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The Global ETD Search service is a free service for researchers
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Showing 31 to 34 of 34 (0.065 seconds)Spelling suggestions: "subject:"ductal carcinoma"" "subject:"structal carcinoma""
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Identificação de fatores diabetogênicos associados ao adenocarcinoma de pâncreas / Identification of diabetogenic factors associated to pancreatic adenocarcinomaSouza, Jean Jorge Silva de 05 September 2006 (has links)
Diabetes melito ou intolerância à glicose estão presentes em até 80% dos pacientes com adenocarcinoma de pâncreas. Portadores desta neoplasia têm resistência à insulina e alteração na secreção de insulina em resposta à glicose, o que pode levar ao aparecimento ou piora de diabetes. Para identificar genes diferencialmente expressos, que podem representar fatores diabetogênicos produzidos pelo adenocarcinoma de pâncreas, utilizou-se a comparação de microarranjos de oligonucleotídeos hibridizados com RNA complementar (cRNA) de tumores pancreáticos de pacientes com e sem diabetes melito no pré-operatório. Uma lâmina foi hibridizada com cRNA de dois pacientes portadores de diabetes melito, e outra com cRNA de dois pacientes com tolerância normal à glicose pelo teste oral. Considerando a expressão ajustada para os controles internos dos microarranjos, 293 genes estavam duas ou mais vezes mais expressos na lâmina dos portadores de diabetes melito; destes, 25 genes estavam pelo menos cinco vezes mais expressos. Duzentos e noventa e sete genes estavam pelo menos duas vezes mais expressos na lâmina dos pacientes com tolerância normal à glicose, dos quais 54 genes estavam cinco ou mais vezes mais expressos nestes indivíduos. Dos genes mais expressos nos tumores dos indivíduos portadores de diabetes melito, três deles, FAM3D, do inglês Family with Sequence Similarity number 3 member D, neuropeptídeo Y (NPY), e proteína de ligação do cálcio S100A8, foram estudados por reação em cadeia da polimerase em tempo real. A expressão do FAM3D foi 4070 (1000-37588) nas amostras de tumores de pacientes com diabetes melito, contra 109 (10-1112) nas de pacientes não-diabéticos (com intolerância à glicose ou com tolerância normal à glicose) (p<0,05). A expressão do NPY foi 0,46 (0,19-0,91) nos tumores dos portadores de diabetes, contra 0,32 (0,21- 0,58) nos tumores dos não-diabéticos (p = NS). Quanto à expressão de S100A8, foi 0,52 (0,27-0,60) nos tumores dos diabéticos, e 0,34 (0,16-1,44) nos não-diabéticos. Estudo imunohistoquímico mostrou que o FAM3D está expresso no núcleo e no citoplasma de células de tumores pancreáticos, tanto de indivíduos com diabetes melito quanto de não-diabéticos, assim como no citoplasma de células de ilhotas pancreáticas e de células ductais normais do pâncreas. Concluímos que o FAM3D é uma proteína expressa em tecido pancreático normal e tumoral, e que existe maior conteúdo do mRNA do FAM3D nos adenocarcinomas de pâncreas de portadores de diabetes melito do que nos de não-diabéticos. / Pancreatic ductal adenocarcinoma is closely related to diabetes mellitus; up to 80% of pancreas adenocarcinoma patients have diabetes or impaired glucose tolerance. Pancreas adenocarcinoma patients have both insulin resistance and altered insulin secretion in response to glucose, and impaired glucose metabolism has been reported in muscle of tumor patients, involving glycogen metabolism and post-receptor insulin signaling. But despite progress in research about this issue, precise mechanisms responsible for the interaction of pancreatic adenocarcinoma and diabetes mellitus remain unknown. The aim of this study was to identify differentially expressed genes between pancreas adenocarcinoma of patients who had and who did not have diabetes mellitus before surgery. Clinical and laboratorial data of 33 patients with pancreatic adenocarcinoma were evaluated, and tumor gene expression was analyzed by microarray method between two patients who had diabetes mellitus and two who did not have glycemic homeostasis impairment, and later used quantitative reverse transcriptase polymerase chain reaction (RT-qPCR) in twelve tumor fragments mRNA to confirm obtained data. Pancreatic adenocarcinoma patients who had diabetes mellitus had higher HOMA-IR (p < 0.05) and a trend to lower HOMA-beta indexes than non-diabetic patients. icroarray revealed 293 genes twice more expressed in the pool of diabetic patients as compared to the pool of normal glucose tolerance patients. Of these, 25 were five times more expressed in diabetic patients? pancreatic adenocarcinomas. Three genes were chosen for RT-qPCR: Family with Sequence Similarity number 3 member D (FAM3D), neuropeptide Y (NPY), and calcium-binding protein S100A8. FAM3D expression was 4070 (1000-37588) in diabetic patients tumors versus 109 (10-1112) in non-diabetic (impaired glucose and normal glucose tolerance) patients? tumors (p<0.05). NPY expression was 0.46 (0.19- 0.91) in diabetic patients and 0.32 (0.21-0.58) in non-diabetic patients? tumors (p=NS). Calcium-binding protein S100A8 expression was 0.52 (0.27-0.60) in diabetic and 0.34 (0.16-1.44) in non-diabetic patients (p=NS). Immunohistochemistry revealed that FAM3D protein was expressed in pancreatic adenocarcinoma cells in a diffuse nuclear and cytoplasmic pattern. It was also expressed in the cytoplasm of islets of Langerhans and normal pancreatic ducts cells. The present study indicates that cytokine-like FAM3D protein is expressed in normal and tumoral pancreatic tissue, and that FAM3D mRNA content is higher in pancreatic adenocarcinoma in diabetic than in non-diabetic patients.
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Identificação de fatores diabetogênicos associados ao adenocarcinoma de pâncreas / Identification of diabetogenic factors associated to pancreatic adenocarcinomaJean Jorge Silva de Souza 05 September 2006 (has links)
Diabetes melito ou intolerância à glicose estão presentes em até 80% dos pacientes com adenocarcinoma de pâncreas. Portadores desta neoplasia têm resistência à insulina e alteração na secreção de insulina em resposta à glicose, o que pode levar ao aparecimento ou piora de diabetes. Para identificar genes diferencialmente expressos, que podem representar fatores diabetogênicos produzidos pelo adenocarcinoma de pâncreas, utilizou-se a comparação de microarranjos de oligonucleotídeos hibridizados com RNA complementar (cRNA) de tumores pancreáticos de pacientes com e sem diabetes melito no pré-operatório. Uma lâmina foi hibridizada com cRNA de dois pacientes portadores de diabetes melito, e outra com cRNA de dois pacientes com tolerância normal à glicose pelo teste oral. Considerando a expressão ajustada para os controles internos dos microarranjos, 293 genes estavam duas ou mais vezes mais expressos na lâmina dos portadores de diabetes melito; destes, 25 genes estavam pelo menos cinco vezes mais expressos. Duzentos e noventa e sete genes estavam pelo menos duas vezes mais expressos na lâmina dos pacientes com tolerância normal à glicose, dos quais 54 genes estavam cinco ou mais vezes mais expressos nestes indivíduos. Dos genes mais expressos nos tumores dos indivíduos portadores de diabetes melito, três deles, FAM3D, do inglês Family with Sequence Similarity number 3 member D, neuropeptídeo Y (NPY), e proteína de ligação do cálcio S100A8, foram estudados por reação em cadeia da polimerase em tempo real. A expressão do FAM3D foi 4070 (1000-37588) nas amostras de tumores de pacientes com diabetes melito, contra 109 (10-1112) nas de pacientes não-diabéticos (com intolerância à glicose ou com tolerância normal à glicose) (p<0,05). A expressão do NPY foi 0,46 (0,19-0,91) nos tumores dos portadores de diabetes, contra 0,32 (0,21- 0,58) nos tumores dos não-diabéticos (p = NS). Quanto à expressão de S100A8, foi 0,52 (0,27-0,60) nos tumores dos diabéticos, e 0,34 (0,16-1,44) nos não-diabéticos. Estudo imunohistoquímico mostrou que o FAM3D está expresso no núcleo e no citoplasma de células de tumores pancreáticos, tanto de indivíduos com diabetes melito quanto de não-diabéticos, assim como no citoplasma de células de ilhotas pancreáticas e de células ductais normais do pâncreas. Concluímos que o FAM3D é uma proteína expressa em tecido pancreático normal e tumoral, e que existe maior conteúdo do mRNA do FAM3D nos adenocarcinomas de pâncreas de portadores de diabetes melito do que nos de não-diabéticos. / Pancreatic ductal adenocarcinoma is closely related to diabetes mellitus; up to 80% of pancreas adenocarcinoma patients have diabetes or impaired glucose tolerance. Pancreas adenocarcinoma patients have both insulin resistance and altered insulin secretion in response to glucose, and impaired glucose metabolism has been reported in muscle of tumor patients, involving glycogen metabolism and post-receptor insulin signaling. But despite progress in research about this issue, precise mechanisms responsible for the interaction of pancreatic adenocarcinoma and diabetes mellitus remain unknown. The aim of this study was to identify differentially expressed genes between pancreas adenocarcinoma of patients who had and who did not have diabetes mellitus before surgery. Clinical and laboratorial data of 33 patients with pancreatic adenocarcinoma were evaluated, and tumor gene expression was analyzed by microarray method between two patients who had diabetes mellitus and two who did not have glycemic homeostasis impairment, and later used quantitative reverse transcriptase polymerase chain reaction (RT-qPCR) in twelve tumor fragments mRNA to confirm obtained data. Pancreatic adenocarcinoma patients who had diabetes mellitus had higher HOMA-IR (p < 0.05) and a trend to lower HOMA-beta indexes than non-diabetic patients. icroarray revealed 293 genes twice more expressed in the pool of diabetic patients as compared to the pool of normal glucose tolerance patients. Of these, 25 were five times more expressed in diabetic patients? pancreatic adenocarcinomas. Three genes were chosen for RT-qPCR: Family with Sequence Similarity number 3 member D (FAM3D), neuropeptide Y (NPY), and calcium-binding protein S100A8. FAM3D expression was 4070 (1000-37588) in diabetic patients tumors versus 109 (10-1112) in non-diabetic (impaired glucose and normal glucose tolerance) patients? tumors (p<0.05). NPY expression was 0.46 (0.19- 0.91) in diabetic patients and 0.32 (0.21-0.58) in non-diabetic patients? tumors (p=NS). Calcium-binding protein S100A8 expression was 0.52 (0.27-0.60) in diabetic and 0.34 (0.16-1.44) in non-diabetic patients (p=NS). Immunohistochemistry revealed that FAM3D protein was expressed in pancreatic adenocarcinoma cells in a diffuse nuclear and cytoplasmic pattern. It was also expressed in the cytoplasm of islets of Langerhans and normal pancreatic ducts cells. The present study indicates that cytokine-like FAM3D protein is expressed in normal and tumoral pancreatic tissue, and that FAM3D mRNA content is higher in pancreatic adenocarcinoma in diabetic than in non-diabetic patients.
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Subtle Controllers: MicroRNAs Drive Pancreatic Tumorigenesis and Progression: A DissertationQuattrochi, Brian J. 13 April 2015 (has links)
Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal malignancies in the United States, with an average five-year survival rate of just 6.7%. One unifying aspect of PDAC is mutational activation of the KRAS oncogene, which occurs in over 90% of PDAC. Therefore, inhibiting KRAS function is likely an effective therapeutic strategy for this disease, and current research in our lab and others is focused on identifying downstream effectors of KRAS signaling that may be therapeutic targets. miRNAs are powerful regulators of gene expression that can behave as oncogenes or tumor suppressors. Dysregulation of miRNA expression is commonly observed in human tumors, including PDAC. The mir-17~92 cluster of miRNAs is an established oncogene in a variety of tumor contexts, and members of the mir-17~92 cluster are upregulated in PDAC, but their role has not been explored in vivo. This dissertation encompasses two studies exploring the role of miRNAs in pancreatic tumorigenesis. In Chapter II, I demonstrate that deletion of the mir-17~92 cluster impairs PDAC precursor lesion formation and maintenance, and correlates with reduced ERK signaling in these lesions. mir-17~92 deficient tumors and cell lines are also less invasive, which I attribute to the loss of the miR-19 family of miRNAs. In Chapter III, I find that Dicer heterozygosity inhibits PDAC metastasis, and that this phenotype is attributable to an increased sensitivity to anoikis. Ongoing experiments will determine whether shifts in particular miRNA signatures between cell lines can be attributed to this phenotype. Together these findings illustrate the importance of miRNA biogenesis, and the mir-17~92 cluster in particular, in supporting PDAC development and progression.
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Role of Ring1B in ephitelial to mesenchimal transition, invasion and migration of mammary epithelial cellsBosch Gutiérrez, Almudena 21 December 2009 (has links)
The Polycomb group (PcG) family of proteins form chromatin-modifying complexes essential for embryonic development, and stem cell renewal and are commonly deregulated in cancer. There are several reports that address the possible implication of PcG proteins in tumor progression and metastasis, but very little is known about the specific role of these proteins in tumor progression and invasion. On the other hand, the molecular processes of the worst cancer prognosis, metastasis, which leads to an incurable disease, are yet incompletely elucidated. Here we show a role for Ring1B, a PcG protein, in three processes related to metastasis: in the Epithelial-mesenchymal transition (EMT), a critical morphogenic event that occurs during embryonic development and during the progression of various epithelial tumors, an in the migration and the invasion of mammary epithelial cells. / Las proteínas del grupo Polycomb (PcG) forman complejos modificadores de la cromatina esenciales en el desarrollo embrionario y en la renovación de las células madre, y su desregulación ha sido asociada al cáncer. Varios estudios muestran la posible implicación de las proteínas de PcG en la progresión tumoral y en la metástasis, pero a pesar de ello se sabe muy poco de los procesos moleculares en los que estas proteínas están participando. Por otro lado, los procesos moleculares responsables del peor pronóstico en cáncer, la metástasis, que continua siendo una enfermedad incurable, siguen sin estar completamente elucidados. En esta disertación mostramos el papel de Ring1B, una proteína del PcG, en tres procesos implicados en la metástasis: en la transición epitelio-mesénquima (EMT), un proceso morfogénico crítico en el desarrollo embrionario y durante la progresión de varios cánceres epiteliales, y en la migración y la invasión de las células epiteliales mamarias.
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