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- Davidsson, Sabina, 1972-
(författare)
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Infection induced chronic inflammation and it's association with prostate cancer initiation and progression
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- An association between cancer development and inflammation has long been suggested. Approximately 20% of all human cancers in adults are assumed to result from chronic inflammation. The aim of this thesis was to investigate if infection-induced chronic inflammation plays a role in prostate carcinogenesis.Our results revealed a greater infiltration of the bacterium Propionibacterium acnes in the prostate tissue obtained from men with prostate cancer compared to men without any histological evidence of the disease. These findings indicate that prostate cancer could potentially be included in the list of cancers with an infectious etiology.Further, we investigated whether chronic inflammation has a role in disease progression. Our results demonstrated that men with lethal prostate cancer had pronounced infiltration of immune cells with suppressive function of the anti-tumor immune response compared to men with a more indolent prostate cancer.Confirmation of our results may open up avenues for targeted prostate cancer treatment by offering men with chronic inflammation alternative therapies such as anti-inflammatory drugs. If the involvement of P. acnes in prostate cancer development is replicated in other studies, vaccination therapies may be feasible. To further individualize prostate cancer therapy, bolstering the anti-tumor immune response in order to reduce tumor progression may be determined to be advantageous for some patients.
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| 2. |
- Lycken, Magdalena, 1973-
(författare)
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Living and dying with prostate cancer : Population-based register studies
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Tailored treatment with adequate timing is essential for the quality of prostate cancer care at all stages. Overtreatment should be avoided due to the side effects, but undertreatment may on the other hand lead to progression and death. This thesis aims to describe the patterns of use for non-curative treatments of prostate cancer, alongside the time trends of disease characteristics of men who die from prostate cancer. The work was based on the National Prostate Cancer Register of Sweden (NPCR).The first study included 45 147 men. The cumulative incidence of castration was 11.6% at ten years after diagnosis, while it was 10.8% for antiandrogen monotherapy. Estimated median durations of castration ranged from four years in the deferred treatment high-risk group to seventeen years in the prostatectomy low-risk group. The second study included 114 cases and 1140 controls. Four men out of ten received androgen deprivation therapy although they had prostate-specific antigen doubling time ≥12 months and biopsy Gleason score ≤7, which was defined as non-adherence to the guidelines of the European Association of Urology. Most of these men had low-risk features at diagnosis. The third study included 8326 men. During the last year before death from prostate cancer, use of opioids increased from 30% to 72%. Men without close relatives and older men had lower probability to receive opioids. The fourth study included 45 850 men. During the study period of 1992 to 2012, the time trend showed a stage shift towards lower risk group at diagnosis, longer disease duration, and higher age at death among men who died from prostate cancer.The first two studies indicate that overtreatment with androgen deprivation therapy is common after curative treatment, why interventions to improve adherence to guidelines are needed. The third study indicates that men without close relatives and older men are disadvantaged with respect to treatment of cancer pain, why they need closer attention from health care providers. The findings in the fourth study may reflect the synergetic effects of prolonged lead time, increased life expectancy, and improvements in the management of prostate cancer during the last two decades.
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| 3. |
- Spetz, Anna-Clara, 1973-
(författare)
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Vasomotor symptoms in men and the role of Calcitonin Gene-Related Peptide
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Hot flushes is a cotmnon phenomenon in women during the menopausal transition. In men treated with castration because of prostate cancer, hot flushes are probably the most cotmnon and distressing side-effect and are as common in these men as in menopausal women but the course of the flushes is unknown. Flushes also occur in healthy aging men, but the prevalence is unknown. The mechanisms behind hot flushes are not fully understood. They are probably caused by instability in the thermoregulatory centre due to a decrease in sex hotmone concentrations. Calcitonin Gene-Related Peptide (CGRP) and perhaps also Neuropeptide Y (NPY) are probably involved in menopausal hot flushes in women and could also be involved in men following therapeutic castration.The aims of this thesis were to compare different methods of castration as regards the occunence and course of hot flushes, and to investigate the prevalence of hot flushes in an unselected population of elderly men. A further aim was to see if CGRP and NPY are involved in hot flushes in men, in the same way as has previously been suggested in women.In this thesis two different modalities of castration therapy were compared: 1. castration by means of estrogens (Polyestradiol phosphate) and 2. total androgen blockade (a. bilateral orchiectomy or b. GnRH-analogue combined with oral anti-androgen). A much lower incidence of hot flushes were seen in the first group (1). Flushes induced by castration with estrogen were also milder and tended to disappear with time.The prevalence of hot flushes in a male population 55 years of age and above was investigated by means of a questionnaire. Thirty per cent of the men repotted flushes and half of these found the flushes distressing, i.e. every sixth man in the study. There was an association between flushes and a number of symptoms that are often related to low testosterone concentrations in the blood.The 24-hour urinaty excretion of CGRP was investigated in 17 men with prostate cancer before and after castration. Thirteen of the 17 men developed hot flushes after castration, but the urinary excretion of CGRP was not significantly altered.Blood-samples were taken during hot flushes in 10 men for analysis of CGRP- and NPY-plasma concentrations. CGRP increased in 6 men (we failed to obtain CGRP measurements in the other men due to technical problems). NPY concentrations were below the detection limit for the analysis in all samples.In conclusion vasomotor symptoms are common in men subjected to castration therapy. Different castration modalities result in different prevalence of hot flushes, something that should be considered when choosing the method of castration for men with prostate cancer. Hot flushes also occur in normal, aging men. The mechanisms behind hot flushes in men and women may be similar. CGRP may be involved in hot flushes in castrated men.In order to be able to develop new treatment regimens for these vasomotor symptoms fmther studies on the mechanisms behind hot flushes should be undertaken, in both castrated and in otherwise healthy elderly men.
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