| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
- Pulkka, OP, et al.
(author)
-
Anagrelide for Gastrointestinal Stromal Tumor
- 2019
-
In: Clinical cancer research : an official journal of the American Association for Cancer Research. - 1557-3265. ; 25:5, s. 1676-1687
-
Journal article (peer-reviewed)
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
- Larne, Olivia, et al.
(author)
-
MIR-183 in prostate cancer cells positively regulates synthesis and serum levels of prostate-specific antigen
- 2015
-
In: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 68:4, s. 581-588
-
Journal article (peer-reviewed)abstract
- Background Factors affecting serum prostate-specific antigen (PSA) levels in men are clinically important, but apart from effects mediated through the androgen receptor, they are poorly understood. Objective To investigate whether microRNA (miRNA) affects the synthesis and serum levels of PSA. Design, setting, and participants Reporter assays with PSA and KLK2 3′ untranslated regions (UTRs) to confirm posttranscriptional regulation was followed by high-throughput screening of the effect of 1129 miRNAs on PSA levels using reverse phase protein arrays (RPPAs) to identify individual regulatory miRNAs. The candidate miRNAs were investigated further in vitro by Western blot, immunofluorometrics, activity assays, quantitative reverse transcriptase polymerase chain reaction, reporter assays, and growth assays. Prostate levels of miR-183 were compared with PSA transcript and serum PSA levels in prostate cancer cohorts. Outcome measurements and statistical analysis RankProd was used to evaluate the RPPAs, and the Student t test was used for the in vitro experiments. The Spearman and Cuzick tests were used in the patient material, and overall survival was analysed by Kaplan-Meier and log-rank analysis. Results and limitations Gain-of-function screenings identified 32 miRNAs that increase PSA levels. One of these, miR-183, was found to bind the 3′ UTR of PSA directly and increase both protein and messenger RNA levels. Prostatic levels of miR-183 and serum PSA showed correlation in a cohort of 74 men. In addition, miR-183 promotes cellular growth in vitro and correlates to clinical parameters such as World Health Organisation grade and clinical progression. Conclusions The synthesis and serum levels of PSA are directly affected by miR-183 and may be a factor to consider when PSA values are evaluated in clinical settings. Patient summary These findings offer novel insights into the regulation of prostate-specific antigen and may eventually affect clinical decision making in prostate cancer. © 2014 European Association of Urology.
|
|
| 11. |
- Mpindi, JP, et al.
(author)
-
Consistency in drug response profiling
- 2016
-
In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 540:7631, s. E5-E6
-
Journal article (peer-reviewed)
|
|
| 12. |
|
|
| 13. |
|
|
| 14. |
|
|
| 15. |
|
|
| 16. |
- Blom, S, et al.
(author)
-
Systems pathology by multiplexed immunohistochemistry and whole-slide digital image analysis
- 2017
-
In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7:1, s. 15580-
-
Journal article (peer-reviewed)abstract
- The paradigm of molecular histopathology is shifting from a single-marker immunohistochemistry towards multiplexed detection of markers to better understand the complex pathological processes. However, there are no systems allowing multiplexed IHC (mIHC) with high-resolution whole-slide tissue imaging and analysis, yet providing feasible throughput for routine use. We present an mIHC platform combining fluorescent and chromogenic staining with automated whole-slide imaging and integrated whole-slide image analysis, enabling simultaneous detection of six protein markers and nuclei, and automatic quantification and classification of hundreds of thousands of cells in situ in formalin-fixed paraffin-embedded tissues. In the first proof-of-concept, we detected immune cells at cell-level resolution (n = 128,894 cells) in human prostate cancer, and analysed T cell subpopulations in different tumour compartments (epithelium vs. stroma). In the second proof-of-concept, we demonstrated an automatic classification of epithelial cell populations (n = 83,558) and glands (benign vs. cancer) in prostate cancer with simultaneous analysis of androgen receptor (AR) and alpha-methylacyl-CoA (AMACR) expression at cell-level resolution. We conclude that the open-source combination of 8-plex mIHC detection, whole-slide image acquisition and analysis provides a robust tool allowing quantitative, spatially resolved whole-slide tissue cytometry directly in formalin-fixed human tumour tissues for improved characterization of histology and the tumour microenvironment.
|
|
| 17. |
|
|
| 18. |
|
|
| 19. |
|
|
| 20. |
|
|
| 21. |
|
|
| 22. |
|
|
