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Introdução: A incidência de tumores adrenocorticais em crianças é particularmente elevada nas regiões sudeste e sul do Brasil, correlacionandose com a ocorrência da mutação germinativa p.R337H do supressor tumoral p53, entretanto, o carcinoma adrenocortical é uma neoplasia endócrina maligna rara em todo o mundo com uma incidência aproximada de 0,5 - 2 casos por milhão por ano. Esta condição é uma doença heterogênea, apresentando frequentemente comportamento clínico agressivo e letal. A cascata de sinalização Wnt é uma via importante de transdução de sinal em cânceres humanos e tem sido implicada na tumorigênese adrenocortical. A atividade desta via de sinalização é dependente da quantidade de beta-catenina citoplasmática e nuclear. Mutações ativadoras no gene da beta-catenina (CTNNB1) foram relatadas em diversas neoplasias humanas. Estudos demonstraram que mutações no gene CTNNB1 são os defeitos genéticos mais frequentemente encontrados em adenomas e em carcinomas adrenocorticais. O estudo destas mutações demonstrou que as alterações no gene CTNNB1 localizam-se principalmente exon 3, que codifica a porção amino terminal da beta- catenina. Objetivos: determinar a ocorrência e a frequência das mutações somáticas no exon 3 do gene CTNNB1. Adicionalmente, determinar a imunorreatividade de beta-catenina e de p53 em tumores adrenocorticais benignos e malignos de crianças e adultos. Correlacionar os resultados da análise de mutações gênicas e os dados de imunorreatividade com as características hormonais, a mutação p.R337H do p53, o diagnóstico histológico e a evolução dos tumores adrenocorticais de crianças e adultos. Métodos: Neste estudo, a análise de imunohistoquímica para beta-catenina e p53 foi realizada em 103 tumores adrenocorticais benignos e malignos (40 crianças e 63 adultos), estando as amostras histológicas alocadas em micromatriz tecidual (TMA). A pesquisa de mutações no exon 3 do gene CTNNB1 foi determinada por seqüenciamento automático em 64 tumores...
Introduction: The incidence of adrenocortical tumors in children is particularly high in the southeastern and southern regions of Brazil, correlating with the occurrence of p.R337H p53 tumor suppressor germline mutation. However, adrenocortical carcinoma is a worldwide rare endocrine malignancy with an approximate incidence of 0.5 to 2 cases per million per year. This condition is a heterogeneous disease and is often lethal. The Wnt signaling pathway is an important signal transduction pathway in human cancers and has been implicated in adrenocortical tumorigenesis. The activity of this signaling pathway is dependent on the amount of nuclear and cytoplasmic beta-catenin. Activating mutations of ?-catenin (CTNNB1) gene have been reported in several human malignancies. Studies have shown that CTNNB1 mutations are the most common genetic defect found in adrenocortical adenomas and carcinomas. The study of these mutations demonstrated that the changes in CTNNB1 gene are mainly located in exon 3, which encodes the amino terminal portion of the beta- catenin. Objectives: to determine the occurrence and frequency of CTNNB1 somatic mutations and the abnormal beta-catenin and p53 accumulation in benign and malignant adrenocortical tumors in both children and adults. We also evaluated the correlation of the gene mutations analysis and immunohistochemistry data with the hormonal characteristics, the p.R337H germline mutation, the histological diagnosis and the prognosis of adrenocortical tumors in children and adults. Methods: In this study, immunohistochemistry for beta-catenin and p53 was performed in 103 benign and malignant (40 children and 63 adults) adrenocortical tumors. The histological samples were allocated in a tissue microarray (TMA). The study of the CTNNB1 gene was performed by direct sequencing of 64 adrenocortical tumors. Results: The beta-catenin abnormal accumulation was similar in benign and malignant adrenocortical tumors of children and adults (15...(au)
Subject(s)
Humans , Male , Female , Child , Adult , Adrenal Cortex Neoplasms , beta Catenin , Adrenal Cortex Hormones , DNA Mutational Analysis , Germ-Line Mutation , /genetics , Neoplasm Invasiveness , Wnt Signaling PathwayABSTRACT
Objective To investigate the effects of S100A6 gene on invasion of human pancreatic cancer cell and possible mechanism. Methods Human pancreatic cancer BxPC3 cell line was transfected with small interfering RNA (siRNA) targeting S1006 gene, the mRNA and protein levels of S100A6 were determined by real time RT-PCR and Western blotting respectively. The invasion ability was evaluated by Transwell chamber. The matrix metalloproteinase-2 (MMP-9) activity of cancer cells was examined by gelatin zymography. Results The levels of mRNA and protein of S100A6 were greatly reduced in a dose and time dependent manner, the number of penetrating cells was greatly reduced in a dose dependent manner. The expression of S100A6 mRNA in 12.5 nmol/L of S100A6 siRNA transfected group decreased from ( 100 ±0.3)％ in control group to (15.3 ±0.2)％ ; while the expression of S100A6 protein decreased from (83.2 ±0. 18 ) ％ to ( 13.5 ± 0. 12) ％ ; the number of penetrating cells decreased from 44.5 ± 2.2 to 7.6 + 1.5 ( P ＜0. 01 ). The MMP-9 activity of siRNA group reduced significantly. Conclusions S100A6 siRNA can inhibit the invasion of pancreatic cancer cells through down-regulation of MMP-9.
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Objective To study the clinicopathologic features and differential diagnosis of deep angiomyxoma(DAM). Methods Seven cases of DAM were collected from 2000 to 2008. All the patients were examined by microscopy and immunohistochemistry. Results 6 patients with DAM were females and 1 was male, with median age of 48.5 years. Median maximum dimension was 5.9cm, with invasive growth pattern. The tumor cells of DAM were infantile, spindle or stellate,diffuse and nodular arrangement. A distinctive histologic feature of DAM was its vascularity. Non-arborizing, thin-wall, ectastic capillaries or more commonly, small thick-wall vessels were dispersed throughout the tumor. Mast cells and extravasated red blood cells were frequently found in the stroma, immunohistochemical study showed that 7 cases were positive for vimentin, desmin, ER and PR, 5 for CD34 and SMA, and negative for S-100 and CK. Conclusion DAM is a rare soft tumor that occurs principally in the vulval and vagina region of woman. Misdiagnosis has happened frequently. Immunohistochemical staining are helpful to diagnosis for DAM, but no significance to distinguish it.
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OBJECTIVE To evaluate the inhibitory effect of HPSE AS-ODN on the invasiveness of human Hep-2 cell lines. METHODS HPSE AS- ODN which was complementary with initiation codon region of HPSE mRNA was designed and synthesized. After embedded by cation lipofectin, it was transfected into Hep-2 cells of human laryngocarcinoma. The expression of HPSE protein and HPSE mRNA in Hep-2 cell lines were detected by flow cytometry and RT- PCR. Meanwhile Matrigel invasive assay was used to measure the inhibitory effect of HPSE AS-ODN on the invasiveness of human Hep-2 cell lines. RESULTS The HPSE protein and HPSE mRNA expression and invasiveness of human Hep-2 cells treated with AS- ODN of different concentrations were significantly decreased as the AS-ODN concentration increasing. There was a significantly difference between control group and each group of AS-ODN respectively (P
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Objective To investigate the expression and clinical significance of tumor infiltrating dendritic cells(TIDCs) within gastric tumor tissues.Methods Immunohistochemistry(IHC),in-situ hybridization(ISH) and flow cytometry were applied to detect the expression of S100,CD83 mRNA and CD83 on DCs in 45 gastric adenocarcinoma tissues.The co-relationship of the S100 and CD83 expression with clinical(pathological) features was analyzed.Results IHC showed that S100 expression was unevenly distributed(within) 42 cancer tissue and CD83 was only expressed in tumor-adjacent tissue and normal tissue.ISH showed that CD83 mRNA was limitedly expressed within 7 samples.S100 expression had no significant(correlation) with clinical pathological features,while CD83 reversely correlated with TNM stages.Detected by flow cytometry,CD83 was expressed in low level in all 45 gastric cancer tissues and negative correlations were found with lymph node metastasis and TNM stages of gastric cancer(r=-0.879,P
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Objective To study the expression of RhoC mRNA in human primary hepatocellular carcinoma(PHCC) and paracarcinoma liver(PCL) tissues .Method Reverse transcription polymerase chain reaction(RT-PCR) was used to detect the expression of RhoC mRNA in the PHCC and PCL tissue of 30 patients with PHCC. Results The opacity density (OD)of RhoC mRNA expression in PHCC tissues was significantly higher than that in PCL tissures(P
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To evaluate possible roles of matrix metalloproteinase (MMP)-1, -2, tissue inhibitor of metalloproteinase (TIMP)-1, -2 and membrane-type-1 matrix metalloproteinase (MT1-MMP) in invasion of human gliomas, expressions of these proteins were investigated in ten cases of human glioma and two meningioma tissues and eight human glioma cell lines. In gelatin zymography, MMP-2 activities of glioblastomas were higher than astrocytomas. The activated form of MMP-2 was seen in five of six cases of glioblastomas, but not in astrocytomas. MMP-9 activity was detected in all cases of malignant astrocytomas but the reactivity of MMP-9 was weaker than that of MMP-2. MT1-MMP mRNA expression in glioblastomas was higher than that in astrocytomas. Five cases of glioblastomas with activated form of MMP-2 had MT1-MMP expressions. In vitro, human glioma cell lines with high expression of MT1-MMP also showed high MMP-2 activity. TIMP-1 transcripts were constitutively present in almost all glioma tissues and cell lines, whereas TIMP-2 mRNA were weak especially in malignant gliomas. Imbalance of TIMP-2/MMP-2 was observed using immunoprecipitation analysis in a glioma cell line. High expression of MMP-2 and MT1-MMP is possibly involved in invasiveness of malignant glioma.
Subject(s)
Humans , Animals , Blotting, Northern/methods , Brain/pathology , Brain Neoplasms/pathology , Brain Neoplasms/enzymology , Enzyme Activation , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 2/genetics , Matrix Metalloproteinase 9/metabolism , Gene Expression Regulation, Enzymologic , Glioma/pathology , Glioma/enzymology , Metalloendopeptidases/genetics , Papio , Tissue Inhibitor of Metalloproteinase-2/genetics , Tissue Inhibitor of Metalloproteinase-1/genetics , Tumor Cells, CulturedABSTRACT
To evaluate possible roles of matrix metalloproteinase (MMP)-1, -2, tissue inhibitor of metalloproteinase (TIMP)-1, -2 and membrane-type-1 matrix metalloproteinase (MT1-MMP) in invasion of human gliomas, expressions of these proteins were investigated in ten cases of human glioma and two meningioma tissues and eight human glioma cell lines. In gelatin zymography, MMP-2 activities of glioblastomas were higher than astrocytomas. The activated form of MMP-2 was seen in five of six cases of glioblastomas, but not in astrocytomas. MMP-9 activity was detected in all cases of malignant astrocytomas but the reactivity of MMP-9 was weaker than that of MMP-2. MT1-MMP mRNA expression in glioblastomas was higher than that in astrocytomas. Five cases of glioblastomas with activated form of MMP-2 had MT1-MMP expressions. In vitro, human glioma cell lines with high expression of MT1-MMP also showed high MMP-2 activity. TIMP-1 transcripts were constitutively present in almost all glioma tissues and cell lines, whereas TIMP-2 mRNA were weak especially in malignant gliomas. Imbalance of TIMP-2/MMP-2 was observed using immunoprecipitation analysis in a glioma cell line. High expression of MMP-2 and MT1-MMP is possibly involved in invasiveness of malignant glioma.
Subject(s)
Humans , Animals , Blotting, Northern/methods , Brain/pathology , Brain Neoplasms/pathology , Brain Neoplasms/enzymology , Enzyme Activation , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 2/genetics , Matrix Metalloproteinase 9/metabolism , Gene Expression Regulation, Enzymologic , Glioma/pathology , Glioma/enzymology , Metalloendopeptidases/genetics , Papio , Tissue Inhibitor of Metalloproteinase-2/genetics , Tissue Inhibitor of Metalloproteinase-1/genetics , Tumor Cells, CulturedABSTRACT
Objective To investigate the expression of vascular endothelial growth factor-C(VEGF-C) and matrix metalloproteinase-7(MMP-7) in gastric carcinoma and their correlation with tumor invasion and(metastasis).Methods Streptavidin peroxidase immunohistochemistry technique(SP)was used to detect the(expression) of VEGF-C and MMP-7 in 60 gastric carcinoma specimens,60 specimens of gastric mucosa(adjacent) to carcinoma,and 30 regional lymph node specimens.Results The positive expression rate of VEGF-C,MMP-7 in gastric carcinoma was markedly higher than that in normal gastric mucosa and gastric mucosa adjacent to carcinoma.The positive expression rates of VEGF-C and MMP-7 in metastatic regional lymph nodes were significantly higher than that in non-metastatic regional lymph nodes(P