| 1. |
- Kehoe, Laura, et al.
(author)
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Make EU trade with Brazil sustainable
- 2019
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
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Journal article (other academic/artistic)
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| 2. |
- Antonelli, Alexandre, 1978, et al.
(author)
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Madagascar's extraordinary biodiversity : Evolution, distribution, and use
- 2022
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 378:6623, s. 962-
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Journal article (peer-reviewed)abstract
- Madagascar's biota is hyperdiverse and includes exceptional levels of endemicity. We review the current state of knowledge on Madagascar's past and current terrestrial and freshwater biodiversity by compiling and presenting comprehensive data on species diversity, endemism, and rates of species description and human uses, in addition to presenting an updated and simplified map of vegetation types. We report a substantial increase of records and species new to science in recent years; however, the diversity and evolution of many groups remain practically unknown (e.g., fungi and most invertebrates). Digitization efforts are increasing the resolution of species richness patterns and we highlight the crucial role of field- and collections-based research for advancing biodiversity knowledge and identifying gaps in our understanding, particularly as species richness corresponds closely to collection effort. Phylogenetic diversity patterns mirror that of species richness and endemism in most of the analyzed groups. We highlight humid forests as centers of diversity and endemism because of their role as refugia and centers of recent and rapid radiations. However, the distinct endemism of other areas, such as the grassland-woodland mosaic of the Central Highlands and the spiny forest of the southwest, is also biologically important despite lower species richness. The documented uses of Malagasy biodiversity are manifold, with much potential for the uncovering of new useful traits for food, medicine, and climate mitigation. The data presented here showcase Madagascar as a unique " living laboratory" for our understanding of evolution and the complex interactions between people and nature. The gathering and analysis of biodiversity data must continue and accelerate if we are to fully understand and safeguard this unique subset of Earth's biodiversity.
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| 3. |
- Corvigno, Sara, et al.
(author)
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Multi-parametric profiling of renal cell, colorectal, and ovarian cancer identifies tumour-type-specific stroma phenotypes and a novel vascular biomarker
- 2017
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In: The journal of pathology. Clinical research. - : WILEY. - 2056-4538. ; 3:3, s. 214-224
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Journal article (peer-reviewed)abstract
- A novel set of integrated procedures for quantification of fibroblast-rich stroma and vascular characteristics has recently been presented allowing discovery of novel perivascular and stromal biomarkers in colorectal, renal cell, and ovarian cancer. In the present study, data obtained through these procedures from clinically well-annotated collections of these three tumour types have been used to address two novel questions. First, data have been used to investigate if the three tumour types demonstrate significant differences regarding features such as vessel diameter, vessel density, and perivascular marker expression. Second, analyses of the cohorts have been used to explore the prognostic significance of a novel vascular metric, 'vessel distance inter-quartile range (IQR)' that describes intra-case heterogeneity regarding vessel distribution. The comparisons between the three tumour types demonstrated a set of significant differences. Vessel density of renal cell cancer was statistically significantly higher than in colorectal and ovarian cancer. Vessel diameter was statistically significantly higher in ovarian cancer. Concerning perivascular status, colorectal cancer displayed significantly higher levels of perivascular PDGFR-beta expression than the other two tumour types. Intra-case heterogeneity of perivascular PDGFR-beta expression was also higher in colorectal cancer. Notably, these fibroblast-dominated stroma phenotypes matched previously described experimental tumour stroma characteristics, which have been linked to differential sensitivity to anti-VEGF drugs. High 'vessel distance IQR' was significantly associated with poor survival in both renal cell cancer and colorectal cancer. In renal cell cancer, this characteristic also acted as an independent prognostic marker according to multivariate analyses including standard clinico-pathological characteristics. Explorative subset analyses indicated particularly strong prognostic significance of 'vessel distance IQR' in T stage 4 of this cancer type. Together, these analyses identified tumour-type-specific vascular-stroma phenotypes of possible functional significance, and suggest 'vessel distance IQR' as a novel prognostic biomarker.
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| 4. |
- Djureinovic, Tatjana, et al.
(author)
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The CHEK2 1100delC variant in Swedish colorectal cancer
- 2006
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In: Anticancer Research. - 0250-7005 .- 1791-7530. ; 26:6C, s. 4885-4888
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Journal article (peer-reviewed)abstract
- BACKGROUND: The cell cycle checkpoint kinase 2 (CHEK2) 1100delC variant has recently been identified at high frequency in families with both breast and colorectal cancer, suggesting the possible role of this variant in colorectal cancer predisposition. PATIENTS AND METHODS: To evaluate the role of CHEK2 ll00delC among Swedish colorectal cancer patients, the variant frequency was determined in 174 selected familial cases, 644 unselected cases and 760 controls, as well as in l8 families used in the genome-wide linkage analysis, where weak linkage was seen for the region harboring the CHEK2 gene. RESULTS: CHEK2 l100delC was found in 1.15% of familial and in 0.93% of unselected cases, compared to 0.66% of controls, showing no significant difference between groups. One out of 45 familial cases with a family history of breast cancer was shown to be a carrier. The variant was not identified in the 18 families included in the linkage analysis. CONCLUSION: The CHEK2 1100delC was not significantly increased in Swedish colorectal cancer patients, however, in order to determine the role of the variant in colorectal cancer families with the history of breast cancer a larger sample size is needed.
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| 5. |
- Edler, David, et al.
(author)
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The expression of the novel CYP2W1 enzyme is an independent prognostic factor in colorectal cancer : a pilot study.
- 2009
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In: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 45:4, s. 705-712
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Journal article (peer-reviewed)abstract
- AIM Cytochrome P450 (CYP) enzymes are important for drug metabolism. A novel cytochrome P450 enzyme, CYP2W1, has recently been identified. This enzyme is mainly found in foetal colon tissue and in tumour tissue. In this pilot study, we have investigated the expression of CYP2W1 in 162 tumours from patients with stages II and III colorectal cancer. METHODS The expression of CYP2W1 enzyme was immunohistochemically detected using a polyclonal antibody. Staining intensity was defined using a visual grading scale from 0 to 3. Grades 0-2 were classified as low, and grade 3 was classified as high expression of CYP2W1. RESULTS About 64% of the tumours expressed a low level of CYP2W1-expression, and 36% expressed a high level. CYP2W1-expression was an independent prognostic factor for overall survival (p=0.007), where a high expression was associated with a worse clinical outcome. CONCLUSIONS Immunohistochemically assessed expression of CYP2W1 is an independent prognostic factor in patients with stages II and III colorectal cancer.
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| 6. |
- Edler, David
(author)
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Thymidylate synthase expression in colorectal cancer : its role as a prognostic factor and a predictive factor in adjuvant 5-fluorouracil-based chemotherapy
- 2001
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Doctoral thesis (other academic/artistic)abstract
- The enzyme thymidylate synthase (TS) plays a central role in DNA synthesis and is therefore an important target for chemotherapeutic treatment. We have studied the prognostic value of immunohistochemically detected TS on slices of formalin-fixed. paraffin embedded stored colorectal tumors using the monoclonal antibody TS 106. The level of TS staining in 25 primary colorectal cancers, arbitrarily scored in grades of 0, 1,2, and 3, correlated with enzyme activity, as measured by a tritium release method. TS was homogenously expressed in two thirds of 48 studied primary colorectal tumors. TS expression, assessed in 70 primary colorectal cancers Dukes' stage A-D, was an independent prognostic factor for time to death in colorectal cancer (p=0.04). Low TS expression (TS grades 0 or 1) correlated with better outcome and high TS expression (TS grades 2 or 3) with worse outcome. 243 patients with rectal cancer Dukes' stage A-C were retrospectively studied. Multivariate analysis showed that TS expression was an independent marker for loco-regional recurrence (p=0.04), distant metastasis (p=0.01) and overall survival (p=0.02). The predictive value of TS expression was studied in colorectal cancers of Dukes' stage B and C from 862 patients who all were included in Nordic adjuvant trials evaluating the efficiency of adjuvant 5- fluorouracil (5-FU) -based chemotherapy. No benefit of adjuvant chemotherapy was found in this group of patients, which was a subgroup of the 2191 included in randomized Nordic studies. In our study group, TS expression was an independent factor for disease-free survival (p=0.05) and overall survival (p=0.05). In the group of 442 patients treated with surgery only, TS expression was an independent prognostic factor (disease-free survival, p<0.001, overall survival, p=0.001), while in the group of patients treated with surgery and 5-FU -based chemotherapy, TS expression was not of prognostic value. Patients with high TS -expressing tumors had a tendency toward improved clinical outcome (not significant), whereas patients whose tumors expressed a low TS level (28% of the patients) had an impaired clinical outcome following adjuvant therapy (overall survival p=0.008). A weak but significant association was found between Ki-67 expression and TS expression (low/high) in rectal cancer (p=0.02). There was no significant correlation between TS and Cyclin A expression (p=0.1). Conclusions: TS levels, immunohistochemically assessed in colorectal cancer, are a prognostic factor independent of Dukes' stage. Patients with Dukes' C tumors with low TS expression, as determined by immunohistochemistry, will, according to our findings, have an impaired survival if they are treated with surgery and 5-FU -based adjuvant chemotherapy compared with surgery alone. Further studies in new patient material are needed to see whether the results of the present study can be reproduced. If this is the case, 5-FU -based adjuvant treatment is to be recommended only to high TS expressors, but not to low TS expressors.
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| 7. |
- Lee, Sarah C., et al.
(author)
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Nano-encapsulated Escherichia coli Divisome Anchor ZipA, and in Complex with FtsZ
- 2019
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1
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Journal article (peer-reviewed)abstract
- The E. coli membrane protein ZipA, binds to the tubulin homologue FtsZ, in the early stage of cell division. We isolated ZipA in a Styrene Maleic Acid lipid particle (SMALP) preserving its position and integrity with native E. coli membrane lipids. Direct binding of ZipA to FtsZ is demonstrated, including FtsZ fibre bundles decorated with ZipA. Using Cryo-Electron Microscopy, small-angle X-ray and neutron scattering, we determine the encapsulated-ZipA structure in isolation, and in complex with FtsZ to a resolution of 1.6 nm. Three regions can be identified from the structure which correspond to, SMALP encapsulated membrane and ZipA transmembrane helix, a separate short compact tether, and ZipA globular head which binds FtsZ. The complex extends 12 nm from the membrane in a compact structure, supported by mesoscale modelling techniques, measuring the movement and stiffness of the regions within ZipA provides molecular scale analysis and visualisation of the early divisome.
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| 8. |
- Loftås, Per, et al.
(author)
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FXYD-3 expression in relation to local recurrence of rectal cancer
- 2016
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In: Radiation Oncology Journal. - : Samsung Medical Center, Sungkyunkwan University School of Medicine, Korea. - 2234-1900 .- 2234-3156. ; 34:1, s. 52-58
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Journal article (peer-reviewed)abstract
- Purpose: In a previous study, the transmembrane protein FXYD-3 was suggested as a biomarker for a lower survival rate and reduced radiosensitivity in rectal cancer patients receiving preoperative radiotherapy. The purpose of preoperative irradiation in rectal cancer is to reduce local recurrence. The aim of this study was to investigate the potential role of FXYD-3 as a biomarker for increased risk for local recurrence of rectal cancer.Materials and Methods: FXYD-3 expression was immunohistochemically examined in surgical specimens from a cohort of patients with rectal cancer who developed local recurrence (n = 48). The cohort was compared to a matched control group without recurrence (n = 81).Results: Weak FXYD-3 expression was found in 106/129 (82%) of the rectal tumors and strong expression in 23/129 (18%). There was no difference in the expression of FXYD-3 between the patients with local recurrence and the control group. Furthermore there was no difference in FXYD-3 expression and time to diagnosis of local recurrence between patients who received preoperative radiotherapy and those without.Conclusion: Previous findings indicated that FXYD-3 expression may be used as a marker of decreased sensitivity to radiotherapy or even overall survival. We were unable to confirm this in a cohort of rectal cancer patients who developed local recurrence.
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| 9. |
- Mezheyeuski, Artur, et al.
(author)
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Stroma-normalised vessel density predicts benefit from adjuvant fluorouracil-based chemotherapy in patients with stage II/III colon cancer
- 2019
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In: British Journal of Cancer. - : NATURE PUBLISHING GROUP. - 0007-0920 .- 1532-1827. ; 121:4, s. 303-311
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Journal article (peer-reviewed)abstract
- BACKGROUND: Identification of biomarkers associated with benefit of adjuvant chemotherapy in stage II/III colon cancer is an important task. METHODS: Vessel density (VD) and tumour stroma were analysed in a randomised-trial-derived discovery cohort (n = 312) and in a stage II/III group of a population-based validation cohort (n = 85). VD was scored separately in the tumour centre, invasive margin and peritumoral stroma compartments and quantitated as VD/total analysed tissue area or VD/stroma area. RESULTS: High stroma-normalised VD in the invasive margin was associated with significantly longer time to recurrence and overall survival (OS) (p = 0.002 and p = 0.006, respectively) in adjuvant-treated patients of the discovery cohort, but not in surgery-only patients. Stroma-normalised VD in the invasive margin and treatment effect were significantly associated according to a formal interaction test (p = 0.009). Similarly, in the validation cohort, high stroma-normalised VD was associated with OS in adjuvant-treated patients, although statistical significance was not reached (p = 0.051). CONCLUSION: Through the use of novel digitally scored vessel-density-related metrics, this exploratory study identifies stroma-normalised VD in the invasive margin as a candidate marker for benefit of adjuvant 5-FU-based chemotherapy in stage II/III colon cancer. The findings, indicating particular importance of vessels in the invasive margin, also suggest biological mechanisms for further exploration.
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| 10. |
- Mezheyeuski, Artur, et al.
(author)
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Treatment-related survival associations of claudin-2 expression in fibroblasts of colorectal cancer
- 2018
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In: Virchows Archiv. - : SPRINGER. - 0945-6317 .- 1432-2307. ; 472:3, s. 395-405
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Journal article (peer-reviewed)abstract
- Claudin-2 is a trans-membrane protein-component of tight junctions in epithelial cells. Elevated claudin-2 expression has been reported in colorectal cancer (CRC). The aim of this study was to investigate the expression patterns of claudin-2 in human CRC samples and analyze its association with clinical characteristics and treatment outcome. TMAs of primary tumors from two cohorts of metastatic CRC (mCRC) were used. Claudin-2 IHC staining was evaluated in a semi-quantitative manner in different regions and cell types. Claudin-2 expression was also analyzed by immunofluorescence in primary cultures of human CRC cancer-associated fibroblasts (CAFs). Initial analyses identified previously unrecognized expression patterns of claudin-2 in CAFs of human CRC. Claudin-2 expression in CAFs of the invasive margin was associated with shorter progression-free survival. Subgroup analyses demonstrated that the survival associations occurred among cases that received 5-FU+oxaliplatin combination treatment, but not in patients receiving 5-FU +/- irinotecan. The finding was validated by analyses of the independent cohort. In summary, previously unreported stromal expression of claudin-2 in CAFs of human CRC was detected together with significant association between high claudin-2 expression in CAFs and shorter survival in 5-FU+oxaliplatin-treated mCRC patients.
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