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Desenvolvimento de membranas como compostos dermo-epidermicosRODAS, ANDREA C.D. 09 October 2014 (has links)
Made available in DSpace on 2014-10-09T12:49:03Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T14:09:49Z (GMT). No. of bitstreams: 0 / Neste trabalho foi estudada a formação de membranas para obtenção de compostos dermo-epidérmicos. A porção dérmica foi desenvolvida utilizando-se mistura de polímeros sintéticos, o poli(álcool vinílico) - PVAl ou poli(vinilpirrolidona) – PVP, com polímero natural, a quitosana. As membranas foram reticuladas pela radiação g ou glutaraldeído. A porção epidérmica destas membranas foi formada por queratinócitos cultivados in vitro, os quais foram semeados sobre as membranas correspondentes e verificada sua interação. As membranas que melhor interagiram com os queratinócitos foram aquelas preparadas com quitosana pela reticulação com glutaraldeído, porém não satisfazendo as características mecânicas de manipulação. As membranas que possuíam as melhores características mecânicas, porém com moderada interação com os queratinócitos, foram as compostas de PVAl, liofilizada e intumescida com quitosana. Os componentes foram caracterizados isoladamente, bem como as membranas formadas pelos mesmos. O PVAl foi caracterizado quanto a sua dose gel e a quitosana quanto à determinação das constantes de Mark-Houwink, grau de acetilação e dissolução em diferentes valores de pH. As membranas foram caracterizadas quanto a sua cinética de intumescimento com água. Na membrana de PVAl com quitosana incorporada foi avaliada sua degradação in vitro, determinada sua cinética de intumescimento com a quitosana e estimado o tamanho do poro. As membranas de quitosana reticuladas com glutaraldeído foram caracterizadas quanto à cinética de intumescimento e verificado o possível desprendimento de glutaraldeído. As duas membranas caracterizadas isoladamente foram unidas para formação de uma única membrana, como a parte dérmica do composto, onde a membrana de PVAl incorporada com quitosana foi recoberta com a membrana de quitosana reticulada com glutaraldeído. Quitosanas de outras procedências foram avaliadas na interação com os queratinócitos. / Tese (Doutoramento) / IPEN/T / Instituto de Pesquisas Energeticas e Nucleares - IPEN/CNEN-SP
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Investigating cellular nanoscale with x-rays from proteins to networksHémonnot, Clément 25 July 2016 (has links)
No description available.
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Humidity Driven Performance of Biological AdhesivesJain, Dharamdeep 24 May 2018 (has links)
No description available.
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Recombinant Proteins for Biomedical ApplicationsKim, Christina Sue Kyung 06 July 2020 (has links)
Both technological and experimental advancements in the field of biotechnology have allowed scientists to make leaps in areas such nucleic acid, antibody, and recombinant protein technologies. Here we focus on the use of recombinant proteins as molecular recognition motifs, wound healing biomaterials, and agents for cell cycle pathway elucidation are discussed.
The author's primary project is described in chapters 2 and 3, and is focused on designed leucine-rich repeat proteins which offer increased stability, modularity, and surface area for binding interactions. These proteins bind at least two muramyl dipeptide ligands with picomolar to nanomolar affinity (Kd1 = 0.04 – 3.5 nM); as measured by fluorescence quenching experiments and ITC. The longest designed repeat, CLRR8, has a Kd app value of 1.0 nM which is comparable to full length native NOD2 protein. Molecular docking simulations revealed the locations of two potential binding sites and their respective interactions. The series of proteins represents a foundation for a high affinity and highly specific molecular recognition scaffold that has the potential to bind a variety of ligands.
Previously the author contributed to the design of recombinant keratin proteins, and the work in Chapter 4 builds on the original design to allow for controlled degradation in wound healing systems. Site-directed mutagenesis was utilized to introduce these degradation sites, and modified keratin proteins were expressed with no differences to native recombinant keratin proteins. Success in engineering a variation of native keratin protein with no issues in expression lay the foundation for further engineering of native keratin or other relevant proteins for improved functionality.
Chapter 5 describes steps towards producing human Aurora borealis (Bora) protein, an important substrate in cell cycle regulation, by in vitro transcription-translation with locked Ser–Pro analogues. This will allow for the elucidation of the active isomerization form to ensure proper cell division. Site-directed mutagenesis successfully introduced the amber codon to relevant Ser-Pro sites at positions 274 and 278. These mutated Bora genes along with modified ribosomes and aminoacyl tRNA will allow for the incorporation of locked dipeptide analogues. Expression of native Bora was carried out as a control, and appeared to express in dimeric form. The experiments carried out in Chapter 5 describe and outline all the molecular biology work completed and to be completed for this novel method of studying cis-trans isomerization in living cells. / Doctor of Philosophy / Sequencing of the human genome and the rapid development of gene editing and recombinant DNA technologies paved the way for a massive shift in the pharmaceutical industry. The first pharmaceutical companies in the 19th century started as fine chemicals businesses. The discovery of penicillin introduced antibiotics, and improved synthetic techniques led to the giants we know as big pharma today. Today, in the 21st century both computing and biotechnology has allowed for great leaps forward in precision medicine. Biotechnology refers to the manipulation of living organisms or their components to produce useful commercial products. In the pharmaceutical industry this refers to genetic engineering for novel pharmaceuticals.
Here, we focus on the use of recombinant technology to create proteins for use in biomedical applications. Recombinant proteins are proteins formed by laboratory methods of molecular cloning. Through this technology, we are able to elucidate sequence-structure-function relationships of proteins, and determine their specific functions. Additionally, recombinant methods allow us to fine tune or modify the sequences of natural proteins to be more effective scaffolds or reagents.
Chapter 3 focuses on the development of synthetic proteins for medical diagnostics. We designed a protein scaffold, based on natural innate immunity proteins, to detect bacteria cell wall components. Chapter 4 focuses on the engineering of keratin protein with applications in wound healing. We introduce controlled degradation of the biomaterial for use in potential drug delivery systems at the wound site. Chapter 5 focuses on the use of recombinant technologies aiding in the elucidation of a regulatory protein's function in cell division.
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Expressão do transcrito da citoqueratina 19 (CK-19) na fração mononuclear do sangue periférico em pacientes com adenocarcinoma de próstata / Cytokeratin 19 expression in the peripheral blood mononuclear fraction of prostate cancer patientsMachado, Marcos Tobias 04 March 2008 (has links)
Introdução: O emprego da técnica de RT-PCR na detecção da expressão de genes epiteliais como a CK-19 no sangue periférico de pacientes com câncer de próstata é uma oportunidade para avaliar a progressão tumoral ao nível molecular na ausência de doença clinicamente mensurável. Material e métodos: Inicialmente 10 pacientes com nível sérico de PSA< 2ng/ml e toque retal sugestivo de hiperplasia prostática benigna foram incluídos como grupo controle através de coleta de sangue única para dosagem do transcrito da CK-19. Subsequentemente,foram seguidos de maneira prospectiva 44 pacientes com câncer de próstata (21 com doença localizada e 23 com doença metastática), com coleta de sangue seriada a cada 3 meses por 18 meses. Foi medida a expressão sérica do transcrito da CK-19 por RT-PCR na fração leucocitária do sangue periférico e correlacionada aos níveis séricos de PSA e outras variáveis clinicas e patológicas. Resultados: Nenhum de 10 pacientes controles apresentou expressão do transcrito da CK-19 no sangue periférico. Nos pacientes com câncer de próstata a expressão do transcrito da CK-19 na entrada do estudo não se correlacionou com o escore de Gleason, estádio clínico e os níveis séricos de DHL, Hemoglobina, PSA, Fosfatase alcalina ou Testosterona. A presença de pelo menos uma dosagem positiva de CK-19 durante o seguimento se correlacionou com o tempo para a progressão bioquímica do PSA na amostra como um todo(p=0,049) e no subgrupo com doença metastática(p=0,032). Conclusão: Não houve expressão do transcrito da CK-19 na fração mononuclear do sangue periférico em homens do grupo controle. Nos pacientes com câncer de próstata não houve correlação entre a expressão do transcrito da CK-19 na entrada do estudo e as principais variáveis clínicas e patológicas de prognóstico. Nos pacientes com câncer de próstata, a presença de pelo menos uma dosagem positiva para o transcrito da CK-19 no seguimento se correlacionou com um menor tempo para recidiva bioquímica , especialmente no subgrupo de pacientes com doença metastática tratados com hormonioterapia / Background: The recent introduction of sensitive RT-PCR-based techniques for the detection of epithelial antigen expression, such as CK-19,in the peripheral blood of prostate cancer patients may provide an opportunity to evaluate early tumor progression at the molecular level, even in the absence of measurable disease. Methods: Ten men with PSA <2ng/ml and digital rectal examination suggestive for benign prostatic hyperplasia were included as controls by only one colleted blood sample to measure of CK-19 transcript. We also studied serially collected blood samples of 44 patients with prostate cancer (21 with localized and 23 with metastatic disease) every three months for 18 months. We measured CK-19 transcript expression in the peripheral blood mononuclear fraction (PBMN) of these samples by RT-PCR and correlated it with PSA values and other clinical and pathologic variables. Results: None of the 10 normal control men showed CK-19 transcript expression in their PBMN. In the patients with prostate cancer, CK-19 transcript positivity at entry did not correlate with Gleason score, clinical stage, DHL, hemoglobin level, PSA, alkaline phosphatase or testosterone levels. Having at least one positive CK- 19 result during follow up correlated significantly with time to PSA progression in all coorte (p = 0.049) and in the subgroup of metastatic disease (p = 0.032). Conclusion: There are no expression of CK-19 transcript in the PBMN of control men. In prostate cancer patients there are no correlation between CK-19 at entry and the most important clinical and pathological prognostic variables. Prostate cancer patients that had at least one CK-19 transcript expression in the peripheral blood present lower time to PSA progression, specially metastatic patients receiving hormonal therapy
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Caracterização clínica e histológica do carcinoma hepatocelular (CHC) secundário à doença hepática gordurosa não alcoólica (DGHNA) / Clinical and histopathological characterization of hepatocellular carcinoma (HCC) in non-alcoholic fatty liver disease (NAFLD)Campos, Priscila Brizolla de 06 November 2017 (has links)
O aumento na incidência do carcinoma hepatocelular (CHC) tem sido atribuído ao aumento da obesidade, diabetes e doença hepática gordurosa não alcoólica. (DHGNA), estando ainda por ser melhor esclarecidos vários aspectos histopatológicos e imuno-histoquímicos. O objetivo deste estudo é avaliar aspectos clínicos e patológicos de pacientes com CHC secundário a DHGNA, assim como relacionar a marcadores imuno-histoquímicos de classe proliferativa. Avaliamos 35 espécimes de CHC de 21 pacientes diagnosticados com DHGNA submetidos a ressecção hepática (12 pacientes) ou a transplante hepático (8 pacientes) ou ambos (1 paciente), de 2005 a 2015. Dados demográficos, clínicos e bioquímicos foram relacionados a características histológicas e reatividade imuno-histoquímica para K19, marcando características de células progenitoras e Ki-67, marcando as células em ciclo celular. Um total de 35 nódulos foram detectados em 21 pacientes. A cirrose estava presente em 12 casos (7 F4A x 4F4B x 1F4C de acordo com estadiamento de Laennec) e 9 pacientes não apresentavam cirrose (estadiamento DHGNA: F2: 6pts, F3 = 3pts). A idade variou de 50 a 77 anos e 16 pacientes eram do sexo masculino (76%). Dezesseis pacientes (76%) apresentavam diabetes mellitus, 17 pacientes (81%) apresentavam hipertensão arterial e 19 pacientes (90%) tinham IMC superior a 25 kg / m2. O CHC ocorreu em 8 pacientes CHILD A, 4 CHILD B e em 9 pacientes sem cirrose. O nível de alfa-fetoproteína foi normal em 13 (62%) pacientes. Dentre os critérios histológicos, 25 (70%) nódulos foram diagnosticados como \"CHC esteatohepatítico\". Embora 63% tenham sido pouco diferenciados (G.3/G.4) de acordo com Edmondson & Steiner (1954), apenas 21% apresentaram níveis elevados de Ki-67 ( > 10%). No caso da K19, também 21% dos pacientes apresentaram expressão positiva ( > 5%), e foi associado a maior inflamação intratumoral (G 2/3). Curiosamente, 75% dos pacientes com alta expressão de Ki-67 ( > 10%) não eram cirróticos. Em conclusão: 1. Nesta casuística cirúrgica, o CHC relacionado com DHGNA foi encontrado em não cirróticos em 42% dos casos, com nível normal de alfafetoproteína em 62%. 2. Os marcadores histológicos de \"CHC esteatohepatítico\" estiveram altamente prevalentes. 3. A imunoexpressão positiva de K19 e Ki-67 ocorreu em apenas 21% dos pacientes, o que pode sugerir que o CHC na síndrome metabólica pode ser preferencialmente \"um subtipo inflamatório e não proliferativo de CHC\" / The increase incidence of hepatocellular carcinoma (HCC) has been attributed to the increase in obesity, diabetes and non-alcoholic fatty liver disease. (NAFLD), and several histopathological and immunohistochemical aspects are still to be better clarified. The aim of this study is to assess clinical and pathological aspects of patients with HCC secondary to NAFLD as well as to related to immunohistochemical markers of proliferative class. We evaluated 35 HCC specimens from 21 patients diagnosed with NAFLD undergoing liver resection (12 patients) or liver transplantation (8 patients) or both (1 patient) from 2005 to 2015. Demographic, clinical and biochemical data were related to histological features and immunohistochemical reactivity for K19, marking characteristics of progenitor cells and Ki-67, marking the cells in cell cycle. A total of 35 nodules were detected from 21 patients. Cirrhosis was present in 12 cases (7 F4A x 4F4B x 1F4C according to Laennec Staging) and 9 patients did not have cirrhosis (NAFLD staging: F2: 6pts, F3=3pts). Ages ranged from 50 to 77 years and 16 patients were male (76%). Sixteen patients (76%) had diabetes mellitus, 17 patients (81%) had arterial hypertension and 19 patients (90%) had BMI above 25kg/m2. HCC occurred in 8 patients Child A, 4 Child B and in 9 patients without cirrhosis. Alpha-fetoprotein level was normal in 13 (62%) patients. Among the histological criteria, 25 (70%) nodules were diagnosed as \"steatohepatitic HCC\". Although 63% were poorly differentiated (G.3/ G.4) according to Edmondson & Steiner (1954), only 21% presented high levels of Ki-67 ( > 10%). In the case of K19, 21% of patients presented positive expression (> 5%), and was associated with greater intratumoral inflammation (G 2/3). Interestingly, 75% of the patients with high Ki67 expression ( > 10%) were non-cirrhotic. In conclusion: 1. In this surgical series, HCC related to NAFLD was found in non-cirrhotic patients in 42% of cases, with a normal level of alpha-fetoprotein in 62%. 2. Histological markers of \"steatohepatitic HCC\" were highly prevalent. 3. Positive immunoexpression of K19 and Ki-67 occurred in only 21% of patients, which might suggest that HCC in metabolic syndrome might be preferentially \"an inflammatory, non-proliferative subtype of HCC\"
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The influence of acid and direct azo dyes and their intermediates on the degradation of wool keratin : the characterisation by yarn strength measurements of the degradation of wool under conditions relevant to dyeing and of the keratin degradation products, by fractionation, electrophoresis and amino acid analysisMcComish, John January 1981 (has links)
The degradation of wool keratin under conditions relevant to those of wool dyeing was investigated using the techniques of gel permeation chromatography (GPC), ion exchange gel chromatography, and amino acid analysis. Physical testing of the treated and untreated wool was also carried out to determine the physical changes occurring, parameters used being percentage elongation at the break, and the breaking strain of the fibre. Samples of wool keratin were immersed in various aqueous solutions at 1000C for 24 hours and the filtered, aqueous, oxidised extracts were analysed* The solutions used varied only in the dye, or dye intermediate present in the treatment solution. All treatment baths contained 10% owf 1.02 x 10 -2 MSulphuric VI acid; 10%owf 7.04x 10 -3 MSodium sulphate VI ; A 100 :1 liquor ratio was used in each case. Some of the dye intermediates showed a marked catalytic effect, particularly in their effect on breaking strain, a decrease of 40% in some cases. The GPC profiles of the extracted proteins were examined in detail and compared against previous workers' results. An explanation of the behaviour of the dyes and intermediates was proposed. The amino acid composition data of the extracted and fractionated proteins were compared against various morphological components extracted by other workers, as was the total gelatin obtained from each treatment.
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Desenvolvimento e an?lise de material comp?sito a base de penas de frango (fibras de queratina-KF) e matriz de poli?ster insaturadoGalv?o, Alcione Olinto 26 August 2011 (has links)
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Previous issue date: 2011-08-26 / Use of natural fibres as a reinforcement material in the manufacture of composites show a series of advantages: availability, biodegradability, low weight and regeneration in relation to synthetic fibres, thus justifying its utilization. In the present research work, composites were developed with chicken feathers (KF), using unsaturated polyester resin as matrix, for diversified applications, mainly in the furniture/timber industry.At present, in Brazil the chicken feathers are used as part of the animal feed, even though this material possesses low aggregated value. The chicken feathers are hollow, light and resistant. After washing with water at room temperature, a part of the chicken feathers were treated with 2% NaOH. Composites were manufactured using treated and untreated chicken feathers with unsaturated orthothalic polyester resin and 1% peroxide as catalyser, obtained in the commerce. Samples with size 150x25x3 mm for mechanical tests were cut by laser in the composite plate. Mechanical analyses were carried out in the Laborat?rio de Metais e Ensaios Mec?nicos UFRN. All the analyses were in accordance with ASTM standards. SEM analyses were also carried out on the samples.In the analyses of the results obtained, it was observed that the composites made with untreated chicken feathers showed better results (Traction 11.406 MPa and 9.107 MPa Bending 34.947 and 20.918 MPa for samples with and without treatment respectively) compared to the composite with treated feathers. Very low values of the water absorption results, evidenced the impermeability characteristic of the feathers. From the SEM images, the structure, fracture and the fibre/matrix adsorption can be evidenced. In the flammability test, it was observed that despite the feathers having sulfur as a constituent, natural inhibitor of flame, no burning support of the composites, because the manufacturing process of the composite / O uso de fibras naturais como refor?o em comp?sitos apresenta uma s?rie de vantagens: abund?ncia, biodegradabilidade, baixo peso e regenerabilidade em rela??o ?s fibras sint?ticas, justificando sua utiliza??o. Na presente pesquisa foram desenvolvidos comp?sitos com penas de frango (KF), utilizando resina de poli?ster n?o-saturado como matriz. Atualmente, no Brasil, as penas de frango s?o utilizadas como parte de ra??o animal, por?m este produto possui um baixo valor agregado. As penas s?o um material oco, leve e resistente. Ap?s a lavagem com ?gua em temperatura ambiente uma parte das penas foi tratada com 2% de NaOH. Foram fabricados dois comp?sitos, um com as penas tratadas e outro sem tratamento, usando o processo de molde fechado por compress?o, utilizando a resina de poli?ster ortoft?lica e 1% de per?xido MEK (per?xido de metil etil cetona) como iniciador, adquiridos no com?rcio local. As amostras com 150x25x3 mm de tamanho para os ensaios mec?nicos foram cortadas a laser na placa do comp?sito. Os ensaios de tra??o e flex?o em tr?s pontos foram realizados no Laborat?rio de Metais e Ensaios Mec?nicos - UFRN. Todas as an?lises estavam de acordo com as normas da ASTM. As amostras resultantes dos ensaios mec?nicas foram avaliadas no MEV. Com base nas observa??es dos resultados nos ensaios mec?nicos, (Tra??o 11,2 Mpa e 8,3 Mpa; Flex?o 34,9 Mpa e 22,9 MPa para as amostras sem e com tratamento respectivamente) observou-se que os comp?sitos refor?ados com as penas sem tratamento apresentaram um melhor comportamento quando foram expostos a carregamentos tanto de tra??o quanto de flex?o. O ensaio de absor??o evidenciou nos valores de absor??o de ?gua, uma das caracter?sticas da prote?na existente nas penas, a queratina, a sua capaciade de impermiabiliza??o a ?gua. Nas imagens do MEV foi poss?vel verificar a estrutura da pena, as regi?es de ruptura do comp?sito e a ades?o fibra/matriz. No ensaio de inflamabilidade, observou-se que apesar das penas terem como constituinte o enxofre, inibidor natural de chama, n?o houve a susten??o da queima nos comp?sitos, devido o processo de fabrica??o do comp?sito
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Caracterização clínica e histológica do carcinoma hepatocelular (CHC) secundário à doença hepática gordurosa não alcoólica (DGHNA) / Clinical and histopathological characterization of hepatocellular carcinoma (HCC) in non-alcoholic fatty liver disease (NAFLD)Priscila Brizolla de Campos 06 November 2017 (has links)
O aumento na incidência do carcinoma hepatocelular (CHC) tem sido atribuído ao aumento da obesidade, diabetes e doença hepática gordurosa não alcoólica. (DHGNA), estando ainda por ser melhor esclarecidos vários aspectos histopatológicos e imuno-histoquímicos. O objetivo deste estudo é avaliar aspectos clínicos e patológicos de pacientes com CHC secundário a DHGNA, assim como relacionar a marcadores imuno-histoquímicos de classe proliferativa. Avaliamos 35 espécimes de CHC de 21 pacientes diagnosticados com DHGNA submetidos a ressecção hepática (12 pacientes) ou a transplante hepático (8 pacientes) ou ambos (1 paciente), de 2005 a 2015. Dados demográficos, clínicos e bioquímicos foram relacionados a características histológicas e reatividade imuno-histoquímica para K19, marcando características de células progenitoras e Ki-67, marcando as células em ciclo celular. Um total de 35 nódulos foram detectados em 21 pacientes. A cirrose estava presente em 12 casos (7 F4A x 4F4B x 1F4C de acordo com estadiamento de Laennec) e 9 pacientes não apresentavam cirrose (estadiamento DHGNA: F2: 6pts, F3 = 3pts). A idade variou de 50 a 77 anos e 16 pacientes eram do sexo masculino (76%). Dezesseis pacientes (76%) apresentavam diabetes mellitus, 17 pacientes (81%) apresentavam hipertensão arterial e 19 pacientes (90%) tinham IMC superior a 25 kg / m2. O CHC ocorreu em 8 pacientes CHILD A, 4 CHILD B e em 9 pacientes sem cirrose. O nível de alfa-fetoproteína foi normal em 13 (62%) pacientes. Dentre os critérios histológicos, 25 (70%) nódulos foram diagnosticados como \"CHC esteatohepatítico\". Embora 63% tenham sido pouco diferenciados (G.3/G.4) de acordo com Edmondson & Steiner (1954), apenas 21% apresentaram níveis elevados de Ki-67 ( > 10%). No caso da K19, também 21% dos pacientes apresentaram expressão positiva ( > 5%), e foi associado a maior inflamação intratumoral (G 2/3). Curiosamente, 75% dos pacientes com alta expressão de Ki-67 ( > 10%) não eram cirróticos. Em conclusão: 1. Nesta casuística cirúrgica, o CHC relacionado com DHGNA foi encontrado em não cirróticos em 42% dos casos, com nível normal de alfafetoproteína em 62%. 2. Os marcadores histológicos de \"CHC esteatohepatítico\" estiveram altamente prevalentes. 3. A imunoexpressão positiva de K19 e Ki-67 ocorreu em apenas 21% dos pacientes, o que pode sugerir que o CHC na síndrome metabólica pode ser preferencialmente \"um subtipo inflamatório e não proliferativo de CHC\" / The increase incidence of hepatocellular carcinoma (HCC) has been attributed to the increase in obesity, diabetes and non-alcoholic fatty liver disease. (NAFLD), and several histopathological and immunohistochemical aspects are still to be better clarified. The aim of this study is to assess clinical and pathological aspects of patients with HCC secondary to NAFLD as well as to related to immunohistochemical markers of proliferative class. We evaluated 35 HCC specimens from 21 patients diagnosed with NAFLD undergoing liver resection (12 patients) or liver transplantation (8 patients) or both (1 patient) from 2005 to 2015. Demographic, clinical and biochemical data were related to histological features and immunohistochemical reactivity for K19, marking characteristics of progenitor cells and Ki-67, marking the cells in cell cycle. A total of 35 nodules were detected from 21 patients. Cirrhosis was present in 12 cases (7 F4A x 4F4B x 1F4C according to Laennec Staging) and 9 patients did not have cirrhosis (NAFLD staging: F2: 6pts, F3=3pts). Ages ranged from 50 to 77 years and 16 patients were male (76%). Sixteen patients (76%) had diabetes mellitus, 17 patients (81%) had arterial hypertension and 19 patients (90%) had BMI above 25kg/m2. HCC occurred in 8 patients Child A, 4 Child B and in 9 patients without cirrhosis. Alpha-fetoprotein level was normal in 13 (62%) patients. Among the histological criteria, 25 (70%) nodules were diagnosed as \"steatohepatitic HCC\". Although 63% were poorly differentiated (G.3/ G.4) according to Edmondson & Steiner (1954), only 21% presented high levels of Ki-67 ( > 10%). In the case of K19, 21% of patients presented positive expression (> 5%), and was associated with greater intratumoral inflammation (G 2/3). Interestingly, 75% of the patients with high Ki67 expression ( > 10%) were non-cirrhotic. In conclusion: 1. In this surgical series, HCC related to NAFLD was found in non-cirrhotic patients in 42% of cases, with a normal level of alpha-fetoprotein in 62%. 2. Histological markers of \"steatohepatitic HCC\" were highly prevalent. 3. Positive immunoexpression of K19 and Ki-67 occurred in only 21% of patients, which might suggest that HCC in metabolic syndrome might be preferentially \"an inflammatory, non-proliferative subtype of HCC\"
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Expressão do transcrito da citoqueratina 19 (CK-19) na fração mononuclear do sangue periférico em pacientes com adenocarcinoma de próstata / Cytokeratin 19 expression in the peripheral blood mononuclear fraction of prostate cancer patientsMarcos Tobias Machado 04 March 2008 (has links)
Introdução: O emprego da técnica de RT-PCR na detecção da expressão de genes epiteliais como a CK-19 no sangue periférico de pacientes com câncer de próstata é uma oportunidade para avaliar a progressão tumoral ao nível molecular na ausência de doença clinicamente mensurável. Material e métodos: Inicialmente 10 pacientes com nível sérico de PSA< 2ng/ml e toque retal sugestivo de hiperplasia prostática benigna foram incluídos como grupo controle através de coleta de sangue única para dosagem do transcrito da CK-19. Subsequentemente,foram seguidos de maneira prospectiva 44 pacientes com câncer de próstata (21 com doença localizada e 23 com doença metastática), com coleta de sangue seriada a cada 3 meses por 18 meses. Foi medida a expressão sérica do transcrito da CK-19 por RT-PCR na fração leucocitária do sangue periférico e correlacionada aos níveis séricos de PSA e outras variáveis clinicas e patológicas. Resultados: Nenhum de 10 pacientes controles apresentou expressão do transcrito da CK-19 no sangue periférico. Nos pacientes com câncer de próstata a expressão do transcrito da CK-19 na entrada do estudo não se correlacionou com o escore de Gleason, estádio clínico e os níveis séricos de DHL, Hemoglobina, PSA, Fosfatase alcalina ou Testosterona. A presença de pelo menos uma dosagem positiva de CK-19 durante o seguimento se correlacionou com o tempo para a progressão bioquímica do PSA na amostra como um todo(p=0,049) e no subgrupo com doença metastática(p=0,032). Conclusão: Não houve expressão do transcrito da CK-19 na fração mononuclear do sangue periférico em homens do grupo controle. Nos pacientes com câncer de próstata não houve correlação entre a expressão do transcrito da CK-19 na entrada do estudo e as principais variáveis clínicas e patológicas de prognóstico. Nos pacientes com câncer de próstata, a presença de pelo menos uma dosagem positiva para o transcrito da CK-19 no seguimento se correlacionou com um menor tempo para recidiva bioquímica , especialmente no subgrupo de pacientes com doença metastática tratados com hormonioterapia / Background: The recent introduction of sensitive RT-PCR-based techniques for the detection of epithelial antigen expression, such as CK-19,in the peripheral blood of prostate cancer patients may provide an opportunity to evaluate early tumor progression at the molecular level, even in the absence of measurable disease. Methods: Ten men with PSA <2ng/ml and digital rectal examination suggestive for benign prostatic hyperplasia were included as controls by only one colleted blood sample to measure of CK-19 transcript. We also studied serially collected blood samples of 44 patients with prostate cancer (21 with localized and 23 with metastatic disease) every three months for 18 months. We measured CK-19 transcript expression in the peripheral blood mononuclear fraction (PBMN) of these samples by RT-PCR and correlated it with PSA values and other clinical and pathologic variables. Results: None of the 10 normal control men showed CK-19 transcript expression in their PBMN. In the patients with prostate cancer, CK-19 transcript positivity at entry did not correlate with Gleason score, clinical stage, DHL, hemoglobin level, PSA, alkaline phosphatase or testosterone levels. Having at least one positive CK- 19 result during follow up correlated significantly with time to PSA progression in all coorte (p = 0.049) and in the subgroup of metastatic disease (p = 0.032). Conclusion: There are no expression of CK-19 transcript in the PBMN of control men. In prostate cancer patients there are no correlation between CK-19 at entry and the most important clinical and pathological prognostic variables. Prostate cancer patients that had at least one CK-19 transcript expression in the peripheral blood present lower time to PSA progression, specially metastatic patients receiving hormonal therapy
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