Oncol2012: 腹腔镜下CO2气腹对结直肠癌细胞表达趋化因子受体CXCR4及CCR7的影响

目的 探讨不同压强、不同作用时间下持续性CO2气腹对结直肠癌细胞表达趋化因子受体的影响。 方法 建立体外气腹模型,选用人结直肠癌细胞株SW480,分别在6、9、12、15mmHg四种不同压强CO2气体下作用1h、2h及4h后,放在与无气腹组(37℃、5%CO2常规培养)相同的环境中分别培养0、24、48、72h后,使用免疫细胞化学法及RT-PCR检测趋化因子受体CXCR4、CCR7的表达。 结果 免疫细胞化学法检测结果显示SW480在相同作用时间下,经6、9、12、15mmHg压强的持续CO2气腹处理后,CXCR4表达下降;经12、15mmHg压强的持续CO2气腹处理后,CCR7表达下降,与无气腹组表达水平的差异均有统计学意义(P＜0.05),上述趋化因子受体表达在气腹处理后常规培养24、48h均增至无气腹组水平(P＞0.05)。CXCR4及CCR7的表达在相同作用时间下,随着压强增高,其表达量逐渐降低;在相同压强下,随着作用时间延长,其表达量无明显差异。 RT-PCR结果显示SW480在相同作用时间下经6、9、12、15mmHg压强的持续CO2气腹处理后,CXCR4 mRNA、CCR7 mRNA表达下降,与无气腹组表达水平的差异均有统计学意义(P＜0.05),上述趋化因子受体的mRNA表达在气腹处理后常规培养48h均增至无气腹组水平(P＞0.05)。CXCR4及CCR7的mRNA表达在相同作用时间下,随着压强增高,其表达量无明显差异;在相同压强下,随着作用时间延长,其表达量也无明显差异。 结论 不同压强CO2气腹能对结直肠癌细胞表面的趋化因子受体表达产生一过性影响,随CO2气腹压强的增高,可抑制趋化因子受体的表达。不同作用时间CO2气腹对结直肠癌细胞表面趋化因子受体的表达无明显影响。     

CO_2气腹压力和持续时间对人结肠癌细胞增殖的影响

目的：研究CO2气腹压力和持续时间对人结肠癌SW480细胞增殖的影响。方法：建立体外模拟CO2气腹环境,在全自动气腹机作用下,维持密闭真空压缩袋内不同压力（9、12、15 mmHg）,不同持续时间（1、2、4 h）作用于SW480细胞,作用后12 h,流式细胞仪观察细胞周期变化;作用后12、24、36、48、60和72 h,MTT法检测细胞增殖情况。结果：流式细胞仪检测细胞周期结果显示,CO2气腹压力对于人结肠癌G0/G1期细胞数值有显著影响（P〈0.01）,对于S期、G2/M期细胞周期无影响。而不同CO2气腹持续作用时间对于各细胞周期无影响（P〉0.05）,CO2气腹压力与作用时间对于各细胞周期不存在交互作用（P〉0.05）;MTT法结果显示CO2气腹下各组人结肠癌SW480细胞在不同压力和持续时间作用后12～72 h检测的平均D（490）值均小于对照组。通过析因设计的方差分析,在CO2气腹作用后12、24、36、48、60和72 h,压力与作用时间对SW480细胞的增值无交互作用（P〉0.05）。压力在24、36 h对SW480细胞的增值有一过性抑制作用（P〈0.01）,在SW480细胞增殖初、后期都无影响（P〉0.05）;不同作用时间对SW480细胞的增值无影响（P〉0.01）。结论：CO2气腹不同压力对结肠癌细胞的增殖有一过性抑制作用,CO2气腹72 h内不同作用时间对结肠癌细胞的增殖未见明显影响。     

Direct contact with bone marrow stromal cells promotes the invasions of SHI-1 leukemia cells

Background Interactions of tumor cells with the microenvironment were deemed to promote the tumor invasion and metastasis.CXC chemokine receptor 4 (CXCR4) and extracellular matrix metalloproteinase ind...     

Expression of chemokine receptors CCR3, CCR5 and CXCR3 on CD4^＋ T cells in CBA/J×DBA/2 mouse model,selectively induced by IL-4 and IL-10, regulates the embryo resorption rate

Background Chemokines and their receptors have been a research focus in transplantation immunology. Chemokines and their receptors play a role in lymphocyte recruitment and differentiation process. This study aimed to observe whether IL-4 and IL-10 may regulate the expression of chemokine receptors CCR3, CCR5 and CXCR3 on CD4^＋ T cells in CBA/J×DBA/2 mouse model and to explore the role of CCR3, CCR5, CXCR3 in immune tolerance in pregnancy. Methods The mouse model of spontaneous abortion （CBA/J×DBA/2） and the normal pregnant mouse model （CBA/J×BALB/c） were used. CBA/J×DBA/2 mice were injected with IL-4 （CBA/J×DBA/2-IL-4）, IL-4 and IL-10 （CBA/J×DBA/2-IL-4＋IL-10）, or normal saline （CBA/J×DBA/2-NS） as a control. The expression of CCR3, CCR5 and CXCR3 on CD4^＋ T cells from mouse peripheral blood was measured by the double-labelled FCM method, and the embryo resorption rate was also examined. Results The embryo resorption rate in the CBA/J×DBA/2 group without any treatment was significantly higher than that in the CBA/J×BALB/c group （17.9% vs 3.7%, P 〈0.01）. The embryo resorption rate in the CBA/J×DBA/2 group immunized with IL-4 or IL-4 together with IL-10 was significantly decreased, compared with that in the control and NS groups respectively. CCR3 expression on CD4^＋ T cells in the CBA/J×DBA/2 group without any treatment was significantly lower than that in the CBA/J×BALB/c group （0.3738±0.3575 vs 1.2190±0.2772, P 〈0.01）; both CCR5 （3.0900±1.5603 vs 1.2390±0.6361, P〈0.01） and CXCR3 （2.4715±0.9074 vs 0.9200±0.5585, P 〈0.01） expressions on CD4^＋ T cells of the CBA/J×DBA/2 group without any treatment were significantly higher than those of the CBA/J×BALB/c group. Significant up-regulation of CCR3 and down-regulation of CXCR3 were found in the CBA/J×DBA/2 group treated with IL-4 （CCR3： 2.0360±0.6944, CXCR3： 1.3510±0.5263, P〈0.01） or IL-4 and IL-10 （CCR3： 1.8160±1.0947, CXCR3：1.0940±0.7168, P〈0.01）. Because of the CCR5, IL-4 and IL-10 （1.9400±0.8504 vs 3.0900±1.5603, P 〈0.05）, but IL-4 alone （2.5310±1.3595 vs 3.0900±1.5603, P 〉0.05） treatment significantly decreased the expression of CCR5 in CBA/J×DBA/2. Conclusions The abnormal expression of CCR3, CCR5 and CXCR3 on CD4^＋ T cells may play an important role in the pathogenesis of spontaneous abortion. The pregnancy immune tolerance may be induced through selective induction of CCR3, CCR5 and CXCR3 expressions by IL-4 together with IL-10.     

Tumorigenesis and spontaneous metastasis by luciferase-labeled human xenograft osteosarcoma cells in nude mice

Background  Osteosarcoma (OS) is the most common primary malignant tumor of bone. Mouse models of human OS can invariably provide greater insight into the complex mechanisms that underlie the development and pathogenesis of this aggressive tumor. Bioluminescence technology favored tracing cancer cells in vivo. In this study, an OS model was described and evaluated using human OS cell line, Saos2, labeled with luciferase (Saos2-luc).

Methods  Saos2 cells were infected by lentivirus loading a firefly luciferase gene. Luciferase expression of Saos2-luc cells was characterized both in vitro and in vivo. Specific biologic and oncologic features of Saos2-luc cells were analyzed. The OS was established as orthotopic xenografts in nude mice. Both orthotopic tumors and spontaneous lung metastasis were analyzed.

Results  Tumorigenesis and spontaneous lung metastasis in nude mice could be monitored in vivo through in vivo imaging system. The enhancement in proliferation, migration and invasion abilities and the attenuation in adhesion ability were observed in Saos2-luc cells compared with Saos2 cells. Furthermore, there were the up-regulation of Osteocalcin, CCR10, CXCR1 and ID1 and the down-regulation of ALP, collagen I, CCR1, CCR3, CXCR3, NID and N-cadherin in Saos2-luc cells compare to Saos2 cells. The rate of spontaneous lung metastasis in Saos2-luc cells was higher than that in Saos2 cells, although without significant difference.

Conclusions  Lentivirus transfection may cause alteration of gene expression profiles and further biological functions. This model can be used in the elucidation of molecular mechanisms of tumorigenesis and the screening of new therapeutic agents.

     

鼻咽癌组织中CCR7和CXCR4的表达及其临床意义

目的探讨CXC族趋化因子受体4（CXCR4）和CC族趋化因子受体7（CCR7）在鼻咽癌（NPC）组织中的表达及其临床意义。方法随机选择2012年1月至2013年10月本院NPC患者60例,取其鼻咽癌组织（病例组）,选择同期鼻咽部炎症患者30例,取其鼻咽部组织（对照组）,采用免疫组织化学检测两组患者的CXCR4和CCR7表达情况。结果病例组CCR7和CXCR4的阳性表达分别为32例和27例,均高于对照组的6例和4例,其差异均有统计学意义（P〈0.05）,Ⅲ期＋Ⅳ期患者的CCR7和CXCR4阳性例数为22例和16例,高于Ⅰ期＋Ⅱ期的10例和11例,其差异均具有统计学意义（P〈0.05）;M1期CCR7阳性例数为24例,高于M0期的8例,差异也具有统计学意义（P〈0.05）;有淋巴结转移的患者CCR7和CXCR4阳性例数分别为23例和24例,未转移者9例和3例,其差异也具有统计学意义（P〈0.05）。结论 CCR7和CXCR4在鼻咽癌中的阳性表达率均明显高于非鼻咽癌组织,且与鼻咽癌临床分期和淋巴结转移有关,CXCR4和CCR7在鼻咽癌的发生和发展中具有重要的意义。     

Role of paxillin in colorectal carcinoma and its relationship to clinicopathological features

Background Colorectal carcinoma is one of the most common malignant tumors.Despite advances in therapy,mortality is still very high.The aim of this study was to evaluate the expression of paxillin in the human colon adenocarcinoma cell line SW480 and its role in cell cycle and apoptosis.We also investigated the expression of paxillin in colorectal carcinoma tissues and its relationship to clinicopathological features and survival.Methods Paxillin short hairpin RNA （shRNA） was constructed and transfected into the colon adenocarcinoma cell line SW480.The influence of paxillin shRNA on the cell cycle and cell apoptosis was analyzed by flow cytometry.Immunohistochemistry staining was used to assess the expression of paxillin and its association with the expression of carcinoembryonic antigen （CEA）,carbohydrate antigen （CA） 19-9,p53 and Bcl-2 in 102 patients with primary colorectal carcinoma.Western blotting was also used to investigate the expression of paxillin.Medical records were reviewed and a clinicopathological analysis was performed.Results In vitro,the percentage of cells in S phase was （45.23±1.05）％,（43.53±1.23）％,and （36.13±0.57）％ in the blank control group,negative control group,and paxillin shRNA group respectively.It was significantly decreased in the paxillin shRNA group （P=0.000）.The early apoptosis index of the paxillin shRNA group （17.2±1.18％） was significantly increased compared to the control shRNA group （（13.17±1.15）％,P=0.013）.Paxillin was positive in 71 （69.6％） patients,and it was found to be overexpressed in tumor tissues compared with normal adjacent tissues.Paxillin positive rate was higher in patients who are less than 50-years old （100.0％ vs.65.6％,P=0.016）.Paxillin expression was associated with a high histologic grade of carcinoma （81.4％ vs.61.0％,P=0.031）,a high rate of regional lymph node metastasis （22.5％ vs.13.0％,P=0.031）,mesenteric artery lymph node metastasis （100.0％ vs.64.8％,P=0.008）,distant metastasis （94.1％ vs.64.7％,P=-0.016） and a high Tumor Node Metastasis （TNM） stage （94.1％,73.2％,60.0％,and 50％,P=0.030）.Multivariate analyses revealed that recurrence was associated with the rate of regional lymph node metastasis （P=0.001） and paxillin expression （P=0.024）.Multivariate analysis indicated that the overall survival is related to the TNM stage （P=0.000）.Conclusions In vitro,paxillin may promote cell proliferation and inhibit apoptosis in SW480 cells.Paxillin may be a potential metastasis predictor,and an independent prognosis factor of recurrence.It may also be related to poor patient outcomes,but was not an independent predictor of survival.     

特异性小干扰RNA抑制诱骗受体3在结肠癌SW480细胞表达的研究

目的研究特异性小干扰RNA(small interfering RNA,siRNA)对诱骗受体3(decoy receptor 3,DcR3)基因在人结肠癌SW480细胞系中的抑制作用。方法设计特异性的DcR3 siRNA序列;构建DcR3的pSUPER表达质粒并鉴定,鉴定成功后用于转染SW480细胞。以RT-PCR的方法检测细胞转染后DcR3 mRNA的表达;以Western blotting的方法检测DcR3蛋白的表达情况,并作统计学处理。结果与对照组相比,本实验设计两段siRNA对SW480细胞中DcR3 mRNA及蛋白表达的抑制作用明显,实验细胞DcR3 mRNA及蛋白表达显著下降(P<0.01)。结论针对DcR3的siRNA质粒转染真核细胞后可抑制其mRNA及蛋白表达,为进一步探讨DcR3的功能及封闭DcR3基因表达而治疗肿瘤奠定了实验基础。     

皮肤归巢T淋巴细胞的趋化性及趋化因子受体的表达

目的 :探讨由接触性过敏原或结核菌素诱发的细胞介导的皮肤炎症反应中 ,皮肤归巢T淋巴细胞的趋化性及其趋化因子受体的表达。方法 :取斑贴试验阳性或结核菌素皮肤反应试验阳性受试者的皮肤标本 ,利用 4 8孔微趋化板技术、流式细胞仪等检测皮肤归巢T淋巴细胞的趋化性及其趋化因子受体的表达。结果 :CC型趋化因子eotaxin、MIP 1α和CXC型趋化因子IL 8对于皮肤归巢T淋巴细胞有趋化效应 ,但这些细胞对RANTES无反应。皮肤归巢T淋巴细胞上CCR3、CCR5、CXCR1和CXCR2呈动态表达 ,而粘附分子ICAM 1则是高表达。在体外培养基中 ,趋化因子受体的表达即趋化运动的能力和粘附分子的表达受IL 2和IL 4的调节。结论 :在细胞介导的皮肤炎症反应中 ,趋化因子及其受体通过与T细胞源性的生长因子IL 2和IL 4的相互作用决定了皮肤归巢T淋巴细胞的定向迁移、粘附、聚集和循环 ,同时也决定了嗜酸性粒细胞和嗜碱性粒细胞的聚集     

Downregulating activated epidermal growth factor receptor has no effect on RBM5 expression

Background  We were interested in determining how the tumor suppressor gene RBM5 is regulated in lung cancers. Previous studies suggested that the gene expression is related to histological subtype and smoking exposure, since in small cell lung cancers the RBM5 gene is deleted whereas in non-small cell lung carcinomas (NSCLC) RBM5 expression is reduced. Of particular interest was the recent finding that in lung adenocarcinomas, a histological subtype of NSCLC, smoking exposure correlated with mutational activity in the transforming growth factor alpha (TGF-a) signaling pathway. Lung adenocarcinomas from smokers were associated with activating KRAS mutations, whereas lung adenocarcinomas from never-smokers were associated with activating epidermal growth factor receptor (EGFR) mutations. We hypothesized that inhibition of RBM5 in lung adenocarcinomas is achieved indirectly via these activating mutations. The objective of the research described herein was to determine if EGFR activation and RBM5 expression are negatively correlated.

Methods  EGFR expression in the lung adenocarcinoma cell line NCI-H1975 was inhibited using small interfering RNA. RBM5 expression was examined by real-time quantitative polymerase chain reaction and Western blotting.

Results  Reduced EGFR expression did not correlate with any change in RBM5 expression at either the RNA or protein level.

Conclusion  These results suggest that RBM5 expression is not directly regulated by EGFR in non-smoker related lung adenocarinomas, and that some other mechanism operates to inhibit either the expression or function of this potential tumour suppressor in lung cancers that retain the RBM5 gene.

     

腹腔镜胆囊切除术气腹对患者凝血系统的影响:一项前瞻性研究

BacKground Laparoscopic cholecystectomy has been widely used in clinical practice during the recent decades; however, the effects of pneumoperitoneum and the surgery on the coagulation system are largely unknown. This clinical study aimed to observe any possible effects of pneumoperitoneum and the surgery on the coagulation system of patients. Methods This was a prospective observational study. The inclusion criteria included （1） patients with chronic cholecystitis and/or cholecystic polyps and （2） patients in the relief stage of acute cholecystitis. The exclusion criteria included （1） patients in the episodic stage of acute cholecystitis and those complicated with cholangiolithiasis; （2） patients with concomitant hematologic diseases, damages to the liver function, malignant tumors or immune system diseases, or patients complicated with thrombotic or hemorrhagic disorders; and （3） patients who had taken anticoagulant medication within a week before surgery. Fifty patients who were hospitalized into our department for elective laparoscopic cholecystectomy between November 2011 and February 2013 were eligible and enrolled into this study. Of the 50 patients, 22 were male and 28 female. The age of the patients ranged from 29 to 78 （mean 56.7±11.5） years. The surgery for each of the 50 patients was performed with the same equipment and conditions. The surgeries for all the patients were performed under general anesthesia with the patients in a 30-degree head-up tilted posture, and the pressure of pneumoperitoneum was maintained at 13 mmHg. Venous blood specimens were taken from each patient before and at the end of pneumoperitoneum （i.e., 0 hour after surgery） and at 8 hours after surgery for determination of prothrombin time （PT）, activated partial thromboplastin time （APTT）, fibrinogen （Fib）, thrombin time （TT）, and D-dimer （DD）. The results of the determinations of these parameters were compared. Results （1） All the patients recovered well without any complicat     

CXCR4在前列腺癌组织中的表达与意义

目的:探讨趋化因子受体在前列腺癌组织中的表达及其意义.方法:采用酶标记免疫组织化学方法检测45例前列腺癌及10例前列腺增生组织中趋化因子受体CCR1、CCR3、CXCR4和CCR5的表达情况,应用ELISA双抗体夹心方法检测相应患者血清中趋化因子SDF-1的含量,并应用免疫发光方法检测相应患者血清中前列腺特异性抗原PSA的含量.结果:在前列腺癌组织上检测到趋化因子受体CXCR4的表达(表达率55.5%),PSA＞20 ng/ml与PSA＜20 ng/ml的前列腺癌组织上CXCR4的表达率分别为61.2%和42.8%,而前列腺增生组织中未发现这4种趋化因子受体的表达;与前列腺增生患者相比,在前列腺癌患者血清中SDF-1含量明显升高[(567.9±90.73)vs(169.1±46.01)pg/ml,P＜0.01].结论:在前列腺癌组织上发现有趋化因子受体CXCR4的表达,其表达可能在前列腺癌的发生、发展和转移中起重要作用.     

Phosphorylation of PTEN increase in pathological right ventricular hypertrophy in rats with chronic hypoxia induced pulmonary hypertension

Background Phosphatase and tensin homologue on chromosome ten （PTEN） acts as a convergent nodal signalling point for cardiomyocyte hypertrophy,growth and survival.However,the role of PTEN in cardiac conditions such as right ventricular hypertrophy caused by chronic hypoxic pulmonary,hypertension remains unclear.This study preliminarily discussed the role of PTEN in the cardiac response to increased pulmonary vascular resistance using the hypoxia-induced PH rats.Methods Male Sprague Dawley rats were exposed to 10％ oxygen for 1,3,7,14 or 21 days to induce hypertension and right ventricular hypertrophy.Right ventricular systolic pressure was measured via catheterization.Hypertrophy index was calculated as the ratio of right ventricular mass to left ventricle plus septum mass.Tissue morphology and fibrosis were measured using hematoxylin,eosin and picrosirius red staining.The expression and phosphorylation levels of PTEN in ventricles were determined by real time PCR and Western blotting.Results Hypoxic exposure of rats resulted in pathological hypertrophy,interstitial fibrosis and remodelling of the right ventricle.The phosphorylation of PTEN increased significantly in the hypertrophic right ventricle compared to the normoxic control group.There were no changes in protein expression in either ventricle.Conclusion Hypoxia induced pulmonary hypertension developed pathological right ventricular hypertrophy and remodelling probablv related to an increased phosohorvlation of PTEN.     

Proliferating cell nuclear antigen involved in the repair process of ouabain-induced brain damage independent of hypertension in rats

Background Ouabain is a mammalian adrenocortical hormone that is involved in the pathogenesis of hypertension by inhibiting Na-K ATPase activity.It also participates in a variety of kinase-mediated signaling pathways associated with Na-K ATPase.Previous studies have shown that ouabain can cause cardiac remodeling independent of elevated blood pressure and that proliferating cell nuclear antigen （PCNA） plays a coordinating role for numerous proteins involved in multiple processes associated with DNA synthesis.Therefore,we hypothesized that ouabain might play a role in the cerebral cortex through signaling pathways independent of hypertension.And PCNA might be involved in this process.Methods Male Sprague-Dawley rats were treated with ouabain or with 0.9% nitric sodium as the control group.Systolic blood pressure was recorded weekly.After four weeks of treatment,morphological changes in the cerebral cortex were analyzed using light and transmission electron microscopy.The expression of PCNA in the cerebral cortex was evaluated by immunohistochemistry,real time quantitative PCR,and Western blotting.Results After 4-week treatment,there was no significant difference in systolic blood pressure compared with the control group,but both structural deterioration and up-regulated expression of PCNA in the brain was induced by ouabain treatment.Conclusions These results suggest that ouabain induces alterations in the brain structure,and this effect is independent of blood pressure.PCNA might be involved in the repair process of ouabain-induced brain damage.     

Fibroblasts weaken the anti-tumor effect of gefitinib on co-cultured non-small cell lung cancer cells

Background Non-small cell lung cancer （NSCLC） is the most common lung malignancy worldwide.The metastatic potential of NSCLC cells has been shown to be associated with the tumor microenvironment,which consists of tumor cells,stroma,blood vessels,immune infiltrates and the extracellular matrix.Fibroblasts can produce numerous extraceilular matrix molecules and growth factors.Gefitinib has been evaluated as a first-line treatment in selected patients,and it has shown favorable efficacy especially in NSCLC,but it is not effective for everyone.Methods In this study,we examined the antitumor activity of gefitinib on lung fibroblasts co-cultured of lung cancer cells.A series of co-culture experiments that employed cell counting kit-8 （CCK8）,transwells,real-time polymerase chain reaction （RT-PCR） and Western blotting with HFL-1 fibroblasts and A549 human lung carcinoma cells were performed to learn more about tumor cell proliferation,migration and invasion; and to determine any change of epithelial mesenchymal transition （EMT）-associated tumor markers vimentin,matrix metallopro-teinase 2 （MMP2） and chemotaxis cytokines receptor 4 （CXCR4） mRNA levels.Results A549 cell proliferation in the presence of HFL-1 cells was not significantly increased compared with A549 cells alone,but A549 cell spheroid body formation was increased after co-culture,and treatment with gefitinib increased further.Our study also revealed that fibroblasts attenuated the lung cancer cell inhibition ratio of migration and invasion after gefitinib treatment in vitro.To further study this mechanism,RT-PCR analysis showed that vimentin,MMP2 and CXCR4 mRNA levels were more highly expressed in the lung cancer cells after co-culture,but did not obviously decrease compared with the control cells following gefitinib treatment.This suggests the mechanism by which fibroblasts attenuate gefitinib-induced expression of EMT-associated tumor markers.Finally,our results demonstrated that co-culture with A549 lung cancer cells does not alter the cell cycle distribution of HFL-1 fibroblasts.Furthermore,HFL-1 fibroblasts had no effect on the cell cycle distribution of HFL-1 cells treated with gefitinib.Conclusion Gefitinib has lower anti-tumor activity on A549 lung cancer cells when co-cultured with HFL-1 fibroblasts.     

变异催乳素受体Delta S2促使p53基因组蛋白甲基化

Background Prolactin （PRL） is a pituitary polypeptide hormone characterized by multiple biological actions includingstimulation of growth in the prostate and formation of secretory alveoli and stimulation of milk protein gene expression inthe mammary gland. PRL exerts its effect by dimerizing its receptor （PRLR） on the plasma membrane and regulating geneexpression through the JAK-Stat signal pathway. We have previously described a natural variant of the PRLR in which the$2 subdomain of the extracellular domain is missing （Delta S2）. Delta S2 PRLRs are dimerized in the absence of PRL andhave constitutive activity in the promotion of breast cancer cell growth. Enhancer of zeste homolog 2 （EZH2）, as one of thehistone-modifying enzymes, is a key factor regulating gene expression by epigenetic modification. We hypothesized thatthese constitutive activated Delta S2 PRLRs played a pathogenic role in breast cancer in part through alterations in theexpression of EZH2 and the trimethylation of histone 3 on lysine 27 （H3K27Me3）.     

Changes of cerebrospinal fluid pressure after thoracic endovascular aortic repair

Background Decreasing the intracranial pressure has been advocated as one of the major protective strategies to prevent spinal cord ischemia after endovascular aortic repair. However, the actual changes of cerebrospinal fluid （CSF） pressure and its relation with spinal cord ischemia have been poorly understood. We performed CSF pressure measurements and provisional CSF withdrawal after thoracic endovascular aortic repair, and compared the changes of CSF pressure in high risk patients and in patients with new onset paraplegia and paraparesis.     

Hydrogen sulfide defends against the cardiovascular risk of Nw-nitro-L-argininemethyl ester-induced hypertension in rats via the nitric oxide/endothelial nitric oxide synthase pathway

Background Dyslipidemia caused by liver injury is a significant risk factor for cardiovascular complications.Previous studies have shown that hydrogen sulfide （H2S） protects against multiple cardiovascular disease states in a similar manner as nitric oxide （NO）,and NO/endothelial nitric oxide synthase （eNOS） pathway is the key route of NO production.The purpose of this study was to investigate whether H2S can ameliorate the high blood pressure and plasma lipid profile in Nw-nitro-L-argininemethyl ester （L-NAME）-induced hypertensive rats by NO/eNOS pathway.Methods Thirty-six 4-week old Sprague-Dawley （SD） male rats were randomly assigned to 6 groups （n=6）：control group,L-NAME group,control ＋ glibenclamide group,control ＋ NaHS group,L-NAME ＋ NaHS group,and L-NAME ＋ NaHS ＋ glibenclamide group.Measurements were made of plasma triglycerides （TG）,low-density lipoprotein （LDL）,high-density lipoprotein （HDL）,total cholesterol （CHO）,glutamic-pyruvic transaminase （ALT） levels after 5 weeks.Then measurements of NO level and proteins expression of eNOS,P-eNOS,AKT,P-AKT were made in liver tissue.Results After 5 weeks of L-NAME treatment,the blood pressure,plasma TG （（1.22±0.12） mmol/L in L-NAME group vs.（0.68±0.09） mmol/L in control group; P ＜0.05） and LDL （（0.54±0.04） mmol/L in L-NAME group vs.（0.28±0.02） mmol/L in control group; P ＜0.05） concentration were significantly increased,and the plasma HDL （（0.26±0.02） mmol/L in L-NAME group vs.（0.69±0.07） mmol/L in control group; P ＜0.05） concentration significantly decreased.Meanwhile the rats treated with L-NAME exhibit dysfunctional eNOS,diminished NO levels （（1.36±0.09） mmol/g protein in L-NAME group vs.（2.34±0.06） mmol/g protein in control group; P ＜0.05） and pathological changes of the liver.H2S therapy can markedly decrease the blood pressure （（37.25±4.46） mmHg at the fifth week; P ＜0.05）,and ameliorate the plasma TG （（0.59±0.06） mmHg）,