| 1. |
- Klionsky, Daniel J., et al.
(author)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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In: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Research review (peer-reviewed)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 2. |
- Jönsson, Göran B, et al.
(author)
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The retinoblastoma gene undergoes rearrangements in BRCA1-deficient basal-like breast cancer.
- 2012
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In: Cancer Research. - 1538-7445. ; 72:16, s. 4028-4036
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Journal article (peer-reviewed)abstract
- Breast tumors from BRCA1 germ line mutation carriers typically exhibit features of the basal-like molecular subtype. However, the specific genes recurrently mutated as a consequence of BRCA1 dysfunction have not been fully elucidated. In this study, we utilized gene expression profiling to molecularly subtype 577 breast tumors, including 72 breast tumors from BRCA1/2 mutation carriers. Focusing on the RB1 locus, we analyzed 33 BRCA1-mutated, 36 BRCA2-mutated and 48 non-BRCA1/2-mutated breast tumors using a custom-designed high-density oligomicroarray covering the RB1 gene. We found a strong association between the basal-like subtype and BRCA1-mutated breast tumors and the luminal B subtype and BRCA2-mutated breast tumors. RB1 was identified as a major target for genomic disruption in tumors arising in BRCA1 mutation carriers and in sporadic tumors with BRCA1 promoter-methylation, but rarely in other breast cancers. Homozygous deletions, intragenic breaks, or microdeletions were found in 33% of BRCA1-mutant tumors, 36% of BRCA1 promoter-methylated basal-like tumors, 13% of non-BRCA1 deficient basal-like tumors, and 3% of BRCA2-mutated tumors. In conclusion, RB1 was frequently inactivated by gross gene disruption in BRCA1-related hereditary breast cancer and BRCA1-methylated sporadic basal-like breast cancer, but rarely in BRCA2-hereditary breast cancer and non-BRCA1-deficient sporadic breast cancers. Together, our findings demonstrate the existence of genetic heterogeneity within the basal-like breast cancer subtype that is based upon BRCA1-status.
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| 3. |
- Aaltonen, Kristina, et al.
(author)
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Association between insulin-like growth factor-1 receptor (IGF1R) negativity and poor prognosis in a cohort of women with primary breast cancer
- 2014
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In: BMC Cancer. - : BioMed Central. - 1471-2407. ; 14:794
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Journal article (peer-reviewed)abstract
- Background: Resistance towards endocrine therapy is a great concern in breast cancer treatment and may partly be explained by the activation of compensatory signaling pathways. The aim of the present study was to investigate if the insulin-like growth factor-1 receptor (IGF1R) signaling pathway was activated or deregulated in breast cancer patients and to explore if any of the markers were prognostic, with or without adjuvant tamoxifen. This signaling pathway has been suggested to cause estrogen independent cell growth and thus contribute to resistance to endocrine treatment in estrogen receptor (ER) positive breast cancer. Methods: The protein expression of IGF1R, phosphorylated Mammalian Target of Rapamycin (p-mTOR) and phosphorylated S6 ribosomal protein (p-S6rp) were investigated by immunohistochemistry using tissue microarrays in two patient cohorts. Cohort I (N = 264) consisted of mainly postmenopausal women with stage II breast cancer treated with tamoxifen for 2 years irrespective of ER status. Cohort II (N = 206) consisted of mainly medically untreated, premenopausal patients with node-negative breast cancer. Distant disease-free survival (DDFS) at 5 years was used as end-point for survival analyses. Results: We found that lower IGF1R expression was associated with worse prognosis for tamoxifen treated, postmenopausal women (HR = 0.70, 95% CI = 0.52 - 0.94, p = 0.016). The effect was seen mainly in ER-negative patients where the prognostic effect was retained after adjustment for other prognostic markers (adjusted HR = 0.49, 95% CI = 0.29 - 0.82, p = 0.007). Expression of IGF1R was associated with ER positivity (p less than 0.001) in the same patient cohort. Conclusions: Our results support previous studies indicating that IGF1R positivity reflects a well differentiated tumor with low metastatic capacity. An association between lack of IGF1R expression and worse prognosis was mainly seen in the ER-negative part of Cohort I. The lack of co-activation of downstream markers (p-mTOR and p-S6rp) in the IGF1R pathway suggested that the prognostic effect was not due to complete activation of this pathway. Thus, no evidence could be found for a compensatory function of IGF1R signaling in the investigated cohorts.
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| 4. |
- Adwall, Linda, et al.
(author)
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Antibiotikaprofylax vid bröstkirurgi? Ja, men inte till alla. Kvalitetsdata fran Uppsala läns landsting ger förslag till riktlinjer
- 2013
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In: Läkartidningen. - Stockholm : Läkartidningen förlag. - 0023-7205 .- 1652-7518. ; 110:5, s. 213-215
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Journal article (other academic/artistic)abstract
- I randomiserade studier har det visats att antibiotikaprofylax minskar infektionsfrekvensen med cirka 30–40 procent vid bröstcancerkirurgi.Statens beredning för medicinsk utvärdering rekommenderar därför sedan 2010 antibiotikaprofylax vid bröstcancerkirurgi.I Uppsala läns landsting fick totalt cirka 10 procent postoperativ infektion efter bröstkirurgi under 2009 och 2010. Ingreppets omfattning relaterar klart till risken för infektion.Vi diskuterar i denna artikel när det kan vara indicerat att ge eller inte ge antibiotikaprofylax vid bröstcancerkirurgi.
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| 5. |
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| 6. |
- Aliasgharzad, Nasser, et al.
(author)
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Acidification of a sandy grassland favours bacteria and disfavours fungal saprotrophs as estimated by fatty acid profiling
- 2010
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In: Soil Biology & Biochemistry. - : Elsevier BV. - 0038-0717. ; 42:7, s. 1058-1064
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Journal article (peer-reviewed)abstract
- We have investigated the structure of a microbial community in semi-natural sandy grassland in southeast Sweden. The sand is rich in lime, but in most places the soil is decalcified in the upper layers, and therefore this site shows a large variation in pH within short distances. We collected samples at three different soil depths (0-10 cm, 10-20 cm and 20-30 cm) and found the pH to range from 5 to 8 in the topsoil and from 4.5 to 9.5 in the deepest layer. The abundance of saprophytic fungi and bacteria was investigated using signature phospholipid fatty acids and arbuscular mycorrhizal fungi (AMF) using the neutral lipid fatty acid 16:1 omega 5. The PLFA pattern of the topsoil was different from that in the other two layers, as indicated by principal component analysis. The saprotrophic fungi were associated with high pH, and bacteria with low pH in these sandy soils. No relation was found between pH and AMF in the topsoil, while a positive relation was found in the deepest soil layer. The saprophytic fungi-to-bacteria ratio was constant with depth, while the AMF-to-bacteria ratio increased with soil depth. The results showed that high soil pH favoured fungal saprophytes in sandy grasslands and that AMF are relatively more abundant than the other two groups in deeper soil layers: particularly so when the pH is high. (C) 2010 Elsevier Ltd. All rights reserved.
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| 7. |
- Andersson-Engels, Stefan, et al.
(author)
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In vivo luminescence imaging and tomography using upconverting nanoparticles as contrast agents
- 2012
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In: 2012 Asia Communications and Photonics Conference. - 2162-108X. ; , s. 2-3
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Conference paper (peer-reviewed)abstract
- Upconverting nanoparticles have recently drawn increasingly attention as contrast agents for optical bioimaging. They enable autofluorescence-free imaging within the tissue optical window, and improved spatial resolution as compared to conventional fluorescence-based contrast agents. (C) 2012 Optical Society of America
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| 8. |
- Anrup, Roland, et al.
(author)
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Centrala universitetsvärden hotas av bolagiseringsidén
- 2013
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In: Dagens nyheter. - 1101-2447.
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Journal article (pop. science, debate, etc.)abstract
- Högskolestiftelser. Förslaget att driva svenska universitet i stiftelseform öppnar för bolagisering. Men det är ingen riktig utredning, utan en politisk pamflett utan eftertanke. Privatisering av universitet hotar både oberoendet, forskningskvaliteten och samhällsnyttan, skriver 36 forskare vid svenska högskolor och universitet.
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| 9. |
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| 10. |
- Beral, V., et al.
(author)
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Ovarian Cancer and Body Size : Individual Participant Meta-Analysis Including 25,157 Women with Ovarian Cancer from 47 Epidemiological Studies
- 2012
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In: PLoS Medicine. - : PUBLIC LIBRARY SCIENCE. - 1549-1277 .- 1549-1676. ; 9:4
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Journal article (peer-reviewed)abstract
- Background: Only about half the studies that have collected information on the relevance of women's height and body mass index to their risk of developing ovarian cancer have published their results, and findings are inconsistent. Here, we bring together the worldwide evidence, published and unpublished, and describe these relationships. Methods and Findings: Individual data on 25,157 women with ovarian cancer and 81,311 women without ovarian cancer from 47 epidemiological studies were collected, checked, and analysed centrally. Adjusted relative risks of ovarian cancer were calculated, by height and by body mass index. Ovarian cancer risk increased significantly with height and with body mass index, except in studies using hospital controls. For other study designs, the relative risk of ovarian cancer per 5 cm increase in height was 1.07 (95% confidence interval [CI], 1.05-1.09; p<0.001); this relationship did not vary significantly by women's age, year of birth, education, age at menarche, parity, menopausal status, smoking, alcohol consumption, having had a hysterectomy, having first degree relatives with ovarian or breast cancer, use of oral contraceptives, or use of menopausal hormone therapy. For body mass index, there was significant heterogeneity (p<0.001) in the findings between ever-users and never-users of menopausal hormone therapy, but not by the 11 other factors listed above. The relative risk for ovarian cancer per 5 kg/m(2) increase in body mass index was 1.10 (95% CI, 1.07-1.13; p<0.001) in never-users and 0.95 (95% CI, 0.92-0.99; p = 0.02) in ever-users of hormone therapy. Conclusions: Ovarian cancer is associated with height and, among never-users of hormone therapy, with body mass index. In high-income countries, both height and body mass index have been increasing in birth cohorts now developing the disease. If all other relevant factors had remained constant, then these increases in height and weight would be associated with a 3% increase in ovarian cancer incidence per decade.
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