Biomarcadores suPAR y citocinas en la detección temprana de cáncer gástrico / suPAR and cytokines as biomarkers in early detection of gastric cancer

El cáncer gástrico (CG) es un problema prevalente a nivel mundial, presentándose aproximadamente 18 millones de casos nuevos en el año 2018, representa el 5.7% del total de cánceres, siendo la quinta neoplasia maligna más común en el mundo. En Guatemala se sitúa entre los primeros cinco cánceres respecto a morbilidad y mor-talidad. El CG se ha asociado de manera contundente a infección por Helicobacter pylori el cual desencadena un proceso inflamatorio crónico; adicionalmente algunas cepas de H. pylori producen toxinas bacterianas capaces de inducir cambios celulares que conllevan al desarrollo del proceso neoplásico. La alta mortalidad por CG en parte, se relaciona con la etapa tardía en la que se diagnostica ya que se requiere el uso de métodos invasivos, lo que dificulta su detección temprana. El objetivo de la presente revisión, fue realizar una narrativa de los estudios y las evidencias científicas, respecto de la identificación de biomarcadores séricos en la detección temprana del cáncer gástrico. Se revisaron dos tipos de biomarcadores, la proteína soluble uPAR (suPAR) que es el receptor del activador del plasminógeno (uroquinasa) y promotora de angiogénesis y por otro lado, la detección sérica de las citocinas IL-1ß, IL-6, TNFα, IL-10, IFNγ, IL-4 e IL-17 en el CG así como su potencial utilidad en su detección temprana. Estos biomarcadores fueron seleccionados por la ventaja que tendrían de ser métodos no invasivos que podrían mejorar la detección, tratamiento y pronóstico de esta enfermedad.

Gastric cancer (GC) is a prevalent problem worldwide, presenting approximately 18 million new cases in 2018, representing 5.7% of all cancers, being the fifth most common malignancy in the world. In Guatemala it is among the first five cancers in terms of morbidity and mortality. CG has been strongly associated with Helicobacter pylori infection, which triggers a chronic inflammatory process; additionally, some strains of H. pylori produce bacterial toxins capable of inducing cellular changes that lead to the development of cancer. The high mortality due to GC in part is related to the late stage in which it is diagnosed since the use of invasive methods is required, making it difficult to detect it early. The objective of this review was to make a narrative of the studies carried out and the scientific evidence regarding the identification of serum biomarkers in the early detection of gastric cancer. Two types of biomarkers were reviewed, the soluble protein uPAR (suPAR) which is the receptor for plasminogen activator (urokinase) and promoter of angiogenesis and, on the other hand, serum detection of cytokines IL-1ß, IL-6, TNFα, IL-10, IFNγ, IL-4 and IL-17 in the CG as well as its potential usefulness in its early detection. These biomarkers were selected for the advantage they would have of being non-invasive methods that could improve the detection, treatment and prognosis of this disease.

Expression of CD44, CD87 and CD123 in Acute Leukemia and Its Correlation with Cellular Immunity / 中国实验血液学杂志

OBJECTIVE@#To investigate the expression of CD44, CD87 and CD123 in acute leukemia and its correlation with cellular immune markers.@*METHODS@#A total of 166 patients with acute leukemia (AL) admitted from May 2014 to February 2017 were enrolled in AL groups. Among these patients, 100 patients suffered from acute myeloid leukemia, 50 patients suffered from acute lymphoid leukemia, and 16 patients showed B/medullary phenotype. At the same time 50 patients with non-acute leukemia were enrolled in the control group. 5 ml of fasting venous blood collected from the patients in each group, and the percentage of CD44, CD87 and CD123 cells was determined by three-color flow cytometry. Symptomatic chemotherapy was given to the patients with confirmed acute leukemia, and the remission was evaluated after 2 treatmen courses. The Complete remission (CR) was recorded and the percentage of CD44, CD87 and CD123 cells under different curative efficacy were recorded. The correlation of the prognosis patients with CD44, CD87 and CD123 was analyzed by SPSS Pearson correlation analysis software.@*RESULTS@#The positive rates of CD44, CD87 and CD123 in AL group were all higher than those in the control group (P＜0. 05). The positive rates of CD44 and CD123 in acute myeloid leukemia group were higher than those in acute lymphoblastic leukemia group and B/myeloid phenotype group (P＜0. 05). The positive rate of CD44 in acute lymphoid leukemia group was higher than that in B/medullary double phenotype group (P＜0.05). The treatment in the patients of AL group was successfully completed. 132 patients reachel to CR and 34 patients to PR+NR after 2 courses. The positive rates of CD44, CD87 and CD123 in CR patients were lower than those in PR+NR patients (P＜0.05). The results of SPSS Pearson correlation analysis showed that the prognosis of patients with acute leukemia negatively correlated with CD44 and CD87 (P＜0.05).@*CONCLUSION@#The expression of CD44, CD87 and CD123 in different phenotype of acute leukemia are different, which correlateds with prognosis. The determination of CD44, CD87 and CD123 can be used to evaluate the prognosis of patients for the reference of clinical treatment.

suPAR na avaliação do prognóstico após permanência na unidade de terapia intensiva: um estudo piloto / suPAR in the assessment of post intensive care unit prognosis: a pilot study

RESUMO Objetivo: Determinar o desempenho da dosagem do receptor ativador de plasminogênio tipo uroquinase solúvel quando da alta da unidade de terapia intensiva para predição da mortalidade após permanência na mesma unidade. Métodos: Durante 24 meses conduziu-se um estudo prospectivo observacional de coorte em uma unidade de terapia intensiva polivalente de oito leitos. Colheram-se os seguintes dados: APACHE II, SOFA, níveis de proteína C-reativa e receptor ativador de plasminogênio tipo uroquinase solúvel, além de contagem de leucócitos no dia da alta da unidade de terapia intensiva, em pacientes que sobreviveram à permanência na unidade de terapia intensiva. Resultados: Durante este período, incluíram-se no estudo 202 pacientes; 29 (18,6%) morreram após alta da unidade de terapia intensiva. Os não sobreviventes eram mais idosos e tinham enfermidades mais graves quando admitidos à unidade de terapia intensiva, com escores de severidade mais elevados, e necessitaram de vasopressores por mais tempo do que os que sobreviveram. As áreas sob a curva Característica de Operação do Receptor para SOFA, APACHE II, proteína C-reativa, contagem de leucócitos e receptor ativador de plasminogênio tipo uroquinase solúvel, no momento da alta da unidade de terapia intensiva, avaliadas como marcadores de prognóstico de morte hospitalar, foram, respectivamente, 0,78 (IC95% 0,70 - 0,86); 0,70 (IC95% 0,61 - 0,79); 0,54 (IC95% 0,42 - 0,65); 0,48 (IC95% 0,36 - 0,58); 0,68 (IC95% 0,58 - 0,78). O SOFA associou-se de forma independente com risco mais elevado de morte no hospital (OR 1,673; IC95% 1,252 - 2,234), assim como para mortalidade após 28 dias (OR 1,861; IC95% 1,856 - 2,555) e mortalidade após 90 dias (OR 1,584; IC95% 1,241 - 2,022). Conclusão: A dosagem do receptor ativador de plasminogênio tipo uroquinase solúvel na alta unidade de terapia intensiva teve um valor prognóstico fraco de mortalidade após a permanência nesta unidade.

ABSTRACT Objective: To determine the performance of soluble urokinase-type plasminogen activator receptor upon intensive care unit discharge to predict post intensive care unit mortality. Methods: A prospective observational cohort study was conducted during a 24-month period in an 8-bed polyvalent intensive care unit. APACHE II, SOFA, C-reactive protein, white cell count and soluble urokinase-type plasminogen activator receptor on the day of intensive care unit discharge were collected from patients who survived intensive care unit admission. Results: Two hundred and two patients were included in this study, 29 patients (18.6%) of whom died after intensive care unit discharge. Nonsurvivors were older and more seriously ill upon intensive care unit admission with higher severity scores, and nonsurvivors required extended use of vasopressors than did survivors. The area under the receiver operating characteristics curves of SOFA, APACHE II, C-reactive protein, white cell count, and soluble urokinase-type plasminogen activator receptor at intensive care unit discharge as prognostic markers of hospital death were 0.78 (95%CI 0.70 - 0.86); 0.70 (95%CI 0.61 - 0.79); 0.54 (95%CI 0.42 - 0.65); 0.48 (95%CI 0.36 - 0.58); and 0.68 (95%CI 0.58 - 0.78), respectively. SOFA was independently associated with a higher risk of in-hospital mortality (OR 1.673; 95%CI 1.252 - 2.234), 28-day mortality (OR 1.861; 95%CI 1.856 - 2.555) and 90-day mortality (OR 1.584; 95%CI 1.241 - 2.022). Conclusion: At intensive care unit discharge, soluble urokinase-type plasminogen activator receptor is a poor predictor of post intensive care unit prognosis.

Soluble urokinase-type plasminogen activator receptor as a measure of treatment response in acute exacerbation of COPD / Receptor do ativador de plasminogênio tipo uroquinase solúvel como medida da resposta ao tratamento da exacerbação aguda da DPOC

ABSTRACT Objective: To evaluate the value of soluble urokinase-type plasminogen activator receptor (suPAR) in the diagnosis of acute exacerbation of COPD (AECOPD) and in monitoring treatment response, analyzing the relationship between suPAR and fibrinogen in AECOPD. AECOPD leads to increased airway inflammation, contributing to an exaggerated release of inflammatory mediators. Methods: We recruited 45 patients with AECOPD and 20 healthy control subjects. Medical histories were taken, and all subjects underwent clinical examination, chest X-ray, pulmonary function tests, and blood gas analysis. On day 1 (treatment initiation for the AECOPD patients) and day 14 (end of treatment), blood samples were collected for the determination of serum suPAR and plasma fibrinogen. Results: Serum levels of suPAR were significantly higher in the AECOPD group than in the control group. In the AECOPD patients, there was a significant post-treatment decrease in the mean serum suPAR level. The sensitivity, specificity, and accuracy of suPAR were 95.6%, 80.0%, and 93.0%, respectively. The Global Initiative for Chronic Obstructive Lung Disease stage (i.e., COPD severity) correlated positively and significantly with serum levels of suPAR and plasma levels of fibrinogen. Conclusions: Monitoring the serum suPAR level can be helpful in the evaluation of the COPD treatment response and might be a valuable biomarker for determining the prognosis of AECOPD. Because serum suPAR correlated with plasma fibrinogen, both markers could be predictive of AECOPD.

RESUMO Objetivo: Avaliar o valor do soluble urokinase-type plasminogen activator receptor (suPAR, receptor do ativador de plasminogênio tipo uroquinase solúvel) no diagnóstico de exacerbação aguda da DPOC (EADPOC) e no monitoramento da resposta ao tratamento, analisando-se a relação entre o suPAR e o fibrinogênio na EADPOC. A EADPOC leva ao aumento da inflamação das vias aéreas, contribuindo para a liberação exagerada de mediadores inflamatórios. Métodos: Foram recrutados 45 pacientes com EADPOC e 20 controles saudáveis. Realizou-se anamnese, e todos os indivíduos foram submetidos a exame clínico, radiografia de tórax, provas de função pulmonar e gasometria arterial. No dia 1 (início do tratamento para os pacientes com EADPOC) e no dia 14 (final do tratamento), foram coletadas amostras de sangue para dosagem de suPAR sérico e de fibrinogênio plasmático. Resultados: Os níveis séricos de suPAR foram significativamente maiores no grupo EADPOC do que no grupo controle. Nos pacientes com EADPOC, houve diminuição significativa da média de suPAR sérico após o tratamento. A sensibilidade, a especificidade e a acurácia do suPAR foram, respectivamente, de 95,6%, 80,0% e 93,0%. O estágio da doença segundo a Global Initiative for Chronic Obstructive Lung Disease (isto é, a gravidade da DPOC) apresentou correlação positiva e significativa com os níveis séricos de suPAR e os níveis plasmáticos de fibrinogênio. Conclusões: O monitoramento do suPAR sérico pode ser útil na avaliação da resposta ao tratamento da DPOC e seria um biomarcador valioso para a determinação do prognóstico da EADPOC. Como o suPAR sérico apresentou correlação com o fibrinogênio plasmático, ambos os marcadores poderiam ser preditores da EADPOC.

Expression of urokinase-type plasminogen activator and its receptor in squamous cell carcinoma of the oral tongue

Abstract Urokinase-type plasminogen activator (uPA) and its receptor (uPAR) act in the proteolysis of basement membrane and extracellular matrix structures, facilitating tumor invasion. The purpose of this study was to evaluate the relationship between these proteins and clinicopathological parameters in squamous cell carcinoma of the oral tongue (SCCOT). Sixty cases of SCCOT were submitted to immunohistochemistry and analyzed semiquantitatively at the invasion front and in the tumor core. The results were associated with lymph node metastasis, clinical stage, locoregional recurrence, clinical outcome and histological grade of malignancy. A higher expression of uPA was observed in cases of tumors of high-grade versus low-grade malignancy (p = 0.010). Moreover, the cases with the worst pattern of invasion presented an overexpression of uPA (p = 0.011). The presence of locoregional recurrence was associated with uPAR (p = 0.039), and the expression of both biomarkers was much higher at the invasion front than in the tumor core (p < 0.001). The results suggest uPA and uPAR are involved in the progression and aggressiveness of SCCOT, mainly at the tumor-host interface.

Effects of MnSOD silence on in vitro tumorigenicity in NCI-H446 cells / 中南大学学报(医学版)

To investigate the effect of manganese superoxide dismutase (MnSOD) silence on the in vitro tumorigenicity in human small cell lung cancer NCI-H446 cells and the underlying mechanisms.
 Methods: Sphere formation cells from NCI-H446 cells were obtained by suspension culture, while the expression of MnSOD and urokinase type plasminogen activator (uPAR) was analyzed by Western blot. Silence of MnSOD was performed by adenovirus infection in the second passage formation cells, and the effect of MnSOD silence on tumorigenicity in NCI-H446 cells was evaluated by sphere formation assay and soft-agar colony formation assay, while the expression of uPAR was analyzed by Western blot.
 Results: Compared with NCI-H446 cells, the sphere formation rate, colony formation rate, and the expression of MnSOD and uPAR were significantly increased in the second passage sphere formation cells in NCI-H446 cells (P<0.05). Silence of MnSOD inhibited the sphere formation rate, colony formation rate, and the expression level of uPAR in the second passage sphere formation cells in NCI-H446 cells.
 Conclusion: MnSOD may promote tumorigenicity in NCI-H446 cells by up-regulation of uPAR expression in vitro.

SCUBE1: a promising biomarker in renal cell cancer

ABSTRACT Purpose To investigate the efficacy of signal peptide-CUB-EGF domain-containing protein 1 (SCUBE-1) as a novel biomarker of renal tumors. Materials and Methods 48 individuals were included in the study. The patient group (Group-1) consisted of 23 subjects diagnosed with renal tumor, and the control group (Group-2) of 25 healthy individuals. Patients diagnosed with renal tumor received surgical treatment consisting of radical or partial nephrectomy. Blood specimens were collected following overnight fasting. Signal peptide-CUB-EGF domain-containing protein 1 (SCUBE-1), soluble urokinase plasminogen activator receptor (suPAR) and carbonic anhydrase IX (CA IX) levels were measured from plasma samples. Patients in groups 1 and 2 were compared in terms of these biochemical parameters. Results The 23-member renal tumor group was made up of 17 (73.91%) male and 6 (26.08%) female patients with a mean age of 58.5±15.7 years (range 25 to 80). The 24-member healthy control group was made up of 16 (64%) male and 9 (36%) female subjects with a mean age of 52.4±9.12 years (range 40 to 67). Analysis revealed significant elevation in SCUBE-1 levels in the renal tumor group (p=0.005). No significant differences were detected between the groups with regard to CA IX or suPAR measurements (p=0.062 vs. p=0.176). Conclusions SCUBE-1 appears to represent a promising biomarker in the diagnosis and follow-up of patients with renal tumor.

Effects of apigenin on self-renewal and uPAR expression in NCI-H446 cell line / 中南大学学报(医学版)

To investigate the effect of apigenin on self-renewal for sphere-forming cells in human small cell lung cancer cell line NCI-H446 and the underlying mechanisms.
 Methods: Sphere-forming cells from NCI-H446 cell line were cultured in stem cell-conditioned culture medium with ultra-low attachment surface plates. The rate of sphere-forming cells in the second passage sphere-forming cells was used to evaluate the inhibitory effects of apigenin on the self-renewal for sphere-forming cells. The protein level of urokinase-type plasminogen activator receptor (uPAR) in spheroids was analyzed by Western blot.
 Results: Apigenin signifcantly inhibited the self-renewal of the second passage sphere-forming cells [0, 5.0, 10.0, 20.0 μmol/L apigenin: (18.2±1.9)%, (13.6±1.7)%, (10.6±1.6)%, (6.9±1.3)%, respectively] and down-regulated uPAR expression in a concentration-dependent manner (P<0.05).
 Conclusion: Apigenin inhibits the self-renewal capacity of sphere-forming cells in NCI-H446 cells, which may be associated with down-regulation of uPAR expression.

Effect of jianpi-jiedu formula on tumor angiogenesis-relevant genes expression in colorectal cancer / 中南大学学报(医学版)

To investigate the effect of the jianpi-jiedu formula (JPJD) on the expression of angiogenesis-relevant genes in colon cancer.
 Methods: Crude extract was obtained from JPJD by water extract method. The effect of JPJD crude extract on colon cancer cell proliferation capacity was determined by MTT assays. The IC50 value was calculated by GraphPad Prism5 software. Affymetrix gene expression profiling chip was used to detect significant differences in expressions of genes after JPJD intervention, and pathway enrichment analysis was performed to analyze the differentially expressed genes. Ingenuity Pathway Analysis software was applied to analyze differentially expressed genes relevant to tumor angiogenesis based on mammalian target of rapamycin (mTOR) signaling pathway and then the network diagram was built. Western blot was used to verify the protein levels of key genes related to tumor angiogenesis.
 Results: JPJD crud extract inhibited the proliferation capacity in colon cancer cells. The IC50 values in 24, 48, and 72 hours after treatment were 13.060, 9.646 and 8.448 mg/mL, respectively. The results of chip showed that 218 genes significantly upgraded, and 252 genes significantly downgraded after JPJD treatment. Most of the genes were related to the function of biosynthesis, metabolism, cell apoptosis, antigen extraction, angiogenesis and so on. There were 12 differentially expressed angiogenesis genes. IPA software analysis showed that the JPJD downregulated expression of sphingomyelin phosphodiesterase 3 (SMPD3), VEGF, vascular endothelial growth factor A (VEGFA), integrin subunit alpha 1 (ITGA1), cathepsin B (CTSB), and cathepsin S (CTSS) genes, while upregulated expressions of GAB2 and plasminogen activator, urokinase receptor (PLAUR) genes in the colorectal cancer cell. Western blot results demonstrated that JPJD obviously downregulated expressions of phospho-mTOR (P-mTOR), signal transducer and activator of transcription 3 (STAT3), hypoxia inducible factor-1α (HIF-1α), and VEGF proteins, while obviously upregulated the level of phospho-P53 (P-P53) protein.
 Conclusion: JPJD may inhibit colorectal tumor angiogenesis through regulation of the mTOR-HIF-1α-VEGF signal pathway.

Bone Marrow Urokinase Plasminogen Activator Receptor Levels are Associated with the Progress of Multiple Myeloma / 中国医学科学杂志(英文版)

<strong>Objective</strong> To determine the mRNA and protein levels of urokinase plasminogen activator receptors (uPAR) in bone marrow fluid and bone marrow tissue from multiple myeloma (MM) patients and assess association of uPAR level with prognosis of MM. <strong>Methods</strong> uPAR levels in bone marrow fluid of 22 MM patients at the stable and progressive stages and 18 iron deficiency anemia patients with normal bone marrow (control) were examined by ELISA. Furthermore, uPAR expression in bone marrow tissue was investigated by RT-PCR and Western blot, respectively. The distribution of uPAR in MM cells was examined using immunofluorescence staining. The pathological changes in different stages of MM patients were studied by HE staining. <strong>Results</strong> uPAR level in bone marrow fluid of MM patients (1.52±0.32 μg/ml) was found to be higher than that in the control group (0.98±0.15 μg/ml). Interestingly, uPAR protein (0.686±0.075 vs. 0.372±0.043, P<0.05) and mRNA (2.51±0.46 vs. 4.46±1.15, P<0.05) expression levels of MM patients at the progressive stage were significantly higher than those at the stable stage. The expression of uPAR in MM bone marrow was confirmed by immunofluorescence staining. Moreover, HE staining revealed a great increased number of nucleated cells and severe impairment of hematopoietic function in the bone marrow of patients with progressive-stage myeloma. <strong>Conclusion</strong> Our study reveals that uPAR expression is positively correlated with the development and progress of MM.

Molecular Image of Superparamagnetic Iron Oxide Nanopariticle Labeled with hATF in Colon Tumor Models / 生物医学工程学杂志

Urokinase plasminogen activator receptor (uPAR) is a membrane protein which is attached to the cellular external membrane. The uPAR expression can be observed both in tumor cells and in tumor-associated stromal cells. Thus, in the present study, the human amino-terminal fragment (hATF), as a targeting element to uPAR, is used to conjugate to the surface of superparamagnetic iron nanoparticle (SPIO). Flowcytometry was used to examine the uPAR expression in different tumor cell lines. The specificity of hATF-SPIO was verified by Prussian blue stain and cell phantom test. The imaging properties of hATF-SPIO were confirmed in vivo magnetic resonance imaging (MRI) of uPAR-elevated colon tumor. Finally, the distribution of hATF-SPIO in tumor tissue was confirmed by pathological staining. Results showed that the three cells in which we screened, presented different expression characteristics, i. e., Hela cells strongly expressed uPAR, HT29 cells moderately expressed uPAR, but Lovo cells didn't express uPAR. In vitro, after incubating with Hela cells, hATF-SPIO could specifically combined to and be subsequently internalized by uPAR positive cells, which could be observed via Prussian blue staining. Meanwhile T2WI signal intensity of Hela cells, after incubation with targeted probe, significantly decreased, and otherwise no obvious changes in Lovo cells both by Prussian blue staining and MRI scans. In vivo, hATF-SPIO could be systematically delivered to HT29 xenograft and accumulated in the tumor tissue which was confirmed by Prussian Blue stain compared to Lovo xenografts. Twenty-four hours after injection of targeting probe, the signal intensity of HT29 xenografts was lower than Lovo ones which was statistically significant. This targeting nanoparticles enabled not only in vitro specifically combining to uPAR positive cells but also in vivo imaging of uPAR moderately elevated colon cancer lesions.

Amiloride reduces proteinuria and inhibits podocyte uPAR in the 5/6 nephrectomy rats / 南方医科大学学报

<p><b>OBJECTIVE</b>To observe the effect of amiloride on the proteinuria of the 5/6 nephrectomy rats.</p><p><b>METHODS</b>To establish the 5/6 nephrectomy rats model and divide the experiment into 3 groups, sham operated group(Sham), 5/6 nephrectomy model group(NTX) and 5/6 nephrectomy with amiloride-treated group (NTX+amiloride, n=15). The concentration of protein and mRNA of uPAR and the change of podocytes motility were detected by coomassiebluestaining, immunofluorence method and real-time PCR.</p><p><b>RESULTS</b>At second week, compared with Control group, the 24 h urine protein of NTX group was significantly increased (47.50 ± 28.05 mg vs 14.28 ± 3.8 mg, P = 0.023). There was no statistical significance in 24-hour urine protein between NTX+amiloride group and NTX group (51.56 ± 21.03 mg vs 47.50 ± 28.05 mg, P = 0.748). The same situation was also observed at the time point of 12 week, comparing with NTX group, 24-hour urine protein decreased in Sham group (188.31 ± 29.82 mg vs 21.32 ± 8.59 mg, P = 0.000) and NTX+amiloride group (188.31 ± 29.82 mg vs 121.37 ± 31.14 mg, P=0.000), with statistical significance when comparing with Sham group, the expression of uPAR mRNA in NTX group was significantly increased (9.74 ± 1.44 vs 1.01 ± 0.13, P = 0.000). In contrast, the expression of uPAR mRNA in NTX rats treated with amiloride was significantly lower than in NTX group (9.74 ± 1.44 vs 5.01 ± 1.36, P = 0.000).</p><p><b>CONCLUSION</b>Amiloride can reduce the proteinuria of the 5/6 nephrectomy rats model of transient proteinuria by inhibiting the induction of uPAR expression.</p>

Urokinase-type plasminogen activator receptor in IgA nephropathy

No abstract available.

Urokinase, urokinase receptor, and plasminogen activator inhibitor-1 expression on podocytes in immunoglobulin A glomerulonephritis

BACKGROUND/AIMS: The purpose of this study was to investigate the expression of urokinase-type plasminogen activator (uPA), uPA receptor (uPAR), and plasminogen activator inhibitor (PAI)-1 on podocytes in immunoglobulin A (IgA) glomerulonephritis (GN). METHODS: Renal biopsy specimens from 52 IgA GN patients were deparaffinized and subjected to immunohistochemical staining for uPA, PAI-1, and uPAR. The biopsies were classified into three groups according to the expression of uPA and uPAR on podocytes: uPA, uPAR, and a negative group. The prevalences of the variables of the Oxford classification for IgA GN were compared among the groups. RESULTS: On podocytes, uPA was positive in 11 cases and uPAR was positive in 38 cases; by contrast, PAI-1 was negative in all cases. Expression of both uPA and uPAR on podocytes was less frequently accompanied by tubulointerstitial fibrosis. CONCLUSIONS: Our results suggest a possible protective effect of podocyte uPA/uPAR expression against interstitial fibrosis.

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.

11R-VIVIT inhibits the expression of urokinase-type plasminogen activator receptor in podocytes / 南方医科大学学报

<p><b>OBJECTIVE</b>To observe the effect of 11R-VIVIT on lipopolysaccharide (LPS)-induced expression of urokinase-type plasminogen activator receptor (uPAR) in podocytes.</p><p><b>METHODS</b>A LPS-induced proteinuria mouse model and in vitro cultured podocytes treated with LPS were both divided into control group, LPS group and LPS+11 R-VIVIT group. The mRNA and protein expressions of uPAR in mouse kidney tissues and the podocytes were measured by real-time qPCR, laser scanning confocal microscopy and Western blotting.</p><p><b>RESULTS</b>Compared with LPS group, LPS+11 R-VIVIT group showed a significantly lowered urine albumin/creatinine ratio (P<0.001) and markedly reduced mRNA and protein expressions of uPAR (PuPAR mRNA<0.001; PuPAR=0.001).</p><p><b>CONCLUSION</b>11R-VIVIT can ameliorate proteinuria probably by decreasing the expression of uPAR in podocytes.</p>

The expression and significance of urokinase-type plasminogen activator and its receptor in squamous cell carcinoma of hypopharynx / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To investigate the expression of urokinase-type plasminogen activator (uPA) and its receptor (uPAR) in squamous cell carcinoma of hypopharynx and reveal the correlation of the major clinicopathological parameters and prognosis.@*METHOD@#Samples of 48 hypopharyngeal carcinoma and 10 normal hypopharyngeal tissue were detected by immunohistochemistry method (SP method) for urokinase-type plasminogen activator (uPA) and its receptor (uPAR). The correlation between the expression of urokinase-type plasminogen activator and its receptor and the major clinicopathological parameters of hypopharyngeal carcinoma were analyzed by rank sum test and Spearman correlation analysis. Overall survival were analyzed according to Kaplan-Meier and log-rank statistics, the prognostic relevance of uPA and uPAR and conventional prognostic factors were analyzed by Cox analysis.@*RESULT@#In 48 hypopharyngeal carcinoma specimens, positive expression rates of uPA and uPAR were 77.1% and 68.75% respectively, which were significantly higher than in normal tissues (P < 0.01). The uPA and uPAR positive expression was correlated with pathological grading, lymph node metastases and growth mode of hypopharyngeal carcinoma. The positive expression rate for uPA and uPAR in patients with lower pathological grading, lymph node metastases and invasion growth mode were significantly higher than in patients with higher pathological grading, non-lymph node metastases and non-invasion growth mode. Patients were followed-up postoperatively. The positive expression of uPA and uPAR were correlated with prognosis (P < 0.05 and P < 0.01). According to Log-rank statistics, patients with positive expression of uPA and uPAR had a significantly shorter survival time than those with negative expression of uPA and uPAR. Multivariate Cox analysis revealed that three independent prognostic factors for overall survival time were clinical stage, invasion growth mode and uPAR expression.@*CONCLUSION@#The positive expression of uPA and uPAR in hypopharyngeal carcinoma were significantly higher than in normal tissues. uPAR is a new independent and strong biologically prognostic factors, which positive expression may be a powerful aid in evaluating metastatic potential and High-Risk patients in early stage of hypopharynx carcinoma ryngeal carcinoma.

Expression of urokinase-type plasminogen activator and urokinase-type plasminogen activator receptor in synovial fluid of patients with temporomandibular disorders / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To investigate the level of urokinase-type plasminogen activator (uPA) and urokinase-type plasminogen activator receptor (uPAR) in synovial fluid of patients with temporomandibular disorders and to analyze their relation with temporomandibular disorders (TMD).</p><p><b>METHODS</b>Synovial fluid was obtained from 64 sides of 56 TMD patients and from 16 sides of 10 asymptomatic healthy volunteers (control). The concentrations of uPA and uPAR in the synovial fluid were measured by ELISA. Forty-eight sides of TMD were divided into 3 groups: arthrosis, structure disorder and osteoarthrosis, each including 16 sides.</p><p><b>RESULTS</b>The levels of uPA and uPAR were significantly higher in the synovial fluid of TMD patients than that in the control group (P < 0.05), and the level of uPA and uPAR in osteoarthrosis group was significantly higher than that in arthrosis and structure disorder group (P < 0.05). However, there was no difference in expression of uPA and uPAR between arthrosis and structure disorder groups (P > 0.05).</p><p><b>CONCLUSIONS</b>uPA and uPAR in the synovial fluid may play a role in the pathogenesis of TMD, and the level of uPA and uPAR in synovial fluid of TMD could be used as a biochemical markers to reflect pathological degree of TMD.</p>

Plasma suPAR level in patients with multiple myeloma / 中国实验血液学杂志

To investigate the changes of plasma suPAR level in patients with multiple myeloma, ELISA was used to detect plasma suPAR level, and routine examination was performed for other clinical indexes in 26 multiple myeloma patients. The results showed that plasma suPAR level in patients was 4.31+/-1.67 ng/ml, which was obviously higher than that in control group (1.87+/-0.27 ng/ml) (p<0.01). Plasma suPAR level in IgM subtype patients was 6.18+/-3.61 ng/ml, which was highest among all the subtypes; the plasma suPAR levels in non-secretion subtype, IgG and IgA subtype were 4.43+/-1.55 ng/ml, 4.00+/-0.95 ng/ml and 3.50+/-1.60 ng/ml respectively. The plasma suPAR levels in all subtypes were higher than that in control group, but there was no differences between these subtypes. SuPAR level was correlated with the blood sedimentation rate, creatinine level and hemoglobin level, plasma cell ratio and M protein level. It is concluded that the change of plasma suPAR level in multiple myeloma contributes to predict the development and prognosis of the disease.

The analysis of plasma Urokinase-type plasminogen activator and Urokinase-type plasminogen activator receptor which unknown factor nosebleed patients / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To investigate the pathogenesis of unknown nosebleed patients.@*METHOD@#The ELISA test were used to detected plasma Urokinase-type plasminogen activator (uPA) and Urokinase-type plasminogen activator receptor (uPAR) level in 19 cases unknown factor nosebleed patients and 36 health persons.@*RESULT@#The results showed uPAR and uPA level in nosebleed group (before treatment) uPAR (0.14 +/- 0.04) microg/L, uPA (0.24 +/- 0.09) microg/L; (after treatment) uPAR (0.08 +/- 0.02) microg/L, uPA (0.18 +/- 0.07) microg/L. And normal group uPAR (0.07 +/- 0.03) microg/L, uPA (0.17 +/- 0.05) microg/L. The uPAR and uPA level in nosebleed group before treatment is higher than that in normal group (P 0.05).@*CONCLUSION@#The reasons of uPAR and uPA level high in unknown factor nosebleed patients were not clear, maybe relation to vascular endothelial cell, smooth muscle cell and neutrophil-monocytic release more uPAR and uPA. So uPAR and uPA density of nostril accumulation is more high in its microenvironment, that fibrinolytic system activated increase and result in its hyperactivity, and happened nosebleed when blood be in hypocoagulable state.