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Dissertations / Theses on the topic 'Prostate Carcinogenesis'
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1
Gao, Meiling. "Role of Sprouty2 in prostate carcinogenesis." Thesis, University of Glasgow, 2011. http://theses.gla.ac.uk/3090/.
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Prostate cancer (PC) is the most common cancer in men. In the UK alone, there are over 30,000 men diagnosed with PC every year. Loss of SPRY2 and activation of receptor tyrosine kinases are common events in PC. However, the molecular basis of their interaction and clinical impact remains to be fully examined. SPRY2 loss may functionally synergise with aberrant cellular signalling to drive PC and to promote treatment resistant disease. Using a combination of in vitro, pre-clinical in vivo models and clinical PC, this thesis shows the impact of SPRY2 loss upon activation of the ErbB signalling system via a positive feedback regulation of the ErbB-PI3K/AKT cascade. Loss of SPRY2 resulted in hyper-activation of PI3K/AKT signalling to drive proliferation and invasion by enhanced internalisation of EGFR/HER2 and their sustained localisation and signalling at the early endosome in a PTEN-dependent manner. This involves activation of p38 MAPK by PI3K to facilitate clathrin-mediated ErbB receptor endocytosis. Furthermore, this thesis suggests a critical role of PI3K/AKT in PC whereby in vitro and in vivo inhibition of PI3K suppresses proliferation and invasion, supporting PI3K/AKT as a target for therapy particularly in patients with PTEN-haploinsufficiency, low SPRY2 and ErbB expressing tumours. In conclusion, SPRY2 is an important tumour suppressor in PC; its loss drives the PI3K/AKT pathway via functional interaction with the ErbB system.
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Nelson, Adam William. "Estrogen receptor beta modulates prostate carcinogenesis." Thesis, University of Cambridge, 2017. https://www.repository.cam.ac.uk/handle/1810/267736.
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Prostate cancer (PC) is characterised by dependence upon androgen receptor (AR) as its driving oncogene. When organ-confined, radical treatment can be curative, however there is no cure for advanced, castration-resistant prostate cancer (CRPC). There is therefore a need to better understand the biology of PC, and how influencing AR can modify disease progression. Estrogen is essential for prostate carcinogenesis with evidence from epidemiological, in vitro, human tissue and animal studies. Most suggests that estrogen receptor beta (ERβ) is tumour-suppressive, but trials of ERβ-selective agents have not improved clinical outcomes. ERβ has also been implicated as an oncogene, therefore its role remains unclear. Additional evidence suggests interplay between ERβ and AR, the mechanisms of which are uncertain. The study hypothesis ‘ERβ is an important modulator of prostate carcinogenesis’ was developed to establish whether targeting ERβ could affect PC progression. Much of the confusion around ERβ stems from use of inadequately validated antibodies and cell line models. The first phase of this work was to test ERβ antibodies using an ERβ-inducible cell system. Eight ERβ antibodies were assessed by multiple techniques, showing that commonly used antibodies are either non-specific or only specific in one modality. Two reliable antibodies were identified. Next, cell lines previously used to study ERβ were assessed using validated antibodies and independent approaches. No ERβ expression was detected; an important finding that casts doubt on previously published ERβ biology. Subsequently, a PC cell line with inducible ERβ expression (LNCaP-ERβ) was developed and validated to enable controlled experiments on the effects of ERβ on proliferation, gene expression and ERβ/AR genomic cross-talk. Phase three of this work focused on ERβ biology in PC and its relationship to AR. Interrogation of clinical datasets showed that greater ERβ expression associated with favourable prognosis. Gene expression data from men treated with androgen deprivation therapy revealed that AR represses ERβ. This was confirmed in vitro. The LNCaP-ERβ cell line was treated with androgen and/or ERβ-selective estrogen. Activated ERβ in the presence of androgen-stimulated AR inhibited cell proliferation and down-regulated androgen-dependent genes. Genome-wide mapping of ERβ binding sites reveals that ERβ antagonises AR through competition for shared DNA binding sites. In conclusion, ERβ expression is down-regulated by AR during malignant transformation of prostate epithelium. We reveal an antagonistic relationship between ERβ and AR whereby sustaining or replacing ERβ may inhibit tumour growth through down-regulation of AR-target genes. In future, an ERβ-selective compound may be used to slow or abrogate PC progression.
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Roberts, Kristen M. "Dietary Bioactives and Human Prostate Carcinogenesis." The Ohio State University, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=osu1429195549.
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Wang, Wanzhong. "Inflammation and prostatic carcinogenesis : a morphological study of the human prostate /." Göteborg : Dept. of Urology, Institute of Clinical Sciences, Sahlgrenska University Hospital, The Sahlgrenska Academy at Göteborg University, 2007. http://hdl.handle.net/2077/9634.
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Xiao, Hong. "Distribution of Metal Ions in Prostate and Urine during Prostate Carcinogenesis." University of Cincinnati / OhioLINK, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1310410436.
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Kwan, Pak-shing, and 關百誠. "Roles of Daxx in mitosis and prostate carcinogenesis." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2009. http://hub.hku.hk/bib/B43085337.
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Kwan, Pak-shing. "Roles of Daxx in mitosis and prostate carcinogenesis." Click to view the E-thesis via HKUTO, 2009. http://sunzi.lib.hku.hk/hkuto/record/B43085337.
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Bantval, Rao Roheet. "Understanding the role of huntingtin interacting protein 1 (HIP1) in prostate carcinogenesis and cancer progression." Thesis, University of Cambridge, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.608064.
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Uegaki, Masayuki. "Downregulation of RalGTPase-activating protein promotes invasion of prostatic epithelial cells and progression from intraepithelial neoplasia to cancer during prostate carcinogenesis." Kyoto University, 2019. http://hdl.handle.net/2433/245310.
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Ling, Ming-tat Patrick, and 凌明達. "The role of Id-1 in prostate development and carcinogenesis." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2003. http://hub.hku.hk/bib/B31244506.
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Omar, Mahmoud Mustafa. "Functional analysis of TSPY and its role in prostate carcinogenesis." Thesis, University of Newcastle Upon Tyne, 2005. http://hdl.handle.net/10443/905.
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Testis specific protein Y chromosome encoded (TSPY) is a multicopy gene located on the human Y chromosome. It has been reported that the human genome harbours between 20 to 40 copies of the gene. Mammalian homologues of human TSPY were also found to be repetitive. The gene is expressed in human foetal and adult testis. The precise function of the expressed TSPY gene product is not fully defined, but it has been postulated to regulate proliferation of testicular spermatogonia. Up-regulation of TSPY expression has been detected in gonadoblastoma, testicular cancer and prostate cancer. The contribution of abnormal expression of TSPY to prostate carcinogenesis has not been investigated. Prostate cancer (CaP) and benign prostate hyperplasia (BPH) are the most common diseases of the human prostate. Prostate cancer is a disease of the elderly and is the second most common cancer and second most common cause of death from cancer among men in UK. In this thesis, the role of TSPY in prostate carcinogenesis was studied in four related aspects. First, TSPY protein and transcript expression pattern in CaP compared to Benign Prostate Hyperplasia (BPH) was studied using a combination of immunohistochemistry and mRNA in situ hybridisation. Second, the ability of TSPY to regulate cellular proliferation was investigated by transfection experiments of the prostate cancer LNCaP cell line. Third, TSPY genomic copy number in prostate cancer was characterised and compared to BPH. Finally, the downstream genes regulated by TSPY were investigated using high density microarray gene profiling method. An anti-human TSPY polyclonal antibody was developed for immunodetection of TSPY expression level in resected prostate tissues. In total, 72 cases of patients with prostate cancer and 20 cases of patients affected with BPH were studied by immunohistochemistry. TSPY was predominantly detected in the prostatic epithelium. In the benign gland, TSPY expression was limited to the basal cells compartment. TSPY expression was significantly up-regulated in prostate cancer when compared to BPH (P<0.0001). Furthermore, increased TSPY expression level was associated with aggressive disease (tumour with high Gleason score; P<0.02) and the presence of bone metastasis at the time of diagnosis (P<0.028). To address the functional role of 3 TSPY in prostate cancer, FLAG-TSPY was cloned and stably transfected into LNCaP cells. The presence of transfected TSPY increased LNCaP proliferation by two fold compared to empty vector control, consistent with a mitogenic function in CaP (P<0.0001). An absolute quantitative real time PCR based on Taqman assay was established and validated. TSPY genomic copy number was determined from comparing 161 samples: CaP-serum (n=47), resected tumour (n=31); BPH-serum (n=27), resected prostate (n=13) and control-serum (n=45). Of the clinical samples analysed, interpersonal variability of TSPY copy numbers was observed with the majority of cases containing between 20 to 50 TSPY copies per genome. Although, there were variability in TSPY copy numbers among individuals, there was no statistically significant correlation between TSPY copy number (serum and prostatic tissue) and the development of prostate cancer. Studying LNCaP stably transfected with TSPY and empty vector control, the key genes mediating the functional effect of TSPY were identified using Affymetrix oligonucleotide microarray method. In total, 332 genes have been altered 1.5 to 90 fold due to the effect of TSPY over-expression. Ten genes were selected and the gene expression levels were confirmed using semi-quantitative RT-PCR method. Gene clustering analysis has indicated changes in genes that regulate cellular differentiation (NRDG1, NF2, C-MAF and BMP11), apoptotic gene (BAX), cell cycle gene (cyclin G), detoxification gene (GST-2A) and genes linked to adhesion (PCDH7a, PLOD2 and IRS 1). In summary, TSPY is over-expressed in prostate cancer. This abnormal expression is linked to prostate cancer progression and metastasis. The up-regulation of TSPY expression is unlikely to be due to increased copy number. Expression of exogenous TSPY in prostate cancer cells enhanced cellular proliferation. The gene meditates its effect by down-regulating the expression pattern of selected differentiation, apoptosis and adhesion genes. Hence, over-expression of TSPY contributes to prostate carcinogenesis.
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Allen, Samantha M. "Characterization of beta subunits of voltage sensitive sodium channels in the LNCaP progression model and in the normal mouse prostate." Access to citation, abstract and download form provided by ProQuest Information and Learning Company; downloadable PDF file, 114 p, 2007. http://proquest.umi.com/pqdweb?did=1253509351&sid=1&Fmt=2&clientId=8331&RQT=309&VName=PQD.
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Wang, Xingya. "The distinct role of cyclooxygenase-2 in prostate and bladder carcinogenesis." Columbus, Ohio : Ohio State University, 2007. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1180488733.
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Al-Buheissi, Salah Zuhdi Zeidan. "Environmental carcinogenesis: a study of carcinogen-metabolizing activity in the human prostate and the risk for prostate cancer." Thesis, Institute of Cancer Research (University Of London), 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.430788.
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Tam, Ngai-chung Neville. "Cellular mechanisms of hormonal carcinogenesis in the prostate gland of the noble rat." Hong Kong : University of Hong Kong, 2000. http://sunzi.lib.hku.hk/hkuto/record.jsp?B21903591.
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Chan, Ching. "Telomerase activation and telomeric repeats alteration in sex hormone-induced prostatic carcinogenesis in the Noble rat /." Hong Kong : University of Hong Kong, 1998. http://sunzi.lib.hku.hk/hkuto/record.jsp?B20522769.
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Kwok, Wai-kei. "Oncogenic function of TWIST in the development and progression of prostate cancer." Click to view the E-thesis via HKUTO, 2007. http://sunzi.lib.hku.hk/hkuto/record/B3893825X.
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譚毅忠 and Ngai-chung Neville Tam. "Cellular mechanisms of hormonal carcinogenesis in the prostate gland of the noble rat." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2000. http://hub.hku.hk/bib/B43894379.
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Heer, Rakesh. "Characterisation of fibroblast growth factors in differentiation and carcinogenesis of the human prostate." Thesis, University of Newcastle Upon Tyne, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.423723.
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Sargsyan, Alex, and Hima Bindu Dubasi. "Milk Consumption and Prostate Cancer: A Systematic Review." Digital Commons @ East Tennessee State University, 2020. https://dc.etsu.edu/etsu-works/8510.
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Prostate cancer is the third most common cancer in men globally, and the most common cancer among men in the United States. Dietary choices may play an important role in developing prostate cancer; in particular, a higher dairy product intake has been associated with an increased risk of developing prostate cancer. The overall positive association between milk consumption and the risk of prostate cancer development and prostate cancer mortality has been well documented in multiple epidemiological studies. However, there is limited literature on the association between types of milk, as classified by fat content (skim, low fat, and whole), and the risk of developing prostate cancer. When further examining current state of the literature on this topic, there is a number of epidemiologic studies assessing the relationship between prostate cancer and milk consumption. On the contrary, very few experimental studies explore this topic. Further experimental research may be necessary to examine the relationship between dairy and dairy products consumption and the increased risk of development of prostate cancer. At this time, there are no formal clinical recommendations regarding dairy products consumption for patients who are at risk of prostate cancer development or who have a history of prostate cancer. In this manuscript, we sought to systematically review the existing literature on the association between milk consumption classified by fat content, and the risk of developing prostate cancer. These findings may be useful for the clinicians who provide recommendations for the patients at risk of developing prostate cancer.
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Sienkiewicz, Marta. "In Vitro Effects of Bisphenol A on Prostate Cells: Searching for Clues of Environmental Carcinogenesis." Thèse, Université d'Ottawa / University of Ottawa, 2012. http://hdl.handle.net/10393/22805.
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Estrogens maintain the appropriate androgen-estrogen balance for normal regulation of the structure and function of the male reproductive tract, including the prostate gland. This research investigated viability of cells and expression of selected genes in prostate carcinoma cells (PC-3) exposed to bisphenol A (BPA), an estrogen-like substance present in a number of plastic materials. PC-3 cells are able to metabolize BPA at concentrations below 100 µM. BPA exposure at concentrations between 1nM and 100 µM does not increase or significantly reduce cell viability of these cells. Although the genes investigated in this study (GSTP1 and MGMT) did not show a significant change in expression following in vitro exposure to BPA, the positive control ethinyl estradiol (EE2) caused an increase in GSTP1 expression at mRNA level. These results indicate that BPA does not affect the viability of prostate cells, and motivate a need for further research to identify other genes that could be affected by BPA.
22
Hendricks, Roshan. "Genetic analysis of the role of androgen metabolism in the pathogenesis of prostate cancer." Thesis, Stellenbosch : Stellenbosch University, 2004. http://hdl.handle.net/10019.1/49973.
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Thesis (MSc)--Stellenbosch University, 2004.ENGLISH ABSTRACT: Prostate cancer (CaP) has the highest incidence of any malignancy affecting South African males. The aetiology of prostate carcinoma indicate that ethnicity is one of the most important risk factors. The causes of these ethnic differences are unknown but presumably involve both environmental and genetic factors. Carcinoma of the prostate is androgen dependent, and it has been suggested that variations in androgen metabolism and synthesis may affect an individuals' risk. Therefore, genes involved in these pathways are candidates for determining CaP susceptibility. In this study two candidate genes in the androgen biosynthetic and metabolic pathway were analysed, viz., the androgen receptor gene (AR), involved in androgen transport and transcriptional activation, and the cytochrome p450c17a gene (CYP17), important for testosterone biosynthesis. Comprehensive mutation detection assays were designed (appropriate for analysis of archival paraffin-embedded material) for almost the entire coding region (excluding polymorphic repeat sequences), and including all splice site junctions of the AR gene, as well as the entire coding region of CYP17. The aim of this study was thus to determine the type and frequencies of genetic variants of these androgen metabolism genes within the diverse South African population, and to determine if the observed ethnic variation in the incidence and progression of CaP can be explained by ethnic-based genetic differences. For high sensitivity mutation detection, the most powerful of the pre-screening methods was used, namely denaturing gradient gel electrophoresis (DGGE). 20 CaP and 25 control benign prostatic hyperplasia (BPH) tissue samples were screened in order to identify possible mutations. Blood samples from the same patients were analysed in order to determine whether mutations are germline and therefore present in all cells of the body. Additional blood samples from the Western Province Blood Transfusion Service (WPBTS) (Refer to section 2.1.2, Table) were also analysed in order to determine the frequency of identified polymorphisms within the general population. Certain polymorphisms were further analysed in paraffin-embedded wax material (exclusively from Blacks) to determine the distribution of these polymorphisms in the Black population. Direct sequencing of mutant-containing DNA fragments was performed to determine the exact location and nature of mutation. Using the AR- DGGE assay 4 novel mutations were identified as well as a previously reported codon 211 (E211) polymorphism. With the CYP17- DGGE assay, 3 novel single nucleotide polymorphisms (SNPs) were detected. Three base variants occured, in codons 36 (L36), 46 (H46) and 65 (S65), as well as intronic substitutions in intron 4 (IVS+58G4C) and intron 6 (IVS-25C7A). Frequencies of SNPs were measured in the CaP and BPH samples. In conclusion, the identified polymorphisms could be used as markers in determining CaP susceptibility and may thus facilitate the identification of individuals with a high- or low-risk of developing carcinoma of the prostate.
AFRIKAANSE OPSOMMING: Prostaatkanker vertoon die hoogste voorkoms van enige kwaardaardigheid wat Suid-Afrikaanse mans aantas. Die etiologie van prostaatkarsinoom dui aan dat etnisiteit een van die mees belangrike risikofaktore is. Oorsake van hierdie etniese verskille is onbekend, maar vermoedelik is omgewing en genetiese faktore albei betrokke. Karsinoom van die prostaat is androgeenafhanklik en daar is voorgestel dat variasies in androgeenmetabolisme en androgeensintese 'n persoon se risiko mag affekteer. Gevolglik, is gene betrokke in hierdie paaie kandidate vir die bepaling van prostaatkanker vatbaarheid. In hierdie studie het ons twee kandidaat gene in die androgeen biosintetiese en metaboliese pad geanaliseer, naamlik, die androgeen reseptor geen (AR), betrokke in androgeen vervoer en aktivering van transkripsie, en die sitokroom p450c17a geen (CYP17), belangrik vir testosteroon biosintese. Ons het omvattende mutasie-bespeurings-essai-sisteme ontwikkel (ook uitvoerbaar op argivale paraffien-bewaarde materiaal), wat amper vir die hele koderende streek van die AR geen gebruik kan word (uitsluitend herhalende polimorfiese reekse) en wat alle splytpunt-aansluitings van die AR geen insluit, asook vir die hele koderende streek van CYP17. Die doel van hierdie studie was dus om die tipe en frekwensies van genetiese variante van androgeen metabolisme gene in ons diverse Suid-Afrikaanse bevolking te bepaal, en om vas te stel of die waarneembare etniese wisseling in die insidensie en vordering van prostaatkanker verstaan kan word deur etnies gebaseerde genetiese verskille. Die mees sensitiewe tegniek wat tans beskikbaar is vir vooraf-sifting vir onbekende mutasies is gekies, naamlik denaturerende gradiënt gel elektroforese (DGGE). Om moontlike mutasies op te spoor, het ons 20 prostaatkanker en 25 benijne prostaathiperplasie (BPH) monsters geanaliseer. Analise was gedoen op bloedmonsters van dieselfde pasiënte om vas te stel of kiemlyn mutasies (in alle liggaamselle) teenwoordig is. Bykomstige bloedmonsters (van die Westelike Provinsie Bloedoortappingsdiens) is ook geanaliseer om die frekwensie van bespeurde polimorfismes in die algemene bevolking te bepaal. Argivale paraffien-bewaarde materiaal (eksklusief van Swartes) is ook geanaliseer om die verspreiding van sekere polimorfismes in die Swart bevolking te bepaal. Direkte DNA volgorde bepaling van mutante DNA fragmente is uitgevoer om die ligging en tipe van mutasies te bepaal. Met die toepassing van ons AR-DGGE mutasiesisteem het ons 4 nuwe mutasies ontdek asook 'n kodon 211 (E211) polimorfisme wat voorheen gevind is. Vyf enkel nukleotied polimorfismes is met die CYP17-DGGE mutasiesisteem opgespoor. Die polimorfismes sluit in: drie basis veranderinge wat voorkom in kodons 36 (L36), 46 (H46) en 65 (S65), asook introniese substitutisies in intron 4 (IVS+58G4C) en intron 6 (IVS-25C7 A). Frekwensies van die polimorfismes was bereken in die prostaatkanker en BPH monsters. Die resultate aangebied in hierdie tesis dui aan dat die gevonde polimorfismes as merkers gebruik kan word om prostaatkanker vatbaarheid te bepaal en daardeur individue te identifiseer met 'n hoë of lae risiko vir prostaatkarsinoom ontwikkeling.
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Dolega, Monika Elzbieta. "Developement of microtechnologies for 3D cell culture to study prostate acini formation and carcinogenesis." Thesis, Grenoble, 2014. http://www.theses.fr/2014GRENS022/document.
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Tout épithélium glandulaire sécrétoire est constitué d'une unité structurale et fonctionnelle commune, l'acinus. C'est une architecture sphérique pluricellulaire parfaitement différentiée et polarisée qui, reconstruite en culture 3D, mime l'organisation réelle du tissu. Etudier les déterminants environnementaux et génétiques qui gouvernent la transformation d'un acinus en sphéroïde s'apparentant à une tumeur est l'un des enjeux majeurs des modèles in vitro. Un des défis actuels est d'adapter ces modèles in vitro à des conditions de culture 3D qui soient compatibles avec la réalisation de cribles génétiques en 3D, basés par exemple sur l'ARN interférence (RNAi). Cependant, les formats standards de culture 3D et les méthodes analytiques ne sont pas compatibles aux cribles haut-débit. Ils ne permettent pas de contrôler la taille et la distribution des acini, sont dépendants d'immuno-marquages et les acquisitions sont longues. Par ailleurs, la microscopie confocale et vidéomicroscopie offrent un champ d'observation restreint qui ne permet pas d'observer un grand nombre de structures 3D en même temps, pour permettre une analyse statistique. Ainsi, dans le but i) de développer des modèles cellulaires appropriés en 3D, ii) d'adresser des questions fondamentales relatives au cancer de la prostate et iii) de réaliser des cribles RNAi dans un contexte plus pertinent que la culture 2D, j'ai développé des outils innovants au format microsystèmes adaptés à l'analyse haut-débit d'un grand nombre d'objets 3D. En optimisant les conditions de culture cellulaire 3D sur le modèle de la lignée cellulaire RWPE1, j'ai pu récapituler les étapes de formation des acini prostatiques et montrer que la formation du lumen est indépendante de la polarité et est gouvernée par deux mécanismes, « hollowing » et cavitationIn all secretory epithelia from glandular tissues, there is a common structural and functional unit, the acinus. It is a well polarized and organized pluricellular structure that is spontaneously reconstructed in 3D culture, therefore closely mimics the real structure we find in vivo. For my purpose, acini are used as models for tumor initiation and cancer development. One of the objectives of Biomics laboratory is to identify the genetic and microenvironmental determinants of prostate acini morphogenesis and polarity. The strategy is based on High-Throughput (HT) RNA interference (RNAi)-based screening. To meet this objective, my project was to develop appropriate 3D cell models which closely mimic the cyst-like and duct-like structure of prostate. By optimizing conventional 3D culture in Matrigel, I could recapitulate prostate acini morphogenesis and showed that lumen formation is independent to the polarity, which appears later. However, the conventional 3D cell culture formats and analytical tools are not suited for HT Screening (HTS). They lack control over acini size, are label-dependant and therefore time-consuming and labor intensive. Also, classical microscopy offers a very limited field of view and hence does not allow observing a large amount of 3D structures for statistical analysis
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Spees, Colleen K. "Dysregulation of p53 Gene Expression in Human Prostate Carcinogenesis and Its Relationship to Angiogenesis." The Ohio State University, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=osu1313523656.
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Wang, Yuzhuo. "The evaluation of biomarkers in sex hormone-induced prostatic carcinogenesis in the Noble (Nb) rat /." Hong Kong : University of Hong Kong, 1997. http://sunzi.lib.hku.hk/hkuto/record.jsp?B18564501.
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Kwok, Wai-kei, and 郭慧琪. "Oncogenic function of TWIST in the development and progression of prostate cancer." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2007. http://hub.hku.hk/bib/B3893825X.
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王玉琢 and Yuzhuo Wang. "The evaluation of biomarkers in sex hormone-induced prostatic carcinogenesis in the Noble (Nb) rat." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1997. http://hub.hku.hk/bib/B3123625X.
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Slater, Sarah Jane. "Does BFR1, a component of the transcription factor (TFIIIB), have a role in prostate carcinogenesis?" Thesis, University of Glasgow, 2016. http://theses.gla.ac.uk/7479/.
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Prostate cancer is the commonest cancer diagnosed in UK men and the second commonest cause of cancer mortality. There is an urgent need to improve our ability to differentiate indolent from aggressive disease to achieve optimal evidence-based treatment choices. Tumourigenesis involves deranged cellular proliferation, which in turn necessitates gene translation to drive protein synthesis. The transcription products of RNA polymerase III (Pol III) play a critical role in protein synthesis. TFIIB-related factor 1 (BRF1) is a vital transcription factor and functions as part of the Pol III transcription apparatus to mediate transcription of transfer RNAs (tRNAs). tRNAs). In this thesis, using a range of in vitro/ in vivo pre-clinical models and clinical resources, I have characterised the status of BRF1 in prostate cancer. Abnormal BRF1 expression has been previously suggested in small pilot studies in a number of tumour types. Our recent immunohistochemistry data showed evidence of upregulated BRF1 expression in clinical prostate tumours. I observed high levels of BRF1 expression in a comprehensive panel of human prostate cancer cell lines. To further examine the functional significance of BRF1 in prostate cancer, BRF1 expression was manipulated. Upon transient over-expression of BRF1, cell proliferation was upregulated in several prostate cancer cell lines. In contrast, when Brf1 expression was reduced, cell proliferation decreased, along with associated G2/M accumulation. To test the in vivo function of BRF1 in prostate carcinogenesis, a genetically engineered mouse model (GEMM) was developed with enhanced Brf1 expression in the prostate, namely Pten-Brf1, while Pten was deleted to recapitulate commonly observed activation of PTEN/AKT pathway in clinical prostate cancer. The Pten-Brf1 mice harboured enhanced growth of their prostate tumours, although they were histologically similar to prostate tumours driven by homozygous Pten deletion (or Pten-). Overall, Pten-Brf1 mice survived significantly shorter period than the control Pten- mice. In summary, my research conducted in this thesis highlights a potential role for BRF1 (as part of the Pol III transcriptional apparatus) in prostate carcinogenesis. Further research is therefore warranted to define its role as a cancer biomarker and as a novel target for therapy.
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Gnanapragasam, Vincent Jeyaseelan. "Fibroblast growth factor 8 as a model of androgen receptor mediated carcinogenesis in human prostate cancer." Thesis, University of Newcastle Upon Tyne, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.247915.
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Wan, Lei. "Dietary Tomato and Lycopene Modulate Critical Androgen-driven mRNA and miRNA Expression in Early Prostate Carcinogenesis." The Ohio State University, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=osu1388489457.
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歐陽雪松 and Xuesong Ouyang. "Differential gene expression during sex hormone-induced prostate carcinogenesis in the rat with emphasis on ID-1 gene and its role inhuman prostate cancer." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2001. http://hub.hku.hk/bib/B29979055.
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Ouyang, Xuesong. "Differential gene expression during sex hormone-induced prostate carcinogenesis in the rat with emphasis on ID-1 gene and its role in human prostate cancer /." Hong Kong : University of Hong Kong, 2001. http://sunzi.lib.hku.hk/hkuto/record.jsp?B24738694.
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Berman-Booty, Lisa Danielle. "Suppression of Carcinogenesis and Tumor Progression by an Energy Restriction-Mimetic Agent in Murine Models of Prostate Cancer." The Ohio State University, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=osu1365512650.
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Di, Kaijun, and 狄凱軍. "The role of Id-1 on the proliferation, motility and mitotic regulationof prostate epithelial cells." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2007. http://hub.hku.hk/bib/B38944704.
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Teichert, Friederike. "Approaches to the discovery of biomarkers of prostate carcinogenesis in TRAMP mice and of chemopreventive efficacy of tea polyphenols." Thesis, University of Leicester, 2008. http://hdl.handle.net/2381/9920.
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To improve prostate cancer management in humans who have, or are at risk of developing, the disease, biomarkers are required to aid early diagnosis and monitoring of response to chemotherapeutic or chemopreventive intervention. In this project metabonomic and peptidomic approaches were used to study biological changes associated with prostate carcinogenesis in a transgenic mouse model (TRAMP, TRansgenic Adenocarcinoma of the Mouse Prostate). Observed changes were compared with pathological alterations. Metabolome and peptidome analyses were conducted in TRAMP mice exposed to chemopreventive intervention with green tea polyphenols (GTP). Effects of consumption of GTP or black tea theaflavins on the plasma and urine metabonome/peptidome in patients with benign prostatic hyperplasia (BPH) were also investigated. Oxidative stress status reflected by urinary 8-oxo-7,8-dihydro-2’-deoxyguanosine (8-oxodG) was assessed in mice and humans on tea polyphenols. Metabonomic profiling revealed that at early stages of carcinogenesis in mice, alterations of tumour levels of choline metabolites resembled the human disease. In contrast, in advanced stages of TRAMP prostate carcinogenesis, phospholipid metabolism is affected differently by malignancy than in its human counterpart. Disturbed prostate-specific citrate metabolism seems common to both human and TRAMP prostate tumours when compared to normal tissue. These results suggest that the TRAMP mouse may be a better model with respect to humans of early stage carcinogenesis with minor proliferative lesions than of more advanced stages of malignancy. Urinary 8-oxodG levels were not affected by presence of prostate cancer or intervention with tea. Metabolic profiling gave evidence for an effect of GTP on energy metabolism in both mice and humans. Although TRAMP and GTP-groupspecific metabonomic and peptidomic changes were found in plasma and urine, none of these metabolites or peptides could be unambiguously identified as biomarkers of carcinogenesis or GTP exposure. Among possible confounding factors which should be taken into consideration in future metabonomic/peptidomic studies is the host’s gut microflora.
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Raymonvil, Aleeshaia Danner. "Serum Iron Concentration and Prostate Cancer in the United States." ScholarWorks, 2017. https://scholarworks.waldenu.edu/dissertations/3257.
Full textAbstract:
Over 2 million adult men in the United States have been diagnosed with prostate cancer, with nearly 200,000 new diagnoses each year. This type of cancer is the leading cause of mortality in U.S. men. One possible risk factor for prostate cancer is a high level of iron in the body, but the association has yet to be confirmed. This study was an investigation of the relationship between serum iron concentration and prostate cancer using data obtained from the 2009-2012 National Health and Nutrition Examination Surveys. This quantitative study involved 1,850 men in the U.S. aged 51 to 70 years. The framework for this research was based on the exposure-disease model. Participants' data were analyzed using chi-squared independence tests and hierarchical logistic regression, while controlling for demographic variables (body mass index, age, ethnicity, poverty-to-income ratio, educational attainment, and hours worked in the last week) to account for potential confounding effects. Serum iron concentration was not found to be significantly associated with prostate cancer diagnosis in this sample. Additional results indicated a significant association between age and prostate cancer, and between ethnicity and prostate cancer, confirming previous research findings. This study contributes to positive social change by confirming the importance of screening for prostate cancer among high-risk populations and by suggesting that it is premature to use serum iron concentration as a screening tool to detect prostate cancer.
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Gonçalves, Bianca Facchim 1986. "Carcinogênese prostática quimicamente induzida por N-metil N-nitrosuréia (MNU) em gerbilos da Mongólia = associação com promotores esteróides ou dieta hiperlipídica = Prostate carcinogenesis chemically induced by N-methyl-N Prostate carcinogenesis chemically induced by N-methyl-Nnitrosourea: association with steroids promoters or high-fat diet." [s.n.], 2013. http://repositorio.unicamp.br/jspui/handle/REPOSIP/317938.
Full textAbstract:
Orientadores: Sebastião Roberto Taboga, Silvana Gisele Pegorin de CamposTese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia
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Resumo: Um dos principais desafios no campo de pesquisa do câncer prostático é a busca por sistemas modelo que permitam a investigação dos aspectos patológicos, bioquímicos e genéticos desta doença. O gerbilo Meriones unguiculatus tem possibilitado a avaliação de lesões prostáticas e sua evolução de estágio benigno para maligno (invasivo) após período relativamente curto de tratamento com o carcinógeno N-Metil-N-Nitrosuréia (MNU), um potente causador de metilação do DNA por ação direta. Assim, o presente trabalho teve por objetivos: 1) Determinar a incidência, multiplicidade e latência tumoral de lesões espontâneas e quimicamente induzidas nos lobos prostáticos ventral e dorsolateral do gerbilo; 2) Investigar se o estradiol exerce papel protetor e/ou promotor sobre neoplasias induzidas por MNU; 3) Avaliar o potencial promotor da dieta hiperlipídica sobre a carcinogênese induzida na próstata ventral; 4) Analisar a participação de produtos alterados de genes ras e do status global de metilação do DNA do epitélio prostático no processo tumoral mediado por MNU. Para tanto foram utilizados animais adultos submetidos à dose única intraperitoneal de MNU (50mg/Kg), exceto o grupo controle. Os grupos experimentais foram submetidos à exposição crônica de andrógeno, estradiol ou dieta hiperlipídica por 14 e 28 semanas. As metodologias aplicadas envolveram análises quantitativas e estatísticas de multiplicidade e incidência de lesões prostáticas, peso corporal, acúmulo de gordura corporal, peso prostático, dosagens hormonais, índice proliferativo, cariometria, frequência de células AR-positivas e basais, status global de metilação e determinação da expressão de proteínas. O modelo de indução tumoral prostática por MNU associado à testosterona no gerbilo se mostrou eficaz, pois reduziu a latência tumoral e permitiu o estudo de estágios avançados da carcinogênese após curto período. As neoplasias se manifestam inicialmente no lobo dorsolateral e requerem um tempo maior para se estabelecer no lobo ventral. No entanto, a progressão de lesões pré-malignas para malignas ocorre de maneira mais significativa no lobo ventral. Isso indica que a progressão tumoral ocorre de maneira distinta entre os lobos prostáticos e que vias alternativas estão possivelmente envolvidas nesse processo. A longa exposição a altas doses de estrógeno foi capaz de prevenir e reduzir a taxa de crescimento tumoral. Apesar dos efeitos terapêuticos contra a progressão neoplásica, a terapia estrogênica levou ao estabelecimento de um epitélio com características distintas da próstata normal, como: mudanças no padrão de metilação do DNA e aumento de células basais e AR positivas. Juntos, esses eventos contribuíram para criar um ambiente epitelial instável que pode provocar a recidiva das lesões em períodos subsequentes. A associação entre MNU e dieta hiperlipídica promoveu aumento na incidência de lesões estimuladas pelo carcinógeno isoladamente, as quais apresentaram maior número de células AR-positivas, ruptura da camada de músculo liso indicando microinvasão tumoral, e alta reatividade para metaloproteinase do tipo 2. A análise molecular indicou alta expressão das proteínas Ras em tecidos induzidos por MNU, sugerindo a participação dessa via na promoção e progressão de tumores prostáticos. Assim, conclui-se que a dieta hiperlipídica pode ser considerada um agente promotor da carcinogênese prostática, e o gerbilo representa um bom modelo para estudos histopatológicos
Abstract: One of the major challenges in the field of prostate cancer research is the search for model systems that allow the investigation of pathological, biochemical and genetic factors of this disease. The gerbil Meriones unguiculatus has enabled the evaluation of prostate lesions and evolution from benign to malignant (invasive) stage after a relatively short period of treatment with the carcinogen N-methyl-N-nitrosourea (MNU), a potent causative of DNA methylation by direct action. Thus, this study aimed to: 1) Determine the incidence, multiplicity, and tumor latency of spontaneous and chemically-induced lesions in ventral and dorsolateral gerbils' prostatic lobes; 2) Investigate whether estradiol exerts protective and/or promoter hole on neoplasms induced by MNU; 3) Evaluate the promotional potential of high-fat diet on induced-carcinogenesis in ventral prostate; 4) Analyze the involvement of altered ras gene products and the global DNA methylation status of prostate epithelium on MNU-mediated tumor process. Therefore, we used adult animals subjected to a single intraperitoneal dose (50mg/kg) of MNU, except the control group. The experimental groups were subjected to chronic exposure of androgen, estradiol or high-fat diet for 14 and 28 weeks. The methodologies involved quantitative and statistical analysis of multiplicity and incidence of prostatic lesions, body weight, body fat accumulation, prostate weight, hormonal measurements, proliferative index, karyometry, frequency of AR-positive and basal cells, global methylation status and determination of protein expression. The model of prostatic tumor induction by MNU associated with testosterone in the gerbil was effective because it reduced tumor latency and allows the study of advanced stages of carcinogenesis after short period. Neoplasms manifest initially in dorsolateral lobe and require a longer time to be established in ventral lobe. However, the progression from premalignant to malignant lesions occurs more significantly in the ventral lobe. This indicates that tumor progression occurs differently between prostatic lobes and alternative pathways maybe possibly involved in this process. Long exposure to high doses of estrogen was able to prevent and reduce the rate of tumor growth. Despite therapeutic effects against neoplastic progression, estrogen therapy led to the establishment of an epithelium with distinct characteristics from normal prostate, such as changes in the pattern of DNA methylation and increased amount of basal cell and ARpositive cells. Together, these events contributed to create an unstable epithelial compartment that can cause lesions recurrence in subsequent periods. The association between MNU and high-fat diet promoted an increase in incidence of lesions stimulated by carcinogen alone, which had a higher number of AR-positive cells, disruption of the smooth muscle layer indicating tumor microinvasion and high reactivity for metalloproteinase type 2. Molecular analysis indicated high expression of Ras proteins in tissues induced by MNU, suggesting the involvement of this pathway in the promotion and progression of prostate tumors. Thus, we conclude that the high-fat diet can be considered a promotional agent of prostate carcinogenesis and that gerbil is a good model for histopathological studies
Doutorado
Biologia Celular
Doutora em Biologia Celular e Estrutural
38
Schröder, Anne [Verfasser]. "Inhibition of the IL-6/STAT3 signaling pathway for therapeutic intervention in prostate carcinogenesis and cancer cell differentiation / Anne Schröder." Aachen : Hochschulbibliothek der Rheinisch-Westfälischen Technischen Hochschule Aachen, 2013. http://d-nb.info/1037106776/34.
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Di, Kaijun. "The role of Id-1 on the proliferation, motility and mitotic regulation of prostate epithelial cells." View the Table of Contents & Abstract, 2007. http://sunzi.lib.hku.hk/hkuto/record/B38588985.
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Pinho, Cristiane Figueiredo. "Papel modulador do raloxifeno durante a carcinogênese prostática em ratos." Botucatu, 2019. http://hdl.handle.net/11449/181762.
Full textAbstract:
Orientador: Wellerson Rodrigo ScaranoResumo: A capacidade de progressão do câncer de próstata para uma fase não-responsiva às terapias de privação androgênica traz à luz a importância do estudo de tratamentos adjuvantes. Pesquisas recentes apontam receptores estrogênicos como possíveis alvos terapêuticos em neoplasias, podendo ser modulados por fármacos como o Raloxifeno, atualmente utilizado na prevenção do câncer de mama e tratamento da osteoporose. Nesse contexto, o objetivo deste estudo foi avaliar os potenciais efeitos histoprotetores e antiproliferativos da terapia com Raloxifeno, durante a carcinogênese prostática. Para isso, 34 ratos Fisher 344 machos foram inoculados com o carcinógeno MNU (15 mg/kg) na cápsula dos lobos ventral e dorsolateral e receberam doses subcutâneas de cipionato de testosterona, duas vezes por semana, durante 220 dias, processo aqui denominado de Indução de Carcinogênese. Posteriormente, foram divididos em dois grupos experimentais para o período de Tratamento: grupo Raloxifeno, recebendo 10 mg/kg de peso corpóreo/dia de Raloxifeno diluído em 0,2 ml de óleo de milho durante 30 dias consecutivos; grupo Induzido, recebendo somente 0,2 ml de óleo de milho (veículo) durante 30 dias consecutivos. Outros 10 animais pertencentes ao grupo Controle receberam veículo duas vezes por semana por 220 dias para simular o processo de Indução e, posteriormente, durante 30 dias consecutivos para simular o período de Tratamento. Após a eutanásia, o sangue e as próstatas ventral e dorsolateral foram coletado... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: Prostate cancer ability to progress to a non-responsive phase to androgen deprivation therapy emphasizes the importance of study on adjuvant treatments. Recent research suggests estrogen receptors as possible therapeutic targets in neoplasias and they can be modulated by drugs such as Raloxifene, currently used in the prevention of breast cancer and treatment of osteoporosis. In this context, this study aimed to evaluate the histoprotective and antiproliferative potential effects of Raloxifene therapy during prostatic carcinogenesis. Thereunto, 34 male Fisher 344 rats were inoculated with the MNU carcinogen (15 mg / kg) in the ventral and dorsolateral lobe capsule and received subcutaneous doses of testosterone cypionate twice a week for 220 days. Subsequently, they were divided into two experimental groups: Raloxifene group, receiving 10 mg/kg of body weight/day of Raloxifene diluted in 0.2 ml of corn oil for 30 consecutive days; Induced group, receiving only 0.2 ml corn oil (vehicle) for 30 consecutive days. Another 10 animals belonging to the Control group received vehicle twice a week for 220 days to simulate the induction process and subsequently for 30 consecutive days to simulate the treatment period. After euthanasia, blood and the ventral and dorsolateral prostate lobes were collected for hormonal dosage, histopathological analysis of the lesions, quantification of mast cells, picrosirius (collagen fibers) and immunostaining for AR (androgen receptor), α-actin and Ki... (Complete abstract click electronic access below)
Doutor
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Mastella, Aline Klein. "AVALIAÇÃO DE MARCADORES INFLAMATÓRIOS E ANTÍGENOS ABO EM PACIENTES COM DIAGNÓSTICO DE CÂNCER DE PRÓSTATA." Universidade Federal de Santa Maria, 2008. http://repositorio.ufsm.br/handle/1/5944.
Full textAbstract:
Prostate cancer (PC) is a disease in men and became the first cause of death by
cancer in Brazil. The carcinogenesis is related to the presence of local inflammatory
process and to the loss of blood group in neoplasic cells. The aim of the study was to
assess the involvement of inflammatory process and the expression of A and B
antigens in prostate cancer. Serological measure of prostatic specific antigen (PSA),
reactive C protein (CRP) and ischemia modified albumin (IMA) was made in healthy,
hyperplasic (BPH) and neoplasic prostate volunteers. PSA values increased when
comparing healthy (1,13 ng/ml), BPH (18,69 ng/ml) and PC (134,68 ng/ml) patients.
IMA showed to be over 0,400 ABSU just in BPH patients. Medium CRP
concentrations did not exceed normal values (5 mg/l) in the studied groups. There
was not a meaningful difference in the evaluation of PSA, CRP and IMA in relation to
the ABO blood group of the patients. The carcinogenesis of prostate seemed to
abolish the expression of A and B antigens in neoplasic cells. Inflammatory feature
showed to be mild in the prostatic alterations and did not reach reference values. IMA
acted as a marker of oxidative stress and patients with BPH demonstrated
concentration above 0,400 ABSU. The diagnosis of BPH must be considered when
IMA is being used as a marker of myocardial ischemia. The ABO blood group of the
volunteers did not show difference in the analysis of PSA, CRP and IMA.O câncer de próstata (CaP) é uma doença que acomete homens e tornou-se a primeira causa de morte por câncer no Brasil. A carcinogênese vem sendo relacionada à presença de processo inflamatório local e também à perda de antígenos eritrocitários nas células neoplásicas. O objetivo do trabalho foi avaliar o envolvimento do processo inflamatório e a expressão dos antígenos A e B em pacientes com CaP. Foi realizada dosagem sorológica do antígeno prostático específico (PSA), da proteína C reativa (PCR) e da albumina modificada pela isquemia (IMA) em pacientes saudáveis e em pacientes com alterações neoplásica ou hiperplásica prostática. Os valores de PSA mostraram-se crescentes na comparação dos pacientes saudáveis (1,13 ng/ml), com HBP (18, 69 ng/ml) e com CaP (134, 68 ng/ml). A IMA apresentou valores em unidade de absorbância acima de 0,400 apenas nos pacientes com HBP, sendo que os grupos sanguíneos O e AB apresentaram as maiores médias. Os valores médios da PCR não ultrapassaram o valor de referência de 5 mg/l nos grupos estudados. Não houve diferença significativa na avaliação de cada variável (PSA, PCR e IMA) em relação à tipagem sanguínea ABO dos pacientes. O processo neoplásico prostático mostrou anular a expressão dos antígenos A e B nas células afetadas. A característica inflamatória mostrou-se branda nas alterações prostáticas estudadas, não ultrapassando o valor de referência. A IMA atuou como um marcador de estresse oxidativo, sendo que os pacientes com HBP mostraram valor médio acima de 0,400 UABS. Tal diagnóstico prostático é útil ser considerado quando a IMA está sendo usada como marcador de isquemia cardíaca. O grupo sanguíneo ABO dos pacientes não mostrou diferença significativa nas determinações de PSA, PCR e IMA.
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Souza, Cristiani Zanetoni Israel de. "Carcinogenese experimental no lobulo ventral da prostata do geribo da Mongolia." [s.n.], 2007. http://repositorio.unicamp.br/jspui/handle/REPOSIP/317917.
Full textAbstract:
Orientador: Sebastião Roberto TabogaTese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia
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Resumo: O câncer de próstata atualmente é o tumor mais comum em homens com mais de 50 anos de idade. Entre os fatores de risco que contribuem para o aumento dessa doença destaca-se o envelhecimento, período em que ocorrem acentuados desequiliorios hormonais. Há muitas dificuldades na obtenção de material humano para estudos do desenvolvimento de tumores prostáticos, pois esta questão esbarra na ética médica. Vários grupos de pesquisa vêm tentando desenvolver, caracterizar e validar modelos roedores para análise do câncer de próstata. Modelos autóctones, nos quais são estudadas as lesões prostáticas espontâneas, têm desempenhado papel relevante nas pesquisas dessa neoplasia. Além disso, inúmeras investigações têm sido feitas sobre a indução experimental de tumores na próstata de roedores de laboratório: ratos, camundongos e cobaias. Em uma primeira etapa deste trabalho, foram realizadas análises morfológicas (estruturais e ultra-estruturais), quantitativas e funcionais dos componentes celulares dos compartimentos epitelial e estromal do lobo ventral da próstata do gerbilo" velho (Meliones unguiculatus). A morfologia prostática nesses animais revelou que em uma mesma glândula puderam ser observadas regiões funcionais com epitélio secretor normal e outras áreas com alterações histopatológicas atípicas. Nesses, o declínio de testosterona esteve associado a alterações proliferativas na glândula, levando ao entendimento da importância desse andrógeno na homeostase e funcionalidade prostática. Devido a essas constatações, em uma segunda etapa, foi feita a indução experimental de tumores na próstata do gerbilo adulto, após tratamento conjugado de N-metil-N-rutrosouréia com propionato de testosterona. Depois de estabelecidos os tumores, as próstatas foram processadas para estudos rustológico, imunocitoquímico e ultra-estrutural. Os resultados mostraram que em gerbilos o surgimento de lesões prostáticas ocorreu em períodos experimentais de até 9 meses e que tanto o cancerígeno como a testosterona, associados ou não, foram indutores de neoplasias. Sugere-se que as células atípicas possam apresentar potencial invasivo pela observação da ruptura da membrana basal pelos métodos de imunocitoquímica para laminina e análise ultra-estrutural. Detectou-se também no gerbilo a expressão da proteína citoplasmática Alfa-Metilacil-CoARacemase (PS04S) em células prostáticas neoplásicas, bem como é observado no câncer prostático do homem. Assim, este trabalho é pioneiro na demonstração da expressão de P504S em roedores. A partir dos resultados apresentados constatou-se que o gerbilo é um modelo animal para estudos de carcinogênese química prostática, que somados aos dados da literatura, levarão ao melhor entendimento da biologia de lesões da próstata
Abstract: The prostate cancer is the most common tumor that attacks men from the 50's decade. Among the risk factors that contribute to this disease's increase stand out the aging process, when hormonal unbalances happen frequendy. Developmental studies of prostatic tumors have been complicated because of difficult in obtaining human material, once this question lies on medical ethics. Researchers group have had tried to develop, characterize and validate some rodent models to analyze the prostate cancer. Autoctone models used to study spontaneous prostatic lesions have performed important role to these kind of neoplasia. ln addition, lots of innstigations have been done about experimental induction of prostatic tumors in rats, mice and guinea pig. ln a first phase of the present work, it was realized in the ventral lobe of old gerbil's prostate veriones unguiculatllm) structural and ultra-structural morphological, quantitative and functional analyzes of the cellular compounds of epithelial and stromal compartments. The prostatic features of theses animaIs revealed that in a same gland could be noted functional regions containing normal secretof)' epithelium and regions completely altered, showing histopathological lesions. A testosterone concentration decrease associated to these prolifera tive sites confmns the importam role of this androgen to the prostatic homeostasis. Because of these data, in the second phase of this. work, it was done a prostatic tumors experimental induction in the adult gerbil, after conjugate treatment of N-metil-N-nitrosourea with testosterone propionate. Once the tumors were established, prostate fragments were processed for histological, immunocytocl)emical and ultra-structural studies. The results showed that in gerbils, the emergence of prostatic lesions happened in experimental periods of until 9 months and both the carcinogen and testosterone, associated or not, was able to induce these adenocarcinomas. The invase potencial of anomalus cells could be proved by ultra-structural analyz~s and by the immunocytochemical test for laminima, noted in the basal membrane disruption. On the other hand, it was observed that gerbil is one of the pioneers in expression of the citoplasmatic protein Alfa-lvletilacilCoARacemase (P504S), which is found in the neoplastic cells, likely in prostatic human cancer. Concluding, this study is pioneer in the demonstration of the P504S expression in rodents. Based on these presented data, it was verified that gerbil is a good experimental model to chemical carcinogenesis research of the prostate, which taken together with previous literature will give a better and profounder understanding of prostatic lesions
Doutorado
Biologia Celular
Doutor em Biologia Celular e Estrutural
43
Chan, Ching, and 陳淸. "Telomerase activation and telomeric repeats alteration in sex hormone-induced prostatic carcinogenesis in the Noble rat." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1998. http://hub.hku.hk/bib/B20522769.
Full textAbstract:
(Uncorrected OCR)
Abstract of thesis entitled
Telomerase activation and telomeric repeats alteration
in sex hormone-induced prostatic carcinogenesis in the Noble rat submitted by
Chan Ching
for the Degree of Master of Philosophy at the University of Hong Kong In November, 1998
Despite its distinction as the most frequently diagnosed cancer and the�second leading cause of cancer deaths in men, little is known about the causes and mechanisms of prostatic carcinogenesis. The animal model, based on the existing sex hormone-induced prostate carcinogenesis in the Noble rat, by substantially increasing the dosage of testosterone while keeping the level of estrogen unchanged has been reported. With this modified protocol, we have successfully induced high incidence of prostate carcinoma in Noble rats. The earliest time of development of dysplasia was two months, carcinoma in situ at 4 months and fully developed carcinoma at six months. The tumor incidence was 92% after 12 months hormonal implantation. This animal model is very useful in the investigation of prostate cancer as its multi -step nature mimics the human situation and its high incidence in relative short time.
Telomerase activation is a characteristic of immortalized tumor cells and is thought to contribute to the mechanism by which these cells abort the normal process of senescence. Telomerase activity has been detected in various human cancers and
there are reports showing that telomeric repeat fragment (TRF) length may be correlated to the staging of tumors. These findings suggested that telomerase activation and TRF length alteration might be useful in prognosis of different cancers. Study of prostate cancer on animal model can compensate for the difficulties in human cancer research, as stage-by-stage investigations are available. In this study, we proposed that telomerase would be activated in sex hormone-induced prostatic carcinogenesis and TRF length alterations might be correlated to the different stages of prostatic carcinogenesis. We have examined the telomerase activation as well as telomeric repeat fragment content alteration in the hormonal induced prostatic carcinogenesis in Noble rat.
Telomerase activation is common in prostate carcinoma and also can be detected in 12% of non-malignant tissues. For the non-prostatic tissues tested, all the testis tissues (n=5) were strongly positive for telomerase activity and only one liver tissue (n=5) showed weak. telomerase activity. The high frequency of telomerase activation in prostatic carcinoma specimens suggested that it might be a useful malignancy marker for prognosis evaluation in prostatic carcinogenesis.
There were alterations of TRF content in dorsal lateral prostate. The ventral prostate tissues have the similar results as the dorsal lateral prostate. It seems that the TRF content in normal tissues is less than that of hyperplasia, dysplasia and carcinoma tissues. However, no obvious relationships between the TRF content and clinicopathological properties of prostatic carcinogenesis were observed. Also, there was no significant relation between the telomerase activation and TRF content in this
study. Hence, the TRF content appear to have no significant correlation with prostatic carcinogenesis.abstract
toc
Anatomy
Master
Master of Philosophy
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Rivera, Calderón Luis Gabriel [UNESP]. "Avaliação da expressão proteica de PTEN, MDM2, P53 e AR em lesões proliferativas da próstata canina." Universidade Estadual Paulista (UNESP), 2014. http://hdl.handle.net/11449/122031.
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000814629.pdf: 620669 bytes, checksum: 55c45e6890c124d8c36422d936178543 (MD5)A próstata canina pode desenvolver espontaneamente lesões proliferativas, associadas com a idade, inflamação e os hormônios, tais como: a hiperplasia prostática benigna (HPB), a atrofia inflamatória proliferativa (PIA) e o carcinoma prostático (CaP). Consequentemente, o cão pode ser usado para o estudo do processo carcinogênico da próstata no homem. Alterações na expressão gênica, proteica e na função do PTEN e TP53 foram detectadas nas lesões pré-neoplásicas e neoplásicas da próstata humana. A super-expressão da oncoproteína MDM2 e a perda de marcação nuclear do receptor andrógeno (AR) foram correlacionados com progressão tumoral e ineficiência ao tratamento anti-andrógeno do CaP no homem. Neste contexto, o objetivo deste estudo foi avaliar a expressão proteica de PTEN, MDM2, p53 e AR para determinar seu papel no processo carcinogênico da próstata canina e validar os resultados obtidos pelo grupo de pesquisa com a técnica de hibridação genômica comparativa (CHG) nesses genes. Com isso, foi construído um microarranjo de tecido (TMA), com 74 amostras da glândula prostática canina, divididas em 18 HPB, 22 PIA, 19 CaP e 15 próstatas de tecido normal. A técnica de imuno-histoquímica para os anticorpos PTEN, MDM2, p53, e AR, foi realizada pelo método de peroxidase e DAB. O PTEN, p53 e AR apresentaram perda de marcação nuclear nos carcinomas prostáticos quando comparados com o tecido prostático normal. Na oncoproteína MDM2, o tecido normal obteve marcação nuclear e citoplasmática discreta enquanto no CaP, mais de 85% das amostras apresentaram super-expressão citoplasmática/nuclear. A perda de marcação nuclear do PTEN, p53 e AR, e o ganho da expressão de MDM2 também foi relatado no CaP do homem, sugerindo que existem semelhanças nas alterações moleculares da rede PTEN/MDM2/p53 e AR em ambas as espécies no processo de carcinogênese prostática. Por conseguinte, a espécie cão é um ...
The canine prostate may spontaneously develop prostatic proliferative lesions, associated with aging, inflammation and hormones, such as: benign prostatic hyperplasia (BPH), proliferative inflammatory atrophy (PIA) and prostatic carcinoma (PCa). Consequently, the dog can be used for the study of carcinogenesis process in the prostate of men. Changes in PTEN and TP53 gene and protein expression and function were detected in preneoplasic and neoplasic lesion of human prostate. MDM2 oncoprotein overexpression and loss of nuclear staining of androgen receptor (AR) were correlated with tumor progression and inefficiency antiandrogen treatment of PCa in men. In this context, the aim of this study was to evaluate PTEN, MDM2, p53 and AR protein expression to determine their role in carcinogenic process of the canine prostate. We built a tissue microarray (TMA), with 74 samples of canine prostate, divided into 18 BPH, PIA 22, 19 PCa and 15 prostates of normal tissue. The immunohistochemistry was carried for PTEN, MDM2, p53, and AR antibodies with peroxidase method and DAB. The PTEN, p53 and AR showed loss of nuclear staining in canine prostate carcinoma compared with normal prostate tissue. MDM2 oncoprotein, in normal tissue was discrete cytoplasmic and we observed nuclear staining in CaP, while more than 85% of the samples showed cytoplasmic/nuclear overexpression. The loss of nuclear staining of PTEN, p53 and AR, and the gain of MDM2 expression was also reported in human PCa, suggesting that there are similarities in the molecular alterations of PTEN/MDM2/p53 network and AR in both species in the process prostate carcinogenesis. Therefore, the dog is a potential model for the study of molecular signaling pathways as PTEN/MDM2/p53 and AR involved in human PCa
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Silva, Tânia Soraia Vieira da. "The role of macroH2A1 in prostate carcinogenesis." Master's thesis, 2015. http://hdl.handle.net/1822/41235.
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Dissertação de mestrado em Genética MolecularProstate cancer (PCa) is the most common noncutaneous malignancy in men and the major cause of cancer-related morbidity and mortality worldwide. Due to genetic and epigenetic deregulations, prostate cancer is characteristically asymptomatic in early stages. Deeper understanding of this mechanisms strength the development of new and improved diagnostic and prognostic tools and, therefore, better treatment strategies. The shuffle of canonical histones, an epigenetic mechanism, is highly conserved among species and expression alterations of these histones variants, such as macroH2A1, are related to cancer development. H2AFY gene codifies two isoforms of the H2A histone variant macroH2A1: macroH2A1.1 and macroH2A1.2. MacroH2A1.1 inhibits cell proliferation and cell migration, whilst macroH2A1.2 has opposite functions. To date, there were studies of this histone variant in several cancer types, but none in PCa. Thus, our aim was to assess whether macroH2A1 is implicated in prostate carcinogenesis. In a large series of prostate samples from Portuguese Oncology Institute-Porto, we found that macroH2A1.1 transcript levels were downregulated in high-grade prostatic intraepithelial neoplasia (PIN) and primary PCa compared to normal prostatic tissues. Moreover, QKI, a splicing regulator that induces macroH2A1.1 expression, presented similar results. Compared with clinicopathological data, macroH2A1.1 and QKI expression were associated with Gleason Score and PSA blood levels. Both transcripts were able to discriminate cancerous from noncancerous prostate tissues. MacroH2A1.1 in vitro overexpression in a PCa Cell line decreased cell viability. Thus, macroH2A1.1 seems to play a critical role in PCa development.
O cancro da próstata é, mundialmente, a neoplasia não-cutânea mais comum do sexo masculino e a maior causa de morbilidade e mortalidade associada ao cancro. Com alterações genéticas e epigenéticas, o cancro da próstata é, inicialmente, assintomático. Uma melhor compreensão sobre estes mecanismos oferece o desenvolvimento de novas e aperfeiçoadas análises diagnósticas e, posteriormente, uma melhor aplicação de tratamentos. A substituição das histonas canónicas, um mecanismo epigenético, encontra-se conservada ao longo da evolução. Alterações da expressão dessas variantes de histonas, como a macroH2A1, correlacionam-se com o desenvolvimento de cancro. O gene H2AFY codifica duas isoformas da variante macroH2A1, da família H2A: macroH2A1.1 e macroH2A1.2. Enquanto a macroH2A1.1 inibe a proliferação e a migração celular, a macroH2A1.2 tem consequências opostas. Até hoje, há registos desta variante de histona em diversos estudos de cancro, embora nenhum em cancro da próstata. Com base no que foi descrito, esta tese tem como principal objectivo determinar se a variante macroH2A1 está associada com o desenvolvimento do carcinoma da próstata. Utilizando uma longa série de amostras de próstata do Instituto Português de Oncologia – Porto, descobrimos que os níveis de transcrito da macroH2A1.1 se encontravam mais baixos em neoplasias intraepiteliais prostáticas (PIN) de alto grau e tecidos primários de cancro da próstata, quando comparados com tecidos nãoneoplásicos de próstata. Adicionalmente, o QKI, um regulador de splicing que induz a expressão da macroH2A1.1, demonstrou resultados semelhantes. Comparando com os dados clinico patológicos, a expressão dos genes macroH2A1.1 e QKI estão associados com o Gleason Score e níveis de PSA no sangue. Ambos os transcritos também discriminam significativamente tecidos primários de cancro da próstata de tecidos não neoplásicos. A sobreexpressão de macroH2A1.1 numa linha de cancro da próstata diminuiu a viabilidade celular. Assim, a macroH2A1.1 parece desempenhar um papel relevante no desenvolvimento de cancro da próstata.
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Mesquita, Diana Sobral. "Phenotypic Impact of ETV4 overxpression in prostate carcinogenesis." Dissertação, 2012. https://repositorio-aberto.up.pt/handle/10216/65057.
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Pinheiro, Pedro Filipe da Costa. "The Role of MIR-375 in Prostate Carcinogenesis." Dissertação, 2013. https://repositorio-aberto.up.pt/handle/10216/70544.
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Mesquita, Diana Sobral. "Phenotypic Impact of ETV4 overxpression in prostate carcinogenesis." Master's thesis, 2012. https://repositorio-aberto.up.pt/handle/10216/65057.
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Pinheiro, Pedro Filipe da Costa. "The Role of MIR-375 in Prostate Carcinogenesis." Master's thesis, 2013. https://repositorio-aberto.up.pt/handle/10216/70544.
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Vieira, Ana Filipa Quintela. "Histone methylases and demethylases: the role of SMYD3 in prostate carcinogenesis." Tese, 2014. https://repositorio-aberto.up.pt/handle/10216/76144.
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