| 1. |
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| 2. |
- Sime, Wondossen, et al.
(författare)
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Discovery of epi-enprioline as a novel drug for the treatment of vincristine resistant neuroblastoma
- 2020
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 21:18
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Tidskriftsartikel (refereegranskat)abstract
- Neuroblastoma is a childhood solid tumour originating from undifferentiated neural progenitor cells of the sympathetic nervous system. Drug resistance of childhood cancer neuroblastoma is a serious clinical problem. In the present study, we aimed to identify novel drugs that can inhibit the growth and survival of chemoresistant neuroblastoma. High-throughput screening identified a small molecule, epi-enprioline that was able to induce apoptosis of vincristine-resistant neuroblastoma cells via the mitochondrial apoptotic pathway. Epi-enprioline reduced tumour growth in multiple preclinical models, including an orthotopic neuroblastoma patient-derived xenograft model in vivo. In summary, our data suggest that epi-enprioline can be considered as a lead compound for the treatment of vincristine-resistant neuroblastoma uncovering a novel strategy, which can be further explored as a treatment for drug-resistant neuroblastoma.
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| 3. |
- Aaltonen, Kristina, et al.
(författare)
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Patient-derived models : Advanced tools for precision medicine in neuroblastoma
- 2023
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Ingår i: Frontiers in Oncology. - : Frontiers Media SA. - 2234-943X. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Neuroblastoma is a childhood cancer derived from the sympathetic nervous system. High-risk neuroblastoma patients have a poor overall survival and account for ~15% of childhood cancer deaths. There is thus a need for clinically relevant and authentic models of neuroblastoma that closely resemble the human disease to further interrogate underlying mechanisms and to develop novel therapeutic strategies. Here we review recent developments in patient-derived neuroblastoma xenograft models and in vitro cultures. These models can be used to decipher mechanisms of metastasis and treatment resistance, for drug screening, and preclinical drug testing. Patient-derived neuroblastoma models may also provide useful information about clonal evolution, phenotypic plasticity, and cell states in relation to neuroblastoma progression. We summarize current opportunities for, but also barriers to, future model development and application. Integration of patient-derived models with patient data holds promise for the development of precision medicine treatment strategies for children with high-risk neuroblastoma.
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| 4. |
- Allaoui, Roni, et al.
(författare)
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Cancer-associated fibroblast-secreted CXCL16 attracts monocytes to promote stroma activation in triple-negative breast cancers
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Triple-negative (TN) breast cancers (ER â ' PR â ' HER2 â ') are highly metastatic and associated with poor prognosis. Within this subtype, invasive, stroma-rich tumours with infiltration of inflammatory cells are even more aggressive. The effect of myeloid cells on reactive stroma formation in TN breast cancer is largely unknown. Here, we show that primary human monocytes have a survival advantage, proliferate in vivo and develop into immunosuppressive myeloid cells expressing the myeloid-derived suppressor cell marker S100A9 only in a TN breast cancer environment. This results in activation of cancer-associated fibroblasts and expression of CXCL16, which we show to be a monocyte chemoattractant. We propose that this migratory feedback loop amplifies the formation of a reactive stroma, contributing to the aggressive phenotype of TN breast tumours. These insights could help select more suitable therapies targeting the stromal component of these tumours, and could aid prediction of drug resistance.
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| 5. |
- Almstedt, Elin, 1988-, et al.
(författare)
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Integrative discovery of treatments for high-risk neuroblastoma
- 2020
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723 .- 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Despite advances in the molecular exploration of paediatric cancers, approximately 50% of children with high-risk neuroblastoma lack effective treatment. To identify therapeutic options for this group of high-risk patients, we combine predictive data mining with experimental evaluation in patient-derived xenograft cells. Our proposed algorithm, TargetTranslator, integrates data from tumour biobanks, pharmacological databases, and cellular networks to predict how targeted interventions affect mRNA signatures associated with high patient risk or disease processes. We find more than 80 targets to be associated with neuroblastoma risk and differentiation signatures. Selected targets are evaluated in cell lines derived from high-risk patients to demonstrate reversal of risk signatures and malignant phenotypes. Using neuroblastoma xenograft models, we establish CNR2 and MAPK8 as promising candidates for the treatment of high-risk neuroblastoma. We expect that our method, available as a public tool (targettranslator.org), will enhance and expedite the discovery of risk-associated targets for paediatric and adult cancers.
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| 6. |
- Askander, Mikael, et al.
(författare)
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Joel Ohlsson
- 2017
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Ingår i: En lundensisk litteraturhistoria : Lunds universitet som litterärt kraftfält - Lunds universitet som litterärt kraftfält. - 9789170612503 ; , s. 339-339
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Bokkapitel (populärvet., debatt m.m.)abstract
- A portrait of the swedish film critic, poet and novelist Joel Ohlsson.
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| 7. |
- Askander, Mikael, et al.
(författare)
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Miranda Landen
- 2017
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Ingår i: En lundensisk litteraturhistoria : Lunds universitet som litterärt kraftfält - Lunds universitet som litterärt kraftfält. - 1401-1301. - 9789170612503
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Bokkapitel (populärvet., debatt m.m.)abstract
- A portrait of the swedish poet and critic Miranda Landén.
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| 8. |
- Back, Jon, 1977-, et al.
(författare)
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the Quest : An Escape Room Inspired Interactive Museum Exhibition
- 2019
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Ingår i: CHI PLAY '19 Extended Abstracts. - New York, NY, USA : ACM Digital Library. ; , s. 81-86
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Konferensbidrag (refereegranskat)abstract
- In this project, we report on designing an interactive museum exhibit in a technology museum, inspired by escape room game mechanics and technology. The project aims to create a deeper more immersed engagement with and interest in the exhibition, and thereby increase the interest in the exhibit's subject. In the game, the players take on the role of grandchildren to a known (fictitious) turn-of-the-century explorer and set out to find the treasures she hid around the world during her years of adventure. Clues to the treasures are hidden within the museum exhibition and by using knowledge found around the exhibition the players can solve the riddles and find the treasure, while also picking up some knowledge along the way.
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| 9. |
- Bengtsson, Bengt Olle, et al.
(författare)
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Bengt Lidforss 1868-1913
- 2017
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Ingår i: En lundensisk litteraturhistoria. : Lunds universitet som litterärt kraftfält - Lunds universitet som litterärt kraftfält. - 9789170612503 ; , s. 146-151
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Bokkapitel (populärvet., debatt m.m.)
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| 10. |
- Bengtsson, Bengt Olle, et al.
(författare)
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Åke Gustafsson 1908-1988
- 2017
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Ingår i: En lundensisk litteraturhistoria. : Lunds universitet som litterärt kraftfält - Lunds universitet som litterärt kraftfält. - 9789170612503 ; , s. 239-240
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Bokkapitel (populärvet., debatt m.m.)
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| 11. |
- Bernhardsson, Katarina, et al.
(författare)
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Ordkonst
- 2017
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Ingår i: En lundensisk litteraturhistoria : Lunds universitet som litterärt kraftfält - Lunds universitet som litterärt kraftfält. - 1401-1301. - 9789170612503 ; 2018, s. 464-467
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Bokkapitel (populärvet., debatt m.m.)
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| 12. |
- Bernhardsson, Katarina, et al.
(författare)
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Q-versen
- 2017
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Ingår i: En lundensisk litteraturhistoria : Lunds universitet som litterärt kraftfält - Lunds universitet som litterärt kraftfält. - 1401-1301. - 9789170612503 ; 2018, s. 292-297
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Bokkapitel (populärvet., debatt m.m.)
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| 13. |
- Bernhardsson, Katarina, et al.
(författare)
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Studentromaner
- 2017
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Ingår i: En lundensisk litteraturhistoria : Lunds universitet som litterärt kraftfält - Lunds universitet som litterärt kraftfält. - 1401-1301. - 9789170612503 ; 2018, s. 254-261
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Bokkapitel (populärvet., debatt m.m.)
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| 14. |
- Bexell, Daniel, et al.
(författare)
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Bone Marrow Multipotent Mesenchymal Stroma Cells Act as Pericyte-like Migratory Vehicles in Experimental Gliomas.
- 2009
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Ingår i: Molecular Therapy. - : Elsevier BV. - 1525-0024 .- 1525-0016. ; 2008:Nov 4., s. 183-190
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Tidskriftsartikel (refereegranskat)abstract
- Bone marrow-derived multipotent mesenchymal stroma cells (MSCs) have emerged as cellular vectors for gene therapy of solid cancers. We implanted enhanced green fluorescent protein-expressing rat MSCs directly into rat malignant gliomas to address their migratory capacity, phenotype, and effects on tumor neovascularization and animal survival. A single intratumoral injection of MSCs infiltrated the majority of invasive glioma extensions (72 +/- 14%) and a substantial fraction of distant tumor microsatellites (32 +/- 6%). MSC migration was highly specific for tumor tissue. Grafted MSCs integrated into tumor vessel walls and expressed pericyte markers alpha-smooth muscle actin, neuron-glia 2, and platelet-derived growth factor receptor-beta but not endothelial cell markers. The pericyte marker expression profile and perivascular location of grafted MSCs indicate that these cells act as pericytes within tumors. MSC grafting did not influence tumor microvessel density or survival of tumor-bearing animals. The antiangiogenic drug Sunitinib markedly reduced the numbers of grafted MSCs migrating within tumors. We found no MSCs within gliomas following intravenous (i.v.) injections. Thus, MSCs should be administered by intratumoral implantations rather than by i.v. injections. Intratumorally grafted pericyte-like MSCs might represent a particularly well-suited vector system for delivering molecules to affect tumor angiogenesis and for targeting cancer stem cells within the perivascular niche.Molecular Therapy (2008); doi:10.1038/mt.2008.229.
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| 15. |
- Bexell, Daniel, et al.
(författare)
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CD133+ and nestin+ tumor-initiating cells dominate in N29 and N32 experimental gliomas.
- 2009
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 125:1, s. 15-22
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Tidskriftsartikel (refereegranskat)abstract
- The current study was designed to critically evaluate the notion that cancer stem cell (CSC)-like cells constitute a subpopulation of cells within experimental gliomas. Virtually all cells within the N29 and N32 rat glioma models homogenously expressed CD133, the stem/progenitor marker nestin as well as the neural lineage markers glial fibrillary acidic protein, betaIII-tubulin, and CNPase in vitro. The phenotype was largely retained on exposure to conditions promoting differentiation in vitro and after intracranial implantation of tumor cells into syngeneic hosts. Unsorted adherently grown cells displayed very high clonogenicity in vitro and robust tumorigenicity in vivo. Single N29 and N32 tumor cells invariably formed clones in vitro, and intracerebral inoculation of as few as 10 adherently growing N29 and N32 tumor cells, respectively, gave rise to a tumor. These results provide an alternative view on CSC-like cells in glioma models: sphere-formation is not a prerequisite for accumulation of tumorigenic cells, and CSC-like cells do not reside within a rare subpopulation of cells in these glioma models. N29 and N32 gliomas may accordingly be used for the development of treatment strategies directed specifically against a practically pure population of brain tumor-initiating CSC-like cells. (c) 2009 Wiley-Liss, Inc.
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| 16. |
- Bexell, Daniel, et al.
(författare)
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Characterization of the subventricular zone neurogenic response to rat malignant brain tumors
- 2007
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Ingår i: Neuroscience. - : Elsevier BV. - 1873-7544 .- 0306-4522. ; 147:3, s. 824-832
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Tidskriftsartikel (refereegranskat)abstract
- The subventricular zone (SVZ) is one of the neurogenic regions of the adult brain. We characterized the neurogenic response of the SVZ to the growth of brain tumors in the rat striatum. Abundant nestin positive cells, most likely representing reactive astrocytes, were found surrounding the tumor. However, we observed no substantial migration of nestin positive cells from the SVZ toward the tumor. Tumor growth resulted in decreased numbers of bromodeoxyuridine positive and Ki-67 positive proliferating cells and a concomitant increase in doublecortin and polysialylated neural cell adhesion molecule immunoreactivity within the SVZ. Neuroblasts were observed in high numbers in the area between the SVZ and the tumor, most likely pointing to the SVZ as the principal source of these cells. Neuroblasts located between the SVZ and the tumor expressed the transcription factor Pbx, a marker for immature striatal neurons. However, no evidence of neuroblast differentiation into fully mature neurons was found. This study thus demonstrates increased neuroblast immunoreactivity within the SVZ ipsilateral to a brain tumor in the striatum. SVZ-derived neuroblasts attracted by the tumor adopt an immature striatal phenotype indicating a region specific reparative mechanism in response to a malignant tumor. (C) 2007 IBRO. Published by Elsevier Ltd. All rights reserved.
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| 17. |
- Bexell, Daniel, et al.
(författare)
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Rat Multipotent Mesenchymal Stromal Cells Lack Long-Distance Tropism to 3 Different Rat Glioma Models
- 2012
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Ingår i: Neurosurgery. - 0148-396X. ; 70:3, s. 731-739
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Viral gene therapy of malignant brain tumors has been restricted by the limited vector distribution within the tumors. Multipotent mesenchymal stromal cells (MSCs) and other precursor cells have shown tropism for gliomas, and these cells are currently being explored as potential vehicles for gene delivery in glioma gene therapy. OBJECTIVE: To investigate MSC migration in detail after intratumoral and extratumoral implantation through syngeneic and orthotopic glioma models. METHODS: Adult rat bone marrow-derived MSCs were transduced to express enhanced green fluorescent protein and implanted either directly into or at a distance from rat gliomas. RESULTS: We found no evidence of long-distance MSC migration through the intact striatum toward syngeneic D74(RG2), N32, and N29 gliomas in the ipsilateral hemisphere or across the corpus callosum to gliomas located in the contralateral hemisphere. After intratumoral injection, MSCs migrated extensively, specifically within N32 gliomas. The MSCs did not proliferate within tumors, suggesting a low risk of malignant transformation of in vivo grafted cell vectors. Using a model for surgical glioma resection, we found that intratumorally grafted MSCs migrate efficiently within glioma remnants after partial surgical resection. CONCLUSION: The findings point to limitations for the use of MSCs as vectors in glioma gene therapy, although intratumoral MSC implantation provides a dense and tumor-specific vector distribution.
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| 18. |
- Bexell, Daniel, et al.
(författare)
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Stem cell-based therapy for malignant glioma.
- 2013
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Ingår i: Cancer Treatment Reviews. - : Elsevier BV. - 1532-1967 .- 0305-7372. ; 39:4, s. 358-365
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Forskningsöversikt (refereegranskat)abstract
- Stem cells have been extensively investigated as tumour-tropic vectors for gene delivery to solid tumours. In this review, we discuss the potential for using stem cells as cellular vector systems in gene therapy for malignant gliomas, with a focus on neural stem cells, and multipotent mesenchymal stromal cells. Tumour cell-derived substances and factors associated with tumour-induced inflammation and tumour neovascularisation can specifically attract stem cells to invasive gliomas. Injected stem cells engineered to produce anti-tumour substances have shown strong therapeutic effects in experimental glioma models. However, the potential caveats include the immunosuppressive functions of multipotent mesenchymal stromal cells, the contribution of stem cells to the pro-tumourigenic stroma, and the malignant transformation of implanted stem cells. In addition, it is not yet known which stem cell types and therapeutic genes will be most effective for the treatment of glioma patients. Here, we highlight the possibilities and problems for translating promising experimental findings in glioma models into the clinic.
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| 19. |
- Bexell, Daniel
(författare)
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Stem cell based therapy of malignant brain tumors
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Malignant brain tumor is a highly invasive and vascularized cancer. Current forms of therapy are not curative and can, at best, prolong survival for patients with this disease. The mean survival is only around 15 months. The aims of the present thesis have been to develop and explore a stem cell based vector system for delivery of therapeutic transgenes to experimental gliomas. First, we investigated the frequency and properties of cancer stem cell (CSC)-like cells in the rat glioma models used in the present thesis. Virtually all cells within both glioma models concomitantly express CD133, nestin as well as the neural lineage markers glial fibrillary acidic protein, βIII-tubulin and CNPase in vitro and in vivo. Unsorted tumor cells displayed very high clonogenic capacity in vitro and robust tumorigenicity in vivo. Thus, CSC-like cells do not reside within a rare sub-population of cells in these glioma models but constitute most, or all, cells. We next examined the subventricular zone (SVZ) response to growth of malignant glioma. Tumor growth resulted in decreased numbers of SVZ proliferating cells, increased SVZ neuroblast immunoreactivity, and migration of striatal neuroblasts from the SVZ toward glioma. Although endogenous neuroblast migration toward gliomas was of moderate magnitude, this indicates a region specific reparative mechanism in response to tumor growth. We continued by implanting rat SVZ-derived neural precursor cells (NPCs) and rat multipotent mesenchymal stroma cells (MSCs) into gliomas. Intratumorally implanted NPCs and MSCs migrated specifically within gliomas and largely avoided normal brain tissue. Importantly, implanted NPCs and MSCs did not proliferate within tumors. This indicates a low risk of development of secondary malignancies. A comparative analysis revealed higher survival and better intratumoral migratory capacity of implanted MSCs, compared to NPCs. Intratumorally implanted MSCs migrated to the majority of the invasive glioma extensions and to a substantial fraction of distant tumor microsatellites. Furthermore, implanted MSCs integrated into tumor blood vessel walls and expressed pericyte markers but not endothelial cell markers. The pericyte marker expression profile and perivascular location of implanted MSCs indicate that these cells act as pericytes within tumors. MSC implantation did not, however, affect tumor microvessel density or the survival of glioma-bearing animals. In summary, gliomas can attract endogenous striatal neuroblasts from the SVZ. However, intratumoral implantation of NPCs and MSCs yields a much more powerful, and tumor-specific, infiltration within gliomas. In particular, pericyte-like MSCs represent a well suited vector system for the delivery of therapeutic transgenes to vascularized and invasive gliomas.
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| 20. |
- Bexell, Daniel, et al.
(författare)
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Toward Brain Tumor Gene Therapy Using Multipotent Mesenchymal Stromal Cell Vectors.
- 2010
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Ingår i: Molecular Therapy. - : Elsevier BV. - 1525-0024 .- 1525-0016. ; May 4, s. 1067-1075
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Tidskriftsartikel (refereegranskat)abstract
- Gene therapy of solid cancers has been severely restricted by the limited distribution of vectors within tumors. However, cellular vectors have emerged as an effective migratory system for gene delivery to invasive cancers. Implanted and injected multipotent mesenchymal stromal cells (MSCs) have shown tropism for several types of primary tumors and metastases. This capacity of MSCs forms the basis for their use as a gene vector system in neoplasms. Here, we review the tumor-directed migratory potential of MSCs, mechanisms of the migration, and the choice of therapeutic transgenes, with a focus on malignant gliomas as a model system for invasive and highly vascularized tumors. We examine recent findings demonstrating that MSCs share many characteristics with pericytes and that implanted MSCs localize primarily to perivascular niches within tumors, which might have therapeutic implications. The use of MSC vectors in cancer gene therapy raises concerns, however, including a possible MSC contribution to tumor stroma and vasculature, MSC-mediated antitumor immune suppression, and the potential malignant transformation of cultured MSCs. Nonetheless, we highlight the novel prospects of MSC-based tumor therapy, which appears to be a promising approach.
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| 21. |
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| 22. |
- Bjerstedt, Sven, et al.
(författare)
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John Karlzén (1903–1960)
- 2017
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Ingår i: En lundensisk litteraturhistoria: Universitetet som litterärt kraftfält under 350 år.. ; , s. 232-233
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Bokkapitel (populärvet., debatt m.m.)
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| 23. |
- Bjerstedt, Sven, et al.
(författare)
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Karl "Bob" Benzon (1862–1914)
- 2017
-
Ingår i: En lundensisk litteraturhistoria: Universitetet som litterärt kraftfält under 350 år.. ; , s. 136-136
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Bokkapitel (populärvet., debatt m.m.)
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| 24. |
- Braekeveldt, Noémie, et al.
(författare)
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Neuroblastoma patient-derived orthotopic xenografts reflect the microenvironmental hallmarks of aggressive patient tumours
- 2016
-
Ingår i: Cancer Letters. - : Elsevier BV. - 1872-7980 .- 0304-3835. ; 375:2, s. 384-389
-
Tidskriftsartikel (refereegranskat)abstract
- Treatment of high-risk childhood neuroblastoma is a clinical challenge hampered by a lack of reliable neuroblastoma mouse models for preclinical drug testing. We have previously established invasive and metastasising patient-derived orthotopic xenografts (PDXs) from high-risk neuroblastomas that retained the genotypes and phenotypes of patient tumours. Given the important role of the tumour microenvironment in tumour progression, metastasis, and treatment responses, here we analysed the tumour microenvironment of five neuroblastoma PDXs in detail. The PDXs resembled their parent tumours and retained important stromal hallmarks of aggressive lesions including rich blood and lymphatic vascularisation, pericyte coverage, high numbers of cancer-associated fibroblasts, tumour-associated macrophages, and extracellular matrix components. Patient-derived tumour endothelial cells occasionally formed blood vessels in PDXs; however, tumour stroma was, overall, of murine origin. Lymphoid cells and lymphatic endothelial cells were found in athymic nude mice but not in NSG mice; thus, the choice of mouse strain dictates tumour microenvironmental components. The murine tumour microenvironment of orthotopic neuroblastoma PDXs reflects important hallmarks of aggressive and metastatic clinical neuroblastomas. Neuroblastoma PDXs are clinically relevant models for preclinical drug testing.
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| 25. |
- Braekeveldt, Noémie, et al.
(författare)
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Neuroblastoma Patient-Derived Orthotopic Xenografts Retain Metastatic Patterns and Geno- and Phenotypes of Patient Tumours.
- 2015
-
Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 136:5, s. 252-261
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Tidskriftsartikel (refereegranskat)abstract
- Neuroblastoma is a childhood tumour with heterogeneous characteristics and children with metastatic disease often have a poor outcome. Here we describe the establishment of neuroblastoma patient-derived xenografts (PDXs) by orthotopic implantation of viably cryopreserved or fresh tumour explants of patients with high risk neuroblastoma into immunodeficient mice. In vivo tumour growth was monitored by magnetic resonance imaging and fluorodeoxyglucose - positron emission tomography. Neuroblastoma PDXs retained the undifferentiated histology and proliferative capacity of their corresponding patient tumours. The PDXs expressed neuroblastoma markers NCAM, chromogranin A, synaptophysin and tyrosine hydroxylase. Whole genome genotyping array analyses demonstrated that PDXs retained patient-specific chromosomal aberrations such as MYCN amplification, deletion of 1p, and gain of chromosome 17q. Thus, neuroblastoma PDXs recapitulate the hallmarks of high-risk neuroblastoma in patients. PDX-derived cells were cultured in serum-free medium where they formed free-floating neurospheres, expressed neuroblastoma gene markers MYCN, CHGA, TH, SYP and NPY, and retained tumour-initiating and metastatic capacity in vivo. PDXs showed much higher degree of infiltrative growth and distant metastasis as compared to neuroblastoma SK-N-BE(2)c cell line-derived orthotopic tumours. Importantly, the PDXs presented with bone marrow involvement, a clinical feature of aggressive neuroblastoma. Thus, neuroblastoma PDXs serve as clinically relevant models for studying and targeting high-risk metastatic neuroblastoma. © 2014 Wiley Periodicals, Inc.
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