A new pseudo-peptide of Arg-Gly-Asp (RGD) with inhibitory effect on tumor metastasis and enzymatic degradation of extracellular matrix

A series of pseudo-peptide analogs of the Arg-Gly-Asp (RGD) sequence of fibronectin have been synthe-sized, and their anti-metastatic effects in mice and inhibitory effects on tumor cell invasion in vitro have been examined. The partially modified retro pseudo-peptide of RGD, R_rev-COCH₂CO-D (FC-63), was more effective in inhibiting tumor metastasis than the original RGDS peptide. Replacement of the malonyl moiety of FC-63 with a carboxyethylene linkage (R_rev-COCH₂CH₂-D, FC-303 ) achieved more potent inhibition of lung metastasis of melanoma cells than FC-63. Among the analogs, FC-336, a p-xylylendiamine derivative having two FC-303 moieties, showed the most potent inhibitory effect on experimental lung metastasis produced by i.v. co-injection with B16-BL6 melanoma or colon 26 M3.1 cells in a dose-dependent manner. Multiple administrations of FC-336 after tumor inoculation also showed efficient therapeutic potency against spontaneous lung metastasis of B16-BL6 melanoma in mice. Furthermore, FC-336 effectively inhibited the invasion, migration and adhesion of tumor cells in vitro, but its inhibitory effects were not more than those of RGDS peptide. Zymography analysis revealed that FC-336 inhibited the degradation of gelatin substrate by matrix metalloproteinases (MMPs) produced by tumor cells, while the RGDS peptide did not affect the enzymatic degradation. These findings indicate that the pseudo-peptides of the RGD sequence, possessing the inhibitory property of the degradation by MMPs differently from original RGD-containing peptides, may be advantageous and useful in preventing tumor metastasis. © Rapid Science 1998     

ELABELA通过调控AKT信号通路影响滋养细胞侵袭的研究

目的 探讨ELABELA(ELA)对妊娠滋养细胞(Bewo细胞)侵袭行为的影响及其可能的作用机制。方法 用siRNA-ELA转染处于对数生长期的Bewo细胞,分为siRNA-ELA转染组,阴性对照组(细胞转染无意义序列)及空白组,细胞转染后于倒置显微镜下观察转染效率,采用实时荧光定量聚合酶链反应(qRT-PCR)检测转染后各组细胞中ELA mRNA表达并明确沉默效率。划痕实验测定各组细胞迁移能力,Transwell实验测定各组细胞的迁移、侵袭能力。蛋白质免疫印迹法检测各组细胞p-AKT、MMP9蛋白表达水平。结果 si-ELA组的ELA表达量明显低于si-NC组及空白组(P<0.001),且si-NC组与空白组差异无统计学意义(P>0.05);siRNA-ELA组细胞的迁移及侵袭能力均明显低于空白组(P<0.01;P<0.01);siRNA-ELA组p-AKT蛋白及MMP9蛋白表达水平明显低于空白组(p-AKT P<0.01;MMP9 P<0.001)。结论 敲低ELA可抑制滋养细胞的侵袭及迁移能力,其机制可能与AKT信号通路有关。     

止消通脉宁对糖尿病微血管合并症患者心功能影响的临床研究

为了探讨中药复方止消通脉宁对有微血管合并症的亚临床期糖尿病心脏病患者心功能的影响 ,我们选择了 63例 2型有微血管合并症的糖尿病患者 ,分为对照组 (2 0例 )和治疗组 (4 3例 ) ,分别使用常规疗法和加用止消通脉宁的治疗方法 ,疗程 4周 ,着重观察心功能、眼底和 2 4h尿白蛋白定量的改变。结果 :止消通脉宁可以明显改善心功能、减少尿白蛋白定量 ,而常规治疗对照组则无明显作用。表明止消通脉宁干预治疗可以改善有微血管合并症的亚临床期糖尿病心脏病患者心功能的异常 ,从而预防和治疗糖尿病心脏病。     

53例涎腺腺样囊性癌MMP—2和MMP—9表达与神经浸润和淋巴结转移的关系

目的研究涎腺腺样囊性癌MMP-2和MMP-9表达情况,评估其与涎腺腺样囊性癌神经浸润和淋巴 结转移的关系。方法选取53例涎腺腺样囊性癌,以抗MMP-2和MMP-9单克隆抗体用Envision法进行免疫 组织化学染色和半定量分析。结果MMP-2和MMP-9在涎腺腺样囊性癌中的表达率分别为67.92％和 79.25％;有神经浸润的腺样囊性癌其MMP-2和MMP-9的表达水平远高于无浸润者(P＜0.05,P＜0.05);随 着MMP-2和MMP-9的表达水平增高,淋巴结转移率也增高(P＜0.05,P＜0.05)。结论提示MMP-2和 MMP-9的高表达与涎腺腺样囊性癌易侵犯神经的特性及发生淋巴结转移密切相关。     

基于络病理论从芳香通络疗法论治冠状动脉微循环障碍

近年来,随着冠脉介入诊疗技术的普及,冠状动脉微循环障碍（CMD）的检出率逐步升高,CMD已成为远期心血管事件的独立预测因子。络病理论认为CMD病位在络,病机为心络瘀阻、心络郁滞/虚滞和心络绌急,通络成为其基本的治法治则。芳香类药物可直接入络搜邪,芳香通络疗法较单纯活血通络法疗效更佳。故而从络病理论、芳香通络疗法的立法依据等方面,对芳香通络疗法治疗CMD进行论述。     

Persistent extramural vascular invasion positivity on magnetic resonance imaging after neoadjuvant chemoradiotherapy predicts poor outcome in rectal cancer

BackgroundIn rectal cancer, extramural vascular invasion (EMVI) is the presence of tumour cells in blood vessels outside the muscular layer, which is associated with poor prognosis. Regression of EMVI on MRI following neoadjuvant chemoradiotherapy or its persistence may have prognostic implications.MethodsThis retrospective study included 52 patients with rectal cancer who underwent total mesorectal excision following long-course neoadjuvant chemoradiotherapy (CRT). EMVI assessments were done on previous pelvic MRIs obtained before neoadjuvant CRT and eight weeks after the completion of neoadjuvant chemoradiotherapy in initially EMVI positive cases.ResultsPersistently EMVI positive patients had worse overall survival and disease-free survival compared to initially EMVI negative patients and patients who returned to negative (p < 0.001 for both). Multivariate analysis identified persistent EMVI positivity after neoadjuvant treatment (HR, 102.9; p = 0.003) as significant independent predictor of worse overall survival; and persistent EMVI positivity (HR, 17.0; p = 0.002), mesorectal fascia involvement after neoadjuvant treatment (HR, 8.0; p = 0.017), and poor differentiation (HR, 10.3, p = 0.012) as significant independent predictors of worse disease-free survival.ConclusionPersistent EMVI positivity after neoadjuvant therapy appears to be an independent factor for poor overall survival; and persistent EMVI positivity as well as mesorectal fascia involvement on post neoadjuvant therapy MRI and poor differentiation appears to be important predictors of poor disease-free survival in rectal cancer patients.     

直肠癌壁外血管侵犯影像学评价的研究进展

直肠癌壁外血管侵犯是影响直肠癌病人预后的重要因素,术前准确诊断壁外血管侵犯,可指导治疗方案的制订,从而改善病人预后和远期生存。MRI检查和CT检查是术前评估直肠癌的主要检查手段。笔者将对影像学检查在直肠癌壁外血管侵犯评价的作用进行综述。     

原发性肝细胞癌微血管侵犯的术前预测模型构建及临床意义

目的构建原发性肝细胞癌(HCC)微血管侵犯(MVI)的术前预测模型并验证其准确性。方法回顾性分析2017年1月至2019年6月行肝切除术的160例HCC患者的临床病理资料,观察患者MVI情况。采用SPSS20.0软件对数据进行处理分析,计数资料采用χ^2检验;计量资料采用t检验;采用单因素和多因素Logistic回归分析影响MVI的独立危险因素,并构建HCC患者MVI的术前预测模型,通过描绘受试者工作特征曲线(ROC)并计算曲线下面积(AUC)从而来评估模型的预测能力,并以术后病理诊断结果为金标准对预测模型进行验证。结果在160例患者中,有MVI者86例,无MVI者74例。对单因素分析有统计学意义的资料进行Logistic多因素分析,结果显示:肿瘤直径、瘤周低回声晕环、甲胎蛋白(AFP)水平、血小板与淋巴细胞比值(PLR)水平、循环肿瘤DNA(ctDNA)浓度是HCC的MVI独立危险因素。根据Logistic回归分析各变量的回归系数构建预测模型,通过绘制ROC曲线,计算出AUC值为0.914(95%CI 0.820~0.962),当最佳临界值为0.069时对HCC患者MVI具有预测价值,灵敏度为86.5%,特异度为87.9%,约登指数为0.74。以术后病理诊断为金标准,验证预测模型,灵敏度为88.4%,特异度为93.2%,两者灵敏度和特异度无统计学差异(P>0.05)。结论基于Logistic多因素回归分析建立预测模型具有较高的灵敏度和特异性,对HCC微血管侵犯的患者具有较高的预测价值,可为HCC患者的术前治疗方案、手术规划提供参考。