| 1. |
- Björklund, Maria, et al.
(författare)
-
From master’s thesis to research publication : a mixed-methods study of medical student publishing and experiences with the publishing process
- 2024
-
Ingår i: BMC Medical Education. - 1472-6920. ; 24:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Medical student master’s theses are often carried out as research projects, and some are published as research papers in journals. We investigated the percentage of master’s theses conducted by 5th -year students at the Medical Degree Program at Lund University, Sweden, that subsequently served as the basis for research publications. In addition, we explored both student and supervisor experiences with the publishing process. Methods: A cohort of four semesters of student data covering the period from 2019 to 2020 (n = 446) was searched in PubMed, Embase and the Web of Science to assess whether they had been published as research papers. Surveys were sent to students (n = 121) and supervisors (n = 77) to explore their experiences with the publishing process. Results: We found that 33% (149 of 446) of the students in the 2019–2020 cohort subsequently published their theses, and 50% of these students were listed as first authors. Most students published original research. Students (n = 21) and supervisors (n = 44) reported that the publishing process was time-consuming and that students needed multilevel support from supervisors to achieve successful publication. The publishing process was reported by 79% of the students to have led to additional learning. Most of the papers (126 of 149, 85%) had a clinical or patient-oriented focus. Conclusion: A high percentage of the student publications in which students are listed as first authors require engagement from both students and supervisors. Supervisors play an essential role in supporting students in a successful publication process. Most of the published papers were either clinical or patient-oriented research.
|
|
| 2. |
- Daams, Renée, et al.
(författare)
-
Deletion of nemo-like kinase in T cells reduces single-positive CD8+thymocyte population
- 2020
-
Ingår i: Journal of Immunology. - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 205:7, s. 1830-1841
-
Tidskriftsartikel (refereegranskat)abstract
- The β-catenin/Wnt signaling pathway plays an important role in all stages of T cell development. Nemo-like kinase (NLK) is an evolutionary conserved serine/threonine kinase and a negative regulator of the Wnt signaling pathway. NLK can directly phosphorylate histone deacetylase 1 (HDAC1), as well as T cell factor/lymphoid enhancer-binding factor (TCF/LEF), causing subsequent repression of target gene transcription. By engineering mice lacking NLK in early stages of T cell development, we set out to characterize the role NLK plays in T cell development and found that deletion of NLK does not affect mouse health or lymphoid tissue development. Instead, these mice harbored a reduced number of single-positive (SP) CD8+ thymocytes without any defects in the SP CD4+ thymocyte population. The decrease in SP CD8+ thymocytes was not caused by a block in differentiation from double-positive CD4+CD8+ cells. Neither TCR signaling nor activation was altered in the absence of NLK. Instead, we observed a significant increase in cell death and reduced phosphorylation of LEF1 as well as HDAC1 among NLK-deleted SP CD8+ cells. Thus, NLK seems to play an important role in the survival of CD8+ thymocytes. Our data provide evidence for a new function for NLK with regard to its involvement in T cell development and supporting survival of SP CD8+ thymocytes.
|
|
| 3. |
- Daams, Renée, et al.
(författare)
-
Nemo-like kinase in development and diseases : Insights from mouse studies
- 2020
-
Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 21:23, s. 1-8
-
Forskningsöversikt (refereegranskat)abstract
- The Wnt signalling pathway is a central communication cascade between cells to orchestrate polarity and fate during development and adult tissue homeostasis in various organisms. This pathway can be regulated by different signalling molecules in several steps. One of the coordinators in this pathway is Nemo-like kinase (NLK), which is an atypical proline-directed serine/threonine mitogen-activated protein (MAP) kinase. Very recently, NLK was established as an essential regulator in different cellular processes and abnormal NLK expression was highlighted to affect the development and progression of various diseases. In this review, we focused on the recent discoveries by using NLK-deficient mice, which show a phenotype in the development and function of organs such as the lung, heart and skeleton. Furthermore, NLK could conduct the function and differentiation of cells from the immune system, in addition to regulating neurodegenerative diseases, such as Huntington’s disease and spinocerebellar ataxias. Overall, generations of NLK-deficient mice have taught us valuable lessons about the role of this kinase in certain diseases and development.
|
|
| 4. |
- Griewahn, Laura, et al.
(författare)
-
SPATA2 restricts OTULIN-dependent LUBAC activity independently of CYLD
- 2023
-
Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 42:1
-
Tidskriftsartikel (refereegranskat)abstract
- SPATA2 mediates the recruitment of CYLD to immune receptor complexes by bridging the interaction of CYLD with the linear ubiquitylation assembly complex (LUBAC) component HOIP. Whether SPATA2 exhibits functions independently of CYLD is unclear. Here, we show that, while Cyld−/− and Spata2−/− mice are viable, double mutants exhibit highly penetrant perinatal lethality, indicating independent functions of SPATA2 and CYLD. Cyld−/−Spata2−/− fibroblasts show increased M1-linked TNFR1-SC ubiquitylation and, similar to Cyld−/−Spata2−/− macrophages and intestinal epithelial cells, elevated pro-inflammatory gene expression compared with Cyld−/− or Spata2−/− cells. We show that SPATA2 competes with OTULIN for binding to HOIP via its PUB-interacting motif (PIM) and its zinc finger domain, thereby promoting autoubiquitylation of LUBAC. Consistently, increased pro-inflammatory signaling in Cyld−/−Spata2−/− cells depends on the presence of OTULIN. Our data therefore indicate that SPATA2 counteracts, independently of CYLD, the deubiquitylation of LUBAC by OTULIN and thereby attenuates LUBAC activity and pro-inflammatory signaling.
|
|
| 5. |
- Grigoryan, Ani, et al.
(författare)
-
Engineering human mini-bones for the standardized modeling of healthy hematopoiesis, leukemia, and solid tumor metastasis
- 2022
-
Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6242 .- 1946-6234. ; 14:666, s. 1-15
-
Tidskriftsartikel (refereegranskat)abstract
- The bone marrow microenvironment provides indispensable factors to sustain blood production throughout life. It is also a hotspot for the progression of hematologic disorders and the most frequent site of solid tumor metastasis. Preclinical research relies on xenograft mouse models, but these models preclude the human-specific functional interactions of stem cells with their bone marrow microenvironment. Instead, human mesenchymal cells can be exploited for the in vivo engineering of humanized niches, which confer robust engraftment of human healthy and malignant blood samples. However, mesenchymal cells are associated with major reproducibility issues in tissue formation. Here, we report the fast and standardized generation of human mini-bones by a custom-designed human mesenchymal cell line. These resulting humanized ossicles (hOss) consist of fully mature bone and bone marrow structures hosting a human mesenchymal niche with retained stem cell properties. As compared to mouse bones, we demonstrate superior engraftment of human cord blood hematopoietic cells and primary acute myeloid leukemia samples and also validate hOss as a metastatic site for breast cancer cells. We further report the engraftment of neuroblastoma patient-derived xenograft cells in a humanized model, recapitulating clinically described osteolytic lesions. Collectively, our human mini-bones constitute a powerful preclinical platform to model bone-developing tumors using patient-derived materials.
|
|
| 6. |
- Jemaà, Mohamed, et al.
(författare)
-
Gene expression signature of acquired chemoresistance in neuroblastoma cells
- 2020
-
Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 21:18
-
Tidskriftsartikel (refereegranskat)abstract
- Drug resistance of childhood cancer neuroblastoma is a serious clinical problem. Patients with relapsed disease have a poor prognosis despite intense treatment. In the present study, we aimed to identify chemoresistance gene expression signatures in vincristine resistant neuroblastoma cells. We found that vincristine-resistant neuroblastoma cells formed larger clones and survived under reduced serum conditions as compared with non-resistant parental cells. To identify the possible mechanisms underlying vincristine resistance in neuroblastoma cells, we investigated the expression profiles of genes known to be involved in cancer drug resistance. This specific gene expression patterns could predict the behavior of a tumor in response to chemotherapy and for predicting the prognosis of high-risk neuroblastoma patients. Our signature could help chemoresistant neuroblastoma patients in avoiding useless and harmful chemotherapy cycles.
|
|
| 7. |
- Jemaà, Mohamed, et al.
(författare)
-
Preferential Killing of Tetraploid Colon Cancer Cells by Targeting the Mitotic Kinase PLK1
- 2020
-
Ingår i: Cellular Physiology and Biochemistry. - : Cell Physiol Biochem Press GmbH and Co KG. - 1015-8987 .- 1421-9778. ; 54:2, s. 303-320
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND/AIMS: Chromosomal instability is a well-known factor in the progression of different types of cancer, including colorectal cancer. Chromosomal instability results in severely rearranged karyotypes and aneuploidy. Tetraploidy constitutes an intermediate phase during the polyploidy/aneuploidy cascade in oncogenesis, and tetraploid cells are particularly resistant to chemotherapy. Whether inhibition of the mitotic protein polo-like kinase 1 (PLK1) prevents the survival of tetraploid colon cancer cells is unknown.METHODS: Diploid and tetraploid cells were transfected with siPLK1 or treated with PLK1 inhibitor Bi2536 in combination with spindle poison. Cell toxicity was assessed via crystal violet staining and clonogenic assay. Flow cytometry assessment analyzed numerous cell apoptotic parameters and cell cycle phases. Synergistic activity between Bi2536 and paclitaxel, vincristine or colchicine was calculated using the CompuSyn software.RESULTS: Inhibition or abrogation of PLK1 prevented the survival of colon cancer cells, specifically tetraploid cells. The cell death induced by PLK inhibition was due to mitotic slippage, followed by the activation of the intrinsic pathway of apoptosis. We further demonstrated that co-treatment of the tetraploid colon cancer cells with a PLK1 inhibitor and the microtubule polymerisation inhibitor vincristine or colchicine, but not the microtubule depolymerisation inhibitor paclitaxel, provoked a lethal synergistic effect.CONCLUSION: PLK1 inhibition together with microtubule-targeting chemicals, serve as a potent therapeutic strategy for targeting tetraploid cancer cells.
|
|
| 8. |
- Jemaà, Mohamed, et al.
(författare)
-
Tetraploidization Increases the Motility and Invasiveness of Cancer Cells
- 2023
-
Ingår i: International Journal of Molecular Sciences. - 1661-6596. ; 24:18
-
Tidskriftsartikel (refereegranskat)abstract
- Polyploidy and metastasis are associated with a low probability of disease-free survival in cancer patients. Polyploid cells are known to facilitate tumorigenesis. However, few data associate polyploidization with metastasis. Here, by generating and using diploid (2n) and tetraploid (4n) clones from malignant fibrous histiocytoma (MFH) and colon carcinoma (RKO), we demonstrate the migration and invasion advantage of tetraploid cells in vitro using several assays, including the wound healing, the OrisTM two-dimensional cell migration, single-cell migration tracking by video microscopy, the Boyden chamber, and the xCELLigence RTCA real-time cell migration. Motility advantage was observed despite tetraploid cell proliferation weakness. We could also demonstrate preferential metastatic potential in vivo for the tetraploid clone using the tail vein injection in mice and tracking metastatic tumors in the lung. Using the Mitelman Database of Chromosome Aberrations in Cancer, we found an accumulation of polyploid karyotypes in metastatic tumors compared to primary ones. This work reveals the clinical relevance of the polyploid subpopulation and the strategic need to highlight polyploidy in preclinical studies as a therapeutic target for metastasis.
|
|
| 9. |
- Ke, Hengning, et al.
(författare)
-
High expression of CD34 and α6-integrin contributes to the cancer-initiating cell behaviour in ultraviolet-induced mouse skin squamous cell carcinoma
- 2020
-
Ingår i: Journal of Cancer. - : Ivyspring International Publisher. - 1837-9664. ; 11:23, s. 6760-6767
-
Tidskriftsartikel (refereegranskat)abstract
- Squamous cell carcinoma caused by ultraviolet light exposure represents over 40% of all malignant diseases. It is one of the most commonly found human tumours. Tumour mass within squamous cell carcinoma consists of various cell types, including cancer-initiating cells that are responsible for tumour progression, metastasis and chemoresistance and implicated in clinical relapse. In the present study, we aimed to characterise whether the cell population with high CD34 and α6-integrin expression behave as cancer-initiating cells within ultraviolet-induced squamous cell carcinoma in mouse skin. CD34highα6-integrinhigh compared to CD34lowα6-integrinhigh cells isolated from ultraviolet-induced squamous cell carcinoma could propagate effectively by displaying greater tumour initiating and self-renewal abilities. Our study suggests that CD34highα6-integrinhigh cells act as initiators upon ultraviolet-induced skin squamous cell carcinoma.
|
|
| 10. |
- Massoumi, Ramin, et al.
(författare)
-
Editorial : Celebration of DNA Day
- 2024
-
Ingår i: Hereditas. - 0018-0661. ; 161:1
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
|
|
