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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

AvaliaÃÃo clinicopatolÃgica de pacientes portadores de tumores malignos de origem nÃo epitelial em regiÃo de cabeÃa e pescoÃo no municÃpio de Fortaleza- Ce / Clinical pathological study of patients with malignant tumors of non-epithelial origin in head and neck

Isabela Alves Pacheco 24 May 2010 (has links)
CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / Tumores malignos de origem nÃo epitelial sÃo considerados raros na regiÃo de cabeÃa e pescoÃo e podem apresentar grande morbidade e mortalidade. Este estudo teve o objetivo de fazer um levantamento dos casos de sarcomas e melanomas em regiÃo de cabeÃa e pescoÃo no perÃodo de 1999 a 2008, em trÃs centros especializados no MunicÃpio de Fortaleza, CearÃ. A coleta de dados foi feita com base nos livros de registros das cirurgias de cabeÃa e pescoÃo e dos prontuÃrios dos centros avaliados. Foram observados 54 casos, sendo 36 sarcomas e 18 melanomas. Quanto à avaliaÃÃo dos sarcomas, observamos que os indivÃduos mais acometidos foram homens adultos, da raÃa parda, na faixa etÃria de 20 a 59 anos, com idade mÃdia de 39,7. A relaÃÃo homem/mulher foi de 1,76:1. O tipo histolÃgico mais prevalente foi o rabdomiossarcoma, e as localizaÃÃes mais acometidas foram face e regiÃo cervical. Em relaÃÃo aos melanomas, homens adultos tambÃm foram predominantes, na faixa etÃria de 20 a 59 anos, com idade mÃdia de 54,6. Verificou-se igual acometimento nas raÃas parda e branca, com 33,3%, cada uma. A relaÃÃo homem/mulher foi de 1,25:1. O tipo histolÃgico mais prevalente foi o melanoma de disseminaÃÃo superficial, e a pele da face foi a localizaÃÃo mais frequente. Na avaliaÃÃo da procedÃncia, houve semelhanÃa em ambas as doenÃas, sendo aproximadamente metade dos pacientes da capital e metade do interior do estado. Quanto ao acompanhamento, a maior parte da amostra foi de pacientes vivos sem evidÃncia de doenÃa na Ãltima consulta, correspondendo a 41,6% nos sarcomas e 44,5% entre os melanomas. A variaÃÃo de terapia tambÃm foi observada em ambos os grupos, sendo os tipos mais comuns de tratamento a associaÃÃo de cirurgia, radioterapia e quimioterapia e cirurgia e radioterapia para sarcomas, e cirurgia, seguida da associaÃÃo de cirurgia e radioterapia para melanomas. Apesar de os tumores malignos de origem nÃo epitelial em cabeÃa e pescoÃo serem lesÃes raras, eles apresentam grande morbidade e mortalidade e dessa forma, necessita-se de que seus aspectos clinicopatolÃgicos sejam estudados e conhecidos, sempre com o objetivo de melhorar as formas de tratamento dessas lesÃes, garantindo assim maiores chances de cura e melhor qualidade de vida para os pacientes acometidos. / Malignant tumors of non-epithelial origin are considered rare in the head and neck region and they can show great morbidity and mortality. The aim of this study was to investigate the cases of sarcomas and melanomas in the head and neck region over the period from 1999 to 2008, in specialized centers located in the Municipality of Fortaleza. The data were collected from the register books of surgery of the head and neck and patient reports at the evaluated centers. Fifty-four cases were observed, being 36 sarcomas and 18 melanomas. As per the evaluation of the sarcomas, we have observed that the most assailed individuals were men with brown skin, ranging from 20 to 59 years old, with median age of 39.7. The relation man/woman was 1.7:1. The most prevailing histological type was the rhabdomyosarcoma, and the most attacked areas were the face and the cervical region. And as per the melanomas, adult men were also prevailing, ranging from 20 to 59 years old, with median age of 54.6. It has also been verified equal assailment in the brown and white races, with 33.3% in each one. The relation man/woman was 1.25:1. The most prevailing histological type was the superficial spreading melanoma, and the face skin was the most frequent location. In the evaluation of the origin, there was similarity in both diseases, being approximately half the patients in the capital city, and half in the stateÂs hinterland. As concerning the monitoring, the greatest part of the sample came from patients alive without evidence of the disease from the last consultation, corresponding to 41.6% in sarcomas and 44.5% in melanomas. The variation of therapy has also been observed in both groups, being the most common types of treatments, the association of surgery, radiotherapy and chemotherapy and surgery and radiotherapy for sarcomas and surgery, followed by surgery and radiotherapy for melanomas. Although malignant tumors of non-epithelial origin are rare in the head and neck region, they can show great morbidity and mortality and it is necessary the better understanding of their clinicalpatological aspects, in order to establish better treatment and life quality to these patients.
2

Etude de la régulation de l’expression de PLAGL1 dans les sarcomes / Regulation of PLAGL1 expression in sarcomas

Peille, Anne-Lise 17 December 2010 (has links)
Non fourni / Non fourni
3

The role of Snail2 transcription factor in osteosarcoma

Sharili, Amir Shaya January 2012 (has links)
No description available.
4

Thick filament regulation of myocardial contraction

Korte, F. Steven, January 2006 (has links)
Thesis (Ph. D.)--University of Missouri-Columbia, 2006. / The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Vita. "August 2006" Includes bibliographical references.
5

NR2C/F telomeric association drives telomere-genome rearrangements in ALT cells / Réarrangements télomères/génome médiés par les facteurs NR2C/F dans les cellules ALT

Marzec, Paulina 06 December 2013 (has links)
L'immortalité cellulaire est toujours accompagnée par l'activation du mécanisme de maintien des télomères. Dans la plupart des cancers humains, ce rôle est assuré par l'enzyme télomérase. Cependant, dans 15 % des tumeurs, la télomérase n'est pas activée et les télomères sont maintenus par l'allongement alternatif des télomères (ALT), voie qui implique la recombinaison des télomères. ALT est plus fréquent dans les tumeurs provenant de tissus mésenchymateux (sarcomes), representant 40-60 % des cas, que dans les tumeurs épithéliales. Comprendre le mécanisme ALT est primordial dans les thérapies anti-cancéreuses puisque certaines drogues inhibant la télomérase conduisent souvent à l'activation de l'ALT.La voie ALT est définie par de caractéristiques typiques des télomères. Dans les cellules ALT, les recombinaisons aberrantes d'ADN ne se limitent pas aux télomères puisque les génomes sont souvent fortement réarrangés. Les liens de ces caractéristiques génomiques anormales et la maintenance des télomères atypique ne sont pas connues, mais l'instabilité du génome contribue certainement à la transformation. Notre équipe a montré que les récepteurs orphelins appartenant aux familles NR2C/F ont été trouvés enrichies dans les télomères des lignées cellulaires ALT. Nous avons proposé que ces facteurs puissent être recrutés aux télomères par liaison directe à la séquence répétée GGGTCA, un site de liaison à haute affinité pour ces protéines. Mon projet vise à comprendre (i) leur mécanisme de liaison et (ii) leur rôle, dans le processus d'ALT.Dans cette étude nous montrons que dans les sarcomes primaires humains, les télomères d'ALT sont souvent liés par des récepteurs nucléaires orphelins des sous-familles NR2C/F, en particulier dans les tumeurs au stade avancé. Ceci suggère un rôle actif de ces facteurs dans la progression tumorale ALT. En utilisant la technique de ChIP-sequencing, nous avons montré que les protéines NR2C/F se lient à une répétition directe amplifiée (DR0) aux télomères, et pas de manière significative à toute autre combinaison de motif GGGTCA. Nous avons également analysé la distribution sur tout le génome de NR2C2/F2 et TRF2, une protéine de liaison des télomères, dans des cellules ALT (-) et ALT (+). Bien qu'il n'y ait que peu de sites génomiques liés par TRF2 dans les cellules ALT (-), nous avons été surpris d'identifier plusieurs centaines de régions liées par TRF2 dans les cellules ALT (+). Plus surprenant, la grande majorité de ces régions spécifiques TRF2 ALT chevauche des sites endogènes de NR2C2/F2. Étant donné que ces sites ne contiennent généralement pas les répétitions des télomères, TRF2 est probablement recruté de façon indirecte. Conformément à cette interprétation, nous montrons que les facteurs NR2C/F entrainent un rapprochement des loci et sont responsables du regroupement atypique des télomeres dans ALT. De plus, un sous-ensemble de ces régions génomiques uniques a des additions hétérogènes des séquences télomeriques ALT, suggérant un rôle dans le recrutement des télomères par des protéines NR2C/F mais aussi une fonction de ciblage de recombinaison génomique. Systématiquement, nous trouvons que ces réarrangements des télomères/génome sont situés à proximité des motifs GGGTCA endogènes. Le caryotype spectral des lignées cellulaires ATL montre que les sites télomériques interstitielles sont fréquemment localisés aux niveaux des sites de translocations/réarrangements entre deux ou plusieurs chromosomes, ce qui est également observé dans les données de ChIPseq. Ces résultats suggèrent que les réarrangements entres les télomères et le génome pourraient participer à la formation d'un caryotype complexe ce qui caractérise environ 50% des sarcomes. De plus, l'addition de sites télomériques interstitielles dans le génome est spécifique des cellules ALT et est favorisée par les dommages de l'ADN. / Cellular immortality is always accompanied by the activation of telomere maintenance mechanism. In most human cancers this role is fulfilled by the telomerase enzyme. However in 15% of tumors, telomerase is not activated and telomeres are maintained by an Alternative Lengthening of Telomeres (ALT) pathway that involves telomere-telomere recombination. Interestingly ALT is more prevalent in tumors originating from mesenchymal tissues (sarcomas), where it is present in 40-60% of cases, than in epithelial tumors. Understanding ALT maintenance is critical since inhibiting telomerase in tumors leads to the activation of ALT. The ALT pathway is operationally defined by typical telomere hallmarks. In ALT cells, aberrant DNA transactions are not restricted to telomeres since genomes are often highly rearranged. Whether these abnormal genomic features are linked to atypical telomere maintenance is not known, but genome instability is certainly contributing to transformation. We have previously shown that orphan receptors of the NR2C/F families were enriched at telomeres in ALT cell lines. We proposed that these factors could be recruited to telomeres through direct binding to the GGGTCA variant repeat, a high affinity binding site for these proteins. My project is aimed at understanding (i) their mechanism of binding and (ii) their role, if any, in the ALT process.We show that in human primary sarcomas, ALT telomeres are often bound by orphan nuclear receptors of the NR2C/F subfamilies, particularly in more advanced-stage tumors. This suggests an active role for these factors in ALT tumor progression. Using ChIP-sequencing, we show that NR2C/F proteins bind to an amplified direct repeat (DR0) at telomeres, and not significantly to any other GGGTCA motif combination. We also analyzed the genome wide distribution of NR2C2/F2 and TRF2, a telomere binding protein, in ALT(-) and in ALT(+) cells. While there are only few genomic sites bound by TRF2 in ALT(-) cells, we were surprised to identify several hundred regions bound by TRF2 in ALT(+) cells. More surprisingly, the great majority of these ALT specific TRF2 regions overlap with endogenous NR2C2/F2 sites. Since these sites usually do not contain telomere repeats, TRF2 is likely indirectly recruited. Consistent with this interpretation, we show that NR2C/F factors drive locus proximity. Moreover, a subset of these unique genomic regions harbor heterogeneous ALT telomere sequence additions, not only suggesting a telomere recruitment role for NR2C/F proteins but also a recombination targeting function in the genome. Consistently, we find these telomere/genome rearrangements are located close to endogenous GGGTCA motifs. Next, we wanted to evaluate a role of these rearrangements in formation of complex karyotype which characterize approximately 50% of sarcomas. We found by spectral karyotyping that interstitial telomeric sites are frequently located at translocation/ rearrangements sites between two or more chromosomes, which we could also observe in our ChIPseq data. Furthermore, we demonstrate that addition of interstitial telomeric sites to the genome is enhanced by DNA damage and specific for ALT genome. Therefore we conclude that NR2C/F factors target telomere proximity to defined NR2C/F regions which enables telomere-genome rearrangements under DNA damage condition. This contributes not only to efficient telomere recombination, but also it drives further genomic instability at selected NR2C/F sites.We believe we identified a new mechanism of telomere dysfunction potentially driving targeted genome instability and mediated by NR2C/F proteins in ALT cells which probably underlie complexity of sarcomas genome. Understanding the ALT mechanism allows designing NR2C/F-targeted therapies in treatment of ALT tumors and therapies for patients treated with anti-telomerase drugs to prevent ALT appearance.
6

Factores de pronóstico en los tumores uterinos con patrón sarcomatoso

Rovirosa Casino, Ángeles 01 July 2003 (has links)
Los factores de pronóstico en los tumores uterinos con patrón sarcomatoso (TUPS) no han estado bien establecidos con la excepción del estadio. Asimismo, la radioterapia (RDT) de modo complementario a la cirugía no han sido un tratamiento consensuado. Con la hipótesis de que no se conoce con la suficiente precisión la influencia de los factores de pronóstico en la supervivencia global específica (SGE), supervivencia libre de enfermedad (SLE), supervivencia libre de recidiva local (SLRL) y supervivencia libre de metástasis (SLM), se ha estudiado la influencia de los diferentes factores de pronóstico en las diferentes supervivencias. Dicho estudio se ha efectuado estratificando a las pacientes por estadios. Así mismo, se ha evaluando el impacto de la radioterapia y se ha efectuado el estudio comparativo de los factores de pronóstico en estos tumores con los del cáncer de cérvix y el de endometrio. Material y métodos: 60 pacientes diagnosticadas y tratadas por TUPS entre 1975 y 1999 en el Hosp. Clínic de Barcelona. Factores de pronóstico estudiados: edad, tipo histológico, índice mitótico, invasión miometrial (IM), invasión vasculolinfática (IVL), necrosis, uni/multicentricidad, tamaño tumoral y la radioterapia. Análisis estadístico: Método actuarial de Kaplan y Maier, test de Log-rank y modelo de riesgo proporcional de Cox. Estudio de los factores pronósticos en la literatura: 21 publicaciones en TUPS entre 1966 y 2001, así como las publicaciones sobre factores de pronóstico en los últimos 10 años para el cáncer de cérvix y el de endometrio. Resultados: 1) En el análisis multivariado se evidenció: en estadios tempranos la influencia de la IVL y el tamaño tumoral mayor a 8 cm. en la SGE, de la invasión miometrial > 50% en la SLE y SLRL, y de la IVL en la SLM. En los estadios avanzados solo se constató la influencia del tipo histológico leiomiosarcoma en la SGE, lo cual pudo ser debido a una mayor incidencia de factores de mal pronóstico en los estadios avanzados. 2) No se evidenció impacto de la RDT en ninguna de las supervivencias; sin embargo, hubo una mayor incidencia de IM e IM > 50% entre las pacientes que recibieron RDT. El 100% de las pacientes con tamaños tumorales < 8 cm. con estadio temprano y tipo histológico carcinosarcoma estaban vivas si habían recibido RDT. 3) Los tumores uterinos con patrón sarcomatoso tienen un comportamiento más parecido al cáncer de endometrio que al cáncer de cérvix en cuanto a la relevancia de los diferentes factores de pronóstico. La IM > 50%, tamaño tumoral > 8 cm., IVL, Indice mitótico y tipo histológico deben de considerarse factores de mal pronóstico en los TUPS; el que tiene más relevancia en la literatura es la invasión miometrial.Conclusiones: El estadio es el factor pronóstico más importante en los TUPS. Al estratificar a las pacientes por estadios la IVL, la IM > 50% y el tamaño tumoral han sido los factores con impacto en los estadios tempranos. Todas las pacientes con IVL fallecieron con metástasis. Podría existir un beneficio de la irradiación en aquellos tumores < 8cm, carcinosarcomas e IM > 50%. En estadios avanzados influyo el tipo leiomiosarcoma. La mayor agresividad de los estadios avanzados podría justificarse por una mayor incidencia de factores de mal pronóstico en comparación con los tempranos, lo que además puede explicar la ausencia de efecto de la irradiación. / Prognostic factors in uterine tumours with a sarcomatous component (UTSC) have not being well stablished with the exception of the stage. Moreover, there is not agreement between authors on the value of complementary radiotherapy to the surgery.The present study was performed with the hypothesis that there is not a precise knowledge of the influence of the different prognostic factors on the specific overall survival (OS), disease-free survival (DFS), local relapse-free survival (LRFS) and distant metastasis-free survival (DMFS). The study of the influence of the different prognostic factors in the different survivals was performed stratifying patients by stage. The impact of irradiation (RDT) was also analyzed and a comparative study of the literature on prognostic factors between cervical and endometrial cancer, and uterine tumours with a sarcomatous component was performed.Matherial and methods: Sixty patients diagnosed and treated at Clinic Hospital of Barcelona. Prognostic factors studied: age, pathologic type, mitotic index, myometrial invasion (MI), vascular and lymphatic space invasion (VLSI), necrosis, unicentricity / multicentriciy, tumoral size and radiotherapy. Statistics: Kaplan and Maier actuarial method, Log-rank method and Cox model of proportional risk. The study of prognostic factors in the literature was done using 21 publications in uterine sarcomas between 1966 and 2001 having more than 45 patients, and those articles on prognostic factors for cervical and endometrial cancer in the last 10 years.Results: 1) Multivariate analysis. In early stages, VLSI and tumor size > 8 cm. had impact on OS, MI > 50% on DFS and LRFS and VSLI on DMFS. Advanced stages: leiomyosarcoma type was the only prognostic factor with impact on OS; a higher incidence of other prognostic factors in advanced stages could have been the responsible. 2) RDT had no impact on the different survival results; nevertheless, there were a higher incidence of MI and MI > 50% in the radiotherapy group. The 100% of the patients having tumoral size < 8 cm., early stages and carcinosarcoma type, were alive if they had received irradiation. 3) In terms of prognostic factors, endometrial carcinoma and uterine tumors with a sarcomatous component have a more similar behaviour in comparison to cervical cáncer. MI> 50%, tumoral size, VLSI, mitotic index and pathologic type should be considered as prognostic factors in uterine sarcomas; the most relevant in the litherature is MI.Conclusions: The most important prognostic factor in uterine sarcomas is the stage. When patients were stratified by stages VLSI, MI>50% and tumoral size > 8 cm. were prognostic factors with impact in early stages. All the patients having VLSI died by distant metastasis. A benefit of irradiation could be found in tumors >8 cm., MI > 50% and carcinosarcoma type. In advanced stages leiomyosarcoma type had impact on survival. The more aggresive behaviour in advanced stages could be explained by a higher incidence of bad prognostic factors in comparison to early stages.
7

The epidemiology of feline injection site sarcomas in the United Kingdom

Dean, Rachel Sarah January 2010 (has links)
No description available.
8

The Rarest of the Rare: A Case of Primary Cardiac Osteosarcoma With a Review of the Literature

Mhadgut, Hemendra, Manthri, Sukesh, Youssef, Bahaaeldin, Jaishankar, Devapiran 01 July 2021 (has links)
A 54-year-old female presented with shortness of breath and cyanosis. Work up with chest X-ray and subsequent echocardiogram revealed an intracardiac bi-atrial mass leading to emergent cardiothoracic resection. Pathology was consistent with a primary cardiac high-grade osteosarcoma. Post-resection staging positron emission tomography-computed tomography (PET-CT) showed hypermetabolic mixed lytic and sclerotic lesion of T10 concerning for metastasis. She received five cycles of adriamycin and ifosfamide chemotherapy before discontinuation due to systolic dysfunction. Nine months later, she developed a high tumor burden with progressive disease and was treated with second-line gemcitabine/docetaxel with disappointing results. She is currently on treatment with cyclophosphamide and topotecan as third-line treatment with an excellent clinico-radiographic response. Osteosarcomas are aggressive with a high incidence of recurrence and metastasis. Fewer than 50 cases of primary cardiac osteosarcomas have been reported in the literature. Even though complete resection can be achieved in some cases, long-term results are usually poor. No standard therapy has been established.
9

Análise imuno-histoquímica de marcadores apoptóticos Bcl-2 e Bax em sarcomas de partes moles de extremidades: um estudo de microarranjos de tecidos

Mühlbeier, Diego Franciel Marques 12 March 2012 (has links)
Made available in DSpace on 2016-08-10T10:38:36Z (GMT). No. of bitstreams: 1 DIEGO FRANCIEL MARQUES MUHLBEIER.pdf: 2283104 bytes, checksum: 4b3910db11a5426da6161c55a1de78bc (MD5) Previous issue date: 2012-03-12 / Sarcomas are a heterogeneous group of tumors that arise from mesenchymal tissues which represent about 1% of all diagnosed solid malignant tumors in adults. Changes that affect the tumor growth such as the deregulation of apoptosis, through overexpression of the Bcl-2 family proteins, have been associated with the prognosis of patients in various types of cancers, including soft tissue sarcomas (SPM). The Bcl-2 family proteins include anti-apoptotic and proapoptotic proteins such as proteins Bcl-2 and Bax, respectively. Despite the evidence, the prognostic value of these proteins, as well as the association with clinicopathological factors, remain controversial. The objective of this study was to investigate the clinical significance of the expression of apoptosis-related markers Bcl-2 and Bax in 86 patients with STS of extremities by immunohistochemical analysis on a tissue microarray construction. Cytoplasmic expression of Bax and Bcl-2 was detected in 25.9% and 66.7% of the cases, respectively. Overexpression of both Bcl-2 and Bax was directly associated with synovial sarcoma, histological grade and clinical stage. A significant association between Bax and Bcl-2 expression was also observed. The 5-year overall survival (OS) for the group was 57%, being lower for cases with Bcl-2 overexpression (47.6% vs 58.3%) and Bax overexpression (50% vs 66.7%), although such difference was not significant. After multivariate analysis, the histological grade remained as an independent prognostic factor (p=0.043, HR=8.0, 95% CI, 1.1-60.1). Bcl-2 family proteins have been tested as therapeutic targets in some clinical studies in several cancers. In our study, overexpression of both Bcl-2 and Bax was associated with histological grade and clinical stage of the tumors, which are classical factors of poor prognosis. Thus, we suggest the use of these proteins as potential prognostic markers in STS of extremities, providing a more appropriate therapeutic planning for each patient. / Os sarcomas constituem um grupo heterogêneo de tumores que surgem a partir de tecidos mesenquimais e que representam cerca de 1% de todos os tumores sólidos malignos diagnosticados em adultos. Alterações que afetam o crescimento tumoral, como a desregulação da apoptose, por meio da hiperexpressão de proteínas da família Bcl-2, têm sido associadas ao prognóstico dos pacientes em diversos tipos de cânceres, incluindo os sarcomas de partes moles (SPM). A família Bcl-2 inclui proteínas pró-apoptóticas e anti-apoptóticas, tais como as proteínas Bax e Bcl-2, respectivamente. Apesar das evidências, o valor prognóstico dessas proteínas, assim como a associação com fatores clínicopatológicos, ainda permanecem controversos. O objetivo desse estudo foi investigar o significado clínico da via da apoptose, por meio da avaliação da expressão imuno-histoquímica de Bcl-2 e Bax, em um grupo de 86 casos de SPM de extremidades, utilizando microarranjos de tecidos (tissue microarray). A expressão citoplasmática de Bcl-2 e Bax foi detectada em 25,9% e 66,7% dos casos, respectivamente. A hiperexpressão de ambos, Bcl-2 e Bax, foi associada aos sarcomas sinoviais, ao grau histológico e ao estadiamento clínico. Uma associação significativa entre a expressão das proteínas Bcl-2 e Bax também foi observada. A sobrevida global em cinco anos foi de 57%, sendo menor para os casos com hiperexpressão de Bcl-2 (47,6% x 58,3%) e Bax (50% x 66,7%), porém, esta diferença não foi estatisticamente significativa. Após análise multivariada, o grau histológico apresentou-se como fator prognóstico independente (p = 0.043, HR = 8.0, IC 95%, 1.1-60.1). Proteínas da família Bcl-2 vêm sendo testadas como alvos terapêuticos em diversos estudos clínicos em vários tipos de cânceres. Em nosso estudo, a expressão de Bcl-2 e Bax foi associada com o grau histológico e o estadiamento clínico, que são fatores clássicos de mau prognóstico. Assim, sugerimos o uso da expressão imunohistoquímica de Bcl-2 e Bax como potencial marcador prognóstico em SPM de extremidades, possibilitando um planejamento terapêutico mais adequado para cada caso.
10

POLIMORFISMO DO GENE TP53 EM SARCOMAS DE PARTES MOLES NO ADULTO

Almeida, Priscilla Silva Rosa de 21 July 2008 (has links)
Made available in DSpace on 2016-08-10T10:39:18Z (GMT). No. of bitstreams: 1 PRISCILLA SILVA ROSA DE ALMEIDA.pdf: 3720637 bytes, checksum: b39a9c071d90058d47a3a8c7aec2c7f3 (MD5) Previous issue date: 2008-07-21 / Soft tissue sarcomas (STS) are tumors with mesodermical origin, comprising about 1% of all adult neoplasms. Because of its effect on the p53 protein coding sequence, and its association with an increased risk for some cancer types, TP53 codon 72 polymorphism has been investigated in several studies. TP53 codon 72 codes for either Arginine (p53Arg), or Proline (p53Pro) at the p53 protein primary sequence. It was demonstrated that such amino acid change affects p53 biochemical and biological properties, and several studies have been developed in order to associate TP53 codon 72 polymorphisms as a risk, and as a prognostic factor for different cancer types. Any published study on the TP53 codon 72 polymorphism in adult soft tissue sarcomas was found in the literature. The present study aimed to investigate TP53Arg/Pro polymorphism as a potential prognostic factor in 100 adult subjects with STS. Patients were assisted at the Hospital Araújo Jorge of the Associação de Combate ao Câncer em Goiás in Goiânia, Brazil. DNA from patients was obtained from formaldehyde-fixed and paraffin-embedded tissue samples stored at the Pathology Department of the institution. Control group included 85 healthy donors randomly selected from Goiânia s population and, for this group, DNA extraction was performed from peripheral blood. Polymorphism genotyping was achieved by using polymerase chain reaction (PCR) with specific primer sets for each polymorphic variant. Statistical analysis was performed by using GenePop Ò web version 3.4 software. In this study, TP53 allelic and genotypic frequencies were investigated for subjects and controls, however, any statistical difference between the two groups was found. Our study supports the evidence that p53Arg is the most frequent allele in Latin American population, but worldwide genic and genetic frequency data are conflicting because of ethnical differences among the studied populations. According to the results, no significant association was demonstrated between TP53 codon 72 polymorphism and clinocopathological characteristics such as gender, age, tumor localization, histology, tumor size, stage, grade, node status, and distant metastasis. The five-year overall survival for the study group was 48.1%. Tumors with p53Pro/Pro genotype demonstrated a reduced survival rate (30%) when compared to p53Arg/Arg (45%), and p53Arg/Pro group (54.9%), but this association was not statistically significant (p = 0.444). In the present study, the p53Arg variant was not statistically associated with a more favorable prognosis in adult STS patients. / Os sarcomas de partes moles (SPM) são tumores de origem mesodérmica, representando cerca de 1% do total das neoplasias em adultos. O polimorfismo do códon 72 do gene TP53 é extensivamente estudado por causar impacto na seqüência codificadora do gene, além de estar associado ao maior risco para o desenvolvimento de alguns tipos de câncer. Este polimorfismo resulta na expressão de arginina (p53Arg) e/ou prolina (p53Pro) na posição 72 da proteína p53. As formas polimórficas de TP53, em relação ao polimorfismo do códon 72, apresentam propriedades bioquímicas e biológicas diferentes, e por esta razão, vários estudos foram conduzidos na tentativa de associar tais formas polimórficas como fator de risco e prognóstico para inúmeras neoplasias. Entretanto, a literatura não relata nenhum estudo que associe este polimorfismo aos sarcomas de partes moles do adulto. Neste contexto, o objetivo do presente estudo foi avaliar o polimorfismo p53Arg/Pro como potencial fator de risco e/ou prognóstico em 100 casos de SPMs em adultos atendidos no Hospital Araújo Jorge da Associação de Combate ao Câncer em Goiás. O grupo controle incluiu 85 indivíduos saudáveis selecionados aleatoriamente da população da cidade de Goiânia. As amostras dos casos constituíram de tecidos fixados em formol e incluídos em parafina e, para a extração de DNA, os tecidos foram previamente desparafinizados. A extração de DNA do grupo controle foi realizada a partir de sangue periférico. Para a genotipagem do polimorfismo, a reação em cadeia da polimerase (PCR) foi realizada utilizando conjuntos de primers específicos para cada variante polimórfica. Após a análise dos dados obtidos, verificou-se que as freqüências alélicas e genotípicas não apresentaram diferenças estatisticamente significativas entre os casos e os controles. Nosso estudo corrobora com as evidências de que o alelo p53Arg é o mais comum em populações latinoamericanas. Entretanto, os dados sobre as freqüências gênicas e genotípicas da literatura mundial são conflitantes, fato que pode ser atribuído às diferenças étnicas descritas entre as populações estudadas. Nenhuma relação estatisticamente significativa foi encontrada entre o polimorfismo do códon 72 de TP53 e as características clínico-patológicas estudadas, como sexo, idade agrupada, localização, histologia, tamanho e grau histológico tumoral, estadiamento e presença de mestástases. A sobrevida global em cinco anos para o grupo estudado foi de 48,1%. As análises de sobrevida em relação ao polimorfismo de TP53 revelaram que os pacientes cujos tumores apresentaram o genótipo p53Pro/Pro tiveram sobrevida inferior (30%), quando comparados ao grupo de pacientes com os genótipos p53Arg/Arg (45%) e p53Arg/Pro (54,9%). Entretanto, essa diferença não foi estatisticamente significativa (p = 0,444). Sabese que a isoforma p53Arg apresenta função apoptótica mais marcante. Esta característica pode conferir ao paciente um melhor prognóstico da doença. No presente trabalho, contudo, não pudemos verificar que esta variante esteve associada a um prognóstico mais favorável em pacientes adultos com SPMs.

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