| 51. |
- Mushtaq, Muhammad, et al.
(författare)
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The MRPS18-2 protein levels correlate with prostate tumor progression and it induces CXCR4-dependent migration of cancer cells
- 2018
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- We have earlier found abnormal expression of the mitochondrial ribosomal protein S18-2 (MRPS18-2, S18-2) in endometrial cancer, compared to the expression in hyperplasia and in normal endometrium. Here we report that expression of S18-2 was increased with disease progression in clinical specimens of prostate cancer (PCa). The level of induction of epithelial to mesenchymal cell transition (EMT) correlated with the expression level of S18-2 in PCa cell lines. Moreover, cells acquired increased ability of migration upon S18-2 overexpression, as was evaluated in zebrafish embryo model and in trans-well assay. We found that this is due to increased CXCR4 cell surface expression. Neutralizing CXCR4 protein or abrogating S18-2 expression in cells significantly reduced their migratory ability directed toward CXCL12. The mRNA expression of TWIST2, encoding one of transcription factors that induce EMT upon CXCR4 increase, positively correlated with the S18-2 protein level. Together, these data suggest that the S18-2 protein induces EMT through the TWIST2/E-cadherin signalling and, consequently, CXCR4-mediated migration of PCa cells.
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| 52. |
- Nowak, Michael, et al.
(författare)
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Prognostic significance of phospho-histone H3 in prostate carcinoma
- 2014
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Ingår i: World journal of urology. - : Springer-Verlag New York. - 0724-4983 .- 1433-8726. ; 32:3, s. 703-707
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Tidskriftsartikel (refereegranskat)abstract
- Prostate cancer is the second most common cancer in men and the sixth most common cause of death from cancer in men worldwide. Currently, a sufficient pathological distinction between patients requiring further treatment and those for which active surveillance remains an option is still lacking, which leads to the problem of overtreatment. Cell proliferation is routinely assessed by detecting Ki-67 antigen. While Ki-67 is expressed throughout the interphase of proliferating cells, phosphorylation of the chromatin constituent histone H3 occurs only during the late G2 phase and mitosis thus providing a more strict assessment of the mitotic activity. We undertook this study to test whether expression of the recently introduced proliferation marker phospho-histone H3 (pHH3) in prostate carcinoma tissue sections exhibits prognostic significance in comparison with Ki-67. Protein expression of pHH3 and Ki-67 was assessed on TMA consisting of paraffin-embedded tissue from men that had undergone radical prostatectomy. The analysis included triplicate tissue cores of a total of 339 tumor foci. Immunohistochemical staining of pHH3 and Ki-67 was performed and analyzed using Definiens imaging software. Prostate cancer tissue exhibited a significantly higher frequency of pHH3-positive cells compared to benign prostate tissue. pHH3 expression was significantly correlated with Ki-67 expression. Furthermore, statistical analysis revealed positive correlation between pHH3 expression and PSA levels at diagnosis and in addition negatively correlated with overall survival. In contrast to Ki-67 staining, pHH3 expression did not correlate with Gleason grade. Our data point to a conceivable role of pHH3 as prognostic biomarker in prostate carcinoma.
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| 53. |
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| 54. |
- Offermann, Anne, et al.
(författare)
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TRIM24 as an independent prognostic biomarker for prostate cancer
- 2019
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Ingår i: Urologic Oncology. - : Elsevier. - 1078-1439 .- 1873-2496. ; 37:9
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Simply applicable biomarkers for prostate cancer patients predicting the clinical course are urgently needed. Recently, TRIM24 has been identified to promote androgen receptor signaling and to correlate with an aggressive prostate cancer phenotype. Based on these data, we proofed TRIM24 as a prognostic biomarker for risk stratification.Materials and Methods: We performed TRIM24 immunohistochemistry on 2 independent cohorts including a total of 806 primary tumors, 26 locally advanced/recurrent tumors, 30 lymph node metastases, 30 distant metastases, and 129 benign prostatic samples from 497 patients as well as on 246 prostate needle biopsies. Expression data were correlated with clinic-pathological data including biochemical recurrence-free survival (bRFS) as endpoint.Results: Benign samples show no or low TRIM24 expression in 94%, while tumor tissues demonstrate significant higher levels. Strongest expression is observed in advanced and metastatic tumors. In multivariate analyses, TRIM24 up-regulation on radical prostatectomy specimens correlates with shorter bRFS independent of other prognostic parameters. 5-(10-) year bRFS rates for TRIM24 negative, low, medium and high expressing tumors are 93.1(93.1)%, 75.4(68.5)%, 54.9(47.5)% and 43.1(32.3)%, respectively. Of interest, tumors diagnosed as indolent disease, TRIM24 expression stratifies patients into specific risk groups. Increased TRIM24 expression associates with higher grade group, positive nodal status and extraprostatic tumor growth. TRIM24 assessment on prostate needle biopsies taken prior to treatment decision at time of initial diagnosis significantly correlates with recurrence after surgery.Conclusion: Using 2 large independent radical prostatectomy specimen cohorts, we found that TRIM24 expression predicts patients' risk to develop disease recurrence with high accuracy and independent from other established biomarkers. Further, this is the first study exploring TRIM24 expression on prostate needle biopsies which represents the clinically relevant tissue type on which biomarkers guide treatment decisions. Thus, we strongly suggest introducing TRIM24 evaluation in prostate needle biopsies in clinical routine as an inexpensive and simple immunohistochemical test.
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| 55. |
- Offermann, Anne, et al.
(författare)
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TRIM24 as Independent Prognostic Marker in Prostate Cancer
- 2018
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Ingår i: Modern Pathology. - : Nature Publishing Group. - 0893-3952 .- 1530-0285. ; 31:Suppl. 2, s. 372-373
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Simply applicable biomarkers for prostate cancer (PCa) predicting the clinical course are urgently needed. Recently, TRIM24 has been identified to promote androgen-receptor signaling and to correlate with poor outcome. Based on these data, we validated TRIM24 as a prognostic biomarker for PCa.Design: We performed TRIM24 immunohistochemistry on two independent cohorts including a total of 806 primary tumors, 26 locally advanced/recurrent tumors, 30 lymph node metastases, 30 distant metastases and 129 benign prostatic samples from 497 patients. Expression data were correlated with clinic-pathological data including biochemical recurrence free survival (bRFS) as endpoint.Results: Benign samples show no/low TRIM24 expression in 94%, while tumors demonstrate significantly higher levels. Strongest expression is observed in metastatic tumors. In multivariate analyses, TRIM24 up-regulation correlates with shorter bRFS independent of other prognostic parameters. 5-(10-) year bRFS rates for TRIM24 negative, low, medium and high expressing tumors are 93.1(93.1)%, 75.4(68.5)%, 54.9(47.5)% and 43.1(32.3)%, respectively. Of interest, tumors diagnosed as indolent disease, TRIM24 expression stratifies patients into specific risk groups. Increased TRIM24 expression associates with higher Grade Group, positive nodal status and extraprostatic tumor growth.Conclusions: Using two large independent cohorts, we found that TRIM24 expression predicts patients’ risk to develop disease recurrence with high accuracy and independently from other established prognostic markers. To our knowledge, TRIM24 is the first prognostic biomarker to be independent, accurate and reproducible on three different primary PCa cohorts. Thus, we strongly suggest introducing TRIM24 in clinical routine as a simple immunohistochemical test.
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| 56. |
- Olsson, Jan, et al.
(författare)
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Antibiotic susceptibility in prostate-derived Propionibacterium acnes isolates
- 2012
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Ingår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS). - HOBOKEN, NJ USA : Wiley-Blackwell. - 0903-4641 .- 1600-0463. ; 120:10, s. 778-785
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to determine antibiotic susceptibility of Propionibacterium acnes isolates from prostate. Prostate-derived P. acnes isolates (n = 24, Umeå & Örebro, Sweden, 2007-2010) and a panel of control strains (n = 25, Sweden) collected from skin and deep infections were assessed for resistance to penicillin G, piperacillin-tazobactam, imipenem, gentamicin, azithromycin, erythromycin, vancomycin, ciprofloxacin, moxifloxacin, tetracycline, tigecycline, fusidic acid, clindamycin, rifampicin, linezolid, daptomycin, trimethoprim-sulfamethoxazole, and metronidazole. In addition, the isolates were tested for inducible clindamycin resistance. All prostate derived P. acnes isolates displayed wild-type distribution of MIC-values, without evidence of acquired resistance. In the reference panel, 5 of 25 isolates had acquired macrolide resistance with cross-resistance to azithromycin, clindamycin, and erythromycin. In addition, one of these isolates was resistant to tetracycline.
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| 57. |
- Penney, K. L., et al.
(författare)
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mRNA expression signature of Gleason grade predicts lethal prostate cancer
- 2011
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Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology. - 0732-183X .- 1527-7755. ; 29:17, s. 2391-2396
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Prostate-specific antigen screening has led to enormous overtreatment of prostate cancer because of the inability to distinguish potentially lethal disease at diagnosis. We reasoned that by identifying an mRNA signature of Gleason grade, the best predictor of prognosis, we could improve prediction of lethal disease among men with moderate Gleason 7 tumors, the most common grade, and the most indeterminate in terms of prognosis.PATIENTS AND METHODS: Using the complementary DNA-mediated annealing, selection, extension, and ligation assay, we measured the mRNA expression of 6,100 genes in prostate tumor tissue in the Swedish Watchful Waiting cohort (n = 358) and Physicians' Health Study (PHS; n = 109). We developed an mRNA signature of Gleason grade comparing individuals with Gleason ≤ 6 to those with Gleason ≥ 8 tumors and applied the model among patients with Gleason 7 to discriminate lethal cases.RESULTS: We built a 157-gene signature using the Swedish data that predicted Gleason with low misclassification (area under the curve [AUC] = 0.91); when this signature was tested in the PHS, the discriminatory ability remained high (AUC = 0.94). In men with Gleason 7 tumors, who were excluded from the model building, the signature significantly improved the prediction of lethal disease beyond knowing whether the Gleason score was 4 + 3 or 3 + 4 (P = .006).CONCLUSION: Our expression signature and the genes identified may improve our understanding of the de-differentiation process of prostate tumors. Additionally, the signature may have clinical applications among men with Gleason 7, by further estimating their risk of lethal prostate cancer and thereby guiding therapy decisions to improve outcomes and reduce overtreatment.
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| 58. |
- Pernar, Claire H., et al.
(författare)
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A Walking Intervention Among Men With Prostate Cancer : A Pilot Study
- 2017
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Ingår i: Clinical Genitourinary Cancer. - New York, USA : Elsevier. - 1558-7673 .- 1938-0682. ; 15:6, s. e1021-e1028
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Tidskriftsartikel (refereegranskat)abstract
- Men diagnosed with prostate cancer have increased risk of disease progression, cardiovascular events, and quality of life impairments. Men with a recent diagnosis randomly assigned to a walking group intervention maintained 10,000 steps per day and experienced improvement in cardiovascular biomarkers compared with usual care. A larger walking group intervention is needed to investigate its potential for improvement in longterm outcomes.BACKGROUND: Men diagnosed with prostate cancer have increased risk for disease progression, cardiovascular events, and impairments in quality of life. This pilot study evaluated the feasibility of a randomized walking group intervention to improve quality of life, circulating biomarkers, and morbidity among men with newly diagnosed prostate cancer.METHODS: Men were recruited at Örebro University Hospital, Sweden, and randomized to an 11-week walking group intervention (n = 21) or usual care (n = 20). The intervention included weekly 1-hour walking group sessions and maintenance of 10,000 steps/day. Outcomes were changes in body composition, clinical factors, biomarkers of cardiovascular health, and quality of life between baseline and end of study. Analysis of covariance was used to compare outcomes in each group adjusted for baseline values.RESULTS: All 41 men randomized completed the 11-week trial. Men assigned to the intervention walked on average 10,644 steps/day, and 92% reported missing 2 or fewer sessions. Both groups experienced similar weight loss at 11 weeks. Men in the intervention had a significant adjusted mean change in high-density lipoprotein of 0.14 mmol/L (95% confidence interval [CI], 0.01-0.27; P = .04), and suggestive adjusted mean changes in low-density lipoprotein of -0.22 mmol/L (95% CI, -0.47 to 0.03; P = .08) and in systolic blood pressure of -8.5 mm Hg (95% CI, -21.2 to 4.2; P = .18), compared with the usual care group.CONCLUSIONS: A walking group intervention among men with recent diagnosis of prostate cancer is feasible and potentially effective in improving cardiovascular health. A larger randomized trial of longer duration is required to elucidate its potential for improvement in longer term outcomes.
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| 59. |
- Rider, Jennifer R., et al.
(författare)
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iNOS expression and lethal prostate cancer in patients with localized disease
- 2017
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Ingår i: Cancer Research. - : American Association for Cancer Research. - 0008-5472 .- 1538-7445. ; :22S
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Tidskriftsartikel (refereegranskat)abstract
- Inducible nitric oxide synthase (iNOS) has demonstrated both tumor-promoting and tumor-inhibiting effects in prostate cancer. However, the relationship between iNOS protein expression and long-term prostate cancer outcomes is unclear. We evaluated iNOS expression in tumor epithelia and stroma in 300 men with localized tumors diagnosed incidentally by transurethral resection of the prostate (TURP) in Sweden. In this extreme case-control design, cases (N=132) died of prostate cancer and controls (N=168) survived at least 8 years following diagnosis without death from prostate cancer or a competing cause. Immunohistochemistry was undertaken with a polyclonal rabbit anti-human NOS2 antibody (Abcam) and the Ventana (Roche) semi-automated staining system. Two observers individually scored the staining according to intensity and number of positive cells from 0-3. The median value across cores in each patient were then categorized as <1, >1-<2, and >2, separately for epithelial and stromal compartments. Odds ratios for lethal prostate cancer were estimated with logistic regression controlling for the matching factors (age, calendar year of diagnosis), as well as tumor stage, Gleason score, and percent tumor. iNOS was expressed by stromal-associated M1 macrophages and fibroblasts, as well as tumor cells. Gleason score was positively associated with both stromal and epithelial iNOS staining. In the stroma, there was no statistically significant association between iNOS expression and lethal prostate cancer after adjustment for clinical covariates. However, the odds of lethal prostate cancer increased with tumor expression of iNOS in the fully adjusted model. Compared to patients with the lowest category of iNOS expression, the odds ratios for lethal prostate cancer were 2.96 (95% CI: 1.26-6.96) for patients in the second category and 3.80 (95% CI: 1.45-9.97) for patients in the top category. These results suggest that iNOS may help to identify patients with aggressive prostate cancer at the time of diagnosis, or may be a therapeutic target. Given previously reported in vitro data suggesting that iNOS promotes proliferation of androgen-independent prostate tumors, future analyses will investigate association between iNOS expression and time to castration-resistant prostate cancer in this patient population.
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| 60. |
- Salim, Agus, et al.
(författare)
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Analysis of incidence and prognosis from 'extreme' case-control designs
- 2014
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Ingår i: Statistics in Medicine. - : Wiley-Blackwell. - 0277-6715 .- 1097-0258. ; 33:30, s. 5388-5398
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Tidskriftsartikel (refereegranskat)abstract
- The significant investment in measuring biomarkers has prompted investigators to improve cost-efficiency by sub-sampling in non-standard study designs. For example, investigators studying prognosis may assume that any differences in biomarkers are likely to be most apparent in an extreme sample of the earliest deaths and the longest-surviving controls. Simple logistic regression analysis of such data does not exploit the information available in the survival time, and statistical methods that model the sampling scheme may be more efficient. We derive likelihood equations that reflect the complex sampling scheme in unmatched and matched extreme' case-control designs. We investigated the performance and power of the method in simulation experiments, with a range of underlying hazard ratios and study sizes. Our proposed method resulted in hazard ratio estimates close to those obtained from the full cohort. The standard error estimates also performed well when compared with the empirical variance. In an application to a study investigating markers for lethal prostate cancer, an extreme case-control sample of lethal cases and the longest-surviving controls provided estimates of the effect of Gleason score in close agreement with analysis of all the data. By using the information in the sampling design, our method enables efficient and valid estimation of the underlying hazard ratio from a study design that is intuitive and easily implemented.
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