| 1. |
- Ma, Ran, et al.
(författare)
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Estrogen Receptor β as a Therapeutic Target in Breast Cancer Stem Cells.
- 2017
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press. - 0027-8874 .- 1460-2105. ; 109:3, s. 1-14
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Tidskriftsartikel (refereegranskat)abstract
- Background: Breast cancer cells with tumor-initiating capabilities (BSCs) are considered to maintain tumor growth and govern metastasis. Hence, targeting BSCs will be crucial to achieve successful treatment of breast cancer.Methods: We characterized mammospheres derived from more than 40 cancer patients and two breast cancer cell lines for the expression of estrogen receptors (ERs) and stem cell markers. Mammosphere formation and proliferation assays were performed on cells from 19 cancer patients and five healthy individuals after incubation with ER-subtype selective ligands. Transcriptional analysis was performed to identify pathways activated in ERβ-stimulated mammospheres and verified using in vitro experiments. Xenograft models (n = 4 or 5 per group) were used to study the role of ERs during tumorigenesis.Results: We identified an absence of ERα but upregulation of ERβ in BSCs associated with phenotypic stem cell markers and responsible for the proliferative role of estrogens. Knockdown of ERβ caused a reduction of mammosphere formation in cell lines and in patient-derived cancer cells (40.7%, 26.8%, and 39.1%, respectively). Gene set enrichment analysis identified glycolysis-related pathways (false discovery rate < 0.001) upregulated in ERβ-activated mammospheres. We observed that tamoxifen or fulvestrant alone was insufficient to block proliferation of patient-derived BSCs while this could be accomplished by a selective inhibitor of ERβ (PHTPP; 53.7% in luminal and 45.5% in triple-negative breast cancers). Furthermore, PHTPP reduced tumor initiation in two patient-derived xenografts (75.9% and 59.1% reduction in tumor volume, respectively) and potentiated tamoxifen-mediated inhibition of tumor growth in MCF7 xenografts.Conclusion: We identify ERβ as a mediator of estrogen action in BSCs and a novel target for endocrine therapy.
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| 2. |
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| 3. |
- Andersson, SO, et al.
(författare)
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Body size and prostate cancer: A 20-year follow-up study among 135006 Swedish construction workers
- 1997
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Ingår i: JOURNAL OF THE NATIONAL CANCER INSTITUTE. - : NATL CANCER INSTITUTE. - 0027-8874. ; 89:5, s. 385-389
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Tidskriftsartikel (refereegranskat)abstract
- Background: Obesity is associated with endocrine changes (e.g., increased estrogen and decreased testosterone in the blood) that have been implicated in the cause of prostate cancer and, therefore, an association between body weight and the risk of develo
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| 4. |
- Bergstrom, R, et al.
(författare)
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Increase in testicular cancer incidence in six European countries: A birth cohort phenomenon
- 1996
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Ingår i: JOURNAL OF THE NATIONAL CANCER INSTITUTE. - : NATL CANCER INSTITUTE. - 0027-8874. ; 88:11, s. 727-733
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Tidskriftsartikel (refereegranskat)abstract
- Background: For unknown reasons, the age-standardized incidence of testicular cancer has shown a rapid increase in virtually all countries (mostly Western) studied. For populations with a sufficiently long period of cancer registration, this development c
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| 5. |
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| 6. |
- Leu, Monica, 1977, et al.
(författare)
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Evaluation of bias in familial risk estimates: a study of common cancers using Swedish population-based registers
- 2008
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Ingår i: Journal of the National Cancer Institute. - 0027-8874. ; 100:18, s. 1318-25
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Tidskriftsartikel (refereegranskat)abstract
- Background Bias in estimates of familial cancer may result if population-based registers fail to identify relatives as affected when disease occurs before the start-up of registration (ie, “left-truncation” of family history). Methods Apparent familial relative risks (among offspring of parents with cancer) of colorectal, lung, breast, and prostate cancers and melanoma in a Swedish cohort were compared with relative risks in a simulated population. The study cohort (approximately 7 million individuals) was based on the Swedish MultiGenerational Register linked to the Swedish Cancer Register for the period 1961–2002. A similar population of related individuals (approximately 7 million) with complete family information was simulated by using the R-package PopLab and used to estimate the sensitivity of the observed family history. This sensitivity was then used to calculate corrected age group–specific and overall risks, which were compared with the apparent familial risks of cancer in the cohort. Result The apparent familial risks for colorectal, lung, breast, and prostate cancers and melanoma were 1.99 (95% confidence interval [CI]=1.85 to 2.14), 2.05 (95% CI=1.86 to 2.26), 1.84 (95% CI=1.76 to 1.92), 2.33 (95% CI=2.19 to 2.48), and 2.68 (95% CI=2.35 to 3.07), with corresponding absolute rates of 3.69, 2.59, 16.05, 10.38, and 2.96 per 10000 person-years, among offspring of parents diagnosed with the same cancer. Corrected age group–specific and overall estimates of the familial risks were close to these apparent risks for all studied cancers (all approximately 2.0), except for melanoma. For melanoma, the corrected estimate of 3.18 (95% CI=2.73 to 3.64) was somewhat larger than the apparent estimate and was not included in the confidence interval for the apparent estimate. When the exposure of interest was a parent affected at a younger age, this bias was more pronounced; the apparent estimate for melanoma changed from 4.07 (95% CI=3.21 to 5.16) to 5.67 (95% CI=4.51 to 6.83) after correction. Conclusions For common cancers, risk estimates from the Swedish MultiGenerational cohort do not generally appear to be biased by left-truncation.
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| 7. |
- Nyren, O, et al.
(författare)
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Smoking and colorectal cancer: A 20-year follow-up study of Swedish construction workers
- 1996
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Ingår i: JOURNAL OF THE NATIONAL CANCER INSTITUTE. - : NATL CANCER INSTITUTE. - 0027-8874. ; 88:18, s. 1302-1307
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Tidskriftsartikel (refereegranskat)abstract
- Background: Although cigarette smoking has consistently been shown to be positively related to the risk of adenomatous polyp development (benign neoplastic growth of epithelial tissue in the colon), most studies of cigarette smoking and the risk of colore
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