| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
- Moro, CF, et al.
(författare)
-
Drug-induced tumor-specific cytotoxicity in a whole tissue ex vivo model of human pancreatic ductal adenocarcinoma
- 2022
-
Ingår i: Frontiers in oncology. - : Frontiers Media SA. - 2234-943X. ; 12, s. 965182-
-
Tidskriftsartikel (refereegranskat)abstract
- Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer. PDAC has a dismal prognosis and an inherent resistance to cytostatic drugs. The lack of reliable experimental models is a severe limitation for drug development targeting PDAC. We have employed a whole tissue ex vivo culture model to explore the effect of redox-modulation by sodium selenite on the viability and growth of PDAC. Drug-resistant tumors are more vulnerable to redox-active selenium compounds because of high metabolic activity and redox imbalance. Sodium selenite efficiently and specifically reduced PDAC cell viability (p <0.02) (n=8) and decreased viable de novo tumor cell outgrowth (p<0.05) while preserving non-neoplastic tissues. Major cellular responses (damaged tumor cells > 90%, tumor regression grades III-IV according to Evans) were observed for sodium selenite concentrations between 15-30 µM. Moreover, selenium levels used in this study were significantly below the previously reported maximum tolerated dose for humans. Transcriptome data analysis revealed decreased expression of genes known to drive PDAC growth and metastatic potential (CEMIP, DDR2, PLOD2, P4HA1) while the cell death-inducing genes (ATF3, ACHE) were significantly upregulated (p<0.0001). In conclusion, we report that sodium selenite has an extraordinary efficacy and specificity against drug-resistant pancreatic cancer in an organotypic slice culture model. Our ex vivo organotypic tissue slice culture model can be used to test a variety of drug candidates for swift and reliable drug responses to individual PDAC cases.
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
- Bosma, M, et al.
(författare)
-
FNDC4 acts as an anti-inflammatory factor on macrophages and improves colitis in mice
- 2016
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7, s. 11314-
-
Tidskriftsartikel (refereegranskat)abstract
- FNDC4 is a secreted factor sharing high homology with the exercise-associated myokine irisin (FNDC5). Here we report that Fndc4 is robustly upregulated in several mouse models of inflammation as well as in human inflammatory conditions. Specifically, FNDC4 levels are increased locally at inflamed sites of the intestine of inflammatory bowel disease patients. Interestingly, administration of recombinant FNDC4 in the mouse model of induced colitis markedly reduces disease severity compared with mice injected with a control protein. Conversely, mice lacking Fndc4 develop more severe colitis. Analysis of binding of FNDC4 to different immune cell types reveals strong and specific binding to macrophages and monocytes. FNDC4 treatment of bone marrow-derived macrophages in vitro results in reduced phagocytosis, increased cell survival and reduced proinflammatory chemokine expression. Hence, treatment with FNDC4 results in a state of dampened macrophage activity, while enhancing their survival. Thus, we have characterized FNDC4 as a factor with direct therapeutic potential in inflammatory bowel disease and possibly other inflammatory diseases.
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
- Hagström, A. L., et al.
(författare)
-
An iterative approach to determine the refractive index of 3D printed 60GHz PLA lenses
- 2018
-
Ingår i: Proceedings of the 14th Loughborough Antennas and Propagation Conference (LAPC 2018). - Piscataway, N.J. : IEEE. - 9781785619694
-
Konferensbidrag (refereegranskat)abstract
- This paper describes an iterative approach to determine quasi-optical properties of standard 3D printer filament material to, in an inexpensive and fast way, construct focusing lenses for millimetre wave systems. Results from three lenses with different focal lengths are shown and discussed. The real part of the permittivity at 60GHz for polylactic acid (PLA) is in this paper determined to be εr=2.74. © 2018 Institution of Engineering and Technology. All rights reserved.
|
|
| 11. |
|
|
| 12. |
|
|
| 13. |
|
|
| 14. |
- Liu, LL, et al.
(författare)
-
Systemic inflammatory syndromes as life-threatening side effects of immune checkpoint inhibitors: case report and systematic review of the literature
- 2023
-
Ingår i: Journal for immunotherapy of cancer. - : BMJ. - 2051-1426. ; 11:3
-
Tidskriftsartikel (refereegranskat)abstract
- Immune checkpoint inhibitors (ICIs) are associated with a wide range of immune-related adverse events. As oncological indications for ICIs widen, their rare side effects become increasingly visible in clinical practice and impact therapy decisions.Here, we report a rare case of early-onset, mild cytokine release syndrome (CRS) in a patient who received ICIs for a metastasized renal cell carcinoma, which led to treatment discontinuation.We further provide a systematic review of the literature of CRS and related life-threatening side effects of ICI treatment, such as hemophagocytic lymphohistiocytosis (HLH). We searched Medline, Embase and the Web of Science Core Collection from inception to October 2021 for reports on CRS, cytokine storm, macrophage activation syndrome, HLH, and related hyperinflammatory disorders in patients with solid cancers receiving ICIs. We found n=1866 articles, which were assessed for eligibility independently by two examiners. Of those, n=49 articles reporting on n=189 individuals were eligible for review. We found that the median time from last infusion to the occurrence of CRS/HLH was approximately nine days, while the onset of symptoms varied from immediately after infusion to one month after treatment. Most patients were treated with either corticosteroids or the anti-interleukin 6 (IL-6) antibody tocilizumab, and although the majority of patients recovered, a few cases were fatal. Concomitant IL-6 and ICI treatment were reported as beneficial for both the antitumoral effect and for limiting side effects. Data from international pharmacovigilance databases underscored that ICI-related CRS and HLH are rare events, but we identified significant differences in reported frequencies, which might suggest substantial under-reporting.The results from this first systematic review of CRS/HLH due to ICI therapy highlight that life-threatening systemic inflammatory complications of ICIs are rare and might be associated with fatal outcome in approximately 10% of patients. Limited data support the use of IL-6 inhibitors in combination with ICIs to augment the antitumoral effect and reduce hyperinflammation.
|
|
| 15. |
|
|
| 16. |
|
|
| 17. |
|
|
| 18. |
|
|
| 19. |
- Bergstrom, A, et al.
(författare)
-
Severe liver disease resembling PSC in mice with K5-Cre mediated deletion of Krüppel-like factor 5 (Klf5)
- 2021
-
Ingår i: Transgenic research. - : Springer Science and Business Media LLC. - 1573-9368 .- 0962-8819. ; 30:5, s. 701-707
-
Tidskriftsartikel (refereegranskat)abstract
- Chronic cholestatic liver diseases including primary sclerosing cholangitis (PSC) present a complex spectrum with regards to the cause, age of manifestation and histopathological features. Current treatment options are severely limited primarily due to a paucity of model systems mirroring the disease. Here, we describe the Keratin 5 (K5)-Cre; Klf5fl/fl mouse that spontaneously develops severe liver disease during the postnatal period with features resembling PSC including a prominent ductular reaction, fibrotic obliteration of the bile ducts and secondary degeneration/necrosis of liver parenchyma. Over time, there is an expansion of Sox9+ hepatocytes in the damaged livers suggestive of a hepatocyte-mediated regenerative response. We conclude that Klf5 is required for the normal function of the hepatobiliary system and that the K5-Cre; Klf5fl/fl mouse is an excellent model to probe the molecular events interlinking damage and regenerative response in the liver.
|
|
| 20. |
|
|
| 21. |
- DAddio, Francesca, et al.
(författare)
-
The IGFBP3/TMEM219 pathway regulates beta cell homeostasis
- 2022
-
Ingår i: Nature Communications. - : Nature Portfolio. - 2041-1723. ; 13:1
-
Tidskriftsartikel (refereegranskat)abstract
- In this new study the Authors demonstrated that the IGFBP3/TMEM219 pathway is a physiological regulator of pancreatic beta cell homeostasis and it is dysregulated in diabetes. IGFBP3/TMEM219 targeting may therefore serve as a therapeutic option in diabetes. Loss of pancreatic beta cells is a central feature of type 1 (T1D) and type 2 (T2D) diabetes, but a therapeutic strategy to preserve beta cell mass remains to be established. Here we show that the death receptor TMEM219 is expressed on pancreatic beta cells and that signaling through its ligand insulin-like growth factor binding protein 3 (IGFBP3) leads to beta cell loss and dysfunction. Increased peripheral IGFBP3 was observed in established and at-risk T1D/T2D patients and was confirmed in T1D/T2D preclinical models, suggesting that dysfunctional IGFBP3/TMEM219 signaling is associated with abnormalities in beta cells homeostasis. In vitro and in vivo short-term IGFBP3/TMEM219 inhibition and TMEM219 genetic ablation preserved beta cells and prevented/delayed diabetes onset, while long-term IGFBP3/TMEM219 blockade allowed for beta cell expansion. Interestingly, in several patients cohorts restoration of appropriate IGFBP3 levels was associated with improved beta cell function. The IGFBP3/TMEM219 pathway is thus shown to be a physiological regulator of beta cell homeostasis and is also demonstrated to be disrupted in T1D/T2D. IGFBP3/TMEM219 targeting may therefore serve as a therapeutic option in diabetes.
|
|
| 22. |
|
|
| 23. |
|
|
| 24. |
|
|
| 25. |
- Gerling, M, et al.
(författare)
-
Stromal Hedgehog signalling is downregulated in colon cancer and its restoration restrains tumour growth
- 2016
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7, s. 12321-
-
Tidskriftsartikel (refereegranskat)abstract
- A role for Hedgehog (Hh) signalling in the development of colorectal cancer (CRC) has been proposed. In CRC and other solid tumours, Hh ligands are upregulated; however, a specific Hh antagonist provided no benefit in a clinical trial. Here we use Hh reporter mice to show that downstream Hh activity is unexpectedly diminished in a mouse model of colitis-associated colon cancer, and that downstream Hh signalling is restricted to the stroma. Functionally, stroma-specific Hh activation in mice markedly reduces the tumour load and blocks progression of advanced neoplasms, partly via the modulation of BMP signalling and restriction of the colonic stem cell signature. By contrast, attenuated Hh signalling accelerates colonic tumourigenesis. In human CRC, downstream Hh activity is similarly reduced and canonical Hh signalling remains predominantly paracrine. Our results suggest that diminished downstream Hh signalling enhances CRC development, and that stromal Hh activation can act as a colonic tumour suppressor.
|
|
| 26. |
- Geyer, N, et al.
(författare)
-
Hedgehog Signaling in Colorectal Cancer: All in the Stroma?
- 2021
-
Ingår i: International journal of molecular sciences. - : MDPI AG. - 1422-0067. ; 22:3
-
Tidskriftsartikel (refereegranskat)abstract
- Hedgehog (Hh) signaling regulates intestinal development and homeostasis. The role of Hh signaling in cancer has been studied for many years; however, its role in colorectal cancer (CRC) remains controversial. It has become increasingly clear that the “canonical” Hh pathway, in which ligand binding to the receptor PTCH1 initiates a signaling cascade that culminates in the activation of the GLI transcription factors, is mainly organized in a paracrine manner, both in the healthy colon and in CRC. Such canonical Hh signals largely act as tumor suppressors. In addition, stromal Hh signaling has complex immunomodulatory effects in the intestine with a potential impact on carcinogenesis. In contrast, non-canonical Hh activation may have tumor-promoting roles in a subset of CRC tumor cells. In this review, we attempt to summarize the current knowledge of the Hh pathway in CRC, with a focus on the tumor-suppressive role of canonical Hh signaling in the stroma. Despite discouraging results from clinical trials using Hh inhibitors in CRC and other solid cancers, we argue that a more granular understanding of Hh signaling might allow the exploitation of this key morphogenic pathway for cancer therapy in the future.
|
|
| 27. |
- Gustafsson, Anders, et al.
(författare)
-
Optical characterisation of InAs quantum dots grown on {110} cleaved GaAs facets
- 2002
-
Ingår i: 7th International Conference on Nanometer-Scale Science and Technology and 21st European Conference on Surface Science.
-
Konferensbidrag (refereegranskat)abstract
- We have grown InAs quantum dots on the {110} cleaved edges of (001) GaAs wafers. The lattice mismatch drives the formation of the quantum dots in a Stranski-Krastanow growth mode. We have investigated the properties of the resulting structures by atomic force microscopy, scanning electron microscopy, transmission electron microscopy and low-temperature cathodoluminescence. The growth of GaAs on the cleaved edge is characterised by triangular features, similar to fish scales on a micron scale. The InAs forms a wetting-layer on the scales and the quantum dots tend to grow near the edges of the scales. The cathodoluminescence spectra are dominated by two peaks, one from the wetting layer and one from the quantum dots. Monochromatic imaging confirms that the quantum dots are located around the edges of the fish scales. Imaging in combination with spot mode spectra reveals that the width of the quantum dot peak comes from a variation in the emission energy of the individual quantum dots
|
|
| 28. |
|
|
| 29. |
- Latacz, Emily, et al.
(författare)
-
Histopathological growth patterns of liver metastasis : updated consensus guidelines for pattern scoring, perspectives and recent mechanistic insights
- 2022
-
Ingår i: British Journal of Cancer. - : Springer Nature. - 0007-0920 .- 1532-1827. ; 127:6, s. 988-1013
-
Forskningsöversikt (refereegranskat)abstract
- The first consensus guidelines for scoring the histopathological growth patterns (HGPs) of liver metastases were established in 2017. Since then, numerous studies have applied these guidelines, have further substantiated the potential clinical value of the HGPs in patients with liver metastases from various tumour types and are starting to shed light on the biology of the distinct HGPs. In the present guidelines, we give an overview of these studies, discuss novel strategies for predicting the HGPs of liver metastases, such as deep-learning algorithms for whole-slide histopathology images and medical imaging, and highlight liver metastasis animal models that exhibit features of the different HGPs. Based on a pooled analysis of large cohorts of patients with liver-metastatic colorectal cancer, we propose a new cut-off to categorise patients according to the HGPs. An up-to-date standard method for HGP assessment within liver metastases is also presented with the aim of incorporating HGPs into the decision-making processes surrounding the treatment of patients with liver-metastatic cancer. Finally, we propose hypotheses on the cellular and molecular mechanisms that drive the biology of the different HGPs, opening some exciting preclinical and clinical research perspectives.
|
|
| 30. |
|
|
| 31. |
|
|
| 32. |
|
|
| 33. |
- Tischer, Karolin, et al.
(författare)
-
Microbial communities along biogeochemical gradients in a hydrocarbon-contaminated aquifer
- 2013
-
Ingår i: Environmental Microbiology. - : Wiley. - 1462-2912 .- 1462-2920. ; 15:9, s. 2603-2615
-
Tidskriftsartikel (refereegranskat)abstract
- Micro-organisms are known to degrade a wide range of toxic substances. How the environment shapes microbial communities in polluted ecosystems and thus influences degradation capabilities is not yet fully understood. In this study, we investigated microbial communities in a highly complex environment: the capillary fringe and subjacent sediments in a hydrocarbon-contaminated aquifer. Sixty sediment sections were analysed using terminal restriction fragment length polymorphism (T-RFLP) fingerprinting, cloning and sequencing of bacterial and archaeal 16S rRNA genes, complemented by chemical analyses of petroleum hydrocarbons, methane, oxygen and alternative terminal electron acceptors. Multivariate statistics revealed concentrations of contaminants and the position of the water table as significant factors shaping the microbial community composition. Micro-organisms with highest T-RFLP abundances were related to sulphate reducers belonging to the genus Desulfosporosinus, fermenting bacteria of the genera Sedimentibacter and Smithella, and aerobic hydrocarbon degraders of the genus Acidovorax. Furthermore, the acetoclastic methanogens Methanosaeta, and hydrogenotrophic methanogens Methanocella and Methanoregula were detected. Whereas sulphate and sulphate reducers prevail at the contamination source, the detection of methane, fermenting bacteria and methanogenic archaea further downstream points towards syntrophic hydrocarbon degradation.
|
|
