| 1. |
- Adolfsson, Jan, et al.
(författare)
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Clinical characteristics and primary treatment of prostate cancer in Sweden between 1996 and 2005
- 2007
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Ingår i: Scandinavian Journal of Urology and Nephrology. - : Informa UK Limited. - 0036-5599 .- 1651-2065. ; 41:6, s. 456-477
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The incidence of prostate cancer is rising rapidly in Sweden and there is a need to better understand the pattern of diagnosis, tumor characteristics and treatment. MATERIAL AND METHODS: Between 1996 and 2005, all new cases of adenocarcinoma of the prostate gland were intended to be registered in the National Prostate Cancer Register (NPCR). This register contains information on diagnosing unit, date of diagnosis, cause of diagnosis, tumor grade, tumor stage according to the TNM classification in force, serum prostate-specific antigen (PSA) levels at diagnosis and primary treatment given within the first 6 months after diagnosis. RESULTS: In total, 72,028 patients were registered, comprising >97% of all pertinent incident cases of prostate cancer in the Swedish Cancer Register (SCR). During the study period there was a considerable decrease in median age at the time of diagnosis, a stage migration towards smaller tumors, a decrease in median serum PSA values at diagnosis, a decrease in the age-standardized incidence rate of men diagnosed with distant metastases or with a PSA level of > 100 ng/ml at diagnosis and an increase in the proportion of tumors with Gleason score <6. Relatively large geographical differences in the median age at diagnosis and the age-standardized incidence of cases with category T1c tumors were observed. Treatment with curative intent increased dramatically and treatment patterns varied according to geographical region. In men with localized tumors and a PSA level of <20 ng/ml at diagnosis, expectant treatment was more commonly used in those aged > or =75 years than in those aged <75 years. Also, the pattern of endocrine treatment varied in different parts of Sweden. CONCLUSIONS: All changes in the register seen over time are consistent with increased diagnostic activity, especially PSA testing, resulting in an increased number of cases with early disease, predominantly tumors in category T1c. The patterns of diagnosis and treatment of prostate cancer vary considerably in different parts of Sweden. The NPCR continues to be an important source for research, epidemiological surveillance of the incidence, diagnosis and treatment of prostate cancer.
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| 2. |
- Varenhorst, Eberhard, 1937-, et al.
(författare)
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The National Prostate Cancer Register in Sweden 1998-2002 : trends in incidence, treatment and survival
- 2005
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Ingår i: Scandinavian Journal of Urology and Nephrology. - : Informa UK Limited. - 0036-5599 .- 1651-2065. ; 39:2, s. 117-123
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To provide a descriptive review of the establishment of the National Prostate Cancer Register (NPCR) in Sweden, to present clinical characteristics at diagnosis and to calculate the relative survival of different risk groups after 5 years. MATERIAL AND METHODS: Since 1998, data on all newly diagnosed prostate cancers, including TNM classification, grade of malignancy, prostate-specific antigen (PSA) level and treatment, have been prospectively collected. For the 35,223 patients diagnosed between 1998 and 2002, relative survival in different risk groups has been calculated. RESULTS: Between 1998 and 2002, 96% of all prostate cancer cases diagnosed in Sweden were registered in the NPCR. The number of new cases increased from 6137 in 1998 to 7385 in 2002. The age-standardized rate rose in those aged < 70 years, while it was stable, or possibly declining from 1999, in the older age groups. The proportion of T1c tumours increased from 14% to 28% of all recorded cases. The age-adjusted incidence of advanced tumours (M1 or PSA > 100 ng/ml) decreased by 17%. The proportion of patients receiving curative treatment doubled. Patients with N1 or M1 disease or poorly differentiated tumours (G3 or Gleason score 8-10) had a markedly reduced relative 5-year survival rate. CONCLUSIONS: It is possible to establish a nationwide prostate cancer register including basic data for assessment of the disease in the whole of Sweden. The introduction of PSA screening has increased the detection of early prostate cancer in younger men and, to a lesser extent, decreased the incidence of advanced disease. The effect of these changes on mortality is obscure but the NPCR in Sweden will serve as an important tool in such evaluation.
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| 3. |
- Haghsheno, Mohammad-Ali, et al.
(författare)
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Low 25-OH Vitamin D Level is Associated with Benign Prostatic Enlargement (BPE).
- 2013
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Ingår i: The Journal of urology. - : Ovid Technologies (Wolters Kluwer Health). - 1527-3792 .- 0022-5347. ; 190:2, s. 608-614
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To test the hypothesis that low levels of vitamin D were associated with Benign Prostatic Enlargement (BPE). We also studied whether body composition, sex hormones, serum SHBG, albumin corrected serum calcium, adiponectin and lipid statuses were associated with BPE. MATERIALS AND METHODS: 184 representative randomly selected men aged 72 - 76 years, enrolled in the Gothenburg arm of the MrOs study, were investigated. Men with a medical history of prostate cancer, prostate operation or medication for BPE were excluded leaving 155 men to be analyzed. A cross-sectional study was conducted in which BPE, as measured by the total prostate gland volume, was related to clinical, anthropometric, endocrine and metabolic factors, using univariate and multivariate analyses with regression models. RESULTS: The median prostate volume was 40 ml. In multivariate models only 25-OH vitamin D, albumin corrected serum calcium, serum SHBG and HDL-cholesterol were significantly and inversely associated with large prostate glands. CONCLUSION: The present report adds four independent factors associated with BPE: Low levels of 25-OH vitamin D, serum calcium, SHBG and HDL-cholesterol.
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| 4. |
- Haghsheno, Mohammad-Ali, et al.
(författare)
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Lower urinary tract symptoms are associated with low levels of serum serotonin, high levels of adiponectin and fasting glucose, and benign prostatic enlargement.
- 2015
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Ingår i: Scandinavian journal of urology. - : Medical Journals Sweden AB. - 2168-1813 .- 2168-1805. ; 49:2, s. 155-161
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Objective. The aim of this study was to test whether lower urinary tract symptoms (LUTS) and urinary incontinence are associated with the metabolic syndrome (MetS). The association between LUTS and benign prostatic enlargement (BPE) was also investigated. Material and methods. A cross-sectional, representative risk factor analysis of LUTS, as measured by the International Prostate Symptom Score (IPSS), and urinary incontinence was conducted. Among 950 representative individuals, aged 69-81 years, the association between clinical, anthropometric, endocrine, metabolic and inflammatory factors on the one hand, as both major and minor aspects of MetS, and LUTS and urinary incontinence, on the other hand, was analysed. The prostate gland volume was measured in a subgroup of 155 randomly selected individuals and the association between LUTS and BPE was estimated. Results. No significant association was found between LUTS or urinary incontinence and the major aspects of the MetS. However, in a multivariate analysis, serum serotonin showed an independent negative correlation with LUTS and with urinary incontinence while fasting serum glucose and serum adiponectin showed a positive correlation with LUTS. Furthermore, in a subgroup of 155 individuals, the prostate gland volume correlated positively with LUTS. Conclusions. The study did not show an association between LUTS or urinary incontinence and the major components of the MetS. However, serum serotonin showed an independent negative correlation with LUTS and with urinary incontinence while fasting serum glucose and serum adiponectin showed a positive correlation with LUTS. The data confirm the general knowledge that BPE may be one of the causative factors of LUTS.
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| 5. |
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| 6. |
- Hammarsten, Jan, et al.
(författare)
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A stage-dependent link between metabolic syndrome components and incident prostate cancer
- 2018
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Ingår i: Nature Reviews Urology. - : Springer Science and Business Media LLC. - 1759-4812 .- 1759-4820. ; 15:5, s. 321-333
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Forskningsöversikt (refereegranskat)abstract
- Metabolic syndrome is associated with increased cancer risk and progression at almost all sites, including the prostate in high-stage prostate cancer. However, several reports have described an inverse relationship between metabolic syndrome and its components and low-stage incident prostate cancer. Such anomalies in cancer research hamper efforts to fight cancer. Evidence suggests that metabolic syndrome and its components have two distinct effects in prostate cancer, concealing prostate cancer in low-stage disease and promoting progression to high-stage incident, nonlocalized, and lethal prostate cancer. The concealment of prostate cancer by metabolic syndrome and its components might be related to bias mechanisms that reduce PSA level and lead to a delayed diagnosis of low-stage prostate cancer, meaning that fewer men with metabolic syndrome are diagnosed with low-stage disease. The inverse link between metabolic syndrome and its components and low-stage incident prostate cancer might simply be the result of such bias and the shortcomings of the diagnostic procedure rather than being related to prostate cancer biology itself. The evidence summarized here supports the hypothesis that the link between metabolic syndrome and its components and incident prostate cancer is a two-way and stage-dependent one, a theory that requires further research. © 2018 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.
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| 7. |
- Josefsson, Andreas, 1979, et al.
(författare)
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Effect of docetaxel added to bicalutamide in Hormone-Naive non-metastatic prostate cancer with rising PSA, a randomized clinical trial (SPCG-14)
- 2023
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Ingår i: Acta Oncologica. - 0284-186X. ; 62:4, s. 372-380
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundHistorically, endocrine therapy was used in a range of scenarios in patients with rising PSA, both as a treatment for locally advanced non-metastatic prostate cancer and PSA recurrence following curative intended therapy. In the present study the objective was to investigate if chemotherapy added to endocrine therapy could improve progression-free survival (PFS).Materials and MethodsPatients with hormone-naive, non-metastatic prostate cancer and rising prostate-specific antigen (PSA), enrolled from Sweden, Denmark, the Netherlands, and Finland, were randomized to long-term bicalutamide (150 mg daily) or plus docetaxel (75 mg/m(2), q3w, 8-10 cycles) without prednisone, after stratification for the site, prior local therapy or not, and PSA doubling time. The primary endpoint was 5-year PFS analyzed with a stratified Cox proportional hazards regression model on intention to treat basis.ResultsBetween 2009 and 2018, a total of 348 patients were randomized; 315 patients had PSA relapse after radical treatment, 33 patients had no prior local therapy. Median follow-up was 4.9 years (IQR 4.0-5.1). Adding docetaxel improved PFS (HR 0.68, 95% CI 0.50-0.93; p = 0.015). Docetaxel showed an advantage for patients with PSA relapse after prior local therapy (HR 0.67, 95% CI 0.49-0.94; p = 0.019). One event of neutropenic infection/fever occurred in 27% of the patients receiving docetaxel. Limitations were slow recruitment, lack of enrolling patients without radical local treatment, and too short follow-up for evaluation of overall survival in patients with PSA relapse.ConclusionDocetaxel improved PFS in patients starting bicalutamide due to PSA relapse after local therapy or localized disease without local therapy. Confirmatory studies of the efficacy of docetaxel in the setting of PSA-only relapse in addition to endocrine therapies may be justified if longer follow-up will show increased metastatic-free survival.
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| 8. |
- Lennernäs, Bo, 1963, et al.
(författare)
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Radical prostatectomy versus high-dose irradiation in localized/locally advanced prostate cancer: A Swedish multicenter randomized trial with patient-reported outcomes.
- 2015
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Ingår i: Acta oncologica (Stockholm, Sweden). - : Informa Healthcare. - 1651-226X .- 0284-186X. ; 54:6, s. 875-881
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Tidskriftsartikel (refereegranskat)abstract
- Background. Treatment of localized prostate cancer (PC) is controversial. This is the first randomized study comparing an open surgery procedure (radical prostatectomy) with a combination of high-dose rate brachytherapy (2 × 10 Gy) and external beam radiotherapy (25 × 2 Gy) in PC patients in Sweden 1996-2001. The two randomization arms were compared regarding differences in patients-reported outcomes, such as complications and health-related quality of life (HRQoL). Material and methods. The patients had localized/locally advanced PC, clinical category T1b-T3a, N0, M0 and PSA ≤ 50 ng/ml. All underwent total androgen blockade (six months). Self-reported HRQoL and symptoms including urinary, bowel, and sexual side effects were investigated prospectively before randomization and 12 and 24 months after randomization. A total of 89 patients were randomized and completed the EORTC QLQ C-33 and EORTC PR-25 questionnaires. Results. Over the study period, there were no discernible differences in HRQoL, or complications between the two groups. Emotional functioning, however, improved statistically significantly over time, whereas Social functioning decreased, and financial difficulties increased. No statistically significant differences in group-by-time interactions were found. The survival rate was 76%. Only eight patients (9%) died of PC. Conclusion. Open radical prostatectomy and the combined high-dose rate brachytherapy with external beam radiation appeared to be comparable in the measured outcomes. It was not possible to draw any conclusion on the efficacy of the two treatments due to insufficient power of the study.
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| 9. |
- Lissbrant, Erik, et al.
(författare)
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Effects of haemorrhagic hypotension on the subcapsular artery and microvasculature of the rat testis.
- 2006
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Ingår i: Int J Androl. - : Wiley. ; 29:3, s. 434-440
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Tidskriftsartikel (refereegranskat)abstract
- Developing germ cells may be sensitive to even moderate reductions in blood flow. Surprisingly, however, experimental evidence suggests that the rat testis may be unable to maintain its blood flow during a decrease in systemic blood pressure. This study was therefore performed in order to answer the following questions: Is the testis able to maintain its blood flow during moderate to major reductions in blood pressure and, if so, at which level of the testicular vasculature (main artery or microcirculation) does this compensatory response take place? Moderate (−20%) and major (−40%) reductions in blood pressure were induced in anaesthetized rats by haemorrhage and the effects on testicular microvascular blood flow and subcapsular testicular artery diameter were examined by using laser Doppler flowmetry and in vivo video-microscopy respectively. Haemorrhagic hypotension led to decreased local testicular blood flow, but the relative reductions in flow were generally only half as large as the reductions in blood pressure. Hypotension also decreased the diameter of the main subcapsular testicular artery. During large reductions in blood pressure the subcapsular testicular artery constricts and testicular blood flow decreases. However, blood flow is reduced proportionally less than the mean arterial pressure, suggesting that local regulatory mechanisms are present in the testicular microvasculature, which may prevent blood flow from falling below a critical level.
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| 10. |
- Mirone, V, et al.
(författare)
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An evaluation of an alternative dosing regimen with tadalafil, 3 times/week, for men with erectile dysfunction: SURE study in 14 European countries.
- 2005
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Ingår i: Eur Urol. - : Elsevier BV. ; 47:6, s. 846-854
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To examine the preference for 2 dosing regimens (on demand or 3 times/week) for tadalafil, a phosphodiesterase 5 inhibitor with a duration of effectiveness up to 36 hours in men with erectile dysfunction (ED). Design and methods: SURE is a 14 European country, multicenter, crossover, and open-label study. Men with ED (N = 4262) were randomized to tadalafil 20 mg treatment on demand (maximum one dose per day and before sexual activity) or 3 times/week for 5–6 weeks. After a 1-week washout period, patients were crossed over to the alternate regimen for 5–6 weeks. The patient's response to a treatment preference question (TPQ) was used to determine the preferred treatment regimen. Results: The mean age of the randomized patients was 55 years and 85.2% reported a history of ED for one year or greater. Overall, the responses of 3861 men to the TPQ assessment showed that 57.8% preferred the on-demand regimen and 42.2% preferred the 3 times/week dosing. Both regimens were efficacious and well tolerated. Conclusions: In this study, while 57.8% of men preferred the on-demand regimen of tadalafil 20 mg, a substantial number (42.2%) preferred the 3 times/week treatment. The two regimens provide additional treatment options by giving men with erectile dysfunction unique flexibility in dosing with tadalafil.
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| 11. |
- Moncado, I, et al.
(författare)
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Sexual intercourse attempt patterns with two dosing regimens of tadalafil in men with erectile dysfunction: Results from the sure study in 14 European countries.
- 2005
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Ingår i: J Sex Med. - : Oxford University Press (OUP). ; 2, s. 668-674
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To describe the pattern of sexual attempts by men with erectile dysfunction (ED) taking tadalafil 20 mg on demand or on an alternative dosing regimen, 3 times/week, and to assess changes in sexual behavior when the patients were exposed to the alternative regimen. Design and Methods. Scheduled use versus on-demand regimen evaluation (SURE) is a multicenter, crossover, open-label study conducted in 14 European countries. Men with ED (N = 4,262) were randomized to tadalafil 20 mg on-demand treatment (maximum one dose per day and before sexual activity) or 3 times/week for 5–6 weeks. After a 1-week washout period, patients were crossed over to the alternative regimen for 5–6 weeks. Results. Nearly half (47%) of the attempts on the on-demand regimen and 71% of the attempts on the 3 times/week treatment were performed by patients more than 4 hours post dosing. Sexual activity occurred throughout the week on both regimens, with the highest percentage of attempts made during the weekend (50% on on-demand and 48% on 3 times/week) and evening and morning hours. The efficacy of tadalafil was more than 70% mean-per-patient success rate (Sexual Encounter Profile question 3) regardless of the time interval post dosing. Conclusions. Patients on tadalafil changed their sexual behavior significantly when on an alternative dosing regimen (3 times/week) and had sexual attempts distributed over a wide period of time post dosing. A substantial number of sexual attempts were performed beyond the first 4 hours post dosing on both regimens (47% for on-demand and 71% for 3 times/week) and preferably in the evening and morning hours. Tadalafil was efficacious regardless of the time interval post dosing—i.e., up to 36 hours. The two treatment regimens, on-demand and 3 times/week, provide an additional option and unique flexibility in dosing for men with ED and their partners.
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| 12. |
- Stranne, Johan, 1970, et al.
(författare)
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One-third of the Swedish male population over 50 years of age suffers from lower urinary tract symptoms.
- 2009
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Ingår i: Scandinavian journal of urology and nephrology. - : Informa UK Limited. - 0036-5599 .- 1651-2065. ; 43:3, s. 199-205
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate the prevalence of and restrictions in various parts of daily life due to lower urinary tract symptoms (LUTS) in an unselected Swedish male population. MATERIAL AND METHODS: A random selection of 3345 men throughout Sweden, aged between 41 and 80, was contacted by telephone and evaluated according to International Prostate Symptom Score (IPSS). The responders were then sent two different questionnaires based on degree of LUTS, IPSS <8 or >7. RESULTS: 2106 men (66%) answered the questionnaire. Of these, 33.4% had an IPSS > 7 and the IPSS increased with age. Of the men with IPSS >7 only 41% had consulted health services for their symptoms and 23% had received treatment. Thirty-seven per cent claimed that their problems had a great negative effect on their quality of life and 77% that they had affected their relationship with their spouse negatively to a great extent. Forty per cent did not consult health services despite their symptoms. In men with an IPSS <8 as many as 33% believed that LUTS would limit them in at least some part of their daily life. CONCLUSIONS: LUTS is a common condition among Swedish men with a severe impact on quality of life and everyday life. Despite readily available medical assistance, two out of five men with LUTS still do not try to obtain a remedy. The data presented here identify a need for improved education regarding LUTS, to increase awareness of the condition and the treatment options that are available.
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| 13. |
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| 14. |
- Winnes, Marta, 1979, et al.
(författare)
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Molecular genetic analyses of the TMPRSS2-ERG and TMPRSS2-ETV1 gene fusions in 50 cases of prostate cancer.
- 2007
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Ingår i: Oncology Reports. ; 17, s. 1033-1036
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Tidskriftsartikel (refereegranskat)abstract
- Recently, gene fusions between the androgen responsive gene TMPRSS2 and members of the ETS-family of DNA-binding transcription factor genes were found in prostate cancer. Recurrent fusions were identified between the 5'-noncoding region of TMPRSS2 and ERG, or less frequently ETV1 or ETV4, resulting in overexpression of normal or truncated ETS-proteins. Herein, we have analyzed a series of 50 prostate cancer samples for expression of TPRSS2-ERG and TMPRSS2-ETV1 fusion transcripts. RT-PCR analysis revealed TMPRSS2-ERG fusion transcripts in 18 of the 50 tumors (36%). None of the tumors expressed a TMPRSS2-ETV1 fusion. Our findings show that the TMPRSS2-ERG fusion is common in prostate cancer and that the related TMPRSS2-ETV1 fusion is very rare. However, the frequency of ERG-fusions in the present study is somewhat lower than previously observed, indicating heterogeneity with regard to expression of ETS-gene fusions in subsets of prostate cancers. Moreover, clinical follow-up studies showed a clear tendency that fusion-positive tumors were associated with lower Gleason grade and better survival than fusion-negative tumors. Our findings suggest that ERG gene fusions might be of prognostic significance in prostate cancer.
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| 15. |
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| 16. |
- Armstrong, Andrew J, et al.
(författare)
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Assessment of the bone scan index in a randomized placebo-controlled trial of tasquinimod in men with metastatic castration-resistant prostate cancer (mCRPC).
- 2014
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Ingår i: Urologic oncology. - : Elsevier BV. - 1873-2496. ; 32:8, s. 1308-1316
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Tidskriftsartikel (refereegranskat)abstract
- Drug development and clinical decision making for patients with metastatic prostate cancer (PC) have been hindered by a lack of quantitative methods of assessing changes in bony disease burden that are associated with overall survival (OS). Bone scan index (BSI), a quantitative imaging biomarker of bone tumor burden, is prognostic in men with metastatic PC. We evaluated an automated method for BSI calculation for the association between BSI over time with clinical outcomes in a randomized double-blind trial of tasquinimod (TASQ) in men with metastatic castration-resistant PC (mCRPC).
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| 17. |
- Aus, Gunnar, 1958, et al.
(författare)
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Individualized screening interval for prostate cancer based on prostate-specific antigen level.
- 2005
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Ingår i: Arch Intern Med. ; 165:16, s. 1857-1861
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Tidskriftsartikel (refereegranskat)abstract
- Background The aim of the present study was to evaluate the future cumulative risk of prostate cancer in relation to levels of prostate-specific antigen (PSA) in blood and to determine whether this information could be used to individualize the PSA testing interval. Methods The study included 5855 of 9972 men (aged 50-66 years) who accepted an invitation to participate in a prospective, randomized study of early detection for prostate cancer. We used a protocol based on biennial PSA measurements starting from 1995 and 1996. Men with serum PSA levels of 3.0 ng/mL or more were offered prostate biopsies. Results Among the 5855 men, 539 cases of prostate cancer (9.2%) were detected after a median follow-up of 7.6 years (up to July 1, 2003). Cancer detection rates during the follow-up period in relation to PSA levels were as follows: 0 to 0.49 ng/mL, 0% (0/958); 0.50 to 0.99 ng/mL, 0.9% (17/1992); 1.00 to 1.49 ng/mL, 4.7% (54/1138); 1.50 to 1.99 ng/mL, 12.3% (70/571); 2.00 to 2.49 ng/mL, 21.4% (67/313); 2.50 to 2.99 ng/mL, 25.2% (56/222); 3.00 to 3.99 ng/mL, 33.3% (89/267); 4.00 to 6.99 ng/mL, 38.9% (103/265); 7.00 to 9.99 ng/mL, 50.0% (30/60); and for men with an initial PSA of 10.00 ng/mL or higher, 76.8% (53/69). Not a single case of prostate cancer was detected within 3 years in 2950 men (50.4% of the screened population) with an initial PSA level less than 1 ng/mL. Conclusions Retesting intervals should be individualized on the basis of the PSA level, and the large group of men with PSA levels of less than 1 ng/mL can safely be scheduled for a 3-year testing interval.
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| 18. |
- Aus, Gunnar, 1958, et al.
(författare)
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Prostate biopsy and anaesthesia: an overview.
- 2005
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Ingår i: Scand J urol Nephrol. - : Informa UK Limited. ; 39:2, s. 124-129
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Forskningsöversikt (refereegranskat)abstract
- Objective. To evaluate the efficacy of different methods for decreasing pain and discomfort in men undergoing transrectal ultrasound-guided prostate biopsies and to propose a clinical standard useful for pain relief. Material and methods. A MEDLINE search using the search terms "anaesthesia" and "prostate biopsy" was performed in November 2004. The search yielded 198 papers, 45 of which were found to relate to the subject and were in the English language. Results. Intravenously administered sedoanalgesia seems to be effective but is cumbersome to handle in everyday practice. In one study, i.v. tramadol has been shown to be effective, and the same goes for diclofenac 100 mg given as a suppository 1 h prior to the biopsy. Inhaled nitrous oxide (Entonox®) works well but is not widely available. A rectally administered gel containing local anaesthetic seems to have very limited efficacy. Periprostatic injection of a local anaesthetic was used in most studies, nearly all of which showed that it was effective in comparison with placebo or rectal gel. A minimum of 10 cm3 seems to be necessary for optimal effect. Conclusion. At the present time, perirectal injection of a local anaesthetic is the preferred method of pain relief in conjunction with transrectal prostate biopsies.
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| 19. |
- Axcrona, Karol, et al.
(författare)
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Androgen deprivation therapy for volume reduction, lower urinary tract symptom relief and quality of life improvement in patients with prostate cancer: degarelix vs goserelin plus bicalutamide.
- 2012
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Ingår i: BJU international. - 1464-410X. ; 110:11, s. 1721-1728
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Tidskriftsartikel (refereegranskat)abstract
- Study Type - Therapy (RCT) Level of Evidence1b What's known on the subject? and What does the study add? Androgen deprivation therapy (ADT) is commonly used as a primary treatment for patients with prostate cancer (PCa) who are not eligible for radical treatment options. ADT is also used in patients with PCa as neo-adjuvant hormone therapy to reduce prostate volume and down-stage the disease before radiotherapy with curative intent. The present study showed that ADT with the gonadotropin hormone-releasing hormone (GhRH) antagonist degarelix is non-inferior to combined treatment with the LHRH agonist goserelin and bicalutamide in terms of reducing prostate volume during the treatment period of 3 months. Degarelix treatment evokes, however, significantly better relief of lower urinary tract symptoms in patients having moderate and severe voiding problems. OBJECTIVE: • To assess the efficacy of monthly degarelix treatment for reduction of total prostate volume (TPV), relief of lower urinary tract symptoms (LUTS) and improvement of quality of life (QoL) in patients with prostate cancer (PCa) using monthly goserelin as active control. METHODS: • This was a randomized, parallel-arm, active-controlled, open-label, multicentre trial on 182 patients treated with either monthly degarelix (240/80mg) or goserelin (3.6mg) for 12 weeks. • For flare protection, goserelin-treated patients also received daily bicalutamide (50mg) during the initial 28 days. • Key trial variables monitored monthly were TPV (primary endpoint), serum testosterone, prostate-specific antigen (PSA), the International Prostate Symptom Score (IPSS) and the Benign Prostate Hyperplasia Impact Index. RESULTS: • In all, 175 patients completed the trial (96.1%). • At week 12, changes in TPV for degarelix and goserelin were similar (-37.2% vs -39.0%) and met the predefined non-inferiority criterion. • Decreases in IPSS were greater in degarelix than in goserelin-treated patients, differences being statistically significant in patients with baseline IPSS > 13 (-6.7 ± 1.8 vs -4.0 ± 1.0; P= 0.02). • The number of patients with an IPSS change of ≥3 over baseline was also significantly higher in patients treated with degarelix (61.0 vs 44.3%, P= 0.02). • Both treatments were safe and well tolerated. CONCLUSIONS: • Medical castration reduces TPV and could also improve LUTS in patients with PCa. • While the short-term efficacy of degarelix and goserelin + bicalutamide was the same in terms of TPV reduction, degarelix showed superiority in LUTS relief in symptomatic patients, which could highlight the different actions of these drugs on extrapituitary gonadotrophin-releasing hormone (GnRH) receptors in the bladder and/or the prostate.
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| 20. |
- Bentmar Holgersson, Magdalena, et al.
(författare)
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Lower prostate cancer risk in Swedish men with the androgen receptor E213 A-allele
- 2017
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Ingår i: Cancer Causes & Control. - : Springer Science and Business Media LLC. - 0957-5243 .- 1573-7225. ; 28:3, s. 227-233
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Tidskriftsartikel (refereegranskat)abstract
- In a previous population-based study on 3369 European men with self-reported prostate cancer (PCa), it was shown that androgen receptor (AR) haplotype designated H2 was associated with high levels of serum PSA (prostate-specific antigen) concentration, and, at the same time, with low risk for PCa. The aim of this study was to replicate this finding in other cohorts, with registry-based cancer diagnosis. Using data from two population-based cohorts; the Malmo Diet and Cancer Study (MDCS, n = 12,121) and the Swedish Osteoporotic fractures in men study (MrOS, n = 1,120), 628 men with PCa and 1,374 controls were identified and genotyped. PCa data were collected from the Swedish national cancer registry. PCa odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for carriers of the particular AR haplotype, tagged by the rs6624304 T-allele. The 15% of men who were carriers of the AR haplotype H2 had approximately one-third lower risk for PCa diagnosis compared to those with the most common H1 variant (OR 0.65; 95% CI 0.45-0.94; p = 0.021). The same trend, although not statistically significant (OR 0.75; 95% CI 0.47-1.24; p = 0.275), was observed in MrOS Sweden. When both cohorts were merged, an even more significant result was observed (OR 0.68; 95% CI 0.51-0.90; p = 0.008). Swedish men with the variant AR haplotype H2, tagged by rs6624304, have significantly lower risk of PCa compared to those with the more common variant.
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| 21. |
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| 22. |
- Bjartell, Anders, et al.
(författare)
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Prediction of clinical progression after radical prostatectomy in a nationwide population-based cohort
- 2016
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Ingår i: Scandinavian Journal of Urology. - : Medical Journals Sweden AB. - 2168-1805 .- 2168-1813. ; 50:4, s. 255-259
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of this study was to create a model for predicting progression-free survival after radical prostatectomy for localized prostate cancer. Material and methods: The risk of biochemical recurrence (BCR) was modelled in a cohort of 3452 men aged 70 years or younger who were primarily treated with radical prostatectomy after being diagnosed between 2003 and 2006 with localized prostate cancer [clinical stage T1c-T2, Gleason score 5-10, N0/NX, M0/MX, prostate-specific antigen (PSA)<20 ng/ml]. The cohort was split into two: one cohort for model development (n = 3452) and one for validation (n = 1762). BCR was defined as two increasing PSA values of at least 0.2 ng/ml, initiation of secondary therapy, distant metastases or death from prostate cancer. Multivariable Cox proportional hazard regression was applied, predictive performance was assessed using the bootstrap resampling technique to calculate the c index, and calibration of the model was evaluated by comparing predicted and observed Kaplan-Meier 1 year BCR. Results: The overall 5 year progression-free survival was 83% after a median follow-up time of 6.8 years in the development cohort and 7.3 years in the validation cohort. The final model included T stage, PSA level, primary and secondary Gleason grade, and number of positive and negative biopsies. The c index for discrimination between high and low risk of recurrence was 0.68. The probability of progression-free survival ranged from 22% to 97% over the range of risk scores in the study population. Conclusions: This model is based on nationwide population-based data and can be used with a fair predictive accuracy to guide decisions on clinical follow-up after prostatectomy. An online calculator for convenient clinical use of the model is available at www.npcr.se/nomogram
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| 23. |
- Bostwick, DG, et al.
(författare)
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Epidemiology and statistical methods in prediction of patient outcome.
- 2005
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Ingår i: Scand J Urol Nephrol Suppl. - : Informa UK Limited. ; 39:216, s. 94-110
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Tidskriftsartikel (refereegranskat)abstract
- Substantial gaps exist in the data of the assessment of risk and prognosis that limit our understanding of the complex mechanisms that contribute to the greatest cancer epidemic, prostate cancer, of our time. This report was prepared by an international multidisciplinary committee of the World Health Organization to address contemporary issues of epidemiology and statistical methods in prostate cancer, including a summary of current risk assessment methods and prognostic factors. Emphasis was placed on the relative merits of each of the statistical methods available. We concluded that: An international committee should be created to guide the assessment and validation of molecular biomarkers. The goal is to achieve more precise identification of those who would benefit from treatment. Prostate cancer is a predictable disease despite its biologic heterogeneity. However, the accuracy of predicting it must be improved. We expect that more precise statistical methods will supplant the current staging system. The simplicity and intuitive ease of using the current staging system must be balanced against the serious compromise in accuracy for the individual patient. The most useful new statistical approaches will integrate molecular biomarkers with existing prognostic factors to predict conditional life expectancy (i.e. the expected remaining years of a patient's life) and take into account all-cause mortality.
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| 24. |
- Bratt, Ola, et al.
(författare)
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Open-label, clinical phase I studies of tasquinimod in patients with castration-resistant prostate cancer.
- 2009
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Ingår i: British journal of cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 101:8, s. 1233-40
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Tasquinimod is a quinoline-3-carboxamide derivative with anti-angiogenic activity. Two open-label phase I clinical trials in patients were conducted to evaluate the safety and tolerability of tasquinimod, with additional pharmacokinetic and efficacy assessments. METHODS: Patients with castration-resistant prostate cancer with no previous chemotherapy were enrolled in this study. The patients received tasquinimod up to 1 year either at fixed doses of 0.5 or 1.0 mg per day or at an initial dose of 0.25 mg per day that escalated to 1.0 mg per day. RESULTS: A total of 32 patients were enrolled; 21 patients were maintained for >or=4 months. The maximum tolerated dose was determined to be 0.5 mg per day; but when using stepwise intra-patient dose escalation, a dose of 1.0 mg per day was well tolerated. The dose-limiting toxicity was sinus tachycardia and asymptomatic elevation in amylase. Common treatment-emergent adverse events included transient laboratory abnormalities, anaemia, nausea, fatigue, myalgia and pain. A serum prostate-specific antigen (PSA) decline of >or=50% was noted in two patients. The median time to PSA progression (>25%) was 19 weeks. Only 3 out of 15 patients (median time on study: 34 weeks) developed new bone lesions. CONCLUSION: Long-term continuous oral administration of tasquinimod seems to be safe, and the overall efficacy results indicate that tasquinimod might delay disease progression.
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| 25. |
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| 26. |
- Bratt, Ola, et al.
(författare)
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Satsa på MRT för diagnostik av prostatacancer.
- 2015
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Ingår i: Läkartidningen. - : Läkartidningen Förlag. - 1652-7518 .- 0023-7205. ; 112:Apr 20, s. DFZ3-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 27. |
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| 28. |
- Bäck, Tom, 1964, et al.
(författare)
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Targeted alpha therapy with astatine-211-labeled anti-PSCA A11 minibody shows antitumor efficacy in prostate cancer xenografts and bone microtumors
- 2020
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Ingår i: Ejnmmi Research. - : Springer Science and Business Media LLC. - 2191-219X. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Targeted alpha therapy (TAT) is a promising treatment for micrometastatic and minimal residual cancer. We evaluated systemic alpha-radioimmunotherapy (alpha-RIT) of metastatic castration-resistant prostate cancer (mCRPC) using the alpha-particle emitter At-211-labeled to the anti-PSCA A11 minibody. A11 is specific for prostate stem cell antigen (PSCA), a cell surface glycoprotein which is overexpressed in more than 90% of both localized prostate cancer and bone metastases. Methods PC3-PSCA cells were implanted subcutaneously (s.c.) and intratibially (i.t) in nude mice. Efficacy of alpha-RIT (two fractions-14-day interval) was studied on s.c. macrotumors (0, 1.5 and 1.9 MBq) and on i.t. microtumors (100-200 mu m; 0, 0.8 or 1.5 MBq) by tumor-volume measurements. The injected activities for therapies were estimated from separate biodistribution and myelotoxicity studies. Results Tumor targeting of At-211-A11 was efficient and the effect on s.c. macrotumors was strong and dose-dependent. At 6 weeks, the mean tumor volumes for the treated groups, compared with controls, were reduced by approximately 85%. The separate myelotoxicity study following one single fraction showed reduced white blood cells (WBC) for all treated groups on day 6 after treatment. For the 0.8 and 1.5 MBq, the WBC reductions were transient and followed by recovery at day 13. For 2.4 MBq, a clear toxicity was observed and the mice were sacrificed on day 7. In the long-term follow-up of the 0.8 and 1.5 MBq-groups, blood counts on day 252 were normal and no signs of radiotoxicity observed. Efficacy on i.t. microtumors was evaluated in two experiments. In experiment 1, the tumor-free fraction (TFF) was 95% for both treated groups and significantly different (p < 0.05) from the controls at a TFF of 66%). In experiment 2, the difference in TFF was smaller, 32% for the treated group versus 20% for the controls. However, the difference in microtumor volume in experiment 2 was highly significant, 0.010 +/- 0.003 mm(3) versus 3.79 +/- 1.24 mm(3) (treated versus controls, respectively), i.e., a 99.7% reduction (p < 0.001). The different outcome in experiment 1 and 2 is most likely due to differences in microtumor sizes at therapy, or higher tumor-take in experiment 2 (where more cells were implanted). Conclusion Evaluating fractionated alpha-RIT with At-211-labeled anti-PSCA A11 minibody, we found clear growth inhibition on both macrotumors and intratibial microtumors. For mice treated with multiple fractions, we also observed radiotoxicity manifested by progressive loss in body weight at 30 to 90 days after treatment. Our findings are conceptually promising for a systemic TAT of mCRPC and warrant further investigations of At-211-labeled PSCA-directed vectors. Such studies should include methods to improve the therapeutic window, e.g., by implementing a pretargeted regimen of alpha-RIT or by altering the size of the targeting vector.
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| 29. |
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| 30. |
- Célind, Jimmy, et al.
(författare)
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Timing of the pubertal growth spurt and prostate cancer
- 2021
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Ingår i: Cancers. - : MDPI. - 2072-6694. ; 13:24
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies of pubertal timing and the risk of prostate cancer have used self-reported markers of pubertal development, recalled in mid-life, and the results have been inconclusive. Our aim was to evaluate the age at the pubertal growth spurt, an objective marker of pubertal timing, and the risk of prostate cancer and high-risk prostate cancer. This population-based cohort study included 31,971 men with sufficient height measurements to calculate age at peak height velocity (PHV). Outcomes were accessed through national registers. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated by Cox regressions with follow up starting at 20 years of age. In total, 1759 cases of prostate cancer including 449 high-risk were diagnosed during follow up. Mean follow up was 42 years (standard deviation 10.0). Compared to quintiles 2–4 (Q2–4), men in the highest age at PHV quintile (Q5) had lower risk of prostate cancer (HR 0.83, 95% CI 0.73–0.94), and of high-risk prostate cancer (0.73; 0.56–0.94). In an exploratory analysis with follow up starting at age at PHV, late pubertal timing was no longer associated with reduced risk of prostate cancer. Later pubertal timing was associated with reduced risk of prostate cancer and especially high-risk prostate cancer. We propose that the risk of prostate cancer might be influenced by the number of years with exposure to adult levels of sex steroids.
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| 31. |
- Crawford, E. David, et al.
(författare)
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FSH suppression and tumour control in patients with prostate cancer during androgen deprivation with a GnRH agonist or antagonist
- 2018
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Ingår i: SCANDINAVIAN JOURNAL OF UROLOGY. - : Medical Journals Sweden AB. - 2168-1805 .- 2168-1813. ; 52:5-6, s. 349-357
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Tidskriftsartikel (refereegranskat)abstract
- Background: Gonadotropin releasing hormone (GnRH) antagonists suppress follicle-stimulating hormone (FSH) to lower levels than GnRH agonists. This may partially explain the differences between these agents on prostate cancer outcomes. In this post-hoc analysis, FSH and prostate specific antigen (PSA) responses and the impact of cross-over from leuprolide to degarelix were evaluated from a 1-year comparative study (CS21) and its extension study (CS21A). Materials and methods: Overall, 610 patients were enrolled in CS21, wherein PSA and FSH levels were evaluated monthly. CS21A evaluated 386 patients, including those previously treated with degarelix (n = 251) who continued to receive degarelix, and those previously treated with leuprolide (n = 135) who crossed-over to receive degarelix. PSA and FSH levels were evaluated in CS21A for 3 months after cross-over. The associations between measurements were assessed using Spearman's correlation coefficient. The impact of class variables on FSH suppression were evaluated using Analysis of Variance. Results: Rapid PSA and FSH suppression was observed and maintained in the degarelix arm (CS21 and CS21A), while patients on leuprolide experienced rising PSA during CS21. Patients crossed-over from leuprolide to degarelix achieved a suppression of FSH and a significant PSA decrease. PSA and FSH levels were significantly (p < .05) correlated at months 1, 3, 6, 12 and 13 in the degarelix arm. Conclusions: Significant FSH suppression with GnRH antagonists may explain its advantage over GnRH agonists in terms of better prostate cancer control. The effect of profound FSH suppression is analogous to the need for profound testosterone suppression for tumor control.
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| 32. |
- Damber, Jan-Erik, 1949, et al.
(författare)
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Andrologi.
- 2012
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Ingår i: Urologi 2ed. eds: Damber JE, Peeker R.. - Lund, Sverige : Lund: Studentlitteratur. - 9789144075921 ; , s. 437-466
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 33. |
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| 34. |
- Damber, Jan-Erik, 1949
(författare)
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Benigna sjukdomar i skrotum.
- 2012
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Ingår i: Urologi 2ed. eds: Damber JE, Peeker R.. - Lund, Sverige : Lund: Studentlitteratur. - 9789144075921 ; , s. 341-349
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 35. |
- Damber, Jan-Erik, 1949
(författare)
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Decreasing mortality rates for prostate cancer: possible role of hormonal therapy?
- 2004
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Ingår i: BJU international. - 1464-4096. ; 93:6, s. 695-701
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Tidskriftsartikel (refereegranskat)abstract
- Within the last decade prostate cancer mortality rates have started to decrease in some countries. Although it is tempting to assume that these trends are a result of earlier diagnosis and aggressive therapeutic intervention, as a consequence of prostate-specific antigen screening, definitive results from randomized trials of screening will not be available for several years. Moreover, there is mounting evidence that the effects of screening cannot be entirely responsible for this reduction in mortality rates. This review explores the possibility that other factors, particularly the increased uptake of early hormonal therapy, are contributing to the observed changes in mortality.
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| 36. |
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| 37. |
- Damber, Jan-Erik, 1949
(författare)
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Endocrine therapy for prostate cancer.
- 2005
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 44:6, s. 605-609
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Forskningsöversikt (refereegranskat)abstract
- Endocrine therapy of prostate cancer has mostly been reserved to patients with advanced stages of the disease. The principle for endocrine treatment of prostate cancer is elimination of stimulatory effects of testicular androgens on the prostate tumour cells. This can be achieved by surgical removal of the testes, by inhibition of pituitary gonadotrohin secretion by GnRH-angonsists or antagonists, by oestrogens or by non-steroidal antiandrogens. Since non-steroidal antiandrogens have fewer side-effects than castrational therapies, there is an increased interest for using endocrine treatment as adjuvant therapy after localized treatment. At least in certain stages of the disease, early hormonal treatment may have survival benefits. The timing of endocrine therapy, the usage of combined androgen blockade and intermittent endocrine therapy will be discussed in this overview.
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| 38. |
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| 39. |
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| 40. |
- Damber, Jan-Erik, 1949
(författare)
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Maligna tumörer i testiklar och skrotum.
- 2012
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Ingår i: Urologi 2ed. eds: Damber JE, Peeker R.. - Lund, Sverige : Lund: Studentlitteratur. - 9789144075921 ; , s. 351-362
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 41. |
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| 42. |
- Damber, Jan-Erik, 1949, et al.
(författare)
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Prostatacancer.
- 2012
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Ingår i: Urologi 2ed. eds: Damber JE, Peeker R.. - Lund, Sverige : Lund: Studentlitteratur. - 9789144075921 ; , s. 307-339
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 43. |
- Damber, Jan-Erik, 1949, et al.
(författare)
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Prostate cancer
- 2008
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Ingår i: Lancet. ; 371:9625, s. 1710-21
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Tidskriftsartikel (refereegranskat)abstract
- In developed countries, prostate cancer is the second most frequently diagnosed cancer, and the third most common cause of death from cancer in men. Apart from age and ethnic origin, a positive family history is probably the strongest known risk factor. Clinically, prostate cancer is diagnosed as local or advanced, and treatments range from surveillance to radical local treatment or androgen-deprivation treatment. Androgen deprivation reduces symptoms in about 70–80% of patients with advanced prostate cancer, but most tumours relapse within 2 years to an incurable androgen-independent state. The recorded incidence of prostate cancer has substantially increased in the past two decades, probably because of the introduction of screening with prostate-specific antigen, the use of improved biopsy techniques for diagnosis, and increased public awareness. Trends in mortality from the disease are less clearcut. Mortality changes are not of the same magnitude as the changes in incidence, and in some countries mortality has been stable or even decreased. The disparity between reported incidence and mortality rates leads to the probable conclusion that only a small proportion of diagnosed low-risk prostate cancers will progress to life-threatening disease during the lifetime of the patient.
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| 44. |
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| 45. |
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| 46. |
- Damber, Jan-Erik, 1949
(författare)
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Sten och tumörsjukdomar i urinvägarna
- 2008
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Ingår i: Läkemedelsboken, Apoteket AB 2007-2008. ; , s. 347-353
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 47. |
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| 48. |
- Damber, Jan-Erik, 1949, et al.
(författare)
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Surgical treatment of localized prostate cancer.
- 2005
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 44:6, s. 599-604
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Forskningsöversikt (refereegranskat)abstract
- Radical retropubic prostatectomy (RRP) is the reference method for treatment of localised, organ confined prostate cancer. Since the introduction of nerve-sparing procedure for RRP in the 1980's, the operation has become widespread and is today one of the most common surgical procedures in Urology. In this overview the indications, operative procedure and side effects of RRP are briefly discussed.
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| 49. |
- Damber, Jan-Erik, 1949-
(författare)
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Testicular blood flow : methodological and functional studies in the rat
- 1978
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Different methods of measuring testicular blood flow in the rat were compared in an attempt to find an accurate method for measuring physiological testicular blood flow. It was found that both the Xenon- 133 clearance technique and the radioactive microsphere technique probably reflect true physiological blood flow in the testis.The microsphere method was used to study some functional aspects of testicular blood flow. There was a significant positive correlation between the testicular blood flow and the outflow of testosterone in the spermatic vein, indicating that testicular hormone secretion may be affected indirectly via a primary effect on testicular blood flow. Intra-arterial infusion of LH caused a significant decrease in the vascular resistance of the testis. However, the effect was small in comparison with the simultaneous effect of LH on plasma testosterone concentration, indicating that blood flow changes are not critically involved in the acute effect of LH on testicular endocrine function. Infusion of epinephrine or norepinephrine did not induce any absolute changes in testicular blood flow, but norepinephrine caused an increase in testicular vascular resistance. Both catecholamines caused significant depressions in plasma testosterone concentration. It was concluded that the catecholamine induced reductions in testosterone concentration were not due to a vascular effect on the testis.Testicular blood flow and Leydig cell function in the cryptorchid and heated testis were also studied. There was a significant increase in relative blood flow in the cryptorchid testis, probably due to an highly altered morphology consisting of a relative increase in interstitial tissue containing blood vessels. Furthermore, it was found that the testosterone levels, in spermatic vein blood from the cryptorchid testis, were highly reduced in comparison to the corresponding values for the scrotal testis and the outflow of testosterone from the cryptorchid testis was estimated to be only 13% of that from the scrotal one. This result suggested that the Leydig cell function was greatly impaired in the cryptorchid testis. The vasculature of the testis is relatively insensitive to local heating since no effects on vascular resistance were observed when warming the testis to abdominal temperature. On the other hand, there was a significant increase in blood flow in the testis at 41 and 43° C, which are temperatures known to induce cessation of spermatogenesis in the rat. The acute response of the testis to LH stimulation was reduced when warming the scrotum to 41 and 43° C. This strongly indicates an impaired Leydig cell function at these temperatures. Since blood flow was increased at these temperatures it was concluded that the reduced Leydig cell responsiveness to LH was unrelated to testicular perfusion.
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| 50. |
- Damber, Jan-Erik, 1949, et al.
(författare)
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The anti-tumour effect of low-dose continuous chemotherapy may partly be mediated by thrombospondin
- 2006
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Ingår i: Cancer Chemother Pharmacol. - : Springer Science and Business Media LLC. - 0344-5704 .- 1432-0843. ; 58:3, s. 354-360
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Tidskriftsartikel (refereegranskat)abstract
- Background: Tumour growth is dependent on angiogenesis. Antiangiogenic chemotherapy, i.e. continuous or metronomic low-dose chemotherapy, is a method for administrating cytostatics at a low and well-tolerated concentration without prolonged breaks. The target is the genetically stable endothelial cells playing a pivotal role in angiogenesis within the tumour. Different mediators could mediate the antiangiogenic effect of metronomic chemotherapy. One of these mediators could be thrombospondin (TSP). TSP is a potent inhibitor of angiogenesis and might therefore be important in controlling tumour growth. This study was designed to evaluate the effects of low-dose continuous or moderate-dose bolus chemotherapy on tumour growth and on tumour expression of TSP. Materials and methods: Rats bearing a malignant prostate tumour (Dunning AT-1) not expressing TSP were treated systemically with cyclophosphamide, doxorubicin or paclitaxel and the combination of cyclophosphamide and doxorubicin. Tumour growth and body weight were measured during the treatment. CD36, one of TSP’s main receptors, was also analysed. The expression pattern of TSP-1, TSP-2 and CD36 was investigated using immunohistochemistry and Western blot analyses. Q-PCR was used to analyse TSP-1 mRNA expression. Results: Low-dose cyclophosphamide and paclitaxel re-induced the expression of TSP in the tumours. However, following a bolus dose of doxorubicin, tumours showed no expression of TSP. Both cyclophosphamide and doxorubicin treatments decreased the tumour weight by more than 60% compared with vehicle controls. When cyclophosphamide and doxorubicin were combined the tumour weight was reduced by 47%, while paclitaxel reduced the tumour weight by 18% compared to the vehicle controls. Conclusions: Systemic low-dose continuous treatment of a rat prostate cancer model with cyclophosphamide and paclitaxel induced the expression of TSP in tumour tissue and inhibited tumour growth. These findings support the hypothesis that the anti-tumour effect of low-dose metronomic chemotherapy, at least with certain chemotherapeutics, is partly mediated by induction of endogenous antiangiogenic factors.
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