umu.sePublications
Change search
Refine search result
1 - 28 of 28
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 1.
    Adamo, Hanibal Hani
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Hammarsten, Peter
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Hägglöf, Christina
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Scherdin, Tove Dahl
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Egevad, Lars
    Stattin, Paer
    Halin Bergström, Sofia
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Prostate cancer induces C/EBP expression in surrounding epithelial cells which relates to tumor aggressiveness and patient outcome2019In: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 79, no 5Article in journal (Refereed)
    Abstract [en]

    Background: Implantation of rat prostate cancer cells into the normal rat prostate results in tumor-stimulating adaptations in the tumor-bearing organ. Similar changes are seen in prostate cancer patients and they are related to outcome. One gene previously found to be upregulated in the non-malignant part of tumor-bearing prostate lobe in rats was the transcription factor CCAAT/enhancer-binding protein- (C/EBP).

    Methods: To explore this further, we examined C/EBP expression by quantitative RT-PCR, immunohistochemistry, and Western blot in normal rat prostate tissue surrounding slow-growing non-metastatic Dunning G, rapidly growing poorly metastatic (AT-1), and rapidly growing highly metastatic (MatLyLu) rat prostate tumors?and also by immunohistochemistry in a tissue microarray (TMA) from prostate cancer patients managed by watchful waiting.

    Results: In rats, C/EBP mRNA expression was upregulated in the surrounding tumor-bearing prostate lobe. In tumors and in the surrounding non-malignant prostate tissue, C/EBP was detected by immunohistochemistry in some epithelial cells and in infiltrating macrophages. The magnitude of glandular epithelial C/EBP expression in the tumor-bearing prostates was associated with tumor size, distance to the tumor, and metastatic capacity. In prostate cancer patients, high expression of C/EBP in glandular epithelial cells in the surrounding tumor-bearing tissue was associated with accumulation of M1 macrophages (iNOS+) and favorable outcome. High expression of C/EBP in tumor epithelial cells was associated with high Gleason score, high tumor cell proliferation, metastases, and poor outcome.

    Conclusions: This study suggest that the expression of C/EBP-beta, a transcription factor mediating multiple biological effects, is differentially expressed both in the benign parts of the tumor-bearing prostate and in prostate tumors, and that alterations in this may be related to patient outcome.

  • 2.
    Bylund, Annika
    et al.
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences.
    Zhang, Jie-Xian
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Nutritional Research.
    Bergh, Anders
    Damber, Jan-Erik
    Widmark, Anders
    Johansson, Anders
    Adlercreutz, Herman
    Åman, Per
    Shepherd, Martin J
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Nutritional Research.
    Rye bran and soy protein delay growth and increase apoptosis of human LNCaP prostate adenocarcinoma in nude mice2000In: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 42, no 4, p. 304-314Article in journal (Refereed)
  • 3. Christensen, G Bryce
    et al.
    Baffoe-Bonnie, Agnes B
    George, Asha
    Powell, Isaac
    Bailey-Wilson, Joan E
    Carpten, John D
    Giles, Graham G
    Hopper, John L
    Severi, Gianluca
    English, Dallas R
    Foulkes, William D
    Maehle, Lovise
    Moller, Pal
    Eeles, Ros
    Easton, Douglas
    Badzioch, Michael D
    Whittemore, Alice S
    Oakley-Girvan, Ingrid
    Hsieh, Chih-Lin
    Dimitrov, Latchezar
    Xu, Jianfeng
    Stanford, Janet L
    Johanneson, Bo
    Deutsch, Kerry
    McIntosh, Laura
    Ostrander, Elaine A
    Wiley, Kathleen E
    Isaacs, Sarah D
    Walsh, Patrick C
    Isaacs, William B
    Thibodeau, Stephen N
    McDonnell, Shannon K
    Hebbring, Scott
    Schaid, Daniel J
    Lange, Ethan M
    Cooney, Kathleen A
    Tammela, Teuvo L J
    Schleutker, Johanna
    Paiss, Thomas
    Maier, Christiane
    Grönberg, Henrik
    Wiklund, Fredrik
    Emanuelsson, Monica
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Farnham, James M
    Cannon-Albright, Lisa A
    Camp, Nicola J
    Genome-wide linkage analysis of 1,233 prostate cancer pedigrees from the International Consortium for prostate cancer Genetics using novel sumLINK and sumLOD analyses.2010In: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 70, p. 735-744Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Prostate cancer (PC) is generally believed to have a strong inherited component, but the search for susceptibility genes has been hindered by the effects of genetic heterogeneity. The recently developed sumLINK and sumLOD statistics are powerful tools for linkage analysis in the presence of heterogeneity. METHODS: We performed a secondary analysis of 1,233 PC pedigrees from the International Consortium for Prostate Cancer Genetics (ICPCG) using two novel statistics, the sumLINK and sumLOD. For both statistics, dominant and recessive genetic models were considered. False discovery rate (FDR) analysis was conducted to assess the effects of multiple testing. RESULTS: Our analysis identified significant linkage evidence at chromosome 22q12, confirming previous findings by the initial conventional analyses of the same ICPCG data. Twelve other regions were identified with genome-wide suggestive evidence for linkage. Seven regions (1q23, 5q11, 5q35, 6p21, 8q12, 11q13, 20p11-q11) are near loci previously identified in the initial ICPCG pooled data analysis or the subset of aggressive PC pedigrees. Three other regions (1p12, 8p23, 19q13) confirm loci reported by others, and two (2p24, 6q27) are novel susceptibility loci. FDR testing indicates that over 70% of these results are likely true positive findings. Statistical recombinant mapping narrowed regions to an average of 9 cM. CONCLUSIONS: Our results represent genomic regions with the greatest consistency of positive linkage evidence across a very large collection of high-risk PC pedigrees using new statistical tests that deal powerfully with heterogeneity. These regions are excellent candidates for further study to identify PC predisposition genes. Prostate (c) 2010 Wiley-Liss, Inc.

  • 4.
    Djusberg, Erik
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Jernberg, Emma
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Thysell, Elin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Golovleva, Irina
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Lundberg, Pia
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Crnalic, Sead
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Widmark, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Brattsand, Maria
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Wikström, Pernilla
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    High Levels of the AR-V7 Splice Variant and Co-Amplification of the Golgi Protein Coding YIPF6 in AR Amplified Prostate Cancer Bone Metastases2017In: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 77, no 6, p. 625-638Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The relation between androgen receptor (AR) gene amplification and other mechanisms behind castration-resistant prostate cancer (CRPC), such as expression of constitutively active AR variants and steroid-converting enzymes has been poorly examined. Specific aim was to examine AR amplification in PC bone metastases and to explore molecular and functional consequences of this, with the long-term goal of identifying novel molecular targets for treatment. METHODS: Gene amplification was assessed by fluorescence in situ hybridization in cryo-sections of clinical PC bone metastases (n = 40) and by PCR-based copy number variation analysis. Whole genome mRNA expression was analyzed using H12 Illumina Beadchip arrays and specific transcript levels were quantified by qRT-PCR. Protein localization was analyzed using immunohistochemistry and confocal microscopy. The YIPF6 mRNA expression was transiently knocked down and stably overexpressed in the 22Rv1 cell line as representative for CRPC, and effects on cell proliferation, colony formation, migration, and invasion were determined in vitro. Extracellular vesicles (EVs) were isolated from cell cultures using size-exclusion chromatography and enumerated by nanoparticle tracking analysis. Protein content was identified by LC-MS/MS analysis. Blood coagulation was measured as activated partial thromboplastin time (APTT). Functional enrichment analysis was performed using the MetaCore software. RESULTS: AR amplification was detected in 16 (53%) of the bone metastases examined from CRPC patients (n = 30), and in none from the untreated patients (n = 10). Metastases with AR amplification showed high AR and AR-V7 mRNA levels, increased nuclear AR immunostaining, and co-amplification of genes such as YIPF6 in the AR proximity at Xq12. The YIPF6 protein was localized to the Golgi apparatus. YIPF6 overexpression in 22Rv1 cells resulted in reduced cell proliferation and colony formation, and in enhanced EV secretion. EVs from YIPF6 overproducing 22Rv1 cells were enriched for proteins involved in blood coagulation and, accordingly, decreased the APTT in a dose-dependent fashion. CONCLUSIONS: AR amplified CRPC bone metastases show high AR-V7 expression that probably gives resistance to AR-targeting drugs. Co-amplification of the Golgi protein coding YIPF6 gene with the AR may enhance the secretion of pro-coagulative EVs from cancer cells and thereby stimulate tumor progression and increase the coagulopathy risk in CRPC patients.

  • 5. Erlandsson, Ann
    et al.
    Carlsson, Jessica
    Lundholm, Marie
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Fält, Anna
    Andersson, Sven-Olof
    Andrén, Ove
    Davidsson, Sabina
    M2 macrophages and regulatory T cells in lethal prostate cancer2019In: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 79, no 4, p. 363-369Article in journal (Refereed)
    Abstract [en]

    Background: Prostate cancer (PCa) is one of the most frequently diagnosed cancers in the world. Emerging evidence suggests that inflammatory cells such as M2 macrophages and regulatory T cells (Tregs) can contribute to cancer progression by suppressing the anti‐tumor immune response. This study investigated the number of CD163‐positive M2 macrophages in PCa tissue. It also investigated the correlation and interaction of M2 macrophages and Tregs.

    Methods: This nested case‐control study included subjects from a cohort of men diagnosed with PCa as an incidental finding during transurethral resection of the prostate. The cases were 225 men who died from PCa, and the controls were 367 men who survived more than 10 years after PCa diagnosis without disease progression. Infiltrating CD163‐positive M2 macrophages and FOXP3/CD4‐positive Tregs in PCa tissue were identified using immunohistochemistry. The correlation and interaction of M2 macrophages and Tregs were assessed using Spearman's rank‐order correlation and a likelihood test, respectively. Logistic regression was used to estimate odds ratios (ORs) for lethal PCa and macrophage counts.

    Results: The number of M2 macrophages and Tregs showed a significant correlation (P < 0.001) but no interactions. The OR for lethal PCa was 1.93 (95%CI: 1.23‐3.03) for men with high numbers of M2 macrophages. Also for cases with uncertain outcome (GS categories 3 + 4 and 4 + 3) high numbers of M2 macrophages does predict a poorer prognosis.

    Conclusions: Our data showed that men with high numbers of M2 macrophages in the prostate tumor environment had increased odds of dying of PCa. It is possible that M2 macrophages, together with other suppressor cells such as Tregs, promote an immunosuppressive environment.

  • 6.
    Halin Bergström, Sofia
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Järemo, Helena
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Nilsson, Maria
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Adamo, Hanibal Hani
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Prostate tumors downregulate microseminoprotein-beta (MSMB) in the surrounding benign prostate epithelium and this response is associated with tumor aggressiveness2018In: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 78, no 4, p. 257-265Article in journal (Refereed)
    Abstract [en]

    Background: Microseminoprotein-beta (MSMB) is a major secretory product from prostate epithelial cells. MSMB synthesis is decreased in prostate tumors in relation to tumor grade. MSMB levels are also reduced in the circulation and MSMB is therefore used as a serum biomarker for prostate cancer. We hypothesized that cancers induce a reduction in MSMB synthesis also in the benign parts of the prostate, and that the magnitude of this response is related to tumor aggressiveness. Reduced levels of MSMB in the circulation could therefore be a consequence of reduced MSMB expression not only in tumor tissue but also in the benign prostate tissue.

    Methods: MSMB expression was analyzed in prostatectomy specimens from 36 patients using immunohistochemistry and qRT-PCR. MSMB expression in the benign prostate tissue was analyzed in relation to Gleason score, tumor stage, and distance to the tumor. Furthermore, Dunning rat prostate tumors with different aggressiveness were implanted into the prostate of Copenhagen rats to study if this affected the MSMB expression in the tumor-adjacent benign rat prostate tissue.

    Results: In prostatectomy specimens, MSMB expression was reduced in prostate tumors but also in the tumor-adjacent benign parts of the prostate. The reduction in tumor MSMB was related to tumor grade and stage, and the reduction in the benign parts of the prostate to tumor grade, stage, and distance to the tumor. Implantation of Dunning cancer cells into the rat prostate resulted in reduced MSMB protein levels in the tumor-adjacent benign prostate tissue. Rapidly growing and metastatic MatLyLu tumors had a more pronounced effect than slow-growing non-metastatic G tumors.

    Conclusion: Our data suggest that aggressive prostate tumors suppress MSMB synthesis in the benign prostate and that this could explain why serum levels of MSMB are decreased in prostate cancer patients. This study suggests that markers for aggressive cancer can be found among factors altered in parallel in prostate tumors and in the adjacent benign tissue.

  • 7.
    Halin, Sofia
    et al.
    Umeå University, Faculty of Medicine, Medical Biosciences, Pathology.
    Hammarsten, Peter
    Umeå University, Faculty of Medicine, Medical Biosciences, Pathology.
    Wikström, Pernilla
    Umeå University, Faculty of Medicine, Medical Biosciences, Pathology.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Medical Biosciences, Pathology.
    Androgen-insensitive prostate cancer cells transiently respond to castration treatment when growing in an androgen-dependent prostate environment.2007In: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 67, no 4, p. 370-7Article in journal (Refereed)
  • 8.
    Häggström, Jenny
    et al.
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Cipriano, Mariateresa
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Plym Forshell, Linus
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Persson, Emma
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Hammarsten, Peter
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Stella, Nephi
    Fowler, Christopher J.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Potential upstream regulators of cannabinoid receptor 1 signaling in prostate cancer: A Bayesian network analysis of data from a tissue microarray2014In: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 74, no 11, p. 1107-1117Article in journal (Refereed)
    Abstract [en]

    BACKGROUND The endocannabinoid system regulates cancer cell proliferation, and in prostate cancer a high cannabinoid CB1 receptor expression is associated with a poor prognosis. Down-stream mediators of CB1 receptor signaling in prostate cancer are known, but information on potential upstream regulators is lacking. RESULTS Data from a well-characterized tumor tissue microarray were used for a Bayesian network analysis using the max-min hill-climbing method. In non-malignant tissue samples, a directionality of pEGFR (the phosphorylated form of the epidermal growth factor receptor) CB1 receptors were found regardless as to whether the endocannabinoid metabolizing enzyme fatty acid amide hydrolase (FAAH) was included as a parameter. A similar result was found in the tumor tissue, but only when FAAH was included in the analysis. A second regulatory pathway, from the growth factor receptor ErbB2 FAAH was also identified in the tumor samples. Transfection of AT1 prostate cancer cells with CB1 receptors induced a sensitivity to the growth-inhibiting effects of the CB receptor agonist CP55,940. The sensitivity was not dependent upon the level of receptor expression. Thus a high CB1 receptor expression alone does not drive the cells towards a survival phenotype in the presence of a CB receptor agonist. CONCLUSIONS The data identify two potential regulators of the endocannabinoid system in prostate cancer and allow the construction of a model of a dysregulated endocannabinoid signaling network in this tumor. Further studies should be designed to test the veracity of the predictions of the network analysis in prostate cancer and other solid tumors.

  • 9.
    Häggström, S
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Bergh, A
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Damber, J E
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Vascular endothelial growth factor content in metastasizing and nonmetastasizing Dunning prostatic adenocarcinoma.2000In: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 45, no 1, p. 42-50Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Tumor angiogenesis is important in progressive tumor growth and metastasis. In the normal rat prostate and in androgen-sensitive prostate tumors androgen ablation causes an involution of the vasculature and a decrease in the vascular endothelial growth factor (VEGF) levels before regression of the prostate gland. To examine whether angiogenesis and metastasis are regulated by VEGF in androgen-insensitive and metastasizing prostate tumors, five Dunning rat prostate cancer sublines were tested; the androgen-sensitive, nonmetastasizing R3327 PAP, and the androgen-insensitive, low metastasizing AT-1, and the three androgen-insensitive, metastasizing AT-2, AT-3, and MatLyLu Dunning prostatic adenocarcinomas.

    METHODS: VEGF levels were quantified in the rat dorsolateral prostate and in the five Dunning sublines using competitive RT-PCR, Western blot, and Elisa. Vascular density was determined by factor VIII staining.

    RESULTS: VEGF mRNA was increased in all tumors compared with normal prostates. The two metastatic sublines AT-3 and MatLyLu and the nonmetastatic subline AT-1 showed the highest VEGF mRNA expression. VEGF protein levels in the prostate gland showed increased expression in the metastatic sublines, AT-2, AT-3, and MatLyLu, compared with the nonmetastatic AT-1 subline and the ventral prostate. VEGF proteins in serum were highest in the metastatic AT-3 subline. The vessel density was highest in the two highly metastatic sublines AT-3 and MatLyLu.

    CONCLUSIONS: Our results suggest that VEGF levels are associated with microvessel density and the previously established metastatic pattern of these rat prostate tumor systems.

  • 10.
    Häggström, S
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Wikström, P
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Bergh, A
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Damber, J E
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Expression of vascular endothelial growth factor and its receptors in the rat ventral prostate and Dunning R3327 PAP adenocarcinoma before and after castration.1998In: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 36, no 2, p. 71-9Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Angiogenesis is important for prostate organogenesis and prostate cancer progression. It is not yet known whether androgens promote part of their control of prostate structure and function by influencing angiogenesis. The aim of this study was to explore the possible androgenic regulation of the angiogenic factor vascular endothelial growth factor (VEGF) and its receptors flt-1 and flk-1/KDR in the rat ventral prostate (VP) and Dunning R3327 PAP adenocarcinoma.

    METHODS: RNA was prepared from VP and tumors of intact and castrated rats. VEGF, flt-1, and flk-1/KDR mRNA levels were determined using competitive RT-PCR.

    RESULTS: VEGF121, VEGF165, and VEGF189 together with flt-1 and flk-1/KDR mRNA were detected. The VEGF, but not flt-1 mRNA levels were significantly decreased in the VP after castration. The Dunning tumor expressed high levels of mRNA for VEGF and its receptors compared to the VP. The flt-1 mRNA level in the tumor increased after castration, while the VEGF mRNA levels were unchanged.

    CONCLUSIONS: Decreased mRNA expression of VEGF, but not flt-1, was found in the rat VP after castration. However, in the Dunning tumor, castration did not alter the expression of VEGF mRNA. Moreover, elevated levels of both mRNA for VEGF and its receptors relative to the VP were observed, indicating that the VEGF system may be important for Dunning tumor development.

  • 11.
    Johansson, Anna
    et al.
    Umeå University, Faculty of Medicine, Medical Biosciences. Umeå University, Faculty of Medicine, Medical Biosciences, Pathology.
    Jones, Jonathan
    Umeå University, Faculty of Medicine, Radiation Sciences. Umeå University, Faculty of Medicine, Radiation Sciences, Diagnostic Radiology.
    Pietras, Kristian
    Kilter, Sigrid
    Umeå University, Faculty of Medicine, Medical Biosciences. Umeå University, Faculty of Medicine, Medical Biosciences, Pathology.
    Skytt, Asa
    Umeå University, Faculty of Medicine, Medical Biosciences. Umeå University, Faculty of Medicine, Medical Biosciences, Pathology.
    Rudolfsson, Stina Häggström
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences. Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Urology and Andrology.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Medical Biosciences. Umeå University, Faculty of Medicine, Medical Biosciences, Pathology.
    A stroma targeted therapy enhances castration effects in a transplantable rat prostate cancer model.2007In: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 67, no 15, p. 1664-1676Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Castration results in a major involution of the normal prostate gland. This process is initiated by effects in the prostate stroma and vasculature. Castration-induced regression of androgen sensitive prostate tumors is however less prominent and hypothetically this could be related to a limited stromal/vascular response. We therefore used animal tumor models to explore the importance of stroma and vascular effects, and if castration effects could be enhanced by a simultaneous therapy targeting the tumor stroma. METHODS: Using rats with Dunning PAP and H tumors, stereological methods, immunohistochemistry, and Western blotting, we studied the tumor response 7 and 28 days after castration and after the addition of stroma targeted therapies. RESULTS: In the normal ventral prostate (VP) nuclear androgen receptors (AR) were rapidly downregulated after castration. In contrast, the Dunning tumors downregulated the AR in the cancerous epithelium, but not in the surrounding stroma. Vascular regulators such as the angiopoietins, tie 2, and PDGF-Rbeta were not decreased in the stroma after castration, as observed in the VP, creating an environment that prevents vascular involution. When a tumor stroma targeted therapy inhibiting the tie 2 receptor and the PDGF-Rbeta simultaneously was added to castration it resulted in a decreased vascular density, increased tumor cell apoptosis and decreased tumor growth compared to castration alone. CONCLUSIONS: The stroma in highly differentiated androgen sensitive Dunning tumors is apparently androgen insensitive. If this unresponsive stroma is targeted the effects of castration can be enhanced.

  • 12.
    Johansson, Mattias
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. International Agency for Research against Cancer, Lyon, France.
    McKay, James D
    Rinaldi, Sabina
    Wiklund, Fredrik
    Adami, Hans-Olov
    Grönberg, Henrik
    Kaaks, Rudolf
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Genetic and plasma variation of insulin-like growth factor binding proteins in relation to prostate cancer incidence and survival2009In: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 69, no 12, p. 1281-1291Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Binding proteins regulate bioavailability of insulin-like growth factor-I (IGF-I) in the circulation and affect apoptosis of tumor cells in the prostate. We analyzed genetic variation within genes coding for IGF binding proteins in relation to prostate cancer incidence and survival. We also investigated if circulating IGFBP3 affects prostate cancer-specific survival. MATERIALS AND METHODS: Eleven haplotype tagging SNPs and two single SNPs in the IGFBP1, IGFBP3, and IGFALS genes were genotyped within the CAncer Prostate in Sweden (CAPS) study including 2,774 cases and 1,736 controls. Plasma samples for analyses of total- and intact IGFBP3 levels were available for 1,521 cases and 909 controls. Complete follow-up of vital status was achieved by linkage to the Swedish Cause of Death Register. RESULTS: We found no clear association between the genetic variants and prostate cancer incidence or survival. The rare allele of the IGFBP3 SNP rs2854744 was associated with elevated plasma levels of total IGFBP3 (P(trend) = 9 x 10(-8)), but not intact IGFBP3 (P(trend) = 0.16). Elevated levels of total- (P(trend) = 0.03) and intact IGFBP3 (P(trend) = 6 x 10(-14)) were associated with increased risk of prostate cancer specific death. Treatment and tumor characteristics accounted for the association with total IGFBP3, whereas the association with intact IGFBP3 was attenuated, but still statistically significant in adjusted analysis (P(trend-adjusted) = 0.0004). Elevated intact IGFBP3 was also significantly associated with increased risk of prostate cancer-specific death among patients who were chemically or surgically castrated (P(trend-adjusted) = 0.0003), and among patients who had not been treated (P(trend-adjusted) = 0.02). CONCLUSIONS: Circulating levels of intact IGFBP3 measured after diagnosis is associated with increased risk of prostate cancer-specific death.

  • 13.
    Josefsson, Andreas
    et al.
    Sahlgrenska Cancer Center, Department of Urology, Institute of Clinical Sciences at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Linder, Anna
    Flondell Site, Despina
    Canesin, Giacomo
    Stiehm, Anna
    Anand, Aseem
    Bjartell, Anders
    Damber, Jan-Erik
    Welén, Karin
    Circulating Tumor Cells as a Marker for Progression-free Survival in Metastatic Castration-naïve Prostate Cancer2017In: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 77, no 8, p. 849-858Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Analysis of circulating tumor cells (CTC) is a promising prognostic marker in castration-resistant prostate cancer (CRPC). The aim of this study was to investigate CTC detection and phenotyping as prognostic biomarkers for response to primary androgen deprivation therapy (ADT) of metastatic prostate cancer (PC).

    METHODS: PC patients presenting with a prostate specific antigen (PSA) >80 ng/ml and/or metastatic disease, intended for ADT were enrolled in the study. CTCs were analysed for expression of PSA prostate specific membrane antigen (PSMA) and epidermal growth factor receptor (EGFR) before and three months after ADT and related to progression.

    RESULTS: At inclusion, 46 out of 53 patients (87%) were CTC-positive with a sensitivity and specificity for distant metastases (M1) of 98% and 75%, respectively. In patients with M1-disease, EGFR-detection in CTC was an independent prognostic marker for progression-free survival, whereas PSA and alkaline phosphatase serum levels, Gleason score, or T-stage were not. EGFR-positive patients had significantly shorter time to progression (5 months) compared to EGFR-negative patients (11 months) (P < 0.05).

    CONCLUSIONS: In this explorative study, CTCs were detected in 98% of M1 patients and detection of EGFR in CTCs was strongly associated with poor outcome, which indicated that phenotypical analysis of CTC could be a promising prognostic marker of ADT-response in castration-naïve metastatic PC patients. Prostate 77:849-858, 2017. © 2017 Wiley Periodicals, Inc.

  • 14.
    Karlsson, Terese
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Sundar, Reshma
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Widmark, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Landström, Maréne
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Persson, Emma
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Osteoblast-derived factors promote metastatic potential in human prostate cancer cells, in part via non-canonical transforming growth factor β (TGFβ) signaling2018In: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 78, no 6, p. 446-456Article in journal (Refereed)
    Abstract [en]

    Background: Transforming growth factor β (TGFβ) functions as a double-edged sword in prostate cancer tumorigenesis. In initial stages of the disease, TGFβ acts as a growth inhibitor upon tumor cells, whereas it in later stages of disease rather promotes invasion and metastatic potential. One well-known cellular source of TGFβ in the bone metastatic site is the bone-forming osteoblasts. Here we have studied the effects by osteoblast-derived factors on metastatic potential in several human prostate cancer cell lines.

    Methods: Effects on metastatic potential in prostate cancer cells by osteoblast-derived factors were studied in vitro using several methods, including Transwell migration and evaluation of formation of pro-migratory protrusions. Confocal microscopy was used to evaluate possible changes in differentiation state in tumor cells by analysis of markers for epithelial-to-mesenchymal transition (EMT). The Matrigel-on-top 3D culture method was used for further assessment of metastatic characteristics in tumor cells by analysis of formation of filopodium-like protrusions (FLPs).

    Results: Osteoblast-derived factors increased migration of PC-3U cells, an effect less prominent in cells overexpressing a mutated type I TGFβ receptor (TβRI) preventing non-canonical TRAF6-dependent TGFβ signaling. Osteoblast-derived factors also increased the formation of long protrusions and loss of cell-cell contacts in PC-3U cells, suggesting induction of a more aggressive phenotype. In addition, treatment with TGFβ or osteoblast-derived factors of PC-3U cells in Matrigel-on-top 3D cultures promoted formation of FLPs, previously shown to be essential for metastatic establishment.

    Conclusions: These findings suggests that factors secreted from osteoblasts, including TGFβ, can induce several cellular traits involved in metastatic potential of PC-3U cells, further strengthening the role for bone cells to promote metastatic tumor cell behavior.

  • 15. Källberg, Eva
    et al.
    Wikström, Pernilla
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Ivars, Fredrik
    Leanderson, Tomas
    Indoleamine 2,3-dioxygenase (IDO) activity influence tumor growth in the TRAMP prostate cancer model2010In: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 70, no 13, p. 1461-1470Article in journal (Refereed)
    Abstract [en]

    Our results argue for a role for IDO mediated immune suppression in the early stages of prostate cancer progression. However, since the intra-tumor IDO expression in J(-/-) mice was indistinguishable from that of C57BL/6 animals the IDO expression in the tumor tissue appears to be irrelevant for TRAMP tumor incidence.

  • 16.
    Lindmark, Fredrik
    et al.
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Jonsson, Björn-Anders
    Umeå University, Faculty of Medicine, Medical Biosciences, Pathology.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Medical Biosciences, Pathology.
    Stattin, Pär
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Urology and Andrology.
    Zheng, S Lilly
    Meyers, Deborah A
    Xu, Jianfeng
    Grönberg, Henrik
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Analysis of the macrophage scavenger receptor 1 gene in Swedish hereditary and sporadic prostate cancer.2004In: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 59, no 2, p. 132-140Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The macrophage scavenger receptor 1 (MSR1) gene on chromosome 8p22 was recently reported as a candidate gene for hereditary prostate cancer (HPC). Here, we further elucidate the role of MSR1 in both Swedish families with HPC and in a cohort of unselected prostate cancer. METHODS: DNA samples from 83 Swedish HPC families and 215 unselected population based cases of prostate cancer as well as 425 age-matched controls were genotyped. RESULTS: A total of 18 variants were identified, including 2 exonic, 7 intronic changes, and 9 changes in the 5'- or 3'-uncoding region. Of the two exonic changes, one previously reported truncation mutation was identified, a R293X nonsense mutation. This mutation was found in 2 of the 83 (2.4%) HPC families. The R293X mutation was found more frequently in men with PC (4.9%) than in unaffected men (2.7%), consistent with previous published results, however our results were not significant (P = 0.16). To additionally test for potential association of common sequence variants and increased risk for the disease, five common polymorphisms (PRO3, INDEL1, IVS5-57, P275A, INDEL7) were genotyped in the group of 215 prostate cancer cases and 425 age-matched controls. No association between any of the five common sequence variants and prostate cancer were found. CONCLUSION: Our results suggest that mutations in MSR1 gene might play a role in prostate cancer susceptibility, particularly the R293X mutation. This study warrants further investigations of the role of MSR1 in prostate cancer etiology.

  • 17.
    Lindström, Sara
    et al.
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Zheng, S Lilly
    Wiklund, Fredrik
    Jonsson, Björn-Anders
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Adami, Hans-Olov
    Augustsson Bälter, Katarina
    Brookes, Anthony J
    Sun, Jielin
    Chang, Bao-Li
    Liu, Wennuan
    Li, Ge
    Isaacs, William B
    Adolfsson, Jan
    Grönberg, Henrik
    Xu, Jianfeng
    Systematic replication study of reported genetic associations in prostate cancer: Strong support for genetic variation in the androgen pathway.2006In: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 66, no 16, p. 1729-1743Article in journal (Refereed)
  • 18. Lu, Lingyi
    et al.
    Cancel-Tassin, Geraldine
    Valeri, Antoine
    Cussenot, Olivier
    Lange, Ethan M.
    Cooney, Kathleen A.
    Farnham, James M.
    Camp, Nicola J.
    Cannon-Albright, Lisa A.
    Tammela, Teuvo L. J.
    Schleutker, Johanna
    Hoegel, Josef
    Herkommer, Kathleen
    Maier, Christiane
    Vogel, Walther
    Wiklund, Fredrik
    Emanuelsson, Monica
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Groenberg, Henrik
    Wiley, Kathleen E.
    Isaacs, Sarah D.
    Walsh, Patrick C.
    Helfand, Brian T.
    Kan, Donghui
    Catalona, William J.
    Stanford, Janet L.
    FitzGerald, Liesel M.
    Johanneson, Bo
    Deutsch, Kerry
    McIntosh, Laura
    Ostrander, Elaine A.
    Thibodeau, Stephen N.
    McDonnell, Shannon K.
    Hebbring, Scott
    Schaid, Daniel J.
    Whittemore, Alice S.
    Oakley-Girvan, Ingrid
    Hsieh, Chih-Lin
    Powell, Isaac
    Bailey-Wilson, Joan E.
    Cropp, Cheryl D.
    Simpson, Claire
    Carpten, John D.
    Seminara, Daniela
    Zheng, S. Lilly
    Xu, Jianfen
    Giles, Graham G.
    Severi, Gianluca
    Hopper, John L.
    English, Dallas R.
    Foulkes, William D.
    Maehle, Lovise
    Moller, Pal
    Badzioch, Michael D.
    Edwards, Steve
    Guy, Michelle
    Eeles, Ros
    Easton, Douglas
    Isaacs, William B.
    Chromosomes 4 and 8 implicated in a genome wide SNP linkage scan of 762 prostate cancer families collected by the ICPCG2012In: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 72, no 4, p. 410-426Article in journal (Refereed)
    Abstract [en]

    BACKGROUND In spite of intensive efforts, understanding of the genetic aspects of familial prostate cancer (PC) remains largely incomplete. In a previous microsatellite-based linkage scan of 1,233 PC families, we identified suggestive evidence for linkage (i.e., LOD?=?1.86) at 5q12, 15q11, 17q21, 22q12, and two loci on 8p, with additional regions implicated in subsets of families defined by age at diagnosis, disease aggressiveness, or number of affected members. METHODS. In an attempt to replicate these findings and increase linkage resolution, we used the Illumina 6000 SNP linkage panel to perform a genome-wide linkage scan of an independent set of 762 multiplex PC families, collected by 11 International Consortium for Prostate Cancer Genetics (ICPCG) groups. RESULTS. Of the regions identified previously, modest evidence of replication was observed only on the short arm of chromosome 8, where HLOD scores of 1.63 and 3.60 were observed in the complete set of families and families with young average age at diagnosis, respectively. The most significant linkage signals found in the complete set of families were observed across a broad, 37cM interval on 4q13-25, with LOD scores ranging from 2.02 to 2.62, increasing to 4.50 in families with older average age at diagnosis. In families with multiple cases presenting with more aggressive disease, LOD cores over 3.0 were observed at 8q24 in the vicinity of previously identified common PC risk variants, as well as MYC, an important gene in PC biology. CONCLUSIONS. These results will be useful in prioritizing future susceptibility gene discovery efforts in thiscommon cancer. Prostate 72: 410-426, 2012. (C) 2011 Wiley Periodicals, Inc.

  • 19. Markt, Sarah C.
    et al.
    Shui, Irene M.
    Unger, Robert H.
    Urun, Yuksel
    Berg, Christine D.
    Black, Amanda
    Brennan, Paul
    Bueno-de-Mesquita, H. Bas
    Gapstur, Susan M.
    Giovannucci, Edward
    Haiman, Christopher
    Henderson, Brian
    Hoover, Robert N.
    Hunter, David J.
    Key, Timothy J.
    Khaw, Kay-Tee
    Canzian, Federico
    Larranga, Nerea
    Le Marchand, Loic
    Ma, Jing
    Naccarati, Alessio
    Siddiq, Afshan
    Stampfer, Meir J.
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Stevens, Victoria L.
    Stram, Daniel O.
    Tjonneland, Anne
    Travis, Ruth C.
    Trichopoulos, Dimitrios
    Ziegler, Regina G.
    Lindstrom, Sara
    Kraft, Peter
    Mucci, Lorelei A.
    Choueiri, Toni K.
    Wilson, Kathryn M.
    ABO Blood Group Alleles and Prostate Cancer Risk: results from the Breast and Prostate Cancer Cohort Consortium (BPC3)2015In: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 75, no 15, p. 1677-1681Article in journal (Refereed)
    Abstract [en]

    BACKGROUND. ABO blood group has been associated with risk of cancers of the pancreas, stomach, ovary, kidney, and skin, but has not been evaluated in relation to risk of aggressive prostate cancer. METHODS. We used three single nucleotide polymorphisms (SNPs) (rs8176746, rs505922, and rs8176704) to determine ABO genotype in 2,774 aggressive prostate cancer cases and 4,443 controls from the Breast and Prostate Cancer Cohort Consortium (BPC3). Unconditional logistic regression was used to calculate age and study-adjusted odds ratios and 95% confidence intervals for the association between blood type, genotype, and risk of aggressive prostate cancer (Gleason score >= 8 or locally advanced/metastatic disease (stage T3/T4/N1/M1). RESULTS. We found no association between ABO blood type and risk of aggressive prostate cancer (Type A: OR = 0.97, 95% CI = 0.87-1.08; Type B: OR = 0.92, 95% CI = n0.77-1.09; Type AB: OR = 1.25, 95% CI = 0.98-1.59, compared to Type O, respectively). Similarly, there was no association between "dose" of A or B alleles and aggressive prostate cancer risk. CONCLUSIONS. ABO blood type was not associated with risk of aggressive prostate cancer. Prostate 75: 1677-1681, 2015. (C) 2015 Wiley Periodicals, Inc.

  • 20.
    Ohlson, Nina
    et al.
    Umeå University, Faculty of Medicine, Medical Biosciences, Pathology.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Medical Biosciences, Pathology.
    Persson, Malin Lindhagen
    Umeå University, Faculty of Medicine, Medical Biosciences, Pathology.
    Wikström, Pernilla
    Umeå University, Faculty of Medicine, Medical Biosciences, Pathology.
    Castration rapidly decreases local insulin-like growth factor-1 levels and inhibits its effects in the ventral prostate in mice.2006In: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 66, no 16, p. 1687-1697Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The mechanisms by which castration induces prostate involution are largely unknown. METHODS: Early responses to castration in mouse ventral prostate (VP) were explored by quantitative microscopy, cDNA array expression, quantitative RT-PCR, and Western blot analysis. As several changes occurred in the insulin-like growth factor (IGF) system this was studied in more detail. Laser micro-dissection was used to localize sites of IGF-1 and IGF-1 receptor (IGF-R1) production. IGF-1 protein levels and IGF-R1 mediated signaling via insulin regulated substrate 1 and 2 (IRS-1 and 2) were examined. IGF-1 was injected into the VP in intact, and castrated mice and effects studied 1 day later. RESULTS: IGF-1 and IGF binding protein 2 (IGFBP-2) mRNA were rapidly reduced whereas IGFBP-3 and IGF-R1 mRNA were increased after castration. IGF-1 was principally produced in the stromal compartment, while IGF-R1 was produced in both epithelial and stromal cells. IGF-1 and IRS-1 protein levels were decreased 1 and 3 days after castration, respectively, while IRS-2 was unchanged. Inactivating phosphorylation of IRS-1 at serine 307 was increased 1 day after castration, and activating phosphorylation at tyrosine 612 was decreased 2 days later. These changes were accompanied by decreased cell proliferation and increased cell death in the glandular and vascular compartment. Local injection of IGF-1 increased vascular density and epithelial cell proliferation in intact mice, but had no effect in castrated animals. CONCLUSION: Decreased IGF-1 levels and action may mediate some of the key features of castration-induced prostate involution.

  • 21.
    Ohlson, Nina
    et al.
    Umeå University, Faculty of Medicine, Medical Biosciences, Pathology.
    Wikström, Pernilla
    Umeå University, Faculty of Medicine, Medical Biosciences, Pathology.
    Stattin, Pär
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Urology and Andrology.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Medical Biosciences, Pathology.
    Cell proliferation and apoptosis in prostate tumors and adjacent non-malignant prostate tissue in patients at different time-points after castration treatment.2005In: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 62, no 4, p. 307-315Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Androgen ablation is the standard treatment for advanced prostate cancer but the short-term cellular effects are largely unknown. METHODS: Sextant prostate biopsies were taken from 77 prostate cancer patients before and 1-10 days after castration treatment. Apoptosis, cell proliferation, and morphology were studied in malignant and non-malignant tissue, using stereological and immunohistochemical methods. RESULTS: Epithelial cell proliferation was significantly decreased both in non-malignant and malignant epithelium already 1 day after therapy. It remained low until day 7, but increased thereafter in the remaining non-malignant epithelial cells and in some tumors. Epithelial cell apoptosis was significantly increased during the first week and then returned to basal levels. The maximal apoptotic indexes, seven- and two-times the intact levels in the non-malignant and malignant glands, respectively, were found at days 3-4 or even earlier in the tumors. Signs of tumor shrinkage such as glandular collapse and decreased tumor cell size were observed from day 3 in most tumors. DISCUSSION: The present study shows that the magnitude and kinetics of the response to castration in the normal human prostate is very similar to the response previously described in rodents. We also demonstrate that most human prostate tumors rapidly respond to castration indicating the need for further evaluation of when and how to best monitor the effects of hormone ablation therapy in prostate cancer patients. (c) 2004 Wiley-Liss, Inc.

  • 22. Olsson, Mats
    et al.
    Lindström, Sara
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Häggkvist, Benjamin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Adami, Hans-Olov
    Bälter, Katarina
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Ask, Birgitta
    Rane, Anders
    Ekström, Lena
    Grönberg, Henrik
    The UGT2B17 gene deletion is not associated with prostate cancer risk2008In: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 68, no 5, p. 571-575Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Deletion polymorphism of the UDP-glucuronosyltransferase 2B17 (UGT2B17) gene has been associated with an increased prostate cancer risk in two previous independent studies. Here we determine the risk in a large-scale population-based case-control study.

    METHODS: Genotyping was conducted with a 5'-nuclease activity assay to distinguish those with one or two UGT2B17 gene copies (ins/del and ins/ins) from individuals homozygous for the deletion (del/del) allele.

    RESULTS: In contrast to previous findings, no association between the UGT2B17 deletion polymorphism and prostate cancer risk was found. Furthermore the UGT2B17 gene deletion did not affect the risk for prostate cancer specific death.

    CONCLUSION: The UGT2B17 deletion polymorphism does not play a major role in prostate cancer susceptibility as previously indicated.

  • 23. Sartor, Oliver
    et al.
    Heinrich, Daniel
    Mariados, Neil
    Mendez Vidal, Maria Jose
    Keizman, Daniel
    Thellenberg-Karlsson, Camilla
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Peer, Avivit
    Procopio, Giuseppe
    Frank, Stephen J.
    Pulkkanen, Kalevi
    Rosenbaum, Eli
    Severi, Stefano
    Trigo, Jose
    Trandafir, Lucia
    Wagner, Volker
    Li, Rui
    Nordquist, Luke T.
    Re-treatment with radium-223: 2-year follow-up from an international, open-label, phase 1/2 study in patients with castration-resistant prostate cancer and bone metastases2019In: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 79, no 14, p. 1683-1691Article in journal (Refereed)
    Abstract [en]

    Background: Radium-223 dichloride (radium-223) is approved for patients with castration-resistant prostate cancer (CRPC), symptomatic bone metastases, and no visceral disease using a dosing regimen of 6 injections (55 kBq/kg intravenously; 1 injection every 4 weeks). Early results from international, open-label, phase 1/2 study NCT01934790 showed that re-treatment with radium-223 was well tolerated with favorable effects on disease progression. Here we report safety and efficacy findings from 2-year follow-up of the radium-223 re-treatment study.

    Methods: Patients with CRPC and bone metastases who completed 6 initial radium-223 injections with no disease progression in bone and later progressed were eligible for radium-223 re-treatment (up to 6 additional radium-223 injections), provided that hematologic parameters were adequate and chemotherapy had not been administered after the initial course of radium-223. Concomitant cytotoxic agents were not allowed during re-treatment but were allowed at the investigator's discretion during follow-up; other concomitant agents for prostate cancer (including abiraterone acetate or enzalutamide) were allowed at investigator's discretion. The primary objective was safety. Exploratory objectives included time to radiographic bone progression, radiographic progression-free survival (rPFS), time to total alkaline phosphatase (tALP), and prostate-specific antigen (PSA) progression, overall survival (OS), time to first symptomatic skeletal event (SSE), and SSE-free survival, all calculated from re-treatment start. Evaluation of safety and exploratory efficacy objectives included active 2-year follow-up. Safety results from active follow-up and updated efficacy are reported.

    Results: Overall, 44 patients were re-treated with radium-223; 29 (66%) completed all 6 injections, and 34 (77%) entered 2-year active follow-up, during which no new safety concerns and no serious drug-related adverse events were noted. rPFS events (progression or death) occurred in 19 (43%) of 44 patients; median rPFS was 9.9 months. Radiographic bone progression occurred in 5 (11%) of 44 patients. Median OS was 24.4 months. Median times to first SSE and SSE-free survival were 16.7 and 12.8 months, respectively. Median time to tALP progression was not reached; median time to PSA progression was 2.2 months.

    Conclusions: Re-treatment with radium-223 in this selected patient population was well tolerated, led to minimal hematologic toxicity, and provided continued disease control in bone at 2-year follow-up.

  • 24.
    Strömvall, Kerstin
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Sundkvist, Kristoffer
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Ljungberg, Börje
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Halin Bergström, Sofia
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Reduced number of CD169(+) macrophages in pre-metastatic regional lymph nodes is associated with subsequent metastatic disease in an animal model and with poor outcome in prostate cancer patients2017In: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 77, no 15, p. 1468-1477Article in journal (Refereed)
    Abstract [en]

    Background: Tumor-derived antigens are captured by CD169+ (SIGLEC1+) sinus macrophages in regional lymph nodes (LNs), and are presented to effector cells inducing an anti-tumor immune response. Reduced CD169 expression in pre-metastatic regional LNs is associated with subsequent metastatic disease and a poor outcome in several tumor types, but if this is the case in prostate cancer has not been explored.

    Methods: CD169 expression was measured with immunohistochemistry in metastasis-free regional LNs from 109 prostate cancer patients treated with prostatectomy (January 1996 to April 2002). Possible associations of CD169 expression with PSA-relapse, prostate cancer death, Gleason score, and other clinical data were assessed using Kaplan-Meier survival- and Cox regression analysis. In addition, the Dunning rat prostate tumor model was used to examine CD169 expression in pre-metastatic LNs draining either highly metastatic MatLyLu- or poorly metastatic AT1-tumors.

    Results: In patients with low CD169 immunostaining in metastasis-free regional LNs, 8 of the 27 patients died from prostate cancer compared with only three of the 82 patients with high immunostaining (P < 0.001). CD169 expression in regional LNs was not associated with PSA-relapse. Rats with highly metastatic tumors had decreased CD169 immunoreactivity in pre-metastatic regional LNs compared with rats with poorly metastatic tumors.

    Conclusion: Low expression of CD169 in metastasis-free regional LNs indicates a reduced anti-tumor immune response. If verified in other studies, CD169 expression in regional LNs could, in combination with other factors, potentially be used as a marker of prostate cancer aggressiveness.

  • 25. Szulkin, Robert
    et al.
    Holmberg, Erik
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Xu, Jianfeng
    Zheng, Sigun
    Palmgren, Juni
    Grönberg, Henrik
    Wiklund, Fredrik
    Prostate cancer risk variants are not associated with disease progression2012In: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 72, no 1, p. 30-39Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Currently used prognostic markers are limited in their ability to accurately predict disease progression among patients with localized prostate cancer. We examined 23 reported prostate cancer susceptibility variants for association with disease progression. METHODS: Disease progression was explored among 4,673 Swedish patients treated for clinically localized prostate cancer between 1997 and 2002. Prostate cancer progression was defined according to primary treatment as a composed event reflecting termination of deferred treatment, biochemical recurrence, local progression, or presence of distant metastasis. Association between single variants, and all variants combined, were performed in Cox regression analysis assuming both log-additive and co-dominant genetic models. RESULTS: Three of the 23 genetic variants explored were nominally associated with prostate cancer progression; rs9364554 (P = 0.041) on chromosome 6q25 and rs10896449 (P = 0.029) on chromosome 11q13 among patients treated with curative intent; and rs4054823 (P = 0.008) on chromosome 17p12 among patients on surveillance. However, none of these associations remained statistically significant after correction for multiple testing. The combined effect of all susceptibility variants was not associated with prostate cancer progression neither among patients receiving treatment with curative intent (P = 0.14) nor among patients on surveillance (P = 0.92). CONCLUSIONS: We observed no evidence for an association between any of 23 established prostate cancer genetic risk variants and disease progression. Accumulating evidence suggests separate genetic components for initiation and progression of prostate cancer. Future studies systematically searching for genetic risk variants associated with prostate cancer progression and prognosis are warranted. Prostate © 2011 Wiley-Liss, Inc.

  • 26.
    Tjon-Kon-Fat, Lee-Ann
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Lundholm, Marie
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Schröder, Mona
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Wurdinger, Thomas
    Thellenberg-Karlsson, Camilla
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Widmark, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Wikström, Pernilla
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Nilsson, Rolf Jonas Andreas
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Platelets harbor prostate cancer biomarkers and the ability to predict therapeutic response to abiraterone in castration resistant patients2018In: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 78, no 1, p. 48-53Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Novel therapies for castration resistant prostate cancer (CRPC) have been introduced in the clinic with possibilities for individualized treatment plans. Best practice of those expensive drugs requires predictive biomarker monitoring. This study used circulating biomarker analysis to follow cancer-derived transcripts implicated in therapy resistance.

    METHOD: The isolated platelet population of blood samples and digital-PCR were used to identify selected biomarker transcripts in patients with CRPC prior chemo- or androgen synthesis inhibiting therapy.

    RESULTS: Fifty patients received either docetaxel (n = 24) or abiraterone (n = 26) therapy, with therapy response rates of 54% and 48%, respectively. Transcripts for the PC-associated biomarkers kallikrein-related peptidase-2 and -3 (KLK2, KLK3), folate hydrolase 1 (FOLH1), and neuropeptide-Y (NPY) were uniquely present within the platelet fraction of cancer patients and not detected in healthy controls (n = 15). In the abiraterone treated cohort, the biomarkers provided information on therapy outcome, demonstrating an association between detectable biomarkers and short progression free survival (PFS) (FOLH1, P < 0.01; KLK3, P < 0.05; and NPY, P < 0.05). Patients with biomarker-negative platelets had the best outcome, while FOLH1 (P < 0.05) and NPY (P = 0.05) biomarkers provided independent predictive information in a multivariate analysis regarding PFS. KLK2 (P < 0.01), KLK3 (P < 0.001), and FOLH1 (P < 0.05) biomarkers were associated with short overall survival (OS). Combining three biomarkers in a panel (KLK3, FOLH1, and NPY) made it possible to separate long-term responders from short-term responders with 87% sensitivity and 82% specificity.

    CONCLUSION: Analyzing tumor-derived biomarkers in platelets of CRPC patients enabled prediction of the outcome after abiraterone therapy with higher accuracy than baseline serum PSA or PSA response.

  • 27.
    Wiklund, Fredrik
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Gillanders, EM
    Albertus, JA
    Bergh, A
    Damber, JE
    Emanuelsson, M
    Freas-Lutz, DL
    Gildea, DE
    Göransson, I
    Jones, MS
    Genome-wide scan of Swedish families with hereditary prostate cancer: suggestive evidence of linkage at 5q11.2 and 19p13.32003In: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 57, no 4, p. 290-297Article in journal (Refereed)
  • 28.
    Wirén, Sara
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. null.
    Stocks, Tanja
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Urologi och andrologi.
    Rinaldi, Sabina
    null.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. null.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. Patologi.
    Stenman, Ulf-Håkan
    null.
    Kaaks, Rudolf
    null.
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Urologi och andrologi.
    Androgens and prostate cancer risk: a prospective study2007In: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 67, no 11, p. 1230-1237Article in journal (Refereed)
    Abstract [en]

    Background: Androgens have been implicated in prostate tumorigenesis, but prospective studies have overall reported no association between circulating levels of androgens and risk of prostate cancer. However, some recent studies have shown that a high level of testosterone increase the risk of non-aggressive tumors but is associated with a decreased risk of aggressive tumors.

    Methods: We prospectively measured plasma levels of total testosterone, androstanediol glucuronide (A-diol-g) and sex hormone binding globuline (SHBG) and calculated estimated levels of free testosterone, in a nested case-control study of 392 cases and 392 matched controls.

    Results: None of the studied hormones were significantly associated with prostate cancer risk in the full study group or in subgroups according to tumor aggressiveness. Odds ratios in the full study group, for top versus bottom quartile, was for total testosterone 1.25 (95% CI = 0.79–2.00; Ptrend = 0.51); free testosterone, 1.31 (95% CI = 0.82–2.07; Ptrend = 0.35); A-diol-g, 0.88 (95% CI = 0.59–1.33; Ptrend = 0.77); and for SHBG, 1.01 (95% CI = 0.64–1.58; Ptrend = 0.94).

    Conclusions: We found no significant associations between androgen levels and risk of prostate cancer in this population-based, non-screened cohort.

1 - 28 of 28
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf