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‣ Steroidogenic Factor 1 Overexpression and Gene Amplification Are More Frequent in Adrenocortical Tumors from Children than from Adults

ALMEIDA, Madson Q.; SOARES, Ibere Cauduro; RIBEIRO, Tamaya C.; FRAGOSO, Maria Candida B. V.; MARINS, Lidiane V.; WAKAMATSU, Alda; RESSIO, Rodrigo A.; NISHI, Mirian Y.; JORGE, Alexander A. L.; LERARIO, Antonio M.; ALVES, Venancio A. F.; MENDONCA, Berenice
Fonte: ENDOCRINE SOC Publicador: ENDOCRINE SOC
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
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Background: Steroidogenic factor 1 (SF-1) is a key determinant of endocrine development and function of adrenal cortex. SF-1 overexpression and gene amplification were previously demonstrated in a small group of pediatric adrenocortical tumors. Objective: Our objective was to determine the frequency of SF-1 protein expression and gene amplification in a large cohort of pediatric and adult adrenocortical tumors. Patients: SF-1 protein expression was assessed in a cohort of 103 adrenocortical tumors from 36 children and 67 adults, whereas gene amplification was studied in 38 adrenocortical tumors ( 17 from children). Methods: Tissue microarray, multiplex ligation-dependent probe amplification, and quantitative real-time PCR were used. Results: Astrong nuclear SF-1 expression was detected by tissue microarray in 56% (20 of 36) and 19% (13 of 67) of the pediatric and adult adrenocortical tumors, respectively (P = 0.0004). Increased SF-1 copy number was identified in 47% (eight of 17) and 10% (two of 21) of the pediatric and adult adrenocortical tumors, respectively (P = 0.02). All adrenocortical tumors with SF-1 gene amplification showed a strong SF-1 staining, whereas most of the tumors (61%) without SF-1 amplification displayed a weak or negative staining (P = 0.0008). Interestingly...

‣ ORAOV1 is amplified in oral squamous cell carcinoma

Xavier, Flávia Caló de Aquino; Rodini, Camila Oliveira; Paiva, Katiucia Batista da Silva; Souza Setubal Destro, Maria Fernanda; Severino, Patricia; Moyses, Raquel A.; Tajara, Eloiza H.; Nunes, Fabio Daumas
Fonte: WILEY-BLACKWELL; MALDEN Publicador: WILEY-BLACKWELL; MALDEN
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
47.459863%
BACKGROUND: Oral cancer overexpressed 1 (ORAOV1) was found as a candidate oncogene in the 11q13 chromosomal region, based on its amplification and overexpression in oral cancer cell lines. Because gene amplification often leads to increased levels of gene expression, we aimed to verify the relationship between ORAOV1 gene status and mRNA expression primarily in oral squamous cell carcinoma (OSCC) by quantitative assay, correlating with clinical and pathological characteristics in patients. METHODS: Levels of ORAOV1 amplification and expression were evaluated by qPCR and RT-qPCR in OSCC cell lines and in tumor and non-tumoral surgical margins from 33 patients with OSCC. All subjects were smokers and habitual alcohol drinkers, mostly men above 40 years of age and with a single primary tumor. RESULTS: ORAOV1 exhibited increased gene expression levels as well as higher copy number in three OSCC cell lines with 11q13 amplified chromosomal region when compared with the OSCC cell line without the amplification (one-way ANOVA, P < 0.05). Weak correlation between ORAOV1 mRNA levels and DNA copy number was seen in tumor samples (Spearman, P = 0.07). Although ORAOV1 was amplified in tumor (Wilcoxon, P < 0.01), high levels of transcripts in margin did not reveal differences in comparison with tumor (Wilcoxon...

‣ Isolamento e caracterização de gene que confere resistência à terbinafina em leishmania major; Identification and characterization of a terbinafine resistance gene in L. major.

Marchini, Julio Flávio Meirelles
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 13/06/2008 Português
Relevância na Pesquisa
57.26761%
A amplificação gênica pode ser compreendida como um mecanismo de regulação de expressão protéica em Leishmania. A exposição a concentrações não letais de diferentes drogas isoladamente, como o metotrexato, a primaquina, cloroquina e antimônio levam à amplificação de regiões específicas como as localizadas no cromossomo 6 e no cromossomo 23. Essas linhagens tornam-se resistentes a estas drogas e eventualmente apresentam resistência cruzada a outras. A terbinafina é uma substância sintética utilizada como antifúngico que age pela inibição da esqualeno epoxidase impedindo a síntese de ergosterol, componente da membrana celular de Leishmania. A exposição do parasita à terbinafina leva à amplificação da região H. A fragmentação da região H permitiu delimitar a resistência a 2,8 kb; fragmento T1. Por mutagênese insercional o gene de resistência à terbinafina foi definido e nomeado HTBF. A proteína codificada pelo HTBF possui uma extremidade N-terminal hidrofílica e C-terminal hidrofóbica com quatro alfa-hélices sendo, supostamente, uma proteína integral de membrana. Possui semelhança com a proteína Yip de Saccharomyces cerevisiae, que participa do transporte vesicular do retículo endoplasmático para o complexo de Golgi. O gene HTBF foi detectado em linhagem sensível de L. major e de outras espécies de Leishmania e seu transcrito em linhagens sensíveis e resistentes de L. major. Levantou-se a hipótese de se tratar de locus de resistência a múltiplas drogas já que as regiões amplificadas...

‣ Sequenciamento e análise de um banco de cDNA de glândulas salivares de Rhynchosciara americana e caracterização do gene RaDup; Sequencing and analysis of a EST Bank from salivary glands of Rhynchosciara americana and characterization of the gene RaDup

Siviero, Fábio
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 20/04/2004 Português
Relevância na Pesquisa
57.17814%
Durante o desenvolvimento deste projeto adotou-se como estratégia o sequenciamento de ESTs, com a finalidade de encontrar mensagens relacionadas com desenvolvimento, metabolismo e principalmente amplificação/politenização em glândulas salivares de Rhynchosciara americana, um díptero (Sciarídeo) que apresenta cromossomos politênicos e amplificação gênica rigidamente regulada ao longo do desenvolvimento larval, tanto neste tecido quanto em outros. Um total de 8193 ESTs foi gerado, estas foram anotadas e categorizadas segundo os termos do Gene Ontology Consortium, proporcionando uma visão geral do status metabólico, como em um Northern eletrônico, de um ponto importante no desenvolvimento desta espécie, quando surgem amplificações gênicas específicas e a glândula salivar necessita secretar as proteínas do casulo. Outros frutos deste seqüenciamento foram a determinação de 91 polimorfismos e a criação de uma tabela de códon usage. Diversos ESTs foram identificados com potencial envolvimento com os endociclos observados neste tecido, destes, RaDup e RaMCM5 foram selecionados para estudo. Suas regiões genômicas foram isoladas e suas localizações cromossômicas foram identificadas, em relação a RaDup, toda a porção codificante de seu mensageiro e 12kb de DNA genômico contendo seu gene foram seqüenciados...

‣ Análise da expressão, amplificação e deleção de EGFR e sua co-expressão com IL13R2 em astrocitomas; Analysis of EGFR expression, amplification and deletion and its coexpression with IL13R 2 in astrocytomas

Carvalho, Priscila Oliveira de
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 30/10/2009 Português
Relevância na Pesquisa
47.492236%
O Receptor do Fator de Crescimento Epidérmico (do inglês, EGFR) é uma proteína de membrana celular que consiste em um domínio extracelular para o acoplamento do ligante e em um domínio intracelular apresentando sítio catalítico de tirosinoquinase. Em ~40% dos GBMs primários é observada a amplificação de EGFR resultando na sua hiperexpressão, o que raramente ocorre em GBM secundário. Mais da metade dos casos de GBM com amplificação do receptor está associado com rearranjo do gene, uma forma deletada de EGFR (EGFRvIII). Adicionalmente, o receptor de interleucina 13 alfa-2 (IL-13R 2), apresenta-se abundante e especificamente hiperexpresso em gliomas de alto grau, em particular, GBM. O objetivo do presente estudo é analisar a expressão, amplificação, e deleção de EGFR em astrocitomas, bem como a coexpressão entre esse gene e o da IL-13R 2. Foram analisadas 145 astrocitomas (22 astrocitomas pilocíticos (AP); 22 astrocitomas grau II (AGII); 17 astrocitomas anaplásico (AA); e 84 GBM) e 17 tecidos cerebrais não tumorais provenientes de cirurgia de epilepsia. A deleção EGFRvIII foi analisada por RT-PCR, e confirmada por PCR em tempo real (RQ-PCR). A expressão relativa de EGFR e IL-13R 2 foi estudada por RQ-PCR utilizando-se o método SYBR Green...

‣ Análise do número de cópias dos genes IGFIR, SF1 e FGFR4 em tumores adrenocorticais de crianças e adultos; Analysis of copy number variations of IGF1R, SF1 and FGFR4 genes in adrenocortical tumors from children and adults

Ribeiro, Tamaya Castro
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Dissertação de Mestrado Formato: application/pdf
Publicado em 30/08/2010 Português
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Introdução: Uma elevada incidência de tumores adrenocorticais pediátricos e de adultos é observada nas regiões sul e sudeste do Brasil. Hiperexpressão dos genes IGF1R, SF1 e FGFR4 tem sido descrita em tumores adrenocorticais. Apesar de hiperexpressão ser um evento comum em diversas neoplasias, ainda não são claros os mecanismos moleculares que seriam responsáveis por essa falha na regulação da expressão. Objetivos: Determinar o número de cópias dos genes IGF1R, SF1 e FGFR4 em tumores adrenocorticais diagnosticados em crianças e adultos. Adicionalmente correlacionaremos os dados de expressão gênica e/ou protéica de IGF1R, SF1 e FGFR4 com o diagnóstico histológico e evolutivo dos tumores adrenocorticais. Pacientes e métodos: Sessenta e quatro pacientes com tumores adrenocorticais foram selecionados para o estudo. Todos os pacientes foram submetidos à avaliação clínica e tratamento cirúrgico. Oito glândulas adrenais normais obtidas em cirurgias renais ou autópsias foram utilizadas como controles. DNA genômico extraído dos tecidos normais e tumorais da glândula suprarrenal foram utilizados como substrato nas reações de multiplex ligation-dependent probe amplification (MLPA) com o intuito de se determinar o número de cópias dos genes IGF1R...

‣ Caracterização do gene LmHUS1 e de sua participação no fenômeno de amplificação gênica em Leishmania spp.; LmHUS1 gene characterization and its participation in the gene amplification in Leishmania spp.

Nunes, Vinícius Santana
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 30/09/2011 Português
Relevância na Pesquisa
67.28663%
O parasita protozoário Leishmania apresenta um genoma plástico e dinâmico onde a amplificação gênica e translocações cromossomais são fenômenos comuns. Tal plasticidade sugere a necessidade de mecanismos robustos de reparo do DNA e de manutenção do genoma. A célula eucariótica desenvolveu sistemas de controle checkpoint que reconhecem estruturas alteradas de DNA e bloqueiam a progressão do ciclo celular permitindo que o reparo do DNA aconteça. Nestas células, o complexo heterotrimérico formado pelas proteínas Hus1, Rad9, e Rad1 participa nas etapas iniciais de reconhecimento e sinalização do estresse replicativo. Neste trabalho mostramos que a proteína Hus1 homóloga de Leishmania major é uma proteína nuclear que melhora a capacidade do parasito em lidar com o estresse replicativo. A análise de northern e PCR em tempo real mostraram que, após a transfecção do gene, a linhagem selecionada apresenta níveis aumentados dos transcritos LmHUS1. A utilização de um anticorpo anti-LmHus1 demonstrou o aumento nos níveis da proteína nestas células. Ainda, a superexpressão de LmHus1 confere resistência às drogas genotóxicas hidroxiuréia (HU) e metil metanosulfonato (MMS), e a resistência à HU correlaciona-se com a redução de dano no DNA após a expressão da LmHus1. A ruptura de um dos alelos LmHUS1 diminui os níveis do seu produto...

‣ Gene amplification in carcinogenesis

Bizari, Lucimari; Silva, Ana Elizabete; Tajara, Eloiza H.
Fonte: Sociedade Brasileira de Genética Publicador: Sociedade Brasileira de Genética
Tipo: Artigo de Revista Científica Formato: 1-7
Português
Relevância na Pesquisa
67.421016%
Gene amplification increases the number of genes in a genome and can give rise to karyotype abnormalities called double minutes (DM) and homogeneously staining regions (HSR), both of which have been widely observed in human tumors but are also known to play a major role during embryonic development due to the fact that they are responsible for the programmed increase of gene expression. The etiology of gene amplification during carcinogenesis is not yet completely understood but can be considered a result of genetic instability. Gene amplification leads to an increase in protein expression and provides a selective advantage during cell growth. Oncogenes such as CCND1, c-MET, c-MYC, ERBB2, EGFR and MDM2 are amplified in human tumors and can be associated with increased expression of their respective proteins or not. In general, gene amplification is associated with more aggressive tumors, metastases, resistance to chemotherapy and a decrease in the period during which the patient stays free of the disease. This review discusses the major role of gene amplification in the progression of carcinomas, formation of genetic markers and as possible therapeutic targets for the development of drugs for the treatment of some types of tumors.

‣ Analysis of EGFR Overexpression, EGFR gene amplification and the EGFRvIII Mutation in portuguese high-grade gliomas

Viana, Marta Pereira; Lopes, José M.; Little, Suzie; Milanezi, Fernanda; Basto, Diana; Pardal, Fernando; Jones, C.; Reis, R. M.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /03/2008 Português
Relevância na Pesquisa
57.16953%
Background: Patients with malignant gliomas do not respond to any current therapy. Epidermal growth factor receptor (EGFR) controls several oncogenic processes, being frequently up-regulated in gliomas due to overexpression, gene amplification and gene mutation. EGFR inhibitors are being tried in gliomas, yet the molecular determinants of therapeutic response are unclear. Materials and Methods: EGFR overexpression, EGFRvIII mutation and EGFR amplification were determined by immunohistochemistry and chromogenic in situ hybridization (CISH) in 27 primary glioblastomas (GBM), 24 anaplastic oligodendrogliomas (AO) and four anaplastic oligoastrocytomas (AOA). Results: EGFR overexpression was associated with EGFR amplification, being found in 48% and 53% GBM, 33% and 40% AO and 75% and 67% AOA, respectively. EGFRvIII was found in 22% GBM, 8% AO and was absent in AOA. No association was observed between EGFR alterations and patient survival. Conclusion: We characterized, for the first time, EGFR molecular alterations in Portuguese patients with malignant glioma and identified a subpopulation of patients presenting putative biomarkers for EGFR-based therapies.

‣ Gene amplification in carcinogenesis

Bizari,Lucimari; Silva,Ana Elizabete; Tajara,Eloiza H.
Fonte: Sociedade Brasileira de Genética Publicador: Sociedade Brasileira de Genética
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/01/2006 Português
Relevância na Pesquisa
67.421016%
Gene amplification increases the number of genes in a genome and can give rise to karyotype abnormalities called double minutes (DM) and homogeneously staining regions (HSR), both of which have been widely observed in human tumors but are also known to play a major role during embryonic development due to the fact that they are responsible for the programmed increase of gene expression. The etiology of gene amplification during carcinogenesis is not yet completely understood but can be considered a result of genetic instability. Gene amplification leads to an increase in protein expression and provides a selective advantage during cell growth. Oncogenes such as CCND1, c-MET, c-MYC, ERBB2, EGFR and MDM2 are amplified in human tumors and can be associated with increased expression of their respective proteins or not. In general, gene amplification is associated with more aggressive tumors, metastases, resistance to chemotherapy and a decrease in the period during which the patient stays free of the disease. This review discusses the major role of gene amplification in the progression of carcinomas, formation of genetic markers and as possible therapeutic targets for the development of drugs for the treatment of some types of tumors.

‣ Packaging Cells Based on Inducible Gene Amplification for the Production of Adeno-Associated Virus Vectors

Inoue, Naoki; Russell, David W.
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /09/1998 Português
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57.15608%
Although vectors based on adeno-associated virus (AAV) offer several unique advantages, their usage has been hampered by the difficulties encountered in vector production. In this report, we describe a new AAV packaging system based on inducible amplification of integrated helper and vector constructs containing the simian virus 40 (SV40) replication origin. The packaging and producer cell lines developed express SV40 T antigen under the control of the reverse tetracycline transactivator system, which allows inducible amplification of chromosomal loci linked to the SV40 origin. Culturing these cells in the presence of doxycycline followed by adenovirus infection resulted in helper and vector gene amplification as well as higher vector titers. Clonal producer cell lines generated vector titers that were 10 times higher than those obtained by standard methods, with approximately 104 vector particles produced per cell. These stocks were free of detectable replication-competent virus. The lack of a transfection step combined with the reproducibility of stable producer lines makes this packaging method ideally suited for the large-scale production of vector stocks for human gene therapy.

‣ The MDM2 gene amplification database.

Momand, J; Jung, D; Wilczynski, S; Niland, J
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 01/08/1998 Português
Relevância na Pesquisa
47.4799%
The p53 tumor suppressor gene is inactivated in human tumors by several distinct mechanisms. The best characterized inactivation mechanisms are: (i) gene mutation; (ii) p53 protein association with viral proteins; (iii) p53 protein association with the MDM2 cellular oncoprotein. The MDM2 gene has been shown to be abnormally up-regulated in human tumors and tumor cell lines by gene amplification, increased transcript levels and enhanced translation. This communication presents a brief review of the spectrum of MDM2 abnormalities in human tumors and compares the tissue distribution of MDM2 amplification and p53 mutation frequencies. In this study, 3889 samples from tumors or xenografts from 28 tumor types were examined for MDM2 amplification from previously published sources. The overall frequency of MDM2 amplification in these human tumors was 7%. Gene amplification was observed in 19 tumor types, with the highest frequency observed in soft tissue tumors (20%), osteosarcomas (16%) and esophageal carcinomas (13%). Tumors which showed a higher incidence of MDM2 amplification than p53 mutation were soft tissue tumors, testicular germ cell cancers and neuro-blastomas. Data from studies where both MDM2 amplification and p53 mutations were analyzed within the same samples showed that mutations in these two genes do not generally occur within the same tumor. In these studies...

‣ Gene Amplification and Overexpression of CDK4 in Sporadic Breast Carcinomas Is Associated with High Tumor Cell Proliferation

An, Han-Xiang; Beckmann, Matthias W.; Reifenberger, Guido; Bender, Hans G.; Niederacher, Dieter
Fonte: American Society for Investigative Pathology Publicador: American Society for Investigative Pathology
Tipo: Artigo de Revista Científica
Publicado em /01/1999 Português
Relevância na Pesquisa
47.502593%
Amplification of the cyclin-dependent kinase 4 (CDK4) gene, located at 12q13-q14, has been found as an alternative genetic alteration to CDKN2A inactivation in various human tumors including malignant gliomas and sarcomas. In the present study, we have evaluated the frequency of the CDK4 gene amplification in sporadic breast cancer by applying a nonradioactive quantitative differential polymerase chain reaction based on fluorescent DNA technology. Fluorescent-labeled polymerase chain reaction products were analyzed with an automated DNA sequencer. Amplification of CDK4 gene was detected in 15 (15.8%) of 95 breast cancers. All tumors with CDK4 gene amplification showed high CDK4 protein expression determined by immunohistochemistry. Furthermore, the mean Ki-67 labeling index in tumors with CDK4 gene amplification was significantly higher than in those without CDK4 gene amplification. No significant associations were observed between CDK4 gene amplification and any specific histopathological parameter. The findings of this study provide the first evidence of CDK4 gene amplification in breast cancer and suggest that CDK4 gene amplification appears to be of importance in the pathogenesis of a subset of sporadic breast cancer.

‣ HER2 gene amplification in esophageal squamous cell carcinoma is less than in gastroesophageal junction and gastric adenocarcinoma

HUANG, JUN-XING; ZHAO, KUN; LIN, MEI; WANG, QI; XIAO, WEI; LIN, MAO-SONG; YU, HONG; CHEN, PING; QIAN, RONG-YU
Fonte: D.A. Spandidos Publicador: D.A. Spandidos
Tipo: Artigo de Revista Científica
Português
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47.55238%
The aim of the present study was to detect the amplification of the human epidermal growth factor receptor 2 (HER2) gene in esophageal squamous cell carcinoma (ESCC), gastroesophageal junction adenocarcinoma (GEJAC) and gastric cancer (GC), as well as to understand the pathological meaning of HER2 gene amplification with regard to clinico-pathological parameters in these types of cancer. HER2 gene amplification was evaluated by fluorescence in situ hybridization (FISH) in surgically obtained specimens from 76 cases of ESCC, 50 of GEJAC and 48 of GC, as well as 21 specimens of tumor-adjacent normal epithelium as a control group. The HER2 gene amplification rates in ESCC, GEJAC and GC were 3.9 (3/76), 24.0 (12/50) and 18.8% (9/48), respectively. The rates of HER2 gene amplification in GEJAC and GC were significantly higher compared with ESCC (χ2=11.563, P<0.001 and χ2=7.375, P<0.007, respectively). HER2 gene amplification was not detected in the normal esophageal or gastric mucosa samples. In ESCC, HER2 gene amplification was correlated with the invasion of the ESCC cells, vascular invasion and lymph node metastasis (χ2=4.789, 3.858 and 5.354, respectively; all P<0.05). However, in GEJAC and GC, no correlations were observed between HER2 amplification and the gender...

‣ EGFR protein expression and gene amplification in squamous intraepithelial lesions and squamous cell carcinomas of the cervix

Li, Qing; Tang, Yongfeng; Cheng, Xue; Ji, Jie; Zhang, Jingmin; Zhou, Xiaojun
Fonte: e-Century Publishing Corporation Publicador: e-Century Publishing Corporation
Tipo: Artigo de Revista Científica
Publicado em 15/01/2014 Português
Relevância na Pesquisa
47.460273%
The purpose of this study was to evaluate the protein expression and gene amplification of epithelial growth factor receptor (EGFR) in intraepithelial neoplasias and squamous cell carcinoma of the cervix and to determine the value of EGFR in carcinogenesis, progression, and prognosis of cervical cancer. EGFR protein expression and gene amplification involved gene copy number in 75 cases of cervical various lesions were evaluated using immunohistochemistry and by fluorescence in situ hybridization (FISH) techniques. Expression of EGFR was observed in 76.00% of the high-grade CIN and 79.17% of the invasive carcinomas. In contrast, there were low levels of EGFR expression in chronic cervicitis (1/10) and low-grade CIN (7/16). There were statistically significant differences among them (P<0.05). Gene amplification was detected in 20.51% high-grade CIN and invasive carcinoma, but there only 4.35% EGFR gene amplification was observed in chronic cervicitis and low grade CIN. Among the 42 patients with negative or low levels of EGFR expression, 26 patients (61.90%) were found to have diploidy and 11 patients (26.20%) to have balanced triploidy. However, among the 20 patients with an intermediate and high levels of EGFR protein expression, 13 (65.00%) were found to have balanced polyploidy or gene amplification. All cases of EGFR gene amplification involved intermediate and high levels of protein expression. EGFR may be involved in the carcinogenesis of the cervix and may be an early event during the carcinogenesis. Overexpression of EGFR protein may result from gene amplification and increases in gene copy number.

‣ Gene amplification of EGFR and its clinical significance in various cervical (lesions) lesions using cytology and FISH

Li, Qing; Cheng, Xue; Ji, Jie; Zhang, Jingmin; Zhou, Xiaojun
Fonte: e-Century Publishing Corporation Publicador: e-Century Publishing Corporation
Tipo: Artigo de Revista Científica
Publicado em 15/04/2014 Português
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47.46893%
The purpose of this study was to investigate the gene amplification and clinical significance of the epithelial growth factor receptor (EGFR) gene in cervical lesions. This study was designed to detect the EGFR gene amplification by liquid-based cytology and fluorescence in situ hybridization (FISH) techniques in 78 cases of cervical various lesions [28 cases of normal control cervix, 26 low grade squamous intraepithelial lesion (LSIL) and 25 high grade squamous intraepithelial lesion (HSIL)]. Positive gene amplification rates of the EGFR gene in normal cervix, LSIL and HSIL were 7.14%, 23.08% and 62.50%, respectively. There was a significantly difference between HSIL and normal control cervix or LSIL (P<0.01). At the same time, the gene amplification rate of EGFR was also significantly different between the cases of LSIL with positive follow-up and negative follow-up (P<0.01). In addition, the correlation between EGFR gene amplification and HPV viral load in the same sample was evaluated in some cases. Then the increase of EGFR gene amplification in HSILs and LSILs with positive follow-up suggests that EGFR gene amplification is associated with the severity of cytologic findings. Therefore, detection of EGFR gene may provide an objective genetic test for the assessment of cells in Pap smears and serves as a screening marker for HSILs or LSILs...

‣ A new pineoblastoma cell line, PER-480, with der(10)t(10;17), der(16)t(1;16), & enhanced MYC expression in the absence of gene amplification.

Kees, U.; Spagnolo, D.; Hallam, L.; Ford, J.; Ranford, P.; Baker, D.; Callen, D.; Biegel, J.
Fonte: ELSEVIER SCIENCE INC Publicador: ELSEVIER SCIENCE INC
Tipo: Artigo de Revista Científica
Publicado em //1998 Português
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57.002075%
Pineoblastoma is a rare, but highly malignant tumor of the central nervous system (CNS) in children and is classified as a central primitive neuroectodermal tumor (PNET). Despite notable recent advances in understanding the molecular genetic basis of malignancies, the pathogenesis of PNETs remains enigmatic. There is scant information on the cytogenetics of PNETs arising in the pineal gland and the only three reported cases did not show any common aberrations. Here we report the establishment and characterization of a new pineoblastoma cell line, PER-480. The biopsy material and the cell line were characterized using light and electron microscopy and immunohistochemical analyses. The cell line was examined for expression of cell surface markers using a panel of monoclonal antibodies and by cytogenetic analysis. MYC family genes were studied at the DNA, RNA, and protein level. Cell line PER-480 showed neuronal differentiation and the karyotype demonstrated two abnormalities, a der(10)t(10;17) and a der(16)t(1;16). An intriguing finding is that all three pineoblastoma cell lines established in our laboratory, PER-452, PER-453, and PER-480, showed enhanced expression but not amplification of a member of the MYC family of proto-oncogenes. Cell line PER-480 reported here will be useful for the further investigation of the molecular genetic basis of central PNETs.; Ursula R. Kees...

‣ HER-2/neu gene amplification in esophageal adenocarcinoma and its influence on survival

Thompson, S.; Sullivan, T.; Davies, R.; Ruszkiewicz, A.
Fonte: Lippincott Williams & Wilkins Publicador: Lippincott Williams & Wilkins
Tipo: Artigo de Revista Científica
Publicado em //2011 Português
Relevância na Pesquisa
67.42482%
Background: HER-2/neu (c-erbB-2, HER2) gene amplification and protein overexpression have been associated with poor prognosis in several solid tumors, including breast and gastric cancer. Its incidence and significance in esophageal adenocarcinoma is unknown. Materials and Methods: Tissue microarrays were successfully constructed from 89 paraffin-embedded archival specimens of esophageal adenocarcinomas for HER2 gene amplification by silver-enhanced in situ hybridization (SISH). No patients had undergone neoadjuvant therapy. Protein overexpression was tested with immunohistochemistry (IHC) using automated immunostaining (Ventana Benchmark). Incidence of HER2 positivity, correlation to clinicopathological variables in esophageal cancer patients, and concordance between SISH and IHC were determined. Results: True HER2 gene amplification was detected in 14 esophageal cancer specimens (16%), and 92% of those with high-level HER2 amplification showed positive HER2 protein overexpression. No significant associations were found among gene amplification and clinicopathological factors. The 5-year survival rates were 57% for esophageal cancer patients with HER2 amplification compared with 32% without, but the difference in overall survival was not significant (P = .37). The correlation between SISH and IHC was statistically significant (P < .0001). Conclusion: While molecular targeting may be possible for approximately 16% of esophageal adenocarcinoma patients...

‣ Evaluation der HER-2/neu-Genamplifikation an Tumorabklatschpräparaten von Mammakarzinomen mittels FISH und deren Wertigkeit im Vergleich zur immunhistochemischen membranassoziierten Proteinüberexpression; Evaluation of HER-2/neu gene amplification in breast cancer imprint preparations using FISH and comparison with immunohistochemical membrane associated protein overexpression

Herzog, Sina
Fonte: Universidade de Tubinga Publicador: Universidade de Tubinga
Tipo: Dissertação
Português
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Die Kenntnis des HER-2/neu-Status von Mammakarzinomzellen ist zur Entscheidung bezüglich einer Immuntherapie mit Herceptin® notwendig. Dieser humanisierte monoklonale Antikörper ist gegen das HER-2/neu-Rezeptorprotein gerichtet, dessen Überexpression auf der Zellmembranoberfläche Voraussetzung für eine wirksame Therapie ist. In den meisten Fällen beruht eine Proteinüberexpression auf einer Amplifikation des HER-2/neu-Gens. In der vorliegenden Arbeit wurde der HER-2/neu-Status von 150 Mammakarzinomen mittels FISH untersucht und mit der immunhistochemischen, membranassoziierten Überexpression des HER-2/neu-Rezeptorproteins verglichen. Die Bestimmung einer Genamplifikation mittels FISH erfolgte an Tumorabklatschpräparaten mit dem PathVysion (TM) HER-2/neu DNA Sonden-Kit der Firma Vysis. Zur Beurteilung der Proteinüberexpression mittels IHC an Formalin-fixierten, in Paraffin-eingebetteten Gewebeproben diente der monoklonale Antikörper CB11 der Firma Novocastra oder der polyklonale Kaninchen Anti-human c-erbB-2 Onkoprotein-Antikörper der Firma Dako. Die FISH war in 133 der 150 angefärbten Tumorabklatschpräparate erfolgreich. Nach den Kriterien der HER-2/CEP17-Ratio zeigten 10,5% der Fälle eine Amplifikation des HER-2/neu-Gens. Bei ausschließlicher Bewertung der Absolutzahl des HER-2/neu-Sondensignals mit Berechnung der durchschnittlichen HER-2/neu-Genkopienzahl pro Tumorzellkern wiesen 9...

‣ DNA sequence templates adjacent nucleosome and ORC sites at gene amplification origins in Drosophila

Liu, Jun; Zimmer, Kurt; Rusch, Douglas B.; Paranjape, Neha; Podicheti, Ram; Tang, Haixu; Calvi, Brian R.
Fonte: Oxford University Press Publicador: Oxford University Press
Tipo: Artigo de Revista Científica
Português
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Eukaryotic origins of DNA replication are bound by the origin recognition complex (ORC), which scaffolds assembly of a pre-replicative complex (pre-RC) that is then activated to initiate replication. Both pre-RC assembly and activation are strongly influenced by developmental changes to the epigenome, but molecular mechanisms remain incompletely defined. We have been examining the activation of origins responsible for developmental gene amplification in Drosophila. At a specific time in oogenesis, somatic follicle cells transition from genomic replication to a locus-specific replication from six amplicon origins. Previous evidence indicated that these amplicon origins are activated by nucleosome acetylation, but how this affects origin chromatin is unknown. Here, we examine nucleosome position in follicle cells using micrococcal nuclease digestion with Ilumina sequencing. The results indicate that ORC binding sites and other essential origin sequences are nucleosome-depleted regions (NDRs). Nucleosome position at the amplicons was highly similar among developmental stages during which ORC is or is not bound, indicating that being an NDR is not sufficient to specify ORC binding. Importantly, the data suggest that nucleosomes and ORC have opposite preferences for DNA sequence and structure. We propose that nucleosome hyperacetylation promotes pre-RC assembly onto adjacent DNA sequences that are disfavored by nucleosomes but favored by ORC.