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- Bill-Axelson, Anna, et al.
(författare)
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Radical prostatectomy versus watchful waiting in localized prostate cancer : the Scandinavian prostate cancer group-4 randomized trial
- 2008
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press. - 0027-8874 .- 1460-2105. ; 100:16, s. 1144-1154
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The benefit of radical prostatectomy in patients with early prostate cancer has been assessed in only one randomized trial. In 2005, we reported that radical prostatectomy improved prostate cancer survival compared with watchful waiting after a median of 8.2 years of follow-up. We now report results after 3 more years of follow-up.METHODS: From October 1, 1989, through February 28, 1999, 695 men with clinically localized prostate cancer were randomly assigned to radical prostatectomy (n = 347) or watchful waiting (n = 348). Follow-up was complete through December 31, 2006, with histopathologic review and blinded evaluation of causes of death. Relative risks (RRs) were estimated using the Cox proportional hazards model. Statistical tests were two-sided.RESULTS: During a median of 10.8 years of follow-up (range = 3 weeks to 17.2 years), 137 men in the surgery group and 156 in the watchful waiting group died (P = .09). For 47 of the 347 men (13.5%) who were randomly assigned to surgery and 68 of the 348 men (19.5%) who were not, death was due to prostate cancer. The difference in cumulative incidence of death due to prostate cancer remained stable after about 10 years of follow-up. At 12 years, 12.5% of the surgery group and 17.9% of the watchful waiting group had died of prostate cancer (difference = 5.4%, 95% confidence interval [CI] = 0.2 to 11.1%), for a relative risk of 0.65 (95% CI = 0.45 to 0.94; P = .03). The difference in cumulative incidence of distant metastases did not increase beyond 10 years of follow-up. At 12 years, 19.3% of men in the surgery group and 26% of men in the watchful waiting group had been diagnosed with distant metastases (difference = 6.7%, 95% CI = 0.2 to 13.2%), for a relative risk of 0.65 (95% CI = 0.47 to 0.88; P = .006). Among men who underwent radical prostatectomy, those with extracapsular tumor growth had 14 times the risk of prostate cancer death as those without it (RR = 14.2, 95% CI = 3.3 to 61.8; P < .001).CONCLUSION: Radical prostatectomy reduces prostate cancer mortality and risk of metastases with little or no further increase in benefit 10 or more years after surgery.
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- de la Torre-Castro, Maricela, 1965-
(författare)
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Humans and Seagrasses in East Africa : A social-ecological systems approach
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The present study is one of the first attempts to analyze the societal importance of seagrasses (marine flowering plants) from a Natural Resource Management perspective, using a social-ecological systems (SES) approach. The interdisciplinary study takes place in East Africa (Western Indian Ocean, WIO) and includes in-depth studies in Chwaka Bay, Zanzibar, Tanzania. Natural and social sciences methods were used. The results are presented in six articles, showing that seagrass ecosystems are rich in seagrass species (13) and form an important part of the SES within the tropical seascape of the WIO. Seagrasses provide livelihoods opportunities and basic animal protein, in from of seagrass associated fish e.g. Siganidae and Scaridae. Research, management and education initiatives are, however, nearly non-existent. In Chwaka Bay, the goods and ecosystem services associated with the meadows and also appreciated by locals were fishing and collection grounds as well as substrate for seaweed cultivation. Seagrasses are used as medicines and fertilizers and associated with different beliefs and values. Dema (basket trap) fishery showed clear links to seagrass beds and provided the highest gross income per capita of all economic activities. All showing that the meadows provide social-ecological resilience. Drag-net fishery seems to damage the meadows. Two ecological studies show that artisanal seaweed farming of red algae, mainly done by women and pictured as sustainable in the WIO, has a thinning effect on seagrass beds, reduces associated macrofauna, affects sediments, changes fish catch composition and reduces diversity. Furthermore, it has a negative effect on i.a. women’s health. The two last papers are institutional analyses of the human-seagrass relationship. A broad approach was used to analyze regulative, normative and cultural-cognitive institutions. Cooperation and conflict take place between different institutions, interacting with their slow or fast moving characteristics, and are thus fundamental in directing the system into sustainable/unsustainable paths. Ecological knowledge was heterogeneous and situated. Due to the abundance of resources and high internal control, the SES seems to be entangled in a rigidity trap with the risk of falling into a poverty trap. Regulations were found insufficient to understand SES dynamics. “Well” designed organizational structures for management were found insufficient for “good” institutional performance. The dynamics between individuals embedded in different social and cultural structures showed to be crucial. Bwana Dikos, monitoring officials, placed in villages or landing sites in Zanzibar experienced four dilemmas – kinship, loyalty, poverty and control – which decrease efficiency and affect resilience. Mismatches between institutions themselves, and between institutions and cognitive capacities were identified. Some important practical implications are the need to include seagrass meadows in management and educational plans, addressing a seascape perspective, livelihood diversification, subsistence value, impacts, social-ecological resilience, and a broad institutional approach.
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- Loskog, Angelica, et al.
(författare)
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Human bladder carcinoma is dominated by T-regulatory cells and Th1 inhibitory cytokines
- 2007
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Ingår i: Journal of Urology. - : Ovid Technologies (Wolters Kluwer Health). - 0022-5347 .- 1527-3792. ; 177:1, s. 353-358
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Immunotherapy has faced limited success, although many solutions have been proposed. Recently regulatory T cells have made a comeback in the immunological arena and the role of these cells in patients with cancer is in focus. It is under evaluation whether the immunological status of patients with cancer may affect their sensitivity to immunotherapy. We are developing immunostimulating gene therapy for treating bladder cancer. In this study we constructed an immunological profile of patients with bladder carcinoma to understand which obstacles must be circumvented. Materials and Methods: Biopsies and blood were used to identify immune cell populations by FACS®, histochemistry and proliferation assays, and cytokine production by polymerase chain reaction. Results: Results indicate that bladder carcinoma is a Tri dominated tumor, as shown by the infiltration of T-regulatory cells expressing FOXP3, and the presence of tumor necrosis factor-β and interleukin-10 mRNA copies. We further noted that circulating patient T cells were unresponsive to polyclonal T-cell activation compared to healthy donor cells. Moreover, CD4+CD25+ T cells were increased in patient blood and could suppress the expansion of allogeneic T cells from healthy donors. Conclusions: Patients with bladder carcinoma show an immunosuppressive regulatory profile, including nonresponsive T cells. Clinical protocols able to effectively counteract these mechanisms are warranted.
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- Segersten, M. Ulrika, et al.
(författare)
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A novel strategy based on histological protein profiling in-silico for identifying potential biomarkers in urinary bladder cancer
- 2009
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Ingår i: BJU International. - 1464-4096 .- 1464-410X. ; 104:11, s. 1780-1785
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To screen a publicly available immunohistochemistry (IHC) based web-atlas, to identify key proteins in bladder cancer that might serve as potential biomarkers. MATERIALS AND METHODS: The first version of the Human Protein Atlas (HPA 1.0), with 660 proteins, was visually examined to identify proteins with a variable staining pattern among the 12 tissue samples representing bladder cancer. None or limited previous characterization in bladder cancer, as well as a supportive Western blot, were also required. The selected proteins were then evaluated in an independent set of patient samples (106 tumour samples of differing stage and grade) represented in a tissue microarray (TMAi). The IHC expression of the identified proteins in the TMAi was scored and related to tumour stage and grade. RESULTS: The expression profiles of the 13 proteins selected from the web-atlas were confirmed in the TMAi. Expression patterns for seven proteins were significantly altered (P < 0.05) with higher stage and/or grade. Three of those (CN130, DSG3, PHF6) lack characterization in bladder cancer, whereas the remaining four proteins have previously been suggested as key proteins/potential biomarkers in cancer, some of them also in bladder cancer. CONCLUSION: New candidate proteins for urinary bladder cancer were identified through screening of the publicly available HPA 1.0. Although further evaluation is necessary, this strategy is promising in the search for new biomarkers, with potential to improve the management of patients with this disease.
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- Vikman, Sofia, et al.
(författare)
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Gene expression in midgut carcinoid tumors : potential targets for immunotherapy
- 2005
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 44:1, s. 32-40
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Tidskriftsartikel (refereegranskat)abstract
- Classical midgut carcinoids are serotonin-secreting tumors derived from enterochromaffin cells in the gut. Metastatic disease represents a therapeutic challenge and immunotherapy implies a novel approach for treatment. In order to define antigens suitable for T-cell therapy with a preferential expression in midgut carcinoid tissue a broad screening of genes with preferential neuroendocrine restriction, genes described as over-expressed in various malignancies, and genes encoding cancer-testis associated antigens was performed. The expression of 32 genes was analyzed by reverse transcription polymerase chain reaction (RT-PCR) in 28 midgut carcinoid specimens, in the cell line BON and in normal tissues. Immunohistochemistry (IHC) was used to evaluate protein expression. Expression is shown of genes that have previously not been observed in midgut carcinoid tumors, such as Survivin and GAGEs. Also the expression is confirmed of genes that encode pivotal proteins in enterochromaffin cells, such as TPH1 and VMAT1, and their tissue-restricted expression is indicated. In addition, gene expression of IA-2 and CDX-2 in normal gastrointestinal (GI) tract and in tumor is shown. Protein expression of TPH, VMAT1, and Survivin was detected in tumor tissue. This study elucidates that TPH1, VMAT1, and Survivin should be further investigated as potential target antigens for T cell-mediated immunotherapy of midgut carcinoids.
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| 7. |
- Vikman, Sofia, et al.
(författare)
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Midgut carcinoid patients display increased numbers of regulatory T cells in peripheral blood with infiltration into tumor tissue
- 2009
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 48:3, s. 391-400
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Our aim was to investigate the immune status of midgut carcinoid patients. Cancer patients generally display suppressed Th1-type immunity that disables mounting of an efficient anti-tumor response. However, little is known about patients with neuroendocrine midgut carcinoids. MATERIAL AND METHODS: Circulating regulatory T cells were determined in patient blood by staining for CD4, CD25 and FoxP3 in flow cytometric analysis. T cell proliferation was measured by Alamar Blue in response to polyclonal activation and the regulatory phenotype of patient CD25+ cells was validated by allogeneic stimulation of CFSE labelled responders. Cytokine levels in patient peripheral blood were measured by ELISA and CBA. Tumor infiltrating T cells were analyzed by immunohistochemistry and immunofluorescence. RESULTS: The results demonstrate that midgut carcinoid patients exhibit increased frequencies of circulating Tregs and patient T cells have a decreased proliferative capacity compared to healthy donors. Systemic Th1-promoting cytokines are reduced. Midgut carcinoid tumors display CD4+ and CD8+ T cell infiltration, always in the presence of regulatory CD4+FoxP3+ cells. DISCUSSION: Midgut carcinoid patients display elevated T regulatory cell numbers and T cell dysfunction. Therapeutic strategies to overcome tumor-induced Th1 immunosuppression are required in combination with anti-tumor vaccinations.
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