| 1. |
- Hiltbrunner, Stefanie, et al.
(författare)
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Urinary Exosomes from Bladder Cancer Patients Show a Residual Cancer Phenotype despite Complete Pathological Downstaging
- 2020
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Invasive urinary bladder cancer shows high recurrence rates after cystectomy even with apparent complete downstaging at cystectomy. Exosomes are nano-sized vesicles important in cell-cell communication, which have been hypothesized to contribute to cancer dissemination and recurrence. The aim of this study was to investigate if pro-carcinogenic exosomes could be detected in urine from histologically downstaged bladder cancer patients. 13 Patients were included in this study. Paired ureter and urine samples from nine patients underwent mass spectrometry, while samples from the remaining patients were used for exosome characterization. At cystectomy, exosomes were isolated from bladder and ureter urine, whereafter quantitative proteome profiling was performed. Urinary exosomes clustered based on whether they came from the bladder, with tumour contact, or the ureters, without tumour contact, even though all came from completely downstaged patients. Proteins overexpressed in exosomes derived from bladder urine contained several oncogenes and were mainly associated with tumour metabolism pathways. Although patients were histologically tumour-free at cystectomy, the bladder urine contained exosomes with a carcinogenic metabolic profile. This suggests a continuous release of exosomes from the bladder, which may promote recurrence at distant sites through metabolic rewiring, even after apparent complete downstaging. These exosomes, coming from either undetected cancer cells or partly transformed cells, are likely to increase the risk of metastasis and encourages cystectomy even in completely downstaged patients.
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| 2. |
- Korsnes, Lars, et al.
(författare)
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Undersizing the Exeter stem in hip hemiarthroplasty increases the risk of periprosthetic fracture
- 2020
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Ingår i: HIP International. - : Sage Publications. - 1120-7000 .- 1724-6067. ; 30:4, s. 469-473
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Tidskriftsartikel (refereegranskat)abstract
- Introduction:: Whether under- or oversizing of the femoral component of cemented hip hemiarthroplasties impacts the risk of periprosthetic fractures (PPF) has only been examined experimentally. This study was carried out to add more knowledge about the risks of PPF in cemented polished tapered hemiarthroplasties.Methods: 20 patients with PPF following hip hemiarthroplasty with cemented Exeter V40 stems were compared to 50 controls who never suffered PPF having received the same type of Exeter hemiprosthesis for the same indication. The difference between stem size and post-hoc radiographic ideal templated size was investigated as a predictor of PPF.Results: Cases had a median size difference to post-hoc templating of –2, while controls had a median size difference of –1 (p = 0.09). An ROC curve constructed to find an optimal cutoff point in size difference between cases and controls arrived at an area under curve of 63%, with –1.5 as the cutoff. Patients with size differences exceeding –1.5 had a statistically significant increased PPF risk (odds ratio = 3.8, 95% confidence interval, 1.1–13.3, p < 0.05). This group covered 55% of all cases.Conclusion: An implanted femoral component that is 2 or more sizes smaller than the template that is shown to be appropriate will increase the risk of PPF in Exeter hip hemiarthroplasties.
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| 3. |
- Krantz, David, et al.
(författare)
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IL-16 processing in sentinel node regulatory T cells is a factor in bladder cancer immunity
- 2020
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Ingår i: Scandinavian Journal of Immunology. - : John Wiley & Sons. - 0300-9475 .- 1365-3083. ; 92:6
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Tidskriftsartikel (refereegranskat)abstract
- In the effort of developing new immunotherapies, the sentinel node (SN) has proven a promising source from which to harness an effective antitumour T cell response. However, tumour immune escape, a process in which regulatory T cells (Tregs) play a central role, remains a major limiting factor. Therefore, there is a clear need to increase the knowledge of Treg function and signalling in sentinel nodes. Here, we set out to explore whether the proteome in SN-resident T cells is altered by the tumour and to identify key proteins in SN T cell signalling, focusing on Tregs. Five patients with muscle-invasive urothelial bladder cancer were prospectively included. Mass spectrometry was performed on two patients, with validation and functional studies being performed on three additional patients and four healthy donors. At cystectomy, SN, non-SN lymph nodes and peripheral blood samples were collected from the patients and T cell subsets isolated through flow cytometry before downstream experiments. Proteomic analysis indicated that growth and immune signalling pathways are upregulated in SN-resident Tregs. Furthermore, centrality analysis identified the cytokine IL-16 to be central in the SN-Treg signalling network. We show that tumour-released factors, through activating caspase-3, increase Treg IL-16 processing into bioactive forms, reinforcing Treg suppressive capacity. In conclusion, we provide evidence that Tregs exposed to secreted factors from bladder tumours show increased immune and growth signalling and altered IL-16 processing which translates to enhanced Treg suppressive function, indicating altered IL-16 signalling as a novel tumour immune escape mechanism.
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| 4. |
- Landin, David, et al.
(författare)
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Immune related proteins and tumor infiltratingCD8+ lymphocytes in hypopharyngeal cancer in relation to human papillomavirus (HPV) and clinical outcome
- 2020
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Ingår i: Head and Neck. - : John Wiley & Sons. - 1043-3074 .- 1097-0347. ; 42:11, s. 3206-3217
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Tidskriftsartikel (refereegranskat)abstract
- Background: Hypopharyngeal cancer (HPSCC) shows a poor clinical outcome, while HPSCC, caused by human papillomavirus (HPV), presents a better outcome. Here, HPCC, immune proteins, and tumor infiltrating CD8+ lymphocytes (CD8+ TILs) were evaluated in relation to HPV and outcome.Methods: Fresh frozen tissue from four HPV-positive HPSCC, 39 HPV-negative HPSCC, and normal samples were analyzed for protein expression by the Proseek immuno-oncology immunoassay. CD8+ TIL numbers evaluated by immunohistochemistry on 144 formalin-fixed biopsies were analyzed in relation to clinical outcome.Results: Proteins differing between HPV-positive and negative HPSCC included CD8A, PD-L1, Fas ligand, and chemokines. High CD8+ TIL numbers were correlated to improve clinical outcome in HPV-negative HPSCC.Conclusions: High expression of immune proteins in HPV-positive HPSCC may explain the better clinical outcome. CD8+ TILs are of relevance for outcome of HPV-negative HPSCC, while tumors with high immune activity but poor patient survival suggest a role for immune therapy.
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