| 1. |
- Schoultz, Elin, et al.
(författare)
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Tissue architecture delineates field cancerization in brafv600e-induced tumor development
- 2022
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Ingår i: DMM Disease Models and Mechanisms. - 1754-8403 .- 1754-8411. ; 15:2
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Tidskriftsartikel (refereegranskat)abstract
- Cancer cells hijack developmental growth mechanisms but whether tissue morphogenesis and architecture modify tumorigenesis is unknown. Here, we characterized a new mouse model of sporadic thyroid carcinogenesis based on inducible expression of BRAF carrying a Val600 Glu (V600E) point mutation (BRAFV600E) from the thyroglobulin promoter (TgCreERT2). Spontaneous activation of this Braf-mutant allele due to leaky activity of the Cre recombinase revealed that intrinsic properties of thyroid follicles determined BRAF-mutant cell fate. Papillary thyroid carcinomas developed multicentrically within a normal microenvironment. Each tumor originated from a single follicle that provided a confined space for growth of a distinct tumor phenotype. Lineage tracing revealed oligoclonal tumor development in infancy and early selection of BRAFV600E kinase inhibitor-resistant clones. Somatic mutations were few, non-recurrent and limited to advanced tumors. Female mice developed larger tumors than males, reproducing the gender difference of human thyroid cancer. These data indicate that BRAFV600E-induced tumorigenesis is spatiotemporally regulated depending on the maturity and heterogeneity of follicles. Moreover, thyroid tissue organization seems to determine whether a BRAFmutant lineage becomes a cancerized lineage. The TgCreERT2; BrafCA/+ sporadic thyroid cancer mouse model provides a new tool to evaluate drug therapy at different stages of tumor evolution.
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| 2. |
- Andersson, M., et al.
(författare)
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Evaluation of response in patients with hepatocellular carcinoma treated with intratumoral dendritic cell vaccination using intravoxel incoherent motion (IVIM) MRI and histogram analysis
- 2023
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Ingår i: Acta Radiologica. - : SAGE Publications. - 0284-1851 .- 1600-0455. ; 64:1, s. 32-41
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Tidskriftsartikel (refereegranskat)abstract
- Background Immunotherapy of hepatocellular carcinoma (HCC) is an emerging method with promising results. Immunotherapy can have an antitumor effect without affecting tumor size, calling for functional imaging methods for response evaluation. Purpose To evaluate the response to intratumoral injections with the immune primer ilixadencel in HCCs with diffusion-weighted magnetic resonance imaging (DW-MRI) using intravoxel incoherent motion (IVIM) and histogram analysis. Material and Methods A total of 17 patients with advanced HCC were treated with intratumoral injections with ilixadencel on three occasions 2-5 weeks apart. The patients were examined with IVIM before each injection as well as approximately three months after the first injection. Results The 10th percentile of perfusion-related parameter D* decreased significantly after the first and second intratumoral injections of ilixadencel compared to baseline (P < 0.05). There was a non-significant trend of lower median region of interest f (perfusion fraction) before injection 2 compared to baseline (P = 0.07). There were significant correlations between the 10th percentile and median of D at baseline and change in tumor size after three months (r = 0.79, P < 0.01 and r = 0.72, P < 0.05, respectively). Conclusion DW-MRI with IVIM and histogram analysis revealed significant reductions of D* early after treatment as well as an association between D at baseline and smaller tumor growth at three months. The lower percentiles (10th and 50th) were found more important. Further research is needed to confirm our preliminary findings of reduced perfusion after ilixadencel vaccinations, suggesting a treatment effect on HCC.
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| 3. |
- Apelgren, Peter, et al.
(författare)
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Vascularization of tissue engineered cartilage-Sequential in vivo MRI display functional blood circulation
- 2021
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Ingår i: Biomaterials. - : Elsevier BV. - 0142-9612 .- 1878-5905. ; 276
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Tidskriftsartikel (refereegranskat)abstract
- Establishing functional circulation in bioengineered tissue after implantation is vital for the delivery of oxygen and nutrients to the cells. Native cartilage is avascular and thrives on diffusion, which in turn depends on proximity to circulation. Here, we investigate whether a gridded three-dimensional (3D) bioprinted construct would allow ingrowth of blood vessels and thus prove a functional concept for vascularization of bioengineered tissue. Twenty 10 x 10 x 3-mm 3Dbioprinted nanocellulose constructs containing human nasal chondrocytes or cell-free controls were subcutaneously implanted in 20 nude mice. Over the next 3 months, the mice were sequentially imaged with a 7 T small-animal MRI system, and the diffusion and perfusion parameters were analyzed. The chondrocytes survived and proliferated, and the shape of the constructs was well preserved. The diffusion coefficient was high and well preserved over time. The perfusion and diffusion patterns shown by MRI suggested that blood vessels develop over time in the 3D bioprinted constructs; the vessels were confirmed by histology and immunohistochemistry. We conclude that 3D bioprinted tissue with a gridded structure allows ingrowth of blood vessels and has the potential to be vascularized from the host. This is an essential step to take bioengineered tissue from the bench to clinical practice.
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| 4. |
- Huang, Junchi, et al.
(författare)
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Magnetic Resonance Imaging as a Tool for Monitoring Intratibial Growth of Experimental Prostate Cancer Metastases in Mice
- 2023
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Ingår i: Methods and Protocols (MP). - 2409-9279. ; 6:6
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Tidskriftsartikel (refereegranskat)abstract
- Bone metastases cause morbidity and mortality in several human cancer forms. Experimental models are used to unravel the mechanisms and identify possible treatment targets. The location inside the skeleton complicates accurate assessment. This study evaluates the performance of magnetic resonance imaging (MRI) of prostate cancer tumors growing intratibially in mice. MRI detected intratibial tumor lesions with a sensitivity and specificity of 100% and 89%, respectively, compared to histological evaluation. Location and some phenotypical features could also be readily detected with MRI. Regarding volume estimation, the correlation between MRI and histological assessment was high (p < 0.001, r = 0.936). In conclusion, this study finds MRI to be a reliable tool for in vivo, non-invasive, non-ionizing, real-time monitoring of intratibial tumor growth.
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| 10. |
- Lundholm, Lukas, et al.
(författare)
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VERDICT MRI for radiation treatment response assessment in neuroendocrine tumors.
- 2022
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Ingår i: NMR in biomedicine. - : Wiley. - 1099-1492 .- 0952-3480. ; 35:6
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Tidskriftsartikel (refereegranskat)abstract
- Non-invasive methods to study changes in the tumor microstructure would enable early assessment of treatment response and thus facilitate personalized treatment. The aim of this study was to evaluate the diffusion MRI model Vascular, Extracellular and Restricted Diffusion for Cytometry in Tumors (VERDICT) for early response assessment to external radiation treatment and to compare the results to those of more studied sets of parameters derived from diffusion-weighted MRI data. Mice xenografted with human small intestine tumors were treated with external radiation treatment, and diffusion MRI experiments were performed on the day before and up to two weeks after treatment. The diffusion models VERDICT, ADC, IVIM, and DKI were fitted to MRI data, and the treatment response of each tumor was calculated based on pre-treatment tumor growth and post-treatment tumor volume regression. Linear regression and correlation analysis were used to evaluate each model and their respective parameters for explaining the treatment response. VERDICT analysis showed significant changes from day -1 to day 3 for the intracellular and extracellular volume fraction, as well as the cell radius index (P < 0.05; Wilcoxon signed-rank test). The strongest correlation between the diffusion model parameters and the tumor treatment response was seen for the ADC, kurtosis-corrected diffusion coefficient, and intracellular volume fraction on day 3 (τ = 0.47, 0.52, and -0.49 respectively, P < 0.05; Kendall rank correlation coefficient). Of all tested models, VERDICT held the strongest explanatory value for the tumor treatment response on day 3 (R2 = 0.75, P < 0.01; linear regression). In conclusion, VERDICT holds potential for early assessment of external radiation treatment and may provide further insight into the underlying biological effects of radiation on tumor tissue. In addition, the results suggested that the time window for assessment of treatment response using dMRI may be narrow.
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