| 1. |
- Acosta, Stefan, et al.
(author)
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Long-term testosterone stimulation induces hyperplasia in the guinea-pig prostate.
- 2004
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In: Prostate Cancer and Prostatic Diseases. - : Springer Science and Business Media LLC. - 1476-5608 .- 1365-7852. ; 7:3, s. 227-231
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Journal article (peer-reviewed)abstract
- The relation between supraphysiologic circulating testosterone levels and prostatic diseases is unclear and difficult to study in men. Animal models may be advantageous. Based on a pilot study, testosterone enantate 50 mg (n=12) or 25 mg (n=12) was administered to guinea-pigs intramuscularly every 3 weeks, for either 7 or 14 months. The histopathology of the prostate was described. Epithelial hyperplasia was found in 14/21 animals receiving testosterone and in 7/12 very old animals, but no such changes were found in the sham or castrated animals. Testosterone stimulation seems to induce epithelial hyperplasia, but not cancer, in the guinea-pig prostate.
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| 2. |
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| 3. |
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| 4. |
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| 5. |
- Andersson, Patiyan, 1978-, et al.
(author)
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Association studies on INS and IRS1polymorphisms: IRS1 G972R is associated with increased prostate cancer risk
- 2008
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In: Prostate Cancer and Prostatic Diseases. - 1365-7852 .- 1476-5608.
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Journal article (peer-reviewed)abstract
- We study the G972R polymorphism in the Insulin receptor substrate 1 gene (IRS1) and the +1127 PstI polymorphism of the Insulin gene (INS), in 120 and 151, respectively, incidentally discovered, histologically verified prostate cancers, and in 185 healthy control subjects. The number of IRS1 R allele was found to be significantly associated with increased risk of prostate cancer. Analysis of the INS +1127 PstI polymorphism shows no significant differences between cases and controls. We conclude that subjects carrying one or two R-alleles at the IRS1 G972R polymorphic site are at an elevated risk of developing prostate cancer.
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| 6. |
- Beckmann, Kerri, et al.
(author)
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Spironolactone use is associated with lower prostate cancer risk : a population-wide case-control study
- 2020
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In: Prostate Cancer and Prostatic Diseases. - : NATURE PUBLISHING GROUP. - 1365-7852 .- 1476-5608. ; 23:3, s. 527-533
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Journal article (peer-reviewed)abstract
- Background Spironolactone, a cheap effective diuretic used to manage hypertension and heart failure, also has anti-androgenic effects through its non-selective binding to steroid receptors, and hence may affect prostate cancer (PCa) risk. This study investigated the association between spironolactone use and PCa risk. For comparison, we also examined associations with thiazide diuretics which do not have anti-androgenic properties. Methods A matched case-control study was undertaken using population-wide data from the Prostate Cancer Data Base Sweden (PCBaSe). All PCa cases diagnosed from 2014 to 2016 were matched by birth year and county with PCa-free controls selected from the general population (1:5). Multivariable conditional logistic regression was used to examine associations between spironolactone use (dose and duration) and PCa risk, and similarly for thiazides. Results Three percent of the 31,591 cases and 4% of the 156,802 controls had been prescribed spironolactone. Multivariable analyses indicated reduced risk of PCa among those ever exposed to spironolactone (odds ratio [OR] 0.83; 95% confidence interval [CI]: 0.76-0.89), with a stronger association for current users (OR: 0.77, 95% CI: 0.69-0.86) than past users (OR: 0.88; 95% CI: 0.79-0.97) and decreasing risk with increasing dose (p-trend < 0.001). No association was observed for thiazide exposure and PCa risk. Biases due to differences in prescribing patterns or frequency of PSA testing may have influenced these findings. Conclusion PCa risk was reduced among men exposed to the diuretic spironolactone. Further investigation of spironolactone's potential chemopreventive effects is warranted.
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| 7. |
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| 8. |
- Bjartell, A., et al.
(author)
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Time-resolved fluorescence imaging (TRFI) for direct immunofluorescence of PSA and alpha-1-antichymotrypsin in prostatic tissue sections
- 1999
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In: Prostate Cancer and Prostatic Diseases. - : Springer Science and Business Media LLC. - 1365-7852 .- 1476-5608. ; 2:3, s. 140-147
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Journal article (peer-reviewed)abstract
- We have developed a direct immunofluorescence technique utilising chelates of the lanthanide ions europium and terbium conjugated to monoclonal IgGs (Mabs) against prostate-specific antigen (PSA) and alpha-1- antichymotrypsin (ACT) for the detection and quantification on the same tissue section. Strong signals without disturbance from tissue autofluorescence were demonstrated in paraffin sections of ten benign and six malignant prostate tissue specimens. The signal intensity increased linearly with the amount of labelled Mab until epitope saturation began. The highest concentrations of bound IgG in tissue sections were 27.3 fmol/pixel for ACT and 7.2 for PSA. Time-resolved fluorescence imaging (TRFI) offers an attractive method for histochemical studies based on specific and quantitative detection of fluorescent lanthanide chelates.
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| 9. |
- Chattopadhyay, Subhayan, et al.
(author)
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Impact of family history of cancer on risk and mortality of second cancers in patients with prostate cancer
- 2019
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In: Prostate Cancer and Prostatic Diseases. - : Springer Science and Business Media LLC. - 1365-7852 .- 1476-5608. ; 22:1, s. 143-149
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Journal article (peer-reviewed)abstract
- Background: Survival rates are increasing in patients with prostate cancer, and second primary cancers (SPCs) are becoming more common in these patients. However, the etiology and clinical consequences of SPCs are not well-known. We define the impact of family history on SPC and causes of mortality in these patients. Patients and methods: A nation-wide cohort study based on the Swedish Family-Cancer Database covering 4.4 million men and 80,449 prostate cancers diagnosed between 1990 and 2015. Relative risks (RRs) and cumulative incidence for SPCs and for familial SPC were calculated for prostate cancer patients. Results: SPC was diagnosed in 6,396 men and more than a third of these patients had a first-degree family history of any cancer; the familial risk was 1.37 (95% CI: 1.27–1.40), compared to 1.10 (1.08–1.16), without a family history. Cumulative incidence by the age of 83 years reached 21% for prostate cancer alone, 28% in those with SPC, and 35% in patients with SPC and family history. Family history was associated with the risk of seven specific SPCs, including colorectal, lung, kidney, bladder and skin (both melanoma and squamous cell) cancers, and leukemia. Colorectal and lung cancers were common SPCs, and family history doubled the risk of these SPCs. In patients with SPC, half of all causes of death were due to SPC and only 12.77% were due to prostate cancer. Most deaths in SPC were caused by lung and colorectal cancers. Conclusions: SPCs were an important cause of death in patients with prostate cancer and family history was an important risk factor for SPCs. Prevention of SPC should be essential when prostate cancer survival rates are being improved and this could start by conducting a thorough assessment of family history at the time of prostate cancer diagnosis.
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| 10. |
- Chesnut, G. T., et al.
(author)
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Estimating patient health in prostate cancer treatment counseling
- 2023
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In: Prostate Cancer and Prostatic Diseases. - : Springer Science and Business Media LLC. - 1365-7852 .- 1476-5608. ; 26, s. 271-275
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Journal article (peer-reviewed)abstract
- Background We assessed the concordance among urologists' judgment of health quartiles for patients with localized prostate cancer, and compared the life expectancy (LE) and ensuing treatment recommendations when following National Comprehensive Cancer Network (NCCN) guidelines based on actuarial life tables versus the Kent model, a validated LE prediction model. Methods NCCN suggests using actuarial life tables and relying on surgeon assessment of patient health to increase (for the best quartile) or decrease (for the worst quartile) LE by 50%. Eleven urologic surgeons allocated quartile of health and recommended treatments for ten patient vignettes. The 10-year survival probability was calculated using the Kent model and compared to the life-table estimate based on health quartile by surgeon consensus. Results Surgeon assessment agreed with the presumed true quartile of health based on a validated model in 41% of cases. For no case did three-quarters of surgeons assign health quartile correctly; in half of cases, <50% of surgeons assigned the correct quartile. The NCCN comorbidity-adjusted LE estimates underestimated risk of death in the best health quartile and overestimated risk of death in the worst health quartile, compared to the Kent model. Patients with LE > 10 years on NCCN estimation were recommended more frequently for surgery (81%) and those with <= 10 years estimated LE were more commonly recommended for radiation (57%) or observation (29%). Conclusions A method based on physician-assessed health quartiles for LE estimation, as suggested by the NCCN guidelines, appears too crude to be used in the treatment counseling of men with localized prostate cancer, as compared to a validated prediction model, such as the Kent model.
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| 11. |
- Dahlman, A., et al.
(author)
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Effect of androgen deprivation therapy on the expression of prostate cancer biomarkers MSMB and MSMB-binding protein CRISP3
- 2010
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In: Prostate Cancer and Prostatic Diseases. - : Nature Publishing Group. - 1365-7852 .- 1476-5608. ; 13:4, s. 369-375
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Journal article (peer-reviewed)abstract
- We have investigated the effects of short-term neoadjuvant and long-term androgen deprivation therapies (ADTs) on β-microseminoprotein (MSMB) and cysteine-rich secretory protein-3 (CRISP3) expression in prostate cancer patients. We also studied if MSMB expression was related to genotype and epigenetic silencing. Using an Affymetrix cDNA microarray analysis, we investigated the expression of MSMB, CRISP3, androgen receptor (AR), KLK3 and Enhancer of Zeste Homologue-2 (EZH2) in tissue from prostate cancer patients receiving (n=17) or not receiving (n=23) ADT before radical prostatectomy. MSMB, CRISP3 and AR were studied in tissue from the same patients undergoing TURP before and during ADT (n=16). MSMB genotyping of these patients was performed by TaqMan PCR. MSMB and KLK3 expression levels decreased during ADT. Expression levels of AR and CRISP3 were not affected by short-term ADT but were high in castration-resistant prostate cancer (CRPC) and metastases. Levels of EZH2 were also high in metastases, where MSMB was low. Genotyping of the MSMB rs10993994 polymorphism showed that the TT genotype conveys poor MSMB expression. MSMB expression is influenced by androgens, but also by genotype and epigenetic silencing. AR and CRISP3 expression are not influenced by short-term ADT, and high levels were found in CRPC and metastases.
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| 12. |
- Dahlman, Anna K, et al.
(author)
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Effect of androgen deprivation therapy on the expression of prostate cancer biomarkers MSMB and MSMB-binding protein CRISP3.
- 2010
-
In: Prostate Cancer and Prostatic Diseases. - : Springer Science and Business Media LLC. - 1476-5608 .- 1365-7852. ; 13, s. 369-375
-
Journal article (peer-reviewed)abstract
- We have investigated the effects of short-term neoadjuvant and long-term androgen deprivation therapies (ADTs) on beta-microseminoprotein (MSMB) and cysteine-rich secretory protein-3 (CRISP3) expression in prostate cancer patients. We also studied if MSMB expression was related to genotype and epigenetic silencing. Using an Affymetrix cDNA microarray analysis, we investigated the expression of MSMB, CRISP3, androgen receptor (AR), KLK3 and Enhancer of Zeste Homologue-2 (EZH2) in tissue from prostate cancer patients receiving (n=17) or not receiving (n=23) ADT before radical prostatectomy. MSMB, CRISP3 and AR were studied in tissue from the same patients undergoing TURP before and during ADT (n=16). MSMB genotyping of these patients was performed by TaqMan PCR. MSMB and KLK3 expression levels decreased during ADT. Expression levels of AR and CRISP3 were not affected by short-term ADT but were high in castration-resistant prostate cancer (CRPC) and metastases. Levels of EZH2 were also high in metastases, where MSMB was low. Genotyping of the MSMB rs10993994 polymorphism showed that the TT genotype conveys poor MSMB expression. MSMB expression is influenced by androgens, but also by genotype and epigenetic silencing. AR and CRISP3 expression are not influenced by short-term ADT, and high levels were found in CRPC and metastases.Prostate Cancer and Prostatic Diseases advance online publication, 3 August 2010; doi:10.1038/pcan.2010.25.
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| 13. |
- Debruyne, Frans
(author)
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Innovators in urology : Introduction
- 2003
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In: Prostate Cancer and Prostatic Diseases. - : Springer Science and Business Media LLC. - 1365-7852 .- 1476-5608. ; 6:Suppl 1, s. 1-1
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Journal article (peer-reviewed)
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| 14. |
- FitzGerald, L. M., et al.
(author)
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Germline variants in IL4, MGMT and AKT1 are associated with prostate cancer-specific mortality : an analysis of 12,082 prostate cancer cases
- 2018
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In: Prostate Cancer and Prostatic Diseases. - : Nature Publishing Group. - 1365-7852 .- 1476-5608. ; 21:2, s. 228-237
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Journal article (peer-reviewed)abstract
- Background Prostate cancer (PCa) is a leading cause of mortality and genetic factors can influence tumour aggressiveness. Several germline variants have been associated with PCa-specific mortality (PCSM), but further replication evidence is needed. Methods Twenty-two previously identified PCSM-associated genetic variants were genotyped in seven PCa cohorts (12,082 patients; 1544 PCa deaths). For each cohort, Cox proportional hazards models were used to calculate hazard ratios and 95% confidence intervals for risk of PCSM associated with each variant. Data were then combined using a meta-analysis approach. Results Fifteen SNPs were associated with PCSM in at least one of the seven cohorts. In the meta-analysis, after adjustment for clinicopathological factors, variants in the MGMT (rs2308327; HR 0.90; p-value = 3.5 x 10(-2)) and IL4 (rs2070874; HR 1.22; p-value = 1.1 x 10(-3)) genes were confirmed to be associated with risk of PCSM. In analyses limited to men diagnosed with local or regional stage disease, a variant in AKT1, rs2494750, was also confirmed to be associated with PCSM risk (HR 0.81; p-value = 3.6 x 10(-2)). Conclusions This meta-analysis confirms the association of three genetic variants with risk of PCSM, providing further evidence that genetic background plays a role in PCa-specific survival. While these variants alone are not sufficient as prognostic biomarkers, these results may provide insights into the biological pathways modulating tumour aggressiveness.
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| 15. |
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| 16. |
- Guo, Jinan, et al.
(author)
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A non-invasive 25-Gene PLNM-Score urine test for detection of prostate cancer pelvic lymph node metastasis
- 2024
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In: Prostate Cancer and Prostatic Diseases. - : Nature Publishing Group. - 1365-7852 .- 1476-5608.
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Journal article (peer-reviewed)abstract
- Background: Prostate cancer patients with pelvic lymph node metastasis (PLNM) have poor prognosis. Based on EAU guidelines, patients with >5% risk of PLNM by nomograms often receive pelvic lymph node dissection (PLND) during prostatectomy. However, nomograms have limited accuracy, so large numbers of false positive patients receive unnecessary surgery with potentially serious side effects. It is important to accurately identify PLNM, yet current tests, including imaging tools are inaccurate. Therefore, we intended to develop a gene expression-based algorithm for detecting PLNM. Methods: An advanced random forest machine learning algorithm screening was conducted to develop a classifier for identifying PLNM using urine samples collected from a multi-center retrospective cohort (n = 413) as training set and validated in an independent multi-center prospective cohort (n = 243). Univariate and multivariate discriminant analyses were performed to measure the ability of the algorithm classifier to detect PLNM and compare it with the Memorial Sloan Kettering Cancer Center (MSKCC) nomogram score. Results: An algorithm named 25 G PLNM-Score was developed and found to accurately distinguish PLNM and non-PLNM with AUC of 0.93 (95% CI: 0.85-1.01) and 0.93 (95% CI: 0.87-0.99) in the retrospective and prospective urine cohorts respectively. Kaplan-Meier plots showed large and significant difference in biochemical recurrence-free survival and distant metastasis-free survival in the patients stratified by the 25 G PLNM-Score (log rank P < 0.001 and P < 0.0001, respectively). It spared 96% and 80% of unnecessary PLND with only 0.51% and 1% of PLNM missing in the retrospective and prospective cohorts respectively. In contrast, the MSKCC score only spared 15% of PLND with 0% of PLNM missing. Conclusions: The novel 25 G PLNM-Score is the first highly accurate and non-invasive machine learning algorithm-based urine test to identify PLNM before PLND, with potential clinical benefits of avoiding unnecessary PLND and improving treatment decision-making.
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| 17. |
- Hammarsten, J, et al.
(author)
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Insulin and free oestradiol are independent risk factors for benign prostatic hyperplasia.
- 2009
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In: Prostate cancer and prostatic diseases. - : Springer Science and Business Media LLC. - 1476-5608 .- 1365-7852. ; 12:2, s. 160-5
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Journal article (peer-reviewed)abstract
- The aetiology of benign prostatic hyperplasia (BPH) remains unclear. The objective of the present study was to test the insulin, oestradiol and metabolic syndrome hypotheses as promoters of BPH. The design was a risk factor analysis of BPH in which the total prostate gland volume was related to endocrine and anthropometric factors. The participants studied were 184 representative men, aged 72-76 years, residing in Göteborg, Sweden. Using a multivariate analysis, BPH as measured by the total prostate gland volume correlated statistically significantly with fasting serum insulin (beta=0.200, P=0.028), free oestradiol (beta=0.233, P=0.008) and lean body mass (beta=0.257, P=0.034). Insulin and free oestradiol appear to be independent risk factors for BPH, confirming both the insulin and the oestradiol hypotheses. Our findings also seem to confirm the metabolic syndrome hypothesis. The metabolic syndrome and its major endocrine aberration, hyperinsulinaemia, are possible primary events in BPH.
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| 18. |
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| 19. |
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| 20. |
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| 21. |
- Jäderling, Fredrik, et al.
(author)
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Preoperative staging using magnetic resonance imaging and risk of positive surgical margins after prostate-cancer surgery
- 2019
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In: Prostate Cancer and Prostatic Diseases. - : Nature Publishing Group. - 1365-7852 .- 1476-5608. ; 22:3, s. 391-398
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Journal article (peer-reviewed)abstract
- Background: It is unclear whether preoperative staging using Magnetic Resonance Imaging (MRI) reduces the risk of positive margins in prostate cancer. We aimed to assess the effect on surgical margins and degree of nerve sparing of a pelvic MRI presented at a preoperative MRI conference. Methods: Single institution, observational cohort study including 1037 men that underwent robot assisted radical prostatectomy between October 2013 and June 2015. Of these, 557 underwent a preoperative MRI combined with a preoperative MRI conference and 410 did not. With whole-mount prostate specimen histopathology as gold standard we assessed the ability of MRI in finding the index tumor and the sensitivity and specificity for extra prostatic extension. We calculated relative risks for positive surgical margins and non-nerve sparing procedure, adjusting for preoperative risk factors using stabilized inverse-probability weighting. Results: MRI detected the index tumor in 80% of the cases. Non-organ confined disease (pT3) at histology was present in the MRI and the non-MRI group in 42% and 24%, respectively. Rate of positive surgical margins comparing the MRI and non-MRI groups was 26.7% and 33.7%, respectively, relative risk 0.79 [95% CI 0.65-0.96], weighted relative risk (wRR) 0.69 [95% CI 0.55-0.86]. The wRR of extensive positive surgical margins was 0.45 [95% CI 0.31-0.67]. Undergoing MRI was also associated with an increased risk of being operated with a non-nerve sparing technique (wRR, 1.84 [95% CI 1.11-3.03]). Conclusions: Our study suggests that preoperative prostate MRI in combination with a preoperative MRI conference affects the degree of nerve-sparing surgery and reduces positive surgical margins.
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| 22. |
- Kalkner, Karl Mikael, et al.
(author)
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Octreotide scintigraphy and Chromogranin A do not predict clinical response in patients with octreotide acetate-treated hormone-refractory prostate cancer
- 2006
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In: Prostate Cancer and Prostatic Diseases. - : Springer Science and Business Media LLC. - 1476-5608 .- 1365-7852. ; 9:1, s. 92-98
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Journal article (peer-reviewed)abstract
- In this pilot study, the predictive value of Octreotide scintigraphy (Octreoscan) and/or Chromogranin-A (CgA) was investigated in patients with hormone-refractory prostate cancer treated with Octreotide acetate. In total, 20 patients with progressive disease and bone metastases entered the trial. At baseline Octreoscan, CgA, PSA, alkaline phosphates (ALP) and two self-administered questionnaires (EORTC QLQ C-30 (v3) and brief pain index) were performed and a diary of the pharmaceutical was started. The treatment consisted of Octreotide (Sandostatin LAR) acetate 30 mg intramuscular injection every month. The blood samples and questionnaires were repeated every month until 3 months. Clinical responder was defined as a patient with increased global health score more than 10 units and stable or decreased pain score without an increase in analgesic. In all, 17 patients were treated per protocol, and four were assessed as clinical responders. Six patients developed a reduction in ALP (median -26%, range -5 to -78%). All patients increased in PSA. At baseline, three patients had a negative Octreoscan and the patients with positive lesions, demonstrated uptake of low intensity. At baseline the CgA was elevated above the normal range in 15 of the patients, and during treatment five patients decreased their CgA to the normal range. Neither baseline Octreoscan nor CgA could identify the clinical reponders. A minority of patients improves their health-related quality of life. The decrease and normalization of CgA levels in five patients during therapy indicates therapeutic activity but Octreoscan and CgA could not identify clinical responders.
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| 23. |
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| 24. |
- Kellokumpu-Lehtinen, P-L, et al.
(author)
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Toxicity in patients receiving adjuvant docetaxel plus hormonal treatment after radical radiotherapy for intermediate or high-risk prostate cancer : a preplanned safety report of the SPCG-13 trial
- 2012
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In: Prostate Cancer and Prostatic Diseases. - : Springer Science and Business Media LLC. - 1365-7852 .- 1476-5608. ; 15:3, s. 303-307
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Journal article (peer-reviewed)abstract
- BACKGROUND: Radical radiotherapy (RD combined with androgen deprivation therapy is currently the standard treatment for elderly patients with localized intermediate- or high-risk prostate cancer (PC). To increase the recurrence-free and overall survival, we conducted an adjuvant, randomized trial using docetaxel (T) in PC patients (Scandinavian Prostate Cancer Group trial 13). METHODS: The inclusion criteria are the following: men > 18 and <= 75 years of age, WHO/ECOG performance status 0-1, histologically proven PC within 12 months before randomization and one of the following: T2, Gleason 7 (4 + 3), PSA > 10; T2, Gleason 8-10, any PSA; or any T3 tumors. Neoadjuvant/adjuvant hormone therapy is mandatory for all patients. The patients were randomized to receive six cycles of T (75 mg m(-2) d 1. cycle 21 d) or no docetaxel after radical RI (with a minimum tumor dose of 74 Gy). This study identifier number is NTC 006653848 (http://www.clinicaltrials.org). RESULTS: In this preplanned safety analysis of 100 patients, T treatment induced grade (G) 3 adverse events (AEs) in 15 patients (30%) and G4 AEs in 30 patients (60%), mainly due to bone marrow toxicity. Neutropenia G3-4 was observed in 72% of the patients, febrile neutropenia was found in 24% of patients, neutropenic infection in 10% of patients and G3 infection without neutropenia in 4% of patients. Nonhematological G3 AEs were rare: anorexia, diarrhea, mucositis, nausea, pain (1 patient each) and fatigue (5). Other severe serious AEs related to T were pulmonary embolism and renal failure. However, only three patients discontinued T before completing the planned six cycles. No deaths had occurred. No patients in the control arm experienced G3-4 toxicities at 12 weeks after the randomization. CONCLUSIONS: Adjuvant docetaxel chemotherapy after radiotherapy has a higher frequency of neutropenia than previous studies on patients with metastatic disease. Otherwise, the treatment was quite well tolerated.
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| 25. |
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| 26. |
- Li, Xinjun, et al.
(author)
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Neighborhood deprivation and prostate cancer mortality: a multilevel analysis from Sweden.
- 2012
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In: Prostate Cancer and Prostatic Diseases. - : Springer Science and Business Media LLC. - 1476-5608 .- 1365-7852. ; 15, s. 128-134
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Journal article (peer-reviewed)abstract
- Background:The objective was to analyze the association between neighborhood deprivation and prostate cancer mortality, after adjusting for individual characteristics.Methods:This study was designed as a follow-up study of prostate cancer mortality between 1 January 1990 and 31 December 2008 in patients aged 25-74 years (a total of 73 159 patients). Multilevel logistic regression analyses were performed with individual-level characteristics at the first level and level of neighborhood deprivation at the second level.Results:The age-standardized prostate cancer mortality rate was 1.5 times higher in men living in high-deprivation neighborhoods than in those living in the most affluent neighborhoods. Mortality rates were also associated with certain individual-level characteristics, that is, age, marital status, family income, educational attainment, immigration status, urban/rural status, mobility and comorbidity. For example, there was a strong relationship between prostate cancer mortality and being unmarried, having a low income or educational attainment, and hospitalization for chronic obstructive pulmonary disease. In the full model, the risk of prostate cancer mortality was 25% higher in men living in the most deprived neighborhoods than in those living in the most affluent neighborhoods.Conclusions:High level of neighborhood deprivation independently predicts prostate cancer mortality. This raises important clinical and public health concerns. Both individual- and neighborhood-level approaches are important in healthcare policies.Prostate Cancer and Prostatic Diseases advance online publication, 11 October 2011; doi:10.1038/pcan.2011.46.
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| 27. |
- Lippolis, Giuseppe, et al.
(author)
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A high-density tissue microarray from patients with clinically localized prostate cancer reveals ERG and TATI exclusivity in tumor cells.
- 2013
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In: Prostate Cancer and Prostatic Diseases. - : Springer Science and Business Media LLC. - 1476-5608 .- 1365-7852. ; 16:2, s. 145-150
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Journal article (peer-reviewed)abstract
- Background:Prostate cancer (PCa) is characterized by high tumor heterogeneity. In 2005, the fusion between the androgen-regulated gene TMPRSS2 and members of the ETS family was discovered in prostate cancer. In particular, fusion of TMPRSS2 with ERG was found in approximately 50% of prostate cancers and considered as an early event in the onset of the disease. The prognostic value of this fusion is still contradictory. Bioinformatics showed that overexpression of SPINK1 gene in a subset of fusion-gene-negative prostate cancers was associated with a poor prognosis. In theory, overexpression of the tumor-associated trypsin inhibitor (TATI) protein encoded by SPINK1 in fusion-gene-negative tumor cells opens the way to selected treatments for genotypically different cases. However, their expression has never been assessed at the cellular level in the same tissue samples.Methods:As ERG expression has been shown to be a surrogate of fusion gene occurrence in prostate cancer, we have used double immunohistochemical staining to assess expression of ERG and TATI on a large tissue microarray comprising 4177 cases of localized prostate cancer.Results:We did not detect any co-expression of ERG and TATI in the same cancer cells, which confirms previous suggestions from in silico studies. ERG was associated with Gleason score (GS), surgical margins and pathological stage, but had no prognostic value in this cohort. TATI was weakly associated with pathological stage but had no significant association with outcome.Conclusions:We here provide a morphological basis for ERG and TATI exclusivity in prostate cancer cells. Future therapies should be based on a combination of different targets in order to eradicate tumor cells with gene fusions and cells expressing other tumor-associated antigens. Further studies are needed to understand why ERG and TATI are not co-expressed in the same prostatic tumor cells.Prostate Cancer and Prostatic Disease advance online publication, 5 March 2013; doi:10.1038/pcan.2013.7.
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| 28. |
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| 29. |
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| 30. |
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| 31. |
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| 32. |
- Peng, Z., et al.
(author)
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An expression signature at diagnosis to estimate prostate cancer patients' overall survival
- 2014
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In: Prostate Cancer and Prostatic Diseases. - : Springer Science and Business Media LLC. - 1365-7852 .- 1476-5608. ; 17:1, s. 81-90
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Journal article (peer-reviewed)abstract
- BACKGROUND: This study aimed to identify biomarkers for estimating the overall and prostate cancer (PCa)-specific survival in PCa patients at diagnosis. METHODS: To explore the importance of embryonic stem cell (ESC) gene signatures, we identified 641 ESC gene predictors (ESCGPs) using published microarray data sets. ESCGPs were selected in a stepwise manner, and were combined with reported genes. Selected genes were analyzed by multiplex quantitative polymerase chain reaction using prostate fine-needle aspiration samples taken at diagnosis from a Swedish cohort of 189 PCa patients diagnosed between 1986 and 2001. Of these patients, there was overall and PCa-specific survival data available for 97.9%, and 77.9% were primarily treated by hormone therapy only. Univariate and multivariate Cox proportional hazard ratios and Kaplan-Meier plots were used for the survival analysis, and a k-nearest neighbor (kNN) algorithm for estimating overall survival. RESULTS: An expression signature of VGLL3, IGFBP3 and F3 was shown sufficient to categorize the patients into high-, intermediate- and low-risk subtypes. The median overall survival times of the subtypes were 3.23, 4.00 and 9.85 years, respectively. The difference corresponded to hazard ratios of 5.86 (95% confidence interval (CI): 2.91-11.78, P<0.001) for the high-risk subtype and 3.45 (95% CI: 1.79-6.66, P<0.001) for the intermediate-risk compared with the low-risk subtype. The kNN models that included the gene expression signature outperformed the one designed on clinical parameters alone. CONCLUSIONS: The expression signature can potentially be used to estimate overall survival time. When validated in future studies, it could be integrated in the routine clinical diagnostic and prognostic procedure of PCa for an optimal treatment decision based on the estimated survival benefit.
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| 33. |
- Rueenauver, K., et al.
(author)
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Prognostic significance of YWHAZ expression in localized prostate cancer
- 2014
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In: Prostate Cancer and Prostatic Diseases. - : Nature Publishing Group. - 1365-7852 .- 1476-5608. ; 17:4, s. 310-314
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Journal article (peer-reviewed)abstract
- BACKGROUND: Prostate cancer (PCa) patients are often over-treated because of the lack of biomarkers needed to distinguish the lethal from the indolent form of PCa. YWHAZ was recently identified as a potential therapeutic target in castration-resistant PCa (CRPC). Therefore, this study focused on determining the prognostic significance of YWHAZ in localized PCa.METHODS: YWHAZ expression was assessed by immunohistochemistry on formalin-fixed paraffin-embedded tissue from 213 men who underwent radical prostatectomy. Kaplan-Meier analysis and Cox proportional-hazards models were, used to assess the prognostic value of YWHAZ intensity.RESULTS: High YWHAZ expression was strongly associated with high Gleason score at the time of diagnosis (P<0.001) and PSA relapse (P=0.001). Importantly, patients with high expression of YWHAZ had a higher risk of CRPC development (P=0.002) and reduced survival time (P=0.002).CONCLUSIONS: Our findings indicate that YWHAZ could serve as a promising prognostic biomarker in localized PCa to predict poor prognosis and to identify a subgroup of tumors, which might benefit from earlier adjuvant or YWHAZ-targeted therapy.
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| 34. |
- Shore, N. D., et al.
(author)
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New considerations for ADT in advanced prostate cancer and the emerging role of GnRH antagonists
- 2013
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In: Prostate Cancer and Prostatic Diseases. - : Springer Science and Business Media LLC. - 1476-5608 .- 1365-7852. ; 16:1, s. 7-15
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Research review (peer-reviewed)abstract
- Androgen deprivation therapy (ADT) is first-line treatment for metastatic prostate cancer (PCa). Gonadotrophin-releasing hormone (GnRH) agonists are the most commonly used ADT but have several theoretical physiologic disadvantages (e.g. initial testosterone surge, potential microsurges upon repeat administration). Testosterone surge delays the intended serologic endpoint of testosterone suppression and may exacerbate clinical symptoms. GnRH antagonists were developed with a view toward overcoming these potential adverse physiologic events. This review evaluates GnRH agonists and antagonists, assessing the potential future role of antagonists in PCa and strategies to minimize ADT adverse events (AEs). Evidence was identified via PubMed search (by GnRH agent and other ADT-related terms), from review article bibliographies, and authors' therapy area knowledge, with articles included by author consensus. Degarelix shows similar efficacy to a GnRH agonist in achieving and maintaining castration, with faster onset and without testosterone surge/microsurges. Phase III data showed that, in the first treatment year, degarelix displayed a lower risk of PSA failure or death (composite endpoint), lower levels of the bone marker serum alkaline phosphatase (in baseline metastatic disease), and fewer musculoskeletal AEs than the agonist leuprolide. Also, crossing over from leuprolide to degarelix after 1 year reduced the risk of PSA failure or death. ADT displays an AE spectrum which can impact quality of life as well as causing significant morbidities. Strategies to improve ADT tolerability have become increasingly important including: a holistic management approach, improved diet and exercise, more specific monitoring to detect and prevent testosterone depletion toxicities, and intermittent ADT allowing hormonal recovery between treatment periods. Clinical studies suggest possible benefits of GnRH antagonists over agonists based on different mechanisms of action. GnRH antagonists should now be considered as an alternative first-line ADT option in advanced PCa. Intermittent ADT and a holistic treatment approach are promising strategies to improve ADT tolerability. Prostate Cancer and Prostatic Diseases (2013) 16, 7-15; doi:10.1038/pcan.2012.25; published online 3 July 2012
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| 35. |
- Soloway, Mark
(author)
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Innovators in urology
- 2002
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In: Prostate Cancer and Prostatic Diseases. - : Springer Science and Business Media LLC. - 1365-7852 .- 1476-5608. ; 5, s. 1-1
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Journal article (peer-reviewed)
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| 36. |
- Ternov, K. K., et al.
(author)
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Quality of life in men with metastatic castration-resistant prostate cancer treated with enzalutamide or abiraterone: a systematic review and meta-analysis
- 2021
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In: Prostate Cancer and Prostatic Diseases. - : Springer Science and Business Media LLC. - 1365-7852 .- 1476-5608. ; 24:4, s. 948-961
-
Research review (peer-reviewed)abstract
- Background Enzalutamide and abiraterone acetate plus prednisone (AAP) have similar efficacy in metastatic castration-resistant prostate cancer (mCRPC), but different mechanisms of action. The aim was to compare patient-reported health-related quality of life (HRQoL) in men treated with enzalutamide vs AAP for mCRPC. Methods We systematically reviewed the literature in June 2020 according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. Patient-reported outcomes (PROs) until the last follow-up were summarised in a narrative synthesis. Short-term changes (12 weeks) in HRQoL, measured by the Functional Assessment of Cancer Therapy-Prostate total score (FACT-P), were compared between treatment groups and were analysed for enzalutamide and AAP in separate meta-analyses. Higher FACT-P scores indicate better HRQoL. Results Eight studies were included in the systematic review, four of which were randomised clinical trials (RCTs) eligible for the meta-analyses. The meta-analyses showed mean within-subject FACT-P changes from baseline to week 12 of -1.3 points (95% confidence interval [CI] -2.7; 0.1) for enzalutamide and 4.7 points (95% CI -0.1; 9.6) for AAP. One RCT and three non-randomised studies directly compared enzalutamide with AAP. The RCT showed better short-term HRQoL for AAP (6.8 FACT-P-points, 95% CI 1.7; 11.8) and better long-term HRQoL for AAP in men >= 75 years (7.35 FACT-P-points, 95% CI 2.59; 12.11). The non-randomised studies showed no difference in long-term HRQoL but had all a serious risk of bias. Limitations of the included studies include that the PRO in the included trials were inconsistently reported and that only one study defined the HRQoL measures in their published protocol. Conclusions AAP seems to be associated with better short-term HRQoL than enzalutamide. This difference was not apparent at longer follow-up, but the long-term studies had serious risks of bias.
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| 37. |
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| 38. |
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| 39. |
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| 40. |
- Väisänen, V., et al.
(author)
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Characterization and processing of prostate specific antigen (hK3) and human glandular kallikrein (hK2) secreted by LNCaP cells
- 1999
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In: Prostate Cancer and Prostatic Diseases. - : Springer Science and Business Media LLC. - 1365-7852 .- 1476-5608. ; 2, s. 91-97
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Journal article (peer-reviewed)abstract
- Prostate specific antigen (PSA, hK3) in serum is predominantly complexed to α-1-antichymotrypsin (ACT), but a minor fraction remains in a free form despite the very large excess of serine protease inhibitors and α-2- macroglobulin. The fraction of free to total PSA is significantly lower in prostate cancer (CAP) compared to benign prostatic hyperplasia (BPH) which provides improved discrimination of these conditions. The molecular nature of free PSA in the circulation and the reason for its varying concentration in malignant and benign conditions is currently not known. The objective of the present investigation was to study the secretion of PSA and human glandular kallikrein 2 (hK2) by the LNCaP prostate cancer cell line, and to purify and characterize both proteins. LNCaP PSA was thoroughly characterized by immunological characterization, SDS-PAGE, isoelectric focusing, gel filtration, aminoterminal sequencing, reverse-phase chromatography, mass spectrometry and enzymatic activity measurements. LNCAP cells produced approximately equal amounts of zymogen (proPSA) and the one-chain mature form of PSA, whereas there was no evidence for the secretion of any internally cleaved forms. LNCaP cells secreted hK2 into the growth medium at about 3-5% of the amount of PSA. One-chain, mature PSA and hK2 obtained when LNCaP cells were grown in the presence of fetal bovine serum, had no enzymatic activity, but were active when the cells were grown in the absence of serum. Using enzymatically active recombinant hK2, it was possible to activate proPSA secreted by LNCaP cells. ProPSA formed two bands with high isoelectric points (8.2 and 8.4), which disappeared when proPSA was converted to mature PSA with hK2. Cancerous cells produce the zymogen forms of PSA, which by their isoelectric pI points seem to be found in serum of prostate cancer patients, but not BPH patients. Mature, one-chain PSA is inactive in the presence of serum. These findings may be highly relevant for the understanding of the generation of free and complexed PSA in the circulation.
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| 41. |
- Welén, Karin, 1970, et al.
(author)
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Pericyte coverage decreases invasion of tumour cells into blood vessels in prostate cancer xenografts.
- 2009
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In: Prostate cancer and prostatic diseases. - : Springer Science and Business Media LLC. - 1476-5608 .- 1365-7852. ; 12:1, s. 41-6
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Journal article (peer-reviewed)abstract
- Androgen-independent prostate cancer is an aggressive disease with high angiogenic and metastatic potential. Increased microvessel density and altered invasion properties have previously been described in LNCaP-19, an androgen-independent subline to LNCaP. To characterize the differences in angiogenesis and invasion, the vessels of these tumour xenografts were investigated with immunohistochemistry, and the influence of tumour cells on endothelial cell migration, proliferation and tube formation was studied in vitro. The blood vessels of LNCaP were found to be stabilized by pericytes more frequently than vessels in LNCaP-19. Further, tumour cell invasion was decreased in pericyte-covered blood vessels in both the tumour types. LNCaP-19 displayed an increased potential to induce endothelial cell migration in vitro. In conclusion, pericyte coverage seems to be important for the invasion of tumour cells into blood vessels. Further, LNCaP-19 has lower pericyte coverage and an increased potential to induce endothelial cell migration, which reflects its high microvessel density.
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| 42. |
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| 43. |
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| 46. |
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| 47. |
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| 48. |
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| 49. |
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| 50. |
- Lilja, Hans
(author)
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Early Diagnosis and Staging.
- 1999
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In: Prostate Cancer and Prostatic Diseases. - 1476-5608. ; 2:S1, s. 15-18
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Journal article (peer-reviewed)abstract
- This report reviews developments in the early diagnosis and staging of prostate cancer and updated on the incidence of postate cancer to discuss the pros and cons of population based screening. Refinements and reliability of various diagnosic procedures are described such as PSA testing, transrectal ultrasound, ratio beteen PSA-level and ultrasound measured prostate volume, rate of change of PSA-level, combination factor equations computed by neural network programs to predict likelihood of prostate cancer, artificial neural network analysis of subvisual transrectal ultrasound information, measurements of different PSA-forms of PSA (in particular percent free PSA), and glandular kallikrein 2.
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