基质金属蛋白酶-9及其组织金属蛋白酶抑制剂-1表达与大肠癌侵袭转移的研究

目的:探讨基质金属蛋白酶-9(MMP鄄9)及其相应组织金属蛋白酶抑制剂-1(TIMP鄄1)在大肠癌组织中的表达与大肠癌侵袭转移的关系。方法:应用免疫组织化学SP法检测了48例大肠癌组织标本及23例正常大肠标本MMP鄄9、TIMP鄄1的表达。结果:48例大肠癌组织MMP鄄9阳性率为87.5%,显著高于正常大肠标本(P<0.05),伴有淋巴结转移或肝转移者MMP鄄9的阳性率明显高于无淋巴结转移或肝转移者(P<0.05)。大肠癌组织TIMP鄄1的阳性率为54.2%,明显高于正常大肠标本(P<0.05);MMP鄄9表达超过TIMP鄄1者,发生淋巴结转移和肝转移的比例明显高于TIMP鄄1表达超过MMP鄄9者。结论:MMP鄄9和TIMP鄄1表达失衡和大肠癌的浸润、淋巴结转移、肝转移密切相关,MMP鄄9有促进肿瘤侵袭转移的作用,TIMP鄄1和大肠癌的侵袭转移呈负相关;MMP鄄9表达超过TIMP鄄1者预后不良。

基质金属蛋白酶-9 mRNA和蛋白在食管癌组织中的表达及其临床意义

目的 探讨基质金属蛋白酶 9(MMP 9)mRNA及蛋白在食管癌组织中的表达。方法 采用半定量RT PCR法及免疫组织化学方法 ,分别检测 40例食管癌及癌旁 2cm与癌旁≥ 5cm组织中MMP 9mRNA及蛋白的表达。结果 食管癌、癌旁 2cm和癌旁≥ 5cm组织中 ,MMP 9蛋白阳性率分别为 72 .5 % ( 2 9/4 0 )、5 2 .5 % ( 2 1/4 0 )和 3 0 .0 % ( 12 /4 0 ) ,MMP 9mRNA阳性率分别为 77.5 % ( 3 1/4 0 )、60 .0 % ( 2 4/4 0 )和 3 7.5 % ( 15 /4 0 ) ,癌组织与癌旁≥ 5cm组织比较 ,有显著性差异 ( χ2 =14 .45 9,P <0 .0 5 )。癌组织中MMP 9mRNA表达水平显著高于癌旁 2cm及癌旁≥ 5cm组织 (P <0 .0 5 )。癌组织中MMP 9mRNA表达水平与临床分期、组织分化程度及淋巴结转移状态密切相关 (相关系数为 0 .8862、0 .7495和 0 .890 7,P <0 .0 5 )。结论 MMP 9在食管癌侵袭及转移过程中发挥重要作用 。

基质金属蛋白酶-9与支气管哮喘

基质金属蛋白酶 9在哮喘患者的支气管肺泡灌洗液、痰、血中都增加。MMP 9mRNA的表达和免疫活性在哮喘患者的支气管镜检物中增加。本文就MMP 9的生物学特征、调节以及与气道炎症、气道重塑、气流阻塞。

HIV感染者/AIDS患者血清基质金属蛋白酶-9表达与T细胞亚群的相关性研究

目的 了解艾滋病病毒 (HIV)感染者及艾滋病 (AIDS)患者血清中基质金属蛋白酶 9(MMP 9)水平表达及与T细胞亚群的相关性。方法 用酶联免疫吸附试验 (ELISA)和流式细胞分析法 ,检测了 1 8例HIV感染者和2 4例AIDS患者血清中MMP 9水平和淋巴细胞中CD+ 3、CD+ 4、CD+ 8的表达及绝对数。结果 HIV感染者组和AIDS患者组MMP 9水平较对照组明显升高 (P <0 0 5 ,P <0 0 1 )。AIDS患者组CD+ 3细胞数较对照组显著减少(P <0 0 5)。HIV感染者组和AIDS患者组CD+ 4计数降低非常明显 (P <0 0 0 1 ) ,CD+ 8计数非常明显升高 (P <0 0 0 1 ,P <0 0 1 ) ,CD+ 4/CD+ 8的比值倒置。AIDS患者组MMP 9水平、CD+ 3、CD+ 4、CD+ 8的表达较HIV感染者组均有明显差异。HIV感染者组和AIDS患者组MMP 9表达与CD+ 4细胞数呈负相关 (P<0 0 5 ,P <0 0 1 ) ,AIDS患者组MMP 9水平与CD+ 8细胞数明显相关 (P <0 0 5)。结论 感染HIV后 ,MMP 9的水平随病情发展而增加 ,CD+ 3、CD+ 4细胞数逐渐减少 。

腹主动脉瘤发病机理的实验研究 Ⅱ.基质金属蛋白酶-9在大鼠腹主动脉瘤模型中的动态表达

目的 :检测MMP 9在大鼠正常动脉及动脉瘤模型组织中的动态表达 ,以探讨其在腹主动脉瘤发病机制中的作用。方法 :Wistar大鼠 5 4只 ,随机均分为 1组正常对照组、4组灌注对照组和 4组实验组。实验组腹主动脉灌注弹力蛋白酶 (2 5U ml) 2ml,灌注对照组灌注生理盐水 2ml,分别于术前、术后即刻、2d、7d、14d测量腹主动脉直径 ,并采用免疫组织化学和分子原位杂交技术动态检测腹主动脉组织中MMP 9的表达。结果 :正常及灌注对照组腹主动脉组织中均未发现MMP 9,而实验组弹力蛋白酶灌注后2～ 14dMMP 9均有不同程度升高 ,第 7d达到高峰 ,第 14d有所回落。结论 :MMP 9分泌的增加可能与炎症反应有关 ,且为腹主动脉瘤形成中不可或缺的一步。

基质金属蛋白酶-9及其mRNA在胃癌中的表达与血管新生的关系

目的 观察基质金属蛋白酶 9(MMP 9)与MMP 9mRNA在胃癌组织及细胞中的表达与作用特点 ,及其与肿瘤浸润、转移及血管新生之间的关系。方法 利用 74例胃癌标本及体外培养人胃低分化腺癌细胞BGC82 3,经连续切片免疫组织化学染色、原位杂交、侵袭实验、酶谱分析及形态定量分析方法 ,进行金属蛋白酶 (MMP) 9、MMP 9mRNA、CD34、α SMA、VEGFR 1、VEGFR 2的检测 ,并结合临床病理参数进行综合分析。结果 MMP 9及其mRNA的表达均与癌组织的浸润深度、分化程度、淋巴结转移密切相关 ;MVD与癌组织的浸润深度、淋巴结转移关系密切 ;BGC82 3细胞MMP 9,MMP 9mRNA ,VEGFR 2染色均为阳性 ,VEGFR 1染色阴性 ;MMP 9抗体可使BGC82 3细胞侵袭细胞数由 6 9± 5个 /40 0倍下降为 (18± 4 )个 /40 0倍 ;直接培养于培养皿表面的BGC82 3细胞有稳定的MMP 9,MMP 2酶原表达 ,但培养于I型胶原包被培养皿表面的BGC82 3细胞MMP 2表达明显增强并出现活化形式 ;BGC82 3细胞与VEGF共孵育 ,条件培养基中MMP 9酶原含量以VEGF剂量依赖的方式增加。结论 胃癌细胞自身具有产生与分泌MMP 9的能力 ,MMP 9对肿瘤的浸润、转移及间质血管新生具有促进作用。

3种肿瘤相关蛋白与直肠癌浸润和转移的关系

[目的]检测直肠癌组织中与浸润转移过程相关的蛋白钙粘素(E-cad)、基质金属蛋白酶-9(MMP-9)、血管内皮细胞生长因子(VEGF)的表达,探讨这些因素与大肠癌浸润、转移的相关性,以期寻找能够进一步判断大肠癌浸润转移潜能的分子生物学指标。[方法]采用免疫组化SP方法检测90例直肠癌中E鄄cad、MMP-9、VEGF的表达。[结果]E-cad的表达随着癌组织的分化程度的降低而降低,随浸润深度的加深及转移的出现逐渐下调。MMP鄄9的表达随着浸润深度的加深及淋巴结转移的出现而逐渐增强。VEGF的表达与淋巴结转移呈正相关。[结论]直肠癌的浸润和转移与E-cad、MMP-9、VEGF的表达具有显著相关性。应用多种抗体检测肿瘤相关蛋白并分析其表达的意义,将有助于判断直肠癌的浸润、转移潜能及预后,为临床治疗方案的选择提供理论依据。

脑星形细胞瘤组织MMP-9表达与瘤周水肿及病理分级的关系

目的:探讨星形细胞瘤组织基质金属蛋白酶9(matrix metalloproteinase,MMP-9)表达与瘤周水肿及病理分级的关系.方法:采用免疫组织化学(S-P)法,用抗MMP-9对40例星形细胞瘤组织标本(病理Ⅰ～Ⅱ级22例,Ⅲ～Ⅳ级18例)进行标记分析,并测定MRI图像上肿瘤瘤周水肿范围.结果:星形细胞瘤的瘤周水肿范围越大,其MMP-9的表达也越高;病理分级Ⅲ-Ⅳ级星形细胞瘤组织中MMP-9的表达明显高于Ⅰ-Ⅱ级.结论:星形细胞瘤组织MMP-9与瘤周水肿及恶性程度密切相关.

Expressions of MMP-2,-9,TIMP-1,-2,-3 mRNA in Rat Uterus during Estrous Cycle

Zymography and in situ hybridization were used to investigate matrixmetalloproteinase -2, -9 (MMP -2, MMP-9) activities and expressions of MMP -2, -9 and TIMP1, -2, -3 (tissue inhibitors of matrix metallo-proteinases) mRNA in the rat uterus during estrouscycle. The relative activity was semiquanted by using densitometric analysis. The MMP-2(67 kDa) activity in every stage during estrpus cycle was detected by zymography. MMP-2activity was highest at proestrus; higher at estrus and metaestrus; lowest at diestrus. Throughin situ hybridization, MMP -2, -9, TIMP -1~ -3 mRNA mainly in hasal stroma cells of uterineendometrium were detected. The positive signals of MMP -2 and -9 mRNAs in hasal stromacells were shown stronger at proestrus, estrus and metaestrus while they showed the weakest atdiestrus. The expression of MMP -2 mRNA coincided with MMP -2 activity change. MMP-2and -9 mRNAs were also highly expressed in uterine circular muscle at estrus. Weak signals ofMMP -9 mRNA were detected in uterine luminal and glandular epithelial cells at estrus.TIMP -1 mRNA in hasal stroma cells was shown as the strongest expression at estrus andmetaestrus; stronger at proestrus and the weakest at diestrus. TIMP-2 mRNA in basal stromacells was stronger at estrus and diestrus; weaker at proestrus and metaestrus. TIMP -1 and -2mRNAs were also highly expressed in uterine luminal and glandular epithelial cells at estrus.TIMP -3 mRNA in hasal stroma cells revealed the strongest expression at estrus; stronger atdiestrus and metaestrus and showed the weakest at proestrus. The mRNA was also highlyexpressed in uterine circular muscle at estrus. In short, our present results provide evidencethat MMP -2, -9 and TIMP -1~ -3 were involved in rat uterine endometrium reconstructionduring estrous cycle.

Alterations of glutathione S-transferase and matrix metalloproteinase-9 expressions are early events in esophageal carcinogenesis

AIM: To investigate the role of glutathione S-transferase (GST) and matrix metalloproteinase-9 (MMP-9) expres-sions in the development and progression of reflux es-ophagitis-Barrett’s metaplasia-dysplasia-adenocarcinoma sequence in the esophagus.METHODS: GST and MMP-9 expressions were analyzed in 51 paraffin-embedded tissue samples by immunohisto-chemistry including patients with reflux esophagitis (n = 7), Barrett’s metaplasia (n = 14), Barrett and esophagi-tis (n = 8), Barrett and dysplasia (n = 7), esophageal adenocarcinoma (n = 8) and a control group without any histological changes (n = 7). Immunostaining was determined semiquantitatively. Statistical analysis with one-way ANOVA, LSD test and correlation analysis were performed. P value of < 0.05 was considered significant.RESULTS: GST expression was significantly higher while MMP-9 expression was significantly lower in control group compared to Barrett’s metaplasia and the other groups. No major changes were observed between Bar-rett, esophagitis, and Barrett and concomitant esophagi-tis. Barrett and concomitant dysplasia, and adenocarci-noma revealed a significant lower expression of GST and higher levels of MMP-9 compared to all other groups. Adenocarcinoma showed almost no expression of GST and significantly higher levels of MMP-9 than Barrett and concomitant dysplasia. Alterations of GST and MMP-9 were inversely correlated (r = - 0.82).CONCLUSION: Decreased GST and increased ex-pression of MMP-9 in Barrett’s metaplasia-dysplasia-adenocarcinoma sequence as compared to normal tissue suggest their association with esophageal tumorigenesis. Loss of GST and gain of MMP-9 in Barrett with dyspla-sia compared to non-dysplastic metaplasia indicate that these alterations may be early events in carcinogenesis. Quantification of these parameters in Barrett’s esopha-gus might be useful to identify patients at higher risk for progression to cancer.

The relationship between matrix metalloproteinases-9 and CD15s antigen in angiogenesis of gastric carcinoma

Objective： To investigate the relationship between matrix metalloproteinases-9 （MMP-9） and sialyl Lewis X （CD15s） antigen in invasion and metastasis of gastric carcinoma. Methods： Expression of CD105, MMP-9 and CD15s in 47 cases of gastric carcinoma undergone radical surgery were evaluated by SP immunohistochemical staining using the respective monoclonal antibody. The microvessel density （MVD） marked with CD105 was detected. Correlation between MVD and MMP-9, CD15s was also statistically analyzed. Results： The MVD in both MMP-9 and CD15s positive expression group was higher significantly than that in MMP-9 or CD15s positive expression alone group, and it was also significantly higher than that in both MMP-9 and CD15s negative expression group. Conclusion： MMP-9 is a marker of invasion and CD15s is a marker of metastasis in gastric carcinoma. Combining detection of MMP-9 and CD15s has certain clinical significance for diagnosis, treatment and assessing the prognosis for gastric caner.

Expressions of cyclooxygenase-2 and matrix metalloproteinase-9 in cervical carcinoma and their clinical significance

Objective: To investigate the expressions of cyclooxygenase (COX)-2 and matrix metalloproteinase (MMP)-9 in cervical carcinoma and their clinical significance. Methods: Immunohistochemistry SP method was used to detect the expres- sions of COX-2 and MMP-9 in 72 cases of invasive carcinoma of cervix (ICC) and 16 cases of normal cervical epithelium remote from tumor (NCE). The relationships between the expressions of COX-2, MMP-9 in ICC and some characteristics relating to clinical pathology of cervical carcinoma such as histological grading, lymph node metastasis, stromal invasion and FIGO stage were analyzed statistically. Results: The rates of the positive expressions of COX-2 and MMP-9 in ICC were significantly higher than those in NCE. COX-2: 88.9% (64/72) in group ICC and 12.5% (2/16) in group NCE, P = 0.000; MMP-9: 94.4% (68/72) in group ICC and 43.8% (7/16) in group NCE, P = 0.000. The expression of COX-2 was positively correlated with lymph node metastasis (r = 0.296, P = 0.012) and stromal invasion (r = 0.257, P = 0.029). The expression of MMP-9 was positively correlated with FIGO stage (r = 0.329, P = 0.005) and histological grading (r = 0.351, P = 0.003). The expression of COX-2 was positively correlated with the expression of MMP-9 in ICC (r = 0.297, P = 0.011). Conclusion: The overexpressions of COX-2 and MMP-9 were closely related to the invasion and growth of cervical carcinoma. The tissue with the overexpression of COX-2 had strong invasion ability. COX-2 and MMP-9 had synergistic effect on proliferation, invasion and metastasis of cancer cells. Detecting the coexpression of COX-2 and MMP-9 may be of value in further understanding the biological behavior and predicting the prognosis of cervical carcinoma.

Contrary Regulation of TIMP-1 and MMP-9 by Hepatocyte Growth Factor Antibody after Lung Injury

Objective To study the influence of hepatocyte growth factor (HGF) antibody on the lung expression level of matrix metalloproteinases-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1). Methods Thirty male Wistar rats were randomly divided into 3 groups: control group, model group, and intervention group. Endotoxin was intratracheally infused in the model and intervention groups. HGF antibody was injected in the rats of the intervention group from day 1 to day 14, while the same volume of saline was injected in the control group. The rats were sacrificed on day 28 after endotoxin treatment. The amounts of MMP-9 mRNA and TIMP-1 mRNA were measured by reverse transcription-polymerase chain reaction, and protein expression levels of MMP-9 and TIMP-1 were measured by immunohistochemistry. Results In the model group, both mRNA and protein expression levels of TIMP-1 were significantly increased, the same as MMP-9. In the intervention group, the increase of TIMP-1 was remarkably reduced compared with the model group, while the mRNA and protein expression levels of MMP-9 were still increased. Conclusion HGF activity may accelerate the repair of lung injury through contrary regulating the expression levels of TIMP-1 and MMP-9.

Serum metrix metalloproteinase-9 combined with homocysteine, IL-6, TNF-α, CRP, HbA11c and lipid profile in the incipient diabetic nephropathy with or without macrovascular diseases

Objective ： To evaluate the changes of serum matrix metalloproteinase-9 （romp-9） in patients of incipient diabetic nephropathy with or without macrovascular disease and to analyze the factors associated with homocysteine（hcy）, interleukin-6（IL-6）, tumor necrosis factor-alpha （TNF-α）, highly sensitive C-reactive protein （hsCRP）, HbAlc and lipid profile in those patients in order to know whether this marker or other factors are more important to induce diabetic macrovascular disease. Methods： Type 2 diabetes mellitus（T2DM） subjects with incipient diabetic nephropathy with or without macrovascular disease were selected for participation and divided into 2 groups. The patients in group 1 （n= 38） used insulin, and patients in group 2 （n=34） were treated with an oral antidiabetic drug. Then serum mmp-9, hey, IL-6 and TNF-α in these patients were measured, and compared to the healthy subjects as control （n= 16）. The results were analyzed by SPSS13. Results： Serum romp-9 and hcy of the patients having incipient diabetic nephropathy with macrovascular disease were higher than that of patients without macrovascular disease （P〈0.01）. For insulin-injected patients, whether they accompanied with macrovascular diseases or not, the serum levels of romp-9, hcy, IL-6 and TNF-α were all lower, but no significant statistics compared with non-insulin used patients or the healthy subjects. The serum level of romp-9 was more correlated with the serum hcy in antidiabetic drug used patients. （P〈0. 000） Conclusion： The serum level of romp-9 plays an important role of pathogenesis in the macrovascular disease in the incipient diabetic patients, and the serum level of hcy also can reflect the severely degree of macrovascular disease in these patients, insulin can reduce these markers.

Elevated plasma level of matrix metalloproteinases-9 and its significance in patients with abdominal aortic aneurysms

Objective: To investigate the changes of the plasma level of MMP-9 (Matrix Metalloproteinase-9, MMP-9) in the patients with abdominal aortic aneurysms (AAAs) before and after the treatment, and evaluate the significance of MMP-9 in the pathogenesis of AAAs. Methods: Blood samples of 35 patients with AAAs and 10 patients with the arterial occlusive diseases (AODs) , which enrolled into the Vascular Surgery Center of Colonge University Hospital from February to August of 2002, were collected before and one month after surgical repair or less-invasive endovascular exclusion. The plasma concentrations of MMP-9 of all the collected samples were measured by means of enzyme-linked immunosorbent assay(ELISA), and compared between the two groups patients at different time point. Results: The mean plasma concentration of MMP-9 of AAAs was significantly higher than that of AODs prior to treatment [(90.3±9.1) ng/ml vs (23.6±7.3) ng/ml, P<0.05], and no apparent difference was showed in the patients with AODs [(23.6±7.3) ng/ml vs (25.3±5.8) ng/ml, P>0.05)] before and after the surgical bypass operation. However, in the patients with AAAs the plasma concentration of MMP-9 was apparently decreased one month after the surgical repair or endovascular exclusion compared with before [(28.6±8.4) ng/ml vs (90.3±9.1) ng/ml, P<0.05)]. No meaningful difference of the mean plasma MMP-9 concentration was seen between two groups after the both being successfully treated [(28.6±8.4) ng/ml vs (25.3±5.8) ng/ml, P>0.05]. Conclusion: Apparent elevation of plasma concentration of MMP-9 in the AAAs and its dramatic decrease after being treated implicated that MMP-9 might play an important role in the formation and development of AAAs. Meanwhile, to investigate the changes of MMP-9 level of AAAs could provide an practical way to facilitate the earlier diagnosis and long term surveillance for AAAs. More importantly, pharmacologic prevention and treatment of AAAs, in which the MMP-9 serves as effective target, might be possible in the future.

巴曲酶治疗糖尿病大鼠局灶性脑缺血再灌注损伤的实验研究

目的观察巴曲酶对糖尿病大鼠局灶性脑缺血再灌注损伤的影响及探讨巴曲酶是否对溶栓并发脑出血有保护作用及可能作用机制。方法腹腔注射链脲佐菌素建立糖尿病大鼠模型 ,血管内细丝栓堵大脑中动脉 (MCA) 2h后拔除线栓制作局灶脑缺血再灌注损伤模型 ,分别用巴曲酶、尿激酶以及两者联合治疗 ,同量注射生理盐水作为对照 ,观察MCA缺血再灌注后 2 4h、48h各组大鼠脑梗死灶体积 ,脑出血发生及 2— 48h基质金属蛋白酶 (MMP) 2、MMP 9的变化。结果各治疗组梗死灶体积及体积百分比比生理盐水组显著减小 ,各治疗组间无显著性差异 ;尿激酶组有 5例发生脑出血 ,巴曲酶组无脑出血 ,联合应用巴曲酶与尿激酶组脑出血发生少于尿激酶组 ,但无显著性 ;巴曲酶组和联合应用巴曲酶与尿激酶组梗死灶周边MMP 2、MMP 9蛋白表达显著低于生理盐水组和尿激酶组。结论巴曲酶溶栓可使糖尿病大鼠局灶性脑缺血再灌注损伤梗死灶体积减小 ,减轻缺血再灌注损伤程度 ,无脑出血并发症 ,这一作用可能与巴曲酶抑制MMP 2和MMP 9的活化有关。

RNF13： a novel RING-type ubiquitin ligase over-expressed in pancreatic cancer

Protein ubiquitination by E3 ubiquitin ligases plays an important role in cancer development. In this study, we provide experimental evidence that a RING-finger-containing protein RNF13 is an ER/Golgi membrane-associated E3 ubiquitin ligase and its RING finger domain is required for the ubiquitin ligase activity. Immunohistochemical analysis of pancreatic ductal adenocarcinoma （PDAC） and paracancerous normal tissues from 72 patients documented RNF13 over-expression in 30 tumor samples （41.7%, 30/72）, and its expression was significantly associated with histological grading （P= 0.024）. In addition, RNF13 was detected in precancerous lesions： tubular complexes in chronic pancreatitis （CP） and pancreatic intraepithelial neoplasia （PanIN） （79.3%, 23/29 and 62.8%, 22/35, respectively）. Moreover, RNF13 staining was significantly correlated with Tenascin-C expression （P = 0.004） in PDAC samples, further supporting the role of RNF13 in cancer progression. Over-expression of wild type but not RING domain-mutant RNF13 in pancreatic MiaPaca-2 cancer cells increased invasive potential and gelatinolytic activity by matrix metalloproteinase-9. Taken together, these findings reveal that RNF13 is a novel E3 ubiquitin ligase involved in pancreatic carcinogenesis; ubiqui-tin-mediated modification of proteins by RNF13 may participate in pancreatic cancer development.

EFFECTS OF GENISTEIN ON INVASION AND MATRIX METALLOPROTEINASE ACTIVITIES OF HT1080 HUMAN FIBROSARCOMA CELLS

Effects of genistein on invasion and matrix metalloproteinase activities were investigated in HT1080 human sarcoma cells.Invasion of HT1080 cells through reconstituted basement membrane was inhibited when the cells were treated with 100 μ mol/L and 200 μ mol/L genistein.At the same concentrations,genistein not only suppressed latent forms of matrix metalloprotinese 2 and 9(MMP 2 and MMP 9) to convert into active forms,but also increase dramatically the tissue inhibitor of metalloproteinase(TIMP 1) mRNA contents and reverse the imbalance of MMPs and TIMPs.However,expressions of MMP 2 and MMP 9 were not significantly affected.Suppression of MMP activation and increase of TIMP 1 expression will decrease matrix degradation by MMPs,and consequently inhibit invasions of the cells.These results emphasized the existence of the imbalance between MMPs and TIMPs in tumor invasion and metastasis formation.The value of genistein as a drug for antiinvasion and anti metastasis chemotherapy was suggested.

Effects of carbon dioxide pneumoperitoneum on metastasis of ovarian carcinoma cell line SKOV_3

The long suspicion of the potential harm of carbon dioxide （CO2） pneumoperitoneum exists in laparoscopic cancer surgery. For better understanding of this problem, we targeted this study at the effects of CO2 pneumoperitoneum on the invasive ability of ovarian carcinoma cell line and the possible mechanism within it. To study the effects of CO2 pneumoperitoneum on carcinoma cell, SKOV3 cells were divided into 2 groups, respectively exposed to pneumoperitoneal CO2-insuffiation and normal conditions. To study the possible mechanism, SKOV3 cells were divided into 3 groups, one was exposed to CO2 pneumoperitoneum, one to N2 and the other to normal conditions served as control. The in vitro adhesive and invasive ability of the cells was analyzed through 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyl tetrazolium bromide （MTT） assay and Boyden filters metastasis model; the expressions of vascular endothelial growth factor C （VEGF-C） and matrix metalloproteinase 9 （MMP9） were determined by reverse transcription polymerase chain reaction（RT-PCR）, and Western blot. We found that the adhesive ratio of SKOV3 cells exposed to CO2 was significantly higher than that of the control group; cells exposed to CO2 invaded the matrigel with a greater number （P〈0.01）; the expression of VEGF-C exposed to both CO2 and N2 was significantly increased compared with control group （P〈0.05）; the MMP9 expression level of CO2 group was higher than that of N2 group, P〈0.05. We concluded that carbon dioxide pneumoperitoneum may improve the adhesive and invasive ability of ovarian carcinoma cell line in vitro and CO2 can also be an independent factor to stimulate the expression of MMP9.

Glucosamine reduces blood-brain barrier disruption by inhibiting the expression of matrix metalloproteinase-9 in experimental autoimmune encephalomyelitis rats

We investigated the effects of glucosamine(GS) on blood-brain barrier(BBB) function and matrix metalloproteinase-9 (MMP-9) expression in rats with experimental autoimmune encephalomyelitis(EAE).Animals were randomly divided into three groups,among which the EAE and GS groups were immunized with complete antigen and pertussis toxin,and the adjuvant group was immunized with complete Freund's adjuvant and pertussis toxin.Rats were treated by peritoneal injection of GS 180 mg/(kg·d) in the GS group and peritoneal injection of phosphate-buffered saline 4.5 mL/(kg·d) in the EAE and adjuvant groups.We proposed to assess the integrity of BBB by calculating cerebrospinal fluid to serum albumin quotient(QA) on days 6,8,10,12,14,16 and 18 post-immunization.At the same time,the brains and spinal cords were removed for MMP-9 immunohistochemical staining. Experiments demonstrated that in the EAE group,QA value and MMP-9 expression were highly elevated and up-regulated and correlated to disease severity.Moreover,there was statistically significantly positive correlation between QA value and MMP-9 expression.In the GS group,we observed that the mean disease onset date was delayed,the incidence and mean score of symptom were suppressed at the peak phase of disease(P<0.05).Furthermore,QA value and MMP-9 expression in the GS group showed stronger inhibition when compared with those of the EAE group(P<0.05).Our study showed that GS would reduce the BBB breakdown and leukocyte trafficking by inhibiting the production of MMP-9 and mitigate EAE.