| 1. |
- Dahlman, A., et al.
(författare)
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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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Ingår i: Prostate Cancer and Prostatic Diseases. - : Nature Publishing Group. - 1365-7852 .- 1476-5608. ; 13:4, s. 369-375
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Tidskriftsartikel (refereegranskat)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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| 2. |
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| 3. |
- Rohrmann, S., et al.
(författare)
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Smoking and the risk of prostate cancer in the European Prospective Investigation into Cancer and Nutrition
- 2013
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 108:3, s. 708-714
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Tidskriftsartikel (refereegranskat)abstract
- Background: Smoking is not associated with prostate cancer incidence in most studies, but associations between smoking and fatal prostate cancer have been reported. Methods: During 1992 and 2000, lifestyle information was assessed via questionnaires and personal interview in a cohort of 145112 European men. Until 2009, 4623 incident cases of prostate cancer were identified, including 1517 cases of low-grade, 396 cases of high grade, 1516 cases of localised, 808 cases of advanced disease, and 432 fatal cases. Multivariable Cox proportional hazards regression models were used to examine the association of smoking status, smoking intensity, and smoking duration with the risk of incident and fatal prostate cancer. Results: Compared with never smokers, current smokers had a reduced risk of prostate cancer (RR = 0.90, 95% CI: 0.83-0.97), which was statistically significant for localised and low-grade disease, but not for advanced or high-grade disease. In contrast, heavy smokers (25+ cigarettes per day) and men who had smoked for a long time (40+ years) had a higher risk of prostate cancer death (RR = 1.81, 95% CI: 1.11-2.93; RR = 1.38, 95% CI: 1.01-1.87, respectively). Conclusion: The observation of an increased prostate cancer mortality among heavy smokers confirms the results of previous prospective studies.
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| 4. |
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| 5. |
- Pérez, Moisés, et al.
(författare)
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The fungal metabolite galiellalactone interferes with the nuclear import of NF-κB and inhibits HIV-1 replication.
- 2014
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Ingår i: Chemico-Biological Interactions. - : Elsevier BV. - 1872-7786 .- 0009-2797. ; 214:Mar 11, s. 69-76
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Tidskriftsartikel (refereegranskat)abstract
- Galiellalactone (GL) is a metabolite produced by the fungus Galiella rufa that presents antitumor and immunomodulatory activities. GL interferes with the binding to DNA of signal transducer and activator of transcription (STAT)-3 and also inhibits other signal pathways such as NF-κB, but the mechanism of action in this pathway remains unknown. In this study we report that GL inhibits vesicular stomatitis virus-recombinant HIV-1 infection and the NF-κB-dependent transcriptional activity of the HIV-LTR promoter. We found that GL prevents the binding of NF-κB to DNA but neither affects the phosphorylation and degradation of NF-κB inhibitory protein, IκBα, nor the phosphorylation and acetylation of the NF-κB p65 subunit. However, GL prevents the association of p65 with the importin α3 impairing the nuclear translocation of this transcription factor. Using a biotinylated probe we found that GL binds to p65 but not to importin α3. Therefore, GL is a dual NF-κB/STAT3 inhibitor that could serve as a lead compound for the development of novel drugs against HIV-1, cancer and inflammatory diseases.
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| 6. |
- Ahlqvist, Kristofer, et al.
(författare)
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Expression of Id proteins is regulated by the Bcl-3 proto-oncogene in prostate cancer.
- 2013
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Ingår i: Oncogene. - : Springer Science and Business Media LLC. - 1476-5594 .- 0950-9232. ; 32:12, s. 1601-1608
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Tidskriftsartikel (refereegranskat)abstract
- B-cell leukemia 3 (Bcl-3) is a member of the inhibitor of κB family, which regulates a wide range of biological processes by functioning as a transcriptional activator or as a repressor of target genes. As high levels of Bcl-3 expression and activation have been detected in different types of human cancer, Bcl-3 has been labeled a proto-oncogene. Our study uncovered a markedly upregulated Bcl-3 expression in human prostate cancer (PCa), where inflammatory cell infiltration was observed. Elevated Bcl-3 expression in PCa was dependent on the proinflammatory cytokine interleukin-6-mediated STAT3 activation. Microarray analyses, using Bcl-3 knockdown in PCa cells, identified the inhibitor of DNA-binding (Id) family of helix-loop-helix proteins as potential Bcl-3-regulated genes. Bcl-3 knockdown reduced the abundance of Id-1 and Id-2 proteins and boosted PCa cells to be more receptive to undergoing apoptosis following treatment with anticancer drug. Our data imply that inactivation of Bcl-3 may lead to sensitization of cancer cells to chemotherapeutic drug-induced apoptosis, thus suggesting a potential therapeutic strategy in PCa treatment.Oncogene advance online publication, 14 May 2012; doi:10.1038/onc.2012.175.
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| 7. |
- Barbieri, Christopher E., et al.
(författare)
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The Mutational Landscape of Prostate Cancer
- 2013
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Ingår i: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 64:4, s. 567-576
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Forskningsöversikt (refereegranskat)abstract
- Context: Prostate cancer (PCa) is a clinically heterogeneous disease with marked variability in patient outcomes. Molecular characterization has revealed striking mutational heterogeneity that may underlie the variable clinical course of the disease. Objective: In this review, we discuss the common genomic alterations that form the molecular basis of PCa, their functional significance, and the potential to translate this knowledge into patient care. Evidence acquisition: We reviewed the relevant literature, with a particular focus on recent studies on somatic alterations in PCa. Evidence synthesis: Advances in sequencing technology have resulted in an explosion of data regarding the mutational events underlying the development and progression of PCa. Heterogeneity is the norm; few abnormalities in specific genes are highly recurrent, but alterations in certain signaling pathways do predominate. These alterations include those in pathways known to affect tumorigenesis in a wide spectrum of tissues, such as the phosphoinositide 3-kinase/phosphatase and tensin homolog/Akt pathway, cell cycle regulation, and chromatin regulation. Alterations more specific to PCa are also observed, particularly gene fusions of ETS transcription factors and alterations in androgen signaling. Mounting data suggest that PCa can be subdivided based on a molecular profile of genetic alterations. Conclusions: Major advances have been made in cataloging the genomic alterations in PCa and understanding the molecular mechanisms underlying the disease. These findings raise the possibility that PCa could soon transition from being a poorly understood, heterogeneous disease with a variable clinical course to being a collection of homogenous subtypes identifiable by molecular criteria, associated with distinct risk profiles, and perhaps amenable to specific management strategies or targeted therapies. (C) 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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| 8. |
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| 9. |
- Fine, Samson W., et al.
(författare)
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A Contemporary Update on Pathology Reporting for Prostate Cancer: Biopsy and Radical Prostatectomy Specimens
- 2012
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Ingår i: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 62:1, s. 20-39
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Forskningsöversikt (refereegranskat)abstract
- Context: The diagnosis of and reporting parameters for prostate cancer (PCa) have evolved over time, yet they remain key components in predicting clinical outcomes. Objective: Update pathology reporting standards for PCa. Evidence acquisition: A thorough literature review was performed for articles discussing PCa handling, grading, staging, and reporting published as of September 15, 2011. Electronic articles published ahead of print were also considered. Proceedings of recent international conferences addressing these areas were extensively reviewed. Evidence synthesis: Two main areas of reporting were examined: (1) prostatic needle biopsy, including handling, contemporary Gleason grading, extent of involvement, and high-risk lesions/precursors and (2) radical prostatectomy (RP), including sectioning, multifocality, Gleason grading, staging of organ-confined and extraprostatic disease, lymph node involvement, tumor volume, and lymphovascular invasion. For each category, consensus views, controversial areas, and clinical import were reviewed. Conclusions: Modern prostate needle biopsy and RP reports are extremely detailed so as to maximize clinical utility. Accurate diagnosis of cancer-specific features requires up-to-date knowledge of grading, quantitation, and staging criteria. While some areas remain controversial, efforts to codify existing knowledge have had a significant impact on pathology practice. (C) 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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| 10. |
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| 11. |
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| 12. |
- Lilja, Hans, et al.
(författare)
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Prediction of Significant Prostate Cancer Diagnosed 20 to 30 Years Later With a Single Measure of Prostate-Specific Antigen at or Before Age 50
- 2011
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Ingår i: Cancer. - : Wiley. - 1097-0142 .- 0008-543X. ; 117:6, s. 1210-1219
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We previously reported that a single prostate-specific antigen (PSA) measured at ages 44-50 was highly predictive of subsequent prostate cancer diagnosis in an unscreened population. Here we report an additional 7 years of follow-up. This provides replication using an independent data set and allows estimates of the association between early PSA and subsequent advanced cancer (clinical stage >= T3 or metastases at diagnosis). METHODS: Blood was collected from 21,277 men in a Swedish city (74% participation rate) during 1974-1986 at ages 33-50. Through 2006, prostate cancer was diagnosed in 1408 participants; we measured PSA in archived plasma for 1312 of these cases (93%) and for 3728 controls. RESULTS: At a median follow-up of 23 years, baseline PSA was strongly associated with subsequent prostate cancer (area under the curve, 0.72; 95% Cl, 0.70-0.74; for advanced cancer, 0.75; 95% Cl, 0.72-0.78). Associations between PSA and prostate cancer were virtually identical for the initial and replication data sets, with 81% of advanced cases (95% Cl, 77%-86%) found in men with PSA above the median (0.63 ng/mL at ages 44-50). CONCLUSIONS: A single PSA at or before age 50 predicts advanced prostate cancer diagnosed up to 30 years later. Use of early PSA to stratify risk would allow a large group of low-risk men to be screened less often but increase frequency of testing on a more limited number of high-risk men. This is likely to improve the ratio of benefit to harm for screening. Cancer 2011;117:1210-9. (C) 2010 American Cancer Society
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| 13. |
- Mack, Natalie A., et al.
(författare)
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beta 2-syntrophin and Par-3 promote an apicobasal Rac activity gradient at cell-cell junctions by differentially regulating Tiam1 activity
- 2012
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Ingår i: Nature Cell Biology. - : Springer Science and Business Media LLC. - 1465-7392 .- 1476-4679. ; 14:11, s. 1169-1180
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Tidskriftsartikel (refereegranskat)abstract
- Although Rac and its activator Tiam1 are known to stimulate cell-cell adhesion, the mechanisms regulating their activity in cell-cell junction formation are poorly understood. Here, we identify beta 2-syntrophin as a Tiam1 interactor required for optimal cell-cell adhesion. We show that during tight-junction (TJ) assembly beta 2-syntrophin promotes Tiam1-Rac activity, in contrast to the function of the apical determinant Par-3 whose inhibition of Tiam1-Rac activity is necessary for TJ assembly. We further demonstrate that beta 2-syntrophin localizes more basally than Par-3 at cell-cell junctions, thus generating an apicobasal Rac activity gradient at developing cell-cell junctions. Targeting active Rac to TJs shows that this gradient is required for optimal TJ assembly and apical lumen formation. Consistently, beta 2-syntrophin depletion perturbs Tiam1 and Rac localization at cell-cell junctions and causes defects in apical lumen formation. We conclude that beta 2-syntrophin and Par-3 fine-tune Rac activity along cell-cell junctions controlling TJ assembly and the establishment of apicobasal polariy.
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| 14. |
- Magnusson, Kristina, et al.
(författare)
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SATB2 in Combination With Cytokeratin 20 Identifies Over 95% of all Colorectal Carcinomas
- 2011
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Ingår i: American Journal of Surgical Pathology. - 0147-5185 .- 1532-0979. ; 35:7, s. 937-948
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Tidskriftsartikel (refereegranskat)abstract
- The special AT-rich sequence-binding protein 2 (SATB2), a nuclear matrix-associated transcription factor and epigenetic regulator, was identified as a tissue type-specific protein when screening protein expression patterns in human normal and cancer tissues using an antibody-based proteomics approach. In this respect, the SATB2 protein shows a selective pattern of expression and, within cells of epithelial lineages, SATB2 expression is restricted to glandular cells lining the lower gastrointestinal tract. The expression of SATB2 protein is primarily preserved in cancer cells of colorectal origin, indicating that SATB2 could function as a clinically useful diagnostic marker to distinguish colorectal cancer (CRC) from other types of cancer. The aim of this study was to further explore and validate the specific expression pattern of SATB2 as a clinical biomarker and to compare SATB2 with the well-known cytokeratin 20 (CK20). Immunohistochemistry was used to analyze the extent of SATB2 expression in tissue microarrays with tumors from 9 independent cohorts of patients with primary and metastatic CRCs (n = 1882). Our results show that SATB2 is a sensitive and highly specific marker for CRC with distinct positivity in 85% of all CRCs, and that SATB2 and/or CK20 was positive in 97% of CRCs. In conclusion, the specific expression of SATB2 in a large majority of CRCs suggests that SATB2 can be used as an important complementary tool for the differential diagnosis of carcinoma of unknown primary origin.
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| 15. |
- Qundos, Ulrika, et al.
(författare)
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Analysis of plasma from prostate cancer patients links decreased carnosine dipeptidase 1 levels to lymph node metastasis
- 2014
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Ingår i: Translational Proteomics. - : Elsevier BV. - 2212-9634 .- 2212-9626. ; 2:1, s. 14-24
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Tidskriftsartikel (refereegranskat)abstract
- There is a need for a better differentiation of aggressive tumors in prostate cancer to design a tailored treatment for each patient, preferably by a minimally invasive analysis of blood samples. In a previous study, we discovered a decrease of plasma levels of carnosine dipeptidase 1 (CNDP1) in association with aggressive prostate cancer. Now this relation has been investigated and characterized further by generating several new antibodies for extended analysis of CNDP1 in plasma. Multi-antibody sandwich assays were developed and applied to 1214 samples from two Swedish cohorts that confirmed decreased levels of CNDP1 in plasma from patients with advanced disease. Therein, data from CNDP1 assays allowed a better differentiation between tumor N stages than clinical tPSA, but did not when classifying T or M stages. Further investigations can now elucidate mechanisms behind decreasing levels of CNDP1 in plasma and primary in regards to lymph node metastasis.
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| 16. |
- Schaar, Viveka, et al.
(författare)
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Multicomponent Moraxella catarrhalis outer membrane vesicles induce an inflammatory response and are internalized by human epithelial cells.
- 2011
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Ingår i: Cellular Microbiology. - : Hindawi Limited. - 1462-5814. ; Dec, s. 432-449
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Tidskriftsartikel (refereegranskat)abstract
- Moraxella catarrhalis is an emerging human respiratory pathogen in patients with chronic obstructive pulmonary disease (COPD) and in children with acute otitis media. The specific secretion machinery known as outer membrane vesicles (OMVs) is a mechanism by which Gram-negative pathogens interact with host cells during infection. We identified 57 proteins in M. catarrhalis OMVs using a proteomics approach combining two-dimensional SDS-PAGE and MALDI-TOF mass spectrometry analysis. The OMVs contained known surface proteins such as ubiquitous surface proteins (Usp) A1/A2, and Moraxella IgD-binding protein (MID). Most of the proteins are adhesins/virulence factors triggering the immune response, but also aid bacteria to evade the host defence. FITC-stained OMVs bound to lipid raft domains in alveolar epithelial cells and were internalized after interaction with Toll-like receptor 2 (TLR2), suggesting a delivery to the host tissue of a large and complex group of OMV-attributed proteins. Interestingly, OMVs modulated the pro-inflammatory response in epithelial cells, and UspA1-bearing OMVs were found to specifically downregulate the reaction. When mice were exposed to OMVs, a pulmonary inflammation was clearly seen. Our findings indicate that Moraxella OMVs are highly biologically active, transport main bacterial virulence factors and may modulate the epithelial pro-inflammatory response.
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| 17. |
- Secin, Fernando P., et al.
(författare)
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The Learning Curve for Laparoscopic Radical Prostatectomy: An International Multicenter Study
- 2010
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Ingår i: Journal of Urology. - : Ovid Technologies (Wolters Kluwer Health). - 1527-3792 .- 0022-5347. ; 184:6, s. 2291-2296
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: It is not yet possible to estimate the number of cases required for a beginner to become expert in laparoscopic radical prostatectomy. We estimated the learning curve of laparoscopic radical prostatectomy for positive surgical margins compared to a published learning curve for open radical prostatectomy. Materials and Methods: We reviewed records from 8,544 consecutive patients with prostate cancer treated laparoscopically by 51 surgeons at 14 academic institutions in Europe and the United States. The probability of a positive surgical margin was calculated as a function of surgeon experience with adjustment for pathological stage, Gleason score and prostate specific antigen. A second model incorporated prior experience with open radical prostatectomy and surgeon generation. Results: Positive surgical margins occurred in 1,862 patients (22%). There was an apparent improvement in surgical margin rates up to a plateau at 200 to 250 surgeries. Changes in margin rates once this plateau was reached were relatively minimal relative to the CIs. The absolute risk difference for 10 vs 250 prior surgeries was 4.8% (95% CI 1.5, 8.5). Neither surgeon generation nor prior open radical prostatectomy experience was statistically significant when added to the model. The rate of decrease in positive surgical margins was more rapid in the open vs laparoscopic learning curve. Conclusions: The learning curve for surgical margins after laparoscopic radical prostatectomy plateaus at approximately 200 to 250 cases. Prior open experience and surgeon generation do not improve the margin rate, suggesting that the rate is primarily a function of specifically laparoscopic training and experience.
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| 19. |
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