Dissertations / Theses: 'Myc Genes'

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James, Leonard Philip. "Myc and Mad target genes /." Thesis, Connect to this title online; UW restricted, 2000. http://hdl.handle.net/1773/5093.

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Cairo, Stefano. "The promyelocytic leukaemia gene product PML interacts with Myc and influences the expression of Myc target genes." Thesis, Open University, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.406451.

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Vulcani-Freitas, Tânia Maria [UNIFESP]. "Perfil de expressão dos genes MYC, MYCN, TERT, ASPM e PRAME em Meduloblastoma." Universidade Federal de São Paulo (UNIFESP), 2010. http://repositorio.unifesp.br/handle/11600/9928.

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Meduloblastoma (MB) é o tumor maligno de sistema nervoso central (SNC) mais comum em criança, compreendendo 20% dos tumores primários de SNC e 40% dos tumores cerebelares da infância. Devido sua forte tendência metastática, o tratamento padrão pós-operatório inclui radio e quimioterapia, cujo impacto causa distúrbios endócrinos e de crescimento, e disfunção neurocognitiva a longo prazo. Frente a esses efeitos negativos, muitas pesquisas em meduloblastoma têm sido realizadas com intuito de obter conhecimento biológico desses tumores para tentar identificar fatores prognósticos moleculares que possam orientar os tratamentos, tornando-os mais específicos e menos agressivos. Alguns estudos em MB têm sugerido que a expressão do oncogene MYC está associada com diminuição da sobrevida e sua superexpressão com maior agressividade do tumor. Por isso, MYC pode ser um indicador importante de prognóstico, além de modulador do comportamento desta doença. Enquanto o gene MYC é expresso em uma variedade de tecidos, a expressão de MYCN, outro membro da família MYC, é restrita a estágios precoces do desenvolvimento embrionário de alguns tecidos apenas, entre eles, o sistema nervoso central e periférico, sendo um mediador importante dos efeitos de ativação na proliferação de células precursoras cerebelares. Dessa forma, quando a expressão de MYCN está desregulada, ela aumenta a tumorigenicidade dessas células podendo dar origem ao MB. Além disso, o gene MYC também é considerado importante regulador da transcrição TERT, gene que codifica uma subunidade catálica de da telomerase, enzima importante para carcinogênese e imortalização de células neoplásicas. A atividade anormal da telomerase está presente em 90% dos cânceres e o aumento de sua atividade está associado a eventos clínicos desfavoráveis. Outro gene importante é o ASPM (abnormal spindle-like microcephaly associated) que desempenha função fundamental na neurogênese e proliferação celular durante o desenvolvimento cerebral. Esse gene codifica uma proteína de centrossomo e fuso mitótico que permite a divisão celular simétrica em células neuroepiteliais durante o desenvolvimento e aumento do tamanho cerebral. Alterações em ASPM é a causa mais comum de microcefalia primária em humanos e de falha de segregação, induzindo a aneuploidias e instabilidade genética. Além desses genes, outro gene estudado recentemente, como alvo em xv imunoterapia, é o gene PRAME que codifica um antígeno tumoral que está presente em vários tumores, incluindo meduloblastoma. O gene PRAME possui baixa ou ausência de expressão em tecidos normais, por isso é pode ser um forte candidato como alvo em imunoterapia, que é um tratamento menos tóxico. OBJETIVOS: O objetivo desse estudo foi investigar a expressão dos genes MYC, MYCN, TERT, ASPM e PRAME em fragmentos tumorais de meduloblastoma de crianças e tentar correlacionar com os parâmetros clínicos e verificar se há correlação de MYC, MYCN, TERT entre si, uma vez que estão correlacionados. MÉTODOS: Análise de expressão gênica foi realizada através de PCR quantitativa em tempo real, utilizando sistema SYBR Green, em 37 amostras tumorais de crianças, com média de idade de 8 anos. Para comparação de perfil de expressão foi usada duas amostra de cérebro normal. A análise estatística foi realizada nos programas Graph Pad Prism 4 e VassarStats RESULTADOS: Todas nossas amostras superexpressaram o gene MYCN com valor de quantificação relativa (RQ) mediana igual a 31 com p=0.001; assim como, todas nossas amostras também superexpressaram o gene ASPM com mediana igual a 586, p<0.0001. Do total de amostras, 95%, 81% e 84% superexpressaram TERT, MYC e PRAME respectivamente, sendo os valores de RQ (mediana) iguais a 322, p=0.01; 9.2, p<0.0001; 33, p<0.0001. Apesar da elevada expressão dos genes estudados na maioria das amostras estudadas, houve apenas correlação estatística entre a superexpressão de MYCN (p=0.008) e os pacientes que foram a óbito, e de TERT e os pacientes que recidivaram (p=0.0431). Não encontramos outra correlação estatística entre a superexpressão dos genes e as características clínicas dos pacientes. CONCLUSÃO: Os genes MYC, MYCN e TERT estavam superexpressos nas amostras de meduloblastoma analisadas em uma freqüência muito superior ao demonstrado na literatura, o que sugere que esses três genes podem ajudar na identificação de tumores agressivos, uma vez que o pognóstico desses pacientes continua baseado apenas em parâmentros clínicos. A superexpressão de ASPM em todas as amostras estudadas sugere que este gene pode estar envolvido na origem de MB, como parte da neurogênse anormal durante o desenvolvimento embrionário, porém estudoas funcionais devem ser realizados para confirmar essa hipótese. Por fim, o gene PRAME pode ser candidato à marcador de célula tumoral em MB, podendo no futuro ser candidato como alvo em imunoterapias.
To investigate the expression of genes MYC, MYCN and TERT in tumor fragments of pediatric medulloblastoma and correlate gene expression profiles with clinical parameters. Analysis of gene expression was performed by quantitative PCR real time in 37 tumor samples and correlated with clinical and pathological data. All 37 samples overexpressed MYCN gene (p= 0.001), 95% and 84% of the samples overexpressed TERT and MYC, respectively (p<0.0001). Twenty nine (78%) of all samples had concomitant high expression of MYC, MYCN and TERT genes together. Seventeen (59%) were high-risk classification, 10 (34%) were metastatic (M+) stage, two (7%) were anaplastic or largecell/ anaplastic subtype, eight (28%) of patients relapsed, beyond thirteen (45%) suffered partial surgical resection. and fourteen (48%) died. We found correlation between MYC, MYCN and TERT expression (p<0.0001). The identification of a subgroup with concomitant overexpression of the three investigated genes suggests the possibility of using more than one aspect of molecular indicative of unfavorable prognosis that characterizes the group with poor outcome. However, in future this may be enhanced by targeted therapy for the product TERT as proposed in some neoplasms. The identification of molecular events in the medulloblastoma categorization aims to help at-risk groups moving towards individualized medicine.
TEDE
BV UNIFESP: Teses e dissertações

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Evans, Joanne R. "The investigation of internal ribosome entry in the c-myc and c-myb genes." Thesis, University of Leicester, 2003. http://hdl.handle.net/2381/29681.

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The c-myc gene contains an internal ribosome entry site (IRES) within its 5' untranslated region. The IRES was shown to have different activities between cell lines suggesting a requirement for protein trans-acting factors that are present in these cell lines in varying amounts. In addition a number of proteins have been shown to interact with the IRES by north-western and UV cross-linking analysis. Investigation of the protein factors involved in c-myc IRES translation identified PCBP1 (Poly (rC) binding protein 1), PCBP2, HnRNPK (heterogeneous nuclear ribonucleoprotein K), UNR (upstream of N-ras) and UNRIP (unr interacting protein) as having a role in c-myc IRES translation, PCBP1, PCBP2, HnRNPK and UNR were found to directly interact with the IRES RNA by UV cross-linking and electrophoretic mobility shift assays (EMSAs). Investigation of the proteins effect on c-myc IRES activity showed stimulation of IRES activity in HeLa cells by PCBP1 and PCBP2. The factor HnRNPK was found to have a slight stimulatory effect in vivo. In addition PCBP1 and PCBP2 were found to stimulate IRES activity in vitro in combination with UNR and UNRIP. Using the yeast three-hybrid system a number of additional proteins were found to interact with the c-myc IRES RNA. A novel Fibrillarin-like protein was identified and shown to strongly interact with the IRES by EMSA. Studies to determine a direct role of this factor in c-myc IRES translation were inconclusive. The study of translation of the c-myc gene identified an IRES within its 5'UTR. Investigation of the role of trans-acting factors in its translation showed a possible role of the factors PCBP2, HnRNPk and ITAF45 (IRES trans-acting factor 45).

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Östergren, Tiolina. "Identification of MYCN and SOX9 target genes and a study of drug treatment effects in medulloblastoma." Thesis, Uppsala universitet, Institutionen för biologisk grundutbildning, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-262085.

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Medulloblastoma (MB) is the most common malignant brain tumor affecting children. The transcription factors MYCN and SOX9 are associated with initiation, maintenance and recurrence of MB and are also connected to more aggressive tumors. In this study, a ChIP was performed to isolate DNA from genes that are transcriptionally regulated by these proteins. Identification of these target genes will reveal new potential drug targets and help us better understand the functions of MYCN and SOX9. The ChIP was not fully optimized during this project and the target genes were not sent for sequencing and identified. To study the connection between SOX9 and recurrence, cells with different levels of SOX9 were treated with drugs, after which cell viability was measured. No significant difference in resistance could be measured. Change in expression level of MYCN, SOX9 and other relevant genes after drug treatment was also studied. The results show an increase in SOX9 and HES1, suggesting that these genes are involved in tumor recurrence.

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Madisen, Linda. "Lymphoid specific elements deregulate c-myc transcription following chromosomal translocation in murine plasmacytoma and human Burkitt's lymphoma cells /." Thesis, Connect to this title online; UW restricted, 1996. http://hdl.handle.net/1773/6324.

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Peres, Raquel Mary Rodrigues 1983. "Instabilidade genômica em neoplasias malignas da mama em função da concentração de alumínio intracelular : Genomic instability association with intracellular aluminum concentration in breast tumors." [s.n.], 2013. http://repositorio.unicamp.br/jspui/handle/REPOSIP/310522.

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Orientador: Luis Otavio Zanatta Sarian
Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: Introdução: A hipótese de que os efeitos do alumínio em células humanas podem ter implicações clínicas tem sido levantada há algum tempo, especialmente no que concerne ao câncer de mama. As evidências laboratoriais mostrando altos níveis de alumínio nos tecidos da mama e os efeitos biológicos conhecidos sobre esse metal não são suficientes para estabelecer uma relação causal entre a exposição ao alumínio e o risco aumentando para o desenvolvimento do câncer de mama. O objetivo deste estudo foi estabelecer a concentração de alumínio nas áreas centrais e periféricas de tumores de mama, assim como na área glandular normal da mama e correlacionar esses achados com a instabilidade dos genes ERBB2, C-MYC e CCND1 e a aneuploidia dos cromossomos que contêm estes genes. Métodos: Para este estudo foram incluídas 176 mulheres com diagnóstico de carcinoma invasor de mama, com tumores maiores de 1cm3, sem quimioterapia neoadjuvante, operadas enter 2008 e 2010 no Hospital da Mulher Prof. Dr. José Aristodemo Pinotti - Centro de Atenção Integral à Saúde da Mulher (CAISM) - UNICAMP. Para a análise da concentração de alumínio intracelular, amostras de 150 pacientes foram consideradas viáveis; para a análise da instabilidade genômica em função da concentração de alumínio, 118 amostras foram consideradas viáveis, definindo o espaço amostral de cada um dos artigos apresentados. As amostras das áreas centrais e periféricas dos tumores de mama e das áreas glandulares normais da mama foram obtidas. A quantificação do alumínio contido nos tecidos da mama foi feita através da técnica de Espectrometria de Absorção Atômica em Forno de Grafite (GFAAS). Uma lâmina de Tissue Microarray (TMA), contendo as amostras de tumor e tecido normal foi utilizado para a realização da técnica de FISH para acessar o status dos genes ERBB2, C-MYC e CCND1 e dos centrômeros dos seus respectivos cromossomos 17, 8 e 11. Os dados clínico-patológicos foram obtidos dos prontuários de pacientes. Resultados: A média da concentração de alumínio encontrada na mama foi de 1,88 mg/kg nas áreas centrais do tumor, 2,10mg/kg nas áreas periféricas do tumor e 1,68mg/kg nas áreas de tecido glandular normal. A amplificação e/ou aneuploidia para ERBB2/CEP17, C-MYC/CEP8 e CCND1/CEP11 foi encontrada em 24%, 36,7% e 29,3% dos tumores, respectivamente. A média da concentração de alumínio nas áreas tumorais (tanto centrais quanto periféricas) não foi significativamente diferente daquela nas áreas de tecido normal. A concentração de alumínio também não foi significativamente associada a nenhum status de amplificação e/ou aneuploidia para os genes/cromossomos em questão. Conclusões: Consideramos importante que estudos experimentais in vitro continuem sendo realizados para elucidar os possíveis efeitos do alumínio nos tumores de mama, quer sejam esses efeitos relacionados ao microambiente tecidual ou mesmo a outras vias de estabilidade genômica
Abstract: Introduction: It has long been hypothesized if the effects of aluminum on human cells may have clinical implications, especially regarding to breast cancer. The current laboratorial evidence showing higher levels of aluminum in breast tissues and the known biological effects of this metal, are not sufficient to establish a causal relationship between aluminum exposure and increased risk of developing breast cancer. The objective of this study was to establish the aluminum concentration in the central and peripheral areas of breast tumors as well as in normal glandular area of the breast and to correlate these findings with the instability of ERBB2, C-MYC and CCND1, and aneuploidy of chromosomes harboring these genes. Methods: This study included 176 women diagnosed with invasive breast carcinoma with tumors larger than 1cm3 without neoadjuvant chemotherapy, operated between 2008 and 2010 at the Women's Hospital Professor. Dr. José Aristodemo Pinotti - Centro de Atenção Integral à Saúde da Mulher (CAISM) - UNICAMP. To analyze the intracellular concentration of aluminum, samples from 150 patients were considered viable; for the analysis of genomic instability as a function of the concentration of aluminum, 118 samples were considered viable. These figures define the sample of each of the two articles that this PhD thesis comprises. Evaluation of tissue aluminum content was carried out using Graphite Furnace Atomic Absorption Spectrometry (GFAAS). A TMA slide containing the tumor and normal samples was used in FISH assays to assess ERBB2, C-MYC and CCND1 and the respective chromosomes 17, 8 and 11 centromeres status. Clinicopathological data were obtained from patients' records. Results: The average aluminum content found in breast was 1.88 mg/kg in the central tumor areas, 2.10 mg/ kg in the peripheral tumor areas and 1.68 mg/ kg in the normal tissue areas. The amplification and/or aneuploid status for the ERBB2/CEP17, C-MYC/CEP8 and CCND1/CEP11 was detected in 24%, 36.7% and 29.3% of the tumors, respectively. The average aluminum content in tumor areas (either central or peripheral) was not significantly different from that in normal tissues. We found that aluminum concentration was not related to any of the gene status. Conclusions: We consider important that in vitro experimental studies continue to be done in order to elucidate the possible effects of aluminum in the development of breast tumors, whether it is influencing the tissue microenvironment or other genome stability pathways
Doutorado
Oncologia Ginecológica e Mamária
Doutora em Ciências da Saúde

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Lee, Sun Young. "The search for Myc-family genes in lepidopteran insects, strategies and applications." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/nq62172.pdf.

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Ibson, Julia Mary. "Structure and expression of myc genes in human small cell lung cancer." Thesis, University of Cambridge, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.330254.

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Souza, Ana Carolina Mamana Fernandes de. "Comparação das técnicas de PCR em tempo real e PCR para o estudo dos genes MYCN, DDX1 e NAG em pacientes portadores de neuroblastoma." Universidade de São Paulo, 2007. http://www.teses.usp.br/teses/disponiveis/5/5136/tde-21062007-141525/.

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O neuroblastoma é o tumor sólido extra-cranial mais comum e mortal da infância, sendo o tempo de sobrevida nos casos mais agressivos ainda muito curto. Uma das esperanças nesses casos é que os estudos moleculares possam fornecer informações sobre os genes ou as vias moleculares que governam a patogênese dos neuroblastomas. Pois, há poucos genes como o MYCN, que foi descrito por estar diretamente ligado ao neuroblastoma. A amplificação deste oncogene ocorre em pouco mais de 25% dos neuroblastomas e é considerada como o mais importante marcador de prognóstico nestes tumores, sendo fortemente relacionada aos estádios avançados da doença e falha no tratamento. Outros genes do amplicon do MYCN, incluindo o DDX1 \"DEAD box polypeptide 1 gene\" e o NAG \"neuroblastoma-amplified gene\", estão sendo observados por se apresentarem co-amplificados com o MYCN. Entretanto, a importância deste fenômeno no prognóstico ainda é desconhecida. Os objetivos deste trabalho foram determinar qual o melhor método para estudar a amplificação dos genes MYCN, DDX1 e NAG, além de esclarecer a importância da coamplificação dos genes DDX1 e NAG no prognóstico. Procedimento: O número de cópias dos genes MYCN, DDX1 e NAG foi determinado por PCR em Tempo Real e PCR convencional em 100 neuroblastomas primários. Os dados da PCR em Tempo Real foram analisados por quantificação absoluta e relativa. Os resultados da PCR convencional foram analisados por eletroforese em gel de agarose, medindo a intensidade das bandas formadas no gel no sistema Kodak. A relevância da amplificação gênica como marcador de prognóstico foi avaliada em 74 pacientes, dos quais nós obtivemos o acompanhamento clínico. Resultados: Nos 74 casos estudados, ambos os métodos demonstraram que a amplificação do MYCN estava associada com os estádios mais avançados da doença. A análise das curvas de sobrevida livre de progressão confirmou que pacientes com ausência de amplificação do MYCN apresentavam maior tempo de sobrevida. Nós também analisamos a amplificação do DDX1 nas mesmas amostras incluindo aquelas com ausência de amplificação de MYCN. Não foi encontrada nenhuma relação entre a co-amplificação com idade ao diagnóstico ou tempo de sobrevida. Conclusões: Os métodos aplicados para calcular o número de cópias dos genes na PCR em Tempo Real mostraram-se equivalentes. A PCR em Tempo Real apresentou maior acurácia nos resultados quando comparada à PCR convencional. A análise da sobrevida não demonstrou relação entre a amplificação dos genes DDX1 e/ou NAG com piora no prognóstico.
Neuroblastoma is the most common and deadly extra-cranial solid childhood tumor. Survival rates for aggressive neuroblastomas are still disappointingly low. One of the hopes is that molecular studies will provide insights into the genes and molecular pathways that govern neuroblastoma pathogenesis. However, at present only a few genes as MYCN have been directly linked to neuroblastoma. MYCN oncogene amplification, occurring in up to 25% of neuroblastomas, has been considered the most important prognostic factor, strongly correlating to advanced stage disease and treatment failure. Another genes in the MYCN amplicon, including the DEAD box polypeptide 1 (DDX1) gene, and neuroblastoma-amplified gene (NAG gene), have been found to be frequently co-amplified with MYCN in NB. But the prognostic significance of the coamplification remains unclear. The aims of this study were to evaluate which is the best method to study the gene amplification of those three genes MYCN, DDX1 and NAG, as well as clarify the prognostic significance of the co-amplification or DDX1 and NAG with MYCN. Procedure: The gene copy numbers of MYCN, DDX1, and NAG were determined by the real-time quantitative polymerase chain reaction and conventional polymerase chain reaction in 100 primary NBs. Real-Time data were analyzed by absolute and relative quantification. For conventional PCR, samples were electrophoresed on a 2% agarose gel and the intensity of each band evaluated by Kodak image software. To evaluate of the prognostic significance of the gene amplification we had only 74 cases in witch we could analyze the follow-up. Results: In all 74 cases, both methods demonstrated that MYCN amplification was associated mainly with advanced cancer stages, and the analysis of overall survival confirmed that patients without MYCN amplification had a cumulative survival significantly higher than patients with oncogene amplification. We also studied DDX1 and NAG amplification for all NB samples even that without MYCN amplification. No relationship between any gene co-amplification status and disease stage, age at diagnosis, or overall survival was found. Conclusions: The two methods used to calculate gene copy number for Real Time PCR assay shown to be equivalent. Real Time PCR assay shown to be more accurate to study gene amplification than conventional PCR assay. Survival analysis pointed out that DDX1 and/or NAG amplification has no additional adverse effect on prognosis.

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Robson, Samuel Charles. "Life or cell death : identifying c-Myc regulated genes in two distinct tissues." Thesis, University of Warwick, 2008. http://wrap.warwick.ac.uk/1064/.

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The c-myc oncogene is over-expressed or deregulated in many human cancers. c-myc encodes a transcription factor, the oncoprotein c-Myc (Myc), which acts as a master regulator of genes involved in such diverse cellular processes as replication and growth, loss of differentiation, invasion, and angiogenesis. Myc can also act as its own tumour suppressor by promoting cell death in the form of apoptosis. Thus, for putative cancer cells to arise, apoptosis must be blocked. Conditional MycERTAM transgenic mice allow regulated activation of Myc in distinct cell populations (skin suprabasal keratinocytes and pancreatic islet β-cells) and have highlighted contrasting behaviour between these two adult tissues in vivo: proliferation in the skin, and apoptosis in the pancreas. Given the crucial dependence on tissue location in vivo, we still do not know enough about the key divergence in Myc-regulated genes and proteins under conditions favouring opposing outcomes. To address this, we performed high-throughput transcriptome analysis using oligonucleotide microarrays. The in vivo transcriptional response to deregulated Myc was analysed for skin keratinocytes and laser-captured pancreatic islets following a time-course of MycERTAM activation. Due to the multi-factorial nature of the experimental design, novel statistical tools were developed allowing the use of linear models for inference of changes in gene-expression based on multiple experimental variables. Comparison of the transcriptional response between the two tissues identified potential signalling pathways which may promote apoptosis of β-cells or survival of skin keratinocytes: the DNA damage response pathway, and the Insulin-like growth factor 1 (Igf1) signalling pathway respectively. In addition, a marked change in expression was detected in members of the steroid hormone-regulated Kallikrein serine protease family in suprabasal keratinocytes but not for β-cells. These have been found to play an important role in regulating Igf1/Igf1-receptor ligation through proteolysis of the Igf1 binding proteins, are previously categorised markers for several human cancers, and may indicate a tissue-specific regulatory mechanism for determining ultimate Myc function in vivo.

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Herter, Eva Kristine [Verfasser], and Peter [Gutachter] Gallant. "Characterization of direct Myc target genes in Drosophila melanogaster and Investigating the interaction of Chinmo and Myc / Eva Kristine Herter ; Gutachter: Peter Gallant." Würzburg : Universität Würzburg, 2015. http://d-nb.info/1119710219/34.

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Herter, Eva Kristine Verfasser], and Peter [Gutachter] [Gallant. "Characterization of direct Myc target genes in Drosophila melanogaster and Investigating the interaction of Chinmo and Myc / Eva Kristine Herter ; Gutachter: Peter Gallant." Würzburg : Universität Würzburg, 2015. http://d-nb.info/1119710219/34.

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Al-Sallami, Dheyaa Abdul Salam. "INTERROGATION OF CHROMOSOME 8Q24.21 REGION FOR GENES CRUCIAL FOR CARCINOGENESIS USING CRISPR-CAS9 APPROACHES." OpenSIUC, 2016. https://opensiuc.lib.siu.edu/theses/1994.

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8q24.21 is a highly amplified region in cancer and associated with many epithelial cancer such as bladder, breast, colorectal and prostate cancer. The proto-oncogene c-myc is located in this region and surrounded by many lncRNAs genes such as PCAT family, CCAT family, PRNCR1. In this study, we used CRISPR-Cas9 constructs to knock out PCAT1, PRNCR1, CASC8, CASC11 and also the sequences between PCAT1-CASC11 and CASC8-CASC11in the prostate cancer cell PC3. The transfected cells with CRISPR-Cas9 targeting CASC11 gene had less proliferation ability comparing with the transfected cells with CRISPR-Cas9 targeting PCAT1, PRNCR1 or CASC8. The role of CASC11 in cancer progression and development is obscure. In our study, The CASC11 Knockout efficiency was 90% compare to the control cell. Furthermore, the study showed the importance of CASC11 in cell proliferation by significantly decreasing in the forming colonies and the growth rate comparing to the control. Also, MMP2, MMP3 and MMP9 expression levels were detected in the transfected cell by using real time PCR and the result revealed the crucial role for CASC11 in metastasis and migration. The slug and vimentin expression levels were reduced in the transfected and the double transfected clones which indicate the possible role of CASC11 in epithelial mesenchymal transition and cell motility. Taken together, our study revealed that the lncRNA CASC11 plays important roles in prostate cancer progression and metastasis by promoting the cell proliferation and migration.

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Melkoumian, Zaroui K. "Pharmacological regulation of c-myc gene expression in human breast cancer cells." Morgantown, W. Va. : [West Virginia University Libraries], 2001. http://etd.wvu.edu/templates/showETD.cfm?recnum=2218.

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Thesis (Ph. D.)--West Virginia University, 2001.
Title from document title page. Document formatted into pages; contains x, 152 p. : ill. (some col.). Vita. Includes abstract. Includes bibliographical references (p. 119-149).

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FOUREL, GENEVIEVE. "Virus de l'hepatite b et hepatocarcinome : activation des genes myc dans deux modeles animaux." Paris 6, 1992. http://www.theses.fr/1992PA066481.

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L'association entre le virus de l'hepatite b (hbv) et le cancer primitif du foie a ete solidement etablie, mais le role du virus reste mal connu. Deux hepadnavirus tres proches, les virus de l'hepatite de la marmotte (whv) et de l'ecureuil (gshv), sont utilises comme modeles pour l'etude des interactions virus/hote et de l'hepatocarcinogenese chez l'homme. Pourtant, le developpement plus rapide et plus frequent des hepatomes chez la marmotte montre que ces virus different de facon notable dans leurs proprietes oncogeniques. Nos donnees experimentales recentes permettent de proposer des bases moleculaires capables de rendre compte de ces variations: - chez la marmotte, l'integration de l'adn viral dans le genome cellulaire joue un role determinant dans le processus tumoral, en activant les oncogenes myc en cis par un mecanisme direct d'insertion d'enhancer, comme pour certains retrovirus oncogeniques. - chez l'ecureuil, par contre, l'integration du virus gshv n'est observee que tres rarement dans les hepatocarcinomes, et aucun evenement d'activation insertionnelle d'un gene myc n'a pu etre mis en evidence. En revanche, l'activation de c-myc par amplification genetique a ete observee dans environ 40% des tumeurs

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Lorenzin, Francesca [Verfasser], and Martin [Gutachter] Eilers. "Regulation of transcription by MYC - DNA binding and target genes / Francesca Lorenzin ; Gutachter: Martin Eilers." Würzburg : Universität Würzburg, 2017. http://d-nb.info/1136272682/34.

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Lopes, Rodrigo Antonio [UNESP]. "Detecção e expressão dos genes supressores p53 E c-Myc em tumores palpebrais de cães." Universidade Estadual Paulista (UNESP), 2008. http://hdl.handle.net/11449/92207.

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Os objetivos deste estudo foram detectar a presença e a expressão dos genes supressores p53 e c-Myc em tumores palpebrais, pelas técnicas de PCR, RTPCR, PCR-ELISA E RT-PCR-ELISA que até o então não foram descritas nestes tumores e nesta espécie. Foram utilizadas 10 amostras de tumores que foram fixados em formol e incluídos em parafina. O material foi obtido junto aos arquivos do Serviço de Patologia Veterinária, sendo nove amostras de tumores localizados nas pálpebras e terceira pálpebra e uma de tumor mamário para controle. Todos os tumores tiveram o seu diagnóstico firmado empregando-se a coloração de H.E e imunoistoquímica para citoqueratina AE1/AE3 e vimentina (V9), marcadores de tecido epitelial e mesenquimal, respectivamente. Os resultados indicaram que os tumores palpebrais e da terceira pálpebra aqui estudados verificou-se a presença do gene supressor p53 em 8 amostras (88,8%, n=8), e entre as amostras positivas (n=8), ele esteve expresso em 75 % delas. O gene supressor c-Myc esteve presente em 5 amostras (55,5%) e com expressão em 100% delas (n=5). Foi possível concluir que os tumores palpebrais e da terceira pálpebra de cães expressam o p-53 e c-Myc identificados pelas técnicas de PCR e RT-PCR, no entanto, as técnicas de PCR ELISA e RT-PCR ELISA foram mais importantes para avaliação da presença e expressão do oncogenes estudados, pois permitiram identificar produtos amplificados que não foram visualizados em gel de agarose.
The aims of this study were to detect the presence and the expression of p53 and c-Myc suppressor genes in eyelid tumors of dogs, by the PCR, RT-PCR, PCR-ELISA and RT-PCR-ELISA techniques, which until then they were not described in these tumors and in this specie. Ten samples of tumors were fixed in formalin and included in paraffin. The material was obtained from the archives of the Department of Veterinary Pathology, being nine samples of epithelial tumors located in the eyelids and the third eyelid, and a breast tumor which was used as a positive control of the reactions. All the samples had reached their diagnosis employing up the HE technique, and the immunohistochemistry for cytokeratin AE1/AE3 and vimentin (V9). The results showed that the eyelid and the third eyelid tumors, here studied, (88.8%, n=8) of them demonstrated the presence of the p53 gene and between the positive samples (n=8), the expression was around 75%. The c-Myc gene was present in 55.5% (n=5) of the samples, with 100% of expression (n=5). Thus, it was possible to conclude that the eyelid and the third eyelid tumors of dogs express the p53 and c-Myc genes, identified by the techniques of PCR and RT-PCR, however, the PCR ELISA and RT-PCR ELISA techniques were of extreme importance for assessing the presence and expression of these studied genes, and they allowed to identify amplified products that were not visible on the electrophoresis on the agarose gel.

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Lopes, Rodrigo Antonio. "Detecção e expressão dos genes supressores p53 E c-Myc em tumores palpebrais de cães /." Araçatuba, 2008. http://hdl.handle.net/11449/92207.

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Resumo: Os objetivos deste estudo foram detectar a presença e a expressão dos genes supressores p53 e c-Myc em tumores palpebrais, pelas técnicas de PCR, RTPCR, PCR-ELISA E RT-PCR-ELISA que até o então não foram descritas nestes tumores e nesta espécie. Foram utilizadas 10 amostras de tumores que foram fixados em formol e incluídos em parafina. O material foi obtido junto aos arquivos do Serviço de Patologia Veterinária, sendo nove amostras de tumores localizados nas pálpebras e terceira pálpebra e uma de tumor mamário para controle. Todos os tumores tiveram o seu diagnóstico firmado empregando-se a coloração de H.E e imunoistoquímica para citoqueratina AE1/AE3 e vimentina (V9), marcadores de tecido epitelial e mesenquimal, respectivamente. Os resultados indicaram que os tumores palpebrais e da terceira pálpebra aqui estudados verificou-se a presença do gene supressor p53 em 8 amostras (88,8%, n=8), e entre as amostras positivas (n=8), ele esteve expresso em 75 % delas. O gene supressor c-Myc esteve presente em 5 amostras (55,5%) e com expressão em 100% delas (n=5). Foi possível concluir que os tumores palpebrais e da terceira pálpebra de cães expressam o p-53 e c-Myc identificados pelas técnicas de PCR e RT-PCR, no entanto, as técnicas de PCR ELISA e RT-PCR ELISA foram mais importantes para avaliação da presença e expressão do oncogenes estudados, pois permitiram identificar produtos amplificados que não foram visualizados em gel de agarose.
Abstract: The aims of this study were to detect the presence and the expression of p53 and c-Myc suppressor genes in eyelid tumors of dogs, by the PCR, RT-PCR, PCR-ELISA and RT-PCR-ELISA techniques, which until then they were not described in these tumors and in this specie. Ten samples of tumors were fixed in formalin and included in paraffin. The material was obtained from the archives of the Department of Veterinary Pathology, being nine samples of epithelial tumors located in the eyelids and the third eyelid, and a breast tumor which was used as a positive control of the reactions. All the samples had reached their diagnosis employing up the HE technique, and the immunohistochemistry for cytokeratin AE1/AE3 and vimentin (V9). The results showed that the eyelid and the third eyelid tumors, here studied, (88.8%, n=8) of them demonstrated the presence of the p53 gene and between the positive samples (n=8), the expression was around 75%. The c-Myc gene was present in 55.5% (n=5) of the samples, with 100% of expression (n=5). Thus, it was possible to conclude that the eyelid and the third eyelid tumors of dogs express the p53 and c-Myc genes, identified by the techniques of PCR and RT-PCR, however, the PCR ELISA and RT-PCR ELISA techniques were of extreme importance for assessing the presence and expression of these studied genes, and they allowed to identify amplified products that were not visible on the electrophoresis on the agarose gel.
Orientador: Alexandre Lima de Andrade
Coorientador: Tereza Cristina Cardoso da Silva
Banca: Débora Aparecida Pires de Campos Zuccari
Banca: Cláudia Valéria Seullner Brandão
Mestre

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20

Cericatto, Rodrigo. "Expressão gênica do receptor estrogênico-a, bcl-2 e c-myc em fibroadenomas e no tecido mamário normal circunjacente." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2003. http://hdl.handle.net/10183/4629.

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21

Su, Yingtao. "Function and regulation of myc-family bHLHZip transcription factors during the animal and plant cell cycle /." Uppsala : Dept. of Plant Biology and Forest Genetics, Swedish University of Agricultural Sciences, 2008. http://epsilon.slu.se/200836.pdf.

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22

Polischouk, Anya. "Molecular factors relevant to the radiosensitivity of human tumours /." Stockholm, 2003. http://diss.kib.ki.se/2003/91-7349-508-5.

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23

Schmidt, Marcelo Kruel. "Expressão imunohistoquímica do C-MYC na seqüência metaplasia-displasia-adenocarcinoma no esôfago." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2005. http://hdl.handle.net/10183/4697.

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Introdução e Objetivos: O esôfago de Barrett (BE) desenvolve-se como conseqüência de uma agressão acentuada sobre a mucosa esofágica causada pelo refluxo gastresofágico crônico. É uma lesão precursora e exerce papel importante no desenvolvimento do adenocarcinoma esofágico (ACE). Inúmeras alterações genéticas estão presentes ao longo da transformação tumoral de uma célula, sendo o c-Myc um dos principais genes envolvidos na carcinogênese humana. O objetivo do presente estudo foi determinar a expressão do c-myc em pacientes com EB e com adenocarcinoma esofágico, e avaliar esta prevalência relacionada com a seqüência metaplasia-displasia-adenocarcinoma. Métodos: A expressão da proteína do C-myc foi determinada através da análise imunohistoquímica em quatro grupos diferentes: 31 pacientes com tecido normal, 43 pacientes com EB sem displasia, 11 pacientes com displasia em EB e 37 pacientes com o adenocarcinoma esofágico. O material foi obtido de peças de biópsias ou de ressecção cirúrgica de pacientes atendidos pelo Grupo de Cirurgia de Esôfago, Estômago e Intestino Delgado (GCEEID) do Hospital de Clínicas de Porto Alegre (HCPA) no período de janeiro 1998 a fevereiro 2004. Dados demográficos e endoscópicos (sexo, idade, raça, tamanho hiatal da hérnia e extensão do epitélio colunar esofágico), e as características morfológicas e histopatológicas tumorais (invasão tumoral, comprometimento linfonodal, e diferenciação histológica do tumor) foram analisados. A expressão de c-Myc foi avaliada usando o sistema de escore de imunorreatividade (Immunoreactive Scoring System – ISS). Resultados: Expressão aumentada do c-myc foi encontrada em apenas 9,7% das amostras de epitélio normal, em 37,2% dos pacientes com EB, em 45,5% dos pacientes com displasia e em 73% dos pacientes com adenocarcinoma, com diferença estatística significativa entre os grupos. Nenhuma associação foi identificada quando a expressão do c-Myc foi comparada as características morfológicas e histológicas do tumor ou aos dados endoscópicos. Entretanto, uma correlação linear da expressão do c-myc ao longo da seqüência metaplasia-displasia-adenocarcinoma foi observada. Conclusão: O estudo demonstrou um aumento significativo da expressão do c-Myc no EB, na displasia, e no adenocarcinoma em relação aos controles, bem como uma progressão linear da positividade deste gene ao longo desta seqüência. Estes resultados apontam para um papel importante deste marcador no desenvolvimento do ACE a partir do EB. Esta expressão aumentada do c-Myc em pacientes com EB poderá ajudar a identificar pacientes com risco elevado para o desenvolvimento de adenocarcinoma, contribuindo para um diagnóstico precoce desta doença.
Background & Aims: Barrett’s esophagus (BE) develops as a result of severe esophageal mucosa injury from gastroesophageal reflux. BE is premalignant lesion and plays important role in the development of esophageal adenocarcinoma. Several genetic alterations have been identified in the transforming process through a normal cell to tumor one, where the c-myc is one of the most important genes involved in the development of human tumors. The aim of the present study was to determine the expression of the c-myc in patients with BE and esophageal adenocarcinoma, and to evaluate this prevalence in relation to the metaplasia-displasia-adenocarcinoma sequence. Methods: The c-myc protein expression was determined by immunohistochemical analysis in four different groups: 31 patients with normal tissue, 43 patients with BE without dysplasia, 11 patients with dysplasia in BE and 37 patients with esophageal adenocarcinoma. The material was obtained from esophageal biopsy or dissection of esophagectomy specimens of patients from the Esophagus, Stomach and Small Bowel Surgery Group of the Hospital de Clínicas de Porto Alegre from January 1998 to February 2004. Demographic and endoscopic data (sex, age, race, hiatal hernia size and intestinal metaplasia extension), and morphologic and histopathologic tumor characteristics (deep tumor invasion, lymph node status, and tumor differentiation) were analyzed. The c-myc expression was assessed using the Imunoreactive Scoring System (IRS). Results: Overexpression of c-myc was found in only 9.6% of normal tissue specimens, 37,2% of Barrett’s esophagus, 45,5% of BE patients with displasia and 73% adenocarcinoma samples, with significant statistic difference among these groups. No association was identified when the c-myc expression was compared with morphologic and histologic tumor features or endoscopic data. However, linear correlation of c-myc overexpression along the metaplasia-displasia-adenocarcinoma sequence was observed. Conclusion: The study demonstrated a significant increase of the expression of c-myc in Barrett’s esophagus, dysplasia and adenocarcinoma in relation to the control group, as well as a linear progression of this gene expression in this sequence. These results put forward to an important role of this marker in the development of ACE from EB. The increased expression of the c-myc in patients with EB may help to identify patients with increased risk for adenocarcinoma development, contributing to an early diagnosis of this disease.

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Tesell, Jessica M. "The Notch1-c-Myc Pathway Mediates Leukemia-Initiating Cell Activity in Mouse T-ALL Models: A Dissertation." eScholarship@UMMS, 2013. http://escholarship.umassmed.edu/gsbs_diss/671.

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Although cure rates have significantly improved for children with T-cell acute lymphoblastic leukemia (T-ALL), 20-30% undergo induction failure or relapse with most succumbing to disease. Leukemia-initiating cells (L-ICs) are hypothesized to be resistant to conventional chemotherapy and radiation and are thereby responsible for disease recurrence. Using an in vivo limiting dilution assay, we previously showed that the murine T-ALL L-IC is quite rare, with only 0.003-0.05% of cells capable of initiating disease, and demonstrated that the L-IC is a subset of the leukemic DN3 thymic progenitor population. Work described in this thesis validates the L-IC assay using two transplantation methods to rule out effects of homing and/or microenvironment on T-ALL L-IC survival and maintenance. Using this assay, we demonstrate that sustained Notch1 signaling is required for T-ALL initiation in vivo and show that treatment with a Notch1 inhibitor reduces or in some cases eliminates the L-IC population. We further analyze the effects of inhibiting c-Myc, a Notch1-regulated gene, on L-IC frequency and uncover an essential role for c-Myc in L-IC survival and expansion. Suppressing c-Myc by using specific shRNAs or a c-Myc inhibitor reduces the L-IC population and interferes with leukemia initiation. Together, these findings reveal a critical role of the Notch1-c-Myc pathway in T-ALL initiation and suggest that therapeutics targeted at this pathway could be used to treat and/or prevent disease relapse in patients.

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PEREIRA, Cynthia Mara Brito Lins. "Expressão dos genes C-MYC, HER-2 e receptores hormonais como preditores de resposta à quimioterapia neoadjuvante em câncer mamário." Universidade Federal do Pará, 2010. http://repositorio.ufpa.br/jspui/handle/2011/2859.

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O câncer de mama é um dos tumores de maior incidência na mulher, e por isso, muitas pesquisas vêm sendo realizadas, desde a avaliação das características epidemiológicas, à dinâmica biocelular e o tratamento desta doença. Na avaliação de respostas ao tratamento, os fatores preditivos são marcadores que auxiliam na escolha da melhor droga a ser usada. Esta dissertação teve o objetivo de avaliar os genes de receptores de estrogênio e progesterona, HER-2 e C-MYC em tumores localmente avançados da mama, como fatores preditivos de resposta à quimioterapia neoadjuvante. Estudaram-se fragmentos da neoplasia maligna mamária de 50 pacientes com carcinoma ductal infiltrativo, com estadiamento clínico E-III e tratadas com quimioterapia neoadjuvante. Utilizaram-se as técnicas de imunohistoquímica e de hibridização in situ por fluorescência (FISH). A análise dos receptores hormonais não apresentou diferença estatisticamente significativa comparando as pacientes com resposta satisfatória à quimioterapia, das insatisfatórias; a análise do HER-2 apresentou significância apenas para as respostas satisfatórias, onde houve baixa amplificação deste gene. Em relação ao C-MYC observou-se uma diferença estatisticamente significativa comparando a alta amplificação deste gene a uma resposta insatisfatória à quimioterapia. O estudo concluiu que o gene C-MYC pode ser um importante marcador de predição nos tratamentos quimioterápicos neoadjuvantes usados em câncer mamário.
Breast cancer is a higher incidence of tumors in women, and therefore many studies have been performed since the assessment of the epidemiological characteristics, the dynamics biocelular and treatment of this disease. In evaluating responses to treatment, the risk factors are markers that help in choosing the best drug to use. This work aimed to evaluate the genes of estrogen and progesterone receptors, HER-2 and C-MYC in locally advanced breast tumors as predictors of response to neoadjuvant chemotherapy. We studied fragments of mammary malignancy in 50 patients with infiltrating ductal carcinoma, with clinical stage III and E-treated with neoadjuvant chemotherapy. We used the techniques of immunohistochemistry and fluorescence in situ hybridization (FISH). The analysis of hormone receptors showed no statistically significant difference comparing patients with satisfactory response to chemotherapy, the poor and the analysis of HER-2 showed significance only for satisfactory answers, where there was poor amplification of this gene. Regarding C-MYC was observed a statistically significant difference comparing the high amplification of this gene to a poor response to chemotherapy. The study concluded that the C-MYC gene may be an important marker for predicting the treatments used in neoadjuvant chemotherapy for breast cancer.

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Popov, Nikita. "Expression and activity of Myc network proteins during cell cycle progression and differentiation /." Sundbyberg, 2004. http://diss.kib.ki.se/2004/91-7349-856-4/.

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Lepique, Ana Paula. "Efeitos de ACTH, PMA e dcAMP na expressão de genes das famílias FOS e JUN do gene C-MYC e na atividade do fator de transcrição AP-1 em células adrenocorticais Y-1." Universidade de São Paulo, 1996. http://www.teses.usp.br/teses/disponiveis/46/46131/tde-18092008-093726/.

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As células Y-1 pertencem a uma linhagem clonal de células funcionais de córtex adrenal de camundongo, que respondem a ACTH. Em células Y-1, ACTH promove a esteroidogênese (função) e tem efeitos regulatórios complexos na transição G0→G1→S do ciclo celular. ACTH promove a transição G0→G1, mas inibe a transição G1→S. É possível que a regulação do ciclo celular por ACTH seja mediada pelo controle da expressão dos proto-oncogenes das famílias fos, jun e myc. Nosso laboratório mostrou, anteriormente, que ACTH induz a expressão dos genes fos e jun, mas inibe c-myc. O objetivo deste trabalho foi identificar pontos de controle na expressão dos genes fos, jun e myc e na atividade dos fatores de transcrição AP-1 (dímeros da proteínas Fos e Jun) por ACTH, derivados de cAMP (ativadores de PKA), PMA (ativador de PKC) e FCS (soro fetal bovino). ACTH, PMA e dcAMP aumentam a atividade de ligação de AP-1 a DNA, independentemente de síntese protéica. Ensaios de elongação de cadeia nascente de RNA (run off transcription) mostram que ACTH, PMA e FCS são fortes indutores de c-fos, c-jun e junB, enquanto dcAMP induz apenas c-fos e junB. Hibridizações Northern permitiram estimar a meia-vida dos mRNAs de c-fos e c-jun em 30 min, independentemente do tratamento com ACTH ou PMA. Diferentemente de c-fos, o mRNA de fosB é superinduzido por ActinomicinaD em células Y-1 tratadas com ACTH e PMA.
The Y-1 cells belong to a clonal lineage of functional mouse adrenocortical cells, which are responsive to ACTH. In Y-1 cells, ACTH promotes esteroidogenesis (function) and has complex effects on the G0→G1→S transition of the Y-1 cell cycle. ACTH induces the G0→G1 transition but inhibits the G1+S transition. Probably, the cell cycle regulation by ACTH is mediated by the expression control of the proto-oncogenes from the fos, jun and myc families. Our laboratory has previously shown that ACTH induces the fos and jun genes expression, but inhibits c-myc expression. The target of this work was to identify control points in the fos, jun and myc genes expression and in the AP-1 transcription factors (Fos and Jun proteins dimers) by ACTH, cAMP derivatives (PKA activators), PMA (PKC activator) and FCS (Fetal Calf Serum). ACTH, PMA and dcAMP raise the AP-1 DNA binding activity, independently of protein synthesis. Run off transcription assays show that ACTH, PMA and FCS are strong c-fos, c-jun and junB inducers, while dcAMP induces only c-fos and junB. Northern hybridisations allowed us to estimate the half life of the fos and jun mRNAs in about 30 min, independently of ACTH or PMA treatment. Differently of c-fos, fosB mRNA is superinduced by ActinomicinD treatment in Y-1 cells treated with ACTH or PMA.

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Marinho, Filho José Delano Barreto. "Participação das vias atm/atr e c-myc/gsh nos efeitos antitumorais da cordiaquinona J induzidos pelo estresse oxidativo." reponame:Repositório Institucional da UFC, 2012. http://www.repositorio.ufc.br/handle/riufc/5557.

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MARINHO FILHO, José Delano Barreto. Participação das vias ATM/ATR e C-MYC/GSH nos efeitos antitumorais da cordiaquinona J induzidos pelo estresse exidativo. 2012. 173 f. Tese (Doutorado em Farmacologia) - Universidade Federal do Ceará. Faculdade de Medicina, Fortaleza, 2012.
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Cordiaquinones are meroterpenoid naphtoquinones from plants belonging to the genus Cordia with several described biological activities, including antifungal, larvicidal and cytotoxic effects. The aim of this study was to evaluate the anticancer potential of a cordiaquinone isolated from the roots of Cordia leucocephala plant. The present study evaluated the cytotoxic potential of cordiaquinone J in several tumor and normal cell lines by MTT assay and its possible mechanism of action. The study of the mechanism of action of cordiaquinones L and M, in human leukemia cells (HL-60) showed induction of cell death by apoptosis, and these effects were related to the induction of oxidative stress. Then the study was continued only with the cordiaquinone J. The cordiaquinone J showed IC50 values ranging from 4.6 to 6.8μM in leukemia cells and 33.6 to 37 μM in normal cells, after 24 hours of incubation. In HL-60 cells was observed apoptosis induction preferentially by extrinsic pathway. The induction of DNA damage by cordiaquinone J observed by comet assay was associated with activation of protein kinases of ATM/ATR pathway. The DNA damage, as well as activation of protein kinases via the ATM / ATR was observed in HL-60 cells but not in normal cells. These effects in HL-60 cells may be related to the depletion of protein expression of glutathione and c-myc observed. The anticancer potential was confirmed in vivo through inhibition of sarcoma-180 tumor by 72.5% after the treatment with 50 mg/kg of cordiaquinone J. The pre-treatment of cells or animals with N-acetyl-L-cysteine abolished most of the in vitro and in vivo observed effects, reinforcing the role of reactive oxygen species generation in cordiaquinone J activity.
As cordiaquinonas são naftoquinonas meroterpenóides isolados de plantas pertencentes ao gênero Cordia com várias atividades biológicas descritas, incluindo atividades antifúngica, larvicida e citotóxica. O objetivo deste trabalho foi avaliar o potencial anticâncer de uma cordiaquinona isolada das raízes da planta Cordia leucocephala. O presente estudo avaliou o potencial citotóxico da cordiaquinona J em várias linhagens de células tumorais e normais pelo teste do MTT e seu possível mecanismo de ação. A cordiaquinona J mostrou valores de CI50 variando de 4,6 a 6,8 μM em células leucêmicas e 33,6 a 37 μM em células normais, após 24 horas de incubação. Nas células HL-60 foi observado indução de apoptose preferencialmente pela via extrínseca. A indução do dano ao DNA observado pelo tratamento com a cordiaquinona J através do ensaio do cometa foi associado com a ativação de proteínas quinases da via ATM/ATR. O dano ao DNA, assim como a ativação das proteínas quinases da via ATM/ATR foi visualizado em células HL-60, mas não em células normais. Estes efeitos em HL-60 podem estar relacionados com a depleção da expressão proteica de glutationa e de c-myc observados. O potencial anticâncer foi confirmado in vivo através da inibição do tumor sarcoma-180 em 72,5% após o tratamento com 50 mg/kg de cordiaquinona J. O pré-tratamento tanto das células quanto dos animais com N-acetil-L-cisteina inibiu todos os efeitos observados in vitro e in vivo reforçando o papel da geração das espécies reativas de oxigênio na atividade antitumoral da cordiaquinona J.

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MENDES, Juliana Melo Macedo. "SUBEXPRESSÃO DOS GENES RB, P53 E MYC MEDIADA POR HPV E SUPEREXPRESSÃO DE GENES ENVOLVIDOS NO PROCESSO INFLAMATÓRIO COX2, PGE2 E EGFR COM IMPORTÂNCIA TERAPÊUTICA EM CÂNCER PENIANO." Universidade Federal do Maranhão, 2017. https://tedebc.ufma.br/jspui/handle/tede/tede/2018.

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FAPEMA.
Penile cancer (PeCa) is a rare neoplasm with higher incidence in regions with low socioeconomic indexes. In Brazil, most of the men afflicted by this disease reside in the North and Northeast. Among the main risk factors are lack of hygiene, phimosis, high-risk human papillomavirus (HPV) infection and chronic inflammation. Although the role of inflammation and HPV infection is known in some cancers, the relationship between these two factors and the disruption of genes involved in the CaPe genesis is not yet well established. Thus, our main goal was to determine the expression of genes involved in the process of chronic inflammation and in the carcinogenesis mediated by HPV infection and the role of the deregulation of these genes in the establishment and progression of penile tumor. For this purpose, fresh and formalin-fixed paraffin-embedded (FFPE) tissues from 55 patients with penile cancer were evaluated. HPV detection and genotyping were carried out by nested PCR and direct sequencing in all samples. A subgroup (N = 37) was evaluated by qRT-PCR to determine COX-2, EGFR, MYC, RB and P53 gene expression. For this, sections of FFPE tissues containing more than 70% tumor cells were analyzed. Protein expression of these genes and PGE2 were determined by immunohistochemistry in the same tumor tissues. An analysis of the association between the clinical-histopathological parameters, presence of HPV, and gene and protein expression was performed. All tumors were classified as epidermoid squamous cell carcinoma. HPV DNA was detected in 80% of tumors, of which 95% had at least one high-risk subtype, and HPV16 was the most frequent subtype (63%). Among the HPV negative samples in the tumor tissue, 14% were positive in the tissue adjacent to the tumor, so that 94% of the patients, in total, were positive for the presence of HPV DNA.. Overexpression was identified in all genes involved in the inflammatory process. EGFR showed overexpression in 84% of the samples, while COX2 and PGE were overexpressed in 40% of the tumors, each. There was an associationbetween the levels of EGFR and COX2 expression, and between COX2 and PGE2. On the other hand, the genes related to HPV infection, MYC, RB and P53, were underexpressed in 97%, 85% and 81% of the samples, respectively. The gene expressions did not show any association with clinical-histopathological variables. This study describes the repression of RB and P53 activity in HPV + tumors, suggesting that there is a mechanism of control of these genes, possibly mediated by the virus. The high detection of HPV infection shows the importance of the immunization of boys in the prevention of penile cancer. Our data emphasize the need to expand the vaccine coverage to cover types of HPV present in penile cancer. The overexpression of EGFR / COX2 / PGE2, and the association found between them, support the possibility of therapeutic use of anti-EGFR and anti-COX drugs in penile tumors.
Câncer peniano (CaPe) é uma neoplasia rara com maior incidência em regiões com baixos índices socioeconômicos. No Brasil, a maior parte dos homens acometidos por essa doença residem nas regiões Norte e Nordeste. Entre os principais fatores de risco estão a falta de higiene, fimose, infecção por papilomavírus humano (HPV) de alto risco e inflamação crônica. Embora o papel d a inflamação e da infecção por HPV sejam conhecidas em alguns cânceres, ainda não é bem estabelecida a relação entre esses dois fatores e a disrupção de genes envolvidos na gênese de CaPe. Assim, neste estudo foi avaliada a expressão de genes envolvidos no processo de inflamação crônica e na infecção pelo HPV e o papel da desregulação desses genes no estabelecimento e progressão de tumor peniano. Para isto, foram avaliadas amostras teciduais frescas e fixadas em formalina embebidas em parafina (FFPE) de 55 pacientes com câncer de pênis. Foram realizadas detecção e genotipagem de HPV por nested PCR e sequenciamento direto em todas as amostras Um subgrupo amostral (N=37) foi avaliado por qRT-PCR para determinação da expressão dos genes COX-2, EGFR, MYC, RB e P53. Para isso, foram usadas secões de tecidos de FFPE contendo mais de 70% de células tumorais. A expressão proteica desses genes e de PGE2 foi determinada por imunohistoquímica em 42 amostras. Foi feita análise de associação entre os parâmetros clínico-histopatológicos, presença de HPV e expressão gênica e proteica. Todos os tumores foram classificados como carcinoma epidermóide de células escamosas. DNA de HPV foi detectado em 80% dos tumores (N=55), dos quais 95% apresentaram, pelo menos, um subtipo de alto risco, e destes, HPV16 foi o subtipo mais frequente (63%). Dentre as amostras negativas para HPV no tecido tumoral, 14% foram positivas no tecido adjacente ao tumor, de modo que 94% dos pacientes, no total, foram positivos para presença de DNA de HPV. Nas amostras nas quais foi feita análise de expressão gênica (N=37), detectou-se 94,4% de infecção, sendo 94% dos infectados possuem, pelo menos um, tipo de alto risco. Foi Identificada superexpressão em todos os genes envolvidos no processo inflamatório. EGFR mostrou superexpressão em 84% das amostras, enquanto COX2 e PGE mostraram-se, cada um, superexpressos em 40% dos tumores. Houve associação entre níveis de expressão de EGFR e COX2, e entre COX2 e PGE2. Por outro lado, os genes relacionados à infecção por HPV, MYC, RB e P53, mostraram-se subexpressos em 97%, 85% e 81% das amostras, respectivamente. A expressão dos genes estudados não mostrou associação com as variáveis clínico-histopatológicas. Este estudo descreve a repressão da atividade de RB e P53 em tumores HPV+, sugerindo que há um mecanismo de controle desses genes em câncer peniano, possivelmente mediado pelo vírus. A alta detecção de infecção por HPV mostra a importância da imunização de meninos na prevenção de câncer peniano, e ressalta-se a necessidade de ampliação da cobertura vacinal de modo a abranger tipos de vírus presentes em câncer peniano. A superexpressão de EGFR/COX2/PGE2, e a associação encontrada entre eles, sustenta a possibilidade de uso terapêutico de drogas anti-EGFR e anti-COX em tumores penianos.

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Kinnon, Sharron. "Functional and molecular analysis of the myc co-operating genes bmi-1 and pim-1 in feline fibroblasts and lymphoma." Thesis, Glasgow Caledonian University, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.313172.

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SOUDON, JACQUES. "Analyse de l'expression des genes c-myc et p53 dans une lignee lymphoblastique t porteuse d'une translocation t(8;14) (q24;q11)." Nantes, 1990. http://www.theses.fr/1990NANT076M.

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Barboza, Regina Felippe. "Estudo dos genes NDRG1, Par-4, osteonectina e pontina, em tecido mamário hiperplásico através de técnica de imunohistoquímica." Universidade de São Paulo, 2011. http://www.teses.usp.br/teses/disponiveis/5/5155/tde-04082011-133848/.

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INTRODUÇÃO: O câncer de mama é uma das mais importantes causas de mortalidade feminina no mundo. Acredita-se que as lesões proliferativas do parênquima mamário sejam marcadoras de risco para câncer ou precursoras do carcinoma mamário. Apesar da intensa pesquisa na área do câncer de mama, os eventos moleculares precoces associados à evolução e progressão do câncer mamário ainda são pouco conhecidos. OBJETIVOS: Com a expectativa de melhor compreender os eventos iniciais da carcinogênese mamária examinamos um conjunto de oitenta e quarto lesões proliferativas mamárias quanto à expressão dos genes N-myc down regulated gene (NDRG1), Prostate Apoptosis Response-4 (PAR-4), Osteonectina e Pontina. A expressão destes genes foi documentada, por trabalhos prévios em nosso laboratório ou por estudos de outros autores, como tendo impacto na evolução do câncer de mama. MÉTODOS: Construímos um TMA com lesões proliferativas da mama e testamos este TMA por método imunohistoquímico para Ndrg1, Par-4, Osteonectina e Pontina, bem como para o receptor de estrógeno e citoqueratinas de alto e baixo peso molecular, com o objetivo de caracterizar as lesões presentes no TMA. A avaliação imunohistoquímica foi feita de forma quantitativa, com o aplicativo e sistema de análise quantitativa para TMA ACIS III, da Dako. RESULTADOS: Após excluirmos amostras não informativas, contamos com 68 amostras de lesões proliferativas mamárias para análise. Nestas, observamos uma notável positividade de NDRG1, em lesões com morfologia apócrina. Observamos ainda alta expressão de NDRG1 em lesões proliferativas mamárias, quando comparadas aos outros tipos de lesões presentes no TMA. Pontina exibiu os mais altos valores de expressão nos casos de lesões proliferativas mamárias, com valor de p estatisticamente significativo. A expressão de PAR-4 foi predominantemente nuclear nas lesões mamárias analisadas no TMA. Osteonectina teve expressão diferenciada no epitélio de lesões hiperplásicas da mama, papilomas e papilomas de pequenos ductos, quando comparada às outras lesões presentes no TMA. CONCLUSÕES: Nossos resultados sugerem uma possível associação entre a expressão de NDRG1 e diferenciação apócrina no parênquima mamário. Esta observação está de acordo com os dados publicados a respeito da superexpressão de NDRG1 e a assinatura apócrina molecular de alguns carcinomas de mama. Também demonstramos superexpressão de NDRG1 em condições hiperproliferativas do parênquima mamário, não associadas à diferenciação apócrina. Até o momento não há informações na literatura que possam explicar a translocação nuclear de Par-4 em lesões benignas da mama observada em nosso estudo. Nossos achados fornecem pela primeira vez evidências de que PAR-4 é ativado em lesões proliferativas da mama, indicando a necessidade de estudos futuros dirigidos à investigação das funções de PAR-4 em tecido mamário não neoplásico. O presente trabalho também indicou uma possível ação coordenada entre a expressão de Osteonectina e NDRG1, pelo menos em lesões apócrinas mamárias. A expressão estromal de Osteonectina pareceu ser menos frequente em lesões mamárias com arquitetura papilífera, quando comparadas a lesões mamárias com tendência a recapitular a arquitetura lobular
INTRODUCTION: Breast cancer is a leading cause of death among women all over the Word. Proliferative lesions of the breast are believed to be precursors of or markers of increased risk for breast carcinoma. Although the active research in the field of breast cancer, the early molecular events associated with cancer evolution and progression are still poorly understood. OBJECTIVES: In order to better understand the early events in the breast carcinogenesis, we examined a set of eighty-four proliferative lesions of the breast for the expression of N-myc down regulated gene (NDRG1), Prostate Apoptosis Response-4 (PAR-4), Osteonectin and Pontin, which expression was previously shown by our laboratory to have impact in breast cancer prognosis. METHODS: A tissue microarray were constructed and immunohistochemically tested for Ndrg1, Par-4, Osteonectin and Pontin together with estrogen receptor, low and high weight cytokeratins, aiming to properly characterize the lesions sorted in the tissue microarray. Immunohistochemistry assessment was made quantitative, with the ACIS III Dako quantitative analysis system and TMA application software. RESULTS: After excluding non informative cores, cores with fibroadipose tissue or mammary parenchyma with normal appearing breast epithelium, we ended up with a TMA with 68 breast lesions. Of those, we observed a noticeable positivity of Ndrg1 for lesions with apocrine morphology. Additionally, all cases of florid epithelial hyperplasia showed variable high immunoexpression levels of protein, when compared to the other sorted out lesions in the TMA. Pontin expression level was highest among the breast hyperplasia cases, with statistically significant p value. PAR-4 protein expression was found to be predominantly localized in the nucleous in the non-malignant breast lesions analyzed. Osteonectin exhibited differentiated expression values in the epithelium of hyperplastic breast lesions, papillomas and multiple papillomas when compared to the other types of breast lesions assorted in the TMA. CONCLUSIONS: Our results suggest a possible association of NDRG1 with apocrine differentiation in the breast parenchyma. This observation are consonant with the publish data about the NDRG1 overexpression and the apocrine signature of some mammary cancers. Additionally, we demonstrated that NDRG1 is also overexpressed in some hyperproliferative breast conditions unassociated with apocrine morphology. At present, there is no data available in the in the literature to explain the nuclear translocation of Par-4 in benign breast lesions as observed in our study. However, our findings provide for the first time evidence that PAR-4 is activated in proliferative lesions of the breast indicating that further clinical and experimental studies aiming to investigate PAR-4 function in non neoplastic breast tissue are warranted. Our study also indicated a possible coordinated expression between Osteonectin and NDRG1, at least in apocrine lesions of the breast. Stromal Osteonectin expression seemed to be less intense in breast lesions with papillary architecture, when compared to breast lesions with tendency to recapitulate breast lobular architecture

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Corral, Marisol. "Caracterisation de genes cellulaires dont l'expression est associee a la cancerisation hepatique." Paris 6, 1987. http://www.theses.fr/1987PA066124.

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Hirth, Carlos Gustavo. "Valor prognóstico de marcadores de diferenciação neuroendócrina e de células-tronco em pacientes submetidos a prostatectomia radical por câncer de próstata localizado." reponame:Repositório Institucional da UFC, 2016. http://www.repositorio.ufc.br/handle/riufc/21568.

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HIRTH, C.G. Valor prognóstico de marcadores de diferenciação neuroendócrina e de células-tronco em pacientes submetidos a prostatectomia radical por câncer de próstata localizado. 2016. 134 f. Dissertação (Mestrado em Patologia) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2016.
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This study aimed to evaluate the new immunohistochemical markers related to neuroendocrine differentiation induction and stem cells with prognostic factors and biochemical recurrence in patients submitted to radical prostatectomy. Therefore, patients operated at the Hospital Walter Cantídio, Federal University of Ceará, in the period of 2008-2013, underwent clinical and outpatient follow-up, between the years 2008-2016. Biochemical recurrence was evaluated and was correlated with pathological characteristics and immunohistochemical reactions. Chromogranin (neuroendocrine differentiation), Aurora Kinase A (AURKA), N-MYC, C-MYC and CD44s were performad in paraffined material. From 74 patients underwent surgery was obtained the followup of 69, in a median period of 41 (2-89) months. Neoplastic neuroendocrine differentiation was associated with seminal vesicles infiltration (p = 0.032) and stage (p = 0.030). C-MYC was associated with Gleason score (p = 0.001) and seminal vesicles infiltration (p = 0.014). AURKA was expressed in rare cases. N-MYC protein was negative in all patients. CD44s was associated with lower preoperative PSA levels and lower Gleason scores. Biochemical recurrence was observed in 27.0% of patients. Recurrence was associated with serum preoperative PSA, Gleason score, seminal vesicle invasion and staging at least in one form of analysis. There was no significant association between recurrence and neuroendocrine differentiation, C-MYC and CD44s expression. Therefore, immunohistochemical detection of neuroendocrine differentiation, expression of C-MYC and loss of CD44s were related to more aggressive carcinomas (PSA, Gleason, seminal vesical invasion and/or stage), but no association with biochemical recurrence. Classic prognostic factors were affirmed like biochemical recurrence predictores.
Este estudo objetivou avaliar novos marcadores imuno-histoquímicos relacionados à indução da diferenciação neuroendócrina e células-tronco com fatores de prognóstico e recorrência bioquímica, em pacientes submetidos à prostatectomia radical. Para tanto, pacientes operados no Hospital Walter Cantídio, Universidade Federal do Ceará, no período de 2008 a 2013, foram submetidos a acompanhamento clínico-ambulatorial, entre os anos de 2008 a 2016. Avaliou-se a proporção daqueles que apresentaram recorrência bioquímica, bem como as características clínico-patológicas e a marcação em reações de imuno-histoquímica para cromogranina (diferenciação neuroendócrina), Aurora quinase A (AURKA), N-MYC, C-MYC e CD44s, em material parafinado. De 74 pacientes submetidos à cirurgia, obteve-se acompanhamento de 69, com tempo de seguimento de 41 (2-89) meses; diferenciação neuroendócrina na neoplasia se associou com infiltração de vesículas seminais (p=0,032) e estadiamento (p=0,030). C-MYC associou-se com escore de Gleason (p=0,001) e infiltração de vesículas seminais (p=0,014). AURKA expressou-se em raros casos. N-MYC foi negativo em todos os pacientes. CD44s se associou com menores níveis de PSA pré-operatório e menores escores de Gleason. Observou-se recorrência bioquímica em 27,0% dos pacientes. Recorrência se associou, em pelo menos uma das formas de análise, com níveis séricos de PSA pré-operatório, escore de Gleason, invasão de vesículas seminais e estadiamento. Não houve associação significativa entre recorrência e diferenciação neuroendócrina, C-MYC e CD44s. Dessa forma, nesse estudo, a detecção imuno-histoquímica da diferenciação neuroendócrina; a expressão de C-MYC e a perda da expressão de CD44s relacionaram-se com carcinomas mais agressivos (PSA, Gleason, infiltração de vesícula seminal e/ou estadiamento), porém sem associação com a recorrência bioquímica; bem como confirma a importância de fatores prognósticos considerados como clássicos em série regional de pacientes com câncer de próstata.

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Zubow, Kristina. "Charakterisierung von Varianten des anti-c-myc-Antikörpers 9E10 mit Keimbahngen-orientierten Aminosäureaustauschen." Doctoral thesis, Humboldt-Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät I, 2007. http://dx.doi.org/10.18452/15604.

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In dieser Arbeit wurde die Affinitätsreifung des murinen anti-c-myc-Peptid-Antikörpers 9E10 analysiert. Hierfür wurden Fab-Fragmente mit Keimbahnrückmutationen gentechnisch hergestellt und in ihrem Bindungsverhalten zum humanen c-myc-Peptid charakterisiert. Das von 9E10 erkannte Epitop besitzt die Aminosäuresequenz EQKLISEEDLLRKR mit den darin sehr selektiv erkannten Schlüsselpositionen LISEXXL.Der 3300-fache Affinitätsgewinn während der 9E10-Reifung kommt sowohl durch eine Zunahme der Assoziations- als auch durch eine Abnahme der Dissoziationsgeschwindigkeit des Komplexes zustande. Der Affinitätsgewinn resultiert weniger aus zusätzlichen Kontakten des Antikörpers zum Peptid, sondern vor allem aus der Beeinflussung der Konformation und/oder der Flexibilität der an der Bindung beteiligten CDRs. Die außergewöhnlich lange CDR-H3 liefert einen wesentlichen Beitrag zur Affinitätsreifung. Die variable leichte Domäne dient dabei mit der langen CDR-L1 und -L3 als eine Bindungsplattform für die flexible CDR-H3. Änderungen in der Spezifität von 9E10 sind vorrangig auf die Reifung der variablen schweren Domäne zurückzuführen. Dabei ist die selektive Erkennung der Schlüsselpositionen im Peptid im Anfangsstadium der Affinitätsreifung von 9E10 stark ausgeprägt.
In this work the affinity maturation of the murine anti c-myc-peptide antibody 9E10 was analysed. Therefore Fab fragments with reversed mutations directed towards germline genes were genetically produced and characterised for their binding to the human c-myc peptide. The epitope recognized by 9E10 consists of the amino acid sequence EQKLISEEDLLRKR of which the key positions LISEXXL are very selectively recognized. The maturation of 9E10 leads to a 3300-fold higher affinity, which is achieved by a faster association as well as by a slower dissociation of the complex. For the gain in affinity formation of additional contacts to the peptide is less important than conformational and/or flexibility changes of the CDRs which are involved in binding. The exceptionally long CDR-H3 contributes essentially to the affinity maturation. The variable light domain serves thereby with its long CDR-L1 and -L3 as a binding platform for the flexible CDR-H3. Changes in specificity of 9E10 are primarily due to maturation of the variable heavy domain. Selective recognition of the key positions in the peptide is already highly pronounced in the initial stage of affinity maturation of 9E10.

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Berggren, Bremdal Karin. "Evolution of MHC Genes and MHC Gene Expression." Doctoral thesis, Uppsala universitet, Evolutionsbiologi, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-122011.

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Polymorphism in coding regions and regions controlling gene expression is the major determinant of adaptive differences in natural populations. Genes of the major histocompatibility complex (MHC) possess a high level of genetic variation, which is maintained by selection over long coalescence times. MHC genes encode antigen-presenting molecules in the adaptive immune system, which protects the host from infectious diseases. However, MHC molecules may also present self-peptides and for most autoimmune diseases there is a genetic factor associated with the MHC. MHC genes have been used to learn about the interplay of selection and historical population events. In domestic dogs and their progenitor, the wolf, I explored factors associated with domestication and breed formation and their influence not only on MHC coding regions but also on the haplotypic structure of the class II region. Polymorphism and strong selection was demonstrated in the proximal promoters of MHC genes in dogs and wolves. Hence, genetic variation associated with MHC gene expression may have at least equal importance for a well functioning immune system. Associations between promoter sequences and particular coding alleles suggested allele-specific expression patterns. SNP haplotypes of the MHC class II region revealed ancestral as well as convergent haplotypes, in which combinations of alleles are kept by selection. Interestingly, weaker allelic associations were found between different genes and between coding regions and promoters in dogs compared to wolves. Potentially, this could cause insufficient defense against infections and predispose dogs to autoimmune diseases. For example, I identified a site in the promoter region that showed a consistent difference between haplotypes conferring susceptibility and protection to diabetes in dogs, which should be investigated further. Furthermore, I investigated how selection and demographic changes associated with glacial and inter-glacial periods have affected MHC variation in European hedgehogs and extended the prevailing knowledge concerning their population history.

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Rico, Vargas Sergio Arturo. "Regulation and dysregulation of B lymphopoiesis in mouse bone marrow: in vivo role of macrophage activation (pristane-treatment and malaria-infection), c-myc, c-kit, and immunoglobulin genes." Thesis, McGill University, 1993. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=41340.

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To examine factors influencing normal and disordered genesis of the B lymphocyte lineage in mouse bone marrow, precursor B cell dynamics have been analysed in conditions predisposing to B cell neoplasias and deficiencies. Double immunofluorescence labeling and stathmokinetic techniques have been used to quantitate the population size and mitotic activity of pro-B cells before $ mu$ chain expression, pre-B cells expressing cytoplasmic $ mu$ chains, and B lymphocytes expressing surface IgM. Two conditions associated with prolonged macrophage activation and B cell neoplasia, pristane oil-treatment and malaria infection, have been found to stimulate the proliferation of pro-B cells but to produce increased cell loss at later cell differentiation stages, suggesting that the stimulation of cells undergoing Ig gene rearrangement may predispose to genetic errors leading to cell death or oncogenesis. During a pretumorous period in E$ mu$-myc transgenic mice a marked stimulation of pro-B and pre-B cells is associated with much subsequent cell loss, suggesting that additional mutations are needed to promote B cell survival and the emergence of a tumorigenic clone. Many early precursor B cells express c-kit but their development is not blocked by a neutralizing anti-c-kit antibody in vivo, suggesting that the role of c-kit can be replaced by alternative signalling systems. The introduction of Ig transgenes in scid mutant mice, unable to rearrange endogenous Ig genes, shows that the survival of successive stages in precursor B cell development depends upon the successful progressive expression of the IgM molecule. The work demonstrates that processes influencing both cell proliferation and loss can be critical in regulating the genesis of both normal and potentially neoplastic B cells in the bone marrow.

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Bonamy, Clément. "Signalisation cellulaire et peptides antimicrobiens : rôle de la voie EGFR dans la régulation de la B-défensine 1 humaine." Thesis, Sorbonne Paris Cité, 2018. https://theses.md.univ-paris-diderot.fr/BONAMY_Clement_2_complete_20181005.pdf.

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La ß-défensine 1 humaine (HBD1) est un peptide antimicrobien codé par le gène DEFB1 et exprimé de manière constitutive par les cellules épithéliales aux interfaces entre le milieu extérieur et l’organisme. De par ses activités antimicrobiennes et facteurs suppresseurs de tumeur, HBD1 joue un rôle central dans le maintien de l’homéostasie et la protection de l’épithélium dans le côlon. Cependant, peu de travaux ont porté sur l’étude de sa régulation génétique. Contrairement aux autres défensines, l’expression d’HBD1 est altérée au cours de l’oncogenèse dans le côlon, comme observé dans d’autres types de cancers. Nous avons montré que la transcription du gène DEFB1 est régulée par l’axe EGFR/MEK/ERK/MYC et que MYC en complexe avec son partenaire MIZ1 réprime la transcription de DEFB1. Ces travaux montrent que la transcription de ce gène est dépendante de voies de signalisation oncogéniques et permettent de décoder le rôle de la voie de signalisation EGFR/MEK/ERK/MYC dans la répression de l’expression d’HBD1 pouvant expliquer la diminution de l’expression d’HBD1 observée dans les cancers colorectaux. Ils permettent également d’ouvrir des pistes de réflexions sur l’intérêt thérapeutique de la régulation d’HBD1 dans le traitement des cancers
The human ß-defensin-1 (HBD1) is an antimicrobial peptide constitutively expressed by epithelial cells at mucosal surfaces. In addition to its microbicidal properties, the loss of HBD1 expression in several cancers suggests that it may also have an anti-tumor activity. Here, we investigated the link between HBD1 expression and cancer signaling pathways in human colon cancer and primary cells. Using available datasets from patient cohorts, we found that HBD1 expression is decreased in colorectal cancer. We demonstrated that inhibiting the Epidermal Growth Factor Receptor (EGFR) increased HBD1 transcription, whereas activating EGFR repressed HBD1 transcription, through the MEK1/2-ERK1/2 pathway that ultimately regulates MYC. We finally present evidence supporting the direct role of MYC, together with the MIZ1 coregulator, in HBD1 regulation. Our work uncovers the role and deciphers the function of the EGFR-ERK-MYC axis as a repressor of HBD1 transcription and contributes to the understanding of HBD1 suppression observed in colorectal cancer. This work opens also the reflection about the therapeutic interest of HBD1 regulation in cancer treatment

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Alves, Carlos Eduardo Fonseca. "Avaliação epigenética dos genes NKX3.1 E CDH1 e expressão do C-MYC, NKX3.1 e E-Caderina por imuno-histoquímica em microarranjo de tecido (TMA) de lesões pré-neoplásicas e neoplásicas na próstata de cães." Botucatu, 2016. http://hdl.handle.net/11449/143108.

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Orientador: Renée Laufer Amorim
Resumo: A próstata canina é um bom modelo para estudos comparados entre o cão e o homem, uma vez que essas duas espécies desenvolvem espontaneamente carcinoma de próstata (CP). Para melhor caracterização do CP canino, a presente pesquisa foi dividia em quatro capítulos que avaliam diferentes aspectos dos CPs em cães. A atrofia inflamatória proliferativa (PIA) é uma lesão pré-neoplásica descritas em humanos e pouco estuda em cães. Nós caracterizamos essa lesão em cães e identificamos uma forte relação entre a localização topográfica da PIA com os CPs. Além disso, foi identificada a perda de expressão gênica e proteica de PTEN e AR na PIA. Esses fatores associados corroboram com o potencial pré-neoplásico desta lesão em cães. Um achado interessante foi a alta expressão de P63 na PIA e em um grupo de CP caninos. Para melhor caracterizar este grupo, foi avaliada a expressão imuno-histoquímica de diferentes citoqueratinas e outras proteínas relacionadas ao desenvolvimento do CP em humanos. Os carcinomas que apresentam expressão de P63 apresentaram padrões morfológicos com escore de Gleason alto e um fenótipo mais agressivo quando comparado à tumores que não apresentação expressão de P63. Posteriormente, a expressão gênica e proteica de E-caderina, NKX3.1 e C-MYC foi avaliada em CP como marcadores nas diferentes lesões. Além disso, nós avaliamos a metilação como mecanismo regulatórios dos genes CDH1 e NKX3.1. Foi possível identificar a perda de E-caderina e NKX3.1 nos tumores, comparado à ... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: The canine prostate gland can be used as a model to human prostatic disease since dogs and men are the only species that spontaneously develop prostate carcinoma (PC). To better characterize the canine PC, this research was divided into four chapters that evaluated different aspects of the PC in dogs. The proliferative inflammatory atrophy (PIA) is a pre-neoplastic lesion described in humans and few studies in dogs describe it as a preneoplastic lesion. This study characterized PIA in dogs and identified a strong relationship between the PIA topography with PC. In addition, we identified the loss of PTEN and AR expression in PIA. These findings demonstrated the potential of PIA as a preneoplastic lesion in dogs. An interesting finding in this research was the high expression of P63 in PIA and a group of PC. This study found a group of PC showing P63 positive expression in neoplastic epithelial cells. Thus, these tumors were selected to better characterize them using immunohistochemistry. These tumors had an aggressive phenotype and presented high expression of AKT and C-MYC and loss of NKX3.1. Further, we selected a usual group of PC and evaluate the expression of E-cadherin, NKX3.1 and C-MYC. In addition, we evaluated the methylation as a regulatory mechanism of CDH1 and NKX3.1 genes. We have identified loss of E-cadherin and NKX3.1 in PC compared to normal prostate and C-MYC overexpression. The expression of E-cadherin was related to overall survival and Gleason score. The ... (Complete abstract click electronic access below)
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40

Schuhmacher, Marino. "Myc-Funktion im Zellwachstum und Identifikation von neuen Myc-regulierten Genen in B-Zellen." Diss., lmu, 2001. http://nbn-resolving.de/urn:nbn:de:bvb:19-1361.

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41

De, Juan Sanjuan Cristina. "Identification of major histocompatibility complex (MHC) class I chain-related (MIC) and HFE genes in cattle." Thesis, University of Bristol, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.434741.

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42

Lear, Justin Navada. "The characterization of a putative Myc-induced gene." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape2/PQDD_0017/MQ54122.pdf.

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43

Straaten, J. P. van. "Studies on the human c-myc gene product." Thesis, University of Cambridge, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.377708.

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44

Jopling, Catherine L. "Internal ribosome entry in the myc gene family." Thesis, University of Leicester, 2001. http://hdl.handle.net/2381/29662.

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The proto-oncogene c-myc is encoded by a transcript in which the 5' UTR contains a potent internal ribosome entry segment (IRES). The N-myc gene shows considerable homology to c-myc and also possesses a 5' UTR that is long and structured. Thus, the potential for internal ribosome entry within this UTR was examined. N-myc was found to contain an IRES that was of comparable activity to that of c-myc in non-neuronal cells, but was specifically activated relative to the c-myc IRES in neuronal cells in which the N-myc transcription is expressed. Furthermore, the activity of the N-myc IRES was specifically inhibited during neuronal differentiation, when N-myc expression is reduced. The trans-acting factor requirements for N-myc IRES function were examined and a candidate protein was found, although not characterised. An IRES was also identified in the 5' UTR of the third well-studied member of the myc gene family, L-myc. An alternative form of the UTR exists in which an intron is retained, but it was not possible to draw any definite conclusions on the IRES activity of this UTR. Translation of both c- and N-myc mRNAs can occur by both cap-dependent and IRES-dependent mechanisms, so the existence of IRESs within these transcripts was intriguing. c-Myc protein levels were analysed during apoptosis and were maintained, despite the apoptotic inhibition of protein synthesis and the short half-life of c-Myc. The activity of the c-myc IRES was maintained during apoptosis and was responsible for this effect. The c-myc IRES was also shown to lie downstream of the p38 mitogen-activated protein kinase signalling pathway.

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Vogel, Teresa Maria [Verfasser]. "Die Expression von MHC Klasse I verwandten Genen (MIC) bei Psoriasis vulgaris / Teresa Maria Vogel." Kiel : Universitätsbibliothek Kiel, 2018. http://d-nb.info/1156264642/34.

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46

Forrest, D. "A study of the myc gene in feline leukaemias." Thesis, University of Glasgow, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.377160.

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47

Gallagher, Ronald Charles John. "Functional analysis of a naturally occurring mutant myc gene." Thesis, University of Glasgow, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.297056.

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48

Gherardi, Samuele <1981&gt. "Myc-mediated control of gene transcription in cancer cells." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2010. http://amsdottorato.unibo.it/2809/.

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The Myc oncoproteins belong to a family of transcription factors composed by Myc, N-Myc and L-Myc. The most studied components of this family are Myc and N-Myc because their expressions are frequently deregulated in a wide range of cancers. These oncoproteins can act both as activators or repressors of gene transcription. As activators, they heterodimerize with Max (Myc associated X-factor) and the heterodimer recognizes and binds a specific sequence elements (E-Box) onto gene promoters recruiting histone acetylase and inducing transcriptional activation. Myc-mediated transcriptional repression is a quite debated issue. One of the first mechanisms defined for the Myc-mediated transcriptional repression consisted in the interaction of Myc-Max complex Sp1 and/or Miz1 transcription factors already bound to gene promoters. This interaction may interfere with their activation functions by recruiting co-repressors such as Dnmt3 or HDACs. Moreover, in the absence of , Myc may interfere with the Sp1 activation function by direct interaction and subsequent recruitment of HDACs. More recently the Myc/Max complex was also shown to mediate transcriptional repression by direct binding to peculiar E-box. In this study we analyzed the role of Myc overexpression in Osteosarcoma and Neuroblastoma oncogenesis and the mechanisms underling to Myc function. Myc overexpression is known to correlate with chemoresistance in Osteosarcoma cells. We extended this study by demonstrating that c-Myc induces transcription of a panel of ABC drug transporter genes. ABCs are a large family trans-membrane transporter deeply involved in multi drug resistance. Furthermore expression levels of Myc, ABCC1, ABCC4 and ABCF1 were proved to be important prognostic tool to predict conventional therapy failure. N-Myc amplification/overexpression is the most important prognostic factor for Neuroblastoma. Cyclin G2 and Clusterin are two genes often down regulated in neuroblastoma cells. Cyclin G2 is an atypical member of Cyclin family and its expression is associated with terminal differentiation and apoptosis. Moreover it blocks cell cycle progression and induces cell growth arrest. Instead, CLU is a multifunctional protein involved in many physiological and pathological processes. Several lines of evidences support the view that CLU may act as a tumour suppressor in Neuroblastoma. In this thesis I showed that N-Myc represses CCNG2 and CLU transcription by different mechanisms. • N-Myc represses CCNG2 transcription by directly interacting with Sp1 bound in CCNG2 promoter and recruiting HDAC2. Importantly, reactivation of CCNG2 expression through epigenetic drugs partially reduces N-Myc and HDAC2 mediated cell proliferation. • N-Myc/Max complex represses CLU expression by direct binding to a peculiar E-box element on CLU promoter and by recruitment of HDACs and Polycomb Complexes, to the CLU promoter. Overall our findings strongly support the model in which Myc overexpression/amplification may contribute to some aspects of oncogenesis by a dual action: i) transcription activation of genes that confer a multidrug resistant phenotype to cancer cells; ii), transcription repression of genes involved in cell cycle inhibition and cellular differentiation.

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Urbani, Nicola. "Association of endogenous viral genes and myb-gene polymorphisms with disease resistance in white leghorns." Thesis, McGill University, 1992. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=56818.

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The incidences of endogenous viral genes (ev-genes) and myb-gene polymorphisms were determined in substrains of strains R, M and G which had been divergently selected or susceptibility to tumour formation induced by Rous Sarcoma virus (RSV) of type A and B. Frequencies of myb gene polymorphisms were also determined in two replicates of strains selected for high and low multiple immune response to challenge with Pasteurella multocida and Mycoplasma gallisepticum. Strains R, M and G were found to contain different sets of ev-genes reflecting their distinct genetic origins. Among eleven ev-genes identified, two showed a significantly increased frequency in the susceptible substrains. One was ev-6, which expresses the viral envelope protein of the endogenous avian leucosis, while the other was a new endogenous viral gene New-E, whose phenotype is unknown. A significant increased incidence of ev-4, reported to be a silent ev-gene, was observed in resistant rather than susceptible substrain. Myb gene polymorphisms were assessed using a cDNA probe and a genomic probe yielding 2 and 3 restriction fragment length polymorphisms (RFLPs) respectively. In strains M and G, only one polymorphism (PM5$ sp+$) observed at an Msp I site located downstream of the last of the c-myb exons was found to be significantly co-selected for susceptibility. Analysis of RFLPs of myb-gene in strains selected for high or low multiple immune response did not reveal any significant response to selection. Rather, polymorphisms seemed to reflect a founder effect as revealed by opposite frequencies obtained in the two replicates. DNA methylation, a possible epigenetic mechanism regulating gene expression, was also investigated in the myb-gene. DNA from semen, blood, spleen, liver and thymus was extracted from organs obtained from chickens at different ages.

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Lemarteleur, Thibault Riou Jean-François. "Etude de ligand de l'ADN G-quadruplexe sur la transcription et la prolifération dans des lignées cellulaires humaines." [S.l.] : [S.n.], 2005. http://scdurca.univ-reims.fr/exl-doc/GED00000160.pdf.

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Dissertations / Theses on the topic 'Myc Genes'

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