Eutopic endometrium and peritoneal,ovarian and bowel endometriotic tissues express a different profile of matrix metalloproteinases-2, -3 and -11, and of tissue inhibitor metalloproteinases-1 and -2

Endometriosis is subsequent to the ability of endometrial glands to invade normal tissues. Matrix metalloproteinases (MMPs)—enzymes that mediate normal tissue turnover, including endometrial breakdown during menstruation—appear to be involved in this invasive process. Here, we examined the immunohistochemical expression of MMP-2, MMP-3, MMP-11, tissue inhibitor metalloproteinase (TIMP)-1 and TIMP-2 in endometrium from women with (n=9) or without endometriosis (n=18) in comparison with peritoneal (n=20), ovarian (n=20) and colorectal endometriosis (n=20). Women with endometriosis showed decreased endometrial MMP-2 expression compared with women without endometriosis (mean±SD positive cells: 24.3±28.3% and 69.3±12.1%), together with loss of MMP-3 expression (0 versus 17.5%±20.2). MMP-11, TIMP-1 and TIMP-2 expression was similar in the two groups. Endometrial MMP-2, -3 and -11 expression and TIMP-1 and -2 expression were similar in women with endometriosis and in those with peritoneal endometriosis. MMP-2, -3 and -11 expression was higher in colorectal endometriosis than in ovarian and peritoneal endometriosis. TIMP-2 expression was lower in colorectal endometriosis (P=0.0002) and ovarian endometriotic cysts (P=0.003) than in peritoneal endometriosis. TIMP-1 expression did not vary according to the location of endometriotic lesions. These results suggest that MMP-2 and -3 and TIMP-2 may be involved in the pathogenesis of endometriosis. Interestingly, MMP-2 and -3 overexpression was related to the infiltrative nature of endometriotic lesions, with possible sequential expression from peritoneal to colorectal endometriosis.     

滋养层细胞侵入相关基因在先兆子痫胎盘中的表达

探讨与滋养层侵入有关的细胞外基质分子相关基因在先兆子痫胎盘中的表达，采用分别点样有220余种人细胞因子相关基因和人类激素相关基因cDNA片段的两款基因芯片，检测经过严格配伍的先兆子痫和正常胎盘组织的基因表达谱差异。结果显示：钙粘蛋白、胶原、整合素、选择蛋白等18种细胞外基质分子基因的表达在先兆子痫和正常胎盘组织间相差2倍以上，且全部表现为在先兆子痫胎盘中的表达增强。先兆子痫患者的胎盘组织中基质金属蛋白酶(MMP)-10、-13、-15和金属蛋白酶组织抑制因子(TIMP)-2、TIMP-3、纤溶酶原、纤溶酶原激活物等的表达均较正常者高。提示胎盘中细胞外基质分子及其降解酶基因表达异常可能与先兆子痫的病理发生关系密切。     

Regulation of tissue-degrading factors and in vitro invasiveness in progression of breast cancer cells

Hormone-independent growth and invasiveness represent phenotypic properties acquired during early progression of breast cancer. We compared human mammary adenocarcinoma cells, MCF-7, which are estrogen-dependent and poorly metastatic, with the estrogen-independent and highly metastatic subline, MCF7/LCC1, with regard to expression of tissue-degrading factors of the matrix metalloproteinase (MMP)-and urokinase (uPA)-dependent degradative pathways, as well as for their in vitro invasive properties. Both cell lines showed low constitutive mRNA expression of the MMP inhibitor TIMP-1. Baseline expression of TIMP-2 mRNA was also very low in MCF-7 cells, whereas the MCF7/LCC1 level was much higher (~10- fold). Furthermore, both cell lines revealed low constitutive capacity to migrate in an in vitro invasion assay. Treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA; 100 nM) induced the mRNAs for TIMP-1 as well as for MMP-1, MMP-9, the uPA receptor, and the uPA inhibitor PAI-1, am ongst which only the responses of MMP-9 and PAI-1 were cell-specific. The mRNA levels of MMP-9 and PAI-1 were ~10-fold and ~15-fold higher in MCF7/LCC1 cells compared to MCF-7 cells. The secretion of immuno-reactive PAI-1 was considerably elevated (. 20-fold) in TPA-treated MCF7/LCC1 cells, whereas the TPA-dependent level of 92-kDa MMP-9 was only ~2-fold higher in MCF7/LCC1 cells than in MCF-7 cells. In both cell lines treatment with TPA was associated with an increase (~10-fold) in in vitro migration, which in the MCF7/LCC1 cells was significantly attenuated by a reconstituted basement membrane extract (Matrigel). These data suggest that TPA-responsive in vitro invasive properties that are probably associ-ated with PAI-1 expression may co-vary with progression from hormone-dependent to -independent breast cancer. © Rapid Science 1998     

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     

Conversion of highly malignant colon cancer from an aggressive to a controlled disease by oral administration of a metalloproteinase inhibitor

In this study, we describe the activity of CT1746, an orally-active synthetic MMP inhibitor that has a greater specificity for gelatinase A, gelatinase B and stromelysin than for interstitial collagenase and matrilysin, in a nude mouse model that better mimics the clinical development of human colon cancer. The model is constructed by surgical orthotopic implantation (SOI) of histologically-intact tissue of the metastatic human colon tumor cell line Co-3. Animals were gavaged with CT1746 twice a day at 100 mg/kg for 5 days after the SOI of Co-3 for 43 days. In this model CT1746 significantly prolonged the median survival time of the tumor-bearing animals from 51 to 78 days. Significant efficacy of CT1746 was observed on primary tumor growth (32% reduction in mean tumor area at day 36), total spread and metastasis (6/20 treated animals had no detectable spread and metastasis at autopsy compared to 100% incidence of secondaries in control groups). Efficacy of CT1746 could also be seen on reducing tumor spread and metastasis to individual organ sites such as the abdominal wall, cecum and lymph nodes compared to vehicle and untreated controls. We conclude that chronic administration of a peptidomimetic MMP inhibitor via the oral route is feasible and results in inhibition of solid tumor growth, spread and metastasis with increase in survival in this model of human cancer, thus converting aggressive cancer to a more controlled indolent disease.     

基于波士顿矩阵的医疗纠纷管理研究

目的针对医疗纠纷赔款案件的危害性进行风险分类分析,为提升科室医疗安全管理水平提供参考。方法分析某院2016年-2019年125例医疗纠纷赔款案件,借鉴波士顿矩阵模型,将医疗纠纷发生科室及原因围绕损害性（均次损害量化值）、损失性［每床位（均次）赔款金额］、发生频次3个指标进行风险分类。结果医疗纠纷赔款案件高发科室主要是骨科（33.6%）和普外科（23.2%）,发生原因主要是责任心不强（22.4%）、手术不当（20.8%）、漏诊误诊（16.8%）。“高床位赔款,高损害风险”科室有心外科及普外科,“高床位赔款,低损害风险”科室有泌尿外科、骨科及神经外科;“高赔款,高损害风险”医疗纠纷原因有漏诊误诊、用药不合理、医疗并发症、手术不当,“低赔款,高损害风险”医疗纠纷原因有院内感染、责任心不强。结论波士顿矩阵模型能够为医疗纠纷防范提供风险评估工具,从而助力科室安全管理。管理者可结合风险评估结果,采取差异化管理策略。     

公立医院优势学科病种绩效管理研究:以骨科为例

目的从循证视角建立公立医院优势学科病种绩效管理工具。方法以波士顿矩阵理论为指导,以“病种均次毛利率、病种均次住院日”为主要指标,“日均毛利率”为辅助指标,采用Microsoft office EXCEL 365 软件进行分析。结果2019年骨科平均住院日为4.99 d,均次平均毛利率为23.62%,日均毛利率平均值为4.73%。骨科200例以上病种、不同亚专科病区病种、同一亚专科病区内不同病种、不同亚专科病区相同病种,绩效均存在差异。结论 管理者应对不同病种绩效指标进行适当校正,探索精细化病种诊疗与管理模式。     

肌动蛋白是大鼠肝细胞核基质的组分之一

目的：证实肌动蛋白存在于大鼠肝细胞核基质中。方法：应用SDS－PAGE法分析大鼠肝细胞核基质的组分,以肌动蛋白多克隆抗体进行Westem Blot免疫印迹检测。结果：核基质蛋白SDS－PAGE图谱中可见相当于肌动蛋白的43KD条带,Westem Blot分析证实核基质中存在肌动 蛋白条带。结论：肌动蛋白是大鼠肝细胞核基质的组分之一。     

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。     

5-氨基水杨酸缓释骨架片的研制

目的 :制备 5_氨基水杨酸缓释骨架片。方法 :采用羟丙基甲基纤维素作为骨架材料 ,湿法制粒压片制备 ,并考察体外释药情况。结果 :5_氨基水杨酸缓释骨架片体外释药符合Higuchi方程。结论 :5_氨基水杨酸缓释骨架片具有显著的缓释效果。