10 results on '"Donnem, T."'
Search Results
2. Low Expression of miR-424-3p is Highly Correlated with Clinical Failure in Prostate Cancer
- Author
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Richardsen, E., Andersen, S., Al-Saad, S., Rakaee, M., Nordby, Y., Pedersen, M. I., Ness, N., Ingebriktsen, L. M., Fassina, A., Taskén, K. A., Mills, I. G., Donnem, T., Bremnes, R. M., and Busund, L. T.
- Published
- 2019
- Full Text
- View/download PDF
3. Differential prognostic impact of platelet-derived growth factor receptor expression in NSCLC.
- Author
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Kilvaer TK, Rakaee M, Hellevik T, Vik J, Petris L, Donnem T, Strell C, Ostman A, Busund LR, and Martinez-Zubiaurre I
- Subjects
- Adult, Aged, Aged, 80 and over, Biomarkers, Tumor, Carcinoma, Non-Small-Cell Lung metabolism, Carcinoma, Squamous Cell metabolism, Female, Humans, Immunohistochemistry methods, Lung Neoplasms pathology, Male, Middle Aged, Platelet-Derived Growth Factor metabolism, Prognosis, Receptor, Platelet-Derived Growth Factor alpha metabolism, Receptor, Platelet-Derived Growth Factor beta metabolism, Receptors, Platelet-Derived Growth Factor metabolism, Stromal Cells metabolism, Tissue Array Analysis methods, Carcinoma, Non-Small-Cell Lung genetics, Receptors, Platelet-Derived Growth Factor genetics
- Abstract
Preclinical evidence suggests that stromal expression of platelet-derived growth factor receptors (PDGFRs) stimulates tumor development and diminishes intratumoral drug uptake. In non-small cell lung cancer (NSCLC), the clinical relevance of stromal PDGFR expression remains uncertain. Tumor specimens from 553 patients with primary operable stage I-IIIB NSCLC was obtained and tissue micro-arrays (TMA) were constructed (Norwegian cohort). Immunohistochemistry (IHC) was used to evaluate the expression of PDGFRα and -β in stromal cells and to explore their impact on patient survival. Results were validated in a non-related cohort consisting of TMAs of 367 stage I (A and B) NSCLC patients (Swedish cohort). High stromal PDGFRα expression was an independent predictor of increased survival in the overall populations and SCC (squamous cell carcinoma) subgroups of both investigated cohorts. PDGFRβ was an independent predictor of poor survival in the overall Norwegian cohort and an independent predictor of increased survival in the ADC (adenocarcinoma) subgroup of the Swedish cohort. Tumors displaying the combination PDGFRα-low/PDGFRβ-high exhibited inferior survival according to increasing stage in the Norwegian cohort. This study confirms that high stromal expression of PDGFRα is a predictor of increased survival in NSCLC. Further exploration of the prognostic impact of PDGFRβ and the relationship between PDGFRα and -β is warranted.
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- 2019
- Full Text
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4. Progesterone Receptors in Prostate Cancer: Progesterone receptor B is the isoform associated with disease progression.
- Author
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Grindstad T, Richardsen E, Andersen S, Skjefstad K, Rakaee Khanehkenari M, Donnem T, Ness N, Nordby Y, Bremnes RM, Al-Saad S, and Busund LT
- Subjects
- Aged, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Multivariate Analysis, Protein Isoforms metabolism, Disease Progression, Prostatic Neoplasms metabolism, Prostatic Neoplasms pathology, Receptors, Progesterone metabolism
- Abstract
The role of steroid hormones in carcinogenesis of the prostate is to some extent unraveled thorough the effect of androgen deprivation therapy on prostate cancer (PCa) progression. Other members of the steroid hormone family, such as progesterone, are also implicated in PCa, but progesterone's role remains undefined. This study aimed to examine the distribution of progesterone receptor isoforms (PGRA, PGRB) in PCa tissue and their association with clinical endpoints. This was conducted retrospectively by collecting radical prostatectomy specimens from 535 patients. Tissue was analyzed using tissue microarray, where representative tumor areas were carefully selected. Protein expression was evaluated through immunohistochemistry, in stromal and epithelial tissue. Associations between receptor expression and clinical data were considered using statistical survival analyses. Herein, we discovered a solely stromal PGRA- and a stromal and epithelial PGRB expression. Further, a high PGRB expression in tumor tissue was associated with an unfavorable prognosis in both univariate and multivariate analyses: Biochemical failure (HR: 2.0, 95% CI: 1.45-2.76, p < 0.001) and clinical failure (HR: 2.5, 95% CI: 1.29-4.85, p = 0.006). These findings are in agreement with our previous investigation on pan-PGR, indicating that the observed negative effect of PGR is represented by PGRB.
- Published
- 2018
- Full Text
- View/download PDF
5. A gender specific improved survival related to stromal miR-143 and miR-145 expression in non-small cell lung cancer.
- Author
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Skjefstad K, Johannessen C, Grindstad T, Kilvaer T, Paulsen EE, Pedersen M, Donnem T, Andersen S, Bremnes R, Richardsen E, Al-Saad S, and Busund LT
- Subjects
- A549 Cells, Aged, Disease-Free Survival, Female, Humans, Lymph Nodes metabolism, Lymph Nodes pathology, Lymphatic Metastasis, Male, Middle Aged, Survival Rate, Carcinoma, Non-Small-Cell Lung metabolism, Carcinoma, Non-Small-Cell Lung mortality, Carcinoma, Non-Small-Cell Lung pathology, Gene Expression Regulation, Neoplastic, Lung Neoplasms metabolism, Lung Neoplasms mortality, Lung Neoplasms pathology, MicroRNAs biosynthesis, RNA, Neoplasm biosynthesis, Sex Characteristics
- Abstract
Micro RNAs (miRNA) are small non-coding RNAs that post-transcriptionally regulate gene expression. Dysregulation of miRNA cluster 143/145 has been reported in several malignancies, but their role in non-small cell lung cancer (NSCLC) remains elusive. This study investigates the prognostic impact of miR-143 and miR-145 in primary tumors and metastatic lymph nodes in NSCLC tissue. Tissue from 553 primary tumors and 143 matched metastatic lymph nodes were collected and tissue microarrays were constructed. In situ hybridization was used to evaluate miR-143 and miR-145 expression in tumor epithelial cells and stromal cells in the primary tumors and lymph nodes. In vivo data was supplemented with functional studies of cell lines in vitro to evaluate the role of miR-143 and miR-145 in NSCLC tumorigenesis. In our cohort, stromal miR-143 (S-miR-143) and miR-145 (S-miR-145) expression in primary tumor tissue were independent prognosticators of improved disease-specific survival (DSS) in female (S-miR-143, HR: 0.53, p = 0.019) and male patients (S-miR-145, HR: 0.58, p = 0.021), respectively. Interesting correlations between the miR cluster 143/145 and previously investigated steroid hormone receptors from the same cohort were identified, substantiating their gender dependent significance.
- Published
- 2018
- Full Text
- View/download PDF
6. Transcription factor PAX6 as a novel prognostic factor and putative tumour suppressor in non-small cell lung cancer.
- Author
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Kiselev Y, Andersen S, Johannessen C, Fjukstad B, Standahl Olsen K, Stenvold H, Al-Saad S, Donnem T, Richardsen E, Bremnes RM, and Rasmussen Busund LT
- Subjects
- Adult, Aged, Aged, 80 and over, Carcinoma, Non-Small-Cell Lung pathology, Cell Line, Tumor, Disease-Free Survival, Female, Gene Expression Regulation, Neoplastic genetics, Gene Knockdown Techniques, Humans, Lymph Nodes pathology, Male, Middle Aged, Neoplasm Staging, Prognosis, Tumor Suppressor Proteins genetics, Biomarkers, Tumor genetics, Carcinoma, Non-Small-Cell Lung genetics, Cell Proliferation genetics, PAX6 Transcription Factor genetics
- Abstract
Lung cancer is the leading cause of cancer deaths. Novel predictive biomarkers are needed to improve treatment selection and more accurate prognostication. PAX6 is a transcription factor with a proposed tumour suppressor function. Immunohistochemical staining was performed on tissue microarrays from 335 non-small cell lung cancer (NSCLC) patients for PAX6. Multivariate analyses of clinico-pathological variables and disease-specific survival (DSS) was carried out, and phenotypic changes of two NSCLC cell lines with knockdown of PAX6 were characterized. While PAX6 expression was only associated with a trend of better disease-specific survival (DSS) (p = 0.10), the pN+ subgroup (N = 103) showed significant correlation between high PAX6 expression and longer DSS (p = 0.022). Median survival for pN + patients with high PAX6 expression was 127.4 months, versus 22.9 months for patients with low PAX6 expression. In NCI-H661 cells, knockdown of PAX6 strongly activated serum-stimulated migration. In NCI-H460 cells, PAX6 knockdown activated anchorage-independent growth. We did not observe any significant effect of PAX6 on proliferation in either of cell lines. Our findings strongly support the proposition of PAX6 as a valid and positive prognostic marker in NSCLC in node-positive patients. There is a need for further studies, which should provide mechanistical explanation for the role of PAX6 in NSCLC.
- Published
- 2018
- Full Text
- View/download PDF
7. High miR-205 expression in normal epithelium is associated with biochemical failure - an argument for epithelial crosstalk in prostate cancer?
- Author
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Nordby Y, Richardsen E, Ness N, Donnem T, Patel HRH, Busund LT, Bremnes RM, and Andersen S
- Subjects
- Aged, Biomarkers, Tumor genetics, Biomarkers, Tumor metabolism, Gene Expression Regulation, Neoplastic genetics, Humans, In Situ Hybridization, Male, Middle Aged, Neoplasm Recurrence, Local metabolism, Neoplasm Recurrence, Local pathology, Neoplasm Recurrence, Local surgery, Prognosis, Prostate pathology, Prostatectomy, Prostatic Neoplasms pathology, Prostatic Neoplasms surgery, Tissue Array Analysis, MicroRNAs metabolism, Prostate metabolism, Prostatic Neoplasms metabolism
- Abstract
Due to insufficient prognostic tools, failure to predict aggressive prostate cancer (PC) has left patient selection for radical treatment an unsolved challenge. This has resulted in overtreatment with radical therapy. Better prognostic tools are urgently warranted. MicroRNAs (miRs) have emerged as important regulators of cellular pathways, resulting in altered gene expressions. miR-205 has previously been observed downregulated in PC, acting as tumor suppressor. Herein, the expression of miR-205 in prostate tissue was examined in a large, well-described cohort of 535 Norwegian prostatectomy patients. Using in situ hybridization, miR-205 expression was semiquantatively measured in normal and tumor tissues from radical prostatectomy specimens. Associations with clinicopathological data and PC relapse were calculated. Expression of miR-205 was lower in tumor epithelium compared to normal epithelium. No association was observed between miR-205 expression in primary tumor epithelium and cancer relapse. In contrast, high expression of miR-205 in normal epithelium was independently associated with biochemical relapse (HR = 1.64, p = 0.003). A prognostic importance of miR-205 expression was only found in the normal epithelium, raising the hypothesis of epithelial crosstalk between normal and tumor epithelium in PC. This finding supports the proposed novel hypothesis of an anti-cancerogenous function of normal epithelium in tumor tissue.
- Published
- 2017
- Full Text
- View/download PDF
8. High expression of PDGFR-β in prostate cancer stroma is independently associated with clinical and biochemical prostate cancer recurrence.
- Author
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Nordby Y, Richardsen E, Rakaee M, Ness N, Donnem T, Patel HR, Busund LT, Bremnes RM, and Andersen S
- Subjects
- Aged, Aged, 80 and over, Biomarkers, Tumor metabolism, Epithelial Cells metabolism, Epithelial Cells pathology, Humans, Immunohistochemistry, Lymphokines genetics, Lymphokines metabolism, Male, Middle Aged, Neoplasm Recurrence, Local genetics, Neoplasm Recurrence, Local mortality, Neoplasm Recurrence, Local surgery, Organ Specificity, Platelet-Derived Growth Factor genetics, Platelet-Derived Growth Factor metabolism, Prognosis, Prostate metabolism, Prostate pathology, Prostatectomy mortality, Prostatic Neoplasms genetics, Prostatic Neoplasms mortality, Prostatic Neoplasms surgery, Proto-Oncogene Proteins c-sis genetics, Proto-Oncogene Proteins c-sis metabolism, Receptor, Platelet-Derived Growth Factor beta metabolism, Retrospective Studies, Signal Transduction, Stromal Cells metabolism, Stromal Cells pathology, Survival Analysis, Tissue Array Analysis, Biomarkers, Tumor genetics, Gene Expression Regulation, Neoplastic, Neoplasm Recurrence, Local diagnosis, Prostatic Neoplasms diagnosis, Receptor, Platelet-Derived Growth Factor beta genetics
- Abstract
Due to a lack of sufficient diagnostic tools to predict aggressive disease, there is a significant overtreatment of patients with prostate cancer. Platelet derived growth factors (PDGFs) and their receptors (PDGFRs) are key regulators of mesenchymal cells in the tumor microenvironment, and has been associated with unfavorable outcome in several other cancers. Herein, we aimed to investigate the prognostic impact of PDGFR-β and its ligands (PDGF-B and PDGF-D) in a multicenter prostatectomy cohort of 535 Norwegian patients. Using tissue microarrays and immunohistochemistry, the expression of ligands PDGF-B and PDGF-D and their corresponding receptor, PDGFR-β, was assessed in neoplastic tissue and tumor-associated stroma. PDGFR-β was expressed in benign and tumor associated stroma, but not in epithelium. High stromal expression of PDGFR-β was independently associated with clinical relapse (HR = 2.17, p = 0.010) and biochemical failure (HR = 1.58, p = 0.002). This large study highlights the prognostic importance of PDGFR-β expression, implicating its involvement in prostate cancer progression even in early stage disease. Hence, analyses of PDGFR-β may help distinguish which patients will benefit from radical treatment, and since PDGFR-β is associated with relapse and shorter survival, it mandates a focus as a therapeutic target.
- Published
- 2017
- Full Text
- View/download PDF
9. Fibroblast miR-210 overexpression is independently associated with clinical failure in Prostate Cancer - a multicenter (in situ hybridization) study.
- Author
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Andersen S, Richardsen E, Moi L, Donnem T, Nordby Y, Ness N, Holman ME, Bremnes RM, and Busund LT
- Subjects
- Aged, Disease-Free Survival, Fibroblasts pathology, Humans, In Situ Hybridization, Male, MicroRNAs genetics, Middle Aged, Prostatic Neoplasms genetics, RNA, Neoplasm genetics, Survival Rate, Fibroblasts metabolism, Gene Expression Regulation, Neoplastic, MicroRNAs biosynthesis, Prostatic Neoplasms metabolism, Prostatic Neoplasms mortality, RNA, Neoplasm biosynthesis
- Abstract
There is a need for better prognostication in prostate cancer (PC). "The micromanager of hypoxia", microRNA-210 (miR-210) is directly linked to hypoxia, is overexpressed in PC and has been implied in tumor cell-fibroblast crosstalk. We investigated the prognostic impact of miR-210 in tumor cells and fibroblasts in PC. Tumor and stromal samples from a multicenter PC cohort of 535 prostatectomy patients were inserted into tissue microarrays. To investigate the expression of miR-210, we used in situ hybridization and two pathologists semiquantitatively scored its expression. Overexpression of miR-210 in tumor cells was not associated to biochemical failure-free survival (BFFS, p = 0.85) or clinical failure-free survival (CFFS, p = 0.09). However, overexpression of miR-210 in fibroblasts was significantly associated to a poor CFFS (p = 0.001), but not BFFS (p = 0.232). This feature was validated in both cohorts. Overexpression of miR-210 was independently associated with a reduced CFFS (HR = 2.76, CI 95% 1.25-6.09, p = 0.012). Overexpression of miR-210 in fibroblasts is independently associated with a poor CFFS. This highlights the importance of fibroblasts and cellular compartment crosstalk in PC. miR-210 is a candidate prognostic marker and potential therapeutic target in PC.
- Published
- 2016
- Full Text
- View/download PDF
10. Estrogen receptors α and β and aromatase as independent predictors for prostate cancer outcome.
- Author
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Grindstad T, Skjefstad K, Andersen S, Ness N, Nordby Y, Al-Saad S, Fismen S, Donnem T, Khanehkenari MR, Busund LT, Bremnes RM, and Richardsen E
- Subjects
- Aged, Disease-Free Survival, Humans, Male, Middle Aged, Prostatectomy, Survival Rate, Aromatase metabolism, Biomarkers, Tumor metabolism, Estrogen Receptor alpha metabolism, Estrogen Receptor beta metabolism, Neoplasm Proteins metabolism, Prostatic Neoplasms metabolism, Prostatic Neoplasms mortality, Prostatic Neoplasms surgery
- Abstract
Androgens are considered important in normal prostate physiology and prostate cancer (PCa) pathogenesis. However, androgen-targeted treatment preventing PCa recurrence is still lacking. This indicates additional mediators contributing to cancer development. We sought to determine the prognostic significance of estrogen receptors, ERα and -β, and the aromatase enzyme in PCa. Tissue microarrays were created from 535 PCa patients treated with radical prostatectomy. Expression of ERα, ERβ and aromatase were evaluated using immunohistochemistry. Representative tumor epithelial (TE) and tumor stromal (TS) areas were investigated separately. Survival analyses were used to evaluate the markers correlation to PCa outcome. In univariate analyses, ERα in TS was associated with delayed time to clinical failure (CF) (p = 0.042) and PCa death (p = 0.019), while ERβ was associated with reduced time to biochemical failure (BF) (p = 0.002). Aromatase in TS and TE was associated with increased time to BF and CF respectively (p = 0.016, p = 0.046). Multivariate analyses supported these observations, indicating an independent prognostic impact of all markers. When stratifying the analysis according to different surgical centers the results were unchanged. In conclusion, significant prognostic roles of ERα, ERβ and aromatase were discovered in the in PCa specimens of our large multicenter cohort.
- Published
- 2016
- Full Text
- View/download PDF
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