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Indlæggelsestiden i forbindelse med kirurgi er blevet kortere. Der er meget lidt viden om, hvordan den umiddelbare postoperative periode forløber. Formålet med undersøgelsen har været at vurdere om korte hospitalsforløb hos patienter, der er opereret for forstørret prostata, bevirker at de pårørende overtager en del af plejen, at undersøge om der kommer en øget belastning på andre dele af sundhedsvæsenet, samt at få en viden om hvordan patienterne har det i de første uger efter operationen. Der er foretaget kvalitative interviews med ti hustruer. Til analyse af interviewene er brugt den fænomenologiske metode, beskrevet af Giorgi og Karlsson. På baggrund af disse interviews er der udarbejdet et spørgeskema, som er udsendt til alle hustruer, hvis ægtefælle i perioden november 2004 til maj 2005 er blevet prostataopereret. Resultaterne fra spørgeskemaundersøgelsen blev sat ind i en access database. Resultatet viser at den første postoperative periode er præget af mange vandladningsgener så som inkontinens, hyppige vandladninger, blødning og urinstop. Gener som også belaster hustruerne. Hustruerne følte sig usikre på om efterforløbet var normalt, og de manglede viden om, hvor de kunne henvende sig med problemer. / The length of stay at hospital after surgery has shortened. Little is known about the immediate post-surgery period. The aim of this study is to assess whether spouses have to take active care of their husbands and to assess if the burden of other part of the health service increases as a result of early discharge after prostatic surgery. Furthermore, the study intends to increase the knowledge about how patients experience the first postoperative weeks. Initially qualitative interviews were conducted with ten spouses. The Phenomological method described by Giorgi and Karlsson was used for analysing the interviews. Based on the experience of this, a questionnaire was prepared and sent to all spouses of patients who had undergone prostatic surgery between November 2004 and May 2005. The results of the questionnaires were put into an access database. The principal finding is that many patients during the first postoperative period experience various urinary problems such as incontinence, frequency, haematuria, and urinary retention. Problems which negatively impacted on the spouses. Furthermore, the spouses were uncertain whether it was common to experience these problems, and they did not know whom to contact when in need of support / <p>ISBN 91-7997-152-0</p>

Objectives: To investigate the effects of serotonin and melatonin (MLT) on the regulation of malignant growth and the activity of serotonin receptors (5HTR1a/-1b) in prostate cancer (PCa) cell lines. Materials and Methods: In four PCa cell lines (LNCaP, 22RV1, PC3, DU145) and two reference cell lines 5HTR1a and -1b, relative mRNA expression levels were assessed. Different serotonin and MLT receptor agonists and antagonists were used in stimulation and inhibition experiments. Results: mRNA expression of 5HTR1b was higher than that of 5HTR1a in all PCa cell lines. Serotonin showed a significant growth stimulatory effect in all PCa lines. The 5HTR1a and -1b agonists/antagonists did not significantly affect viability. MLT inhibited viability only in PC3 cells. Similarly, the 5HTR1a antagonist induced apoptotic changes in PC3 cells only at 10–4M, while the 5HTR1b antagonist induced necrosis at 10–4M in all cell lines. Cell cycle alterations were seen in PC3 and DU145 cells under the influence of the 5HTR1a antagonist. Conclusions: Serotonin receptor antagonists and agonists as well as MLT influence viability and apoptosis of PCa cell lines at supraphysiologic concentrations. In contrast to other reports, our results do not support a regulatory role of serotonin or MLT receptor activation or inhibition in PCa growth. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Orientador: Sebastião Roberto Taboga / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-17T17:10:13Z (GMT). No. of bitstreams: 1 Rochel-Maia_SabrinaSantos_D.pdf: 11931909 bytes, checksum: 6487540b50b593f34ec82d39617d9a12 (MD5) Previous issue date: 2010 / Resumo: O presente trabalho teve por objetivos: 1) Avaliar a atividade das MMPs na próstata de gerbilos machos e fêmeas adultos intactos, procurando comparar a glândula prostática de machos e fêmeas nas diferentes fases do ciclo estral (artigo I); 2) Avaliar o efeito da testosterona sobre o lobo ventral masculino e sobre a próstata feminina quanto à localização de MMP-2 e TIMP-2, enzimas envolvidas na remodelação estromal e na progressão do câncer (artigo II) e 3) Caracterizar a distribuição dos receptores de estrógeno, ER? e ER?, nos tecidos prostáticos de gerbilos machos e fêmeas controles e submetidos à manipulação hormonal (artigo III). Foram realizados experimentos de castração (7 ou 21 dias) nos gerbilos machos adultos, além de experimentos de aplicação hormonal (7 ou 21 dias) em fêmeas adultas na fase de proestro (cipionato de T, 1 mg/kg ou DHEA, 1 mg/kg). Os tecidos foram avaliados por análises bioquímicas, histológicas e imuno-histoquímicas. A atividade gelatinolítica das MMPs obtida por zimografia difere entre os lobos prostáticos masculinos e a glândula feminina, que apresenta os níveis mais altos para MMP-2 e -9, provavelmente devido à constante remodelação estromal promovida pelo ciclo estral. Com relação ao ciclo estral, a maior atividade de MMP-2 e -9 foi encontrada na fase estro, indicando influência do estrógeno. A castração elevou a expressão de MMP-2 na próstata ventral masculina, e o mesmo efeito foi observado após 21 dias de aplicação de T nas fêmeas, indicando que MMPs e TIMPs são influenciados por andrógenos, mas de forma distinta entre machos e fêmeas uma vez que tanto a falta como o excesso de T levaram ao mesmo efeito, provavelmente, devido a machos e fêmeas apresentarem diferentes padrões de expressão para os receptores nucleares, responsáveis por regular a resposta hormonal pelos tecidos. Segundo o estudo há notável diferença na imunolocalização de ER? entre machos e fêmeas, cujas células estromais prostáticas apresentaram duas vezes mais ER? do que as células estromais da próstata ventral masculina. Esse número foi reduzido drasticamente após aplicação de T por 21 dias nas fêmeas, mas não após a castração dos machos. A reação ao ER? foi similar entre machos e fêmeas intactos, mas a castração dos machos ou a aplicação hormonal nas fêmeas promoveu resposta específica, como total ausência após 21 dias de T nas fêmeas ou intensa imunoreação em algumas regiões da próstata após 21 dias de castração nos machos. Adicionalmente, lesões epiteliais presentes nos grupos experimentais tiveram reação ER?-positivas e ER?-negativas, corroborando os estudos que relacionam o ER? com o desenvolvimento e progressão de doenças prostáticas e o ER? como um fator de prevenção e tratamento do câncer. Os resultados obtidos reforçam o conceito de que o equilíbrio estrógeno/testosterona é essencial para a homeostase prostática, e que tanto andrógenos quanto estrógenos atuam sobre as células epiteliais, através dos receptores nucleares, mas também sobre o compartimento estromal, regulando componentes como as MMPs. No caso da próstata feminina, essa interação é ainda mais complexa pois envolve as alterações cíclicas do ciclo estral / Abstract: The present study aimed to: 1) Acess the activity of MMPs in the prostate gland of intact adult male and female gerbils, trying to compare the male prostate lobes with the female gland in different phases of the estrous cycle (Article I); 2) Evaluate the effect of testosterone on ventral prostate of males and on female prostate in the proestrus phase over the location of MMP-2 and TIMP-2, enzymes involved in stromal remodeling and cancer progression (Article II); and 3) Characterize the distribution of estrogen receptors, ER? and ER? in prostatatic tissue of male and female controls and under hormonal manipulation (Article III). Castration experiments (7 and 21 days) were conducted in adult male gerbils as well as hormone injection experiments (7 and 21 days) in adult females in the proestrus phase (T cypionate, 1 mg/kg or DHEA, 1 mg/kg). Tissues were evaluated by biochemical, histological and immunohistochemical methods. The gelatinolytic activity of MMPs, measured by zymography gel, differs from male prostatic lobes and the female gland, which presents the highest levels of MMP-2 and -9, probably due to its constant stromal remodeling promoted by the estrous cycle. Regarding the estrous cycle, the highest activity of MMP-2 and -9 was found in the estrus phase, indicating the influence of estrogen. Castration increased the expression of MMP-2 in the male ventral prostate, and this same effect was observed after 21 days of T injection in females, indicating that MMP and TIMP regulatory mechanism is also influenced by androgens, although differently between males and females since both the failure as the excess of T lead to the same effect, probably due to males and females presenting different patterns of expression for nuclear receptors, which are responsible for regulating the hormonal response by the tissues. According to our results, there is a remarkable difference in the immunolocalization of ER? between males and females, whose stromal cells presented two times more ER? than stromal cells of the male ventral prostate. This number was drastically reduced after 21 days of T injection in females, but not after castration of males. The immunoreaction to ER? was similar between intact males and females, but the castration of males or the hormonal injection in females promoted specific response, such as total absence of reaction after 21 days of T treatment in females or intense immunoreaction in some regions of ventral prostate after 21 days of castration. Additionally, epithelial lesions found in the experimental groups, were ER?-positives and ER?-negative, corroborating studies that relate ER? with the development and progression of prostatic diseases and ER? as a factor in preventing and treating cancer. The results obtained in this study therefore reinforce the concept that the estrogen/testosterone balance is essential for prostate homeostasis, and that either androgens or estrogens have an effect on the prostatic epithelial cells, via nuclear receptors, but also on the stromal compartment by regulating components such as MMPs. In the case of the female prostate, this interaction is even more complex since it involves the cyclical changes of the estrous cycle / Doutorado / Biologia Celular / Doutor em Biologia Celular e Estrutural

Orientador: Laura Sterian Ward / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-06T20:05:49Z (GMT). No. of bitstreams: 1 LimaJunior_MarioMacielde_M.pdf: 2114915 bytes, checksum: 56c9d6904dd7e0a16ab5565b0d280b7c (MD5) Previous issue date: 2006 / Resumo: O câncer de próstata (CaP) é atualmente a neoplasia maligna mais prevalente no mundo, após os tumores de pele. A incidência dessa enfermidade tem crescido nas últimas décadas devido, principalmente; ao aumento da longevidade da população. Atualmente o CaP tem sido detectado em estágios menos avançados do que no passado. As melhorias dos métodos de diagnóstico contribuem para a detecção precoce dessa neoplasia. Os polimorfismos de genes que codificam enzimas envolvidas na metabolização de drogas e de xenobióticos, como as do sistema Glutationa S-transferase (GST) e Citocromo P450 (CYP), podem estar implicados no risco e prognóstico para neoplasias. Foram avaliados os genótipos de GSTT1, GSTM1, GSTP1, GSTO1 e CYP1A1 em 125 pacientes portadores de câncer de próstata e em 100 indivíduos com hiperplasia prostática benigna. Tempo e atividade ocupacional, tabagismo e outros dados relevantes da história natural da doença foram obtidas por meio de entrevistas. Não foram encontrados quaisquer associações entre os genótipos estudados e o risco de câncer de próstata, tanto avaliando os diferentes genótipos em separado como em combinações, através de análise de regressão logística uni ou multivariada. Não houve associação entre os genótipos estudados e fatores clínicos de risco para câncer de próstata ou quaisquer parâmetros de agressividade do tumor ao diagnóstico ou durante o seguimento. Nossos dados permitem concluir que os genótipos de GST e CYP1A1 não estão associados à susceptibilidade ao câncer de próstata ou à sua evolução na população brasileira estudada / Abstract: Prostate cancer is currently the most common malignancy worldwide, second only to skin tumors. The incidence of prostate cancer has risen dramatically over the last decade, more than can be explained just by the increase in longevity. It is also apparent that prostate cancer is now being detected at less advanced stages than in the past. Increased awareness of the disease and improved detection methods are thought to contribute to this earlier detection. The polymorphic inheritance of human drug-metabolizing enzymes, such as those encoded by the Glutathione-S-Transferase (GST) and the Cytochrome P450 (CYP) systems, may be implicated in both cancer risk and prognostic. We compared GSTT1, GSTM1, GSTO1, GSTP1 e CYP1A1 genotypes of 125 prostate cancer and 100 benign prostatic hyperplasia patients. Lifetime occupational history, cigarette-smoking, and other anamnestic data were obtained through interviews. None of the studied polymorphisms was found associated to prostate cancer risk either considered in separate or in combination, in uni ou multivariate regression logistic analysis. Also, there was no association between genotypes and possible clinical factors of risk, or any parameter of tumor agressiveness at diagnosis or during follow-up. Our data suggest that GST and CYP1A1 genotypes are not associated to the susceptibility to prostate cancer or its outcome in the Brazilian population / Mestrado / Clinica Medica / Mestre em Clinica Medica

Orientador: Sebastião Roberto Taboga / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-09T15:30:54Z (GMT). No. of bitstreams: 1 Souza_CristianiZanetoniIsraelde_D.pdf: 8114014 bytes, checksum: 02df40337836deefc11fdc588dbdccb0 (MD5) Previous issue date: 2007 / 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

Objectives: To investigate the effects of serotonin and melatonin (MLT) on the regulation of malignant growth and the activity of serotonin receptors (5HTR1a/-1b) in prostate cancer (PCa) cell lines. Materials and Methods: In four PCa cell lines (LNCaP, 22RV1, PC3, DU145) and two reference cell lines 5HTR1a and -1b, relative mRNA expression levels were assessed. Different serotonin and MLT receptor agonists and antagonists were used in stimulation and inhibition experiments. Results: mRNA expression of 5HTR1b was higher than that of 5HTR1a in all PCa cell lines. Serotonin showed a significant growth stimulatory effect in all PCa lines. The 5HTR1a and -1b agonists/antagonists did not significantly affect viability. MLT inhibited viability only in PC3 cells. Similarly, the 5HTR1a antagonist induced apoptotic changes in PC3 cells only at 10–4M, while the 5HTR1b antagonist induced necrosis at 10–4M in all cell lines. Cell cycle alterations were seen in PC3 and DU145 cells under the influence of the 5HTR1a antagonist. Conclusions: Serotonin receptor antagonists and agonists as well as MLT influence viability and apoptosis of PCa cell lines at supraphysiologic concentrations. In contrast to other reports, our results do not support a regulatory role of serotonin or MLT receptor activation or inhibition in PCa growth. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

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.

Die transurethrale Resektion der Prostata (TURP) ist eine elektrochirurgische Behandlung der gutartigen Vergrößerung der Prostata. Hierbei treten sehr selten gebrochene Resektionsschlingen auf, deren Ursachen in der Literatur unzureichend dokumentiert sind. In dieser Arbeit erfolgt die Untersuchung der Eignung von Methoden zur Schlingenverschleißanalyse bei der TURP. Es gilt die aktuell offenen Fragen zu klären, wie sich zum Beispiel der Schlingenverschleiß äußert, ob dieser Ursache für gebrochene Schlingen während einer Operation ist und ob er Einfluss auf den Leistungseintrag ins Prostatagewebe und damit auf Ihre Temperaturverteilung hat. Angewandt werden erstmals vier experimentelle Methoden zur Verschleißanalyse in Kombination. Gemessene Geometrieänderungen stehen in Zusammenhang mit einer gemessenen verschleißbedingten Impedanzänderung, welche hier erstmals in‑situ erfolgt. Diese liefert auch Informationen über Defekte im nichtsichtbaren Bereichen der Resektionsschlingen. Es geht auch hervor, dass aufgrund üblicher Nutzungsdauern der Schlingenverschleiß als Ursache für Schlingenbrüche während der Dauer einer Operation mit sehr großer Wahrscheinlichkeit auszuschließen ist. Aufbauend auf den Messergebnissen werden durch Finite Elemente Simulationen Informationen über den Leistungseintrag ins Prostatagewebe gewonnen. Die Auswertung der simulierten räumlichen Temperaturverteilung zeigt keine Vergrößerung von betroffenen Gewebearealen mit verschleißbedingtem Temperaturanstieg.:1 Einleitung 2 Grundlagen und Stand der Forschung 3 Lösungsansatz und Methoden 4 Versuchsumgebungen zur experimentellen Umsetzung 5 Ergebnisse der experimentellen Untersuchungen 6 Numerische Methoden 7 Ergebnisse aus den numerischen Methoden 8 Diskussion 9 Zusammenfassung / The transurethral resection of the prostate (TURP) is an electrosurgical treatment of benign prostatic hyperplasia. In the literature, broken resection loops are rarely discussed and the reasons for their occurrence are insufficiently documented. The purpose of the present work is to investigate the suitability of methods for loop wear analysis in TURP. The aim is to clarify the currently open questions such as: Does material wear on the loop surface lead to broken resection loops during the surgery procedure? How does material wear influence the power input into the prostate tissue and thus the resulting temperature distribution in the tissue? For the first time, four experimental methods for loop wear analysis are applied in combination. As a result, the experimental investigation show that it was possible to measure a wear-related impedance change in-situ, matching to the wear-related geometry change of the resection loop. Moreover, the measured impedance led to information about loop defects in an invisible part of the resection electrode. For the duration of the surgery procedure, the loop wear can be ruled out as the cause of broken loops with a very high probability. Finite element analyses were used for evaluating the spatial temperature distribution of the prostate tissue. The simulation model based on the measurement results. The simulated spatial temperature distribution does not show any enlargement of affected tissue areas due to wear-induced temperature increase.:1 Einleitung 2 Grundlagen und Stand der Forschung 3 Lösungsansatz und Methoden 4 Versuchsumgebungen zur experimentellen Umsetzung 5 Ergebnisse der experimentellen Untersuchungen 6 Numerische Methoden 7 Ergebnisse aus den numerischen Methoden 8 Diskussion 9 Zusammenfassung