Research Progress of Targeting uPA-uPAR System in Tumor Therapy / 肿瘤防治研究

The uPA-uPAR system is highly expressed in various tumor tissues. This system can promote the degradation of extracellular matrix proteins, as well as combine with vitronectin and integrin to transmit intracellular signal transduction. Subsequently, it mediates the occurrence and development of tumors. In recent years, a series of therapeutic programs that target this system has achieved notable results in tumor treatment, and some of them have been under the clinical trial stage, thus providing new ideas for tumor targeted therapy. Therefore, this paper intends to provide a review of research progress on the gene therapy, drug therapy, and immunotherapy targeting uPA-uPAR system.

Interlocuções entre acolhimento e crise psíquica: percepção dos trabalhadores de uma Unidade de Pronto-Atendimento / Interlocution between reception and psychic crisis: perception of an Emergency Care Unit workers

Resumo A Lei da Reforma Psiquiátrica Brasileira (RPB) dispõe sobre os cuidados e sobre a atenção à pessoa em crise psíquica e, a partir desse documento, tais demandas passaram a ser ponto-chave para os serviços de saúde, inclusive para as unidades de urgência e de emergência. Com base nessa normativa, objetivou-se analisar as noções que os profissionais apresentam com relação ao acolhimento e à crise psíquica. Optou-se pela pesquisa qualitativa exploratória, que realizou entrevistas semiestruturadas com 11 profissionais de distintos setores de uma Unidade de Pronto Atendimento no interior do Rio Grande do Sul. Utilizou-se a análise de conteúdo, em que se constataram duas categorias emergentes: 1) Noção de crise psíquica para os profissionais da UPA e 2) Noções e as práticas de acolhimento à crise psíquica exercida pelos(as) trabalhadores(as) da UPA. Os resultados evidenciam que tanto a noção de crise psíquica quanto as práticas de acolhimento empregadas pelos trabalhadores, de uma forma geral, estão associadas ao modelo biomédico, com dificuldade para ampliar a compreensão e os modos de acolher sujeitos em crise. Nesse sentido, a noção dos trabalhadores da UPA em estudo, com relação ao acolhimento da pessoa em crise psíquica, está desarticulado com o que preconiza a RPB.

Abstract The Brazilian Psychiatric Reform Law provides for the care and attention to the person in a mental crisis and based on this document, such demands became a key point for health services, including emergency units and of emergency. Based on this normative, we aimed to analyze the notions that professionals have regarding reception and the psychic crisis. We used exploratory qualitative research, which conducted semi-structured interviews with 11 professionals from different sectors of an Emergency Care Unit (ECU) in the interior of Rio Grande do Sul state, Brazil. Content analysis was used, in which two emerging categories were found: 1) Notion of psychic crisis for ECU professionals and 2) Notions and practices of reception to the psychic crisis exercised by ECU workers. The results show that both the notion of psychic crisis and the welcoming practices employed by workers, in general, are associated with the biomedical model, with difficulty to broaden the understanding and ways of welcoming individuals in crisis. In this sense, the notion of ECU workers under study, in relation to the reception of the person in a mental crisis, is not articulated with what the Psychiatric Reform Law advocates.

To Compare the Efficacy of Ulipristal acetate and Mifepristone in Management of Uterine Fibroids in Symptomatic Patients of Reproductive Age Group

Introduction: Uterine myomas incidence is variable asmost of the patients are asymptomatic but most commonclinical feature which makes women seek their treatment aremenorrhagia and iron deficiency anaemia leading to chronicfatigue. Study aimed to compare the efficacy of UPA andmifepristone in medical management of uterine fibroids insymptomatic patients of reproductive age group.Material and methods: A prospective randomizedobservational study was carried out, in women with single ormultiple uterine leiomyoma. Exclusion criteria: severe anemia,using any hormonal therapy, with suspected carcinomas orwith adnexal masses. 100 patients were randomly allocatedto two subgroups; group A receiving 5 mg UPA and groupB receiving 25 mg Mifepristone daily, for 13 weeks. PBACwas used to assess menstrual blood loss and Likert scorefor other symptoms. Baseline variables: uterine size andvolume, Myoma size and volume, number, hemoglobin, liverfunction tests were noted and reassessed at 1, 3 and 6 months.Endometrial sampling was done initially and at the end tostudy.Results: Mean fibroid volume reduction was 35.23% in groupA and 33.45% after 13 weeks’ treatment in group B. Meanreduction in menorrhagia: 84% in group A and 52.5% in groupB. 91% cases experienced amenorrhoea in group A and 72%in group B.Conclusion: UPA 5mg was better at achieving significantreduction in menorrhagia and achieving amenorrhoeic state ascompared to Mifepristone.

Mouse models for hepatitis B virus research / 한국실험동물학회지

Hepatitis B virus (HBV) infection remains a major global health problem; indeed, there are 250 million carriers worldwide. The host range of HBV is narrow; therefore, few primates are susceptible to HBV infection. However, ethical constraints, high cost, and large size limit the use of primates as suitable animal models. Thus, in vivo testing of therapies that target HBV has been hampered by the lack of an appropriate in vivo research model. To address this, mouse model systems of HBV are being developed and several are used for studying HBV in vivo. In this review, we summarize the currently available mouse models, including HBV transgenic mice, hydrodynamic injection-mediated HBV replicon delivery systems, adeno-associated virus-mediated HBV replicon delivery systems, and human liver chimeric mouse models. These developed (or being developed) mouse model systems are promising and should be useful tools for studying HBV.

A real-time qPCR method to identify diatom UPA gene for the drowning diagnosis / 中国法医学杂志

Objective To establish a Real-time quantitative PCR method (qPCR) for the detection of diatom UPA barcoding genes and evaluate its application in the drowning diagnosis. Methods The homologous sequences of diatoms UPA gene was obtained by Blast from GeneBank, based on which the universal primers for diatoms were designed. DNA were extracted from 2 common human symbiotic bacteria (Escherichia coli, Bifidobacterium longum), 3 species of planktonic bacteria, 15 species of planktonic algae, tissue samples (lung, liver and kidney) from human cadavers (28 drowning victims, 1 victims by non-drowning in the water, 3 victims deaths on land) in 32 cases. The specificity, sensitivity and repeatability of the designed primers were tested. The positive rates of diatoms detection in the drowning cases were calculated. The results of the real-time quantitative method were evaluated comparatively by Microwave Digestion-Vacuum Filtration-Automated Scanning Electron Microscopy (MD-VF-Auto SEM) and PCR-Capillary Electrophoresis (PCR-CE). Results The results showed that the primers UPA99 had strong specificity for the diatomaceae (Synedra radians, Navicula sp., Melosira varians, Cyclotella sp. and Nitzschia sp.) DNA. The melting curve of the amplified product was smooth; the peak was narrow; the melting temperature was (87±1)℃. The sensitivity of qPCR method was 1.56×10-5ng/μL with the detection range of 1.56×102ng/mL~1.56×10-5ng/μL, in contrast with the PCR-CE method (1.56×10-3ng/μL). This real-time PCR method showed high repeatability and stability with the coefficient of variation less than 2%. The detection rate of lung, liver and kidney was 89.3%, 71.4% and 64.3% respectively. Conclusion The established qPCR method, based on the universal primers designed for diatom UPA gene, has high specificity, high sensitivity and good repeatability. With a promising prospect for application, qPCR is suitable for drowning diagnosis.

Expression of uPA in eutopic endometrial glandular epithelial cells and its relationship with invasiveness in endometriosis / 实用医学杂志

Objective To discuss the expression of urokinasc-type plasminogen activator (uPA) and its relationship with invasiveness in eutopic endometrial glandular epithelial cells in patients with endometriosis (EMS).Methods Nine cases of eutopic endometrial glandular epithelial cells of EMS patients and normal endometrium were cultivated and identified respectively by primary cell culture,and the expression of uPA was detected via western blot and RT-PCR,and the relationship between nPA and the migration and invasiveness of glandular epithelial cells was analyzed in Transwell chamber.Results The expression of uPA and mRNA was significantly increased in eutopic endometrial glandular epithelial cells than that in normal endometrium,indicating statistical significance (all P ＜ 0.05);the cell invasiveness of EMS eutopic endometrial glandular epithelial cells was significantly enhanced when compared with that of normal cells,which was statistically significant (P ＜ 0.05).Conclusion The expression of uPA in EMS eutopic endometrial glandular epithelial cells increases significantly,and it is obviously correlated with cell invasion and migration,revealing uPA is closely related with the occurrence of EMS.

Correlation between 1H-MRS and the expression of VEGF,MMP-9 and uPA in brain glioma / 实用放射学杂志

Objective To evaluate the relationship between 1H-MRS features of brain glioma and its pathological grade and invasiveness, and the correlation between those features and the expression of VEGF, MMP-9 and uPA.Methods The brain gliomas in 55 patients confirmed by pathology were divided into two groups: high grade and low one.An analysis of intragroup and intergroup differences in some metabolite ratios of 1H-MRS in the tumor parenchyma was conducted.The expression of MMP-9,VEGF and uPA in brain glioma was detected,and the correlation between the above three parameters and changes in metabolite ratios of 1H-MRS were explored.Results There was significant difference and correlation in Cho/Cr and Cho/NAA ratio in the tumor parenchyma between high and low grade(P0.05).Conclusion VEGF and MMP-9 play an important role in the development of brain glioma.Cho/Cr and Cho/NAA ratios provide an important reference for preoperative grading of brain gliomas and indirectly reflect the expression of VEGF and MMP-9.

Effects of simvastatin on expressions of uPA/PAI-1 in neutrophils in rats with septic shock / 实用医学杂志

Objective To explore the effects of simvastatin on the protein expressions of urokinase-typeplasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1). Methods Male Sprague–Dawley rats were divided into saline group , LPS group and LPS plus simvastatin group , and were then pretreated with simvastatin (1 mg/kg) for 30 minutes before addition of LPS (8 mg/kg). Changes in left ventricular pressure were recorded. Ninety minutes after LPS injection, whole blood was collected from the inferior vena cava, and neutrophils were separated. The neutrophils were then lysed to detect levels of uPA and PAI-1. Results Left ventricular systolic pressure (LVSP: mmHg), maximal differential of left ventricular pressure (+dp/dtmax:mmHg/s), and heart rate (beats/min) were markedly decreased at different time points after administration of LPS, and maximal differential of left ventricular pressure increased in the rats receiving LPS as compared with those receiving saline, although the differences between the control and LPS groups were not statistically significant. LPS caused a great decline in uPA content and an elevation in PAI-1 content in neutrophils, but simvastatin diminished the impact of LPS on neutrophils. Conclusion Simvastatin plays a role in protection of cardiac function in rats with LPS-induced septic shock , and controls expressions of uPA and PAI-1 in neutrophils.

The establishment of the uPA inducible expression system / 中国比较医学杂志

Objective To establish uPA inducible expression system using recombinant retroviral system for the further construction of inducible uPA-SCID animal model .Methods The Inducible expression system need to construct two plasmids:pLNHXO1O2-Alb-GLUC-FMN2A -rtTA and pLNHXO5O6-TRE2-uPA-IRES-ZsGreen respectively. Both plasmids were based on retroviral vector pLNHX , Albumin promoter gene ( Alb) and rtTA gene or uPA gene and ZsGreen were obtained by PCR reaction and inserted into pLNHX .The Gaussia enzyme fluorescent element ( GLUC) was used to monitor rtTA expression in pLNHXO1O2-Alb-GLUC-FMN2A-rtTA, and the ZsGreen for uPA expression monitoring in pLNHXO5O6-TRE2-uPA-IRES-ZsGreen.The correct constructed plasmids were transfected into packaging cell line GP 2-293 to gain recombinant viral particles .NIH/3T3 cells were infected with these viral particles and selected with G 418.Gene expression in the surviving cells was confirmed by the PCR method .Results The recombinant retroviral vectors harbouring target genes were successfully cloned .The rtTA gene in pLNHXO1O2-Alb-GLUC-FMN2A-rtTA was expressed, and uPA can be induced to express in pLNHXO5O6-TRE2-uPA-IRES-ZsGreen by doxycycline (Dox) when the plasmid transfected into the HepG-Tet-on cell.The constructed recombinant two retroviral vectors were transfected into GP 2-293 packaging cells respectively to gain infectious viral particles .Then,NIH/3T3 cells were infected with these viral particles and single-cell clones which stably expressed the transgenes were successfully established .Conclusion This study primarily established uPA inducible expression system , it laid a foundation for the murine model of inducible liver damage , and provided a novel technical platform for further building the liver humanised murine models for viral hepatitis studying .

Expression and clinical significance of Hpa and uPA in thyroid carcinoma / 中华内分泌外科杂志

Objective To study the relationship between heparanase( Hpa) , urokinase type plasminogen activator( uPA) expression and lymph node metastasis in thyroid carcinoma.Methods Immunohistochemieal SP method was used to analyze the expression of Hpa and uPA in 113 cases of thyroid carcinoma and 134 cases of be-nign thyroid nodules.The expression of Hpa and uPA in thyroid carcinoma and its clinical significance were ana-lyzed.Results The positive expression rate of Hpa and uPA in thyroid carcinoma and benign nodular thyroid tis-sue were 82.30%,16.42%and 89.38%, 11.19%.The positive expression rate of Hpa and uPA in carcinoma tissues with lymph metastasis and without metastasis were 93.94%,100% and 65.96%,74.47%.Expression of Hpa and uPA in thyroid carcinoma group was significantly higher than that of benign thyroid nodules group( P<0.001) .The rate of positive expression in lymph metastatic tissues were significantly higher than those in tissue without metastasis( P<0.001) .Hpa and uPA expression in thyroid carcinoma tissues was positively correlated( r=0.437, P=0.021).Conclusion The expression of Hpa and uPA is closely related with the occurrence and metastasis of thyroid carcinoma.

Effect of chinese traditional herb Epimedium grandiflorum C.Morren and its extract Icariin on osteoarthritis via suppressing NF-kB pathway.

Osteoarthritis (OA), which is also called degenerative arthritis, is the leading cause of disabilities in the old people. The Chinese traditional herb Epimedium grandiflorum had long been found to attenuate osteoarthritis process, but the detailed mechanism was not clear. To study the mechanisms of E. grandiflorum in the treatment of osteoarthritis, rabbit osteoarthritis model combined with D-galactose was used. After different treatments for 10 weeks, cartilage sections were analyzed by immunohistochemistry for uPA, uPAR and PAI expression level. E. grandiflorum could significantly attenuate OA condition and decrease uPA, uPAR and PAI expression. The extract of E. grandiflorum, icariin also had a similar effect when compared with E. grandiflorum treatment alone. Rabbit chondrocytes were further isolated to be stimulated by TNFα combined with different reagents treatment. Here, icariin treatment significantly reduced nuclear factor kappa B NF-B (P65) activity, decreased uPA expression level and increased IBα protein level. The results indicated that E. grandiflorum and its extract icariin could attenuate OA condition, reduce the expression of uPA and uPAR and increase PAI in experimental rabbit model and this effect may be conducted by suppressing NF-kB activity by increasing IkBα level.

Atenção às urgências: a integração das Unidades de Pronto Atendimento 24h (UPA 24h) com a rede assistencial domunicípio do Rio de Janeiro / Emergency care: the integration of Units Ready Service 24h (24h UPA) of the healthcare network municipality of Rio de Janeiro

Na última década, os serviços de urgência têm figurado com destaque na agenda governamental. No município do Rio de Janeiro, o processo de implantação e expansão das Unidades de Pronto Atendimento (UPA 24h) foi o fio condutor da política de saúde local,tendo sido exaltado como modelo a ser seguido na estruturação da rede de urgência e emergência. Definidas como unidades de atuação intermediária entre a atenção primária e a rede hospitalar, essas unidades devem compor com estes uma rede articulada de atenção àsurgências. Assim, esse trabalho tem como objetivo analisar o processo de integração das UPA 24h na rede assistencial do município do Rio de Janeiro, procurando discutir as implicações dessa estratégia na reorientação do modelo assistencial no Sistema Único de Saúde. Foi feitapesquisa em bancos de dados para identificação e caracterização das unidades de saúde integrantes da rede de urgências do município bem como levantamento de legislação edocumentos pertinentes à implantação e expansão das UPA e à estruturação da rede de urgência e emergência (RUE). Foram realizadas ainda nove entrevistas com gestores estaduale municipal, além de coordenadores das UPA e unidades básicas de saúde da área programática 3.1. A análise dos dados recorreu à estatística descritiva simples e o conjunto de dados e entrevistas foi discutido à luz da Teoria da Estruturação de Anthony Giddens. Osresultados do estudo apontaram para um cenário de pouca integração entre as UPA e os outros componentes da rede de urgência e emergência.

Os fatores relacionados a esse panorama foram: as deficiências estruturais da rede de serviços - insuficiência da atenção primária,sucateamento físico da estrutura hospitalar, escassez de leitos de enfermaria e UTI; e a fragmentação gerencial, representada pela ausência de governança unificada na rede e peloprocesso de transferência da gestão dessas unidades para organizações sociais. Identificou-se também que as UPA tem acolhido uma demanda assistencial de baixo risco que não encontra respostas na atenção básica. Conclui-se que, apesar do pesado investimento político e financeiro para a implantação e expansão dessas unidades na rede assistencial do município, essa estratégia não logrou contornar os graves problemas de integração entre as unidades desaúde. Além disso, ficaram evidentes a baixa prioridade para a atenção primária em saúde por parte dos governantes locais e as repercussões produzidas pelo subdimensionamento desse nível de atenção: ineficiência e pouco prestígio perante os usuários. Nesse contexto, observase que a ênfase nas UPA para a estruturação da RUE pouco contribuiu até o presente para odesenvolvimento de redes de atenção à saúde e reorientação do modelo assistencial no SUS.

Expression of Annexin Ⅱ and uPA in thyroid cancer and their clinical significances / 中华内分泌外科杂志

Objective To explore the role of Annexin Ⅱ and urokinase-type plasminogen activator(uPA) proteins in the development and lymph node metastasis of thyroid cancer.Methods Immunohistochemistry was used to detect the expression of Annexin Ⅱ and uPA proteins in 35 cases of papillary thyroid cancer tissues,10 cases of thyroid adenoma tissues,16 cases of nodular goiter tissues and 7 cases of normal thyroid tissues.Results The positive expression rate of Annexin Ⅱ and uPA protein was significantly higher in papillary thyroid cancer than in normal thyroid tissues,nodular goiter tissues and thyroid adenoma tissues( P ＜0.05 ).The expression of Annexin Ⅱ and uPA protein was positively correlated in papillary thyroid cancer tissues(P ＜0.05).The expression of Annexin Ⅱ protein in thyroid cancer tissues was associated with tumor size and lymph node metastasis while the expression of uPA protein was only related to lymph node metastasis.Conclusions Annexin Ⅱ and uPA proteins are involved in the occurrence and development of papillary thyroid cancer.They also play a facilitating role in lymph node metastasis of papillary thyroid cancer.

Effects of gastrin on NF-κB signaling pathway in human colon cancer cells / 中国药理学通报

Aim To investigate the effects of gastrin-17 on NF-κB signaling pathway in human colon cancer cells-Colo320WT.Methods All subjects were divided into four groups: control, gastrin-17,gastrin-17+L365,260 (gastrin-17 receptor blocker) and L365,260 group.Concerning gastrin-17 group,Colo320WT cells were treated by gastrin-17 for 12 h.Concerning gastrin-17+L360,265 group, Colo320WT cells were pretreated by L365,260 for 30 min and then were treated by gastrin-17 for 12 h.Concerning L365,260 group,Colo320WT cells were pretreated by L365,260 for 30 min.NF-κB DNA binding activity was determined by electrophoretic mobility shift assay (EMSA). Expressions of uPA protein and mRNA were assayed by Western blot and RT-PCR, respectively.Results NF-κB DNA binding activity increased more greatly in the Colo320WT cells stimulated by gastrin than that of the control group. And the expressions of uPA protein and mRNA were up-regulated more markedly than those of the control group. The above responses resulting from gastrin-17 were partly blocked by gastrin-17 receptor blocker, L365,260.Conclusion Gastrin-17 may activate NF-κB signaling pathway in human colonic cancer cells Colo320WT.

Expression of cyclooxygenase-2, urokinase plasminogen activator and thrombospondin-1 in gastric carcinoma and surrounding peripheral lymph nodes / 第二军医大学学报

Objective: To investigate the expression of cyclooxygenase-2 (COX-2), urokinase plasminogen activator(u-PA), and thrombospondin-1 (TSP-1) in gastric carcinoma and the surrounding lymph nodes, so as to discuss their roles in the invasion and metastasis of gastric carcinoma. Methods: The expression of COX-2, u-PA, and TSP-1 in the samples was examined by tissue microarray and S-P immunohistochemistry staining. Results: The positive rates of COX-2, u-PA, and TSP-1 in gastric carcinoma were 67.7%, 78.1%, and 78.6%, respectively, which were significantly higher than those in the surrounding lymph nodes (40.0%, 6.7%, and 40.0%, respectively, P0.05). COX-2, u-PA, and TSP-1 expression was not significantly different between metastatic lymph nodes and corresponding gastric carcinoma. COX-2 expression was positively correlated with u-PA, and TSP-1 expression. TSP-1 expression was not correlated with u-PA expression. Conclusion: COX-2, u-PA, and TSP-1 are highly expressed in the gastric carcinoma. COX-2 expression is correlated with depth of invasion. U-PA expression is significantly related with depth of invasion and lymph node metastasis.

Expression of Urokinase-type Plasminogen Activator (uPA), uPA Receptor, and Plasminogen Activator Inhibitor-1 in Oral Squamous Cell Carcinoma / Oral Science International

We investigated whether the expression levels of urokinase-type plasminogen activator (uPA), uPA receptor (uPAR), and plasminogen activator inhibitor-1 (PAI-1) correlate with clinicopathological features of oral squamous cell carcinoma (SCC). We immunohistochemically examined the expression levels of uPA, uPAR, and PAI-1 in 160 biopsy specimens of oral SCC. Positive stainings for uPA, uPAR, and PAI-1 were observed mainly in SCC cells, and their intensity and number of positive cells were related to lymph node involvement (<i>p</i> < 0.001, <i>p</i> < 0.001, and <i>p</i> < 0.001, respectively). The expression levels of uPA and uPAR were also related to the pattern of invasion (<i>p</i> < 0.05 and <i>p</i> < 0.001, respectively), while both were associated with tumor size (<i>p</i> < 0.05). Moreover, a poor survival rate was related to the expression of uPAR (<i>p</i> < 0.01) and PAI-1 (<i>p</i> < 0.05). These findings suggest that the uPA system may regulate the invasion and metastasis of oral SCC cells.

Study on the relationship among the NF-?B activation,uPA expression and apoptosis induced by 5- Fu in HCT116 human carcinoma cell line / 肿瘤研究与临床

Objective To study the relationship among apoptosis,NF-KB activation and uPA expres- sion in human colon carcinoma cell line HCTll6 induced by 5-fluorouracil,and to observe the effect of in- hibiting activity of NF-KB by PDTC on apoptosis as well as expression of uPA.Methods Cell apoptosis was analysed by Annexin V-FITC.Fluctuation of NF-KB and uPA was detected by semi-quantitative immuno- histochemistry.Results 5-fluorouracil could induce apoptosis and activate NF-KB.PDTC could significantly increase the apoptosis and suppress the activation of NF-KB induced by 5-fluorouracil.There was a positive correlation between the changes of uPA and NF-KB.Conclusion 5-fluorouracil could induce apoptosis,ac- tivate NF-KB and up-regulate expression of uPA of HCT116 cells.The mechanism of enhanced apoptosis by PDTC may be related to suppressing activation of NF-?B and down-regulating expression of uPA.

Effect of Chinese Hebal Compound of Different Treating Principles on uPA of Cholestasis-induced Liver Fibrosis Rat / 中国中医药信息杂志

Objective To study the effects of the Chinese herbal compound (Erzhiwan, Shixiaosan and combined formula) on cholestasis-induced liver fibrosis rat’s uPA. Methods Bile duct ligation method was used to make the model of cholestasis-induced liver fibrosis. One week after the operation, the rats were randomly divided into five group (model group, UDCA group, Erzhiwan group, Shixiaosan group and hefang group). Each medicine intervention group was given corresponding medicine by intragastric administration. Sham and model group were given sodium chloride with equal dosage. At the end of 4th week, all rats were sacrificed and sampled. General state of health, hepatic function (ALT, AST, ALP, TBil) and pathological histology of hepatic tissue were recorded and measured. Results Compared with the sham group, the level of ALT, AST, ALP, TBil and the degree of liver fibrosis in model group were advanced significantly. Compared with model group, three Chinese herbal compound decreased serum level of ALP, ALT and AST (P

Increase of p-P38 and uPA expression in human breast cancer / 基础医学与临床

Objective To study the expression and the significance of phosphorylated P38(p-P38) and uPA in breast cancer tissues.Methods Immunohistochemistry(S-P) was used to test the protein expression of p-P38 and uPA in 60 specimens from 50 patients with breast cancer.Western blotting was adopted to detect the protein expression of p-P38 and uPA in breast cancer cells and uPA protein expression after incubation with SB203580,an specific inhibitor of P38 MAPK blocked P38 MAPK signaling pathway.Results The positive rates of p-P38 protein and uPA protein in breast cancer tissues were 56.7%and 60.0% respectively.The protein expression level of p-P38 and uPA in breast cancer tissues was significantly higher than that in adjacent normal tissues(P

Hepatocyte Growth Factor/c-Met Signaling in Regulating Urokinase Plasminogen Activator in Human Stomach Cancer: A Potential Therapeutic Target for Human Stomach Cancer

BACKGROUND: Up-regulation of the hepatocyte growth factor (HGF), its transmembrane tyrosine kinase receptor (c-Met), and urokinase type plasminogen activator (uPA), is associated with the development and metastasis of various types of cancers. However, the mechanisms by which HGF/c-Met signaling mediates cancer progression and metastasis are unclear. METHODS: We investigated the roles of HGF/c-Met in tumor progression and metastasis in NUGC-3 and MKN-28 stomach cancer cell lines. RESULTS: Treatment with HGF increased c-Met phosphorylation in a dose-dependent manner, as well as increasing cell proliferation. HGF treatment also increased the protein level and the activity of uPA in NUGC-3 and MKN-28 cells. A monoclonal antibody against human uPA receptor (uPAR), mAb 3936, inhibited HGF-mediated tumor cell invasion in a dose-dependent manner. Down-regulation of uPA using uPA-shRNA induced a decrease in in vitro cell invasion in NUGC-3 cells. CONCLUSIONS: These results suggest that NUGC-3 and MKN-28 cells express functional c-Met, which may provide a therapeutic target for interfering with metastases of cancer cells by inhibiting uPA and uPAR-mediated proteolysis.