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Sökning: L773:1365 7852 OR L773:1476 5608

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  • Andersson, Patiyan, 1978-, et al. (författare)
  • Association studies on INS and IRS1polymorphisms: IRS1 G972R is associated with increased prostate cancer risk
  • 2008
  • Ingår i: Prostate Cancer and Prostatic Diseases. - 1365-7852 .- 1476-5608.
  • Tidskriftsartikel (refereegranskat)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.
  • Beckmann, Kerri, et al. (författare)
  • Spironolactone use is associated with lower prostate cancer risk : a population-wide case-control study
  • 2020
  • Ingår i: Prostate Cancer and Prostatic Diseases. - : NATURE PUBLISHING GROUP. - 1365-7852 .- 1476-5608. ; 23:3, s. 527-533
  • Tidskriftsartikel (refereegranskat)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.
  • Dahlman, Anna K, et al. (författare)
  • Effect of androgen deprivation therapy on the expression of prostate cancer biomarkers MSMB and MSMB-binding protein CRISP3.
  • 2010
  • Ingår i: Prostate Cancer and Prostatic Diseases. - : Nature Publishing Group. - 1476-5608 .- 1365-7852. ; 13, s. 369-375
  • Tidskriftsartikel (refereegranskat)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.
  • FitzGerald, L. M., et al. (författare)
  • Germline variants in IL4, MGMT and AKT1 are associated with prostate cancer-specific mortality : an analysis of 12,082 prostate cancer cases
  • 2018
  • Ingår i: Prostate Cancer and Prostatic Diseases. - : Nature Publishing Group. - 1365-7852 .- 1476-5608. ; 21:2, s. 228-237
  • Tidskriftsartikel (refereegranskat)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.
  • Hammarsten, J, et al. (författare)
  • Insulin and free oestradiol are independent risk factors for benign prostatic hyperplasia.
  • 2009
  • Ingår i: Prostate cancer and prostatic diseases. - : Nature Publishing Group. - 1476-5608 .- 1365-7852. ; 12:2, s. 160-5
  • Tidskriftsartikel (refereegranskat)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.
  • Jäderling, Fredrik, et al. (författare)
  • Preoperative staging using magnetic resonance imaging and risk of positive surgical margins after prostate-cancer surgery
  • 2019
  • Ingår i: Prostate Cancer and Prostatic Diseases. - : Nature Publishing Group. - 1365-7852 .- 1476-5608. ; 22:3, s. 391-398
  • Tidskriftsartikel (refereegranskat)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.
  • Kalkner, Karl Mikael, et al. (författare)
  • Octreotide scintigraphy and Chromogranin A do not predict clinical response in patients with octreotide acetate-treated hormone-refractory prostate cancer
  • 2006
  • Ingår i: Prostate Cancer and Prostatic Diseases. - : Nature Publishing Group. - 1476-5608 .- 1365-7852. ; 9:1, s. 92-98
  • Tidskriftsartikel (refereegranskat)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.
  • Kellokumpu-Lehtinen, P-L, et al. (författare)
  • 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
  • Ingår i: Prostate Cancer and Prostatic Diseases. - 1365-7852 .- 1476-5608. ; 15:3, s. 303-307
  • Tidskriftsartikel (refereegranskat)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.
  • Peng, Z., et al. (författare)
  • An expression signature at diagnosis to estimate prostate cancer patients' overall survival
  • 2014
  • Ingår i: Prostate Cancer and Prostatic Diseases. - 1365-7852 .- 1476-5608. ; 17:1, s. 81-90
  • Tidskriftsartikel (refereegranskat)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.
  • Rueenauver, K., et al. (författare)
  • Prognostic significance of YWHAZ expression in localized prostate cancer
  • 2014
  • Ingår i: Prostate Cancer and Prostatic Diseases. - : Nature Publishing Group. - 1365-7852 .- 1476-5608. ; 17:4, s. 310-314
  • Tidskriftsartikel (refereegranskat)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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