirmed the diagnosis of transitional cell carcinoma.Pathological staging showed Ta(1 case);T1 (8),T2(9),and grading showed G1(8);G2(10).16 cases(88.9％)were followed up form 6-132 months.The overall 5-year survival rate was 87.5％.Of the 25％ patient showed bladder recurrence in post-operation 6-24 months.2 cases died of tumor recurrence and metastasis in post-operation 36-48 months.Conclusions The primary transitional cell carcinoma of ureter was uncommon and has poor prognosis.Ureter carcinoma with lower stage and grade might have better prognosis.Kidney-sparing surgery is a feasible treatment option in patients with lower stage and grade.The long-term follow up is meticulous.

Objective To investigate the effects of bedside blinding method of active indwelling of nasojejunal tube combined with the nasogastric tube gastrointestinal decompression for patients with severe stroke.Methods 50 patients with severe stroke were selected and divided into two groups by using random number tables,which are the observation group and the control group,with 25 cases in each group.The patients in the observation group were treated with bedside blinding method of active indwelling of nasojejunal tube combined with the nasogastric tube gastrointestinal decompression,while the patients in the control group simply received bedside indwelling of nasogastric tube.The enteral nutritional goal -rate of target feeding volume on the 7th day and the 14th day after admission and trace the incidence of gastric stasis,the reflux and aspiration,the aspiration pneumonia in the patients of the two groups within 14 days and the situation of the days of mechanical ventilation,the days in ICU and the 30 -day mortality of patients were compared in the two groups.Results The enteral nutritional goal -rate of target feeding volume on the 7th day and the 14th day in the observation group were superior to those of the control group[The goal -rate of target feeding volume on the 7th day:88% vs.64%,χ2 =3.947,P =0.047;the goal -rate of target feeding volume on the 14th day:80% vs.52%,χ2 =4.367,P =0.037].Meanwhile the incidence of gastric stasis,the reflux and aspiration,the aspiration pneumonia in the patients of the observation group within 14 days were significantly lower than those in the patients of the control group within 14 days[The gastric retention rate:8% vs.56%(14 /25 ),χ2 =10.784,P =0.001;the reflux rate:0% vs.24%(6 /25),χ2 =4.735,P =0.03;the aspiration rate:8% vs.32%,χ2 =4.500,P =0.034;the incidence of aspiration pneumonia:24% vs.68%,χ2 =9.742,P =0.002].The days of mechanical ventilation and the days in ICU of the patients in the observation group are far less than those of the patients in the control group[The days of mechanical ventilation:(11.16 ±4.86)d vs.(13.72 ±3.67)d,t =-2.101,P =0.041;the days in ICU:(15.36 ±5.66)d vs.(18.72 ±2.99)d,t =-2.625,P =0.012].While there was no significant difference between the two groups on the 30 -day mortality(24% vs.32%,χ2 =0.397,P =0.529).Conclusion The bedside blinding method of active indwelling of nasojejunal tube combined with the nasogastric tube gastrointestinal decompression can significantly improve the enteral nutritional goal -rate of target feeding volume for patients with severe stroke and greatly reduce the incidence of gastric stasis,the reflux and aspiration,the aspiration pneumonia,and limit the days of mechanical ventilation and the days in ICU.Accordingly,it has the value of popularization in the clinical application.

TNF-related apoptosis-inducing ligand (TRAIL) has been proposed as a promising cancer therapy that preferentially induces apoptosis in cancer cells, but not most normal tissues. However, many cancers are resistant to TRAIL by mechanisms that are poorly understood. In this study, we showed that tunicamycin, a naturally occurring antibiotic, was a potent enhancer of TRAIL-induced apoptosis through downregulation of survivin. The tunicamycin-mediated sensitization to TRAIL was efficiently reduced by forced expression of survivin, suggesting that the sensitization was mediated at least in part through inhibition of survivin expression. Tunicamycin also repressed expression of cyclin D1, a cell cycle regulator commonly overexpressed in thyroid carcinoma. Furthermore, silencing cyclin D1 by RNA interference reduced survivin expression and sensitized thyroid cancer cells to TRAIL; in contrast, forced expression of cyclin D1 attenuated tunicamycin-potentiated TRAIL-induced apoptosis via over-riding downregulation of survivin. Collectively, our results demonstrated that tunicamycin promoted TRAIL-induced apoptosis, at least in part, by inhibiting the expression of cyclin D1 and subsequent survivin. Of note, tunicamycin did not sensitize the differentiated thyroid epithelial cells to TRAIL-induced apoptosis. Thus, combined treatment with tunicamycin and TRAIL may offer an attractive strategy for safely treating resistant thyroid cancers.
Anti-Bacterial Agents/*pharmacology ; *Apoptosis ; Cell Line, Tumor ; Cyclin D1/*antagonists & inhibitors/metabolism ; *Down-Regulation ; Humans ; Microtubule-Associated Proteins/*genetics/metabolism ; TNF-Related Apoptosis-Inducing Ligand/*metabolism ; Tunicamycin/*pharmacology

TNF-related apoptosis-inducing ligand (TRAIL) has been proposed as a promising cancer therapy that preferentially induces apoptosis in cancer cells, but not most normal tissues. However, many cancers are resistant to TRAIL by mechanisms that are poorly understood. In this study, we showed that tunicamycin, a naturally occurring antibiotic, was a potent enhancer of TRAIL-induced apoptosis through downregulation of survivin. The tunicamycin-mediated sensitization to TRAIL was efficiently reduced by forced expression of survivin, suggesting that the sensitization was mediated at least in part through inhibition of survivin expression. Tunicamycin also repressed expression of cyclin D1, a cell cycle regulator commonly overexpressed in thyroid carcinoma. Furthermore, silencing cyclin D1 by RNA interference reduced survivin expression and sensitized thyroid cancer cells to TRAIL; in contrast, forced expression of cyclin D1 attenuated tunicamycin-potentiated TRAIL-induced apoptosis via over-riding downregulation of survivin. Collectively, our results demonstrated that tunicamycin promoted TRAIL-induced apoptosis, at least in part, by inhibiting the expression of cyclin D1 and subsequent survivin. Of note, tunicamycin did not sensitize the differentiated thyroid epithelial cells to TRAIL-induced apoptosis. Thus, combined treatment with tunicamycin and TRAIL may offer an attractive strategy for safely treating resistant thyroid cancers.
Anti-Bacterial Agents/*pharmacology ; *Apoptosis ; Cell Line, Tumor ; Cyclin D1/*antagonists & inhibitors/metabolism ; *Down-Regulation ; Humans ; Microtubule-Associated Proteins/*genetics/metabolism ; TNF-Related Apoptosis-Inducing Ligand/*metabolism ; Tunicamycin/*pharmacology

Glucosamine, a naturally occurring amino monosaccharide, has been reported to play a role in the regulation of apoptosis more than half century. However the effect of glucosamine on tumor cells and the involved molecular mechanisms have not been thoroughly investigated. Glucosamine enters the hexosamine biosynthetic pathway (HBP) downstream of the rate-limiting step catalyzed by the GFAT (glutamine:fluctose-6-phosphate amidotransferase), providing UDP-GlcNAc substrates for O-linked beta-N-acetylglucosamine (O-GlcNAc) protein modification. Considering that O-GlcNAc modification of proteasome subunits inhibits its activity, we examined whether glucosamine induces growth inhibition via affecting proteasomal activity. In the present study, we found glucosamine inhibited proteasomal activity and the proliferation of ALVA41 prostate cancer cells. The inhibition of proteasomal activity results in the accumulation of ubiquitinated proteins, followed by induction of apoptosis. In addition, we demonstrated that glucosamine downregulated proteasome activator PA28gamma and overexpression of PA28gamma rescued the proteasomal activity and growth inhibition mediated by glucosamine. We further demonstrated that inhibition of O-GlcNAc abrogated PA28gamma suppression induced by glucosamine. These findings suggest that glucosamine may inhibit growth of ALVA41 cancer cells through downregulation of PA28gamma and inhibition of proteasomal activity via O-GlcNAc modification.
Acetylglucosamine/chemistry/metabolism ; Alloxan/pharmacology ; Apoptosis/*drug effects ; Autoantigens/genetics/*metabolism ; Cell Line, Tumor ; Cell Proliferation/*drug effects ; Gene Expression Regulation, Neoplastic ; Glucosamine/*pharmacology ; Humans ; Male ; Phosphorylation ; Prostatic Neoplasms/*enzymology ; Proteasome Endopeptidase Complex/*antagonists & inhibitors/genetics/metabolism ; RNA, Small Interfering/genetics ; Ubiquitinated Proteins/metabolism

Objective:To investigate the effect of gap junction protein Cx43 inhibitor carbenoxolone (CBX) on cognitive function and its possible mechanism in epileptic rats.Methods:One hundred and twenty Wistar rats were randomly divided into sham-operated group, epilepsy group, epilepsy+solvent group, and epilepsy+CBX group ( n=30). The models of temporal lobe epilepsy in the later three groups were prepared by injection of kainic acid in the hippocampus. Intraperitoneal injection of CBX (20 mg/kg) or equal amount of normal saline were given to the rats in the epilepsy+CBX group and epilepsy+solvent group 30 min before modeling. Western blotting was used to detect the protein expressions of phosphorylated (p)-Cx43 and microtubule associated protein light chain 3 (LC3) in the hippocampus 6, 12, and 24 h after modeling; the protein localization of p-Cx43 and LC3 in the hippocampus and optical density of their positive cells were detected by immunohistochemistry 24 h after modeling; the learning and memory abilities of rats were tested by Morris water maze experiment 30 d after modeling. Results:Western blotting results showed that as compared with those in the sham-operated group, p-CX43 and LC3 protein expressions in the hippocampal CA3 regions of epilepsy group and epilepsy+solvent group were significantly increased at 6, 12 and 24 h after modeling ( P<0.05); as compared with the epilepsy group and epilepsy+solvent group, the epilepsy+CBX group had statistically decreased p-CX43 and LC3 protein expressions in the hippocampal CA3 regions at each time point ( P<0.05). Immunohistochemical staining showed that p-CX43 was localized at the cell membrane and cytoplasm of hippocampal astrocytes; LC3 was located at the cytoplasm of hippocampal neurons. As compared with those in the sham-operated group, the optical density values of p-CX43 and LC3 positive cells in hippocampal CA3 regions of epilepsy group and epilepsy+solvent group were increased ( P<0.05). As compared with those in the epilepsy group and the epilepsy+solvent group, the optical density values of p-CX43 and LC3 positive cells in the hippocampal CA3 regions of the epilepsy+CBX group were significantly decreased ( P<0.05). Morris water maze test results showed that as compared with that in the sham-operated group, the escape latency in the epilepsy group and epilepsy+solvent group was significantly prolonged ( P<0.05); as compared with that in the epilepsy group and epilepsy+solvent group, the latency in the epilepsy+CBX group was significantly shortened ( P<0.05). Conclusion:CBX can weaken the neuronal autophagy and reduce the damage to cognitive function by inhibiting the p-Cx43 protein expression in the astrocytes of the hippocampal CA3 regions.