Search

Your search keyword '"Lyng H"' showing total 253 results
Start Over Author "Lyng H"
253 results on '"Lyng H"'

1. ALDH1A1 drives prostate cancer metastases and radioresistance by interplay with AR- and RAR-dependent transcription

Author

Gorodetska, I., Offerman, A., Püschel, J., Lukiyanchuk, V., Gaete, D., Kurzyukova, A., Freytag, V., Fjeldbo, C., Di Gaetano, S., Schwarz, F., Patil, S., Borkowetz, A., Erb, H., Baniahmad, A., Mircetic, J., Lyng, H., (0000-0002-7017-3738) Löck, S., Linge, A., Lange, T., Knopf, F., Wielockx, B., (0000-0003-1776-9556) Krause, M., Perner, S., (0000-0002-3375-1500) Dubrovska, A., Haider, M.-T., Gorodetska, I., Offerman, A., Püschel, J., Lukiyanchuk, V., Gaete, D., Kurzyukova, A., Freytag, V., Fjeldbo, C., Di Gaetano, S., Schwarz, F., Patil, S., Borkowetz, A., Erb, H., Baniahmad, A., Mircetic, J., Lyng, H., (0000-0002-7017-3738) Löck, S., Linge, A., Lange, T., Knopf, F., Wielockx, B., (0000-0003-1776-9556) Krause, M., Perner, S., (0000-0002-3375-1500) Dubrovska, A., and Haider, M.-T.

Abstract

Rationale: Current therapies for metastatic osseous disease frequently fail to provide a durable treatment response. To date, there are only limited therapeutic options for metastatic prostate cancer, the mechanisms that drive the survival of metastasis-initiating cells are poorly characterized, and reliable prognostic markers are missing. A high aldehyde dehydrogenase (ALDH) activity has been long considered a marker of cancer stem cells (CSC). Our study characterized a differential role of ALDH1A1 and ALDH1A3 genes as regulators of prostate cancer progression and metastatic growth. Methods: By genetic silencing of ALDH1A1 and ALDH1A3 in vitro, in xenografted zebrafish and murine models, and by comparative immunohistochemical analyses of benign, primary tumor, and metastatic specimens from patients with prostate cancer, we demonstrated that ALDH1A1 and ALDH1A3 maintain the CSC phenotype and radioresistance and regulate bone metastasis-initiating cells. We have validated ALDH1A1 and ALDH1A3 as potential biomarkers of clinical outcomes in the independent cohorts of patients with PCa. Furthermore, by RNAseq, chromatin immunoprecipitation (ChIP), and biostatistics analyses, we suggested the molecular mechanisms explaining the role of ALDH1A1 in PCa progression. Results: We found that aldehyde dehydrogenase protein ALDH1A1 positively regulates tumor cell survival in circulation, extravasation, and metastatic dissemination, whereas ALDH1A3 plays the opposite role. ALDH1A1 and ALDH1A3 are differentially expressed in metastatic tumors of patients with prostate cancer, and their expression levels oppositely correlate with clinical outcomes. Prostate cancer progression is associated with the increasing interplay of ALDH1A1 with androgen receptor (AR) and retinoid receptor (RAR) transcriptional programs. Polo-like kinase 3 (PLK3) was identified as a transcriptional target oppositely regulated by ALDH1A1 and ALDH1A3 genes in RAR and AR-dependent manner. PLK3 contributes to the

Published
2024

2. A DWI-based hypoxia model shows robustness in an external prostatectomy cohort.

Author

Salamanca, M. Fernandez, Hompland, T., Deregowska-Cylke, M., Van der Poel, H., Bekers, E., Guimaraes, M. A. S., Lyng, H., Van der Heide, U. A., Schoots, I. G., and Van Houdt, P. J.

Subjects
PEARSON correlation (Statistics), DIFFUSION magnetic resonance imaging, BLOOD volume, ABSOLUTE value, DIFFUSION coefficients
Abstract

Introduction: Prostate cancer hypoxia is a negative prognostic biomarker. A promising MRI-based tool to assess hypoxia is the 'Consumption and Supply based Hypoxia' (CSH) model based on diffusion-weighted imaging (DWI). The aim of the study was to validate the association between the CSH hypoxia fraction (HFDWI) with pathological Grade Group (pGG) and pathological T-staging (pTstage) in an external prostatectomy cohort. Methods: Apparent diffusion coefficient (ADC) and fractional blood volume (fBV) maps were assessed from DWI data from 291 prostatectomies and combined by the CSH model. HFDWI was calculated for each lesion after median scaling of ADC and fBV to address differences in acquisition and analysis between centers. The absolute HFDWI values and the associations of HFDWI between pGG < 3 versus ≥ 3, and pTstage = 2 versus = 3 in the Netherlands Cancer Institute (NKI) cohort were compared to the obtained by original cohort (Oslo cohort). Statistical T- and Mann-Whitney tests (p<0.05) were performed. Pearson correlation was determined between HFDWI and individual pGG groups. Results: The HFDWI showed comparable absolute values and similar metric performance as in the original published cohort. Higher HFDWI values were observed for higher pGG(Oslo: 0.27; NKI: 0.24) compared to lower pGG (Oslo: 0.11; NKI: 0.17). Similar results were obtained for pTstage. Furthermore, HFDWI demonstrated a significant positive correlation with pGG groups 1-5 (r = 0.41, p<0.001). Conclusion: The CSH model exhibited sufficient robustness in the external cohort, suggesting a plausible reflection of true hypoxia and enabling the use of the HFDWI metric for further research into prostate cancer and hypoxia. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

18. Vascular responses to radiotherapy and androgen-deprivation therapy in experimental prostate cancer

Author

Roe, K., Mikalsen, L.T., Kogel, A.J. van der, Bussink, J., Lyng, H., Ree, A.H., Marignol, L., and Olsen, D.R.

Subjects
Translational research [ONCOL 3], skin and connective tissue diseases
Abstract

Contains fulltext : 110167.pdf (Publisher’s version ) (Open Access) BACKGROUND: Radiotherapy (RT) and androgen-deprivation therapy (ADT) are standard treatments for advanced prostate cancer (PC). Tumor vascularization is recognized as an important physiological feature likely to impact on both RT and ADT response, and this study therefore aimed to characterize the vascular responses to RT and ADT in experimental PC. METHODS: Using mice implanted with CWR22 PC xenografts, vascular responses to RT and ADT by castration were visualized in vivo by DCE MRI, before contrast-enhancement curves were analyzed both semi-quantitatively and by pharmacokinetic modeling. Extracted image parameters were correlated to the results from ex vivo quantitative fluorescent immunohistochemical analysis (qIHC) of tumor vascularization (9 F1), perfusion (Hoechst 33342), and hypoxia (pimonidazole), performed on tissue sections made from tumors excised directly after DCE MRI. RESULTS: Compared to untreated (Ctrl) tumors, an improved and highly functional vascularization was detected in androgen-deprived (AD) tumors, reflected by increases in DCE MRI parameters and by increased number of vessels (VN), vessel density (VD), and vessel area fraction (VF) from qIHC. Although total hypoxic fractions ( HF) did not change, estimated acute hypoxia scores (AHS)--the proportion of hypoxia staining within 50 mum from perfusion staining--were increased in AD tumors compared to in Ctrl tumors. Five to six months after ADT renewed castration-resistant (CR) tumor growth appeared with an even further enhanced tumor vascularization. Compared to the large vascular changes induced by ADT, RT induced minor vascular changes. Correlating DCE MRI and qIHC parameters unveiled the semi-quantitative parameters area under curve (AUC) from initial time-points to strongly correlate with VD and VF, whereas estimation of vessel size (VS) by DCE MRI required pharmacokinetic modeling. HF was not correlated to any DCE MRI parameter, however, AHS may be estimated after pharmacokinetic modeling. Interestingly, such modeling also detected tumor necrosis very strongly. CONCLUSIONS: DCE MRI reliably allows non-invasive assessment of tumors' vascular function. The findings of increased tumor vascularization after ADT encourage further studies into whether these changes are beneficial for combined RT, or if treatment with anti-angiogenic therapy may be a strategy to improve the therapeutic efficacy of ADT in advanced PC.

Published
2012

22. Model-based estimation of transcript concentrations from spotted microarray data

Author

Frigessi, A., Wiel, van de, M.A., Holden, M., Glad, I.K., Lyng, H., and Statistics

Abstract

In this paper a bootstrap algorithm Much data from spotted microarrays remain unused because obtained with different protocols, platforms or designs, making comparisons across experiments impossible. We have developed a model-based method, which provides absolute transcript levels. Transcript levels are universal, and can be included in further analyses with similar estimates obtained with different techniques in other laboratories. It is a first step both towards genuine meta-analyses, including comparisons across different organisms, and the building of data bases of transcript levels in cells. Our method is based on statistical modelling incorporating all available information about the experiment, from target preparation to image analysis, coherently propagating uncertainties from data to estimates. It requires some genes spotted in replicates, their number being related to the levels of experimental factors included in the model, but not to the number of spotted genes. No uncertainty in the estimates caused by decimated data sets, indirect comparisons, normalisation or imputation of missing values, is introduced, leading to a far more precise analysis of microarray data than provided by conventional methods. Using a flexible Bayesian technique we estimate the highly multivariate joint posterior distribution of all transcripts, which enables extended exploitation of the data. In the present work we apply our method to cervical cancer data. We show that the estimated transcript concentrations are accurate and reproducible, and demonstrate improved statistical tools for selecting genes based on their concentration in highly unbalanced experimental settings.

Published
2004

28. Validation of oligoarrays for quantitative exploration of the transcriptome

Author

Nygaard, V., Liu, FT, Holden, M., Kuo, W.P., Trimarchi, J., Ohno-Machado, L., Cepko, C.L., Frigessi, A., Glad, I.K., van de Wiel, M.A., Hovig, E., Lyng, H., Nygaard, V., Liu, FT, Holden, M., Kuo, W.P., Trimarchi, J., Ohno-Machado, L., Cepko, C.L., Frigessi, A., Glad, I.K., van de Wiel, M.A., Hovig, E., and Lyng, H.

Abstract

Background: Oligoarrays have become an accessible technique for exploring the transcriptome, but it is presently unclear how absolute transcript data from this technique compare to the data achieved with tag-based quantitative techniques, such as massively parallel signature sequencing (MPSS) and serial analysis of gene expression (SAGE). By use of the TransCount method we calculated absolute transcript concentrations from spotted oligoarray intensities, enabling direct comparisons with tag counts obtained with MPSS and SAGE. The tag counts were converted to number of transcripts per cell by assuming that the sum of all transcripts in a single cell was 5·10

Published
2008
Full Text
View/download PDF

31. Genome-wide estimation of transcript concentrations from spotted cDNA microarray data

Author

Frigessi, A., van de Wiel, M.A., Holden, M., Svendsrud, D.H., Glad, I.K., Lyng, H., Frigessi, A., van de Wiel, M.A., Holden, M., Svendsrud, D.H., Glad, I.K., and Lyng, H.

Abstract

A method providing absolute transcript concentrations from spotted microarray intensity data is presented. Number of transcripts per µg total RNA, mRNA or per cell, are obtained for each gene, enabling comparisons of transcript levels within and between tissues. The method is based on Bayesian statistical modelling incorporating available information about the experiment from target preparation to image analysis, leading to realistically large confidence intervals for estimated concentrations. The method was validated in experiments using transcripts at known concentrations, showing accuracy and reproducibility of estimated concentrations, which were also in excellent agreement with results from quantitative real-time PCR. We determined the concentration for 10 157 genes in cervix cancers and a pool of cancer cell lines and found values in the range of 105–1010 transcripts per µg total RNA. The precision of our estimates was sufficiently high to detect significant concentration differences between two tumours and between different genes within the same tumour, comparisons that are not possible with standard intensity ratios. Our method can be used to explore the regulation of pathways and to develop individualized therapies, based on absolute transcript concentrations. It can be applied broadly, facilitating the construction of the transcriptome, continuously updating it by integrating future data.

Published
2005
Full Text
View/download PDF

42. The tumour hypoxia marker pimonidazole reflects a transcriptional programme associated with aggressive prostate cancer.

Author

Ragnum, H B, Vlatkovic, L, Lie, A K, Axcrona, K, Julin, C H, Frikstad, K M, Hole, K H, Seierstad, T, and Lyng, H

Subjects
PROSTATE cancer, BIOMARKERS, HYPOXEMIA, IMMUNOHISTOCHEMISTRY, DNA repair, CANCER cell proliferation
Abstract

Background:The hypoxia marker pimonidazole is a candidate biomarker of cancer aggressiveness. We investigated the transcriptional programme associated with pimonidazole staining in prostate cancer.Methods:Index tumour biopsies were taken by image guidance from an investigation cohort of 52 patients, where 43 patients received pimonidazole before prostatectomy. Biopsy location within the index tumour was verified for 46 (88%) patients, who were included for gene expression profiling and immunohistochemistry. Two independent cohorts of 59 and 281 patients were used for validation.Results:Expression of genes in proliferation, DNA repair and hypoxia response was a major part of the transcriptional programme associated with pimonidazole staining. A signature of 32 essential genes was constructed and showed positive correlation to Ki67 staining, confirming the increased proliferation in hypoxic tumours as suggested from the gene data. Positive correlations were also found to tumour stage and lymph node status, but not to blood prostate-specific antigen level, consistent with the findings for pimonidazole staining. The association with aggressiveness was confirmed in validation cohorts, where the signature correlated with Gleason score and had independent prognostic impact, respectively.Conclusions:Pimonidazole staining reflects an aggressive hypoxic phenotype of prostate cancer characterised by upregulation of proliferation, DNA repair and hypoxia response genes. [ABSTRACT FROM AUTHOR]

Published
2015
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results