| 1. |
- George, Julie, et al.
(författare)
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Comprehensive genomic profiles of small cell lung cancer
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 524:7563, s. 47-U73
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Tidskriftsartikel (refereegranskat)abstract
- We have sequenced the genomes of 110 small cell lung cancers (SCLC), one of the deadliest human cancers. In nearly all the tumours analysed we found bi-allelic inactivation of TP53 and RB1, sometimes by complex genomic rearrangements. Two tumours with wild-type RB1 had evidence of chromothripsis leading to overexpression of cyclin D1 (encoded by the CCND1 gene), revealing an alternative mechanism of Rb1 deregulation. Thus, loss of the tumour suppressors TP53 and RB1 is obligatory in SCLC. We discovered somatic genomic rearrangements of TP73 that create an oncogenic version of this gene, TP73Dex2/3. In rare cases, SCLC tumours exhibited kinase gene mutations, providing a possible therapeutic opportunity for individual patients. Finally, we observed inactivating mutations in NOTCH family genes in 25% of human SCLC. Accordingly, activation of Notch signalling in a pre-clinical SCLC mouse model strikingly reduced the number of tumours and extended the survival of the mutant mice. Furthermore, neuroendocrine gene expression was abrogated by Notch activity in SCLC cells. This first comprehensive study of somatic genome alterations in SCLC uncovers several key biological processes and identifies candidate therapeutic targets in this highly lethal form of cancer.
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| 2. |
- Pauksen, Karlis, et al.
(författare)
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Granulocyte-macrophage colony-stimulating factor as immunomodulating factor together with influenza vaccination in stem cell transplant patients
- 2000
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Ingår i: Clinical Infectious Diseases. - : Oxford University Press (OUP). - 1058-4838 .- 1537-6591. ; 30:2, s. 342-348
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Tidskriftsartikel (refereegranskat)abstract
- The effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on the serological response at influenza vaccination was studied in 117 patients who had undergone stem cell transplantation (SCT). The vaccine response was evaluated as significant increases in levels of influenza hemagglutination-inhibition (HAI) antibodies and of IgG antibodies measured by enzyme-linked immunosorbent assay (ELISA). There was no difference in antibody response to either influenza A or B in 64 patients who received GM-CSF at vaccination, compared with the 53 who did not. In the subgroup of allogeneic SCT patients, HAI showed that the response rate to the influenza B vaccine was significantly higher in the treatment group (P<.05). ELISA showed that autologous SCT patients with breast cancer who received GM-CSF had a better response to influenza A (P<.05) and B (P<.01). At early vaccination, 4-12 months after stem cell transplantation, these responses were more pronounced. GM-CSF appears to improve the response to influenza vaccination in some groups of SCT patients, but only to a limited extent.
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| 3. |
- Thunberg, Ulrica, 1967-, et al.
(författare)
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Anti-Staphylococcal humoral immune response in patients with chronic rhinosinusitis
- 2019
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Ingår i: Rhinology Online. - : European Rhinologic Society. - 2589-5613. ; 2, s. 50-58
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Tidskriftsartikel (refereegranskat)abstract
- Background: Staphylococcus aureus (S. aureus) can behave both as a harmless commensal and as a pathogen. Its significance in the pathogenesis of chronic rhinosinusitis (CRS) is not yet fully understood. This study aimed to determine serum antibody re-sponses to specific staphylococcal antigens in patients with CRS and healthy controls, and to investigate the correlation between specific antibody response and severity of symptoms.Methodology: Serum samples from 39 patients with CRS and 56 healthy controls were analysed using a protein microarray to investigate the antibody response to S. aureus specific antigens, with a focus on immunoglobulin G (IgG) directed toward stap-hylococcal components accessible to the immune system. Holm-Bonferroni corrections were applied in all analyses. Information about growth of S. aureus in nares and maxillary sinus was taken from a previous study based on the same individuals. Clinical symptoms were assessed using a scoring system.Results: IgG antibody levels toward staphylococcal TSST-1 and LukF-PV were significantly higher in the CRS patient group com-pared to healthy controls, and levels of anti-TSST-1 antibodies were significantly higher in the CRS patient group with S. aureus in maxillary sinus than in controls. There were no correlations between the severity of symptoms and levels of serum anti-staphylo-coccal IgG antibody levels for LukF-PV and TSST-1.Conclusions: TSST-1 and LukF-PV could be interesting markers for future studies of the pathogenesis of CRS.
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