| 1. |
- Ehlén, Åsa, et al.
(författare)
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Tumors with non-functional RB1 are killed by reduced gamma-tubulin levels.
- 2012
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Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 287:21, s. 17241-17247
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Tidskriftsartikel (refereegranskat)abstract
- In various tumors inactivation of growth control is achieved by interfering with the RB1 signaling pathway. Here, we describe that RB1 and γ tubulin proteins moderate each other's expression by binding to their respective gene promoters. Simultaneous reduction of RB1 and γ tubulin protein levels result in an E2F1-dependent upregulation of apoptotic genes such as caspase 3. We report that in various tumors types, there is an inverse correlation between the expression levels of γ tubulin and RB1 and that in tumor cell lines with a non-functioning RB1, reduction of γ tubulin protein levels leads to induction of apoptosis. Thus, the RB1/γ tubulin signal network can be considered as a new target for cancer treatment.
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| 2. |
- Hadziabdic, Emina, 1978-, et al.
(författare)
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Development of a group-based diabetes education model for migrants with type 2 diabetes, living in Sweden
- 2020
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Ingår i: Primary Health Care Research and Development. - : Cambridge University Press (CUP). - 1463-4236 .- 1477-1128. ; 21
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To develop a diabetes education model based on individual beliefs, knowledge and risk awareness, aimed at migrants with type 2 diabetes, living in Sweden.Background: Type 2 diabetes is rapidly increasing globally, particularly affecting migrants living in developed countries. There is ongoing debate about what kind of teaching method gives the best result, but few studies have evaluated different methods for teaching migrants. Previous studies lack a theoretical base and do not proceed from the individuals' own beliefs about health and illness, underpinned by their knowledge, guiding their health-related behaviour.Methods: A diabetes education model was developed to increase knowledge about diabetes and to influence self-care among migrants with type 2 diabetes. The model was based on literature review, on results from a previous study investigating knowledge about diabetes, on experience from studies of beliefs about health and illness, and on collaboration between researchers in diabetes care and migration and health and staff working in a multi-professional diabetes team.Findings: This is a culturally appropriate diabetes education model proceeding from individual beliefs about health and illness and knowledge, conducted in focus-group discussions in five sessions, led by a diabetes specialist nurse in collaboration with a multi-professional team, and completed within three months. The focus groups should include 4-5 persons and last for about 90 min, in the presence of an interpreter. A thematic interview guide should be used, with broad open-ended questions and descriptions of critical situations/health problems. Discussions of individual beliefs based on knowledge are encouraged. When needed, healthcare staff present at the session answer questions, add information and ensure that basic principles for diabetes care are covered. The diabetes education model is tailored to both individual and cultural aspects and can improve knowledge about type 2 diabetes, among migrants and thus increase self-care behaviour and improve health.
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| 3. |
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| 4. |
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| 5. |
- Jongsma, Helen, et al.
(författare)
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Markedly reduced chronic nociceptive response in mice lacking the PAC1 receptor
- 2001
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Ingår i: NeuroReport. - 1473-558X. ; 12:10, s. 2215-2219
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Tidskriftsartikel (refereegranskat)abstract
- The neuropeptide pituitary adenylate cyclase activating polypeptide (PACAP) has been proposed to have a role in nociception. Here we have used the formalin test, thermal laser stimulation and mechanical von Frey stimulation to investigate possible alteration of PAC1-/- mice nociceptive behaviour. Our finding, that PAC1-/- mice have a substantial, 75% decrease in nociceptive response during the late phase, provides clear evidence that the specific PACAP-receptor PAC1 is involved in the mediation of nociceptive responses during chronic conditions such as inflammation. PAC1-/- mice had small or no changes in the response to mechanical and thermal laser stimulation. This suggests a limited, if any, involvement of PAC1 in nociception after short-lasting stimuli. Injury-induced changes in DRG neuropeptide expression were more pronounced in PAC1-/- mice, implying neuroregulatory functions of PAC1.
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| 6. |
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| 7. |
- Karlsson, Jenny, et al.
(författare)
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Arsenic trioxide-induced neuroblastoma cell death is accompanied by proteolytic activation of nuclear Bax.
- 2007
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Ingår i: Oncogene. - : Springer Science and Business Media LLC. - 1476-5594 .- 0950-9232. ; 26:42, s. 6150-6159
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Tidskriftsartikel (refereegranskat)abstract
- Arsenic trioxide (As2O3) is toxic to multidrug-resistant neuroblastoma cells in vivo and in vitro. In neuroblastoma, As2O3 does not exert its cell death-promoting effects via a classical apoptotic pathway. A death mechanism involving proteolytic cleavage of Bax to a p18 form seems to be of importance, because inhibition of Bax cleavage coincides with diminished cell death. As existing models of cell death implicate Bax in the intrinsic apoptotic pathway, triggering death after Bax translocation to the mitochondria, we investigated the cellular localization of p18 Bax by subcellular fractionation. After As2O3 treatment, p18 Bax was only present in nuclei-enriched, mitochondria-depleted fractions. Cytoplasmic p21 Bax levels decreased, whereas total (p21 and p18) nuclear Bax increased. Overexpressed p21 Bax localized to the cytoplasm and nuclei, whereas overexpressed p18 Bax localized to extra-nuclear structures only. The inability of overexpressed p18 Bax to locate to the nucleus, and the As2O3-induced reduction of p21 Bax in the cytosol, suggest an As2O3-induced mechanism where p18 Bax gets cleaved and 'trapped' in the nucleus. This model is strengthened by the observation that calpain, the protease responsible for p18 Bax generation, is present in the nuclei, and that nuclear calpain is induced by increasing As2O3 and Ca2+ levels.
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| 8. |
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| 9. |
- Lindkvist, Karin, et al.
(författare)
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Staphylococcal enterotoxin H induces V alpha-specific expansion of T cells.
- 2003
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Ingår i: Journal of Immunology. - 1550-6606. ; 170:8, s. 4148-4154
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Tidskriftsartikel (refereegranskat)abstract
- Staphylococcal enterotoxin H (SEH) is a bacterial superantigen secreted by Staphylococcus aureus. Superantigens are presented on the MHC class II and activate large amounts of T cells by cross-linking APC and T cells. In this study, RT-PCR was used to show that SEH stimulates human T cells via the V domain of TCR, in particular V10 (TRAV27), while no TCR V-specific expansion was seen. This is in sharp contrast to all other studied bacterial superantigens, which are highly specific for TCR V. It was further confirmed by flow cytometry that SEH stimulation does not alter the levels of certain TCR V. In a functional assay addressing cross-reactivity, V binding superantigens were found to form one group, whereas SEH has different properties that fit well with V reactivity. As SEH binds on top of MHC class II, an interaction between MHC and TCR upon SEH binding is not likely. This concludes that the specific expansion of TCR V is not due to contacts between MHC and TCR, instead we suggest that SEH directly interacts with the TCR V domain.
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| 10. |
- Munksgaard Persson, Matilda, et al.
(författare)
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HIF-2 alpha Expression Is Suppressed in SCLC Cells, Which Survive in Moderate and Severe Hypoxia When HIF-1 alpha Is Repressed
- 2012
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Ingår i: American Journal of Pathology. - : Elsevier. - 0002-9440 .- 1525-2191. ; 180:2, s. 494-504
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Tidskriftsartikel (refereegranskat)abstract
- Small cell lung carcinoma (SCLC) is extremely aggressive and frequently metastasizes widely in its early stage. Because tumor hypoxia is related to aggressive tumor behavior and the hypoxic adaptation of SCLC is poorly documented, we stained SCLC tumors arranged in a tissue microarray for hypoxia-inducible factor (HIF)-1 alpha and HIF-2 alpha proteins. We found an overall lack of HIF-2 alpha protein expression, which was confirmed in large tumor sections. HIF-1 alpha protein was strongly expressed in most tumors, frequently adjacent to necrotic regions. In concordance, cultured SCLC but not non-small cell lung carcinoma cells showed no or extremely low levels of HIF-2 alpha mRNA and no HIF-2 alpha protein at hypoxia. HIF-1 alpha was stabilized after 4 hours at hypoxia, and its accumulation increased up to 96 hours. SCLC cells survived well and showed net proliferation and low cell death in modest (1% oxygen) and severe (0.1% oxygen) hypoxia. HIF-1 alpha repression virtually did not influence cell death or viability despite reduced levels of hypoxia-inducible genes, such as BNIP3 and BNIP3L. At 1% oxygen no increased autophagy (LC3B-II activation) or NF-kappa B signaling were detected, whereas the unfolded protein response was activated at severe hypoxia. Our data indicate that HIFs are not exclusively required for SCLC cell survival at modest or severe hypoxia and that additional, yet uncharacterized, hypoxia-driven adaptation pathways may become activated.
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