Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Background: The optimal extent of the prostate biopsy remains controversial. There is a need to avoid detection of insignificant cancer but not to miss significant and curable tumors. In alternative treatments of prostate cancer, repeated sextant biopsies are used to estimate the response. The aim of this study was to investigate the reliability of a repeated systematic sextant biopsy as the standard biopsy technique in patients with significant tumors which are being considered for curative treatment. Methods: Systematic sextant biopsy was performed in vitro in 92 radical prostatectomy specimens. Of these patients, 81 (88.0%) had palpable lesions. Results: Of the 92 investigated patients, 70 (76.1%) had potentially curable pT2-3pN0 prostate cancers. In these patients, the cancer was detected only in 72.9% of cases by a repeated in vitro biopsy. In the pT2 tumors, there was a detection rate of only 66.7%. Conclusions: This study underlines the fact that a considerable number of significant and potentially curable tumors remain undetected by the conventional sextant biopsy. A negative sextant biopsy does not rule out significant prostate cancer. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

The guidelines for the curative treatment of prostate cancer presented by the German Society of Urology are discussed. They are based on the current knowledge of the outcomes of surgical and radiotherapeutic treatment for prostate cancer. Radical prostatectomy is recommended as the first-line treatment for organ-confined prostate cancer in patients with an individual life expectancy of at least 10 years. Radiotherapy can be considered as an alternative treatment modality, although current knowledge does not allow a definite assessment of the relative value of radiotherapy compared to radical prostatectomy. Locally advanced cT3 prostate cancer is overstaged in about 20% and curative treatment is possible in selected cases. Guidelines represent rules based on the available evidence. This implies that exceptions must be made whenever appropriate and that guidelines have to be reviewed regularly as new information becomes available. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Objective The main objective of this thesis was to explore the effects of diet on gastrointestinal symptoms in prostate cancer patients treated with local curative radiotherapy, by evaluating dietary intake prior to treatment (Study I), the psychometric properties of a new questionnaire on patient-reported gastrointestinal side effects (Study II), and the effect of a dietary intervention on acute and long-term gastrointestinal symptoms up to 2 years after radiotherapy completion (Study III-IV). Methods A total of 130 men with localized prostate cancer referred to dose-escalated radiotherapy (ED2 87-102 Gy, α/β=3 Gy) were recruited to a dietary intervention trial. Patients were randomized to receive either standard care plus the dietary intervention of a fibre- and lactose-restricted diet (intervention group, IG; n=64) or standard care alone (standard care group, SCG; n=66). Data on gastrointestinal symptoms and dietary intake were collected pre-treatment and at seven time points during a follow-up period of 26 months. Results Prior to treatment, grain products and milk products were major sources of energy. Unbalanced fatty acid intake and low intake of selenium were observed (Study I). Validation of the Gastrointestinal Side Effects Questionnaire (GISEQ) revealed satisfactory internal consistency, moderate concurrent validity and adequate responsiveness (Study II). There were no significant effects of the intervention on acute or long-term gastrointestinal symptoms, but a tendency towards lower prevalence and severity of bloating and diarrhoea in the IG compared to the SCG during radiotherapy. Gastrointestinal symptoms were predominantly mild, and the frequency of clinically relevant symptoms was merely a few percent. Dietary adherence in the IG was initially good, but tended to decline beyond 12 months post-radiotherapy (Study III-IV). Conclusions A fibre- and lactose-restricted diet was not superior to the habitual diet in reducing gastrointestinal symptoms in patients undergoing high-dose, small-volume radiotherapy for localized prostate cancer. The GISEQ enables assessment of patient-perceived change in symptoms, but further work is needed to strengthen its psychometric qualities. It is suggested that continued research in this area target patient categories referred to irradiation of larger pelvic volumes with a higher risk of gastrointestinal symptoms, and that dietary interventions incorporate established strategies to enhance adherence and effectiveness.

The objectives were to 1) conduct a meta-analysis to assess the association between alpha-linolenic acid (ALA) and prostate cancer; 2) analyze a trial of ALA on coronary heart disease with PSA as a post hoc outcome; 3) assess the effect of trial serum and also ALA directly on LNCaP cell growth. 1) The ALA meta-analysis of prospective and case-control studies showed no overall effect on prostate cancer. However, removal of one study from the analysis of prospective studies changed the result to a significant protective effect (RR=0.91; 95%CI:0.83,0.99). 2) No significant treatment difference was seen in the change in PSA in the randomized controlled trial. 3) The ALA treatment serum from the clinical trial did not affect LNCaP cell growth. However, ALA decreased LNCaP cell growth in a dose dependent manner when added to cell culture. The results provide no positive evidence for an effect of ALA on prostate cancer.

The objectives were to 1) conduct a meta-analysis to assess the association between alpha-linolenic acid (ALA) and prostate cancer; 2) analyze a trial of ALA on coronary heart disease with PSA as a post hoc outcome; 3) assess the effect of trial serum and also ALA directly on LNCaP cell growth. 1) The ALA meta-analysis of prospective and case-control studies showed no overall effect on prostate cancer. However, removal of one study from the analysis of prospective studies changed the result to a significant protective effect (RR=0.91; 95%CI:0.83,0.99). 2) No significant treatment difference was seen in the change in PSA in the randomized controlled trial. 3) The ALA treatment serum from the clinical trial did not affect LNCaP cell growth. However, ALA decreased LNCaP cell growth in a dose dependent manner when added to cell culture. The results provide no positive evidence for an effect of ALA on prostate cancer.

The objective of this thesis research is to develop microelectronic acoustic technology towards biosensor applications. The development of a simple and robust resonator that employs simple microelectronic fabrication techniques for its construction could provide the foundation for a cost-effective sensor platform. Subsequent development of an appropriate surface chemistry treatment would functionalize the resonator as a biosensor. Implementation of this design in an array configuration allows for the development of ligand microarrays, which subsequently allows for multi-ligand recognition signatures as well as testing redundancy. The applications for such a tool extend to a myriad of applications, but the focus of this research is to develop this technology towards an early cancer detection capability. Specifically, I develop a solidly-mounted resonator with thin-film ZnO as my active piezoelectric layer. These resonators undergo an extensive development process to arrive at a final device design and are fully characterized throughout by X-ray diffraction and scattering analysis. Employing silane chemistry, these resonators are functionalized as immunosensors by covalently binding antibodies to the surface of the device. The quality of the surface chemistry is fully assessed using water contact angle, atomic force microscopy and confocal laser scanning microscopy. Functionalized biosensors are then used to quantify the concentration of known proteins marker in both a purified medium and a physiologically-relevant medium.

In chronic illnesses, such as prostate cancer, multiple health outcomes need to be considered. This project focused on two types of health outcomes: health-related quality of life (HRQoL) and cognitive function. The first aim was to investigate cognitive effects of pharmacological androgen-suppressing treatment. Numerous studies have shown cognitive performance to be associated with sex hormones. One of the main groups of drugs used for hormonal ablation in men with prostate cancer, the luteinising hormone releasing hormone (LHRH) agonists, has been associated with adverse cognitive effects in controlled studies in women and in case reports of female and male patients. However, there have been no published studies on the effect of LHRH agonists and other androgen-suppressing treatments on cognitive functioning in male patients. The second aim was to investigate the effect of treatments on HRQoL in men with prostate cancer. There are few randomised treatment studies of HRQoL in these patients. The third aim was to study additional predictors of HRQoL, examining stress and coping theory as a theoretical basis for understanding individual differences in HRQoL. The fourth aim was to examine patients' subjective experiences of prostate cancer. To investigate these questions, 82 men with non-localised prostate cancer were randomly assigned to receive leuprorelin (LHRH agonist), goserelin (LHRH agonist), cyproterone (steroidal antiandrogen), or close clinical monitoring. These patients and 20 community volunteers matched for age, marital status, and general health undertook medical, psychosocial, and cognitive assessments before treatment and after 6 and 12 months of treatment. The main question for statistical analysis was whether dependent variables would show Group x Time interactions in the predicted directions. Compared with baseline assessments, men administered androgen suppression monotherapy performed worse in 3/12 tests of attention, memory, and executive function. Twenty-six percent of men randomised to active treatment demonstrated clinically significant decline in one or more cognitive tests at 6 months compared with baseline performance. By contrast, no community volunteers or patients randomised to close monitoring showed decline in test performance. Men on hormonal treatments reported impaired sexual function on treatment compared with baseline assessments. Men assigned to close monitoring and cyproterone treatment reported increased emotional distress over time. Groups did not differ in change in existential satisfaction, subjective cognitive function, physical symptoms, or social and role functioning. For individuals, hormonal treatments were more frequently associated with decreased physical, sexual, social and role functioning, but were also associated with improved HRQoL for some individuals. In hierarchical regression analysis, HRQoL was lower for men who had more comorbid illnesses, a history of neurological dysfunction, higher threat appraisals, or higher use of emotion-focused coping strategies. Coping strategies also showed some longitudinal associations with HRQoL, even when earlier levels of HRQoL had been taken into account. Subjective reports demonstrated that many patients viewed prostate cancer as a relatively manageable problem. Several patients said that other health problems affected them more than prostate cancer, whereas no patient said that prostate cancer was worse than other problems. Comments about the seriousness of prostate cancer were equally divided between patients who reported it as very serious (14.3% of patients) and those who saw it as a relatively minor problem (14.3%). Other patient observations were grouped into categories of personal responses to prostate cancer, health, and health research; life circumstances that were not directly associated with health; attributions about medication; and function prior to the study. The results demonstrated that pharmacological androgen suppression therapy was associated with impaired memory, attention, and executive function in male patients. Hormonal treatments and close monitoring had differential effects on patients' HRQoL, particularly in terms of sexual function and emotional distress. HRQoL was also associated with appraisal and coping, to a greater extent than it was associated with medical variables, supporting the applicability of stress and coping theory for these patients. Observations from participants placed these findings in the context of participants' concerns, demonstrating that issues such as cognitive and sexual function were relevant for these patients. These findings suggest that cognitive function should be given increased attention as a health outcome, not only in "neurological" disorders but also in other "non-neurological" conditions such as prostate cancer. They also support continued efforts to understand both beneficial and adverse effects of treatments for chronic illness on HRQoL and individual factors that affect health outcomes.

<p>The vitamin D metabolite 1,25(OH)2D3 has long been known to inhibit growth of prostate cancer cells and this mainly through a VDR-mediated pathway controlling target gene expression, resulting in cell cycle arrest, apoptosis and differentiation. Another major way in which 1,25(OH)2D3 inhibits cell growth in prostate cancer is via membrane-initiated steroid signalling, which triggers activation of signal cascades upon steroid binding to a receptor complex, leading to induction of genes regulating cell growth, proliferation and apoptosis. The main prostate cancer inhibiting membrane-initiated route is the TGFβ signalling pathway, elicited by the protein TGFβ. In this experiment the activating effects of 1,25(OH)2D3 on TGFβ in prostate cancer cells, as well as two other important proteins downstream in this cascade, Smad2 and 3, were investigated. PC-3 cells were incubated for 3, 5, 10, 30 and 60 minutes as well as 38 hours both together with 1,25(OH)2D3 of the concentrations 10-10 and 10-7 M and without. As the downstream cascade protein JNK is a known activator of Smad2/3, this procedure was also repeated with a JNK inhibitor. An ELISA assay scanning for activated TGFβ was then performed on supernatants from the cells treated without JNK inhibitor. In addition, a Western Blot scanning for activated Smad2 and 3 was performed on supernatants from all groups of treatment. The analysis of the result values showed that 10-10 M 1,25(OH)2D3 significantly lowered the content of active TGFβ in PC-3 cells within 3 and 5 minutes. Unfortunately the Western Blot was unsuccessful and needs therefore be repeated.</p>

Recent advances in radiation therapy have provided the possibility of combining different modalities, energies and particles in different parts of the treatment. However, there are very limited data on the clinical effectiveness of these modalities. The purpose of this study was the determination of the parameters D50 and γ for the prostate adenocarcinoma, the rectum and the penile bulb using different radiobiological models, when proton and photon beams are combined. / Πρόσφατες εξελίξεις στην ακτινοθεραπεία παρέχουν την δυνατότητα συνδυασμού διαφόρων μονάδων, ενεργειών και σωματιδίων σε διαφορετικά τμήματα της θεραπείας. Ωστόσο, υπάρχουν πολύ περιορισμένα δεδομένα που αφορούν στην κλινική αποτελεσματικότητα αυτών των συνδυασμών. Ο σκοπός αυτής της εργασίας ήταν ο προσδιορισμός των παραμέτρων D50 και γ για το αδενοκαρκίνωμα του προστάτη το ορθό καθώς και τον βολβό του πέους με τη χρήση διαφόρων ραδιοβιολογικών μοντέλων, στην περίπτωση της συνδυασμένης χρήσης δέσμεων φωτονίων και πρωτονίων.