| 1. |
- Alexeyev, Oleg, et al.
(författare)
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Association between the presence of bacterial 16S RNA in prostate specimens taken during transurethral resection of prostate and subsequent risk of prostate cancer (Sweden)
- 2006
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Ingår i: Cancer Causes and Control. - Dordrecht : Kluwer Academic Publishers. - 0957-5243 .- 1573-7225. ; 17:9, s. 1127-1133
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To study bacterial 16S RNA in archival prostate samples from 352 patients with benign prostate hyperplasia (BPH) and evaluate whether the presence of bacterial DNA was different in those who later developed prostate cancer (n = 171) and in the matched controls that did not progress to cancer (n = 181).Methods: 16S DNA PCR followed by cloning and sequencing the positive samples.Results: In 96/352 (27%) of the prostate tissue specimens 16S RNA were detected. Sequence analysis revealed Propionibacterium acnes as the predominant microorganism (23% of 16S RNA positive patients). The second most frequent isolate—Escherichia coli was found in 12 (12%) patients. The other isolates included Pseudomonas sp. (3 patients), Actinomyces sp. (2), Streptococcus mutans (1), Corynebacterium sp. (2),Nocardioides sp. (1), Rhodococcus sp. (1) Veillonella sp. (2). In P. acnes positive samples 62% exhibited severe histological inflammation versus 50% in the bacteria-negative group (p = 0.602). The presence of P. acnes in the prostate was associated with prostate cancer development (OR 2.17, 95% CI 0.77–6.95).Conclusions: This study has revealed P. acnes as the most common bacteria in the prostate in BPH. Further studies are needed to clarify its role in contributing to the development of prostatic inflammation and prostate cancer.
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| 2. |
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| 3. |
- Olsson, Jan, et al.
(författare)
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Chronic prostatic infection and inflammation by propionibacterium acnes in a rat prostate infection model
- 2012
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Ingår i: PLOS ONE. - : Public library of science. - 1932-6203. ; 7:12, s. e51434-
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Tidskriftsartikel (refereegranskat)abstract
- Chronic inflammation in the prostate, seen as infiltration of inflammatory cells into the prostate gland in histological samples, affects approximately half the male population without indication of prostate disease, and is almost ubiquitous in patients diagnosed with benign prostate hyperplasia and cancer. Several studies have demonstrated the Gram-positive bacterium Propionibacterium acnes to be frequently present in prostate tissue from men suffering from prostate disease. P. acnes has been shown to be associated with histological inflammation in human prostatectomy specimens, and also to induce strong inflammatory response in prostate-derived tissue culture models. The present paper describes a rat model for assessment of the pathogenic potential of P. acnes in prostate. Prostate glands of Sprague Dawley rats (n = 98) were exposed via an abdominal incision and live P. acnes or, in control rats, saline were injected into the ventral and dorso-lateral lobes. Rats were sacrificed 5 days, 3 weeks, 3 months and 6 months post infection, and prostate tissue was analyzed for bacterial content and histological inflammation. Rat sera were assessed for levels of CRP and anti-P. acnes IgG. Live P. acnes could be recovered from the dorso-lateral lobes up to 3 months post infection, while the ventral lobes were cleared from bacteria at that time. In samples up to 3 months post infection, the dorso-lateral lobes exhibited intense focal inflammation. CRP and IgG levels were elevated throughout the span of the experiment, and reached maximum levels 3 weeks and 3 months post infection, respectively. We show that P. acnes have the potential to cause chronic infection in previously healthy prostate, and that the infection has potential to cause chronic histological inflammation in the infected tissue. The high prevalence of P. acnes in human prostate tissue calls for resolution of pathogenic details. The present rat model suggests that complications such as chronic inflammation may be induced by P. acnes infection.
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| 4. |
- Alsing Johansson, Todd, et al.
(författare)
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Bacterial Contamination of Equine Dentistry Equipment—Effect of Cleaning and Disinfection
- 2021
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Ingår i: Animals. - : MDPI AG. - 2076-2615. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Simple Summary Some of the equipment used in equine dentistry is difficult to clean and disinfect. Since it is vital to avoid the spread of infections in equine healthcare it is important to develop practical and easy-to-follow methods for cleaning and disinfecting dental equipment. The aim of this study was to investigate hygiene in equine dentistry. Dental equipment and the head support, where horses rest their head during dental care, were sampled for the amount of bacteria between each patient before and after dental care as well as after cleaning and/or disinfecting. The amount of bacteria was, in general, high on dental equipment and the head support after dental procedures. Bacteria were found in different amounts on most of the dental equipment after cleaning or disinfecting, which indicates a risk for spreading infections when using the equipment. For the head support, cleaning and/or disinfecting generally resulted in a reduced amount of bacteria, indicating a lowered risk for spreading infections. There is a great need for evidence-based guidelines on hygiene in equine dentistry to decrease the risk of transmitting infections between patients, facilities, and stables. Equine dentistry has developed immensely and human dental equipment, such as handpieces, are often used. Measures to avoid the spread of infectious microorganisms are important, but this is challenging since handpieces are difficult to decontaminate. Thus, it is necessary to develop effective IPC measures in equine dentistry. The aim of this study was to contribute to the evidence needed for future evidence-based guidelines on IPC by investigating hygiene in equine dentistry. Used handpieces and dummies (i.e., handpieces not used during dental procedure, reflecting environmental bacterial contamination) and the head support were sampled each day before the first patient, for each patient after treatment, and after decontamination. All equipment was sampled with 3M (TM) Swab Samplers and the head support additionally sampled with dip slides. After dental procedures, the detected bacterial load was often high on used handpieces, dummies, and the head support. After decontamination, handpieces did not meet the criteria for high-level disinfected equipment. In all but one case decontamination of the head support resulted in a lowered bacterial load. There is a great need for evidence-based guidelines on hygiene in equine dentistry, including IPC measures, to decrease the risk of spreading infectious microorganisms between patients, facilities, and stables.
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| 5. |
- Bergh Drott, Johanna, et al.
(författare)
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Propionibacterium acnes infection induces upregulation of inflammatory genes and cytokine secretion in prostate epithelial cells
- 2010
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Ingår i: BMC Microbiology. - : BioMed Central. - 1471-2180. ; 10, s. 126-
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Tidskriftsartikel (refereegranskat)abstract
- Background: The immune stimulating bacterium Propionibacterium acnes is a frequent colonizer of benign and malignant prostate tissue. To understand the pathogenesis of the earliest phase of this infection, we examined the P. acnes triggered immune response in cultivated prostate epithelial cells.Results: Prostate epithelial cells are triggered to secrete IL-6, IL-8 and GM-CSF when infected with P. acnes. The secretion of cytokines is accompanied by NFκB related upregulation of the secreted cytokines as well as several components of the TLR2-NFκB signaling pathway.Conclusions: P. acnes has potential to trigger a strong immune reaction in the prostate glandular epithelium. Upon infection of prostate via the retrograde urethral route, the induced inflammatory reaction might facilitate bacterial colonization deeper in the prostate tissue where persistent inflammation may impact the development of prostate diseases as hyperplasia and/or malignancy.
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| 6. |
- Bergh Drott, Johanna
(författare)
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The role of microorganisms in prostate cancer development
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Prostate cancer is the most common cancer among Swedish men, but the aetiology of this disease is largely unknown. There is evidence for a linkage between chronic inflammation and prostate cancer. The mechanisms causing prostate inflammation and how this could promote tumour development and progression are however largely unknown. Chronic inflammatory infiltrates are common findings in prostate tissue samples and infection is proposed to be one possible cause for this inflammation. Inflammatory cells release free radicals, cytokines, and growth factors that facilitate increased cell proliferation, DNA damage, mutations, and angiogenesis. However, the present literature on the presence of microbes in prostate tissue and their possible linkage to inflammation and cancer development is limited. Therefore, the aim of this thesis was to investigate if microorganisms are present in prostate tissue and to evaluate their role in inducing prostatitis and prostate epithelial neoplasia.The presence of microorganisms (virus, bacteria and fungi) was studied in clinical prostate tissue samples to evaluate whether or not the occurrences of microorganisms were different in patients that later developed cancer compared with matched controls that did not. Viruses, bacteria and fungi were found in prostate tissues. Out of eight different viruses investigated, EBV and JC virus were detected, but there were no differences in occurrence in the case group compared to the control group. The fungus Candida albicans was present in a very small proportion of the prostate tissue samples. The predominant bacterium was Propionibacterium acnes and the second most prevalent was Escherichia coli. The presence of Propionibacterium acnes was associated with inflammation and subsequent prostate cancer development. Propionibacterium acnes was further evaluated for its capacity to induce an inflammatory response both in vitro and in vivo. Live Propionibacterium acnes induced a strong immune reaction in prostate epithelial cells in vitro with up-regulation of inflammatory genes and secretion of pro-inflammatory cytokines. Infection with Propionibacterium acnes in rat prostate resulted in a lobe specific inflammation with the most intense inflammation in the dorso-lateral prostate, lasting up to 3 months post-inoculation. Propionibacterium acnes inflammation was also associated with altered epithelial cell morphology, signs of DNA damage and increased cell proliferation.Taken together, this thesis shows that different viruses and bacteria can be found in prostate tissue. Propionibacterium acnes, the most abundant among the bacteria detected and more prevalent in the cancer than in the control group, exhibits strong prostatitis promoting properties both in vitro and in vivo. In addition, Propionibacterium acnes can induce some of the epithelial changes known to occur during prostate neoplasia formation. This thesis therefore suggests that Propionibacterium acnes induced chronic prostatitis could promote prostate cancer development. Further studies are needed to elucidate the molecular interplay linking Propionibacterium acnes induced inflammation and the formation of a pre-neoplastic state that could evolve into prostate cancer.
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| 7. |
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| 8. |
- Bergh, Johanna, et al.
(författare)
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No link between viral findings in the prostate and subsequent cancer development
- 2007
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Ingår i: British Journal of Cancer. - London : Nature Publishing Group. - 0007-0920 .- 1532-1827. ; 96:1, s. 137-139
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Tidskriftsartikel (refereegranskat)abstract
- In an investigation of 201 prostate tissue samples from patients with benign prostate hyperplasia that later progressed to prostate cancer and 201 matched controls that did not, there were no differences in the prevalence of adenovirus, herpesvirus, papilloma virus, polyoma virus and Candida albicans DNA.
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| 9. |
- Bobbio, Emanuele, et al.
(författare)
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Echocardiography in inflammatory heart disease: A comparison of giant cell myocarditis, cardiac sarcoidosis, and acute non-fulminant myocarditis
- 2023
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Ingår i: IJC Heart and Vasculature. - 2352-9067. ; 46
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Tidskriftsartikel (refereegranskat)abstract
- Background: Giant cell myocarditis (GCM) and cardiac sarcoidosis (CS) are, in contrast to acute non-fulminant myocarditis (ANFM), rare inflammatory diseases of the myocardium with poor prognosis. Although echocardiography is the first-line diagnostic tool in these patients, their echocardiographic appearance has so far not been systematically studied. Methods: We assessed a total of 71 patients with endomyocardial biopsy-proven GCM (n = 21), and CS (n = 25), as well as magnetic resonance-verified ANFM (n = 25). All echocardiographic examinations, performed upon clinical presentation, were reanalysed according to current guidelines including a detailed assessment of right ventricular (RV) dysfunction. Results: In comparison with ANFM, patients with either GCM or CS were older (mean age (±SD) 55 ± 12 or 53 ± 8 vs 25 ± 8 years), more often of female gender (52% or 24% vs 8%), had more severe clinical symptoms and higher natriuretic peptide levels. For both GCM and CS, echocardiography revealed more frequently signs of left ventricular (LV) dysfunction in form of a reduced ejection fraction (p < 0.001), decreased cardiac index (p < 0.001) and lower global longitudinal strain (p < 0.001) in contrast to ANFM. The most prominent increase in LV end-diastolic volume index was observed in CS. In addition, RV dysfunction was more frequently found in both GCM and CS than in ANFM (p = 0.042). Conclusions: Both GCM and CS have an echocardiographic and clinical appearance that is distinct from ANFM. However, the method cannot further differentiate between the two rare entities. Consequently, echocardiography can strengthen the initial clinical suspicion of a more severe form of myocarditis, thus warranting a more rigorous clinical work-up.
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| 10. |
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| 11. |
- Felton, Adam, et al.
(författare)
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Replacing monocultures with mixed-species : Ecosystem service implications of two production forest alternatives in Sweden
- 2016
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Ingår i: Ambio. - : Springer Science and Business Media LLC. - 0044-7447 .- 1654-7209. ; 45:Suppl. 2, s. 124-139
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Tidskriftsartikel (refereegranskat)abstract
- Whereas there is evidence that mixed-species approaches to production forestry in general can provide positive outcomes relative to monocultures, it is less clear to what extent multiple benefits can be derived from specific mixed-species alternatives. To provide such insights requires evaluations of an encompassing suite of ecosystem services, biodiversity, and forest management considerations provided by specific mixtures and monocultures within a region. Here, we conduct such an assessment in Sweden by contrasting even-aged Norway spruce (Picea abies)-dominated stands, with mixed-species stands of spruce and birch (Betula pendula or B. pubescens), or spruce and Scots pine (Pinus sylvestris). By synthesizing the available evidence, we identify positive outcomes from mixtures including increased biodiversity, water quality, esthetic and recreational values, as well as reduced stand vulnerability to pest and pathogen damage. However, some uncertainties and risks were projected to increase, highlighting the importance of conducting comprehensive interdisciplinary evaluations when assessing the pros and cons of mixtures.
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| 12. |
- Felton, Adam, et al.
(författare)
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Replacing monocultures with mixed-species stands : Ecosystem service implications of two production forest alternatives in Sweden
- 2016
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Ingår i: Ambio. - : Springer Science and Business Media LLC. - 0044-7447 .- 1654-7209. ; 45, s. 124-139
-
Tidskriftsartikel (refereegranskat)abstract
- Whereas there is evidence that mixed-species approaches to production forestry in general can provide positive outcomes relative to monocultures, it is less clear to what extent multiple benefits can be derived from specific mixed-species alternatives. To provide such insights requires evaluations of an encompassing suite of ecosystem services, biodiversity, and forest management considerations provided by specific mixtures and monocultures within a region. Here, we conduct such an assessment in Sweden by contrasting even-aged Norway spruce (Picea abies)-dominated stands, with mixed-species stands of spruce and birch (Betula pendula or B. pubescens), or spruce and Scots pine (Pinus sylvestris). By synthesizing the available evidence, we identify positive outcomes from mixtures including increased biodiversity, water quality, esthetic and recreational values, as well as reduced stand vulnerability to pest and pathogen damage. However, some uncertainties and risks were projected to increase, highlighting the importance of conducting comprehensive interdisciplinary evaluations when assessing the pros and cons of mixtures.
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| 13. |
- Hakamies-Blomqvist, Liisa, et al.
(författare)
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Quality of life in patients with metastatic breast cancer receiving either docetaxel or sequential methotrexate and 5-fluorouracil : A multicentre randomised phase III trial by the Scandinavian breast group
- 2000
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Ingår i: European Journal of Cancer. - 0959-8049 .- 1879-0852. ; 36:11, s. 1411-7
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to evaluate the effects of two alternative chemotherapy regimes on the quality of life (QoL) of patients with advanced breast cancer. In a multicentre trial, 283 patients were randomised to receive either docetaxel (T) or sequential methotrexate and 5-fluorouracil (MF). QoL was assessed at baseline and before each treatment using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30). Initial compliance in the QoL study was 96% and the overall compliance 82%. QoL data were available for 245 patients (T 130 and 115 MF). Both treatment groups showed some improvement in emotional functioning during treatment, with a significant difference favouring the MF group at treatment cycles 5 and 6. In the T group, the scores on the other functional scales remained stable throughout the first six cycles. There were significant differences favouring the MF group on the social functioning scale at treatment cycle 6 and on the Global QoL scale at treatment cycles 5 and 6. On most symptom and single-item scales there were no statistically significant differences between the groups. However, at baseline, the T patients reported more appetite loss, at treatment cycles 2-4, the MF patients reported more nausea/vomiting, and at treatment cycle 6, the T patients reported more symptoms of fatigue, dyspnoea and insomnia. There were no statistically significant differences between the groups in the mean change scores of the functional and symptom scales. Interindividual variance was, however, larger in the T group. Differences in QoL between the two treatment groups were minor. Hence, given the expectancy of comparable QoL outcomes, the choice of treatment should be made on the basis of the expected clinical effect.
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| 14. |
- Hakamies-Blomqvist, Liisa, et al.
(författare)
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Timing of quality of life (QoL) assessments as a source of error in oncological trials
- 2001
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Ingår i: Journal of Advanced Nursing. - : Wiley. - 0309-2402 .- 1365-2648. ; 35:5, s. 709-16
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Tidskriftsartikel (refereegranskat)abstract
- AIM OF THE STUDY: To produce an empirical estimate of the nature and magnitude of the error produced by incorrect timing quality of life (QoL) measurements in patients receiving chemotherapy. DESIGN: In a multicentre trial, 283 patients were randomized to receive either docetaxel (T) or sequential methotrexate and 5-fluorouracil (MF). The QoL was assessed at baseline and before each treatment using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). The study design was retrospective. Data were analysed using t-tests. RESULTS: Erroneous timing affected the QoL findings in both treatment arms. At baseline, there were statistically significant differences in the MF group on the nausea/vomiting scale, with ill-timed assessment showing more symptoms, and in the T group on the physical functioning scale with ill-timed assessments indicating better QoL. The mean scores of correct vs. incorrect timings over the first 14 cycles showed statistically significant differences on several scales. In the MF group, ill-timed assessments indicated significantly worse physical functioning and global QoL, and significantly more of the following symptoms: fatigue, nausea/vomiting, insomnia, appetite loss, and constipation. In the T group, ill-timed assessment showed better physical functioning, less dyspnoea and more insomnia than correctly timed assessments. The reasons for erroneous timing were not always detectable retrospectively. However, in some cases the MF group, being in standard treatment, seemed to have followed a clinical routine not involving the active participation of the study nurse responsible, whereas patients in the experimental T group were more consistently taken care of by the study nurses. CONCLUSIONS: Incorrect timing of QoL assessments in oncological trials jeopardises both the reliability of the QoL findings within treatment and the validity of QoL outcome comparisons between treatments. This issue should be emphasized in the planning of both the study design and clinical routines.
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| 15. |
- Hall, Per, et al.
(författare)
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Hormone-replacement therapy influences gene expression profiles and is associated with breast-cancer prognosis : a cohort study
- 2006
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Ingår i: BMC Medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 4, s. 16-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Postmenopausal hormone-replacement therapy (HRT) increases breast-cancer risk. The influence of HRT on the biology of the primary tumor, however, is not well understood. Methods: We obtained breast-cancer gene expression profiles using Affymetrix human genome U133A arrays. We examined the relationship between HRT-regulated gene profiles, tumor characteristics, and recurrence-free survival in 72 postmenopausal women. Results: HRT use in patients with estrogen receptor ( ER) protein positive tumors (n = 72) was associated with an altered regulation of 276 genes. Expression profiles based on these genes clustered ER-positive tumors into two molecular subclasses, one of which was associated with HRT use and had significantly better recurrence free survival despite lower ER levels. A comparison with external data suggested that gene regulation in tumors associated with HRT was negatively correlated with gene regulation induced by short-term estrogen exposure, but positively correlated with the effect of tamoxifen. Conclusion: Our findings suggest that post-menopausal HRT use is associated with a distinct gene expression profile related to better recurrence-free survival and lower ER protein levels. Tentatively, HRT-associated gene expression in tumors resembles the effect of tamoxifen exposure on MCF-7 cells.
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| 16. |
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| 17. |
- Ivshina, Anna V., et al.
(författare)
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Genetic reclassification of histologic grade delineates new clinical subtypes of breast cancer
- 2006
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Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 66:21, s. 10292-10301
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Tidskriftsartikel (refereegranskat)abstract
- Histologic grading of breast cancer defines morphologic subtypes informative of metastatic potential, although not without considerable interobserver disagreement and clinical heterogeneity particularly among the moderately differentiated grade 2 (G2) tumors. We posited that a gene expression signature capable of discerning tumors of grade 1 (G1) and grade 3 (W) histology might provide a more objective measure of grade with prognostic benefit for patients with G2 disease. To this end, we studied the expression profiles of 347 primary invasive breast tumors analyzed on Affymetrix microarrays. Using class prediction algorithms, we identified 264 robust grade-associated markers, six of which could accurately classify G1 and G3 tumors, and separate G2 tumors into two highly discriminant classes (termed G2a and G2b genetic grades) with patient survival outcomes highly similar to those with G1 and G3 histology, respectively. Statistical analysis of conventional clinical variables further distinguished G2a and G2b subtypes from each other, but also from histologic G1 and G3 tumors. In multivariate analyses, genetic grade was consistently found to be an independent prognostic indicator of disease recurrence comparable with that of lymph node status and tumor size. When incorporated into the Nottingham prognostic index, genetic grade enhanced detection of patients with less harmful tumors, likely to benefit little from adjuvant therapy. Our findings show that a genetic grade signature can improve prognosis and therapeutic planning for breast cancer patients, and support the view that low- and high-grade disease, as defined genetically, reflect independent pathobiological entities rather than a continuum of cancer progression.
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| 18. |
- Keskitalo, E. Carina H., 1974-, et al.
(författare)
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Adaptation to Climate Change in Swedish Forestry
- 2016
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Ingår i: Forests. - Basel : MDPI AG. - 1999-4907. ; 7:2
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Tidskriftsartikel (refereegranskat)abstract
- Adaptation to climate change in forestry has become a growing concern, in part due to the impact of storms and other events that have raised the awareness of such risks amongst forest owners. Sweden is one of Europe's most densely-forested countries, with this sector playing a major role economically. However adaptation has, to a large extent, been limited to the provision of recommendations to forest managers, most of which have only been partially implemented. This paper summarizes research with direct implications for adaptation to climate change within the forestry sector in Sweden. The focus is based in particular on providing examples of adaptations that illustrate the specific Swedish orientation to adaptation, in line with its relatively intensive forest management system. The paper thus illustrates a specific Swedish orientation to adaptation through active management, which can be contrasted with approaches to adaptation in other forestry systems, in particular those with limited management or management based on maintaining natural forests in particular.
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| 19. |
- Klapwijk, Maartje, et al.
(författare)
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Capturing complexity : Forests, decision-making and climate change mitigation action
- 2018
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Ingår i: Global Environmental Change. - : Elsevier. - 0959-3780 .- 1872-9495. ; 52, s. 238-247
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Tidskriftsartikel (refereegranskat)abstract
- Managed forests can play an important role in climate change mitigation due to their capacity to sequester carbon. However, it has proven difficult to harness their full potential for climate change mitigation. Managed forests are often referred to as socio-ecological systems as the human dimension is an integral part of the system. When attempting to change systems that are influenced by factors such as collective knowledge, social organization, understanding of the situation and values represented in society, initial intentions often shift due to the complexity of political, social and scientific interactions. Currently, the scientific literature is dispersed over the different factors related to the socio-ecological system. To examine the level of dispersion and to obtain a holistic view, we review climate change mitigation in the context of Swedish forest research. We introduce a heuristic framework to understand decision-making connected to climate change mitigation. We apply our framework to two themes which span different dimensions in the socio-ecological system: carbon accounting and bioenergy. A key finding in the literature was the perception that current uncertainties regarding the reliability of different methods of carbon accounting inhibits international agreement on the use of forests for climate change mitigation. This feeds into a strategic obstacle affecting the willingness of individual countries to implement forest-related carbon emission reduction policies. Decisions on the utilization of forests for bioenergy are impeded by a lack of knowledge regarding the resultant biophysical and social consequences. This interacts negatively with the development of institutional incentives regarding the production of bioenergy using forest products. Normative disagreement about acceptable forest use further affects these scientific discussions and therefore is an over-arching influence on decision-making. With our framework, we capture this complexity and make obstacles to decision-making more transparent to enable their more effective resolution. We have identified the main research areas concerned with the use of managed forest in climate change mitigation and the obstacles that are connected to decision making.
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| 20. |
- Li, Jingmei, et al.
(författare)
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Breast cancer genetic risk profile is differentially associated with interval and screen-detected breast cancers
- 2015
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Ingår i: Annals of Oncology. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 0923-7534. ; 26:3, s. 517-522
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Tidskriftsartikel (refereegranskat)abstract
- Background: Polygenic risk profiles computed from multiple common susceptibility alleles for breast cancer have been shown to identify women at different levels of breast cancer risk. We evaluated whether this genetic risk stratification can also be applied to discriminate between screen-detected and interval cancers, which are usually associated with clinicopathological and survival differences. Patients and methods: A 77-SNP polygenic risk score (PRS) was constructed for breast cancer overall and by estrogen-receptor (ER) status. PRS was inspected as a continuous (per standard deviation increment) variable in a case-only design. Modification of the PRS by mammographic density was evaluated by fitting an additional interaction term. Results: PRS weighted by breast cancer overall estimates was found to be differentially associated with 1,865 screen-detected and 782 interval cancers in the LIBRO-1 study (age-adjusted ORperSD [95% confidence interval]=0.91 [0.83-0.99], p=0.023). The association was found to be more significant for PRS weighted by ER-positive breast cancer estimates (ORperSD=0.90 [0.82-0.98], p=0.011). This result was corroborated by two independent studies (combined ORperSD=0.87 [0.76-1.00], p=0.058) with no evidence of heterogeneity. When enriched for “true” interval cancers among nondense breasts, the difference in the association with PRS in screen-detected and interval cancers became more pronounced (ORperSD=0.74 [0.62-0.89], p=0.001), with a significant interaction effect between PRS and mammographic density (pinteraction=0.017). Conclusion: To our knowledge, this is the first report looking into the genetic differences between screendetected and interval cancers. It is an affirmation that the two types of breast cancer may have unique underlying biology.
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| 21. |
- Malfatti, Edoardo, et al.
(författare)
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A New Muscle Glycogen Storage Disease Associated with Glycogenin-1 Deficiency
- 2014
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Ingår i: Annals of Neurology. - : Wiley. - 0364-5134. ; 76:6, s. 891-898
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Tidskriftsartikel (refereegranskat)abstract
- We describe a slowly progressive myopathy in 7 unrelated adult patients with storage of polyglucosan in muscle fibers. Genetic investigation revealed homozygous or compound heterozygous deleterious variants in the glycogenin-1 gene (GYG1). Most patients showed depletion of glycogenin-1 in skeletal muscle, whereas 1 showed presence of glycogenin-1 lacking the C-terminal that normally binds glycogen synthase. Our results indicate that either depletion of glycogenin-1 or impaired interaction with glycogen synthase underlies this new form of glycogen storage disease that differs from a previously reported patient with GYG1 mutations who showed profound glycogen depletion in skeletal muscle and accumulation of glycogenin-1. Ann Neurol 2014;76:891-898
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| 22. |
- Mufic, Johanna, 1991-
(författare)
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“Quality Problems” in Swedish Municipal Adult Education : The Micropolitics of Quality Construed in the Audit Society
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this thesis was to analyze and critically scrutinize how quality is construed in an audit process in Swedish Municipal Adult Education (MAE) and the discursive effects. Drawing on adult education policy documents and observations of a quality audit process, as well as the Swedish Schools Inspectorate’s (SSI) Day, this study also contributes to the uncharted field of how the micropolitics of “quality” is being produced in the Audit society within adult education. By applying Carol Bacchi’s post-structural, Foucault-influenced ‘What’s the “problem” represented to be?’ approach, it became possible to analyze the politics of “quality” on a micro level. The results indicate that quality seems to be construed as a ‘lack’ or a ‘problem’ in Swedish MAE policy and during the quality audit that SSI carried out in MAE. Moreover, principals, teachers and heads of education seem to be held responsible for this lack as the increased need for flexibility and individualization is stressed as a solution to the ‘quality problem’. There also seems to be an ambiguity of how quality should be addressed, defined, audited, and produced in MAE, as the SSI seem to struggle with making quality measurable for it to be auditable. The analysis shed light on two different logics that underpin the way that quality is construed; on the one hand, it is construed as something elusive that can be used to pinpoint quality in teaching and schools. And on the other hand, it is construed as something quantitative and limiting that has effects on what can be said and done in MAE. There also seems to be a hierarchy between different ‘problems’ during the SSI’s audit of MAE which also have consequences for what can be said and done about quality in this context.
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| 23. |
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| 24. |
- Papworth, Karin, et al.
(författare)
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Osteopontin but not parathyroid hormone-related protein predicts prognosis in human renal cell carcinoma
- 2013
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Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 52:1, s. 159-165
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To evaluate the relationship between osteopontin (OPN) in serum and plasma and parathyroid hormone-related protein (PTHrP) in serum, plasma and tumour tissue, and to assess the prognostic impact of OPN and PTHrP in human renal cell carcinoma (RCC).Material and methods. The study included 269 patients with RCC. In 189 patients, immunohistochemical (IHC) PTHrP tumour tissue expression was evaluated, and OPN and PTHrP in serum were assessed. In 80 patients, plasma OPN and PTHrP were analysed. Tumour type, TNM stage, nuclear grade and RCC-specific survival were also registered. In a sub-group, IHC expression of CD 31 was assessed. The prognostic information of the factors was analysed using uni- and multivariate analyses.Results. The median OPN level was 2.3 times higher in plasma than in serum. Serum OPN was significantly higher in patients with papillary RCC compared to clear cell RCC and chromophobe RCC. Both serum and plasma OPN levels were positively correlated to TNM stage and nuclear grade. Multivariate analysis showed that serum and plasma OPN levels were independent prognostic factors for RCC-specific survival, along with TNM stage. Immunohistochemical expression of PTHrP associated to TNM stage but not to nuclear grade or serum OPN. Furthermore, IHC expression of PTHrP was positively correlated to serum PTHrP but inversely to tumour CD31 expression. Plasma PTHrP was increased in 20% of the patients and related to TNM stage but not to nuclear grade. Plasma OPN was significantly higher in patients with increased PTHrP levels, compared to those with normal levels.Conclusion. Plasma OPN levels differed between RCC types, and in clear cell RCC, both serum and plasma OPN levels were independent predictors of survival. We found no evidence for prognostic value related to circulating levels or the IHC expression of PTHrP.
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| 25. |
- Pawitan, Yudi, et al.
(författare)
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Gene expression profiling spares early breast cancer patients from adjuvant therapy : derived and validated in two population-based cohorts
- 2005
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Ingår i: Breast cancer research : BCR. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 7:6, s. R953-64
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Adjuvant breast cancer therapy significantly improves survival, but overtreatment and undertreatment are major problems. Breast cancer expression profiling has so far mainly been used to identify women with a poor prognosis as candidates for adjuvant therapy but without demonstrated value for therapy prediction. METHODS: We obtained the gene expression profiles of 159 population-derived breast cancer patients, and used hierarchical clustering to identify the signature associated with prognosis and impact of adjuvant therapies, defined as distant metastasis or death within 5 years. Independent datasets of 76 treated population-derived Swedish patients, 135 untreated population-derived Swedish patients and 78 Dutch patients were used for validation. The inclusion and exclusion criteria for the studies of population-derived Swedish patients were defined. RESULTS: Among the 159 patients, a subset of 64 genes was found to give an optimal separation of patients with good and poor outcomes. Hierarchical clustering revealed three subgroups: patients who did well with therapy, patients who did well without therapy, and patients that failed to benefit from given therapy. The expression profile gave significantly better prognostication (odds ratio, 4.19; P = 0.007) (breast cancer end-points odds ratio, 10.64) compared with the Elston-Ellis histological grading (odds ratio of grade 2 vs 1 and grade 3 vs 1, 2.81 and 3.32 respectively; P = 0.24 and 0.16), tumor stage (odds ratio of stage 2 vs 1 and stage 3 vs 1, 1.11 and 1.28; P = 0.83 and 0.68) and age (odds ratio, 0.11; P = 0.55). The risk groups were consistent and validated in the independent Swedish and Dutch data sets used with 211 and 78 patients, respectively. CONCLUSION: We have identified discriminatory gene expression signatures working both on untreated and systematically treated primary breast cancer patients with the potential to spare them from adjuvant therapy.
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| 26. |
- Routa, Johanna, et al.
(författare)
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The timber and energy biomass potential of intensively managed cloned Norway spruce stands
- 2013
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Ingår i: Global Change Biology Bioenergy. - : Wiley. - 1757-1693 .- 1757-1707. ; 5:1, s. 43-52
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Tidskriftsartikel (refereegranskat)abstract
- We used ecosystem model simulations to study the timber and energy biomass potential offered by intensively managed cloned Norway spruce stands. More specifically, we analysed how the use of cloned trees compared with non-cloned trees, together with thinning, nitrogen (N) fertilisation and rotation length (from 60 to 100 years), affects the annual mean production of timber (i.e., saw logs, pulpwood) and energy biomass (i.e., stumps and harvesting residuals in the final felling) and its economic profitability [annual mean of net present value (NPV) with a 2% interest rate]. Furthermore, we employed a life cycle analysis/emission calculation tool to assess the total net CO2emissions per unit of energy (kg CO2 MW h−1) produced based on energy biomass. We found that both the annual mean production of timber and the NPV increased substantially, regardless of the management regime, if cloned trees with an annual growth increase of up to 30% compared with non-cloned trees were used in regeneration. In general, the use of a short rotation with N fertilisation clearly increased the annual mean of the NPV. Consequently, the use of cloned trees also clearly increased the annual mean production of energy biomass and decreased the total net CO2 emissions per unit of energy produced based on energy biomass. However, the total annual net CO2emissions were the lowest if a long rotation was used with N fertilisation. To conclude, the use of cloned trees together with intensive management could potentially be highly beneficial for the cost-efficient and sustainable production of timber and energy biomass in an integrated way.
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| 27. |
- Ruiz, Mario, 1984, et al.
(författare)
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Sphingosine 1-phosphate mediates adiponectin receptor signaling essential for lipid homeostasis and embryogenesis.
- 2022
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Cells and organisms require proper membrane composition to function and develop. Phospholipids are the major component of membranes and are primarily acquired through the diet. Given great variability in diet composition, cells must be able to deploy mechanisms that correct deviations from optimal membrane composition and properties. Here, using lipidomics and unbiased proteomics, we found that the embryonic lethality in mice lacking the fluidity regulators Adiponectin Receptors 1 and 2 (AdipoR1/2) is associated with aberrant high saturation of the membrane phospholipids. Using mouse embryonic fibroblasts (MEFs) derived from AdipoR1/2-KO embryos, human cell lines and the model organism C. elegans we found that, mechanistically, AdipoR1/2-derived sphingosine 1-phosphate (S1P) signals in parallel through S1PR3-SREBP1 and PPARγ to sustain the expression of the fatty acid desaturase SCD and maintain membrane properties. Thus, our work identifies an evolutionary conserved pathway by which cells and organisms achieve membrane homeostasis and adapt to a variable environment.
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| 28. |
- Sandlund, Johanna, 1979-
(författare)
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Angiogenesis in human renal cell carcinoma : hypoxia, vascularity and prognosis
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Angiogenesis is recognised as a critical step in tumour progression. The angiogenic switch is activated by various trigger signals, such as hypoxia, low pH, and genetic mutations. Renal cell carcinoma (RCC) is often an aggressive tumour, and advanced disease has limited treatment options and bad prognosis. This study was focused on markers of angiogenesis in RCC: endoglin (CD105) and CD31 assessing microvessel density (MVD), and carbonic anhydrase (CA) IX and hypoxia-inducible factor (HIF)-2α expressed at hypoxia. Upregulation of HIF is also associated with inactivation of the von Hippel-Lindau (VHL) tumour suppressor gene, which is common in conventional/clear cell (c)RCC. Method: A tumour bank containing 308 tumours from patients operated 1982-2003 was used. The tumours were well characterised regarding tumour type, TNM stage, nuclear grade, tumour size, and patient survival. The tumours were prepared in tissue microarrays and fresh frozen in whole sections. To analyse the expression of endoglin, CD31, CA IX, and HIF-2α mRNA, immunohistochemistry and real-time PCR were used. Results: There was a higher endoglin expression in cRCC than in papillary (p)RCC and chromophobe (ch)RCC, and a higher CD31 expression in cRCC than in pRCC. MVD correlated inversely to TNM stage and nuclear grade in cRCC. There was also an inverse correlation between tumour diameter and CD31 expression in cRCCs. Patients with cRCC with high MVD had a more favourable prognosis than patients with lower MVD. Endoglin and CD31 were not independent prognostic factors. The CA IX expression was higher in cRCC than in pRCC and chRCC. Patients with cRCC expressing low CA IX had a significantly less favourable prognosis compared with those with higher expression. CA IX is an independent prognostic factor. There was a higher HIF-2α mRNA expression in cRCC than in pRCC and chRCC. In cRCC, there was a significant inverse correlation between HIF-2α mRNA expression, and TNM stage and nuclear grade. There was also an inverse correlation between HIF-2α mRNA expression and tumour size among patients with cRCC. HIF-2α was not an independent prognostic factor. Conclusion: In these studies, the factors related to hypoxia and vascularity were all inversely correlated to tumour aggressiveness in cRCC. MVD, CA IX, and HIF-2α expression were also higher in cRCC than in pRCC and chRCC. The relationship between angiogenesis, vascularity, and hypoxia is ambiguous. A line of reasoning including mutations increasing angiogenesis in advanced disease may also be applied to RCC. Measurements of individual angiogenic factors seem to provide prognostic information, and can potentially be combined in patient monitoring and treatment.
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| 29. |
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| 30. |
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| 31. |
- Smeds, Johanna, et al.
(författare)
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Ductal carcinoma in situ of the breast with different histopathological grades and corresponding new breast tumour events : analysis of loss of heterozygosity
- 2005
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 44:1, s. 41-9
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Tidskriftsartikel (refereegranskat)abstract
- To compare chromosomal alterations in ductal carcinoma in situ (DCIS) of different histopathological grades and to study aberrations between primary DCIS and corresponding ipsi- or contralateral new in situ or invasive tumours, a study was undertaken of the pattern of loss of heterozygosity (LOH) at chromosomal regions in which LOH has previously been described in invasive breast cancer. LOH was analysed using 19 microsatellite markers located on chromosomes 3p, 6q, 8p, 8q, 9p, 11p, 11q, 16q, 17p, and 17q in 30 women with a primary DCIS. Eleven women with DCIS of grade 1 and 19 with grade 3 according to the EORTC classification system were included. In six patients LOH was also analysed in a subsequent new breast cancer. Fractional allelic loss (FAL, the ratio of chromosomal arms where allelic loss was detected divided by the total number of chromosomal arms with informative markers) was statistically significantly higher in grade 1 DCIS compared with grade 3 (p=0.02) for the 19 loci, indicating that the amount of allelic loss does not correlate with increasing aggressiveness of the studied tumours. Also observed was a complete heterogeneity of LOH in the primary DCIS and their corresponding new events, suggesting that these events probably developed from genetically divergent clones.
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| 32. |
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| 33. |
- Söder, Josefin, et al.
(författare)
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Effects of a physical exercise programme on bodyweight, body condition score and chest, abdominal and thigh circumferences in dogs
- 2024
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Ingår i: BMC Veterinary Research. - : BioMed Central (BMC). - 1746-6148. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundResearch on the effects of physical exercise on canine body composition is limited. The aim of this study was to investigate the effects of a physical exercise programme on bodyweight, body condition score (BCS) and chest, abdominal and thigh circumferences in dogs. Twenty-one healthy dogs of different breeds exercised together with their owners during an eight-week programme consisting of jogging and strength exercises. Standardised measurements were performed in triplicates with a measuring tape on standing dogs. Chest circumference was measured at three anatomical locations, abdomen at two and thigh at one. Data on bodyweight, BCS (9-point scale) and circumferences were analysed with mixed model repeated measures analyses to evaluate changes after the programme and effects of target distance.ResultsSeven dog owners choose a target distance of 2 km and 14 owners choose 5-10 km. Mean BCS decreased (P = 0.007) after the programme (5.1 +/- 0.9 vs. 4.7 +/- 0.6) but there was no effect of target distance. Almost all chest and abdominal circumference measurements decreased (P <= 0.007) with the 2 km group driving the reduction in chest circumference and the 5-10 km group driving the reduction in abdominal circumference. In contrast, thigh circumference (28.8 +/- 0.4 vs. 30.2 +/- 0.4) increased (P = 0.007) while bodyweight was maintained. There were positive correlations between BCS and abdominal/chest ratios before and after the programme (Pearson correlation; R square <= 0.43, P <= 0.0012) but the mean ratio remained constant.ConclusionsResults indicated a redistribution between total body fat and muscle mass in body composition of normal weight to slightly overweight dogs after the physical exercise programme. The use of bodyweight alone was not a reliable evaluation method to complement the BCS assessment. However, repeated measurements of chest, abdominal and thigh circumference might aid in the assessment of body composition in dogs performing physical exercise. Further research should include a control group and objective evaluations of total body fat and lean mass, in order to investigate the effectiveness of physical exercise as a freestanding method for decreasing BCS and increasing muscle mass in overweight dogs.
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| 34. |
- Wennmalm, Kristian, et al.
(författare)
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Gene expression in 16q is associated with survival and differs between Sørlie breast cancer subtypes
- 2007
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Ingår i: Genes, Chromosomes and Cancer. - : Wiley. - 1045-2257 .- 1098-2264. ; 46:1, s. 87-97
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Tidskriftsartikel (refereegranskat)abstract
- We have investigated the relationship between gene expression and chromosomal positions in 402 breast cancer patients. Using an overrepresentation approach based on Fisher's exact test, we identified disproportionate contributions of specific chromosomal positions to genes associated with survival. Our major finding is that the gene expression in the long arm of chromosome 16 stands out in its relationship to survival. This arm contributes 36 (18%) and 55 (11%) genes to lists negatively associated with recurrence-free survival (set to sizes 200 and 500). This is a highly disproportionate contribution from the 313 (2%) genes in this arm represented on the used Affymetrix U133A and B microarray platforms (Bonferroni corrected Fisher test: P < 2.2 x 10(-16)). We also demonstrate differential expression in 16q across tumor subtypes, which suggests that the ERBB2, basal, and luminal B tumors progress along a high grade-poor prognosis path, while luminal A and normal-like tumors progress along a low grade-good prognosis path, in accordance with a previously proposed model of tumor progression. We conclude that important biological information can be extracted from gene expression data in breast cancer by studying non-random connections between chromosomal positions and gene expression. This article contains Supplementary Material available at http://www.interscience.wiley.com/jpages/1045-2257/suppmat.
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