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- Adolfsson, Per, et al.
(författare)
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Lysophosphatidic acid stimulates proliferation of cultured smooth muscle cells from human BPH tissue : Sildenafil and papaverin generate inhibition
- 2002
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Ingår i: The Prostate. - : Wiley. - 0270-4137 .- 1097-0045. ; 51:1, s. 50-58
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Tidskriftsartikel (refereegranskat)abstract
- Background The endogenous substance lysophosphatidic acid (LPA) has been found to generate proliferation of cultured smooth muscle cells (SMC). Therefore, the effect of LPA on human benign prostate hyperplasia (BPH) could be of interest.Methods The proliferative effect of LPA on cultured human prostatic SMC from specimens obtained at trans-urethral resection of the prostate (TURP) because of BPH, was analyzed by [3H]-thymidine and [35S]-methionine incorporation. In addition, LPA stimulated BPH SMC were treated with papaverin, forskolin, sildenafil or zaprinast, well known to increase the intracellular level of cAMP or cGMP.Results LPA produced a dose-dependent increase in BPH SMC, both regarding DNA- and protein-synthesis with EC50 values of 3 and 10 μM, respectively. Furthermore, both papaverin, a general phosphodiesterase inhibitor regarding cAMP hydrolyzes, and forskolin, an adenylyl cyclase stimulating agent, inhibited the LPA-stimulated DNA replication in a dose dependent manner with IC50 = 2.5, and 0.35 μM, respectively. cGMP increasing agents, such as the NO-donors SIN-1 and SNAP, produced a weak anti-proliferative response. However, both phosphodiesterase 5 inhibitors sildenafil (Viagra®) and zaprinast efficiently blocked DNA replication. In addition, when the protein synthesis was examined, we found that the LPA response was significantly inhibited by forskolin and papaverin.Conclusions The major conclusion of this investigation is that the endogenous serum component LPA, is able to promote human BPH SMC growth. In addition, our study indicates that cyclic nucleotides can inhibit this effect. Future clinical studies will be needed to determine if different specific phosphodiesterase inhibitors per se or in combination could represent a new therapeutic possibility for the treatment of BPH.
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| 2. |
- Aus, Gunnar, et al.
(författare)
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Prognostic Factors and Survival in Node-Positive (N1) Prostate Cancer : A Prospective Study Based on Data from a Swedish Population-Based Cohort
- 2003
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Ingår i: European Urology. - 0302-2838 .- 1873-7560. ; 43:6, s. 627-631
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Tidskriftsartikel (refereegranskat)abstract
- Objective: At presentation of prostate cancer, patients with proven lymph node metastasis (N1) are comparatively rare. It is difficult to give prognostic information based on the present literature. The aim of this study was to evaluate the impact of known risk factors in patients with pelvic node involvement and without distant metastasis. Methods: From the population-based, prospective prostate cancer tumour registry of the South–East Region in Sweden, we collected data on all 181 patients with N1, M0 prostate cancer diagnosed from January 1987 to October 2000 with a follow-up to December 2001. Mean follow-up was 62 months. Pre-operative risk factors as age, T-category, serum PSA, tumour grade and also primary treatment given was correlated to the outcome. Results: Median age at diagnosis was 65 years. Cancer-specific survival was highly variable with 5-year survival of 72%, a median of 8 years and the projected 13-year figure was 31%. T-category, age, PSA or treatment did not affect the outcome while poorly differentiated tumours had a tendency towards lower cancer-specific survival (p=0.0523) when compared to well and moderately differentiated tumours. Conclusions: This population-based cohort of prostate cancer patients with pelvic node involvement treated principally with non-curative intent had a median cancer-specific survival of 8 years. Preoperatively known risk factors seem to have but a modest impact on the prognosis for patients in this stage of the disease.
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| 6. |
- Sandblom, G, et al.
(författare)
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A population-based study of pain and quality of life during the year before death in men with prostate cancer
- 2004
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 90:6, s. 1163-1168
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Tidskriftsartikel (refereegranskat)abstract
- In order to explore how health-related quality of life changes towards the end of life, a questionnaire including the EuroQOI form and the Brief Pain Inventory form was sent to all men with prostate cancer in the county of Östergötland, Sweden, in September 1999. Responders who had died prior to 1 January 2001 were later identified retrospectively. Of the 1442 men who received the questionnaire, 1243 responded (86.2%). In the group of responders, 167 had died within the study period, 66 of prostate cancer. In multivariate analysis, pain as well as death within the period of study were found to predict decreased quality of life significantly. Of those who died of prostate cancer, 29.0% had rated their worst pain the previous week as severe. The same figure for those still alive was 10.5%. On a visual analogue scale (range 0-100), the mean rating of quality of life for those who subsequently died of prostate cancer was 54.0 (95% confidence interval ±5.2) and those still alive was 70.0 (±1.2). In conclusion, hearth-related quality of life gradually declines during the last year of life in men with prostate cancer. This decline may partly be avoided by an optimised pain management. © 2004 Cancer Research UK.
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| 8. |
- Sandblom, Gabriel, et al.
(författare)
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Clinical consequences of screening for prostate cancer : 15 Years follow-up of a randomised controlled trial in Sweden
- 2004
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 46:6, s. 717-723
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Tidskriftsartikel (refereegranskat)abstract
- Objective:To test the feasibility of a population-based prostate cancer screening programme in general practice and explore the outcome after a 15-year follow-up period.Methods:From the total population of men aged 50–69 years in Norrköping (n = 9026) every sixth man (n = 1494) was randomly selected to be screened for prostate cancer every third year over a 12-year period. The remaining 7532 men were treated as controls. In 1987 and 1990 only digital rectal examination (DRE) was performed, in1993 and 1996 DRE was combined with a test for Prostate-Specific Antigen (PSA). TNM categories, grade of malignancy, management and cause of death were recorded in the South-East Region Prostate Cancer Register.Results:There were 85 (5.7%) cancers detected in the screened group (SG), 42 of these in the interval between screenings, and 292 (3.8%) in the unscreened group (UG). In the SG 48 (56.5%) of the tumours and in the UG 78 (26.7%) were localised at diagnosis (p < 0.001). In the SG 21 (25%) and in the UG 41 (14%) received curative treatment. There was no significant difference in total or prostate cancer-specific survival between the groups.Conclusions:Although PSA had not been introduced in the clinical practice at the start of the study, we were still able to show that it is possible to perform a long-term population-based randomised controlled study with standardised management and that screening in general practice is an efficient way of detecting prostate cancer whilst it is localised. Complete data on stage, treatment and mortality for both groups was obtained from a validated cancer register, which is a fundamental prerequisite when assessing screening programmes.
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