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1.
Rev. ADM ; 77(6): 287-294, nov.-dic. 2020. ilus, tab
Article in Spanish | LILACS | ID: biblio-1150870

ABSTRACT

Introducción: El carcinoma oral de células escamosas (COCE) es una neoplasia epitelial maligna que se presenta frecuentemente entre la quinta y sexta década de la vida. Su compleja patogénesis incluye el proceso de angiogénesis y la regulación del microambiente tumoral como mecanismos de progresión tumoral. Objetivo: Determinar la relación entre las variables clínicas e histológicas del COCE con la inmunoexpresión de VEGF, FGF-1, FGFR-1, TGFB-1, TGFBR-II y CD105. Material y métodos: Nueve casos de COCE; tres bien (BD), tres moderado (MD) y tres pobremente diferenciados (PD) obtenidos del Departamento de Patología y Medicina Bucal, División de Estudios de Postgrado e Investigación. Se aplicó la técnica de inmunohistoquímica por peroxidasa para identificar la expresión de VEGF, FGF-1, FGFR- 1, TGFB-1, TGFBR-II y CD105. El análisis de inmunoexpresión se realizó con el programa ImageJ. Se aplicó la prueba de Kruskal-Wallis y correlación de Spearman (p < 0.05). Resultados: La inmunoexpresión de VEGF fue mayor en los COCE PD, FGFR-1 fue positivo en los BD, mientras que FGF, TGFB-1 y TGFBR-II fueron negativos. El análisis de microdensidad vascular (MVD) indicó mayor número de vasos CD105 positivos en los carcinomas BD, seguidos de los PD y MD. Conclusión: Considerando los resultados obtenidos podemos concluir que la angiogénesis es un fenómeno constante independiente del grado de diferenciación que durante el proceso de transformación de una neoplasia requerirá la formación de vasos sanguíneos y que este proceso puede ser modulado por factores de crecimiento tales como los analizados en este trabajo (AU)


Introduction: Oral squamous cell carcinoma (OSCC) is a malignant epithelial neoplasm that frequently occurs between the fifth and sixth decade of life. Its complex pathogenesis includes the angiogenesis process and the regulation of the tumor microenvironment as mechanisms of tumor progression. Objective: To determine the relationship between the clinical and histological variables of OSCC with the immunoexpression of VEGF, FGF-1, FGFR-1, TGFB- 1, TGFBR-II and CD105. Material and methods: Nine cases of OSCC; three well (WD), three moderate (MD) and three poorly differentiated (PD) obtained from the Oral Medicine and Pathology Department, Division of Graduate Studies and Research. The peroxidase immunohistochemistry technique was performed to identify the expression of VEGF, FGF-1, FGFR-1, TGFB-1, TGFBR-II and CD105. The immunoexpression analysis was performed with the ImageJ software. The Kruskal-Wallis and Spearman correlation test were performed (p < 0.05). Results: VEGF immunoexpression was higher in PD OSCC, while FGFR-1 was predominantly positive in WD; FGF, TGFB-1 and TGFBR-II were negative. Vascular microdensity analysis (MVD) indicated a greater number of CD105 positive vessels in WD carcinomas, followed by PD and MD. Conclusion: Considering the results obtained, we can conclude that angiogenesis is a constant phenomenon independent of the degree of differentiation; that during the transformation process of a neoplasm it will require the formation of blood vessels and that this process can be modulated by growth factors such as those analyzed in this work (AU)


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Carcinoma, Squamous Cell/immunology , Fibroblast Growth Factor 1 , Vascular Endothelial Growth Factor A , Blood Vessels , Immunohistochemistry , Statistical Analysis , Histological Techniques , Intercellular Signaling Peptides and Proteins , Receptor, Fibroblast Growth Factor, Type 1 , Endoglin , Mexico
2.
Article in Chinese | WPRIM | ID: wpr-774345

ABSTRACT

OBJECTIVE@#To study the value of flow cytometric scoring system in the diagnosis of myelodysplastic syndromes (MDS).@*METHODS@#The phenotypes of erythroid and immature cells were analyzed retrospectively in 130 MDS patients, 19 healthy controls and 89 pathological controls, all of them were well clinically immunophenotyped. The 4-parameter scoring system reported in the literature was studied, including myeloblast-related cluster size, B-progenitor-related cluster size, lymphocyte to myeloblast CD45 ratio, and granulocyte to lymphocyte side scatter ratio. The two flow cytomatric parameters of the erythroid scoring system were analyzed, including CD36 coefficient of variation (CV) and CD71CV. According to our previous study, the percentage of CD117CD105 myeloid progenitor cells and the proportion of CD105 cells in CD117 cells were selected to establish a two-parameter scoring system, and compared with the four-parameter scoring system and the erythroid scoring system.@*RESULTS@#The sensitivity of the four-parameter scoring system and the erythroid scoring system for the diagnosis of low-risk MDS was 43.5% and 63.0%, and the specificity was 87.0% and 63.9%, respectively. After combining the two scoring systems, the sensitivity to diagnose low-risk MDS was 73.9% and the specificity was 62.0%. The sensitivity of the two-parameter scoring system for the diagnosis of low-risk MDS was 76.1% with a specificity of 81.5%. Combined with the four-parameter scoring system, the sensitivity was increased to 78.3%, but the specificity was reduced to 71.3%. After combining with the erythroid scoring system, the sensitivity reached 87.0%, but the specificity was reduced to 54.6%.@*CONCLUSION@#Using the two-parameter scoring system alone can achieve great sensitivity and specificity in the diagnosis of low risk MDS.


Subject(s)
Endoglin , Flow Cytometry , Humans , Immunophenotyping , Myelodysplastic Syndromes , Diagnosis , Proto-Oncogene Proteins c-kit , Retrospective Studies
3.
Rev. Ciênc. Méd. Biol. (Impr.) ; 17(3): 392-397, nov 19, 2018. tab, ilus
Article in Portuguese | LILACS | ID: biblio-1248140

ABSTRACT

Introdução: a endoglina (ENG, CD105) é um co-receptor da família transforming growth factor-beta e participa da regulação de processos celulares como proliferação, diferenciação, migração e apoptose. ENG é mais conhecida por sua expressão em células endoteliais, desempenhando papel importante na angiogênese e vasculogênese, porém sua expressão já foi associada a diferentes desfechos patogênicos, inclusive devido a mutações no gene ENG. Objetivos: descrever a frequência de variantes genéticas no gene ENG, comparar com populações ancestrais e analisar as variantes genéticas que possam estar envolvidas em processos patogênicos em outras populações. Metodologia: foi utilizado o banco de dados do programa SCAALA (Social Change Asthma and Allergy in Latin America) para a população do estudo, sendo genotipado 1309 indivíduos usando o chip Illumina 2.5 Human Omni Bead e feitas análises in silico utilizando plataformas on-line. Resultados: as variantes genéticas rs10987746, rs10121110, rs11792480 e rs16930129 apresentaram frequência de menor alelo entre 16 a 48% na população estudada, as quais foram mais reiteradamente próximas do padrão africano que do europeu. Os SNVs foram relacionados aos mecanismos regulatórios genéticos conhecidos, pressupondo que essas variantes não estejam envolvidas diretamente em processos funcionais. Conclusão: são necessárias maiores investigações referentes aos mecanismos funcionais deste gene, visto que a endoglina participa de uma gama de processos celulares importantes e mais esforços devem ser feitos para estudos genéticos na população brasileira, considerando a mistura de populações.


Introduction: the endoglin (ENG, CD105) is a coreceptor of the family transforming growth factor-beta and participates in the regulation of cellular processes such as proliferation, differentiation, migration and apoptosis. ENG She is best known for your expression in endothelial cells, playing an important role in angiogenesis and vasculogenesis, but its expression has already been associated with different pathogenic outcomes, including due to mutations in the ENG gene. Objectives: describe the frequency of genetic variants in the ENG gene in the population of northeastern Brazil, compare with ancestral populations and analyze genetic variants that may be involved in pathogenic processes in other populations. Methodology: we used the SCAALA program database (Social Change Asthma and Allergy in Latin America) for the population of the study, and the DNA of 1309 individuals were genotyped using the Illumina chip 2.5 Human Omni Bead and made in silico analysis. Results: the SNVs rs10987746, rs10121110, rs11792480 and rs16930129 presented lower allele frequency between 16 to 48% in the population studied, which were more consistently next African European standard. The SNVs were related to known genetic regulatory mechanisms assuming that these variants are not directly involved in functional processes. Conclusion: further investigation regarding the functional mechanisms of this gene are necessary, since the endoglin participates in a range of important cellular processes and more efforts should be made for genetic studies in the Brazilian population, considering the mixture of populations.


Subject(s)
Humans , Child, Preschool , Child , Genetic Variation/genetics , Polymorphism, Single Nucleotide/genetics , Endoglin/genetics , Gene Frequency/genetics , Genotype , Brazil
4.
Article in Chinese | WPRIM | ID: wpr-687979

ABSTRACT

<p><b>OBJECTIVE</b>To carry out genetic testing for a family affected with pulmonary hypertension (PH) as the initial sign of hereditary hemorrhagic telangiectasia (HHT).</p><p><b>METHODS</b>High throughput sequencing was performed to detect potential mutation in the coding regions of endoglin (ENG), activin receptor-like kinase 1 (ACVRL1) and mothers against decapentaplegic homolog 4 (SMAD4) genes.</p><p><b>RESULTS</b>A pathogenic heterozygous c.814C>T (p.Gln272Ter) mutation of the ACVRL1 gene was identified in the proband. Her mother and two sons have carried the same mutation.</p><p><b>CONCLUSION</b>The c.814C>T (p.Gln272Ter) mutation of the ACVRL1 gene probably underlies the disease in this family. Genetic testing should be recommended to HHT patient, in particular those with pulmonary hypertension.</p>


Subject(s)
Activin Receptors, Type II , Genetics , Child , Endoglin , Genetics , Female , Genetic Testing , High-Throughput Nucleotide Sequencing , Humans , Hypertension, Pulmonary , Genetics , Male , Middle Aged , Mutation , Telangiectasia, Hereditary Hemorrhagic
5.
IBJ-Iranian Biomedical Journal. 2017; 21 (5): 312-320
in English | IMEMR | ID: emr-188488

ABSTRACT

Background: The use of biomarkers for diagnosis of Preeclampsia [PE], a life-threatening pregnancy disorder, could reduce serious complications of this disease. In this study, we investigated dysregulation of endoglin [Eng] expression and diagnostic accuracy of soluble endoglin [sEng] in PE patients


Methods: For this case-control study, 26 mild and 15 severe preeclamptic women along with 20 normotensive controls were recruited. The expression level of Eng [the co-receptor of TGF-[31] was evaluated using qRT-PCR


Also, the serum concentration of soluble Eng and expression of membranous Eng were determined by ELISA and immunohistochemistry


Results: A significant up-regulation in Eng mRNA and sEng levels was observed in PE patients versus normal controls. Immunohistochemistry [IHC] showed up-regulation of membranous Eng staining in syncytiotrophoblast and cytotrophoblast cells of PE patients


The serum levels of sEng were significantly increased in all patients [mild, sever, early- and late-onset] as compared to healthy pregnant women [P<0.001]. Receiver-operating characteristic [ROC] curve analysis revealed that sEng had the highest accuracy in distinguishing PE from normal pregnancies with cut-off value of 20.4, sensitivity of 92.1%, specificity of 90%, and area under the curve [AUC] of 0.94 [95% Cl: 0.88-1.00]


Conclusions: Our data showed that the up-regulation of Eng mRNA along with its membranous and soluble form in PE patients leads to defect in angiogenesis pathway. Also, the results of this study revealed sEng potential as a marker for diagnosis of PE and its severity


Subject(s)
Humans , Women , Young Adult , Adult , Endoglin , Biomarkers , Pregnancy Complications , Pregnant Women , RNA, Messenger , Case-Control Studies , Iran
6.
Clinics ; 71(11): 639-643, Nov. 2016. tab, graf
Article in English | LILACS | ID: biblio-828547

ABSTRACT

OBJECTIVE To investigate immunohistochemical markers of angiogenesis and their association with pathological prognostic features in hepatocellular carcinoma and cirrhotic liver. METHODS Vascular endothelial growth factor, CD105, and cyclooxygenase-2 were immunohistochemically detected in 52 hepatocellular carcinoma tissue samples and 48 cirrhotic liver tissue samples. Semiquantitative measurements of vascular endothelial growth factor and cyclooxygenase-2 were evaluated considering the degree and intensity of immunostaining based on a 7-point final scoring scale. CD105 microvascular density (MVD-CD105) was measured using automated analysis. Morphological aspects evaluated in the hepatocellular carcinoma samples included size (≤2 and >2 cm), differentiation grade, and microvascular invasion. RESULTS The mean vascular endothelial growth factor immunoreactivity score was slightly higher in the hepatocellular carcinoma samples (4.83±1.35) than the cirrhotic liver (4.38±1.28) samples. There was a significant and direct correlation between these mean scores (rs=0.645, p=0.0001). Cyclooxygenase-2 was expressed in all the cirrhotic liver samples but was only found in 78% of the hepatocellular carcinoma samples. The mean cyclooxygenase-2 score was higher in the cirrhotic liver samples (4.85±1.38) than the hepatocellular carcinoma samples (2.58±1.68), but there was no correlation between the scores (rs=0.177, p=0.23). The mean CD105 percentage in the hepatocellular carcinoma samples (11.2%) was lower than that in the cirrhotic samples (16.9%). There was an inverse relationship in MVD-CD105 expression between the hepatocellular carcinoma and cirrhotic samples (rs=-0.78, p=0.67). There were no significant associations between vascular endothelial growth factor expression and morphological characteristics. Cyclooxygenase-2 and CD105 were associated with hepatocellular carcinoma differentiation grade (p=0.003 and p=0.05, respectively). CONCLUSION Vascular endothelial growth factor, cyclooxygenase-2, and MVD-CD105 were highly expressed in cirrhotic liver compared to hepatocellular carcinoma and might be involved in liver carcinogenesis. Additionally, cyclooxygenase-2 and CD105 might be involved in hepatocellular carcinoma differentiation grade.


Subject(s)
Humans , Male , Female , Adolescent , Adult , Middle Aged , Aged , Young Adult , Carcinoma, Hepatocellular/pathology , Cyclooxygenase 2/metabolism , Endoglin/metabolism , Liver Cirrhosis/metabolism , Liver Neoplasms/pathology , Vascular Endothelial Growth Factors/metabolism , Biomarkers, Tumor/metabolism , Carcinoma, Hepatocellular/blood supply , Carcinoma, Hepatocellular/metabolism , Endothelium, Vascular/metabolism , Immunohistochemistry , Liver Neoplasms/blood supply , Liver Neoplasms/metabolism , Neoplasm Grading , Statistics, Nonparametric
7.
Chinese Medical Journal ; (24): 1474-1481, 2014.
Article in English | WPRIM | ID: wpr-322244

ABSTRACT

<p><b>BACKGROUND</b>Recent studies have indicated that human nucleus pulposus contain mesenchymal stem cells (NP-MSCs). However, the immunophenotypic variation of NP-MSCs in vitro was unclear. The present study was conducted to address the immunophenotypic variation of mesenchymal stem cells in nucleus pulposus under continuous proliferation in vitro and show the difference between mesenchymal stem cells and nucleus pulposus cell.</p><p><b>METHODS</b>Tissue samples were obtained from thoracolumbar burst fracture patients and degenerative disc disease patients who underwent discectomy and fusion procedures. Flow cytometric and laser scanning confocal microscope (LSCM) were used to detect the variation of mesenchymal stem cells in nucleus pulposus which were expressing CD105 and CD24 in condition with or without transforming growth factor β1 (TGF-β1).</p><p><b>RESULTS</b>More than 90% of the analyzed primary cells of mesenchymal stem cells in nucleus pulposus fulfilled the general immunophenotyping criteria for MSCs, such as CD44, CD105 and CD29, but the marker of mature NP cells characterized as CD24 was negative. In continuous cultures, the proportion of mesenchymal stem cells which were expressing CD44, CD105 and CD29 in nucleus pulposus gradually decreased. The mesenchymal stem cells in nucleus pulposus cells were positive for CD105 and CD29, with slight positivity for CD44. The CD24 expression gradually increased in proliferation. Biparametric flow cytometry and laser scanning confocal microscopy confirmed the presence of cells which were expressing CD105 and CD24 independently, and only a small part of cells expressed both CD105 and CD24 simultaneously. TGF-β1 could stimulate mesenchymal stem cells in nucleus pulposus to express CD24.</p><p><b>CONCLUSIONS</b>Non-degenerative and degenerative NP contains mesechymal stem cells. The variation of CD24 can be used as a marker to identify the NP-MSCs differentiation into NP-like cells.</p>


Subject(s)
Adult , Antigens, CD , Metabolism , CD24 Antigen , Metabolism , Cell Differentiation , Physiology , Cells, Cultured , Endoglin , Female , Flow Cytometry , Humans , Hyaluronan Receptors , Metabolism , Integrin beta1 , Metabolism , Intervertebral Disc , Cell Biology , Metabolism , Male , Mesenchymal Stem Cells , Cell Biology , Metabolism , Receptors, Cell Surface , Metabolism , Young Adult
8.
Article in Chinese | WPRIM | ID: wpr-237287

ABSTRACT

<p><b>OBJECTIVE</b>To analyze clinical features of 4 families with hereditary hemorrhagic telangiectasia (HHT) and potential mutations of ENG, ACVRL1 and SMAD4 genes.</p><p><b>METHODS</b>Four unrelated HHT patients and their affected family members were analyzed. All exons and flanking regions of ENG, ACVRL1 and SMAD4 genes were analyzed with PCR and direct sequencing and multiplex ligation-dependent probe amplification (MLPA) methods.</p><p><b>RESULTS</b>Eleven patients from the 4 families were enrolled in this study. Two ENG and 1 ACVRL1 mutations were identified, among which an ENG mutation (c.207G>A; p.L69L) and an ACVRL1 mutation (c.817C>T; p.L273L) have been previously reported. In addition, a novel ENG mutation (c.1004A>T; p.Q335L) has been found in 3 different families. Similar mutations were not detected in 200 healthy individuals. No mutations of ENG, ACVRL1 and SMAD4 were found in the fourth family.</p><p><b>CONCLUSION</b>A novel mutation c.1004A>T (p. Q335L) of ENG has been identified in patients with HHT. And there is significant phenotypic variability and genetic heterogeneity with the disease.</p>


Subject(s)
Activin Receptors, Type II , Genetics , Adolescent , Adult , Amino Acid Sequence , Antigens, CD , Genetics , Endoglin , Female , Genetic Testing , Humans , Male , Molecular Sequence Data , Mutation , Receptors, Cell Surface , Genetics , Smad4 Protein , Genetics , Telangiectasia, Hereditary Hemorrhagic , Diagnosis , Genetics
9.
Article in Chinese | WPRIM | ID: wpr-749548

ABSTRACT

OBJECTIVE@#To study the early gene diagnosis of hereditary hemorrhagic telangiectasia (HHT) induced severe nosebleed.@*METHOD@#Clinical features of 23 family members in two HHT pedigrees were examined. Genomic DNA was extracted from peripheral blood samples. PCR amplification was conducted to screen ENG and ACVRL-1 genes with their specific primers. Direct sequencing was performed to detect the mutation. Mutation analysis was carried out to evaluate its significance.@*RESULT@#A heterozygous c. 263A > G mutation was identified in exon 3 of ACVRL-1 in 6 out of 11 members in NMG-1 pedigree. In GD-2 pedigree, 5 of 11 members carried c. 199C > G mutation. Mutation detection rate was 100% in subjects with nosebleed history and 25% in family members without epistaxis.@*CONCLUSION@#Gene diagnosis characterized by high sensitivity and specificity is of great practi-cal significance and early genetic screening should be a clinical routine test for HHT induced severe nosebleed.


Subject(s)
Activin Receptors, Type II , Genetics , Adolescent , Adult , Antigens, CD , Genetics , DNA Mutational Analysis , Endoglin , Epistaxis , Diagnosis , Genetics , Exons , Female , Genetic Testing , Humans , Male , Middle Aged , Pedigree , Receptors, Cell Surface , Genetics , Telangiectasia, Hereditary Hemorrhagic , Diagnosis , Genetics , Young Adult
10.
Article in English | WPRIM | ID: wpr-819821

ABSTRACT

OBJECTIVE@#To investigate possible mechanism of toxicarioside A in HS-5 bone stromal cells.@*METHODS@#HS-5 bone stromal cells were cultured in media supplemented with various concentrations of toxicarioside A or control DMSO (not treatment). Endoglin and TGF-β were detected by Northern and Western blot analysis and quantified in a standard method. Downstream molecules of endoglin and TGF-β (Smad1, Smad2 and their active phosphorylated counterparts, pSmad1 and pSmad2) were also detected and quantified by Western blot analysis. In addition, cell proliferation assay and small interfering RNA (siRNA) against endoglin were used to certificate the function of endolgin in the HS-5 cells.@*RESULTS@#Compared with the not treated (0 μg/mL) or DMSO treated control HS-5 cells, HS-5 cells treated with toxicarioside A were found significant attenuation of endolgin and TGF-β expression. Significant inhibition of cell proliferation was also found in the HS-5 cells treated with toxicarioside A. ALK1-related Smad1 and ALK5-related Smad2 were decreased in HS-5 cells treated with toxicarioside A. In addition, phosphorylated Smad1 (pSmad1) and Smad2 (pSmad2) were also found attenuation in toxicarioside A-treated HS-5 cells. RNA interference showed that blockage of endoglin by siRNA also decreased Smad1 and Smad2 expression in HS-5 cells.@*CONCLUSIONS@#Our results indicate that toxicarioside A can influence bone marrow stromal HS-5's function and inhibit HS-5 cell proliferation by alteration of endoglin-related ALK1 (Smad1) and ALK5 (Smad2) signaling.


Subject(s)
Antiaris , Antigens, CD , Metabolism , Blotting, Northern , Blotting, Western , Bone Marrow Cells , Metabolism , Cardenolides , Pharmacology , Cell Line , Cell Proliferation , Endoglin , Humans , Male , Receptors, Cell Surface , Metabolism , Signal Transduction , Smad1 Protein , Metabolism , Smad2 Protein , Metabolism , Stromal Cells , Transforming Growth Factor beta , Metabolism
11.
Chinese Medical Journal ; (24): 2045-2050, 2011.
Article in English | WPRIM | ID: wpr-319149

ABSTRACT

<p><b>BACKGROUND</b>Progranulin is a newly discovered 88-kDa glycoprotein originally purified from the highly tumorigenic mouse teratoma-derived cell line PC. Its expression is closely correlated with the development and metastasis of several cancers. However, no immunohistochemical evidence currently exists to correlate progranulin expression with clinicopathologic features in breast carcinoma biopsies, and the role of progranulin as a new marker of metastatic risk and prognosis in breast cancer has not yet been studied. The aim of this study was to investigate the clinicopathologic and prognostic implications of progranulin expression in breast carcinoma and its correlation with tumor angiogenesis.</p><p><b>METHODS</b>Progranulin expression was determined immunohistochemically in 183 surgical specimens from patients with breast cancer and 20 tissue samples from breast fibroadenomas. The tumor angiogenesis-related biomarker, vascular endothelial growth factor was assayed and microvessel density was assessed by counting vascular endothelial cells in tumor tissues labeled with endoglin antibody. The relationship between progranulin expression and the clinicopathologic data were analyzed.</p><p><b>RESULTS</b>Progranulin proteins were overexpressed in breast cancer. The level of progranulin expression was significantly correlated with tumor size (P = 0.004), lymph node metastasis (P < 0.001) and TNM staging (P < 0.001). High progranulin expression was associated with higher tumor angiogenesis, reflected by increased vascular endothelial growth factor expression (P < 0.001) and higher microvessel density (P = 0.002).</p><p><b>CONCLUSION</b>Progranulin may be a valuable marker for assessing the metastasis and prognosis of breast cancer, and could provide the basis for new combination regimens with antiangiogenic activity.</p>


Subject(s)
Antigens, CD , Metabolism , Breast Neoplasms , Metabolism , Endoglin , Female , Humans , Immunohistochemistry , In Vitro Techniques , Intercellular Signaling Peptides and Proteins , Metabolism , Middle Aged , Receptors, Cell Surface , Metabolism , Vascular Endothelial Growth Factor A , Metabolism
12.
Chinese Medical Journal ; (24): 2883-2889, 2011.
Article in English | WPRIM | ID: wpr-292784

ABSTRACT

<p><b>BACKGROUND</b>Recombinant human endostatin (rh-endostatin, Endostar) has been proved to be an inhibitor of angiogenesis. Docetaxel has been also considered as a common chemotherapeutic agent with inhibition of angiogenesis of malignancies. However, their function has been seldom compared and a best synergism protocol is not determined. This study aimed to compare the effects of two drugs, investigate their combined impact on human umbilical vein endothelial cells (HUVECs), a molecular basis and find ideal protocols to inhibit endothelial cell proliferation.</p><p><b>METHODS</b>HUVECs on confluent growth or activated by vascular endothelial growth factor (VEGF) were treated by rh-endostatin or/and docetaxel at respective gradient concentration in following operations as cell proliferation determined by MTT assay, cell cycle distribution, apoptosis and markers of CD146, CD62E and CD105 detected by flow cytometery, the structure of the channel formed by HUVECs measured by tube formation count.</p><p><b>RESULTS</b>Rh-endostatin exhibited time dependent inhibition of proliferation while docetaxel showed both time and dose dependent inhibition. HUVECs accumulated in G(0)-G(1) with decreased numbers of cells in G(2) after a single treatment of rh-endostatin or that followed by docetaxel treatment. Cells accumulated in G(2) after both a single docetaxel and simultaneous administration. Both the number of cells in G(0)-G(1) and apoptotic cells were increased by docetaxel followed by rh-endostatin treatment. The number of non-apoptotic cells at G(0)-G(1) was increased by first administering rh-endostatin then docetaxel. Sequential treatment of docetaxel followed by rh-endostatin resulted in the greatest increase in apoptosis (34.7%) and the second highest apoptosis was seen with simultaneous administration (18.2%). Expression of CD146 and CD105 on confluent HUVECs was reduced at certain doses of rh-endostatin and/or docetaxel. However, rh-endostatin reduced CD105 without any apparent impact on either CD146 or CD62E expression, whereas these markers were down-regulated by docetaxel after pre-activation by VEGF. Rh-endostatin treatment maintained tube-like structures for a limited time. In contrast, docetaxel swiftly reduced tube formation. Simultaneous treatment, or docetaxel followed by rh-endostatin, exhibited a stronger inhibition on tube formation than either agent alone.</p><p><b>CONCLUSIONS</b>Both rh-endostatin and docetaxel can inhibit HUVEC proliferation while the high apoptotic rate after combined administration was probably owing to different sequent administration by docetaxel followed by rh-endostatin or simultaneous treatment. Both proliferation and adhesion molecules on HUVECs of confluent growth are down-regulated by the two drugs. The rh-endostatin decreased proliferation markers, but only slightly modified adhesion molecules, while both markers were down-regulated by docetaxel on HUVECs activated by VEGF. Rh-endostatin could maintain adhesion of HUVECs at first then induce cells apoptosis to damage tube formation. We hypothesize that it could lead to vascular normalization in short time. In contrast, docetaxel can suppress HUVEC proliferation, adhesion, and reduced tube formation swiftly due to its cytotoxicity. Combined treatments can induce a synergistic inhibition of tube formation.</p>


Subject(s)
Antigens, CD , Metabolism , Apoptosis , CD146 Antigen , Metabolism , Cell Proliferation , E-Selectin , Metabolism , Endoglin , Endostatins , Pharmacology , Flow Cytometry , Human Umbilical Vein Endothelial Cells , Cell Biology , Humans , Receptors, Cell Surface , Metabolism , Recombinant Proteins , Pharmacology , Taxoids , Pharmacology
13.
Chinese Journal of Oncology ; (12): 513-516, 2011.
Article in Chinese | WPRIM | ID: wpr-320183

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the expression of indoleamine 2, 3-dioxygenase (IDO) in breast cancer and its correlation with clinicopathologic factors and prognosis.</p><p><b>METHODS</b>The expression of IDO, CD31, CD105 proteins in 40 specimens of breast cancer were assessed by immunohistochemistry.</p><p><b>RESULTS</b>The overexpression rate of IDO in breast cancer was 67.5% (27/40), and expression of IDO was closely associated with clinical stage and lymph nodes metastasis. The disease-free survival rate in patients with IDO overexpression was not significantly lower than that in patients with negative or low expression of IDO (P > 0.05). Moreover, the expression of IDO was positively correlated with CD105-labeled microvessel density (r = 0.659, P < 0.05).</p><p><b>CONCLUSIONS</b>Expression of IDO is associated with clinical stage and lymph nodes metastasis, and microvessel densitty. IDO expression may promote the growth and metastasis of breast cancer, probably via the increased agiogenesis. A larger sample study is needed to verify whether the prognosis of beast cancer is significantly correlated with IDO expression.</p>


Subject(s)
Adenocarcinoma , Allergy and Immunology , Pathology , Adult , Aged , Antigens, CD , Metabolism , Breast Neoplasms , Allergy and Immunology , Pathology , Carcinoma, Ductal, Breast , Allergy and Immunology , Pathology , Carcinoma, Medullary , Allergy and Immunology , Pathology , Disease-Free Survival , Endoglin , Female , Follow-Up Studies , Humans , Immunohistochemistry , Indoleamine-Pyrrole 2,3,-Dioxygenase , Metabolism , Lymphatic Metastasis , Microvessels , Allergy and Immunology , Middle Aged , Neoplasm Staging , Platelet Endothelial Cell Adhesion Molecule-1 , Metabolism , Receptors, Cell Surface , Metabolism , Survival Rate
14.
Acta Physiologica Sinica ; (6): 267-271, 2011.
Article in Chinese | WPRIM | ID: wpr-335991

ABSTRACT

The present study aims to investigate the effects of soluble endoglin (sEng) on invasive ability of cultured cytotrophoblasts of first trimester of pregnancy. Cytotrophoblasts of normal 6 to 8-week pregnancy were cultured by trypsin digestion method, and were incubated with cell culture medium without (control group) and with 10 μg/L sEng (sEng group), respectively for 24 h. The invasive ability was determined by transwell invasion assay, and expressions of MMP-2, MMP-9 mRNA and protein were detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot, respectively. The results showed that the invasive ability of cytotrophoblasts in sEng group was lower than that in control group (P < 0.05). Compared with control group, the expressions of MMP-2 and MMP-9 mRNA and protein of cytotrophoblasts were significantly lower (P < 0.05). In conclusion, sEng may participate in the genesis of preeclampsia by affecting the invasive ability of cytotrophoblasts through regulation of the expression of MMP-2 and MMP-9.


Subject(s)
Antigens, CD , Pharmacology , Cell Movement , Physiology , Cells, Cultured , Endoglin , Female , Humans , Matrix Metalloproteinase 2 , Genetics , Metabolism , Matrix Metalloproteinase 9 , Genetics , Metabolism , Placentation , Physiology , Pre-Eclampsia , Pregnancy , Pregnancy Trimester, First , RNA, Messenger , Genetics , Metabolism , Receptors, Cell Surface , Trophoblasts , Cell Biology
15.
Chinese Journal of Cancer ; (12): 396-402, 2010.
Article in English | WPRIM | ID: wpr-292572

ABSTRACT

<p><b>BACKGROUND AND OBJECTIVE</b>The expression of transcription factor Elf-1 and inhibitor of apoptosis survivin in non-small cell lung cancer (NSCLC) is correlated with the angiogenic factor vascular endothelial growth factor (VEGF), and are both factors affecting the cell cycle. This study investigated the expression of Elf-1, survivin, and intratumoral microvessel density (iMVD) assessed by monoclonal antibody CD105 in NSCLC, and explored their correlations with clinicopathologic features and angiogenesis of NSCLC.</p><p><b>METHODS</b>PowerVision(TM)-9000 immunohistochemistry was used to evaluate the expression of Elf-1, survivin, and CD105 in tissue microarrays containing 60 specimens of NSCLC and 9 specimens of normal tissue. Western blot analysis was used to evaluate the protein levels of Elf-1 and survivin in 17 specimens of NSCLC and 5 specimens of normal tissue.</p><p><b>RESULTS</b>Elf-1 and survivin were detected in 1 of the 9 normal tissues. The positive rates of Elf-1 and survivin in NSCLC were 70.0% and 65.0%, respectively. The expression levels of both Elf-1 and survivin were significantly related to tumor differentiation, lymphatic metastasis, clinical stage, and postoperative survival time (P < 0.05). Overexpression of both were related to poor prognosis: the survival rates were significantly lower in patients with positive expression than in those with negative expression (P < 0.01). Elf-1 expression was positively correlated with survivin expression (r = 0.769, P < 0.01). Elf-1 and survivin expressions were positively correlated with iMVD (r = 0.446, P < 0.01; r = 0.435, P < 0.01).</p><p><b>CONCLUSIONS</b>The expression of Elf-1 and survivin in NSCLC is related to differentiation, lymphatic metastasis, clinical stage, and prognosis, and both are positively correlated with iMVD. Detection their combined expression can help to predict the malignant behavior of NSCLC. Blocking the activity of Elf-1 and survivin may be a new way to inhibit angiogenesis in NSCLC.</p>


Subject(s)
Adult , Aged , Antigens, CD , Metabolism , Carcinoma, Non-Small-Cell Lung , Metabolism , Pathology , Carcinoma, Squamous Cell , Metabolism , Pathology , Cell Differentiation , Endoglin , Female , Humans , Inhibitor of Apoptosis Proteins , Metabolism , Lung Neoplasms , Metabolism , Pathology , Lymphatic Metastasis , Male , Microvessels , Metabolism , Middle Aged , Neoplasm Staging , Neovascularization, Pathologic , Metabolism , Pathology , Nuclear Proteins , Metabolism , Receptors, Cell Surface , Metabolism , Survival Rate , Transcription Factors , Metabolism
16.
Article in Chinese | WPRIM | ID: wpr-266317

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the possibility of microvessel density (MVD) and blood vessel invade (BVI) as the indexes in predicting prognosis of rectal carcinoma at stages I to II.</p><p><b>METHODS</b>Tumor tissues from 380 patients who underwent resection of stage I or II rectal cancer were analyzed for MVD and BVI by immunohistochemical S-P method with anti-CD105 and anti-CD 34 antibody. Binary and multivariable Cox regression was applied to indicate independent factors associated with overall survival.</p><p><b>RESULTS</b>CD105 was present in the neovascularity of the cancer tissue but not in the normal tissue, while CD34 was present in the tumor tissue and the normal tissue. BVI on CD34 staining was significantly higher than that on HE staining. Multivariable analysis revealed that TNM stage, CD34-BVI, histologic type, and CD105-MDV were independent risk factors to predict the possibility of poor prognosis of stage I or II rectal cancer. CD34-BVI or CD105-MVD positivity had a hazard ratio of 4.483 (95% confidence interval 2.861-7.026) for mortality.</p><p><b>CONCLUSION</b>The expressions of CD34-BVI and CD105-MVD are independent factors to predict the possibility of poor survival of stage I or II rectal carcinoma. Detection of CD105-MVD combined with CD34-BVI may help predict clinical outcome and design further individualized adjuvant treatment.</p>


Subject(s)
Adult , Aged , Aged, 80 and over , Antigens, CD , Metabolism , Antigens, CD34 , Metabolism , Endoglin , Female , Humans , Male , Microvessels , Pathology , Middle Aged , Neoplasm Staging , Neovascularization, Pathologic , Pathology , Prognosis , Receptors, Cell Surface , Metabolism , Rectal Neoplasms , Diagnosis , Pathology
17.
Article in Chinese | WPRIM | ID: wpr-749102

ABSTRACT

OBJECTIVE@#To explore the expressions of thymidine phosphorylase (TP), midkine (MK) and MVD marked with CD105 antibody in laryngeal squamous cell carcinoma (LSCC) and their clinical significance.@*METHOD@#The expressions of TP, MK and CD105 in LSCC tissues of 43 cases were studied by immunohistochemical staining.@*RESULT@#The positive expression rates of TP and MK in LSCC were 67.4% and 60.5% respectively, the mean value of MVD was 6.01 +/- 1.78. MVD was significantly higher in tumor tissue with both positive TP and MK than in that with both negative TP and MK (7.07 +/- 3.26 vs. 4.03 +/- 1.90, P < 0.05). The expression of TP, MK and CD105 were all correlated with T-stage and lymph node metastasis. Positive TP, MK expression and high MVD were all associated with a poor survival, and positive expression of both TP and MK in tumors conferred a poorer prognosis than negative expression of those factors in tumors, but only the lymph node metastasis and MVD were independent prognostic factors on multivariate analysis.@*CONCLUSION@#Both TP and MK are important for angiogenesis in LSCC. TP, MK and angiogenesis are all closely correlated with the progress of LSCC and the lymph node metastasis. The lymph node metastasis and MVD marked with CD105 antibody were independent prognostic factors. TP and MK may affect the progression and prognosis of tumor by promotion of angiogenesis. A combinative detection of TP, MK and CD105 can be as valuable tumor marker and prognostic factor for LSCC.


Subject(s)
Adult , Aged , Antigens, CD , Metabolism , Carcinoma, Squamous Cell , Metabolism , Pathology , Endoglin , Female , Humans , Laryngeal Neoplasms , Metabolism , Pathology , Lymphatic Metastasis , Male , Middle Aged , Midkine , Neoplasm Staging , Neovascularization, Pathologic , Nerve Growth Factors , Metabolism , Prognosis , Receptors, Cell Surface , Metabolism , Thymidine Phosphorylase , Metabolism
18.
Chinese Medical Journal ; (24): 128-132, 2008.
Article in English | WPRIM | ID: wpr-255753

ABSTRACT

<p><b>BACKGROUND</b>Rupture of unstable plaque with subsequent thrombus formation is the common pathophysiological substrate of acute coronary syndrome (ACS). It is of potential significance to explore the blood indexes predicting plaque characteristics. We investigated the relationship among soluble CD105, hypersensitive C-reactive protein (hs-CRP), and coronary plaque morphology.</p><p><b>METHODS</b>A clinical study from April 2004 to December 2006 was conducted in 130 patients who were divided into 3 groups: 56 patients (43.1%) in stable angina (SA) group, 52 patients (40.0%) in unstable angina (UA) group and 22 patients (16.9%) in acute myocardial infarction group. The concentrations of soluble CD105 and hs-CRP were measured in all of the patients by cardioangiography (CAG). Plasma samples of arterial blood were collected prior to the procedure. The levels of soluble CD105 and hs-CRP were measured by enzyme-linked immunosorbent assay (ELISA).</p><p><b>RESULTS</b>Unstable and ruptured plaque was found more frequently in patients with acute myocardial infarction and UA. External elastic membrane cross-sectional area (EEM CSA), plaque area, lipid pool area and plaque burden were significantly larger in the ruptured and unstable plaque group. Positive remodeling, thinner fabric-cap, smaller minimal lumen cross-sectional area (MLA), dissection and thrombus were significantly more frequent in the ruptured and unstable plaque group. Remodeling index (RI) was positively correlated with the levels of soluble CD105 in the UA group (r = 0.628, P < 0.01) and the acute myocardial infarction group (r = 0.639, P < 0.01). The levels of soluble CD105 and hs-CRP were higher in the ruptured plaque group. Soluble CD105 > 4.3 ng/ml was used to predict ruptured plaque with a receiver operating characteristic (ROC) curve area of 0.77 (95% confidence interval (CI), 66.8% - 87.2%), a sensitivity of 72.8%, a specificity of 78.0% and an accuracy of 70.2% (P < 0.01), similarly for hs-CRP > 5.0 mg/ml with a ROC curve area of 0.70 (95% CI, 59.2% - 80.2%), a sensitivity of 70.2%, a specificity of 76.2% and an accuracy of 67.2% (P < 0.01).</p><p><b>CONCLUSIONS</b>The plaque characteristics correlate with the clinical presentation. The elevation of soluble CD105 and hs-CRP is related to the plaque instability and rupture.</p>


Subject(s)
Aged , Angina Pectoris , Blood , Pathology , Antigens, CD , Blood , C-Reactive Protein , Coronary Vessels , Diagnostic Imaging , Pathology , Endoglin , Female , Humans , Male , Middle Aged , Myocardial Infarction , Blood , Pathology , Receptors, Cell Surface , Blood , Ultrasonography, Interventional , Methods
19.
Chinese Journal of Oncology ; (12): 266-269, 2008.
Article in Chinese | WPRIM | ID: wpr-348116

ABSTRACT

<p><b>OBJECTIVE</b>To assess the effect of endostatin on growth and neoplastic angiogenesis in transplanted human lung adenocarcinoma Calu-6 tumor in nude mice.</p><p><b>METHODS</b>To treat Calu-6 tumor-bearing mice with endostatin at different doses, and to record the changes of the tumor size. The expressions of survivin, VEGF, COX-2 and MVD in tumor tissue were examined by immunohistochemistry staining, circulating endothelial cells (CECs) by flow cytometry and mRNA of CD146 and CD105 by RT-PCR and real-time PCR.</p><p><b>RESULTS</b>After endostatin treatment, the tumor size was conspicuously shrunk, and the expressions of survivin, COX-2 and VEGF protein and MVD in tumor tissue decreased concomitantly with the significant difference between each of trial groups and control group (all P < 0.05). Both CECs and mRNA of CD146 and CD105 diminished remarkably. A positive correlation between both exhibition and change of amount of activated CECs and survivin, VEGF expression and MVD count in tumor tissue was found.</p><p><b>CONCLUSION</b>Endostatin can decrease the expression of survivin, COX-2, VEGF and MVD, and to inhibit the growth of transplanted tumor. Activated CECs may probably serve as an ideal marker to predict the efficacy and prognosis of anti-angiogenesis therapy.</p>


Subject(s)
Adenocarcinoma , Pathology , Angiogenesis Inhibitors , Pharmacology , Animals , Antigens, CD , Metabolism , Antineoplastic Agents , Pharmacology , CD146 Antigen , Metabolism , Cell Line, Tumor , Cyclooxygenase 2 , Metabolism , Dose-Response Relationship, Drug , Endoglin , Endostatins , Pharmacology , Endothelial Cells , Pathology , Female , Humans , Inhibitor of Apoptosis Proteins , Lung Neoplasms , Metabolism , Pathology , Mice , Mice, Inbred BALB C , Mice, Nude , Microtubule-Associated Proteins , Metabolism , Microvessels , Pathology , Neoplasm Transplantation , RNA, Messenger , Metabolism , Random Allocation , Receptors, Cell Surface , Metabolism , Tumor Burden , Vascular Endothelial Growth Factor A , Metabolism
20.
Article in Chinese | WPRIM | ID: wpr-747567

ABSTRACT

OBJECTIVE@#To evaluate the clinical significance of microvessel density (MVD) and investigate the relationship of Endoglin (CD105), VEGF and p53 protein and their significance of clinical pathology.@*METHOD@#Pathologic paraffin-embedded tissues and clinic data of 40 patients with primary squamous cell carcinoma of larynx were studied. Serial sections were respectively stained with Endoglin (CD105), VEGF and p53 by immunohistochemistry and its expressions were investigated. Microvessel density (MVD) highlighted by Endoglin (CD105) were counted according to a standard protocol.@*RESULT@#Endoglin (CD105) expression in tumour tissue was significantly higher than in normal mucosa (P < 0.05). The mean MVD value for Endoglin (CD105) was 14. 90 +/- 7.40. The mean CD105-MVD value of T3 and T4 tumours showed a significantly higher staining than that of T1 and T2 tumours; The mean CD105-MVD value of tumours with metastasis was also higher than that of tumours with no metastasis (P < 0.05); The expression of VEGF was observed in cytoplasm of tumour cell and its positive rate was 77.5% in laryngeal carcinoma, which was significantly correlated with TNM stage and pathological differentiation of laryngeal carcinoma (P < 0.05). The expression of p53 protein was mainly observed in nucleolus of tumour cell and its positive rate was 67.5%, which was significantly correlated with metastasis of lymph node. Positive relevance was found between CD105-MVD and VEGF (r = 0.641, P < 0.01); Positive relevance was also found between CD105-MVD and p53 (r = 0.534, P < 0.01).@*CONCLUSION@#Endoglin (CD105) is a marker of tumour angiogenesis for its significant associated with active angiogenesis in laryngeal carcinoma. The study shows that CD105-MVD in laryngeal carcinoma is an independent indicator of predicting invasion, metastasis and recurrence, and evaluating prognosis of malignant tumours. CD105-MVD, VEGF and p53 could be important indicators to evaluate invasion, metastasis and recurrence of laryngeal carcinoma.


Subject(s)
Adult , Aged , Aged, 80 and over , Antigens, CD , Metabolism , Biomarkers, Tumor , Metabolism , Endoglin , Female , Humans , Laryngeal Neoplasms , Metabolism , Pathology , Male , Microvessels , Pathology , Middle Aged , Neoplasm Staging , Neovascularization, Pathologic , Receptors, Cell Surface , Metabolism , Tumor Suppressor Protein p53 , Metabolism , Vascular Endothelial Growth Factor A , Metabolism
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