| 1. |
- 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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| 2. |
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| 3. |
- 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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| 4. |
- Jellvert, Åsa, et al.
(författare)
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Castration is a prerequisite for the inhibitory effect of metronomic chemotherapy on the growth of experimental castration-resistant prostate cancer.
- 2018
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Ingår i: Acta oncologica (Stockholm, Sweden). - 1651-226X. ; 57:7, s. 895-901
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Tidskriftsartikel (refereegranskat)abstract
- Low-dose metronomic chemotherapy (LDMC) is an alternative for treatment of patients with late-stage prostate cancer (PC) not susceptible to regular chemotherapy due to its severe side effects. The exact working mechanisms of LDMC have not been established, although anti-angiogenic effects have been identified. In PC, several studies show clinical effects from LDMC but the mode of action and the role of androgen signaling for its effect are not known. In this study, we used a xenograft model to evaluate the effect of LDMC on PC growth in relation to androgen deprivation.Subcutaneous human castration-resistant PC xenografts were treated with LDMC using cyclophosphamide (CPA). Treatment effect was compared to treatment with maximum tolerated dose (MTD) and also between intact and castrated mice. Microvessel density (MVD), and factors important for angiogenesis were analyzed with immunohistochemistry and real-time-PCR.Tumors treated with LDMC were 50% smaller than untreated controls. Tumors in non-castrated mice were not affected by LDMC, but in an androgen receptor (AR) negative tumor model, tumor inhibiting effect were seen in both intact and castrated animals, indicating mechanism via AR. MTD resulted in similar growth inhibition as LDMC in castrated mice, but resulted in severe weight loss. Despite that LDMC induced TSP1 mRNA expression, and the hypoxic area in the tumors was slightly increased, no decrease in MVD was detected.This study shows that a low-dose metronomic scheduling of CPA was as efficient as MTD treatment, and resulted in fewer side effects. It also demonstrates that a functional androgen signaling axis inhibits this effect despite the castration-resistance of the tumor cells. The anti-angiogenic nature of the effect of LDMC could not be confirmed and further studies to elucidate the working mechanism for treatment response are needed.
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| 5. |
- Reza Felix, Mariana, et al.
(författare)
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Bone Scan Index as an Imaging Biomarker in Metastatic Castration-resistant Prostate Cancer : A Multicentre Study Based on Patients Treated with Abiraterone Acetate (Zytiga) in Clinical Practice
- 2016
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Ingår i: European Urology Focus. - : Elsevier BV. - 2405-4569. ; 2:5, s. 540-546
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Tidskriftsartikel (refereegranskat)abstract
- Background Abiraterone acetate (AA) prolongs survival in metastatic castration-resistant prostate cancer (mCRPC) patients. To measure treatment response accurately in bone, quantitative methods are needed. The Bone Scan Index (BSI), a prognostic imaging biomarker, reflects the tumour burden in bone as a percentage of the total skeletal mass calculated from bone scintigraphy. Objective To evaluate the value of BSI as a biomarker for outcome evaluation in mCRPC patients on treatment with AA according to clinical routine. Design, setting, and participants We retrospectively studied 104 mCRPC patients who received AA following disease progression after chemotherapy. All patients underwent whole-body bone scintigraphy before and during AA treatment. Baseline and follow-up BSI data were obtained using EXINI BoneBSI software (EXINI Diagnostics AB, Lund, Sweden). Outcome measurements and statistical analysis Associations between change in BSI, clinical parameters at follow-up, and overall survival (OS) were evaluated using the Cox proportional hazards regression models and Kaplan-Meier estimates. Discrimination between variables was assessed using the concordance index (C-index). Results and limitations Patients with an increase in BSI at follow-up of at most 0.30 (n = 54) had a significantly longer median survival time than those with an increase of BSI >0.30 (n = 50) (median: 16 vs 10 mo; p = 0.001). BSI change was also associated with OS in a multivariate Cox analysis including commonly used clinical parameters for prognosis (C-index = 0.7; hazard ratio: 1.1; p = 0.03). The retrospective design was a limitation. Conclusions Change in BSI was significantly associated with OS in mCRPC patients undergoing AA treatment following disease progression in a postchemotherapy setting. BSI may be a useful imaging biomarker for outcome evaluation in this group of patients, and it could be a valuable complementary tool in monitoring patients with mCRPC on second-line therapies. Patient summary Bone Scan Index (BSI) change is related to survival time in metastatic castration-resistant prostate cancer (mCRPC) patients on abiraterone acetate. BSI may be a valuable complementary decision-making tool supporting physicians monitoring patients with mCRPC on second-line therapies.
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| 6. |
- Stattin, Pär, et al.
(författare)
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Dashboard report on performance on select quality indicators to cancer care providers
- 2016
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Ingår i: Scandinavian journal of urology. - : Informa UK Limited. - 2168-1805 .- 2168-1813. ; 50:1, s. 21-28
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Cancer quality registers are attracting increasing attention as important, but still underutilized sources of clinical data. To optimize the use of registers in quality assurance and improvement, data have to be rapidly collected, collated and presented as actionable, at-a-glance information to the reporting departments. This article presents a dashboard performance report on select quality indicators to cancer care providers. Materials and methods: Ten quality indicators registered on an individual patient level in the National Prostate Cancer Register of Sweden and recommended by the National Prostate Cancer Guidelines were selected. Data reported to the National Prostate Cancer Register are uploaded within 24 h to the Information Network for Cancer Care platform. Launched in 2014, What''s Going On, Prostate Cancer provides rapid, at-a-glance performance feedback to care providers. Results: The indicators include time to report to the National Prostate Cancer Register, waiting times, designated clinical nurse specialist, multidisciplinary conference, adherence to guidelines for diagnostic work-up and treatment, and documentation and outcome of treatment. For each indicator, three performance levels were defined. Conclusion: What's Going On, a dashboard performance report on 10 selected quality indicators to cancer care providers, provides an example of how data in cancer quality registers can be transformed into condensed, at-a-glance information to be used as actionable metrics for quality assurance and improvement.
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| 7. |
- Westerberg, Marcus, et al.
(författare)
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Temporal changes in survival in men with de novo metastatic prostate cancer : nationwide population-based study
- 2020
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 59:1, s. 106-111
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Tidskriftsartikel (refereegranskat)abstract
- Background: There have been large changes in the pattern of detection, work-up and treatment of men with prostate cancer during the last two decades. Therefore, we aimed to investigate temporal changes in survival in men with metastatic prostate cancer.Methods: Population-based cohort study in Prostate Cancer data Base Sweden of 13,709 men with de novo metastatic prostate cancer diagnosed between 1998 and 2015. Overall survival in four calendar periods were compared by the use of Kaplan-Meier analyses and Cox regression models including age at diagnosis, T stage and serum levels of prostate-specific antigen (PSA).Results: Between 1998-2001 and 2010-2015, median survival increased with 6 months for all men. The largest increase in survival was 14 months in men age 60-69 at diagnosis and in multivariable analysis risk of death decreased for men diagnosed in 2010-2015 compared to 1998-2001, hazard ratio (HR) 0.77 (95% CI: 0.68-0.86). The median PSA at date of diagnosis decreased with 46% from 181 ng/mL in 1998 to 98 ng/mL in 2015.Conclusions: There was an increase in survival among men with de novo metastatic prostate cancer in Sweden between 1998 and 2015. This increase was due to a decreased cancer extent indicated by lower PSA levels with ensuing longer lead times and speculatively also due to an increased use of chemotherapy in the latest time period. Given the increasing use of systemic treatment for advanced prostate cancer, our results are likely heralding larger increases in survival in men with metastatic prostate cancer in the near future.
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| 8. |
- Westerberg, M., et al.
(författare)
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Temporal changes in survival in men with de novo metastatic prostate cancer: nationwide population-based study
- 2020
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 59:1, s. 106-111
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Tidskriftsartikel (refereegranskat)abstract
- Background: There have been large changes in the pattern of detection, work-up and treatment of men with prostate cancer during the last two decades. Therefore, we aimed to investigate temporal changes in survival in men with metastatic prostate cancer. Methods: Population-based cohort study in Prostate Cancer data Base Sweden of 13,709 men with de novo metastatic prostate cancer diagnosed between 1998 and 2015. Overall survival in four calendar periods were compared by the use of Kaplan-Meier analyses and Cox regression models including age at diagnosis, T stage and serum levels of prostate-specific antigen (PSA). Results: Between 1998-2001 and 2010-2015, median survival increased with 6 months for all men. The largest increase in survival was 14 months in men age 60-69 at diagnosis and in multivariable analysis risk of death decreased for men diagnosed in 2010-2015 compared to 1998-2001, hazard ratio (HR) 0.77 (95% CI: 0.68-0.86). The median PSA at date of diagnosis decreased with 46% from 181 ng/mL in 1998 to 98 ng/mL in 2015. Conclusions: There was an increase in survival among men with de novo metastatic prostate cancer in Sweden between 1998 and 2015. This increase was due to a decreased cancer extent indicated by lower PSA levels with ensuing longer lead times and speculatively also due to an increased use of chemotherapy in the latest time period. Given the increasing use of systemic treatment for advanced prostate cancer, our results are likely heralding larger increases in survival in men with metastatic prostate cancer in the near future.
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