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- Bylund, Annika, 1954-
(författare)
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Phytoestrogens and prostate cancer : experimental, clinical, and epidemiological studies
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Dietary factors may affect development and progression of prostate cancer. Experimental and epidemiological studies have suggested an effect of phytoestrogens on prostate cancer. Lignans are the predominant phytoestrogen in a Western diet. The effects of a diet rich in phytoestrogens and in particular lignans, as compared to a control diet, were assessed in several prostate cancer models. In paper I, 70 athymic nude mice with transplanted subcutaneous LNCaP tumours, an androgen sensitive human prostate cancer cell line, were fed one out of six phytoestrogen rich diets or a control diet after tumour injection. The rye diet, with high lignan content, decreased tumour take and growth, decreased secretion of prostate specific antigen and increased apoptosis. Addition of fat to the rye diet decreased the beneficial effects. In paper II, transgenic mice designed to develop prostate cancer (TRAMP) were fed rye bran or a control diet from the age of four weeks. Rye bran decreased prostate epithelial cell volume by 20%, and increased cell apoptosis by 31% as compared to the control diet. In paper III, we examined the effects of 7-hydroxymatairesinol (HMR), a purified lignan, in nude mice with subcutaneous LNCaP tumours in two different concentrations as compared to a control diet. Mice on the HMR diets had a reduced tumour take rate, lower total tumour volume, increased proportion of non-growing tumours, and increased apoptosis as compared to the control diet. Paper IV was a three week intervention study exploring the effects of rye bran bread vs. a control diet in men with prostate cancer. The men in the rye group had increased levels of plasma enterolactone and in biopsies from the prostate after the intervention an increase in apoptosis was observed in comparison with biopsies obtained before the intervention. In paper V, we examined the association between plasma levels of enterolactone, and risk of prostate cancer in a nested case control study. In the Northern Sweden Health and Disease Cohort, enterolactone concentrations were measured in plasma obtained at a mean time of 5 years before diagnosis from 265 cases of prostate cancer, and from 525 matched controls. We found no significant association between plasma enterolactone and risk of prostate cancer. Men with very low enterolactone levels (bottom decile) however, had significantly higher risk of prostate cancer. Phytoestrogen rich diet including soy, rye bran, substances purified from rye, and a purified lignan (HMR) all inhibited prostate tumour growth. However, it cannot be concluded that the effects observed were due solely to lignans as other components in rye grain such as tannins, phytic acid, ferulic acid, vitamins and minerals may have contributed to the beneficial effects. Thus, additional studies are needed to further elucidate the effects of phytoestrogens on prostate cancer development and progression.
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- Fant, Federica, 1972-
(författare)
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Optimization of the perioperative anaesthetic care for prostate cancer surgery : clinical studies on pain, stress response and immunomodulation
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Prostate cancer (PC) is the most common cancer form in men. Surgery is the treatment of choice for localized form of PC and half of all surgical procedures are radical retropubic prostatectomies (RRP). In the first two studies, we compared the efficacy of thoracic epidural analgesia to patientcontrolled analgesia (PCA) with intravenous morphine (I) and to patientcontrolled local analgesia by intra-abdominal injection of local anaesthetic(LA) (II) in treating postoperative pain after RRP. In studies III and IV we evaluated the effects of thoracic epidural analgesia compared to PCA with morphine in reducing the surgical stress reaction, inflammatory response (III) as well as the immune suppression (IV) following RRP. In studies I and II, we found better pain relief both at rest and on coughing, lower morphine consumption and better respiratory function postoperatively in patients having epidural analgesia. However, we did not register differences in time to home readiness or length of hospital stay. Painmanagement did not significantly affect health-related quality of life. In study III, early surgical stress response (plasma glucose and cortisol) was reduced two hours after the skin incision in patients having epidural analgesia compared with those having intravenous morphine analgesia but no differences in inflammatory mediators were seen except IL-17 which was lower in the epidural group. In study IV, no differences were found between epidural and PCA groups in leucocyte subpopulations, immunecell activation after mitogen stimulation or in natural killer cell cytotoxicityas a measure of innate immunity. We observed a low incidence of side effects and postoperative complications in all studies with no differences between the groups. In summary, thoracic epidural analgesia provided better postoperative pain relief, improved respiratory function and reduction in early stress response to radical retropubic prostatectomy, without any significant effects on inflammation or immune suppression.
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- Svensson, Maria, 1980-
(författare)
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Assessing the ERG rearrangement for clinincal use in patients with prostrate cancer
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In Sweden, close to 10 000 men are annually diagnosed with prostate cancer (PCa) and approximately 2400 men die of their disease each year. Today there is no reliable marker that can separate patients who will have an aggressive type of disease that requires treatment, from patients who will have a more indolent clinical course and can be left untreated. This further leads to the current problem of over treatment of men with PCa. Hence, there is an urgent need for reliable prognostic markers that can be used at time of diagnosis. With the discovery of recurrent gene rearrangements in PCa, most commonly ERG rearrangements, hope came that this aberration could play a role in diagnosis and/or prognosis of the disease.The aim of this thesis was to investigate the clinical implication of ERG rearrangements in the management of PCa.The work in this thesis supports the findings from previous studies, suggesting that the ERG rearrangement is a sign of a more aggressive type of cancer. The major findings are that in multifocal PCa, the ERG rearranged cancer foci are more prone to metastatic dissemination compared to foci without the ERG rearrangement and that patients harboring the ERG rearrangement have a faster disease progression leading up to earlier start of hormonal treatment. Furthermore, the results add an additional level of complexity in a subset of PCa tumors that harbor multiple gene rearrangements on the cellular level. The result also show that the newly available ERG antibody is highly predictive of ERG rearrangement and is appropriate to use when faced with limitations in tissue amounts.The findings in this thesis indicate that the ERG rearrangement has a potential role in the clinical management of PCa but further studies arerequired.
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