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- Dahlblom, Mats, et al.
(författare)
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Vertical temperature gradients in apartments with hydronic radiator heating
- 2019
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Ingår i: Cold Climate HVAC 2018 : Sustainable Buildings in Cold Climates - Sustainable Buildings in Cold Climates. - Cham : Springer International Publishing. - 9783030006617 - 9783030006624 ; , s. 575-585
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Konferensbidrag (refereegranskat)abstract
- A vertical temperature stratification normally exists in rooms during the heat-ing season in cold climates. An expression of the gradient in apartments heated by hydronic radiator heating systems with exhaust ventilation has ear-lier been developed assuming a dependency of the outdoor temperature. The expression was used by a public real estate owner when re-calculating meas-ured indoor temperature at 2.1 m above floor to 1.2 m above floor represent-ing the occupancy zone and used for individual metering and billing of space heating cost. To validate the suggested expression temperature measurements have been made at four heights in living rooms in apartments built in the 70’s. The heights includes 0.0, 0.1, 1.1 and 1.7 m above floor. The theoreti-cal expression has been compared to the full-scale measurements and in general the expression overestimates the vertical temperature gradient. The measured gradients are generally very low. The thermal comfort in the aspect of vertical temperature gradient is good for the studied period.
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| 4. |
- Bagge, Niklas, 1987-, et al.
(författare)
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Assessment of concrete bridges - Structural capacity : Experiences from full-scale testing to failure of a bridge in Kiruna
- 2017
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Ingår i: Proceedings of the 23rd Nordic Concrete Research Symposium, Oslo, Norway: Nordic Concrete Federation. - Oslo : Nordic Concrete Federation. ; , s. 263-266
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Konferensbidrag (refereegranskat)abstract
- To calibrate methods for condition assessment of prestressed concrete (PC) bridges, tests were carried out on a 55 year old five-span bridge with a length of 121 m in Kiruna in northern Sweden. Both non-destructive and destructive full-scale tests were performed. This paper presents results regarding methods for assessment of the structural capacity of concrete bridges.
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| 7. |
- Bhadury, Joydeep, et al.
(författare)
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Hypoxia-regulated gene expression explains differences between melanoma cell line-derived xenografts and patient-derived xenografts.
- 2016
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Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 7:17
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Tidskriftsartikel (refereegranskat)abstract
- Cell line-derived xenografts (CDXs) are an integral part of drug efficacy testing during development of new pharmaceuticals against cancer but their accuracy in predicting clinical responses in patients have been debated. Patient-derived xenografts (PDXs) are thought to be more useful for predictive biomarker identification for targeted therapies, including in metastatic melanoma, due to their similarities to human disease. Here, tumor biopsies from fifteen patients and ten widely-used melanoma cell lines were transplanted into immunocompromised mice to generate PDXs and CDXs, respectively. Gene expression profiles generated from the tumors of these PDXs and CDXs clustered into distinct groups, despite similar mutational signatures. Hypoxia-induced gene signatures and overexpression of the hypoxia-regulated miRNA hsa-miR-210 characterized CDXs. Inhibition of hsa-miR-210 with decoys had little phenotypic effect in vitro but reduced sensitivity to MEK1/2 inhibition in vivo, suggesting down-regulation of this miRNA could result in development of resistance to MEK inhibitors.
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| 8. |
- Einarsdottir, Berglind Osk, 1979, et al.
(författare)
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A patient-derived xenograft pre-clinical trial reveals treatment responses and a resistance mechanism to karonudib in metastatic melanoma
- 2018
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Ingår i: Cell Death & Disease. - : Springer Science and Business Media LLC. - 2041-4889. ; 9:8
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Tidskriftsartikel (refereegranskat)abstract
- Karonudib (TH1579) is a novel compound that exerts anti-tumor activities and has recently entered phase I clinical testing. The aim of this study was to conduct a pre-clinical trial in patient-derived xenografts to identify the possible biomarkers of response or resistance that could guide inclusion of patients suffering from metastatic melanoma in phase II clinical trials. Patient-derived xenografts from 31 melanoma patients with metastatic disease were treated with karonudib or a vehicle for 18 days. Treatment responses were followed by measuring tumor sizes, and the models were categorized in the response groups. Tumors were harvested and processed for RNA sequencing and protein analysis. To investigate the effect of karonudib on T-cell-mediated anti-tumor activities, tumor-infiltrating T cells were injected in mice carrying autologous tumors and the mice treated with karonudib. We show that karonudib has heterogeneous anti-tumor effect on metastatic melanoma. Thus, based on the treatment responses, we could divide the 31 patient-derived xenografts in three treatment groups: progression group (32%), suppression group (42%), and regression group (26%). Furthermore, we show that karonudib has anti-tumor effect, irrespective of major melanoma driver mutations. Also, we identify high expression of ABCB1, which codes for p-gp pumps as a resistance biomarker. Finally, we show that karonudib treatment does not hamper T-cell-mediated anti-tumor responses. These findings can be used to guide future use of karonudib in clinical use with a potential approach as precision medicine.
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| 9. |
- Forsberg, Elin, et al.
(författare)
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HER2 CAR-T Cells Eradicate Uveal Melanoma and T-cell Therapy-Resistant Human Melanoma in IL2 Transgenic NOD/SCID IL2 Receptor Knockout Mice
- 2019
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Ingår i: Cancer Research. - 0008-5472. ; 79:5, s. 899-904
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Tidskriftsartikel (refereegranskat)abstract
- Chimeric antigen receptors (CAR) can transmit signals akin to those from activated T-cell receptors when bound to a cell surface target. CAR-expressing T cells against CD19 can cause curative effects in leukemia and lymphoma and is approved for clinical use. However, no CAR-T therapy is currently approved for use in solid tumors. We hypothesize that the resistance of solid tumors to CAR-T can be overcome by similar means as those used to reactivate tumor-infiltrating T lymphocytes (TIL), for example, by cytokines or immune checkpoint blockade. Here we demonstrate that CAR-T cells directed against HER2 can kill uveal and cutaneous melanoma cells in vitro and in vivo. Curative effects in vivo were only observed in xenografts grown in a NOD/SCID IL2 receptor gamma (NOG) knockout mouse strain transgenic for human IL2. The effect was target-specific, as CRISPR/Cas9-mediated disruption of HER2 in the melanoma cells abrogated the killing effect of the CAR-T cells. The CAR-T cells were also able to kill melanoma cells from patients resistant to adoptive T-cell transfer (ACT) of autologous TILs. Thus, CAR-T therapy represents an option for patients that do not respond to immunotherapy with ACT of TIL or immune checkpoint blockade. In addition, our data highlight the use of IL2 transgenic NOG mice as models to prove efficacy of CAR-T-cell products, possibly even in a personalized manner. Significance: These findings demonstrate that a novel humanized mouse model can help clinical translation of CAR-T cells against uveal and cutaneous melanoma that do not respond to TIL therapy or immune checkpoint blockade.
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| 10. |
- Holmberg, Carl Jacob, et al.
(författare)
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Surgery for gastrointestinal metastases of malignant melanoma - a retrospective exploratory study
- 2019
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Ingår i: World Journal of Surgical Oncology. - : Springer Science and Business Media LLC. - 1477-7819. ; 17
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundCutaneous melanoma has a rapidly increasing incidence in Sweden, and it has more than doubled in the last two decades. In recent years, new systemic treatments for patients with metastatic disease have increased overall survival. The role of surgery in the metastatic setting has been unclear, and no randomized data exist. Many surgeons still perform metastasectomies; however, the exact role probably has to be redefined. The aim of this single-institution study was to retrospectively examine the safety and efficacy of surgery in abdominal melanoma metastases and to identify prognostic and predictive factors.MethodsRetrospective analysis of a consecutive series of all patients with stage IV melanoma with gastrointestinal metastases that underwent abdominal surgery at a single center between January 2010 and December 2018. Fifteen patients who underwent in total 18 abdominal procedures, both acute and elective, were identified and included in the study.ResultsOut of 18 laparotomies, six (33%) were emergency procedures due to ileus (n=4), small bowel perforation (n=1), and abdominal abscess (n=1). Twelve procedures (66%) were elective with the most common indication being persistent anemia (58%, n=7), abdominal pain and anemia (33%, n=4), and abdominal pain (8%, n=1). All procedures were performed by laparotomy. There were 19 small bowel resections, 3 partial colon resections, and 2 omental resections. Radical resection was possible in 56% (n=10) of cases and 67% (n=8) when only considering elective procedures. In 17 of 18 procedures (94%), there were mild or no surgical complications (Clavien-Dindo grades 0-I). The median overall survival was 14months with a 5-year survival of 23%.ConclusionsPatients with abdominal melanoma metastases can safely undergo resection with a high grade of radical procedures when performed in the elective setting.Trial registrationClinicalTrials.gov, NCT03879395. Registered 15 March 2019.
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