| 1031. |
- Aaltonen, K. E., et al.
(författare)
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Gene expression of breast cancer related genes in circulating tumour cells (CTCs) from patients with metastatic breast cancer
- 2015
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534. ; 26:Suppl. 3, s. 15-15
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Detection of circulating tumour cells (CTCs) in peripheral blood has an established prognostic significance in patients with metastatic breast cancer. Change in the number of detected CTCs is also an indication of response to therapy. Characterisation of CTCs could provide easily accessible treatment predictive information of present cancer cells within the patient and could reveal important knowledge about the metastatic process. The aim of this pilot study was to characterize CTCs with regard to both treatment predictive and more experimental markers by analysing the expression of genes associated with breast cancer.Methods: Blood samples from twelve patients with metastatic breast cancer included in the ongoing CTC-MBC study at Lund University, Sweden (Clinical Trials Id. NCT01322893) were analysed in this pilot study. Systemic treatment included endocrine, targeted and chemotherapy regimen. Blood samples were collected before start of 1st line therapy and at four time points. If progression occurred, a new round of samples was taken. CTCs were isolated from whole blood using the commercial kits AdnaTest EMT1/stem cell and AdnaTest EMT2/stem cell (AdnaGen AG, Langenhagen, Germany). With this method, CTCs are captured using antibodies directed against EpCAM and MUC-1 (EMT1-kit) or EpCAM, HER2 and EGFR (EMT2-kit). Gene expression analyses from CTCs at each time point was performed by TATAA Biocenter (Gothenburg, Sweden) using qPCR. 38 breast cancer related genes were analysed including the oestrogen receptor (ESR), HER2, VEGFR2, ALDH1, PI3K, PTEN and TWIST1.Results: Using positive expression of pseudo-markers EpCAM, MUC1 and HER2 as definition of CTCs, 6 of 12 patients were positive for CTCs. However, gene expression of additional markers in potential CTCs suggests complex patterns such as an increase in TWIST1, ALDH1 and SATB1 at time of progression.Conclusions: We present gene expression data from CTCs isolated before and during therapy in metastatic breast cancer patients. This type of characterisation could provide information of importance for treatment response and clinical outcome.Clinical trial identification: NCT01322893, March 24 2011
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| 1032. |
- Aaltonen, Kristina E., et al.
(författare)
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Molecular characterization of circulating tumor cells from patients with metastatic breast cancer reflects evolutionary changes in gene expression under the pressure of systemic therapy
- 2017
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Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 8:28, s. 45544-45565
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Tidskriftsartikel (refereegranskat)abstract
- Resistance to systemic therapy is a major problem in metastatic breast cancer (MBC) that can be explained by initial tumor heterogeneity as well as by evolutionary changes during therapy and tumor progression. Circulating tumor cells (CTCs) detected in a liquid biopsy can be sampled and characterized repeatedly during therapy in order to monitor treatment response and disease progression. Our aim was to investigate how CTC derived gene expression of treatment predictive markers (ESR1/HER2) and other cancer associated markers changed in patient blood samples during six months of first-line systemic treatment for MBC. CTCs from 36 patients were enriched using CellSearch (Janssen Diagnostics) and AdnaTest (QIAGEN) before gene expression analysis was performed with a customized gene panel (TATAA Biocenter). Our results show that antibodies against HER2 and EGFR were valuable to isolate CTCs unidentified by CellSearch and possibly lacking EpCAM expression. Evaluation of patients with clinically different breast cancer subgroups demonstrated that gene expression of treatment predictive markers changed over time. This change was especially prominent for HER2 expression. In conclusion, we found that changed gene expression during first-line systemic therapy for MBC could be a possible explanation for treatment resistance. Characterization of CTCs at several time-points during therapy could be informative for treatment selection.
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| 1033. |
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| 1034. |
- Aaltonen, Kristina, et al.
(författare)
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Laser capture microdissection (LCM) and whole genome amplification (WGA) of DNA from normal breast tissue - optimization for genome wide array analyses.
- 2011
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Ingår i: BMC Research Notes. - : Springer Science and Business Media LLC. - 1756-0500. ; 4, s. 69-69
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Tidskriftsartikel (refereegranskat)abstract
- Background Laser capture microdissection (LCM) can be applied to tissues where cells of interest are distinguishable from surrounding cell populations. Here, we have optimized LCM for fresh frozen normal breast tissue where large amounts of fat can cause problems during microdissection. Since the amount of DNA needed for genome wide analyses, such as single nucleotide polymorphism (SNP) arrays, is often greater than what can be obtained from the dissected tissue, we have compared three different whole genome amplification (WGA) kits for amplification of DNA from LCM material. In addition, the genome wide profiling methods commonly used today require extremely high DNA quality compared to PCR based techniques and DNA quality is thus critical for successful downstream analyses. Findings We found that by using FrameSlides without glass backing for LCM and treating the slides with acetone after staining, the problems caused by excessive fat could be significantly decreased. The amount of DNA obtained after extraction from LCM tissue was not sufficient for direct SNP array analysis in our material. However, the two WGA kits based on Phi29 polymerase technology (Repli-g® (Qiagen) and GenomiPhi (GE Healthcare)) gave relatively long amplification products, and amplified DNA from Repli-g® gave call rates in the subsequent SNP analysis close to those from non-amplified DNA. Furthermore, the quality of the input DNA for WGA was found to be essential for successful SNP array results and initial DNA fragmentation problems could be reduced by switching from a regular halogen lamp to a VIS-LED lamp during LCM. Conclusions LCM must be optimized to work satisfactorily in difficult tissues. We describe a work flow for fresh frozen normal breast tissue where fat is inclined to cause problems if sample treatment is not adapted to this tissue. We also show that the Phi29-based Repli-g® WGA kit (Qiagen) is a feasible approach to amplify DNA of high quality prior to genome wide analyses such as SNP profiling.
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| 1035. |
- Aaltonen, Kristina, et al.
(författare)
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Patient-derived models : Advanced tools for precision medicine in neuroblastoma
- 2023
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Ingår i: Frontiers in Oncology. - : Frontiers Media SA. - 2234-943X. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Neuroblastoma is a childhood cancer derived from the sympathetic nervous system. High-risk neuroblastoma patients have a poor overall survival and account for ~15% of childhood cancer deaths. There is thus a need for clinically relevant and authentic models of neuroblastoma that closely resemble the human disease to further interrogate underlying mechanisms and to develop novel therapeutic strategies. Here we review recent developments in patient-derived neuroblastoma xenograft models and in vitro cultures. These models can be used to decipher mechanisms of metastasis and treatment resistance, for drug screening, and preclinical drug testing. Patient-derived neuroblastoma models may also provide useful information about clonal evolution, phenotypic plasticity, and cell states in relation to neuroblastoma progression. We summarize current opportunities for, but also barriers to, future model development and application. Integration of patient-derived models with patient data holds promise for the development of precision medicine treatment strategies for children with high-risk neuroblastoma.
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| 1036. |
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| 1037. |
- Aaltonen, Mikko, et al.
(författare)
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Comparing Employment Trajectories before and after First Imprisonment in Four Nordic Countries
- 2017
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Ingår i: British Journal of Criminology. - : Oxford University Press (OUP). - 0007-0955 .- 1464-3529. ; 57:4, s. 828-847
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Tidskriftsartikel (refereegranskat)abstract
- Employment plays a crucial role in the re-entry process and in reducing recidivism among offenders released from prison. But at the same time, imprisonment is generally regarded as harmful to post-release employment prospects. Little is known, however, about whether or not offenders’ employment trajectories before and after imprisonment are similar across countries. As a first step towards filling this gap in research, this paper provides evidence on employment trajectories before and after imprisonment in four Nordic welfare states: Denmark, Finland, Norway and Sweden. Using data gathered from administrative records on incarcerated offenders, the analysis focuses on individuals imprisoned for the first time and who served a prison sentence less than one year in length. Results show that although employment trajectories develop in mostly similar ways before and after imprisonment across these countries, important differences exist.
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| 1038. |
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| 1039. |
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| 1040. |
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