To see the other types of publications on this topic, follow the link: Oncogenes.
Dissertations / Theses on the topic 'Oncogenes'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 dissertations / theses for your research on the topic 'Oncogenes.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse dissertations / theses on a wide variety of disciplines and organise your bibliography correctly.
1
SCHAFFHAUSER, CHRISTOPHE. "Les oncogenes viraux." Strasbourg 1, 1987. http://www.theses.fr/1987STR10692.
Full text
2
Pandey, Vijay. "Secreted oncogenes in endometrial carcinoma." Thesis, University of Auckland, 2010. http://hdl.handle.net/2292/8195.
Full textAbstract:
Endometrial carcinoma is the most common malignancy of the female reproductive tract and the incidence in developed countries is rising. Poor survival of late stage and recurrent endometrial carcinoma patients, particularly with an aggressive histologic subtype, necessitate the development of new therapeutic modalities for advanced stage and recurrent endometrial carcinoma. Recent published data have demonstrated elevated levels of human growth hormone (hGH) in endometriosis and endometrial adenocarcinoma. Herein, I demonstrate that autocrine production of hGH can enhance the in vitro and in vivo oncogenic potential of endometrial carcinoma cells. Forced expression of hGH in endometrial carcinoma cell lines RL95-2 and AN3 resulted in an increased total cell number through enhanced cell cycle progression and decreased apoptotic cell death. In addition, autocrine hGH expression in endometrial carcinoma cells promoted anchorage-independent growth and increased cell migration/invasion in vitro. In a xenograft model of human endometrial carcinoma, autocrine hGH enhanced tumor size and progression. Changes in endometrial carcinoma cell gene expression stimulated by autocrine hGH was consistent with the altered in vitro and in vivo behavior. Functional antagonism of hGH in wild-type RL95-2 cells significantly reduced cell proliferation, cell survival, and anchorage- independent cell growth. These studies demonstrate a functional role for autocrine hGH in the development and progression of endometrial carcinoma and indicate potential therapeutic relevance of hGH antagonism in the treatment of endometrial carcinoma. I further provided evidence for the functional role of the neurotrophic factor artemin (ARTN) in progression of endometrial carcinoma. Increased ARTN protein expression was observed in endometrial carcinoma and ARTN protein expression in endometrial carcinoma was significantly associated with higher tumor grade and invasiveness. Forced expression of ARTN in endometrial carcinoma cells significantly increased total cell number as a result of enhanced cell cycle progression and cell survival. In addition, forced expression of ARTN significantly enhanced anchorage-independent growth and invasiveness of endometrial carcinoma cells. Moreover, forced expression of ARTN increased tumor size in xenograft models and produced highly proliferative, poorly differentiated and invasive tumors. The ARTN stimulated increases in oncogenicity and invasion were mediated by increased expression and activity of AKT1. siRNA mediated depletion or antibody inhibition of ARTN significantly reduced oncogenicity and invasion of endometrial carcinoma cells. Thus, inhibition of ARTN may be considered as a potential therapeutic strategy to retard progression of endometrial carcinoma. Furthermore, I demonstrated that ARTN stimulates the oncogenicity and invasiveness of endometrial carcinoma cells. Herein, I demonstrate that ARTN modulates the sensitivity of endometrial carcinoma cells to agents used to treat latestage endometrial carcinoma. Forced expression of ARTN in endometrial carcinoma cells decreased sensitivity to doxorubicin and paclitaxel. Accordingly, depletion of ARTN by small interfering RNA or functional inhibition of ARTN with antibodies significantly increased sensitivity of endometrial carcinoma cells to doxorubicin and paclitaxel. Forced expression of ARTN in endometrial carcinoma cells abrogated doxorubicininduced G2-M arrest and paclitaxel-induced apoptosis. ARTN increased CD24 expression in endometrial carcinoma cells by transcriptional up-regulation, and CD24 was partially correlated to ARTN expression in endometrial carcinoma. Forced expression of CD24 in endometrial carcinoma cells stimulated cell proliferation and oncogenicity, enhanced cell invasion, and decreased sensitivity to doxorubicin and paclitaxel. Depletion of CD24 in endometrial carcinoma cells abrogated ARTNstimulated resistance to doxorubicin and paclitaxel. ARTN-stimulated resistance to doxorubicin and paclitaxel in endometrial carcinoma cells is therefore mediated by the specific regulation of CD24. Functional inhibition of ARTN may therefore be considered as an adjuvant therapeutic approach to improve the response of endometrial carcinoma to specific chemotherapeutic agents.
3
Scully, Jaqueline Susan. "Insertion of oncogenes into mouse mammary epithelium." Thesis, University of Cambridge, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.315287.
Full text
4
Williams, Alistair Robert William. "Expression of oncogenes in human colorectal neoplasms." Thesis, University of Edinburgh, 1988. http://hdl.handle.net/1842/19415.
Full text
5
Imler, Jean-Luc. "Identification d'une cible transcriptionnelle pour les oncogenes." Université Louis Pasteur (Strasbourg) (1971-2008), 1988. http://www.theses.fr/1988STR13193.
Full text
6
Gerlinger, Emmanuel. "Proto-oncogenes et developpement embryonnaire : etude bibliographique." Université Louis Pasteur (Strasbourg) (1971-2008), 1989. http://www.theses.fr/1989STR1M202.
Full text
7
Jaggi, Rolf. "Interaction of oncogenes with the glucocorticoid receptor /." Bern, 1989. http://www.ub.unibe.ch/content/bibliotheken_sammlungen/sondersammlungen/dissen_bestellformular/index_ger.html.
Full text
8
Kemble, David J. "A biochemical study on the regulation of the SRC and FGFR family of protein tyrosine kinases /." View online ; access limited to URI, 2009. http://0-digitalcommons.uri.edu.helin.uri.edu/dissertations/AAI3367994.
Full text
9
Jenkins, Brendan John. "Activating point mutations in the common ?gb?s[beta]-subunit of the human GM-CSF, IL-3 and IL-5 receptors : implications for receptor function and role in disease / by Brendan John Jenkins." Title page, contents and summary only, 1998. http://web4.library.adelaide.edu.au/theses/09PH/09phj518.pdf.
Full text
10
Bartel, Courtney A. "Novel Roles for FAM83 Oncogenes in Breast Cancer." Case Western Reserve University School of Graduate Studies / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=case1512682785418426.
Full text
11
Collins-De, Peyer Laurence. "Screening of a rat thymus and a human hippocampus cDNA library for a novel fyn-related oncogene." Thesis, Hong Kong : University of Hong Kong, 1999. http://sunzi.lib.hku.hk/hkuto/record.jsp?B21253870.
Full text
12
Chen, Leilei. "Identification and characterization of CHD1L in hepatocellular carcinoma." Click to view the E-thesis via HKUTO, 2010. http://sunzi.lib.hku.hk/hkuto/record/B44139810.
Full text
13
McCarthy, E. C. "Analysis of the subcellular and tissue-specific expression of the tumoursuppressor protein PTEN in Drosophila : regulation and function." Thesis, University of Kent, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.270708.
Full text
14
Foster, Keith. "Molecular genetic analysis of non-familial renal cell carcinoma." Thesis, University College London (University of London), 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.289811.
Full text
15
Morland, Sarah J. "A molecular genetic analysis of endometriosis and the association with ovarian cancer." Thesis, University of Southampton, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.323802.
Full text
16
McKibbon, Valerie Lynn. "Dopaminergic and glutamatergic mechanisms influence immediate-early gene expression in rodent brain." Thesis, University of Cambridge, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.283934.
Full text
17
Xu, Zhi. "Yes associated protein (YAP) in hepatocellular carcinoma oncogenic functions and molecular targeting /." Click to view the E-thesis via HKUTO, 2009. http://sunzi.lib.hku.hk/hkuto/record/B43278589.
Full text
18
Scheijen, Gemma Petronella Helena. "Characterization of the Myc collaborating oncogenes Bmi1 and Gfi1." [S.l. : Amsterdam : s.n.] ; Universiteit van Amsterdam [Host], 2001. http://dare.uva.nl/document/84673.
Full text
19
Sinha, S. "The role of oncogenes in experimental rat liver cancer." Thesis, Open University, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.234898.
Full text
20
Abram, Clare L. "Expression of oncogenes in mouse mammary epithelium by transplantation." Thesis, University of Cambridge, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.307957.
Full text
21
Riedinger, Christiane. "Tumour suppressors and oncogenes : Structure, function and drug design." Thesis, University of Oxford, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.533846.
Full text
22
Lucas, John Mark. "Regulation of the C-MYC and FGF-4 Oncogenes /." The Ohio State University, 1994. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487859879939229.
Full text
23
Zhang, Juan. "ONCOGENES INVOLVED IN CANCER CELL PROGRESSION AND CELL SURVIVAL." OpenSIUC, 2012. https://opensiuc.lib.siu.edu/theses/830.
Full textAbstract:
Serum is an essential component of cell cultural medium. Besides nutrients, it supplies various growth factors which are indispensable for growth, proliferation, and survival. Prolonged serum starvation treatment usually will induce cell to enter a quiescent state (G0) or go to apoptosis. In the present study, we hypothesized that some microRNAs (miRNAs) may promote cancer cell survival under prolonged serum starvation treatment. We used cell culture medium without any serum to culture HCT-116 wild type cells infected with the miRNA library consisting of over 600 miRNA precursors in a lentiviral vector. Finally, we enriched miR944 and miR596 from the screening experiments and identified them capable of conferring serum starvation resistance.. We also found that the expression of c-myc and p53 as well as the phosphorylation of mTOR s2448 are affected by ectopic expression of miR596 and miR944 while cultured in medium with or without serum supplying. These proteins are closely related to the cell survival under stress, which may suggest a possible mechanism for miR596 and miR944. Experiments are underway to identify direct target genes of miR596 and miR944. The other project that I studied is about the function of Leukemia related protein 16 (LRP16) in breast cancer progression. Available evidence suggests that LRP16 is a co-activator of estrogen receptor a (ERa) in promoting ERa-positive breast cancer cell proliferation. Our experiments indicate that LRP16 is upregulated only in primary breast cancer tissues (StageⅡ) and MCF7 cell lines, but not in highly metastasis StageⅢ breast cancer tissues and MDA-MB-231 cell lines. The ectopic expression of LRP16 in MCF7 and 231 cell lines causes an opposite effect on cell proliferation. Although it was originally hypothesized that LRP16 may promote cell proliferation by influencing the production or phosphorylation of p65, or other NF-κB family members, we could not provide direct evidence to support this. Therefore, we did not go further.
24
Murcia, Rosero Lada. "Selective killing of Ras-malignant tisues by exploiting oncogene-induced DNA damage = Eliminación selectiva de tejidos malignos dependientes de RAS mediante la explotación del daño en el ADN inducido por oncogenes." Doctoral thesis, Universitat de Barcelona, 2019. http://hdl.handle.net/10803/668212.
Full textAbstract:
Most human solid tumors present signs of genomic instability. Activated oncogenes have been proposed to induce genomic instability through the generation of replicative stress. In this thesis, we have sown that the expression of a constitutively active form of RAS oncogene promotes accelerated G1/S transition which leads to replicative stress and genomic instability. The resulting DNA damage present in these cells should activate the DDR response, however, RasV12 cells impair DNA damage signaling. Furthermore, RasV12 expression inhibits apoptosis through ERK.
RAS is one of the most commonly mutated oncogenes, yet efficient therapies to treat RAS dependent tumors are still lacking. With this in mind, and based on our previous results, we decided to try to exploit the DNA damage present in these cells to selectively target them. In order to do so, we induced extra DNA damage with ionizing radiation and depleted ERK to promote the death of the cells. We used this strategy on RAS dependent tumors both benign and malignant tumors, and successfully targeted and killed tumor cells. We propose that MEK inhibitors, that are being used in the treatment of metastatic melanomas, could be combined with radiation to improve the therapeutic outcomes.
Aside from the previously described autonomous effects, we have also observed that RasV12 expression in the wing imaginal discs induces a non-autonomous phenotype. Wild type cells adjacent to RAS cells display signs of DNA damage, apoptosis and autophagy. The role of these non-autonomous effects is not clear; however, we hypothesize that they may play a role in metabolically supporting tumor growth.La mayoría de tumores sólidos presentan signos de inestabilidad genómica. Se ha propuesto que la activación de oncogenes puede generar inestabilidad genómica mediante la inducción de estrés replicativo. En esta tesis hemos demostrado que la expresión de una forma constitutivamente activa del oncogén RAS en células epiteliales de Drosophila promueve una aceleración de la transición entre las fases G1 y S del ciclo celular. Esto lleva a una inducción de estrés replicativo y deriva en inestabilidad genómica. El daño en el ADN resultante de este proceso debería de activar la respuesta al daño en el ADN, sin embargo, esta se encuentra bloqueada. Además, la expresión de RasV12 inhibe la muerte celular gracias a los altos niveles de activación de ERK. Ras es uno de los oncogenes más comúnmente mutados, sin embargo seguimos sin terapias para tratar tumores dependientes de Ras que sean seguras y efectivas. Con esto en mente, y basándonos en nuestros resultados anteriores, decidimos tratar de explotar en daño en el ADN presente en estas células para destruirlas de forma selectiva. A estos efectos, indujimos más daño mediante irradiación e inhibimos la expresión ERK para promover la muerte de estas células. Usamos esta estrategia tanto en tumores benignos como malignos y en ambos casos logramos destruir de forma selectiva las células tumorales. Proponemos que los inhibidores de MEK, que se usan para el tratamiento de melanomas metastáticos, podrían combinarse con radiación para mejorar los efectos terapéuticos. A parte de los efectos autónomos descritos con anterioridad, también hemos observado que la expresión de RasV12 induce un fenotipo no autónomo. Las células normales adyacentes a las células Ras presentan signos de daño en el ADN, apoptosis y autofagia. El papel de estos efectos no autónomos no está claro, hipotetizamos que podrían jugar un papel en sustentar metabólicamente el crecimiento del tumor.
25
Bennett, Julie Denise. "Cell cycle regulation of B-myb transcription." Thesis, Imperial College London, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.362337.
Full text
26
溫錫剛 and Shek-kong Thomas Wan. "Establishment and characterization of human ovarian surface epithelialcells immortalized by human papilloma viral oncogenes." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1997. http://hub.hku.hk/bib/B31236236.
Full text
27
Littlewood, Trevor David. "An investigation of the functions of the c-Myc oncoprotein." Thesis, Anglia Ruskin University, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.357338.
Full text
28
Feng, Liang. "Molecular analysis of the ewings sarcoma oncogene transcriptional activation domain /." View Abstract or Full-Text, 2002. http://library.ust.hk/cgi/db/thesis.pl?BIOL%202002%20FENG.
Full textAbstract:
Thesis (M. Phil.)--Hong Kong University of Science and Technology, 2002.Includes bibliographical references (leaves 74-85). Also available in electronic version. Access restricted to campus users.
29
Wan, Shek-kong Thomas. "Establishment and characterization of human ovarian surface epithelial cells immortalized by human papilloma viral oncogenes /." Hong Kong : University of Hong Kong, 1997. http://sunzi.lib.hku.hk/hkuto/record.jsp?B18656456.
Full text
30
Dutenhefner, Simone Elisa. "Pesquisa da mutação T1799A do gene BRAF e a presença de metástases linfáticas no carcinoma papilífero da tireoide." Universidade de São Paulo, 2011. http://www.teses.usp.br/teses/disponiveis/5/5132/tde-24012012-163817/.
Full textAbstract:
Muitos pacientes submetidos à tireoidectomia por Carcinoma Papilífero da Tireoide (CPT) têm doença linfonodal subclínica no momento da cirurgia. A mutação BRAF T17799A (V600E) é um evento comum no CPT e alguns estudos demonstram correlação entre a mutação e características de maior agressividade tumoral, incluindo a presença de metástases linfonodais. O esvaziamento eletivo do compartimento central ganha aceitação, uma vez que alguns estudos evidenciam que a presença de metástases linfonodais aumenta o risco de recidiva e mortalidade. Devido ao grande potencial de complicações do esvaziamento do compartimento central, o objetivo deste trabalho foi avaliar a associação entre a presença da mutação BRAF T17799A (V600E), a presença de metástases linfonodais e fatores clínicos e histopatológicos de pior prognóstico. Métodos: 51 casos consecutivos de pacientes com CPT foram submetidos à tireoidectomia total e ao esvaziamento eletivo ou terapêutico do compartimento central. Em todos os pacientes foi pesquisada a mutação BRAF T17799A (V600E) no tecido tireoidiano com Carcinoma Papilífero de Tireoide. Resultados: Cinquenta e quatro por cento (54,9%) dos pacientes apresentaram metástases linfonodais. Seis pacientes apresentaram metástases laterais confirmadas por punção aspirativa por agulha fina no pré-operatório e 22 pacientes (43%) apresentaram metástases não detectadas no pré ou no intra operatório A mutação BRAF T17799A (V600E) foi encontrada em 15 pacientes portadores de CPT (29,4%). A presença da mutação não teve associação estatisticamente significante para sexo, idade, tamanho do tumor, extensão extratireoidiana, multicentricidade, embolização angiolinfática e metástases linfonodais. As metástases linfonodais se associaram à multifocalidade (p = 0,005) e invasão angiolinfática (p = 0,003) na análise univariada. Conclusão: A presença da mutação BRAF T17799A (V600E) não se associou à metástases linfonodais em nosso estudo. A multifocalidade e a detecção de invasão angiolinfática no CPT foram os fatores mais importantes na predição de metástases linfonodaisBackground: Many patients undergoing thyroidectomy for Papillary Thyroid Carcinoma (PTC) have subclinical node disease at the time of surgery. The BRAF T17799A (V600E) mutation is a common event in PTC and some studies have demonstrated a correlation between the mutation and aggressive characteristics including lymph node metastasis. Prophylactic Central Node Dissection (CND) is gaining acceptance in the treatment of PTC as studies have shown nodal disease increases local recurrence and may alter mortality. Given the potential complications of CND, the aim of this study was to determine the correlation among BRAF mutation, lymph node metastasis and clinical and histopathological factors of worse prognosis. Methods: A total of 51 consecutive cases of patients with PTC underwent total thyroidectomy and routine prophylactic (CND) or therapeutic neck dissection when metastases were found. All patients were tested for the BRAF mutation. Results: Overall, positive lymph nodes were found in Fifty four per cent9% of patients. Six patients had lateral metastases confirmed by fine needle aspirative cytology and 22 patients (43%) had occult metastases. The BRAF mutation was found in 15 patients (29.4%). BRAF was not correlated with sex, age, size of tumor, multifocality, extrathyroid extension or lymph node metastases. Lymph node metastases were correlated with multifocality (p = 0.005) and angiolymphatic invasion (p = 0.003) in univariate. Conclusions: The BRAF mutation was not correlated with lymph node metastases in our study. Multifocality and angiolymphatic invasion were important factors for predicting lymph node metastases
31
Velasco, Sánchez Ana. "Oncogenes y genes supresores de tumores en carcinoma de endometrio." Doctoral thesis, Universitat de Lleida, 2012. http://hdl.handle.net/10803/110545.
Full textAbstract:
El objetivo principal de este trabajo ha sido la identificación de alteraciones moleculares que participen de manera significativa en el desarrollo y la progresión del cáncer de endometrio, con el propósito de añadir mas claves para el descubrimiento de nuevas dianas de diagnosis y terapias individuales contra esta patología. El trabajo ha sido centrado en el estudio de modificaciones en el ADN de las células que forman el tejido tumoral en una serie de pacientes con carcinoma endometrial, en concreto, en el análisis mutacional de los genes PIK3CA y FGFR2 y el análisis de hipermetilación del promotor de los genes RASSF2A y SPRY2, elementos que forman parte de importantes vías de transducción de señales implicadas principalmente en procesos de crecimiento y diferenciación celular. Por un lado, hemos advertido cierto grado de variabilidad en el patrón de expresión de los genes estudiados en los tejidos tumoral y no tumoral y esas diferencias de expresión son, en parte, debidas a la existencia de hipermetilación en las regiones promotoras de los genes implicados. Así mismo, la presencia de mutaciones en regiones génicas que codifican partes de la proteína claves para su función en la célula es también un factor que modifica el patrón de expresión entre tejidos. En concreto, tras el análisis de la expresión inmunohistoquímica de RASSF1A y la presencia o ausencia de metilación en la zona promotora del gen RASSF1A se detectaron tumores con niveles de expresión reducidos y presencia de hipermetilación en el promotor, ambos fenómenos asociados de manera estadísticamente significativa. Lo mismo ocurre, aunque en un grado distinto, con la expresión de SPRY2 en algunos tumores en asociación con la presencia de hipermetilación en el promotor del gen. A través de este análisis hemos descubierto que la expresión de SPRY2 presenta variabilidad en las glándulas endometriales de los tejidos no tumorales a lo largo del ciclo menstrual. Por otro lado hemos visto como el gen PIK3CA se encuentra frecuentemente mutado en las células que forman los tumores de carcinoma de endometrio y que, además, es un suceso que coincide con la presencia de mutaciones en el gen PTEN. Sin embargo, la frecuencia de mutaciones en el gen FGFR2 se ha mostrado baja aunque su expresión a nivel inmunohistoquímico refleja diferencias entre carcinoma de tipo endometrioide y no endometrioide. Por ultimo, añadir una revisión de uno de los fenómenos que ocurren de manera mas frecuente durante la formación y el progreso de los tumores en carcinoma de endometrio: el concepto de “pérdida de heterocigosidad”. En este trabajo hemos considerado primordial incluir un obra en la que se realiza una incursión a los mecanismos moleculares a través de los cuales se produce la pérdida de heterocigosidad, asi como los métodos que se utilizan para su detección y el significado de algunos patrones de pérdida de heterocigosidad en determinadas regiones cromosómicas en carcinoma de endometrio.L'objectiu principal d'aquest treball ha estat la identificació d'alteracions moleculars que participin de manera significativa al desenvolupament i la progressió del càncer d'endometri, amb el propòsit d'afegir més claus pel descobriment de noves dianes de diagnosi i teràpies individuals contra aquesta patologia. El treball ha estat centrat en l’estudi de modificacions en l’ADN de les cèl-lules que formen el teixit tumoral en una sèrie de pacients amb carcinoma endometrial, en concret, en l’anàlisi mutacional del gens PIK3CA i FGFR2 i l’anàlisi de hipermetilació del promotor dels gens RASSF1A i SPRY2, elements que formen part d’importants vies de transducció de senyals implicades principalment en processos de creixement i diferenciació cel-lular. En primer lloc hem advertit cert grau de variabilitat en el patró d'expressió dels gens estudiats entre els teixits tumoral i no tumoral i aquestes diferències d'expressió són, en part, degudes a l'existència de hipermetilació en les regions promotores dels gens implicats. Així mateix, la presencia de mutacions en regions gèniques que codifiquen parts de la proteïna claus per la seva funció a la cèl-lula, és també un factor que modifica el patró d'expressió entre entre els teixits tumoral i no tumoral. En concret, després de l’anàlisi immunohistoquímic de l’expressió de RASSF1A i la presència o absència de metilació a la zona promotora del gen RASSF1A, es van detectar tumors amb nivells d’expressió reduïts i presència de hipermetilació en el promotor, ambdós fenòmens associats de manera estadísticament significativa. El mateix passa, encara que amb diferent grau, amb l’expressió de SPRY2 en alguns tumors en associació amb la presència de ipermetilació en el promotor del gen. A través d’aquest anàlisi hem descobert que l’expressió de SPRY2 presenta variabilitat en les glàndules endometrials dels teixits no tumorals al llarg del cicle menstrual. D'altra banda hem vist com el gen PIK3CA es troba freqüentment mutat en les cèl-lules que formen els tumors de carcinoma d'endometri i coincideix amb la presència de mutacions en el gen PTEN. No obstant això, la freqüència de mutacions en el gen FGFR2 s'ha mostrat baixa encara que la seva expressió a nivell inmunohistoquímic reflecteix diferencies entre carcinoma de tipus endometrioide y no endometrioide. Finalment, afegir una revisió d'un dels fenòmens més freqüent en la formació i el progrés dels tumors en carcinoma d'endometri: el concepte de "pèrdua de heterozigositat". En aquest treball hem considerat primordial incloure una obra en que es realitza una incursió als mecanismes moleculars a través dels quals es produeix la pèrdua de heterozigositat, aixi com els mètodes que s'utilitzen en la seva detecció i el significant d'alguns patrons de pèrdua de heterozigositat en determinades regions cromosòmiques en carcinoma d'endometri.
The main point of this study was the identification of molecular alterations that participate in the development and progression of endometrial cancer, in order to add more keys to the discovery of new targets for diagnosis and therapies against this disease. The work has been focused on the study of molecular alterations of DNA from tumour tissues in a series of endometrial carcinoma patients, above all, mutational analysis of PIK3CA and FGFR2 genes and analysis of promoter hyper methylation of SPRY2 and RASSF2A genes, together forming part of signal transduction pathways that are involved in processes of growth and cell differentiation. To begin with, we noticed some variability in the gene expression pattern examined between tumour and normal tissue, and these differences are partly due to hyper methylation in promoter regions at the involved genes. Likewise, mutations in gene regions encoding key protein domains in the cell are also a factor that modifies the gene expression pattern between tumour and normal tissue. In particular, after analysing the immunohistochemical expression of RASSF1A and the presence or absence of methylation in the RASSF1A gene promoter we detected tumours with low expression levels and promoter hyper methylation. The same applies, albeit in a different degree, with SPRY2 expression in some tumours in association with the presence of gene promoter hyper methylation. Through this analysis we found some SPRY2 expression variability in endometrial glands from non-tumour tissues throughout the menstrual cycle. On the other hand we have seen that the PIK3CA gene is frequently mutated in tumour cells from endometrial carcinoma, and this is also a PTEN gene mutation coincident event. However, FGFR2 gene mutation ratio has shown to be low although immunohistochemical expression reflects differences between endometrioid endometrial carcinoma and no-endometrioid type. Finally, we wanted to add a review of one of the phenomena, which occurs more frequently during the formation and progress of tumours in endometrial carcinoma: LOH "loss of heterozygosity". We have considered essential include a review work about the molecular mechanisms through which loss of heterozygosity is produced, the methods used in their detection and significance of some patterns of loss of heterozygosity in specific chromosomal regions in endometrial carcinoma.
32
Ewels, Philip Andrew. "Spatial organisation of proto-oncogenes in human haematopoietic progenitor cells." Thesis, University of Cambridge, 2013. https://www.repository.cam.ac.uk/handle/1810/245861.
Full textAbstract:
The eukaryotic cell nucleus is a highly organised organelle, with distinct specialised sub- compartments responsible for specific nuclear functions. Within the context of this functional framework, the genome is organised, allowing contact between specific genomic regions and sub-compartments. Previous work has shown that genes in both cis and trans can make specific contacts with each other. I hypothesise that such a preferred juxtaposition may impact the propensity for specific cancerinitiating chromosomal translocations to occur. In this thesis, I describe how I have extended and developed a ligation based proximity assay known as enriched 4C. I have coupled this technique with high throughput sequencing to determine genomic regions that spatially co-associate with the proto-oncogenes MLL, ABL1 and BCR. In addition to further developing the laboratory protocol, I have created bioinformatics tools used in the analysis of the sequencing data. I find that the association profiles of the three genes show strong correlation to the binding profile of RNA polymerase II and other active marks, suggesting that transcribed genes have a propensity to associate with other transcribed regions of the genome. Each gene also exhibits a unique repertoire of preferred associations with specific regions of the genome. Significantly, I find that the most frequent trans association of BCR is telomeric chromosome 9, encompassing its recurrent translocation partner gene ABL1. Interestingly, ABL1 is not at the maximum point of interaction. I use DNA-fluorescence in-situ hybridisation to validate the e4C association. My data supports a hypothesis that gene transcription has a direct role on genome organisation. I suggest that preferred co-associations of genes at transcription factories may promote the occurrence of specific chromosomal translocations.
33
Kiberu, Samuel. "Apoptosis, cell proliferation and role of oncogenes in lymphoreticular malignancies." Thesis, University of Leicester, 1998. http://hdl.handle.net/2381/29571.
Full textAbstract:
This study was conducted using paraffin embedded material of randomly selected lymphoma cases from the archives of Leicester Royal Infirmary. The cases had been confirmed by immunophenotyping and immunocytogenetic analysis of B and T cell gene rearrangements using PCR (Polymerase chain reaction). These included 20 each of low grade and high grade non Hodgkin's lymphomas of both sexes and age groups 4-84 yrs. Prognostic information was obtained from the case notes. An in situ End labelling technique was used to study apoptotic indices. Cell proliferation rates were studied by in situ hybridisation method to detect histone using mRNA digoxigenin-11-dUTP probe. Bcl-2 expression was assessed using antigen retrieval and an immunoperoxidase technique. Apoptotic indices, proliferation rates, Bcl-2 expression and tumour grade were correlated to each other. Flowcytometric study of four cell lines (HL-60, Raji, C88 and DP16-1) was also undertaken as regards apoptosis, cell proliferation and oncogene expression. Apoptosis was assessed using existing techniques on thymocytes. Cell proliferation was assessed using proliferation markers like Ki-67, PCNA and BrdUrd. The study showed that the high grade lymphomas had the highest apoptotic indices and proliferation rates. More of the low grade tumours were Bcl-2 positive. Most mortalities occurred in tumours which had high proliferation rates and were Bcl-2 negative suggesting that those two parameters were bad prognostic indicators. A larger and extended study would be required to confirm my observations. For the cell lines apoptosis showed an inverse correlation with cell proliferation. There appeared to be a link between apoptosis and cell differentiation and the role of oncogenes was established. The information derived from cell lines could be exploited in designing drugs which produce apoptosis, cell differentiation and counteracting cell proliferation thus reducing tumour load.
34
Gottardo, Nicholas G. "Oncogenes and prognosis in childhood T-cell acute lymphoblastic leukaemia." University of Western Australia. School of Paediatrics and Child Health, 2008. http://theses.library.uwa.edu.au/adt-WU2009.0039.
Full textAbstract:
[Truncated abstract] The treatment of childhood acute lymphoblastic leukaemia (ALL) is one of the great success stories of paediatric oncology, transforming a universally fatal disease into one where 75 to 90% of children are now cured. Although in the past survival for children with T-cell ALL (T-ALL) lagged behind that of children with pre-B ALL, the use of contemporary intensified treatment strategies has significantly diminished this difference, with many investigators reporting similar cure rates for both groups of patients. Despite these marked improvements, numerous challenges still face physicians treating children with T-ALL. Firstly, there have been no additional major improvements in outcome over the last decade, despite additional treatment intensification. Secondly, effective regimens remain elusive for treating children with relapsed T-ALL or patients with resistant disease. Finally, there is a need to identify patients currently potentially overtreated and thus unnecessarily subjected to acute and long term toxicities without benefit. A major challenge therefore, is the identification of novel reliable prognostic markers, in order to identify patients at high risk of relapse and conversely those least likely to relapse, to guide therapy appropriately. Children predicted with a high risk of relapse would be candidates for intensification of therapy and/or novel experimental agents. Conversely, patients predicted to be at low risk of relapse could be offered clinical trials using reduced intensity therapy, thereby minimising toxicity. '...' Crucially, the 3-gene predictor was validated in a completely independent cohort of T-ALL patients, also treated on CCG style therapy. Our 3-gene predictor appears to identify a high risk group of patients which require alternative therapeutic strategies in order to attain a cure. This study has also identified a potential novel agent for the treatment of T-ALL, which may be used as an anthracycline potentiator or anthracycline-sparing agent. We hypothesised that genes associated with a relapse signature provide promising targets for novel therapies. We tested the hypothesis that CFLAR, an inhibitor of the extrinsic apoptotic pathway and a member of the 3-gene predictor may be involved in the development of resistance to chemotherapy. To test our hypothesis we used a novel agent, 2-cyano-3, 12-dioxooleana-1,9 (11)-dien-28-oic acid (CDDO), previously shown to inhibit CFLAR protein, in two cell lines established in our laboratory from paediatric patients diagnosed with T-ALL. We found that CDDO displayed single agent activity at sub-micromolar concentrations in both cell lines tested. Importantly, minimally lethal doses of CDDO resulted in significant enhancement of doxorubicin mediated cytotoxicity in one of the cell lines assessed. The findings presented as part of this thesis have revealed the value of gene expression analysis of childhood T-ALL for identifying novel prognostic markers. This study has shown that expression profiles may provide better prognostic information than currently available clinical variables. Additionally, genes that constitute a relapse signature may provide rational targets for novel therapies, as demonstrated in this study, which assessed a potential novel agent for the treatment of T-ALL.
35
Persson, Fredrik. "Studies of fusion oncogenes and genomic imbalances in human tumors /." Göteborg : Göteborg University, Lundberg Laboratory for Cancer Research, Dept. of Pathology, Sahlgrenska Academy at Göteborg University, 2007. http://hdl.handle.net/2077/7368.
Full text
36
Maxwell, Marius. "Expression of proto-oncogenes and growth factors in glioblastoma multiforme." Thesis, University of Oxford, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.259967.
Full text
37
Mellon, Killian. "C-ERBB oncogenes and cell cycling in human bladder cancer." Thesis, University of Newcastle Upon Tyne, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.333949.
Full text
38
Arends, Mark J. "Regulation of tumour growth and apoptosis by oncogenes and papillomaviruses." Thesis, University of Edinburgh, 1992. http://hdl.handle.net/1842/19771.
Full textAbstract:
The role of HPV genomes in human cervical neoplasia was re-examined using a new, sensitive PCR-based assay. This demonstrated increasing HPV prevalence with increasing grade of histological abnormality in cervical neoplasia. In contrast, HPV was not observed in histologically normal epithelium from a control group of women defined without reference to attendance at gynaecological or sexually transmitted disease clinics. HPV 16 was associated more with squamous cell carcinomas, and HPV 18 with cancers showing glandular differentiation - the histological type with a poorer prognosis. HPV 18 had a higher cancer/CIN prevalence ratio than HPV 16 indicative of a more rapid transition from CIN to carcinoma. Thus, HPV 18 appeared to be a more aggressive type than HPV 16. A rodent fibroblast model was developed to investigate the effects of HPVs and the myc and ras oncogenes on tumour cell apoptosis and growth rate. These genes were introduced into immortalised fibroblasts, which were studied both in vitro and in vivo. Regardless of the introduced genes, fibroblast proliferation in vitro differed little between the resulting cells lines. In contrast, the rates of cell death (which was uniformly effected by apoptosis) differed widely. Each tumour cell line had a characteristic rate of apoptosis, which determined large differences between the lines in their rates of population expansion in vitro. The tumours produced by subcutaneous injection of these cells into immune suppressed mice also showed large differences in size, which demonstrated a consistent relationship to the relative frequencies of mitosis and apoptosis. Thus, apoptosis appeared to be a major determinant of tumour growth in vitro and in vivo. The ratio of apoptosis to mitosis appeared to be characterised by the genes inserted into these cells. The c-myc oncogene and high risk HPV genomes stimulated tumour cell apoptosis. HPV 18 was associated with lower levels of tumour cell apoptosis than HPV 16. In contrast, the activated ras oncogene suppressed apoptosis, either alone or in combination with the other genes, contributing to the faster growth of ras transfected fibroblasts.
39
Wallingford, John Beckett. "Tumor suppressors and oncogenes in the development of Xenopus laevis /." Digital version accessible at:, 1998. http://wwwlib.umi.com/cr/utexas/main.
Full text
40
PANDINI, CECILIA. "MYC and MINCR characterization in ALS: oncogenes role in neurodegeneration." Doctoral thesis, Università degli studi di Pavia, 2020. http://hdl.handle.net/11571/1370056.
Full text
41
Santiago, Marília Bueno 1986. "Avaliação dos polimorfismos SLC23A2-05 e KRAS-LCS6 entre portadores de carcinoma de células escamosas de cabeça e pescoço." [s.n.], 2011. http://repositorio.unicamp.br/jspui/handle/REPOSIP/308579.
Full textAbstract:
Orientador: Carmen Silvia BertuzzoDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
Made available in DSpace on 2018-08-18T22:32:33Z (GMT). No. of bitstreams: 1 Santiago_MariliaBueno_M.pdf: 1534598 bytes, checksum: 1b88c82597c2b286ee6cd5c4c13cec4b (MD5) Previous issue date: 2011
Resumo: O câncer é um dos problemas mais comuns da medicina atual, com cerca de 481.100 novos casos por ano, atingindo mais de um terço da população mundial. O câncer de cabeça e pescoço em sua maioria é representado por neoplasias epiteliais do tipo carcinoma de células escamosas (CEC) que acometem as vias superiores aéro-digestivas. A grande maioria dos casos é representada por tumores esporádicos. Estudos têm associado o CEC a alguns polimorfismos como o Kras-LCS6, que reduz significativamente o tempo de vida em pacientes com tumores de cabeça e pescoço e sugere que esta variante pode alterar o fenótipo ou a resposta terapêutica da doença e o polimorfismo associado ao transporte sódio dependente de vitamina C, SLC23A2-05, que modifica o risco de câncer de cabeça e pescoço em indivíduos portadores do HPV16 Humano, HPV positivos têm risco aumentado, enquanto nos negativos este risco se reduz. O objetivo do presente estudo foi avaliar a prevalência dos polimorfismos Kras-LCS6 e SLC23A2-05 em uma amostra de pacientes com carcinoma de células escamosas de cabeça e pescoço, verificando a importância desses polimorfismos no acometimento e na gravidade da doença, através de um estudo de associação. Foi utilizada a técnica de PCR associada a digestão enzimática. Foram avaliados 165 casos e 230 controles para cada polimorfismo. No polimorfismo Kras-LCS6 a freqüência gênica dos alelos T e G encontradas foram de 0,91 e 0,09 na amostra do grupo caso e 0,90 e 0,10 na amostra controle. Para o polimorfismo SLC23A2-05 a freqüência gênica dos alelos C e G foram de 0,47 e 0,53, respectivamente, tanto no grupo de caso quanto no grupo controle. Da análise do teste de regressão logística, nenhuma associação foi encontrada entre os polimorfismos analisados e o CEC, bem como com o estadiamento da doença
Abstract: Cancer is one of the most common problems in medicine today, with approximately 481,100 new cases per year, reaching more than a third of the world population. Head and neck cancer is mostly represented by type of skin cancer squamous cell carcinoma affecting the upper aero-digestive pathways. The majority of cases is represented by sporadic tumors Studies have associated some gene polymorphisms with head and neck squamous cell carcinoma (HNSCC) as the Kras-LCS6, which reduces significantly the survival in patients with head and neck tumors and suggests that this variant may alter the phenotype of the disease or therapeutic response and polymorphisms associated with sodium-dependent vitamin C, SLC23A2-05, which modifies the risk of head and neck cancer in individuals with the Human HPV16, positive HPV have an increased risk, while in the negative this risk is reduced. The aim of this study was to evaluate the prevalence of polymorphisms Kras-LCS6 and SLC23A2-05 in a sample of patients with head and neck squamous cell carcinomas, verifying the importance of these polymorphisms in the onset and severity of the disease, through a study of association. We used the PCR method combined with PCR-RFLP. We evaluated 165 cases and 230 controls for each gene polymorphism. In Kras-LCS6 Polymorphism found the gene frequency of 0.91 and 0.09 T and G alleles in the sample of patients and 0.90 and 0.10 in the control sample. For the SLC23A2-05 polymorphism gene frequency of the C and G alleles were 0.47 and 0.53, respectively, both in the patient group and control group. In logistic regression test analysis, we don't found any association between two polymorphisms studied and HNSCC, as well as with the disease staging
Mestrado
Ciencias Biomedicas
Mestre em Ciências Médicas
42
Bellmunt, i. Tarragó Anna. "Role of MAF in bone metastasis." Doctoral thesis, Universitat de Barcelona, 2017. http://hdl.handle.net/10803/482079.
Full textAbstract:
The identification of genes that mediate metastasis is pivotal to better understand the mechanism, to develop novel drugs and to stratify patients with highest risk and consecutively administrate them preventive treatments. Despite significant advances on knowledge, diagnosis and treatment of cancer, metastasis remains the major cause of cancer-associated deaths.
Bone is one of the most common organs affected by metastatic lesions for its permeability and favorable conditions for cellular growth. Constant remodeling in bone homeostasis implies an incessant degradation of the bone that release high concentrations of growth factors into the microenvironment. Thereby, growth factors benefit both, formation of new bone and/or tumor cell growth. Although the importance of bone metastatic lesions in cancer patients and the advances on the knowledge of this process, few treatments are currently administrated to patients that suffer this disease, specifically Denosumab and Zoledronic acid (ZOL). Importantly, these treatments can improve the symptoms of bone lesions but cannot cure or reverse metastasis. This fact reflects the need to detect and tackle new targetable elements to reduce bone metastatic lesions.
Many molecular mechanisms have been described in bone metastasis, but only one predictor gene has been identified, MAF. MAF is a transcription factor that has been previously involved in carcinogenesis, specially in multiple myeloma (MM) and human angioimmunoblastic T-cell lymphomas (AITLs). Recently, MAF contribution has been associated for the first time with breast cancer bone metastasis.
In this thesis, we determined the role of MAF in several contexts. As a first approach we demonstrated that MAF is also a predictive marker of bone metastasis in prostate cancer (PC) patients. However, regarding androgen-independent PC cell lines, an overexpression of MAF was not enough to drive colonization of the mouse bone. Secondly, we report the beneficial effect of MAF downregulation on preventing skeletal metastasis in BoM2, a highly bone metastatic MCF7-derived cell line. MAF impinged bone colonization in a higher degree that other treatments against bone metastasis, such as PTHrP antagonist or recombinant OPG. This fact identifies MAF as a new potential target to focus on the generation of new drugs. Finally, MAF showed a tendency to redirect metastases to other organs than bone in the presence of ZOL treatment in vivo. Thus, we validated the association between MAF overexpression and an increase on extraskeletal metastases after ZOL preventive treatment in non-postmenopausal BC patients.
Moreover, a mouse model was generated to better understand the biology of MAF- derived bone metastasis within complete stromal interactions. We designed a transgenic mouse model to express MAF in the mammary gland in an inducible manner. To this end, we generated two constructs; the first contains rtTA, renilla and katushka under MMTV promoter, and the second contains MAF, luciferase and tGFP under Tet-On promoter. We demonstrated the incorporation of several copy numbers of both transgenes in two independent colonies and we detected transgene expression under doxycycline activation by means of luminescent signal. Even though both colonies incorporated several copy number of the transgene, their expression was soft and some relevant leakiness was observed in the non-treated MAF mice. No differences were
observed in terms of mammary gland development between transgene-expressing MAF mice and wild-type mice, as well as no tumor initiation was detected in any group. Notably, MAF Tg mouse was crossed with MMTV-PyMT to generate double Tg mice (PyMT-MAF). PyMT-MAF tumor growth presented no significant differences compared to PyMT in terms of time to tumor formation and growth rate. Importantly, no bone metastases were observed at 3-month-old mice of any group. Thus, the generation of this animal model provided new insights to generate a novel bone metastatic mouse model.La identificació de gens implicats en el procés de la metàstasis és bàsica per tal d’entendre el mecanisme d’aquest procés, per reconèixer els pacients amb més risc de patir-lo i tractar-los selectivament i finalment pel desenvolupament de nous fàrmacs. Recentment, s’ha identificat el gen MAF com a predictor d’un alt risc de patir metàstasis òssia en pacients de càncer de mama. En aquesta tesi hem determinat el paper de MAF en diferents contexts. Per una banda, hem demostrat que MAF és un marcador predictiu de les metàstasis òssies també en pacients amb càncer de pròstata. Tot i així, una sobreexpressió de MAF en cèl·lules de càncer de pròstata andrògen-independents no va ser suficient per conduir la colonització a l’òs. Per altra banda, hem demostrat que reduir els nivells de MAF en les cèl·lules BoM2, derivades de les cèl·lules de càncer de mama MCF7, redueix la tendència d’aquestes cèl·lules a metastatitzar a l’òs. Cal destacar que aquest efecte és superior al d’altres tractaments com poden ser OPG recombinant o el pèptid antagonista de PTHrP, indicant MAF com a element potencial per a la generació de nous fàrmacs. Finalment, MAF afecta el patró de metàstasis de les cèl·lules ER- de càncer de mama després del tractament preventiu amb àcid Zoledronic, tal com s’observa en pacients. Per abordar el paper de MAF en el càncer de mama tenint en compte les interaccions amb l’estroma i el sistema immunitari, es va dissenyar un model animal transgènic que sobreexpressava MAF en la glàndula mamària de forma induïble. Es va demostrar la incorporació de vàries còpies del transgen en el ADN genòmic i també es va detectar, per senyal bioluminiscent, la inducció per doxiciclina de l’expressió del transgen. Cal destacar que l’expressió era feble i en molts casos inespecífica i independent al tractament amb doxiciclina. El desenvolupament mamari en aquest model no demostrava cap alteració com tampoc es va detectar cap indici de formació de tumor. Aquest model es va creuar amb MMTV-PyMT, i els tumors de les femelles doble transgèniques (PyMT-MAF) no van presentar cap diferència en el temps necessari per a la formació de tumors ni en la velocitat de creixement comparat amb PyMT. De manera destacable, no es van observar metàstasis òssies en el moment del sacrifici. D’aquesta manera, la generació del ratolí MAF transgènic ens va donar noves perspectives per enfocar la generació d’un nou model animal que generi metàstasis òssies.
43
Dix, Flora Lucy. "Ceramide synthase 4 : a novel metabolic regulator of oncogene-induced senescence." Thesis, University of Edinburgh, 2018. http://hdl.handle.net/1842/29624.
Full textAbstract:
Senescence is a cell stress program characterized by a stable cell cycle arrest and thus aims to protect against replication of potentially harmful cells. In oncogene-induced senescence (OIS) the cell cycle arrest is brought about by activation of an oncogene. This in turn initiates a DNA damage response and subsequently, the DDR induces p53-p21 and RB tumour suppressor pathways. The metabolism of senescent cells is highly altered, notably there is increased secretion of proteins and increased functional activity of certain metabolic enzymes. There have been many recent studies investigating the role of specific metabolic pathways in OIS and how they may be targeted for therapeutic benefit. This thesis aims to identify novel metabolic regulators of OIS, by combining high throughput RNAi screening and LC-MS based methods. This thesis has identified and validated 17 essential OIS metabolic genes; in this list, there was enrichment for genes involved in lipid biosynthetic processes. Lipid metabolism was an attractive focus for this thesis as it has not been extensively studied in current literature. Next, ceramide synthase 4 (CERS4) was extensively validated as a key enzyme for both OIS and replicative senescence. Using LC-MS based lipidomics, CERS4-driven rewiring of lipid metabolism in OIS was revealed and this corresponded with an accumulation of ceramides due to increased de novo ceramide synthesis. It was then confirmed OIS-related ceramide is mechanistically linked to cell cycle via the PP1-RB-E2F axis. Ceramide activates PP1, which physically binds to RB in a CERS4-dependent manner. PP1 is then able to dephosphorylate and activate RB, which inhibits transcription of E2F targets (cell cycle genes). Overall, this thesis identifies a metabolic checkpoint that links altered lipid metabolism with OIS.
44
Barbieri, Raquel Bueno 1985. "Perfil genético de suscetibilidade ao desenvolvimento de carcinoma medular de tireoide." [s.n.], 2012. http://repositorio.unicamp.br/jspui/handle/REPOSIP/310291.
Full textAbstract:
Orientadores: Laura Sterian Ward, Janete CeruttiDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
Made available in DSpace on 2018-08-20T07:05:33Z (GMT). No. of bitstreams: 1 Barbieri_RaquelBueno_M.pdf: 1118684 bytes, checksum: aea72fb3df76b68d6756c422b46ffc56 (MD5) Previous issue date: 2012
Resumo: Polimorfismos de genes baixa penetrância têm sido consistentemente associados com a suscetibilidade a uma série de tumores humanos, incluindo o câncer de tireóide. A fim de determinar seu papel no carcinoma medular de tireóide (CMT), foi utilizado o método TaqMan® SNP Genotyping em 138 pacientes com CMTH, 47 pacientes com CMT-s e um grupo controle de 578 indivíduos para genotipagem dos polimorfismos CYP1A2*F (rs762551), CYP1A1m1 (rs4646903), NAT2 C282T (rs1041983), GSTP1 codon 105 (rs1695), TP53 codon 72 (rs1042522). Este estudo demonstrou uma associação entre a presença de alelos polimórficos de CYP1A2*F, GSTP1 e NAT2 e o desenvolvimento de CMTH. A herança do alelo C em homozigose do gene CYP1A 2*F influencia o desenvolvimento de CMTH em mais de 2 vezes. Pacientes que apresentaram o alelo T em homozigose para o gene NAT2 possuem uma probabilidade 3 vezes maior para o desenvolvimento de CMTH e os indivíduos que herdaram o alelo G do gene GSTP1 em homozigose apresentam maior probabilidade de desenvolvimento de CMTH. Uma análise estatística de regressão logística, ajustada para sexo, idade, etnia, tabagismo e os genes CYP1A*F, CYP1A1m1, NAT, GSTP1 e TP53 para os pacientes com CMTH demonstrou que, quando considerado o tamanho do tumor como estimativa de agressividade, o sexo masculino apresentou-se como fator de proteção ao aumento do tamanho do tumor (OR=0,12; p=0,0072). Considerando a recidiva local como estimativa de agressividade, o genótipo alterado do gene GSTP1 apresentou-se como fator de risco para presença de recidiva local (OR=1,17; p=0,035). A análise de regressão logística mostrou que a herança do genótipo C/C dos genes NAT2 (OR=3,87; IC95%=2,11-7,10; p=2,2x10-5) e TP53 (OR=3,87 IC95%=1,78-6,10; p=2,8x10-4) aumentou o risco de CMT-s. Uma análise de regressão indicou que o genótipo C/C do gene TP53 contribui com 8,07% do risco CMT-s. Não foi possível identificar qualquer relação entre os polimorfismos de NAT2 e TP53, sugerindo que são fatores independentes de risco para o CMT-s. Em conclusão, foi demonstrado que os genes de detoxificação e genes de apoptose e controle do ciclo celular estão envolvidos na suscetibilidade ao desenvolvimento de CMT-s e CMTH e podem modular a suscetibilidade à doença
Abstract: Polymorphisms in low penetrance genes have been consistently associated with susceptibility to a variety of human tumors, including thyroid cancer. In order to determine its role in medullary thyroid carcinoma (MTC) TaqMan® SNP Genotyping method was used in 138 patients with HMTC, 47 patients with MTC-s and a control group of 578 for genotyping of polymorphisms CYP1A2*F (rs762551), CYP1A1m1 (rs4646903), NAT2 C282T (rs1041983), GSTP1 codon 105 (rs1695) and TP53 codon 72 (rs1042522). This study demonstrated an association between the presence of polymorphic alleles of CYP1A2 F, GSTP1 and NAT2 and the development of HMTC. The legacy of the C allele in homozygous CYP1A2*F gene influences the development of CMTH in more than two times. Patients who had the T allele in homozygous for the NAT2 gene have a three times more likely to develop HMTC and individuals who have inherited the G allele of GSTP1 gene in homozygous are more likely to develop CMTH. A statistical analysis of logistic regression, adjusted for sex, age, ethnicity, smoking and genes CYP1A*F, CYP1A1m1, NAT, GSTP1, and TP53, in patients with HMTC, showed that, when considering the size of the tumor as an estimate of aggression, sex male presented himself as a protective factor to the increase in tumor size (OR=0.12; p=0.0072). Considering the estimate of local recurrence and aggressiveness, the altered gene GSTP1 genotype appeared as a risk factor for presence of local recurrence (OR=1.17; p=0.035). The logistic regression analysis showed that the genotypes of the NAT2 gene C/C (OR=3.87; 95%CI=2.11-7.10, p=2.2x10-5) and TP53 C/C (OR=3.87; 95%CI=1.78-6.10; p=2.8x10-4) inheritance increased the risk of sporadic MTC. A regression analysis showed that genotype C/C TP53 gene accounts for 8.07% of sporadic MTC risk. In addition, there was no association between the investigated genes and clinical or pathological features of aggressiveness of the tumors or the outcome of MTC patients. In conclusion, we demonstrated that detoxification genes and apoptotic and cell-cycle control genes are involved in the susceptibility of MTC-s and HMTC and may modulate the susceptibility to the disease
Mestrado
Ciencias Basicas
Mestre em Clinica Medica
45
Mahmoudi, Massoud. "Induction of Interferon Messenger RNA and Expression of Cellular Oncogenes in Human Lymphoblastoid Cells." Thesis, North Texas State University, 1986. https://digital.library.unt.edu/ark:/67531/metadc798199/.
Full textAbstract:
The purposes of this study was to demonstrate the induction of alpha interferon mRNA in Sendai virus-induced Namalava cells, to follow the level of alpha interferon mRNA synthesis at the transcriptional level, and to determine whether the Namalava cell line expresses the c-myc oncogene and to what degree. The amount of c-myc message deteted in Namalva cell RNA was about one-tenth that of Daudi cell RNA, whereas no difference in the amount of the c-Ha-ras message was observed between the two cell lines.
46
Sandros, Jens. "Salivary gland tumorigenesis a cytogenetic and molecular study /." Göteborg : Faculty of Odontology, University of Göteborg, University of Göteborg, 1989. http://catalog.hathitrust.org/api/volumes/oclc/20361247.html.
Full text
47
Kwek, Chin Kiat Women's & Children's Health Faculty of Medicine UNSW. "Isolation and characterisation of inhibitors of leukaemia with translocatins involving the mixed lineage leukaemia oncogene." Awarded by:University of New South Wales, 2007. http://handle.unsw.edu.au/1959.4/38520.
Full textAbstract:
Acute lymphoblastic leukaemia is the most common childhood cancer with cure rates of approximately 80%. This success can be attributed to the introduction of risk stratification for patients and employment of intensified treatment regimes for patients with high risk disease. However, the identification of prognostically important leukaemia subtypes, unfortunately, is an labour-intensive process. In addition, despite the success in treating childhood ALL, specific subgroups of patients nevertheless still have poor survival rates. This is particularly true for leukaemias characterised by chromosomal translocations involving the MLL oncogene on chromosome 11q23. By using a novel bioinformatics approach, GeneRave, a set of 12 classifier genes (PTPRK, FOS, ENG, Lgal-S1, TCFL5, LRMP, CTGF, IGJ, MX1, PENK, CD3D and HBG1) was selected from a publicly available U95 Affymetrix microarray dataset. Real time PCR carried out on a blinded cohort of 58 primary ALL samples yielded an accuracy of 86%. The absence of PENK gene expression in the majority of ALL samples tested appears to have decreased the overall accuracy. Nevertheless, the results indicate that this method of classification can be easily and quickly performed and therefore may be useful as an adjunct to routinely used methodology in the diagnostic classification of childhood ALL. Parellal screening of a 34,000 chemical small molecules library identified 30 ???hits??? that exhibited specificity toward leukaemia, and many of which shared structural similarity. The cytotoxic effect of these compounds was further investigated in a panel of 19 cell lines that included 3 MLL-translocated (MV411, THP-1 and PER-485), 7 non-MLL-translocated leukaemias (REH, Jurkat, K562, HL60, Hal-01, UOB-B, NB4), 2 immortalized normal blood cell lines, 4 non-leukaemic tumour cell lines (Calu6, MCF7, BE(2)-C, and HeLa) and 3 normal cell lines (HSF, MCF10a and MRC5). In particular, two compounds were identified, SM6 and SM7, that were highly effective at killing MLL-translocated cell lines in the low micromolar range while having little or no effect on the other cell lines. Treatment of PER-485 cells with SM6 and SM7 showed mark down-regulation of the MLL chimaeric fusion protein together with its down-stream targets. One other more broadly acting anti-leukaemia compounds were also identified.
48
Tang, Dongjiang. "Functional studies of SEI-1 and eIF5A2 : candidate oncogenes isolated from frequently amplified regions of ovarian carcinomas /." Click to view the E-thesis via HKUTO, 2006. http://sunzi.lib.hku.hk/hkuto/record/B36889775.
Full text
49
Lee, Wing-sang, and 李榮生. "The prognostic significance of DJ-1 in patients with renal cell carcinoma of clear cell type." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2009. http://hub.hku.hk/bib/B42925095.
Full text
50
Fallows, Sarah Aileen Sharon. "A study of p53 in epithelial ovarian cancer." Thesis, Queen's University Belfast, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.263321.
Full text