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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. |
- Jerlström, Tomas, 1969-
(författare)
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Clinical aspects of cystectomy and urinary diversion
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this thesis was to explore different aspects of treatment of advanced urinary bladder cancer with radical cystectomy, pelvic lymph node dissection, and urinary diversion. Surgery that carry a high risk of complications as well as mortality. Aside from complications and risk of recurrance, patients have to cope with lifelong postoperative changes of body function, including sexual function, and body image, all affecting quality of life (QoL). The thesis comprises four papers. In the first paper, we compared functional outcome and QoL following two types of ileal orthotopic neobladder substitution. The results suggest that the S-shaped substitute entails better functional results than the U-shaped substitute, with better continence, especially at night. There was no difference in QoL. The second paper reports results from the first year of registration in the nation-wide Swedish Cystectomy Register. Analysis of risk factors for complications showed that high age and prolonged operation are associated with increased risk of short-term complications. The third paper investigated whether preoperative chemotherapy in patients with muscle-invasive bladder cancer (MIBC) affects the risk of shortterm complications after radical cystectomy, using data from the Cystectomy Register covering 1340 patients of whom 39 percent received preoperativevchemotherapy. We found no such increase in risk. In the fourth paper, we analysed the results of a validation study of the Cystectomy Register. The validation showed 17 percent more low grade complications, three percent more high grade complications, and five percent more readmissions, within 90 days of surgery. Hence, a third-party validation may improve the validity of the register
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| 4. |
- Ugge, Henrik, 1987-
(författare)
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Inflammation and prostate carcinogenesis : influence of immune characteristics and early-adulthood exposure to inflammatory conditions on prostate cancer risk
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Chronic inflammation has been implicated in the development of several types of cancer, and evidence from observational and animal studies suggests that it may play a role also in prostate carcinogenesis. Recent observations have brought Cutibacterium acnes (C. acnes) forward as a possible causative agent in pro-oncogenic prostatic inflammation. However, evidence also suggest that underlying immune characteristics contribute to prostate cancer risk. The overall aim of this thesis was to explore potential mechanisms underlying the proposed link between inflammation and prostate cancer, by evaluating associations between inflammatory conditions during early adulthood, circulating inflammation markers, and prostate cancer. Due to the suggested role of C. acnes in both diseases, we aimed to investigate whether acne vulgaris is a determinant of prostate cancer. Using prospectively collected data from Swedish national registers, we observed that presence of acne during early adulthood conferred an increased risk of prostate cancer later in life. Similarly, we found that appendicitis before late adolescence – a proposed marker of individual immune characteristics – to be positively associated with subsequent prostate cancer. We further evaluated whether prostatic C. acnes infection is linked with elevated systemic levels of IL6 and CXCL8, two inflammation markers previously associated with prostate cancer. No association was observed, however, potentially explained by the subclinical low-grade infection typically caused by C. acnes. Finally, we evaluated 52 circulating inflammation markers as determinants for prostate cancer in a population-based case-control study. In this hypothesis-generating study, we identified CX3CL1, CCL21, PDGF-BB, CCL11 and IL10 as candidate markers for evaluation in prospective studies. If confirmed, these markers may hint at targetable molecular pathways involved in prostate carcinogenesis.
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