Prostatacancer är den sjätte mest förekommande cancertypen i världen, och den tredje vanligaste cancertypen bland män. De olika typer av behandlingar som finns idag botar oftast inte sjukdomen. Det är därför viktigt att utveckla bättre behandlingsmetoder. Det är sedan tidigare känt att mangan kan orsaka apoptos i olika celltyper. Det ger en möjlighet att använda mangan för att hämma cancer och det är därför viktigt att veta vilka apoptotiska markörer som är involverade. Syftet med projektet var att undersöka om de sker en ökning av de apoptotiska markörerna kluven Kaspas-3 och kluven PARP efter manganbehandling av prostatacancerceller. Därefter kunna avgöra om manganbehandlingen har orsakat celldöd genom att inducera apoptos. Under projektet odlades prostatacancerceller (PC3) som sedan behandlades med 200 µM mangan under 6, 24 och 48 timmar. Därefter mättes mängden av proteinerna kluven Kaspas-3 och kluven PARP med hjälp av ett sandwich-ELISA kit. En tydlig stegvis ökning av apoptosmarkörerna med inkuberingstid hade förväntats. Det förväntade resultatet erhölls inte, för kluven Kaspase-3 ledde manganbehandlingen t.o.m. till en sänkning av koncentrationen. Det kan ha uppstått problem vid analysen som t.ex dålig lysering av cellerna eller ojämn tillväxt av dem. Det behövs fler studier för att utreda detta och för att undersöka andar potentiella apoptosmarkörer. / Prostate cancer is the sixth most common cancer type in the world, and the third most common cancer type among men. The different types of treatments that are available today do not usually cure the disease. It is therefore important to develop better treatment methods. It has previously been stated that manganese can cause apoptosis in different cell types. It provides an opportunity to use manganese to inhibit cancer and it is therefore important to know which apoptotic markers that are involved. The purpose of the project was to investigate whether an increase in the apoptotic markers cleaved Kaspas-3 and cleaved PARP after manganese treatment of prostate cancer cells. Thereafter, it can determine whether manganese treatment has caused cell death by inducing apoptosis. During the project prostate cancer cells (PC3-cells) were cultivated, then treated with 200 µM manganese for 6, 24 and 48 hours. The amount of the proteins cleaved Kaspas-3 and cleaved PARP was measured by using a sandwich ELISA kit. A clear gradual increase of apoptotic markers with incubation time was expected. The expected result was not obtained, for cleaved Kaspase-3 manganese treatment even decreased the concentrations. There may have been problems with the performance of the analysis such as poor lysis of the cells or uneven growth of the cells. More studies are required to investigate this and other potential apoptotic markers.

A indicação de biópsia para o diagnóstico precoce do câncer prostático baseia-se na dosagem sérica do PSA e nos achados do toque retal. O PSA é uma kalecreina estando seus genes reguladores ligados aos andrógenos. Drogas que afetam o metabolismo dos andrógenos podem afetar a produção de PSA. A finasterida é uma droga sintética que inibe a conversão de testosterona em DHT pela enzima 5 AR. O uso da finasterida na dose de 5mg/dia para o tratamento da HPB causa redução do volume prostático de 20 a 30% e diminuição dos valores dos PSA em aproximadamente 50% do seu valor inicial após 6 meses. O uso da finasterida na dose de 1mg/dia para o tratamento da AAM foi aprovado pelo FDA em 1997. Um estudo realizado em 2007 avaliou a alteração do nível do PSA em homens com mais de 40 anos fazendo uso de finasterida 1mg/dia para tratamento da AAM. Os resultados revelaram redução dos valores do PSA semelhante à verificada nos pacientes portadores de HPB. Não existem estudos prospectivos sobre o tema incluindo pacientes mais jovens. O objetivo do nosso trabalho foi verificar as alterações da dosagem do PSA, da testosterona sérica total e do volume prostático em indivíduos com menos de 40 anos de idade com em uso de finasterida 1mg/dia. Selecionamos 52 pacientes que após avaliação inicial preenchiam os critérios de inclusão. Foram dosados os níveis séricos do PSA e da testosterona, e mensurado o volume prostático através da ultrassonografia transabdominal, no início do estudo (T0) e um ano após o uso da finasterida (T2). No intervalo, 6 meses após o início da droga, foi solicitada apenas nova dosagem de PSA (T1). O valor médio na avaliação inicial (T0) da dosagem do PSA, da testosterona total plasmática e do volume prostático mensurado pela ultrassonografia transabdominal foi de 0,398 ng/ml (0,14- 0,78); 735,77 ng/dl (548-927) e 21,35 ml (15-31ml) respectivamente. Foi observada uma redução do valor médio do PSA de 9,21% após 6 meses do uso da droga (p=0,001). Após 12 meses do uso da finasterida verificamos uma redução de 10,51% do valor do PSA em relação à dosagem inicial (p<0,001) e uma diminuição do valor médio do volume prostático 21,37 ml para 20,03 ml (p<0,001). Não foi detectada alterações nos níveis de testosterona. Diferentemente de estudos anteriores em que, em homens fazendo uso de finasterida 1mg/dia, houve redução de 40% e 50% dos valores do PSA nas faixas etárias de 40 a 49 anos e 50 a 59 anos, nosso trabalho revelou reduções inferiores. Nosso estudo traz importantes questionamentos em relação a como deve ser feita a correção dos valores do PSA nos pacientes que começaram a utilizar finansterida 1mg antes dos 40 anos de idade e que se apresentam para avaliação prostática. Outro ponto de interesse é se a hiperplasia do componente epitelial observada durante envelhecimento masculino poderia ser inibida pelo uso da finasterida desde a juventude, pois sabemos que indivíduos portadores de deficiência congênita de 5AR não apresentam alopecia e nem tão pouco desenvolvem HPB. / The indication of biopsy for early diagnosis of prostate cancer is based on serum PSA levels and digital rectal examination findings. PSA is a kalecreine and its regulatory genes are modulating by androgens. Drugs affecting the androgens metabolism can affect the production of PSA. Finasteride is a synthetic drug, which inhibits the conversion of testosterone to DHT by the enzyme 5 AR. There are two subtypes of 5AR enzymes, Type 1 that predominates in non-prostatic tissues such as liver and skin, and Type 2, which predominates in the prostate and scalp but is also expressed in other tissues. The use of Finasteride 5mg / day for the treatment of BPH is well known. After six months we observe a decrease in prostate volume by 20 to 30% and also a decrease in total serum PSA concentration of approximately 50%. The use of Finasteride at 1mg / day for the treatment of MAA has been approved by the FDA in 1997. In 2007 a study evaluated the change in total serum PSA concentration in men over 40 years taking Finasteride 1 mg / day to treat MAA. The results showed a reduction in PSA values similar to that observed in patients treated of BPH. There are no prospective studies including younger patients. The aim of our study was to assess the changes in total serum PSA concentration, total serum testosterone concentration and prostate volume in patients younger than 40 years of age in use of Finasteride 1mg / day for MAA. We prospectively selected 52 patients with MAA and indication for treatment with Finasteride who met the inclusion criteria. Serum levels of total PSA and total testosterone and prostate volume, measured by transabdominal ultrasound, were obtained at baseline (T0) and one year after started the drug (T2). In the interval, 6 months after started drug, only serum total PSA concentration was measured (T1). The median value at baseline (T0), for total PSA, total testosterone and prostate volume was 0.398 ng / ml (0.14 to 0.78); 735.77 ng / dl (548-927) and 21.35 ml (15-31ml) respectively. A reduction of 9.21% on total PSA concentration was detected 6 months after started the drug (p = 0.001). After 12 months we observed a 10.51% decrease in total serum PSA concentration, when compared with the baseline value, (p <0.001). A reduction in the median value of prostate volume from 21.37 ml to 20.03 ml (p < 0.001) was also detected at the same period. There were no detectable changes in testosterone levels. They reported a decrease of 40% and 50% in total PSA concentration for groups between 40-49 and 50-59 of age respectively. In our study we observed lower reductions. Our finding may be explained by the fact that the epithelial component of the prostate gland has not yet started the hyperplasia process, so the conversion of testosterone into DHT by blocking 5AR by Finasteride would cause less impact. The fact that the values of plasma testosterone not have changed is not surprising since Finasteride is not considered an anti androgenic drug, it means that the synthesis of the testosterone is not affected by its use. Our study highlights important questions about how the adjustment of PSA values should be done in patients who began taking Finasteride 1mg / day before 40 years of age and present for prostate evaluation. Another point of interest is whether the hyperplasia of the epithelial component, observed during the aging process, could be inhibited by the use of Finasteride. This hypothesis can be corroborate by the fact that individuals with congenital deficiency of 5AR do not present alopecia or develop BPH. In conclusion the use of Finasteride 1mg /day reduces the total serum PSA value by 10,51% after one year. Prostate volume is also reduced by 6,3% in the same period.

Le cancer de la prostate est la deuxième cause de mortalité chez l’homme en France. L’IRM multiparamétrique est considérée comme la technique la plus prometteuse pour permettre une cartographie du cancer, ouvrant la voie au traitement focal, alternatif à la prostatectomie radicale. Néanmoins, elle reste difficile à interpréter et est sujette à une forte variabilité inter- et intra-expert, d’où la nécessité de développer des systèmes experts capables d’aider le radiologue dans son diagnostic. Nous proposons un système original d’aide au diagnostic (CAD) offrant un second avis au radiologue sur des zones suspectes pointées sur l’image. Nous évaluons notre système en nous appuyant sur une base de données clinique de 30 patients, annotées de manière fiable et exhaustive grâce à l’analyse des coupes histologiques obtenues par prostatectomie. Les performances mesurées dans des conditions cliniques auprès de 12 radiologues, sans et avec notre outil, démontrent l’apport significatif de ce CAD sur la qualité du diagnostic, la confiance des radiologues et la variabilité inter-expert. La création d’une base de corrélations anatomo-radiologiques est une tâche complexe et fastidieuse. Beaucoup d’études n’ont pas d’autre choix que de s’appuyer sur l’analyse subjective d’un radiologue expert, entâchée d’incertitude. Nous proposons un nouveau schéma de classification, basé sur l’algorithme du séparateur à vaste marge (SVM), capable d’intégrer, dans la fonction d’apprentissage, l’incertitude sur l’appartenance à une classe (ex. sain/malin) de certains échantillons de la base d’entraînement. Les résultats obtenus, tant sur des exemples simulés que sur notre base de données cliniques, démontrent le potentiel de ce nouvel algorithme, en particulier pour les applications CAD, mais aussi de manière plus générale pour toute application de machine learning s’appuyant sur un étiquetage quantitatif des données / Prostate cancer is one of the leading cause of death in France. Multi-parametric MRI is considered the most promising technique for cancer visualisation, opening the way to focal treatments as an alternative to prostatectomy. Nevertheless, its interpretation remains difficult and subject to inter- and intra-observer variability, which motivates the development of expert systems to assist radiologists in making their diagnosis. We propose an original computer-aided diagnosis system returning a malignancy score to any suspicious region outlined on MR images, which can be used as a second view by radiologists. The CAD performances are evaluated based on a clinical database of 30 patients, exhaustively and reliably annotated thanks to the histological ground truth obtained via prostatectomy. Finally, we demonstrate the influence of this system in clinical condition based on a ROC analysis involving 12 radiologists, and show a significant increase of diagnostic accuracy, rating confidence and a decrease in inter-expert variability. Building an anatomo-radiological correlation database is a complex and fastidious task, so that numerous studies base their evaluation analysis on the expertise of one experienced radiologist, which is thus doomed to contain uncertainties. We propose a new classification scheme, based on the support vector machine (SVM) algorithm, which is able to account for uncertain data during the learning step. The results obtained, both on toy examples and on our clinical database, demonstrate the potential of this new approach that can be extended to any machine learning problem relying on a probabilitic labelled dataset

La castration représente le traitement de référence du cancer de la prostate à un stade avancé. Cependant, la plupart des patients rechute du fait notamment de l’émergence de variants tronqués constitutivement actifs du récepteur des androgènes (RA). Le microenvironnement tumoral, en particulier les fibroblastes associés au cancer (CAFs), favorisent largement la progression tumorale. Ils sont très hétérogènes et dérivent de plusieurs types cellulaires dont les cellules souches mésenchymateuses (MSCs). Afin de mettre à jour l’impact des variants du RA sur le microenvironnement tumoral, mon projet de thèse a porté sur l’étude des effets de ces variants du RA sur la différenciation des MSCs en CAFs. Les résultats obtenus m’ont permis de démontrer un impact positif du variant RA Q641X sur l’expression du facteur de différenciation VEGF par les cellules tumorales, ainsi que sur l’expression des marqueurs de différenciation en CAFs FSP-1, CXCL12, PDGFR-β, ainsi que VEGF, au niveau des MSCs. Ces données suggèrent que le variant RA Q641X est capable d’induire la différenciation des MSCs en CAFs, soulignant ainsi l’importance de développer de nouvelles stratégies thérapeutiques ciblant ces variants du RA. / Androgen ablation therapy remains the most common treatment for patients with advanced prostate cancer. However, most patients will relapse due to the emergence of truncated constitutively active androgen receptor (AR) variants. The tumor microenvironment is another necessary feature driving prostate cancer progression. Cancer associated fibroblasts (CAFs) are the major specialized stromal cells that favor tumor progression. These cells are very heterogeneous and derive from several other cell types as mesenchymal stem cells (MSCs). In order to highlight the impact of AR variants on surrounding tumor stroma, the aim of my project was to investigate the effects of these AR variants on MSCs differentiation into CAFs. I noticed that the expression of VEGF, a CAF differentiation factor, was upregulated in tumor cells expressing AR Q641X variant. Similarly, the expression of CAF differentiation markers FSP-1, CXCL12, PDGFR-β, and VEGF was enhanced in MSCs in presence of AR Q641X variant. These data highlight an unknown property of AR Q641X variant in prostate tumor cells that is its ability to induce MSCs differentiation into CAFs, underlining the urgent need to develop novel strategies targeting these AR variants.

<p>Prostate cancer is one leading cause of cancer-related death among men in Western countries. The standard therapies for localized prostate cancer include radical prostatectomy and radiation therapy. Such measures are relatively effective in the short term, but many patients ultimately relapse. These patients may benefit from a combination of standard therapy and oncolytic virus therapy. My work aimed to develop viruses for this purpose.</p><p>TARP is a protein that in males is specifically expressed in prostate epithelial and cancer cells. In my thesis, I characterized the TARP promoter and showed that TARP expression is regulated at the transcriptional level by testosterone through binding of the androgen receptor in the proximal TARP promoter. I further developed TARP promoter-based regulatory sequences for prostate-specific gene expression. A sequence comprising a PSA enhancer, a PSMA enhancer and the TARP promoter was constructed and designated PPT. An adenoviral vector containing the PPT sequence shielded from transcriptional interference by an H19 insulator showed high prostate-specific transcriptional activity in human cells both in the presence and absence of testosterone. However, in experimental murine prostate cancer the PPT sequence is not active. Therefore, a two-step transcriptional amplification (TSTA) system was used together with the PPT sequence to develop an adenovirus that confers prostate-specific transgene expression also in murine cells.</p><p>I constructed a conditionally replicating adenovirus where the E1A gene expression is controlled by an H19 insulator-shielded PPT regulatory sequence, Ad[I/PPT-E1A]. This virus exhibited absolute prostate specificity in terms of E1A expression, viral replication and cytolysis <i>in vitro</i> and <i>in vivo</i>. Importantly, our virus is active both in the presence and absence of testosterone, which may prove beneficial for patients treated by hormonal withdrawal. </p><p>Hopefully, my work will improve existing gene therapy strategies for prostate cancer and in the long term improve the prognosis for patients with prostate cancer.</p>

Prostate cancer is one leading cause of cancer-related death among men in Western countries. The standard therapies for localized prostate cancer include radical prostatectomy and radiation therapy. Such measures are relatively effective in the short term, but many patients ultimately relapse. These patients may benefit from a combination of standard therapy and oncolytic virus therapy. My work aimed to develop viruses for this purpose. TARP is a protein that in males is specifically expressed in prostate epithelial and cancer cells. In my thesis, I characterized the TARP promoter and showed that TARP expression is regulated at the transcriptional level by testosterone through binding of the androgen receptor in the proximal TARP promoter. I further developed TARP promoter-based regulatory sequences for prostate-specific gene expression. A sequence comprising a PSA enhancer, a PSMA enhancer and the TARP promoter was constructed and designated PPT. An adenoviral vector containing the PPT sequence shielded from transcriptional interference by an H19 insulator showed high prostate-specific transcriptional activity in human cells both in the presence and absence of testosterone. However, in experimental murine prostate cancer the PPT sequence is not active. Therefore, a two-step transcriptional amplification (TSTA) system was used together with the PPT sequence to develop an adenovirus that confers prostate-specific transgene expression also in murine cells. I constructed a conditionally replicating adenovirus where the E1A gene expression is controlled by an H19 insulator-shielded PPT regulatory sequence, Ad[I/PPT-E1A]. This virus exhibited absolute prostate specificity in terms of E1A expression, viral replication and cytolysis in vitro and in vivo. Importantly, our virus is active both in the presence and absence of testosterone, which may prove beneficial for patients treated by hormonal withdrawal. Hopefully, my work will improve existing gene therapy strategies for prostate cancer and in the long term improve the prognosis for patients with prostate cancer.

Background: Tissue factor (TF) is a 47 kDa transmembrane glycoprotein known as the main initiator of blood coagulation. TF is over-expressed on many malignant cells and apart from increasing the risk of thrombosis, the presence of TF/FVIIa also promotes the progression of cancer and metastasis by intracellular signaling. TF expressing microparticles (MP) are, moreover, often found in the circulation of cancer patients. Aim: The aim of this thesis was to study different aspects of TF activity, e.g. the importance of procoagulant MP and TF-induced intracellular signaling pathways, with focus on cell migration (chemotaxis) and apoptosis. Results: The TF signaling complexes were shown to prevent apoptosis induced by serum starvation and TRAIL in cancer cells by reduced activation of caspase-8 in a PI3k/AKT-dependent manner. FVIIa also decreased transcription of pro-apoptotic genes in cancer cells treated with TRAIL. Simvastatin triggered apoptosis by transcriptional reduction of BCL-2 due to cytosolic retention of NFκB. Simvastatin also inactivated the PI3k/AKT pathway and reduced the production of the MP-like prostasomes which, respectively, impaired the anti-apoptotic signaling by TF and reduced the procoagulant activity in the vicinity of prostate cancer cells. Intracellular events conducted by the TF/FVIIa complex selectively enhanced PDGF-BB induced chemotaxis which was partly explained by the TF/FVIIa-induced transactivation of the PDGFβ-receptor. This was dependent on Src-family members and engagement of PAR2. Conclusions: The results presented in this thesis extend the current knowledge of TF-mediated signaling. We report the TF complexes to govern the extrinsic pathway of apoptosis, present data on FVIIa-dependent regulation of apoptosis-related genes, and exclude known surface proteins as transmitters of the anti-apoptotic signals. We moreover describe TF/FVIIa to transactivate the PDGFβ-receptor and play a decisive role in the potentiated chemotaxis toward PDGF-BB in a number of cell types. Finally, we explain the mechanism behind simvastatin-induced apoptosis in cancer cells and how statins interfere with TF-dependent signaling and coagulation.

BACKGROUND: Prostate cancer is by far the most common cancer among Swedish men. Some patients have an aggressive lethal disease, but the majority of affected men have long expected survival. Unfortunately, the diagnostic tools available are insufficient in predicting disease aggressiveness. Novel prognostic markers are therefore urgently needed. Furthermore, metastatic prostate cancer is generally treated with castration, but the long-term effects are insufficient. Additional studies are therefore needed to explore how the effects of this therapy can be enhanced. Prostate growth and regression is beside testosterone controlled by locally produced regulators. Vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) are two of the major regulators in the normal prostate and in prostate tumours. MATERIALS AND METHODS: VEGF and EGFR were explored in the prostate, by treating rats with either anti-VEGF or anti-EGFR treatment during castration and testosterone-stimulated prostate growth. Rats with implanted androgen-independent prostate tumours were treated with an inhibitor of both VEGF receptor-2 (VEGFR-2) and EGFR. Stereological techniques, immunohistochemistry, western blotting and quantitative real-time PCR were used to evaluate these experiments. Furthermore, prostate tissue from untreated prostate cancer patients was used to retrospectively explore the expression of phosphorylated-EGFR (pEGFR) in relation to outcome. RESULTS: Anti-VEGF treatment during testosterone-stimulated prostate growth, inhibited vascular and prostate growth. Anti-EGFR treatment during castration and testosterone-stimulated prostate growth resulted in enhanced castration effects and inhibited prostate growth. Anti-vascular treatment of androgen-independent prostate cancer with an inhibitor of VEGFR-2 and EGFR, that targets the normal and tumour vasculature, enhanced the effects of castration. Low immunoreactivity for pEGFR in prostate epithelial cells, both in the tumour and also in the surrounding non-malignant tissue, was associated with good prognosis. CONCLUSIONS: Anti-vascular treatment, with an inhibitor of VEGFR-2 and EGFR, in combination with castration could be an effective way to treat androgen-insensitive prostate tumours. VEGF and EGFR signalling are necessary components in testosterone-stimulated prostate growth. Phosphorylation of EGFR could be a useful prognostic marker for prostate cancer patients. Tumours may affect the surrounding non-malignant tissue and pEGFR immunoreactivity in the morphologically normal prostate tissue can be used to retrieve prognostic information.

La apigenina (4', 5, 7 trihidroxiflavona), flavonoide presente en distintos vegetales, tiene numerosas características saludables por las cuales elegimos un derivado hidrosoluble, la apigenina potásica, para el presente estudio.Hemos estudiado su actividad frente a la inflamación aguda, al cáncer de próstata y a los daños causados por las radiaciones, tanto ionizantes como no ionizantes (radiación UV), utilizando diversas técnicas, tanto in vitro como en modelos in vivo. Este flavonoide demostró actividad antiinflamatoria, reduciendo la inflamación hasta un 78%. Asimismo, la apigenina potásica mostró actividad quimiopreventiva frente al cáncer de próstata, al reducir la viabilidad y la migración e inducir apoptosis in vitro, y aumentar la supervivencia de animales con tumores. Además, la apigenina potásica presentó efecto geno- y citoprotector frente a la radiación ionizante (radiación &#947; y X), con un factor de protección de un 27-35 % en linfocitos humanos, y de un 50-86 % en dos líneas celulares de próstata. Por último, el flavonoide ha demostrado proteger frente al fotoenvejecimiento causado por la radiación UV, reduciendo la displasia epitelial y la elastosis dérmica, dos marcadores de cáncer cutáneo; además, ha sido posible detectar la apigenina en diversos tejidos, entre ellos el cerebro. / Apigenin (4', 5, 7 trihidroxyflavone), a flavonoid present in different plants, shows some healthy characteristics for which a water soluble derivated, potassium apigenin, was chosen for this study.It has been studied the activity of potassium apigenin against acute inflammation, prostate cancer and the effect of ionising and non-ionising (UV) radiations, using different techniques, both in vitro and in vivo models.This flavonoid showed anti-inflammatory effects, inhibiting the inflammation by up to 78%. It also demonstrated chemopreventive activity against prostate cancer, by reducing the cell viability and migration, inducing apoptosis and increasing the animal survival. Moreover, potassium apigenin showed genoprotector and citoprotector effects against ionising radiation (radiation &#947; and X), with a protection factor of 27-35% in human lymphocytes and of 50-86% in two prostate cell lines. Finally, the flavonoid protected from the photoaging induced by UV radiation, diminishing epithelial dysplasia and dermal elastosis, two markers of skin cancer; furthermore, potassium apigenin was detected in some tissues, brain among them.

Prostate segmentation in trans rectal ultrasound (TRUS) and magnetic resonance images (MRI) facilitates volume estimation, multi-modal image registration, surgical planing and image guided prostate biopsies. The objective of this thesis is to develop computationally efficient prostate segmentation algorithms in both TRUS and MRI image modalities. In this thesis we propose a probabilistic learning approach to achieve a soft classification of the prostate for automatic initialization and evolution of a deformable model for prostate segmentation. Two deformable models are developed for the TRUS segmentation. An explicit shape and region prior based deformable model and an implicit deformable model guided by an energy minimization framework. Besides, in MRI, the posterior probabilities are fused with the soft segmentation coming from an atlas segmentation and a graph cut based energy minimization achieves the final segmentation. In both image modalities, statistically significant improvement are achieved compared to current works in the literature. / La segmentació de la pròstata en imatge d'ultrasò (US) i de ressonància magnètica (MRI) permet l'estimació del volum, el registre multi-modal i la planificació quirúrgica de biòpsies guiades per imatge. L'objectiu d'aquesta tesi és el desenvolupament d'algorismes automàtics per a la segmentació de la pròstata en aquestes modalitats. Es proposa un aprenentatge automàtic inical per obtenir una primera classificació de la pròstata que permet, a continuació, la inicialització i evolució de diferents models deformables. Per imatges d'US, es proposen un model explícit basat en forma i informació regional i un model implícit basat en la minimització d'una funció d'energia. En MRI, les probalitats inicials es fusionen amb una imatge de probabilitat provinent d'una segmentació basada en atlas, i la minimització es realitza mitjançant tècniques de grafs. El resultat final és una significant millora dels algorismes actuals en ambdues modalitats d'imatge.