Expression of Matrix Metalloproteinases 1, 2, 9 and Their Tissue Inhibitor-1 in Cartilage-Forming Osteal Tumors

The expression of MMP-1, -2, -9 and TIMP-1 was studied in 10 benign cartilage-forming osteal tumors (5 osteochondromas and 5 chondromas) and 39 chondrosarcomas (14 central, 4 periosteal, 7 dedifferentiated, and 14 secondary tumors). No expression of MMP and TIMP-1 was detected in benign cartilage-forming osteal tumors. In chondrosarcomas, the expression of MMP-1 was detected in 84.6%, of MMP-2 in 71.8, of MMP-9 in 97.4, and of TIMP-1 in 82.4% cases, the levels of expression of these markers varied from 10 to 60%. The expression of MMP-1 was not associated with patient gender, maximum size and degree of differentiation of the tumor, but was linked with age. The expression of MMP-1 was more often detected in central and dedifferentiated chondrosarcomas; the expression of MMP-1(+) was significantly associated with 3-year relapse-free and 5-year overall survival of the patients. The expression of MMP-1 in the tumor was associated with unfavorable course of the disease. The values of MMP-2 expression in chondrosarcomas did not reflect the main clinical morphological characteristics of the disease and its prognosis. The level of MMP-9 protein expression in chondrosarcomas ≥40% is prognostically unfavorable, while <40% is a favorable factor for 3-year relapse-free survival. The risk of disease relapse within 1 year after the beginning of therapy was maximum in T₃ tumors with expression of MMP-9 protein ≥40%. No relationships between the parameters of TIMP-1 expression in chondrosarcomas and the main clinical morphological characteristics of the disease and its prognosis were detected.     

Matrix Metalloproteinases 2, 7, 9 and Tissue Inhibitor of Matrix Metalloproteinase-1 in the Sera of Patients with Bone Tumors

Comparative enzyme immunoassay of matrix metalloproteinases (MMP-2, -7, -9) and their tissue inhibitor-1 (TIMP-1) in the sera of 26 healthy individuals and 54 patients with primary osteal tumors before therapy revealed elevated TIMP-1 levels in the patients with classical central and periosteal osteosarcomas in comparison with the control. In patients, the level of MMP-9 signifi cantly decreased compared to that in healthy individuals, while the levels of MMP-2 and MMP-7 remained unchanged. No differences in serum levels of MMP and TIMP-1 associated with gender, age, primary osteal tumor location and size were detected. Overall 3-year survival of patients with classical central osteosarcoma with serum level of MMP-9 below its median was higher than that of patients with MMP-9 level equal to above the median (90.9±8.7 and 50.8±23%, respectively).     

Clinical Significance of Matrix Metalloproteinases in Blood Plasma of Patients with Gastric Cancer

Bulletin of Experimental Biology and Medicine - Plasma levels of MMP-2, MMP-7, and MMP-9 and their tissue inhibitor TIMP-2 were measured in 89 patients with gastric cancer and the relationship...     

Matrix Metalloproteinase-9 and Tissue Inhibitors of Matrix Metalloproteinase-1 in Plasma of Patients Co-Infected with HCV and HIV

Abstract

Background: Accelerated progression of hepatic fibrosis has been shown in patients co-infected with hepatitis C virus (HCV) and HIV. Liver fibrosis is a dynamic process in which the altered balance between matrix metalloproteinases (MMPs) and their specific inhibitors (TIMPs) may play a major role. Method: The involvement of MMP-9 and TIMP-1 in HCV liver disease progression in patients co-infected with HIV was evaluated. Plasma concentrations of human MMP-9 and TIMP-1 were assessed in 76 HIV-infected patients; 27 were co-infected with HCV and 49 were HCV negative. 18 healthy donors were included as controls. Results: Patients with HIV infection exhibited a striking increase in TIMP-1 levels; this is more evident in patients with advanced CD4 depletion. There was no elevation in the plasma concentrations of the MMP-9. The highest levels of TIMP-1 were found in the HIV/HCV co-infected patients. The values of TIMP-1 in HIV-infected patients with chronic HCV hepatitis were significantly higher than in HIV-positive individuals without HCV infection, even including those with low CD4 count. No significant differences were seen in the MMP-9 levels. Conclusion: These findings suggest that the altered balance between circulating MMP-9 and TIMP-1 during HIV infection may play an important role in exacerbating liver fibrosis progression in patients co-infected with HCV.     

胃癌患者术后血清CA19-9、CA72-4和MG7-Ag检测的临床意义

为了探讨胃癌患者术后血清CA19-9、CA72-4和MG7-Ag检测的临床意义,本文对170例Ⅲ期胃癌行根治术的患者进行术前及术后每两个月检测患者血清CA19-9、CA72-4和MG7-Ag,术后定期进行胸片、B超和CT等影像学检查,并对疑有局部复发的患者行胃镜检查.结果表明:全组中有101例患者发现了复发(其中血源性复发83例,局部复发18例).CA19-9、CA72-4和MG7-Ag对复发患者阳性率分别为62.4%、67.3%和59.4%;三项联合检测的阳性率为95.0%,除MG7-Ag外,以上阳性率均显著高于术前(分别为48.5%,51.5%、57.0%和76.4%).标志物出现异常的时间比影像学发现病灶早14个月至晚4个月(中位时间为4.2±2.5个月).三项标志物中,CA19-9异常与复发后的生存时间有显著相关性.联合检测CA19-9、CA72-4和MG7-Ag有助于预测胃癌术后复发,而CA19-9可作为判断胃癌术后预后的独立因素.     

Expression of Matrix Metalloproteinases and Their Tissue Inhibitors in Human Brain Tumors

In this study, we investigated the expression patterns of 15 matrix metalloproteinases (MMPs) and three tissue inhibitors of metalloproteinase in gliomas, medulloblastomas, and normal brain tissue. By Northern blot analysis we found increased levels of mRNAs encoding for gelatinase A, gelatinase B, two membrane-type MMPs (mt1- and mt2-MMP), and tissue inhibitors of metalloproteinase-1 in glioblastomas and medulloblastomas. We observed a significant increase of mt1-MMP, gelatinase A, gelatinase B, and tissue inhibitors of metalloproteinase-1 in glioblastomas as compared with low-grade astrocytomas, anaplastic astrocytomas, and normal brain. In medulloblastomas, the expression of mt1-MMP, mt2-MMP, and gelatinase A were also increased, but to a lesser extent than that observed in glioblastomas. These data were confirmed at the protein level by immunostaining analysis. Moreover, substrate gel electrophoresis showed that the activated forms of gelatinases A and B were present in glioblastomas and medulloblastomas. These results suggest that increased expression of mt1-MMP/gelatinase A is closely related to the malignant progression observed in gliomas. Furthermore, the present study demonstrates, to our knowledge for the first time, that medulloblastomas express high levels of MMP.     

基质金属蛋白酶9及热休克蛋白60检测对早期胃癌的诊断价值

目的 探讨血浆基质金属蛋白酶9(MMP-9)与热休克蛋白60(HSP-60)联合检测对早期胃癌患者的诊断价值.方法 选取我院收治的临床疑诊早期胃癌136例患者,根据患者确诊诊断分为:对照组(70例,排除胃癌诊断)和研究组(66例,确诊胃癌诊断).检测并比较两组患者MMP-9、HSP-60 、CA19-9、CA72-4以及CEA水平差异.采用Logistic回归分析影响早期胃癌发生的临床因素.运用ROC曲线评估MMP-9与HSP-60对诊断早期胃癌患者的最佳值.结果 研究组血浆MMP-9、HSP-60、CA19-9、CA72-4与CEA水平均高于对照组(P均＜0.05).多因素Logistic回归分析结果显示,血浆MMP-9与HSP-60是早期胃癌发生的危险因素(P＜0.05).血浆MMP-9与HSP-60诊断早期胃癌的ROC曲线下面积分别为0.781和0.667(P=0.024,0.011).当MMP-9≥ 364.5 μg/L和HSP60 ≥2.84 μg/L为cut-off值,对判断早期胃癌发生的灵敏度为53.0％,特异性为81.4％,准确度为67.6％,ROC曲线下面积为0.862.结论 血浆MMP-9与HSP-60联合检测对早期胃癌发生具有较好的诊断价值.     

Comparative Study of Antinuclear Antibody Detection by Indirect Immunofluorescence and Enzyme Immunoassay in Lupus Patients

To evaluate the value of immunofluorescent and ELISA techniques in early diagnosis of systemic lupus erythematosus (SLE) and to find out whether there is a correlation between Antinuclear antibodies (ANA) pattern and prognosis by observing clinical score changes using British Isles Lupus Assessment Group score. The study included 75 SLE patients, 11 disease control group, and 18 healthy control group. ANA and ds-DNA antibodies detection were done by ELISA and Immunofluorescence for all groups. Immunofluorescence technique is more sensitive for ANA and ds-DNA detection than ELISA technique (100% versus 90.7%,and 93% versus 89.3% respectively); ELISA showed 89.7 % specificity for ANA detection compared to 86.2% for Immunofluorescence, and both have 100% specificity for ds-DNA detection ;homogenous ANA pattern, showed statistically significant higher BILAG score compared to speckled pattern either at the start of the study or after the follow up period (p = 0.000); and ds-DNA titer showed statistically significant decrease in titer after therapy (p = 0.01). ANA detection by Immunofluorescence is more sensitive and effective screening assay in patients with clinical features of SLE and both ds-DNA titer by ELISA and BILAG score for severity index are considered the best markers for follow-up.     

Comparative Studies with Penicillinase,Horseradish Peroxidase,and Alkaline Phosphatase as Enzyme Labels in Developing Enzyme Immunoassay of Cortisol

Abstract

Relative merit of different enzyme labels for measuring cortisol directly in serum by competitive enzyme immunoassay (ELISA) was examined. Cortisol-21-hemisuccinate was labeled separately with penicillinase, horseradish peroxidase (HRP), and alkaline phosphatase (ALP) under identical reaction conditions. Antibody developed in rabbits against cortisol-3-0-(carboxymethyl)-oxime-bovine serum albumin was used to coat polystyrene tubes that were precoated with anti-rabbit gamma globulin (ARGG). Cortisol standards were prepared in steroid-free human serum in buffer (1:4) contaning 8-anilino-1-naphthalene sulfonic acid (8-ANS). Assay buffer also consisted 8-ANS. The assay involved adding standard cortisol or serum sample to antibody-coated tubes, followed by addition of enzyme label and buffer, and incubation for 2 h at 37°C. The whole procedure took 3 h for completion. All three labels proved to be sensitive, with a slope around ?2.0. Although penicillinase as an enzyme label was highly sensitive and stable compared with others, the assays were not always accurate and precise, especially at low concentrations of cortisol. This was mainly due to the color reagent used for measuring penicillinase activity. Serum samples that underwent 2–3 freeze-thaw cycles gave high values with HRP label compared with ALP. Therefore, utilizing ALP as an enzyme label, an ELISA was developed and its performance was comparable with some of the commercial kits already in the market.     

微量元素、HP及COX-2与胃癌的相关性研究

为了研究微量元素、HP与胃癌发生的相关性 ,取甘肃河西地区 5 0例胃癌患者作为研究组 (R组 ) ,取当地 5 0例健康志愿者作为对照组 (C组 ) ,监测血清微量元素、组织中幽门螺旋杆菌 (HP)以及环氧合酶 - 2 (COX- 2 )的表达。结果显示胃癌组血清微量元素 Cu/ Zn、Fe值高于对照组 (P<0 .0 1,0 .0 5 ) :Zn、Mn低于对照组 (P<0 .0 1,0 .0 5 ) ,经多因素非条件 L ogistic回归分析 ,进入方程的有 Zn(P<0 .0 1)。胃癌组 HP感染率和 COX- 2表达阳性率分别为 88%和 78% ,而对照组则分别为 4 2 %和 0 (P<0 .0 5 ) ,提示 Zn降低可能为胃癌发生的癌前因素 ,其可诱发 HP的感染和 COX- 2的高表达而发生胃癌 ,测定血清中微量元素可提高胃癌的诊断率 ,调整体内微量元素结构可达到对胃癌的化学干预     

血清CA19-9、sICAM-1、LDH在结直肠癌患者血清中的表达及其用于预后评估的价值

目的探讨血清CA19-9、sICAM-1、LDH在结直肠癌患者血清中的表达及其用于预后评估的价值。方法选取我院于2013年1月至2015年1月诊断的120例结直肠癌患者作为研究对象,另选我院同期体检正常者110例为对照组研究对象。对所有研究对象进行入院后血清CA19-9、sICAM-1、LDH水平检测,随后在患者入院后展开为期5年的随访,分析两组血清CA19-9、sICAM-1、LDH水平差异,研究组患者血清CA19-9、sICAM-1、LDH水平与患者病理特征差异,研究组患者血清CA19-9、sICAM-1、LDH水平与临床分期、临床分型、随访情况的相关性以及Logistic分析。结果研究组患者血清CA19-9、sICAM-1、LDH水平明显高于健康对照组(P <0.05);研究组患者临床分期Ⅲ期和临床随访死亡患者的CA19-9、sICAM-1、LDH水平明显高于Ⅱ期患者和临床随访生存患者(P<0.05)。不同临床分型研究组患者血清CA19-9、sICAM-1、LDH水平从高到低依次为侵润型、溃疡型、肿块型(P<0.05);患者血清CA19-9、sICAM-1、LDH水平越高,患者临床分期、临床分型以及随访死亡情况越为严重(P <0.05);血清CA19-9、sICAM-1、LDH均为结直肠癌患者五年生存的独立危险因素。结论血清CA19-9、sICAM-1、LDH与结直肠癌患者临床分期、临床分型以及生存情况密切相关,对于患者的预后预测具有积极意义。     

CA19-9、CA72-4和CEA在阿帕替尼治疗胃癌患者中的变化及意义

目的 探讨阿帕替尼治疗前后胃癌患者血清糖链抗原19-9(carbohydrate antigen 19-9,CA19-9)、糖链抗原72-4(carbohydrate antigen 72-4,CA72-4)和癌胚抗原(carcinoembryonic antigen,CEA)的变化及其与临床疗效的关系.方法 选取我院收治的62例晚期胃癌患者作为研究对象,回顾性分析阿帕替尼治疗前后患者血清中CA19-9、CA72-4和CEA的水平,并根据临床疗效部分缓解(PR)、稳定(SD)和进展(PD)的例数,计算疾病缓解率(RR)和疾病控制率(DCR),并分为疾病控制(DC)组和非DC组,比较各组治疗前后血清CA19-9、CA72-4和CEA水平变化,并比较两组之间治疗前后各指标水平差异.结果 阿帕替尼治疗后血清CA19-9和CA72-4水平显著降低(P＜0.05),而CEA无显著性变化(P＞0.05).阿帕替尼治疗晚期胃癌的PR率为3.22％,SD率为41.94％,PD率为54.84％.阿帕替尼治疗后,DC组血清CA19-9、CA72-4和CEA水平显著下降(P＜0.05),而非DC组CA19-9、CA72-4无显著性差异(P＞0.05),CEA水平显著升高(P＜0.05).治疗前,DC组和非DC组CA19-9、CA72-4和CEA水平无显著性差异(P＞0.05),治疗后DC组三个指标水平均显著低于非DC组(P＜0.05).对患者用药不良反应发生率分析,结果显示无严重不良反应终止治疗病例.结论 血清CA19-9、CA72-4和CEA水平在阿帕替尼治疗后病情得到控制的胃癌患者中显著降低,可用于阿帕替尼治疗胃癌的效果评价.     

Matrix metalloproteinases 2, 7, and 9 in tumors and sera of patients with breast cancer

Enzyme immunoassay showed that the content of matrix metalloproteinases (MMP) 2 and 7 in tumors was higher than in the adjacent histologically intact tissue in 91 and 76% patients with breast cancer, respectively, while MMP-9 levels in the tumor and intact tissue were virtually the same. Serum concentrations of MMP-2 and MMP-7 did not correlate with their levels in the tumors, were within the normal range, and virtually did not decrease after removal of the primary tumor. Serum levels of MMP-9 in patients were significantly lower than in the control and increased after surgery in 85% patients. No clear-cut relationship between the studied parameters and clinical morphological prognostic factors of breast cancer was detected.     

胃癌患者手术前后血清SE-CAD、CEA和CA19-9检测的临床意义

目的:探讨了胃癌患者手术治疗前后血清SE-CAD、CEA和CA19-9水平的变化及意义.方法:分别应用酶免法和放免法测定了32例胃癌患者手术治疗前后血清SE-CAD、CEA和CA19-9水平的变化,并与30名正常健康人作比较.结果:胃癌患者手术前血清SE-CAD、CEA和CA19-9水平显著地高于正常人组(P＜0.01),手术治疗后6个月则与正常人组比较无显著性差异(P＞0.05).结论::检测胃癌患者血清中SE-CAD、CEA和CA19-9水平的变化对临床观察预后有重要的临床价值.     

血浆纤维蛋白原和CA724水平在胃癌患者的变化及临床意义

目的 探讨血浆纤维蛋白原（FIB）和糖类抗原724（CA724）水平在胃癌的变化及临床意义。方法 选取我院2015年1月~2017年12月经病理证实的胃癌患者50例设为胃癌组,另选30例胃良性病变患者设为胃良性病变组,30例健康体检者设为对照组,比较各组血浆FIB和CA724水平及联合检测在胃癌患者中的变化。结果 胃癌组患者血浆FIB和CA724水平［（6.12±1.55）g/L、（43.76±6.29）ng/ml）］高于对照组［（2.87±0.54）g/L、（2.41±0.26）U/ml）］,差异具有统计学意义（P＜0.05）,胃良性病变病变血浆FIB水平（3.46±0.75）g/L高于对照组,差异具有统计学意义（P＜0.05）,而CA724水平（3.66±0.73）ng/ml与对照组比较,差异无统计学意义（P＞0.05）;胃癌组血浆FIB和CA724联合检测高于单项检测,差异具有统计学意义（P＜0.05）。结论 血浆FIB和CA724水平有助于协助诊断胃癌,且两者联合检测能提高胃癌患者诊断敏感性和准确性。     

Elevated Plasma Matrix Metalloproteinase-9 and Its Correlations with Severity of Disease in Patients with Ventilator-Associated Pneumonia

Ventilator-associated pneumonia (VAP) increases patient mortality and medical expenditure, and a real-time and reliable method for the rapid diagnosis of VAP may help reduce fatal complications. Matrix metalloproteinases-9 (MMP-9) is considered significant in the pathogenesis of lung inflammation and infection. Therefore, we examined its relationship with the clinical course of VAP. This retrospective observational study recruited 30 healthy volunteers, 12 patients who used mechanical ventilation without the development of VAP (hereafter, patients without VAP), and 30 patients with a clinical diagnosis of VAP (hereafter, patients with VAP). The activity and level of plasma MMP-9 were determined through a gelatin zymography assay and ELISA. Our results report that both plasma MMP-9 activity and concentration were significantly elevated in the acute stage of patients with VAP when compared with control group and patients without VAP (p < 0.001). Subsequently, the plasma MMP-9 of patients with VAP decreased significantly after antibiotic treatment. Furthermore, plasma MMP-9 concentration was positively correlated with the clinical pulmonary infection score (r = 0.409, p = 0.007), WBCs (r = 0.620, p < 0.001), and neutrophils counts (r = 0.335, p = 0.035). In addition, plasma MMP-9 is an excellent tool for recognizing VAP when the cutoff level is set to 92.62 ng/mL (AUC = 0.863, 95% CI = 0.761 to 0.932). In conclusions, we concluded that MMP-9 levels play a role in the development of VAP and might have the potential to be applied in the development of VAP therapies.     

Urokinase and Tissue Plasminogen Activators and Their PAI-1 Inhibitor in Tumors of Patients with Oral Mucosal Cancer: Relationship with the Main Clinical Morphological Factors

Enhanced activation of plasminogen by the urokinase pathway (uPA elevation) in patients with cancer of the oral mucosa paralleled by an increase of PAI-1 level in the tumor compared to the adjacent mucosa was shown by enzyme immunoassay. No statistically significant associations of the level of the studied proteins in the tumor with such prognostic factors as location, growth form, histological structure, differentiation degree, size, and dissemination of the primary tumor, involvement of the regional lymph nodes, and stage of the disease were detected.     

Matrix metalloproteinases-2, -3 and -9 in human term placenta

Matrix metalloproteinases (MMPs) are zinc-dependent enzymes that degrade the components of the extracellular matrix (ECM) and are known to be the main mediators of human placentation and parturition. Although there are many studies on the roles and distribution of MMPs in human term placenta, so far none of the studies has investigated the distribution of MMP-2, -3 and -9 in different cells of various placental sites. In this study, we aimed to determine the distribution and enzymatic activities of MMP-2, -3 and -9 with regard to different regions of term human placenta, such as amnion, basal plate, chorionic plate, decidua, chorion laeve, Nitabuch's stria, umbilical cord and placental villi. Eighteen normal human term placentas were obtained after vaginal deliveries. Immunohistochemistry and zymography were performed for MMP-2, -3 and -9 on placental tissue sections and protein extracts, respectively. Nearly all tissues showed immunoreactivity for MMPs. The strongest enzymatic activity for MMP-2 was seen in areas where invasive trophoblast cells invaded maternal tissues. MMP-9 had the highest enzymatic activity at the contact region of fetal and maternal parts, suggesting the importance of MMP-9 in separation of the placenta from the uterine wall during labor. MMP-3 had a similar localization to MMP-9, suggesting that besides gelatinases like MMP-2 and -9, MMP-3 (stromelysin-1) may also have important roles during labor. This study describes the site-specific distribution and activities of MMPs and therefore might help in elucidating the molecular mechanisms in pathologies such as premature rupture of membranes.     

川崎病患儿血清MMP-9、TIMP-1、ET-1水平的变化及其临床意义

目的探讨川崎病（KD）患儿不同时期血清基质金属蛋白酶（MMP-9）、组织基质金属蛋白酶抑制物（TIMP-1）、内皮素-1（ET-1）水平的变化及其与冠状动脉病变之间的关系。方法采用酶联免疫吸附法（ELISA）、放免法（RIA）对34例KD患儿急性期、治疗后5d、亚急性期和恢复期血清MMP-9、TIMP-1、ET-1水平进行检测,并与34例正常健康儿童进行对照。同时应用心脏彩超检测KD患儿冠状动脉的病变。结果KD患儿不同时期血清MMP．9、TIMP．1、ET-1水平及MMP-9／TIMP-1比值组间有差异。KD患儿血清MMP-9、TIMP-1、MMP-9／TIMP-1及ET-1（292．56±28．65）μg／L、（394．50±46．80）μg／L、（0．75±0．11）、（80．65±14．00）pg／ml均明显高于正常对照组（27．53±11．67）／μg／L、（100．47±32.96）μg/L、（0．28±0．10）、（52．70±11．39）pg／ml,其中冠脉扩张组血清MMP-9／TIMP-1显著高于无扩张组,且与冠脉扩张程度呈正相关（r=0．83）,而扩张组血清MMP-9、ET-1水平与无扩张组之间无显著差异,血清TIMP-1水平低于无扩张组。结论血清MMP-9、TIMP-1、ET-1可能参与了川崎病的病理发病机制,血清MMP-9／TIMP-1持续失衡,可作为预测川崎病并发冠状动脉炎,尤其是冠状动脉扩张的生化指标之一。     

Expression and Content of Protein LC3B in Gastric Cancer Tissue,Relationship with Expression of mTOR,AMPK in Gastric Cancer Tissue and HER2 and PD-L1 Status of the Tumor

Bulletin of Experimental Biology and Medicine - We studied the mechanisms by which microRNA-126 regulates proliferation and migration of human umbilical vein endothelial cells (HUVEC) cultured in a...