| 1. |
- Johansson, Carl-Johan, et al.
(author)
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Sågverksnytt nr 1
- 2013
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Reports (other academic/artistic)
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| 2. |
- Lintula, S, et al.
(author)
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Relative concentrations of hK2/PSA mRNA in benign and malignant prostatic tissue
- 2005
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In: The Prostate. - : Wiley. - 0270-4137 .- 1097-0045. ; 63:4, s. 324-329
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Journal article (peer-reviewed)abstract
- BACKGROUND. Prostate-specific antigen (PSA/KLK3) and human kallikrein 2 (hK2/KLK2) belong to the human kallikrein gene family. These two highly homologous genes are specifically expressed in the prostate under androgen control. Expression of these is regulated by similar mechanisms but changes in their relative expression have been observed in prostate cancer. METHODS. We determined the relative levels of PSA and hK2 mRNA in benign and malignant prostate tissue using a quantitative reverse transcription-polymerase chain reaction (RT-PCR) method. The mRNA of PSA and hK2 are reverse transcribed and amplified in one reaction with the same primers. RESULTS. The variation in the ratio of hK2/PSA mRNA was remarkably small, the difference between the highest and lowest values being three-fold. The ratio was significantly higher in WHO grade 2 compared to normal or benign prostatic hyperplasia tissue (P=0.032 and P=0.035, respectively) and in grade 3 compared to normal or benign prostatic hyperplasia tissue (P=0.006 in both). CONCLUSIONS. The new quantitative RT-PCR technique facilitates very accurate quantitation of the relative mRNA levels of homologous genes. Using this method we have shown that the ratio of hK2/PSA mRNA is higher in cancerous than in benign prostatic tissue.
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| 3. |
- Lippolis, Giuseppe, et al.
(author)
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A high-density tissue microarray from patients with clinically localized prostate cancer reveals ERG and TATI exclusivity in tumor cells.
- 2013
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In: Prostate Cancer and Prostatic Diseases. - : Springer Science and Business Media LLC. - 1476-5608 .- 1365-7852. ; 16:2, s. 145-150
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Journal article (peer-reviewed)abstract
- Background:Prostate cancer (PCa) is characterized by high tumor heterogeneity. In 2005, the fusion between the androgen-regulated gene TMPRSS2 and members of the ETS family was discovered in prostate cancer. In particular, fusion of TMPRSS2 with ERG was found in approximately 50% of prostate cancers and considered as an early event in the onset of the disease. The prognostic value of this fusion is still contradictory. Bioinformatics showed that overexpression of SPINK1 gene in a subset of fusion-gene-negative prostate cancers was associated with a poor prognosis. In theory, overexpression of the tumor-associated trypsin inhibitor (TATI) protein encoded by SPINK1 in fusion-gene-negative tumor cells opens the way to selected treatments for genotypically different cases. However, their expression has never been assessed at the cellular level in the same tissue samples.Methods:As ERG expression has been shown to be a surrogate of fusion gene occurrence in prostate cancer, we have used double immunohistochemical staining to assess expression of ERG and TATI on a large tissue microarray comprising 4177 cases of localized prostate cancer.Results:We did not detect any co-expression of ERG and TATI in the same cancer cells, which confirms previous suggestions from in silico studies. ERG was associated with Gleason score (GS), surgical margins and pathological stage, but had no prognostic value in this cohort. TATI was weakly associated with pathological stage but had no significant association with outcome.Conclusions:We here provide a morphological basis for ERG and TATI exclusivity in prostate cancer cells. Future therapies should be based on a combination of different targets in order to eradicate tumor cells with gene fusions and cells expressing other tumor-associated antigens. Further studies are needed to understand why ERG and TATI are not co-expressed in the same prostatic tumor cells.Prostate Cancer and Prostatic Disease advance online publication, 5 March 2013; doi:10.1038/pcan.2013.7.
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| 4. |
- Paju, A, et al.
(author)
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Expression and characterization of trypsinogen produced in the human male genital tract
- 2000
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In: American Journal of Pathology. - 1525-2191. ; 157:6, s. 2011-2021
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Journal article (peer-reviewed)abstract
- Trypsinogen is a serine proteinase produced mainly by the pancreas, but it has recently been found to be expressed also in several cancers such as ovarian and colon cancer and in vascular endothelial cells. In this study, we found that trypsinogen-1 and -2 are present at high concentrations (median levels, 0.4 and 0.5 mg/L, respectively) in human seminal fluid and purified them to homogeneity by immunoaffinity and anion exchange chromatography. Purified trypsinogen isoenzymes displayed a M(r) of 25 to 28 kd in sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting. Most of the trypsinogen-1 purified from seminal fluid was enzymatically active whereas trypsinogen-2 occurred as the proform, which could be activated by enteropeptidase in vitro. Immunohistochemically, trypsinogen protein was detected in the human prostate, urethra, utriculus, ejaculatory duct, seminal vesicles, deferent duct, epididymal glands, and testis. Expression of trypsinogen mRNA in the same organs was demonstrated by in situ hybridization. Trypsinogen mRNA was also detected in the prostate and seminal vesicles by reverse transcriptase-polymerase chain reaction and Northern blotting. Isolated trypsin was shown to activate the proenzyme form of prostate-specific antigen. These results suggest that trypsinogen isoenzymes found in seminal fluid are produced locally in the male genital tract and that they may play a physiological role in the semen.
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| 5. |
- Stenman, Mathias, et al.
(author)
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Trypsin-2 degrades human type II collagen and is expressed and activated in mesenchymally transformed rheumatoid arthritis synovitis tissue
- 2005
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In: American Journal of Pathology. - 1525-2191 .- 0002-9440. ; 167:4, s. 1119-1124
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Journal article (peer-reviewed)abstract
- It has traditionally been believed that only the human collagenases (matrix metalloproteinase-1, -8, and -13) are capable of initiating the degradation of collagens. Here, we show that human trypsin-2 is also capable of cleaving the triple helix of human cartilage collagen type II. We purified human trypsin-2 and tumor-associated trypsin inhibitor by affinity chromatography whereas collagen type II was purified from cartilage extracts using pepsin digestion and salt precipitation. Degradation of type II collagen and gelatin by trypsin-2 was demonstrated with sodium dodecyl sulfate-polyacrylamide gel electrophoresis, zymography, and mass spectrometry, and tumor-associated trypsin inhibitor specifically inhibited this degradation. Although human trypsin-2 efficiently digested type II collagen, bovine trypsin did not. Furthermore, immunohistochemical staining detected trypsin-2 in the fibroblast-like synovial lining and in stromal cells of human rheumatoid arthritis synovial membrane. These findings were confirmed by reverse transcriptase-polymerase chain reaction and nucleotide sequencing. Trypsin-2 alone and complexed with alpha(1)-proteinase inhibitor were also detected in the synovial fluid of affected joints by time-resolved immunofluorometric assay, suggesting that trypsin-2 is activated locally. These results are the first to assess the ability of human trypsin to cleave human type II collagen. Thus, trypsin-2 and its regulators should be further studied for use as markers of prognosis and disease activity in rheumatoid arthritis.
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| 6. |
- Andersson, Mattias K, 1979, et al.
(author)
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The multifunctional FUS, EWS and TAF15 proto-oncoproteins show cell type-specific expression patterns and involvement in cell spreading and stress response
- 2008
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In: BMC Cell Biology. - : Springer Science and Business Media LLC. - 1471-2121. ; 9
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Journal article (peer-reviewed)abstract
- BACKGROUND: FUS, EWS and TAF15 are structurally similar multifunctional proteins that were first discovered upon characterization of fusion oncogenes in human sarcomas and leukemias. The proteins belong to the FET (previously TET) family of RNA-binding proteins and are implicated in central cellular processes such as regulation of gene expression, maintenance of genomic integrity and mRNA/microRNA processing. In the present study, we investigated the expression and cellular localization of FET proteins in multiple human tissues and cell types. RESULTS: FUS, EWS and TAF15 were expressed in both distinct and overlapping patterns in human tissues. The three proteins showed almost ubiquitous nuclear expression and FUS and TAF15 were in addition present in the cytoplasm of most cell types. Cytoplasmic EWS was more rarely detected and seen mainly in secretory cell types. Furthermore, FET expression was downregulated in differentiating human embryonic stem cells, during induced differentiation of neuroblastoma cells and absent in terminally differentiated melanocytes and cardiac muscle cells. The FET proteins were targeted to stress granules induced by heat shock and oxidative stress and FUS required its RNA-binding domain for this translocation. Furthermore, FUS and TAF15 were detected in spreading initiation centers of adhering cells. CONCLUSION: Our results point to cell-specific expression patterns and functions of the FET proteins rather than the housekeeping roles inferred from earlier studies. The localization of FET proteins to stress granules suggests activities in translational regulation during stress conditions. Roles in central processes such as stress response, translational control and adhesion may explain the FET proteins frequent involvement in human cancer.
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| 9. |
- Behboudi, Afrouz, 1967, et al.
(author)
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Molecular classification of mucoepidermoid carcinomas-prognostic significance of the MECT1-MAML2 fusion oncogene.
- 2006
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In: Genes, chromosomes & cancer. - : Wiley. - 1045-2257 .- 1098-2264. ; 45:5, s. 470-81
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Journal article (peer-reviewed)abstract
- Mucoepidermoid carcinomas (MECs) of the salivary and bronchial glands are characterized by a recurrent t(11;19)(q21;p13) translocation resulting in a MECT1-MAML2 fusion in which the CREB-binding domain of the CREB coactivator MECT1 (also known as CRTC1, TORC1 or WAMTP1) is fused to the transactivation domain of the Notch coactivator MAML2. To gain further insights into the molecular pathogenesis of MECs, we cytogenetically and molecularly characterized a series of 29 MECs. A t(11;19) and/or an MECT1-MAML2 fusion was detected in more than 55% of the tumors. Several cases with cryptic rearrangements that resulted in gene fusions were detected. In fusion-negative MECs, the most common aberration was a single or multiple trisomies. Western blot and immunohistochemical studies demonstrated that the MECT1-MAML2 fusion protein was expressed in all MEC-specific cell types. In addition, cotransfection experiments showed that the fusion protein colocalized with CREB in homogeneously distributed nuclear granules. Analyses of potential downstream targets of the fusion revealed differential expression of the cAMP/CREB (FLT1 and NR4A2) and Notch (HES1 and HES5) target genes in fusion-positive and fusion-negative MECs. Moreover, clinical follow-up studies revealed that fusion-positive patients had a significantly lower risk of local recurrence, metastases, or tumor-related death compared to fusion-negative patients (P = 0.0012). When considering tumor-related deaths only, the estimated median survival for fusion-positive patients was greater than 10 years compared to 1.6 years for fusion-negative patients. These findings suggest that molecularly classifying MECs on the basis of an MECT1-MAML2 fusion is histopathologically and clinically relevant and that the fusion is a useful marker in predicting the biological behavior of MECs.
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| 10. |
- Biel, Anders, 1948, et al.
(author)
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Emotions, Morality and Public Goods: The WTA-WTP Disparity Revisited
- 2006
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Reports (other academic/artistic)abstract
- Empirical evidence suggests that people´s maximum willingness to pay for having a good is often substantially lower than their minimum willingness to accept not having it, and that this discrepancy tends to be especially large when valuing public goods. This paper hypothesizes that differences in emotions (e.g. regret) and moral perceptions can account for much of this discrepancy for public goods. A simple, real-money dichotomous-choice experiment is set up to test these hypotheses, which are largely supported.
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