| 1. |
- Franklin, Oskar, 1985-, et al.
(author)
-
Novel prognostic markers within the CD44-stromal ligand network in pancreatic cancer
- 2019
-
In: Journal of Pathology. - : John Wiley & Sons. - 0022-3417 .- 1096-9896. ; 5:2, s. 130-141
-
Journal article (peer-reviewed)abstract
- The dense stroma in pancreatic cancer tumours is rich in secreted extracellular matrix proteins and proteoglycans. Secreted hyaluronan, osteopontin and type IV collagen sustain oncogenic signalling by interactions with CD44s and its variant isoform CD44v6 on cancer cell membranes. Although well established in animal and in vitro models, this oncogenic CD44-stromal ligand network is less explored in human cancer. Here, we use a pancreatic cancer tissue microarray from 69 primary tumours and 37 metastatic lymph nodes and demonstrate that high tumour cell expression of CD44s and, surprisingly, low stromal deposition of osteopontin correlate with poor survival independent of established prognostic factors for pancreatic cancer. High stromal expression of hyaluronan was a universal trait of both primary tumours and metastatic lymph nodes. However, hyaluronan species of different molecular mass are known to function differently in pancreatic cancer biology and immunohistochemistry cannot distinguish between them. Using gas-phase electrophoretic molecular mobility analysis, we uncover a shift towards high molecular mass hyaluronan in pancreatic cancer tissue compared to normal pancreas and at a transcriptional level, we find that hyaluronan synthesising HAS2 correlates positively with CD44. The resulting prediction that high molecular mass hyaluronan would then correlate with poor survival in pancreatic cancer was confirmed in serum samples, where we demonstrate that hyaluronan >27 kDa measured before surgery is an independent predictor of postoperative survival. Our findings confirm the prognostic value of CD44 tissue expression and highlight osteopontin tissue expression and serum high molecular mass hyaluronan as novel prognostic markers in pancreatic cancer.
|
|
| 2. |
- Li, Xingru, et al.
(author)
-
Ex Vivo Organoid Cultures Reveal the Importance of the Tumor Microenvironment for Maintenance of Colorectal Cancer Stem Cells
- 2020
-
In: Cancers. - : MDPI. - 2072-6694. ; 12:4
-
Journal article (peer-reviewed)abstract
- Colorectal cancer (CRC) is a heterogeneous disease, with varying clinical presentations and patient prognosis. Different molecular subgroups of CRC should be treated differently and therefore, must be better characterized. Organoid culture has recently been suggested as a good model to reflect the heterogeneous nature of CRC. However, organoid cultures cannot be established from all CRC tumors. The study examines which CRC tumors are more likely to generate organoids and thus benefit from ex vivo organoid drug testing. Long-term organoid cultures from 22 out of 40 CRC tumor specimens were established. It was found that organoid cultures were more difficult to establish from tumors characterized as microsatellite instable (MSI), BRAF-mutated, poorly differentiated and/or of a mucinous type. This suggests that patients with such tumors are less likely to benefit from ex vivo organoid drug testing, but it may also suggest biological difference in tumor growth. RNA sequencing analysis of tumor sections revealed that the in vivo maintenance of these non-organoid-forming tumors depends on factors related to inflammation and pathogen exposure. Furthermore, using TCGA data we could show a trend towards a worse prognosis for patients with organoid-forming tumors, suggesting also clinical differences. Results suggest that organoids are more difficult to establish from tumors characterized as MSI, BRAF-mutated, poorly differentiated and/or of a mucinous type. We further suggest that the maintenance of cell growth of these tumors in vivo may be promoted by immune-related factors and other stromal components within the tumor microenvironment.
|
|
| 3. |
- Skulason, Skuli, et al.
(author)
-
A way forward with eco evo devo : an extended theory of resource polymorphism with postglacial fishes as model systems
- 2019
-
In: Biological Reviews. - : John Wiley & Sons. - 1464-7931 .- 1469-185X. ; 94:5, s. 1786-1808
-
Research review (peer-reviewed)abstract
- A major goal of evolutionary science is to understand how biological diversity is generated and altered. Despite considerable advances, we still have limited insight into how phenotypic variation arises and is sorted by natural selection. Here we argue that an integrated view, which merges ecology, evolution and developmental biology (eco evo devo) on an equal footing, is needed to understand the multifaceted role of the environment in simultaneously determining the development of the phenotype and the nature of the selective environment, and how organisms in turn affect the environment through eco evo and eco devo feedbacks. To illustrate the usefulness of an integrated eco evo devo perspective, we connect it with the theory of resource polymorphism (i.e. the phenotypic and genetic diversification that occurs in response to variation in available resources). In so doing, we highlight fishes from recently glaciated freshwater systems as exceptionally well‐suited model systems for testing predictions of an eco evo devo framework in studies of diversification. Studies on these fishes show that intraspecific diversity can evolve rapidly, and that this process is jointly facilitated by (i) the availability of diverse environments promoting divergent natural selection; (ii) dynamic developmental processes sensitive to environmental and genetic signals; and (iii) eco evo and eco devo feedbacks influencing the selective and developmental environments of the phenotype. We highlight empirical examples and present a conceptual model for the generation of resource polymorphism – emphasizing eco evo devo, and identify current gaps in knowledge.
|
|
| 4. |
- Öhlund, Carl, et al.
(author)
-
Calf compression for prevention of thromboembolism following hip surgery
- 1983
-
In: Acta Orthopaedica. - : Informa Healthcare. - 1745-3674 .- 1745-3682 .- 0001-6470. ; 54:6, s. 896-899
-
Journal article (peer-reviewed)abstract
- A prospective, randomized trial of the effect of graded compression of the calf was done in 62 patients operated on electively for hip disease. After total hip arthroplasty, compression reduced the number of positive fibrinogen uptake tests by two-thirds, significant only in males, who seem to run a higher risk of thrombosis than females.
|
|
| 5. |
|
|
