| 1. |
- Wennerberg, Erik, et al.
(författare)
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Human anaplastic thyroid carcinoma cells are sensitive to NK cell-mediated lysis via ULBP2/5/6 and chemoattract NK cells
- 2014
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Ingår i: Clinical Cancer Research. - 1078-0432. ; 20:22, s. 5733-5744
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Anaplastic thyroid carcinoma (ATC) is one of the most aggressive forms of cancer with no curative therapies available. To date, strategies to target ATC by immunotherapy have not been evaluated. We investigated whether ATC would be a suitable target for natural killer (NK) cell-based immunotherapy.EXPERIMENTAL DESIGN: We first established seven new cell lines from ATC tumors, three from papillary thyroid carcinoma tumors and analyzed them together with eight additional ATC cell lines. Cells were analyzed for sensitivity to lysis by NK cells and their ability to chemoattract and regulate the activity of NK cells. In addition, fresh tumor samples and peripheral blood from six patients with ATC were analyzed for NK cell infiltration and phenotype.RESULTS: We observed that ATC cell lines are sensitive to lysis by ex vivo expanded NK cells and that the lysis was abrogated upon blockade of NKG2D. Sensitivity of thyroid cancer cell lines to NK cell-mediated lysis correlated with surface expression of UL16-binding protein 2 on tumor cells. Moreover, ATC cell lines produced high levels of CXCL10 and stimulated migration of expanded NK cells and ATC tumors were enriched for NK cells expressing the cognate chemokine receptor CXCR3. However, compared with NK cells in peripheral blood, ATC tumor-derived NK cells displayed a suppressed phenotype with a downregulated expression of NKG2D. In vitro, suppression of NK cell-mediated lysis and NKG2D expression by ATC cells was restored upon neutralization of prostaglandin-E2.CONCLUSIONS: ATC cell lines are sensitive to NK cell-mediated lysis via ULBP2/5/6 and chemoattract CXCR3-positive NK cells. Patients with ATC may benefit from NK cell-based immunotherapy.
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| 2. |
- Anderud, Jonas, et al.
(författare)
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Guided bone augmentation using a ceramic space-maintaining device
- 2014
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Ingår i: Oral surgery, oral medicine, oral pathology and oral radiology. - : Elsevier. - 2212-4403 .- 2212-4411. ; 118:5, s. 532-538
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Tidskriftsartikel (refereegranskat)abstract
- Objective. The purpose of this study was to evaluate 3-dimensionally whether vertical bone augmentation can be achieved using a hollow hydroxyapatite space-maintaining device in a rabbit calvarial model. Furthermore, different inner surface topographies, different permeabilities, and different porosities of the ceramic were tested to determine the optimal conditions for bone regeneration.
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| 3. |
- Anderud, Jonas, et al.
(författare)
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Guided bone augmentation using ceramic space-maintaining devices : The impact of chemistry
- 2015
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Ingår i: Clinical, Cosmetic and Investigational Dentistry. - : Nakladatelstvi Lidove noviny. - 1179-1357. ; 7, s. 45-53
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of the study was to evaluate histologically, whether vertical bone augmentation can be achieved using a hollow ceramic space maintaining device in a rabbit calvaria model. Furthermore, the chemistry of microporous hydroxyapatite and zirconia were tested to determine which of these two ceramics are most suitable for guided bone generation. 24 hollow domes in two different ceramic materials were placed subperiosteal on rabbit skull bone. The rabbits were sacrificed after 12 weeks and the histology results were analyzed regarding bone-to-material contact and volume of newly formed bone. The results suggest that the effect of the microporous structure of hydroxyapatite seems to facilitate for the bone cells to adhere to the material and that zirconia enhance a slightly larger volume of newly formed bone. In conclusion, the results of the current study demonstrated that ceramic space maintaining devices permits new bone formation and osteoconduction within the dome.
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| 4. |
- Anderud, Jonas, et al.
(författare)
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The impact of surface roughness and permeability in hydroxyapatite bone regeneration membranes
- 2015
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Ingår i: Clinical Oral Implants Research. - : Blackwell Munksgaard. - 0905-7161 .- 1600-0501. ; 27:8, s. 1047-1054
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Tidskriftsartikel (refereegranskat)abstract
- Background: One of the crucial aspects in guided bone regeneration is the space maintenance. This is normally created by a membrane, which should primarily be accepted by the surrounding tissues without causing any adverse reactions. The impact of surface topography, biological acceptance as well as permeability of these membranes has been carefully discussed in the literature. Purpose: The purpose of this study was to evaluate histologically the bone forming properties inside of hollow hydroxyapatite space-maintaining devices with different inner surfaces and different permeabilities in an animal calvaria model in vivo. Materials and methods: A total of 36 hollow domes with three different designs made of hydroxyapatite were surgically attached to the skulls of rabbits. Group 1 had a moderately rough inner surface. Group 2 had a smooth inner surface. Group 3 had the same properties as Group 1 but had macroscopic holes on the top. The domes were left to heal for 12 weeks and were then processed for undecalcified ground sectioning. Histological evaluations were performed using a light microscope and scanning electron microscopy. The bone-implant contact (BIC) percentage along the device was calculated. Results: The median percentage of BIC was higher for Group 1 compared with Group 2 (P = 0.004). Group 1 produced a larger median BIC compared with Group 3 (P < 0.0001). Conclusions: Within the limits of this preclinical study, these findings suggest that a moderately rough inner surface of a ceramic membrane along with a non-permeable device produces more bone than a smooth inner surface.
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| 5. |
- Bougas, Kostas, et al.
(författare)
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Bone apposition to laminin-1 coated implants : Histologic and 3D evaluation
- 2013
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Ingår i: International Journal of Oral and Maxillofacial Surgery. - : Elsevier BV. - 0901-5027 .- 1399-0020. ; 42:5, s. 677-682
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Tidskriftsartikel (refereegranskat)abstract
- Laminin-1 has been reported as one of the factors responsible for the nucleation of calcium phosphates and, in vitro, has been reported to selectively recruit osteoprogenitors. This article focused on its in vivo effects, and evaluated the effect of laminin-1 local application on osseointegration. Polished cylindrical hydroxyapatite implants were coated with laminin-1 (test) and the bone responses in the rabbit tibiae after 2 and 4 weeks were evaluated and compared to the non-coated implants (control). Before the samples were processed for histological sectioning, they were three-dimensionally analysed with micro computed tomography (μCT). Both evaluation methods were analysed with regards to bone area around the implant and bone to implant contact. From the histologic observation, new bone formation around the laminin-1 coated implant at 2 weeks seemed to have increased the amount of supporting bone around the implant, however, at 4 weeks, the two groups presented no notable differences. The two-dimensional and three-dimensional morphometric evaluation revealed that both histologic and three-dimensional analysis showed some tendency in favour of the test group implants, however there was no statistical significance between the test and control group results.
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| 6. |
- Brun, Eva, et al.
(författare)
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Early prediction of treatment outcome in head and neck cancer with 2-18FDG PET
- 1997
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 36:7, s. 741-747
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Tidskriftsartikel (refereegranskat)abstract
- The development of alternative treatment regimens in clinical oncology has increased the need for early prediction of cancer therapy outcome. The aim of this study was, early in the treatment phase, to identify patients with advanced head and neck cancer, responding or not responding to initiated therapy. The tumour metabolic rate of glucose (MRgl) examined by 2-18FDG-PET was determined in 17 patients before and after the first weeks of either radiotherapy (16-35 Gy) or one course of combination chemotherapy. Metabolic values uptake values normalized to plasma activity integrals--were correlated to loco-regional outcome, as evaluated 5-6 weeks after completion of treatment. Initial low tumour MRgl (<20 micromol/min/100 g tissue), in primary lesions or regional metastases, predicted a local complete response. When a high initial tumour MRgl was found, the magnitude of the reduction of MRgl in the second PET examination might be an adjunct in predicting local tumour response.
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| 7. |
- Brun, Eva, et al.
(författare)
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FDG PET studies during treatment: Prediction of therapy outcome in head and neck squamous cell carcinoma.
- 2002
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Ingår i: Head and Neck. - : Wiley. - 1043-3074. ; 24:2, s. 127-135
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Positron emission tomography (PET) provides metabolic information of tissues in vivo. The purpose of this study was to assess the value of PET with 2-[(18) F] fluoro-2-deoxy-D-glucose (FDG) in prediction of therapy outcome (tumor response, survival, and locoregional control) in locally advanced HNSCC. METHODS: Between 1993 and 1999 47 patients underwent PET before (PET(1)) and after (PET(2)) 1 to 3 weeks of radical treatment with evaluation of metabolic rate (MR) and standardized uptake value (SUV) of FDG. All patients received radiotherapy, and 10 also received neoadjuvant chemotherapy. Median follow-up time was 3.3 years. RESULTS: Low and high MR FDG at PET(2), with median value as cutoff, was associated with complete remission in 96% and 62% (p =.007), with 5-year overall survival in 72% and 35% (p =.0042) and with local control in 96% and 55% (p =.002), respectively. CONCLUSIONS: FDG PET in the early phase of treatment of HNSCC is associated with tumor response, survival, and local control. Copyright 2002 John Wiley & Sons, Inc.
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| 8. |
- Evans Axelsson, Susan, et al.
(författare)
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Targeting free prostate-specific antigen for in vivo imaging of prostate cancer using a monoclonal antibody specific for unique epitopes accessible on free prostate-specific antigen alone
- 2012
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Ingår i: Cancer Biotherapy and Radiopharmaceuticals. - : Mary Ann Liebert Inc. - 1084-9785 .- 1557-8852. ; 27:4, s. 243-251
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Tidskriftsartikel (refereegranskat)abstract
- This study investigated the feasibility of targeting the free, unbound forms of prostate-specific antigen (fPSA) for in vivo imaging of prostate adenocarcinomas (PCa), as PSA is produced and secreted at abundance during every clinical stage and grade of PCa, including castration-resistant disease. We injected 125I-labeled monoclonal antibody PSA30 (specific for an epitope uniquely accessible on fPSA alone) intravenously in male nude mice carrying subcutaneous xenografts of LNCaP tumors (n=36). Mice were sacrificed over a time course from 4 hours to 13 days after injecting 125I-labeled PSA30. Tissue uptake of 125I-PSA30 at 48 and 168 hours after intravenous injection was compared with two clinically used positron emission tomography radiopharmaceuticals, 18F-fluoro-deoxy-glucose (18F-FDG) or 18F-choline, in cryosections using Digital AutoRadiography (DAR) and also compared with immunohistochemical staining of PSA and histopathology. On DAR, the areas with high 125I-PSA30 uptake corresponded mainly to morphologically intact and PSA-producing LNCaP cells, but did not associate with the areas of high uptake of either 18F-FDG or 18F-choline. Biodistribution of 125I-PSA30 measured in dissected organs ex vivo during 4 to 312 hours after intravenous injection demonstrated maximum selective tumor uptake 24–48 hours after antibody injection. Our data showed selective uptake in vivo of a monoclonal antibody highly specific for fPSA in LNCaP cells. Hence, in vivo imaging of fPSA may be feasible with putative usefulness in disseminated PCa.
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| 9. |
- Högmo, Anders, et al.
(författare)
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Base of tongue squamous cell carcinomas, outcome depending on treatment strategy and p16 status. A population-based study from the Swedish Head and Neck Cancer Register
- 2022
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Ingår i: Acta Oncologica. - : Taylor & Francis. - 0284-186X .- 1651-226X. ; 61:4, s. 433-440
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Tidskriftsartikel (refereegranskat)abstract
- Background: The base of tongue squamous cell carcinoma (BOTSCC) is mainly an HPV-related tumor. Radiotherapy (EBRT) ± concomitant chemotherapy (CT) is the backbone of the curatively intended treatment, with brachytherapy (BT) boost as an option. With four different treatment strategies in Sweden, a retrospective study based on the population-based Swedish Head and Neck Cancer Register (SweHNCR) was initiated.Material and methods: Data on tumors, treatment and outcomes in patients with BOTSCC treated between 2008 and 2014 were validated through medical records and updated as needed. Data on p16 status were updated or completed with immunohistochemical analysis of archived tumor material. Tumors were reclassified according to the UICC 8th edition.Results: Treatment was EBRT, EBRT + CT, EBRT + BT or EBRT + CT + BT in 151, 145, 82 and 167 patients respectively (n = 545). A p16 analysis was available in 414 cases; 338 were p16+ and 76 p16−. 5-year overall survival (OS) was 68% (95% CI: 64–72%), with76% and 37% for p16+ patients and p16− patients, respectively. An increase in OS was found with the addition of CT to EBRT for patients with p16+ tumors, stages II–III, but for patients with tumor stage I, p16+ (UICC 8) none of the treatment strategies was superior to EBRT alone.Conclusion: In the present retrospective population-based study of BOTSCC brachytherapy was found to be of no beneficial value in curatively intended treatment. An increase in survival was found for EBRT + CT compared to EBRT alone in patients with advanced cases, stages II and III (UICC 8), but none of the regimes was significantly superior to EBRT as a single treatment modality for stage I (UICC 8), provided there was p16 positivity in the tumor. In the small group of patients with p16− tumors, a poorer prognosis was found, but the small sample size did not allow any comparisons between different treatment strategies.
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| 10. |
- Magnusson, Sofia E, et al.
(författare)
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Dysregulated Fc receptor function in active rheumatoid arthritis
- 2014
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Ingår i: Immunology Letters. - : Elsevier BV. - 0165-2478 .- 1879-0542. ; 162:1 Pt A, s. 200-206
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Tidskriftsartikel (refereegranskat)abstract
- Given the critical role of Fc gamma receptors (FcgammaR) as primary targets for autoantibody-mediated effects an important issue is how the FcgammaR pathway is affected in autoimmune disorders. Here we investigated the FcgammaR function in monocytes from rheumatoid arthritis (RA) patients in relation to immunoglobulin levels and disease activity. Peripheral blood was obtained from 30 RA patients with clinical acute joint synovitis (active RA), 28 RA patients with no clinical signs of acute joint synovitis (non-active RA) and 34 healthy controls. Prior the functional studies the monocytes were characterized of their FcgammaRI (CD64), II (CD32), IIb (CD32b) and III (CD16) expression as well as their cell surface bound IgG. The monocytic FcgammaR function was assessed by binding of human IgG1 and IgG3 immune complexes (IC) and TNF secretion in vitro. IgG anti-citrullinated peptide antibodies (ACPA) were analyzed in the plasma. We found that monocytes from active RA patients had increased levels of FcgammaRI, II and cell surface IgG concurrently with impaired FcgammaR function. This was evident by reduced IgG1-IC binding and decreased TNF secretion in response to IgG3-IC. In contrast, monocytes from non-active RA patients displayed a normal FcgammaR function and had increased FcgammaRIIb expression together with elevated FcgammaRI, II and cell surface IgG. The ACPA levels did not differ in active and non-active RA patients but correlated with the monocytic FcgammaRIII expression in the patients. In conclusion, active RA patients display a dysregulated FcgammaR function that may represent a novel phenotypic and likely pathogenetic marker for active RA. A disease and FcgammaR function controlling effect is suggested by the increased inhibitory FcgammaRIIb in non-active RA.
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