• Refine Query
  • Source
  • Publication year
  • to
  • Language
  • 599
  • 148
  • 145
  • 49
  • 40
  • 37
  • 21
  • 14
  • 13
  • 10
  • 8
  • 7
  • 7
  • 5
  • 2
  • Tagged with
  • 1302
  • 1302
  • 144
  • 109
  • 108
  • 107
  • 105
  • 91
  • 90
  • 87
  • 84
  • 83
  • 82
  • 74
  • 71
  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1171

Correlation between PET/MRI image features andpathological subtypes for localized prostate cancer / Korrelation mellan PET-/MR-bildegenskaper och patologiska undertyper för lokal prostatacancer

Lindahl, Jens January 2021 (has links)
Prostate cancer is the most common cancer in Sweden. Patients with the condition have a good prognosis in general and most cases can be treated. Localized prostate cancer is primarily treated via surgery or radiation therapy and is diagnosed with the help of different imaging modalities, such as magnetic resonance imaging, MRI, and positron emission tomography, PET. The diagnosis is confirmed and the aggressiveness of the cancer is determined through biopsies. Samples from a small part of the prostate are extracted and then examined. This could mean that parts of higher aggressiveness may be missed, which in turn could lead to under-treatment of the cancer. The aggressiveness of a lesion can be described by Gleason Score, GS, which is determined by an visual assessment of the shape, size and arrangement of the cells. The aim of this study was to correlate GS with in-vivo images using MRI and PET. This was accomplished by investigating image data from PSMA PET, Acetate PET, Ktrans MRI and T2-weighted MRI from a cohort of 26 prostate cancer patients containing 74 lesions. Regions of interests, ROI:s, were created and applied on all images. Statistics such as median and max value were extracted from each ROI. The statistics were combined to get a wide range of descriptive variables for each respective imaging modality. These were normalised against a certain zone of the prostate or only the absolute value. The results indicated that PSMA PET, Acetate PET and Ktrans MRI were correlated to GS, while T2-weighted MRI was not. Data also indicated that PSMA PET, Acetate PET and Ktrans MRI give complementary information to each other, which could indicate that a combination of the modalities would better predict GS. The implications of these findings could affect both the diagnostics and the treatment of prostate cancer.
1172

Physician Role in Physical Activity for African-American Males Undergoing Radical Prostatectomy for Prostate Cancer

Williams, Faustine, Imm, Kellie R., Colditz, Graham A., Housten, Ashley J., Yang, Lin, Gilbert, Keon L., Drake, Bettina F. 01 April 2017 (has links)
Purpose Physical activity is recognized as a complementary therapy to improve physical and physiological functions among prostate cancer survivors. Little is known about communication between health providers and African-American prostate cancer patients, a high risk population, regarding the health benefits of regular physical activity on their prognosis and recovery. This study explores African-American prostate cancer survivors’ experiences with physical activity prescription from their physicians. Methods Three focus group interviews were conducted with 12 African-American prostate cancer survivors in May 2014 in St. Louis, MO. Participants’ ages ranged from 49 to 79 years, had completed radical prostatectomy, and their time out of surgery varied from 7 to 31 months. Results Emerged themes included physician role on prescribing physical activity, patients’ perceived barriers to engaging in physical activity, perception of normalcy following surgery, and specific resources survivors’ sought during treatment. Of the 12 men who participated, 8 men (67%) expressed that their physicians did not recommend physical activity for them. Although some participants revealed they were aware of the importance of sustained physical activity on their prognosis and recovery, some expressed concerns that urinary dysfunction, incontinence, and family commitments prevented them from engaging in active lifestyles. Conclusions Transitioning from post radical prostatectomy treatment to normal life was an important concern to survivors. These findings highlight the importance of physical activity communication and prescription for prostate cancer patients.
1173

Biomarqueurs pronostiques dans le cancer de la prostate : mieux prédire pour mieux traiter

Bienz, Marc Nicolas 04 1900 (has links)
No description available.
1174

Que reste-t-il de leurs amours ? : étude exploratoire, clinique et projective de patients traités pour un cancer de la prostate / What has left of their loves ? : exploratory, clinical and projective study of patients treated for prostate cancer

Van Doren, Anne-Sophie 14 November 2017 (has links)
Maladie de l'homme mûr, le cancer de la prostate nécessite des traitements qui rendent le patient impuissant, parfois de manière irréversible. Cela fait écho psychiquement à l'appréhension d'une castration qui n'a pas attendu l'avènement de cette quasi-réalité pour s'avérer l'un des moteurs psychiques de l'angoisse des hommes et de leur dynamique identificatoire, narcissique et objectale. Le cancer de la prostate se révélant être tabou dans notre société, ces hommes sont sommés de souffrir en silence. À l'appui d'une double méthodologie composée d'entretiens et d'épreuves projectives auprès de 17 patients atteints d'un cancer de la prostate (et, dans une visée comparative, de 2 patients atteints d'un cancer du rein et de 2 patients venant pour un simple dépistage), nous nous sommes proposée de discerner comment cette détresse interdite pouvait expliquer en partie la mise en avant d'une position hyper phallique ("même pas peur, même pas triste, même pas mal"). Revendiquer de n'être ni touché ni ébranlé par ce qui arrive permettrait ainsi à ces hommes de pallier une décompensation dépressive, peut-être pire que tout pour eux, car "anti-virile", dans le sens où un homme n'est censé ni chuter, ni s'effondrer, ni se plaindre. C'est pourquoi, dans la filiation des travaux de C. Chabert et de F. Neau, nous avons proposé l'idée d'un "masculin hypomane" ; il serait une défense contre le mouvement mélancolique (à entendre comme traitement narcissique de la perte) insupportable et comme retournement de la passivité en activité contre l'être pénétré (par la maladie, les explorations médicales), l'être traversé (par l'angoisse, le temps qui passe) et l'être excité (par l'autre, son désir). Portée par un faux masculin abritant le genre neutre dans le latent et durcie par un hyperinvestissement narcissique, cette solution serait à la fois coûteuse et mortifère, mais aussi salvatrice et trophique pour le sujet, déplaçant alors les frontières entre normal et pathologique. En effet, elle protégerait le sujet contre les affres de l'effondrement dépressif dans le manifeste, soutiendrait son identité virile déjà bien malmenée. Elle lui permettrait de se défendre contre le mouvement mélancolique qui infiltre le latent et, enfin, elle contiendrait l'excitation désorganisatrice de la pulsion sexuelle derrière les remparts de la pulsion de mort dans sa valence anarchiste. La dimension performative de la virilité nous a ainsi permis d'envisager la clinique de la passation (mais également la relation clinique et les mouvements transférentiels pendant les entretiens) comme un espace potentiellement traumatique (car elle peut, certes, mettre en lumière et révéler une sensibilité à la castration à travers l'implicite de performance) mais aussi, comme un espace transitionnel et thérapeutique. Ce qui semble très important pour la construction future de projets thérapeutiques concernant ces patients. / A disease affecting older men, prostrate cancer requires treatment that renders patients impotent, sometimes permanently. Psychically speaking, this resonates with the fear of castration, which does not await the advent of this quasi-reality to emerge as one of the psychic driving forces of men's anxiety and of their identity-related, narcissistic and objectal dynamic. In today's society, prostrate cancer is a taboo subject; men suffering from the condition are thus forced to suffer in silence. We met 17 patients with prostate cancer and, in a comparative way, 2 patients with kidney cancer and 2 healthy patients. Using projective methods and semi-directive interviews, we attempted to discern how this forbidden distress could partly explain why patients chose to adopt a hyperphallic stance ("Ain't scared, ain't sad, doing just fine !"). Claiming to be neither affected nor shaken by unfolding events would allow these men to mitigate depressive decompensation, which might be the worst thing for them because it would be unmanly insofar as a man must never fall, collapse or complain. Drawing from the studies undertaken by C. Chabert and F. Neau, we thus put forward the notion of "masculine hypomania". This would not only be a defense against unbearable melancholia (construed as the narcissistic treatment of loss), but would also be the reversal of passivity into action against the penetrated being (by disease and medical explorations), the permeated being (by anxiety and the passing of time) and the excited being (by the other and his desire). Driven by narcissistic hyperinvestment, this solution would be costly and mortifying on the one hand, and life-saving and nourishing on the other, moving boards between normality and pathology. Indeed, it would enable patients to defend themselves against depressive decompensation, to support shaken male identity, to defend themselves against melancholic movement and, at last, to contain excitation of the sexual drive through the death instinct in its anarchist valency. The performative dimension of manhood allowed to consider the clinical perspective of test administration (but also clinical relationship and transference during interviews) as a potentially traumatic space (because it could reveal a sensitivity to castration behind the implicit of performance), but also as a transitional and therapeutic space, which seems very important for the construction of therapeutic projects for these patients in the future.
1175

Titre de la thèse : Perturbation du rythme circadien et risque de cancer de la prostate : rôle du travail de nuit, des gènes circadiens et de leurs interactions / Disruption of Circadian Rhythm and Risk of Prostate Cancer : the Role of Night Work, Circadian Genes and Their Interactions

Wendeu-Foyet, Meyomo 19 December 2018 (has links)
En 2007, le Centre International de Recherche sur le Cancer (CIRC) a classé le “travail de nuit entrainant une perturbation du rythme circadien” comme probablement cancérogène pour l'homme (groupe 2A) sur la base de preuves suffisantes chez l’animal mais limitées chez l'Homme. A ce jour, peu d’études se sont intéressées au rôle du travail de nuit et des gènes de l’horloge dans la survenue du cancer de la prostate. Dans ce contexte, nous avons étudié le rôle du travail de nuit, des gènes circadiens ainsi que leurs interactions dans le risque de cancer de la prostate, à partir des données d’EPICAP, étude cas-témoins réalisée en population générale), incluant 819 cas et 879 témoins. Un questionnaire standardisé a permis de recueillir des informations détaillées sur le travail de nuit, qu’il soit fixe ou rotatif. La réalisation d’un prélèvement biologique a permis un génotypage de l’ADN pour l’étude des gènes de l’horloge. Globalement, nous n’avons pas mis en évidence d’association entre le travail de nuit et le cancer de la prostate quelle que soit l'agressivité du cancer de la prostate, alors que nous avons observé une augmentation du risque chez les hommes ayant un chronotype du soir. Une durée d’exposition d’au moins 20 ans au travail de nuit fixe associée au cancer de la prostate agressif et de manière plus prononcée en combinaison avec des nuits de longue durée (en moyenne de plus de 10 heures par nuit) ou avec un nombre maximal de nuits consécutives supérieur à 6. Nous avons observé une association significative avec le cancer de la prostate pour les gènes NPAS2 et PER1, alors que seul le gène RORA était significatif pour les cancers agressifs. L’analyse de l’interaction entre les gènes de l’horloge et le travail de nuit dans le risque de survenue de cancer de la prostate a révélé des interactions significatives avec les gènes RBX1, CRY1, NPAS2 et PRKAG2. Les résultats de notre étude renforcent l'hypothèse d'un lien entre le travail de nuit en tant que facteur de perturbation du rythme circadien et le risque de cancer de la prostate et fournissent également de nouvelles preuves d'un lien potentiel avec les variants des gènes de l’horloge. Ces résultats, pourraient contribuer à l’identification de nouveaux facteurs de risque modifiables pour le cancer de la prostate pouvant être accessibles à la prévention. Des recherches plus approfondies aideront à mieux cerner les mécanismes biologiques impliquant les gènes circadiens dans le développement du cancer de la prostate ainsi que leurs interactions avec le travail de nuit. / In 2007, the International Agency for Research on Cancer (IARC) classified "shift work leading to a disruption of circadian rhythm» as probably carcinogenic to humans (Group 2A) on the basis of sufficient evidence in animals but limited evidence in humans. To date, few studies have focused on the role of night work and clock genes in prostate cancer occurrence. In this context, we studied the role of night work, circadian genes and their interactions in prostate cancer risk, using data from EPICAP, a population-based case-control study, including 819 cases and 879 controls. A standardized questionnaire was used to collect detailed information on both fixed and rotating night work. Biological samples were also collected for DNA genotyping and for prostate cancer-clock genes association study. Overall, we did not find an association between night work and prostate cancer whatever the disease aggressiveness, while we observed an increased risk in men with an evening chronotype. At least 20 years of exposure to fixed night work was associated with aggressive prostate cancer and this was more stricken in combination with long nights (on average more than 10 hours per night shift) or more than 6 consecutive night shifts. We observed a significant association with prostate cancer for the clock genes NPAS2 and PER1, while only RORA was significant for aggressive cancers. We found significant interaction between clock genes and night work in the risk of prostate cancer for RBX1, CRY1, NPAS2 and PRKAG2. Our results provide support for the hypothesis that night work disrupting circadian rhythm could be associated with prostate cancer and they also provide new evidence of a potential link between clock genes variants and prostate cancer. These results may particularly contribute to the identification of new prostate cancer risk factors that could be modifiable and available for prevention. Further studies are warranted to better understand the biological mechanisms involving circadian genes in the development of prostate cancer and their interactions with night work.
1176

A Meta-Analysis of Association Between One-Carbon Metabolism Gene Polymorphisms and Risk of Prostate Cancer

Tazari, Mahmood 01 January 2015 (has links)
Prostate cancer is the most common cancer among men. The purpose of this quantitative, meta-analysis study was to examine one-carbon metabolism gene polymorphisms in a group of genes to determine their association with prostate cancer risk. The genetic epidemiology theory provided the framework for the study. The data collected were from published articles. From over 2,800 individual studies, 20 articles were retained for results and data abstraction, following the title, abstract screen, and full text screening in the second phase. The data were analyzed by a meta-analysis statistical method, combining the results from selected studies to estimate the overall association. According to study results by the adjusted p-values of fixed model, there was a significant association between decreased risk of prostate cancer and the variant of Allele T, Genotype TT, and the recessive model of C667T polymorphism. In the random model, the adjusted p-values show a significant association between decreased risk of prostate cancer, the variant of Genotype TT, and recessive model. There was an increased risk of prostate cancer in A1298C polymorphism by adjusted p-value on the variant of Genotype AC, in the fixed model. This study leads to positive social change by providing information on an optimization surveillance strategy to ensure valid screening test for prostate disease reporting. Future studies with a greater number of samples are needed, including gene-gene and gene-environment interaction to verify study results.
1177

DEVELOPMENT OF MITHRAMYCIN ANALOGUES WITH IMPROVED EFFICACY AND REDUCED TOXICITY FOR TREATMENT OF ETS-DEPENDENT TUMORS IN EWING SARCOMA AND PROSTATE CANCER

Eckenrode, Joseph Michael 01 January 2019 (has links)
Introduction: Genetic rearrangements in Ewing sarcoma, prostate, and leukemia cells result in activation of oncogenic ETS transcription factor fusions. Mithramycin (MTM) has been identified as an inhibitor of EWS-FLI1 transcription factor, a gene fusion product responsible for oncogenesis in Ewing sarcoma. Despite preclinical success, a phase I/II clinical trial testing MTM therapy in refractory Ewing sarcoma was terminated. Liver and blood toxicities resulted in dose de-escalation and sub-therapeutic exposures. However, the promise of selectively targeting oncogenic ETS transcription factors like EWS-FLI1 prompted us to undertake the discovery of more selective, less toxic analogues of MTM. MTM is a potent inhibitor of ubiquitous SP1 transcription factor, likely inducing non-specific toxicity. In collaboration with two medicinal chemistry groups, two semi-synthetic efforts were implemented to develop novel analogues of MTM. The first effort utilized the biosynthetic product mithramycin SA (MTMSA) to modify C3-side chain. The second effort utilized an oxime linker directly formed on MTM’s C3-side chain (MTM-oxime; MTMox). Here I present the pharmacological assessment of over 75 novel MTM analogues towards selectively targeting oncogenic ETS transcription factors, like EWS-FLI1, over ubiquitous transcription factors, like SP1. Methods: Novel MTM analogues were evaluated for selective cytotoxicity against ETS fusion-dependent cell lines. Selectively cytotoxic analogues were evaluated for inhibitory effects on several gene promoters in TC-32 reporter cell lines, a Ewing sarcoma cell line dependent on EWS-FLI1, transfected with luciferase reporter vector. Cloned reporter vectors incorporated NR0B1 (EWS-FLI1 binding), β-actin (SP1 binding) and CMV (non-specific) gene promoters. Furthermore, gene (mRNA) and protein expression changes of EWS-FLI1 and SP1, as well as regulated target genes, namely NR0B1, VEGFA and BCL-2 were evaluated with MTM analogue treatments. The MTM analogues with most selective activity in vitro were administered to mice by intravenous bolus dose for pharmacokinetic analysis. The MTM analogues with highest systemic exposure from each semi-synthetic effort, namely MTMSA-Trp-A10 and MTMox-24, were further evaluated. Metabolic stabilities in whole blood, plasma, and tumor cell matrices, and across multiple species were compared with MTM. Moreover, intrinsic hepatic clearances were estimated using mouse liver microsomes. Tumor and liver distributions were estimated in tumor bearing mice. Additionally, the effect of organic anionic transporter polypeptides (OATP) on distribution of MTM was investigated. Maximum tolerated doses were evaluated for lead MTM analogues, having both selective activities in vitro and high systemic exposure, compared to MTM. Complete blood cell counts and plasma alanine aminotransferase activity were measured to evaluate dose-dependent blood and liver toxicities, respectively. ETS fusion-dependent and non-dependent cell lines were implanted subcutaneously into immunocompromised mice for efficacy studies. Average tumor volumes and survival were tracked for mice receiving treatment, compared to MTM and vehicle treatment. Results: Evaluation of MTM analogues from both semi-synthetic efforts revealed that conjugation of MTM C3-side chain with tryptophan (Trp) and/or phenylalanine (Phe) improved selective cytotoxicity against ETS fusion-dependent cell lines. This was highlighted by MTMSA-Trp-A2 (also refer to as MTMSA-Phe-Trp) and MTMSA-Trp-A10 (also refer to as MTMSA-Trp-Trp), with selective indices of 19.1 and 15.6, respectively, compared to MTM (1.5). Similarly, MTMox-23 (also refer to as MTMox-Phe-Trp) and MTMox-20 (also refer to as MTMox-Trp) had selectivity indices of 4.6 and 4.5, respectively. These selectively cytotoxic MTM analogues inhibited EWS-FLI1-mediated transcription 10-fold more effectively than both non-specific CMV-mediated and SP1-mediated (via β-actin promoter) transcription in TC-32 reporter cell lines. Moreover, gene (mRNA) and protein expression of EWS-FLI1 and regulated gene, NR0B1, were inhibited with MTM analogue treatment (GI50, 6-hour) in TC-32 cells. Similarly, SP1 and target genes, VEGFA and BCL-2, gene (mRNA) and protein expressions were also inhibited with MTM analogue treatment (GI50, 6-hour) in TC-32 cells. Conjugation of Trp and/or Phe to C3-side chain of MTM increased systemic exposure in vivo. Most impressively, the addition of two Trp residues, namely MTMSA-Trp-A10 and MTMox-24 (also refer to as MTMox-Trp-Trp), resulted in systemic exposure increases of 218- and 42-fold, respectively, after intravenous (IV) bolus dose. Metabolically, tryptophan/phenylalanine conjugated MTM analogues are liable to esterase activity on carboxy-methyl functional group. Very rapid de-methylation in biological matrix was observed with MTMox-24, compared to MTMSA-Trp-A10, suggesting a regiospecific effect. However, esterase activity was limited to rodent matrices and demethylation occurred at significantly diminished rates in non-human primate and human plasma. MTM analogues were not susceptible to p450-mediated metabolism, with negligible loss in mouse liver microsome assay compared to verapamil control. MTM (1mg/kg) and MTMox-24 (6mg/kg) were detected in subcutaneously implanted (flank) LL2 tumors and liver homogenates after IV bolus dose. Interestingly, MTMSA-Trp-A10 (2mg/kg) was not. Despite a 3-fold increase in systemic exposure with rifampin oral pretreatment, an OATP inhibitor, exposure of MTM was unaffected in Oatp knockout mouse model. Exposure of MTM in liver tissue was 8.4-fold higher compared to tumor tissue with low tissue clearance. This agrees with the lack of metabolism observed in liver microsomes and may provide a mechanism for clinically observed liver toxicity. MTMSATrp-A10 had a single maximum tolerated dose (MTD) of 0.75mg/kg, compared to 1mg/kg for MTM, administered by IV bolus. In contrast, MTM-oxime analogues (MTMox-20, -23, -24 and -25) had single maximum tolerated doses of 20 – 25mg/kg. These increased tolerances are the result of additive differences in whole blood stability, cytotoxicity and systemic exposure. At a dose of 0.75mg/kg, administered every 3 days, MTMSA-Trp-A10 did not result in an efficacious result in tumor xenograft studies. These studies remain under further investigation, but the result may indicate high plasma protein binding of MTMSA-Trp-A10 and lack of free fraction available within tumor. The most selective MTM-oxime analogue in vitro, MTMox-23, significantly inhibited TC-32 (EWS-FLI1+) tumor xenograft growth (p=0.0025, day 16, one-way ANOVA multiple comparisons test) compared to MTM (p=0.1174, day 16) and extending survival for 17 days out of 48 days on study (p=0.0003, Log Rank (Mantel-Cox) single comparison test) with treatment at MTD every 3 days, compared to vehicle. Additionally, the MTM-oxime analogue with highest systemic exposure, MTMox-24, also significantly inhibited TC-32 (EWS-FLI1+) tumor xenograft growth (p=0.0003, day 21, one-way ANOVA multiple comparisons test) compared to MTM (p=0.032, day 21) and extending survival for 12 days out of 37 days on study (p=0.0004, Log Rank (Mantel-Cox) single comparison test) with treatment, compared to vehicle. Conclusion: These studies in whole highlight the importance of exposure (pharmacokinetics; PK), toxicity and efficacy (pharmacodynamics; PD) relationships. The cytotoxicity and high systemic exposure of MTMSA-Trp-A10 directly contributes to its lower tolerated dose. However, despite a similar tolerated dose to MTM, systemic exposure remains 163-fold higher at the MTD. High systemic exposure may be attributed to high plasma protein binding, but also reduces the exposure of free MTMSA-Trp-A10 within the tumor tissue, which drives the efficacious response. In contrast, the less cytotoxic and rapidly de-methylated MTM-oxime analogues allow for 25-fold higher tolerances in mice. This unique metabolism and clearance may prevent exposures required to induced systemic blood and liver toxicities induced by MTM. Moreover, at these highly tolerated doses, the initial systemic exposure at MTD is highest among analogues tested, which resulted in an efficacious response with MTMox-23 and MTMox-24 treatment in tumor xenograft models. It remains to be determined if these PK/PD relationships can be reproduced in additional animal models, including human, without inducing toxicity. Nonetheless, these initial studies in mice demonstrate that a more selective, more tolerated analogue of MTM has potential for clinical success in treating ETS fusion-dependent tumors.
1178

Einfluss des Insulin-ähnlichen Wachstumsfaktors I auf die Androgenrezeptor-Signaltransduktion in Prostatakrebszellen

Schmidt, Siw 07 November 2007 (has links)
Die im Rahmen dieser Arbeit durchgeführten Untersuchungen zum Einfluss der Wachstumsfaktoren IGF-I, EGF und dem Zytokin IL-6 auf den Androgenrezeptor-Signalweg zeigten in verschiedenen Prostatakarzinom-zelllinien schon nach zwei Stunden eine deutliche Degradation des Androgenrezeptor-Proteins. Die ausschließlich auf Protein-Ebene stattfindende, Wachstumsfaktor-induzierte negative Regulation des Androgenrezeptors konnte durch einen schnellen Androgeneffekt wieder aufgehoben werden. Mittels Luziferase-Reportergen-Assays wurde kein Einfluss der Wachstums-faktorwirkung auf die transkriptionelle Aktivität des Androgenrezeptors nachgewiesen. Darüber hinaus konnte eine signifikant reprimierende Wirkung durch IGF-I und EGF in Kombination mit geringen Mengen DHT beobachtet werden. Weitere Resultate dieser Arbeit deuten auf einen, durch den PI3-Kinase-Signalweg vermittelten, proteasomalen Abbauprozess des Rezeptors hin. Da die Suppression der downstream gelegenen Proteinkinase Akt keine Veränderung hinsichtlich der Degradation aufwies, konzentrierte sich die weiterführende Arbeit auf eine mögliche direkte Regulation des Androgen-rezeptors durch die PI3-Kinase. Unter Verwendung von rekombinanten GST-Fusionsproteinen konnte in Interaktionsstudien unter in vitro Bedingungen eine Phosphotyrosin-unabhängige Bindung zwischen der C-SH2-Domäne der p85-Untereinheit der PI3-Kinase und dem N- und C-Terminus des Androgenrezeptors nachgewiesen werden. Durch die nähere Charakterisierung dieser Bindungsbereiche mit Hilfe von Peptidarrays und anschließenden Alanin-Substitutionen war es möglich, für den N-Terminus 18, für den C-Terminus des Androgenrezeptors 6 und für die p85-C-SH2-Domäne der PI3-Kinase 11 Aminosäuren zu identifizieren. Die durch gezielte Punktmutagenese an diesen Aminosäurepositionen hergestellten Androgenrezeptor-Einzel- und -Mehrfachmutanten wiesen in Bindungsstudien dennoch Interaktion zur PI3-Kinase auf. Eine von Anderson und Kollegen postulierte Phosphotyrosin-unabhängige Bindung der SH2-Domänen der p85-Untereinheit der PI3-Kinase durch sogenannte „basic-X-basic“-Motive wurde ebenfalls in Interaktionstests zwischen der PI3-Kinase und dem Androgenrezeptor überprüft. Aufgrund der Tatsache, dass einige der identifizierten Aminosäuren auf dem Androgenrezeptor Teil eines „basic-X-basic“-Bindungsmotives sind, wurden Kombinationsmutanten generiert, die sowohl im N-Terminus als auch im C﷓Terminus des Androgenrezeptors ein bzw. zwei zerstörte „basic-X-basic“-Motive enthielten. Untersuchungen zum Bindungsverhalten dieser Mutanten zeigten zwar weiterhin Interaktion zur p85-C-SH2-Domäne der PI3-Kinase, jedoch der durch Western-blot-Analyse überprüfte IGF-I-induzierte Degradationseffekt des Androgenrezeptor-Proteins konnte mit zwei der verwendeten Androgenrezeptor-Kombinationsmutanten nicht mehr beobachtet werden.
1179

NOVEL AI APPROACHES FOR INTEGRATING NON-IMAGING AND IMAGING ACROSS LENGTH SCALES FOR DISEASE RISK STRATIFICATION

Hiremath, Amogh 26 August 2022 (has links)
No description available.
1180

Genetic Diversity and Treatment Resistance in Prostate Cancer Cell Lines

Donix, Lukas 05 June 2023 (has links)
Die Dissertationsarbeit untersucht genetische Varianten in Zellkulturmodellen des metastatischen und kastrationsresistenten Prostatakarzinoms. Außerdem werden Mechanismen der Chemoresistenz, insbesondere der Resistenz gegen Cisplatin und Docetaxel in diesen Zelllinien untersucht. / This Dissertation evaluates genetic variants found in cell culture models of metastatic castration resistant prostate cancer. Furthermore, mechanisms of resistance against the chemotherapeutic drugs cisplatin and docetaxel are investigated in these cell lines.

Page generated in 0.3282 seconds