| 1. |
- Gretarsson, Sigurdur, et al.
(författare)
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Substantial intrinsic variability in chemoradiosensitivity of newly established anaplastic thyroid cancer cell-lines
- 2020
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Ingår i: Acta Oto-Laryngologica. - : Informa UK Limited. - 1651-2251 .- 0001-6489. ; 140:4, s. 337-343
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Tidskriftsartikel (refereegranskat)abstract
- Background: Well characterized human cell lines are needed for preclinical treatment studies of anaplastic thyroid cancer (ATC).Aims/Objectives: The aim was to establish, verify and characterize a panel of ATC cell lines.Material and methods: Cell lines were established from ATC fine-needle aspiration biopsies and characterized genetically and functionally regarding treatment sensitivities.Results: Eight cell lines were established in vitro and the anaplastic thyroid origin was verified. Seven of the cell lines were also grown as xenografts. The cell lines harboured complex karyotypes with modal numbers in hyperdiploid to near-pentaploid range. Five were TP53 mutated and three carried the BRAFV600E mutation. None had rearrangements of RET. For doxorubicin, IC50 ranged from 0.42 to 46 nmol/L and for paclitaxel from 1.6 to 196 nmol/L. Radiation sensitivity varied between 2.6 and 6.3 Gy. Two of the BRAF mutated cell lines displayed high sensitivity to vemurafenib, while the third was similar to the wild-type ones.Conclusions and significance: We describe a series of new ATC cell lines demonstrating large heterogeneity in the response to cytostatic drugs and the BRAF inhibitor vemurafenib. The observations are relevant to future attempts to optimize treatment combinations for ATC.
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| 2. |
- Hafström, Anna, et al.
(författare)
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Patients with cutaneous head and neck melanoma, particularly elderly with more advanced primary tumors, seem to benefit from initial CT staging before considering a sentinel lymph node biopsy
- 2020
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Ingår i: Acta Oto-Laryngologica. - : Informa UK Limited. - 0001-6489 .- 1651-2251. ; 140:9, s. 795-802
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Tidskriftsartikel (refereegranskat)abstract
- Background: The role of CT scanning at the time of diagnosis for patients with primary cutaneous head and neck melanoma (cHNM) clinically asymptomatic for metastatic disease remains unclear. Aim: To determine the positive yield of initial CT scanning before considering sentinel lymph node biopsy (SLNB) staging. Materials and methods: A retrospective review was performed on 170 consecutive patients with cHNM referred to a tertiary head and neck academic center for SLNBs from 2014 through 2018. Results: Initial CTs identified occult melanoma metastases in 7.1% and other advanced malignancies in 4.7%. The overall CT yield for patients >65 years (n = 115) was 13.9%, and 5.5% for patients <65 (only occult melanoma metastases). The SLNB yield did not differ between older (11.5%) and younger patients (10.2%). Patients with more advanced primary tumors were upstaged more often by both staging procedures. Multivariate analysis indicated a true-positive CT finding as the strongest prognostic factor for OS (p<.001). Conclusions and significance: The CT yield was >11% and higher for older than for younger patients. The findings suggest that CT imaging may be considered before SLNB staging, potentially identifying metastatic melanoma disease as well as other occult malignancies, enabling especially older patients to bypass the SLNB procedure.
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| 3. |
- Jimenez, David Gomez, et al.
(författare)
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Subpopulations of organoid-forming cells have different motility
- 2020
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Ingår i: Applied Sciences (Switzerland). - : MDPI AG. - 2076-3417. ; 10:13
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Tidskriftsartikel (refereegranskat)abstract
- Cancer stem cells from oropharyngeal squamous cell carcinoma (OPSCC) have the ability to self-renew and differentiate into heterogeneous three-dimensional structures carrying features of tumor cells. Here, we describe a simple and label-free method for generating tumor organoids, and imaging them using live digital holographic microscopy (DHM) on the basis of the phase shift caused by light passing through the cells. We show early events of cell aggregation during tumor-organoid formation, and display their heterogeneity in terms of optical parameters up to an optical volume of 105 μm3. Lastly, by sorting OPSCC epithelial cells, we demonstrate that CD44+ cells displayed greater motility and tumor-forming capacity than those of CD44- cells. These results were in line with previous reports highlighting increased invasive and tumorigenic potential in tumor cells expressing high levels of CD44. Our method provides insight into the formation of tumor organoids, and could be used to assess stemness-associated biomarkers and drug screenings on the basis of tumor organoids.
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| 4. |
- Mikus, Maria, et al.
(författare)
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Allergome-wide peptide microarrays enable epitope deconvolution in allergen-specific immunotherapy
- 2020
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Ingår i: Journal of Allergy and Clinical Immunology. - : Mosby Inc.. - 0091-6749 .- 1097-6825.
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Tidskriftsartikel (refereegranskat)abstract
- Background: The interaction of allergens and allergen-specific IgE initiates the allergic cascade after crosslinking of receptors on effector cells. Antibodies of other isotypes may modulate such a reaction. Receptor crosslinking requires binding of antibodies to multiple epitopes on the allergen. Limited information is available on the complexity of the epitope structure of most allergens. Objectives: We sought to allow description of the complexity of IgE, IgG4, and IgG epitope recognition at a global, allergome-wide level during allergen-specific immunotherapy (AIT). Methods: We generated an allergome-wide microarray comprising 731 allergens in the form of more than 172,000 overlapping 16-mer peptides. Allergen recognition by IgE, IgG4, and IgG was examined in serum samples collected from subjects undergoing AIT against pollen allergy. Results: Extensive induction of linear peptide-specific Phl p 1– and Bet v 1–specific humoral immunity was demonstrated in subjects undergoing a 3-year-long AIT against grass and birch pollen allergy, respectively. Epitope profiles differed between subjects but were largely established already after 1 year of AIT, suggesting that dominant allergen-specific antibody clones remained as important contributors to humoral immunity following their initial establishment during the early phase of AIT. Complex, subject-specific patterns of allergen isoform and group cross-reactivities in the repertoires were observed, patterns that may indicate different levels of protection against different allergen sources. Conclusions: The study highlights the complexity and subject-specific nature of allergen epitopes recognized following AIT. We envisage that epitope deconvolution will be an important aspect of future efforts to describe and analyze the outcomes of AIT in a personalized manner.
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| 5. |
- Nilsson, Johan S., et al.
(författare)
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Immune phenotypes of nasopharyngeal cancer
- 2020
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 12:11, s. 1-17
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Tidskriftsartikel (refereegranskat)abstract
- Nasopharyngeal cancer (NPC) features intralesional immune cells, but data are lacking on presence/distribution of T-cells and dendritic cells (DCs). Based on intralesional distribution of lymphocytes, a series of NPC biopsies (n = 48) were classified into “inflamed”, “excluded”, and “deserted” phenotypes. In addition, CD8+ T-cells and CD207+ DCs were quantified. The data were analyzed in relation to Epstein–Barr virus-encoded small RNA (EBER), Epstein-Barr virus (EBV) DNA, and survival. Separately, data on gene expression from a public database were analyzed. 61.7% of NPC lesions were “inflamed”, 29.8% were “excluded”, and 8.5% were “deserted”. While CD8+ cells were present in cancer cell areas and in surrounding stroma, CD207+ cells were observed largely in cancer cell areas. High CD8+ T-cell presence was associated with EBV+ disease, but no such pattern was observed for CD207+ DCs. There was a difference in disease-free survival in favor of “inflamed” over “excluded” NPC. Gene expression analysis revealed differences between NPC and control tissue (e.g., with regard to interferon activity) as well as between subgroups of NPC based on CD8 expression (high vs. low). In conclusion, NPC lesions are heterogeneous with regard to distribution of CD8+ T-cells and CD207+ DCs. NPC can be classified into immune phenotypes that carry prognostic information. CD207+ DCs may represent a target for immunotherapy with potential to facilitate the antigen cross-presentation necessary to execute cytotoxic T-lymphocyte responses.
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| 6. |
- Nilsson, Johan S., et al.
(författare)
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Transoral robotic surgery in the management of head and neck squamous cell cancer with unknown primary
- 2020
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Ingår i: Acta Oto-Laryngologica. - : Informa UK Limited. - 0001-6489 .- 1651-2251. ; 140:1, s. 84-88
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Tidskriftsartikel (refereegranskat)abstract
- Background: Transoral robotic surgery (TORS) assisted base of the tongue (BOT) resection has been suggested as part of the work-up for head and neck squamous cell cancer with unknown primary (HNSCC-CUP). Success rates vary with regard to identification of primary BOT lesions, and cases with likely such lesions appear to be included in previous reports. Objectives: To analyse the possible benefits of a superficial TORS-assisted BOT resection in thoroughly investigated HNSCC-CUP. Material and methods: Retrospectively, 13 patients subjected to superficial TORS-assisted BOT resections due to HNSCC-CUP, where previous thorough work-ups including PET-scans had been performed and primary lesions had still not been identified, were reviewed. Results: Nodal status, according to the TNM-8 classification, was N1, N2, N2a, N2b, N2c, and N3, respectively, for 7, 1, 1, 4, 0, and 0 patients. In 38% of the cases, T1 BOT cancers were identified using superficial TORS-assisted BOT resections and treatments adjusted. Conclusion: Addition of a superficial TORS-assisted BOT resection to the work-up of HNSCC-CUP frequently identifies primary lesions and alters the treatment for this group of patients even after thorough work-up.
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