| 51. |
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| 52. |
- Butt, Salma, et al.
(författare)
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Parity and age at first childbirth in relation to the risk of different breast cancer subgroups.
- 2009
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 125, s. 1926-1934
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the present study was to examine parity and age at first childbirth, in relation to the risk of specific breast cancer subgroups. A prospective cohort, The Malmö Diet and Cancer Study, including 17,035 women were followed with linkage to Swedish Cancer Registry until December 31, 2004. A total of 622 incident breast cancers were diagnosed during follow-up and were evaluated regarding invasiveness, tumour size, axillary lymph node status, Nottingham grade, tumour proliferation (Ki67), HER2, cyclin D1 and p27. The tumours were also examined for WHO type and hormone receptor status. Nulliparity was associated with an overall increased risk of breast cancer, although not statistically significant (the relative risk was 1.39 with a 95% confidence interval of 0.92-2.08). Nulliparity was also associated with large tumours (>20 mm) (1.89: 0.91-3.91), high Ki67 levels (1.95: 0.93-4.10), high cyclin D1 levels (2.15: 0.88-5.27), grade III (2.93: 1.29-6.64) and HER2 positive tumours (3.24: 1.02-10.25). High parity was not statistically significantly associated with any specific breast cancer subgroup. Older age at first childbirth (>30) was associated with a slightly increased risk of breast cancer (1.39: 0.94-2.07). There was a statistically significant association between late first childbirth and lobular type (2.51: 1.01-6.28), grade III tumours (2.67: 1.19-6.02), high levels of cyclin D1 (2.69: 1.18-6.12) and low levels of p27 (2.23: 1.15-4.35). We conclude that nulliparity and late first childbirth are associated with relatively more aggressive breast cancer subgroups. (c) 2009 UICC.
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| 53. |
- Butt, Salma, et al.
(författare)
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Parity in relation to survival following breast cancer.
- 2009
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Ingår i: European Journal of Surgical Oncology. - : Elsevier BV. - 1532-2157 .- 0748-7983. ; 35, s. 702-708
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Tidskriftsartikel (refereegranskat)abstract
- AIM: The present study examines the association between parity and survival following breast cancer diagnosis. METHODS: Medical records of 4453 women diagnosed with breast cancer in Malmö, Sweden, between 1961 and 1991 were analysed. All women were followed until 31 December 2003, using the Swedish Cause-of-Death Registry. Breast cancer specific mortality rate was calculated in different levels of parity. Corresponding relative risks, with 95% confidence intervals (CI), were obtained using Cox's proportional hazards analysis. All analyses were adjusted for potential prognostic factors and stratified for age, menopausal status and diagnostic period. RESULTS: As compared to women with one child, nulliparity (RR 1.27: 95% CI 1.09-1.47), and high parity (four or more children) (1.49: 1.20-1.85) were positively associated with a high mortality from breast cancer. When adjusted for potential confounders, the association was only statistically significant for high parity (1.33: 1.07-1.66). In the analyses stratified on age and menopausal status, there was a similar positive association between high parity and breast cancer death in all strata, although only statistically significant among women older than 45years of age or postmenopausal. Nulliparity was associated with breast cancer death in women that were younger than 45years of age (1.28: 0.79-2.09) or premenopausal (1.30: 0.95-1.80), but these associations did not reach statistical significance. There was no association between nulliparity and breast cancer death in women older than 45years of age or postmenopausal. All associations were similar in analyses stratified for diagnostic period. CONCLUSION: Women with four or more children have a poor breast cancer survival as compared to women with one child.
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| 54. |
- Deyou, Tsegaye, et al.
(författare)
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Rotenoids, Flavonoids, and Chalcones from the Root Bark of Millettia usaramensis
- 2015
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Ingår i: Journal of Natural Products. - : American Chemical Society (ACS). - 0163-3864 .- 1520-6025 .- 0974-5211. ; 78:12, s. 2932-2939
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Tidskriftsartikel (refereegranskat)abstract
- Five new compounds, 4-O-geranylisoliquiritigenin (1), 12-dihydrousararotenoid B (2), 12-dihydrousararotenoid C (3), 4'-O-geranyl-7-hydroxyflavanone (4), and 4'O-geranyl-7-hydroxydihydroflavanol (5), along with 12 known natural products (6-17) were isolated from the CH2Cl2/MeOH (1:1) extract of the root bark of Millettia usaramensis ssp. usaramensis by chromatographic separation. The purified metabolites were identified by NMR spectroscopic and mass spectrometric analyses, whereas their absolute configurations were established on the basis of chiroptical data and in some cases also by X-ray crystallography. The crude extract was moderately active (IC50 = 11.63 mu g/mL) against the ER-negative MDB-MB-231 human breast cancer cell line, and accordingly compounds 6, 8, 9, 10, 12, and 16 also showed moderate to low cytotoxic activities (IC50 25.7-207.2 mu M). The new natural product 1 exhibited antiplasmodial activity with IC50 values of 3.7 and 5.3 mu M against the chloroquine-sensitive 3D7 and the chloroquine-resistant Dd2 Plasmodium falciparum strains, respectively, and was also cytotoxic to the HEK293 cell line.
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| 55. |
- Dolatabadi, Soheila, et al.
(författare)
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Cell Cycle and Cell Size Dependent Gene Expression Reveals Distinct Subpopulations at Single-Cell Level
- 2017
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Ingår i: Frontiers in Genetics. - : Frontiers Media SA. - 1664-8021. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Cell proliferation includes a series of events that is tightly regulated by several checkpoints and layers of control mechanisms. Most studies have been performed on large cell populations, but detailed understanding of cell dynamics and heterogeneity requires single-cell analysis. Here, we used quantitative real-time PCR, profiling the expression of 93 genes in single-cells from three different cell lines. Individual unsynchronized cells from three different cell lines were collected in different cell cycle phases (GO/G1 - S - G2/M) with variable cell sizes. We found that the total transcript level per cell and the expression of most individual genes correlated with progression through the cell cycle, but not with cell size. By applying the random forests algorithm, a supervised machine learning approach, we show how a multi-gene signature that classifies individual cells into their correct cell cycle phase and cell size can be generated. To identify the most predictive genes we used a variable selection strategy. Detailed analysis of cell cycle predictive genes allowed us to define subpopulations with distinct gene expression profiles and to calculate a cell cycle index that illustrates the transition of cells between cell cycle phases. In conclusion, we provide useful experimental approaches and bioinformatics to identify informative and predictive genes at the single-cell level, which opens up new means to describe and understand cell proliferation and subpopulation dynamics.
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| 56. |
- Dolatabadi, Soheila, et al.
(författare)
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JAK–STAT signalling controls cancer stem cell properties including chemotherapy resistance in myxoid liposarcoma
- 2019
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 145:2, s. 435-449
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Tidskriftsartikel (refereegranskat)abstract
- Myxoid liposarcoma (MLS) shows extensive intratumoural heterogeneity with distinct subpopulations of tumour cells. Despite improved survival of MLS patients, existing therapies have shortcomings as they fail to target all tumour cells. The nature of chemotherapy-resistant cells in MLS remains unknown. Here, we show that MLS cell lines contained subpopulations of cells that can form spheres, efflux Hoechst dye and resist doxorubicin, all properties attributed to cancer stem cells (CSCs). By single-cell gene expression, western blot, phospho-kinase array, immunoprecipitation, immunohistochemistry, flow cytometry and microarray analysis we showed that a subset of MLS cells expressed JAK–STAT genes with active signalling. JAK1/2 inhibition via ruxolitinib decreased, while stimulation with LIF increased, phosphorylation of STAT3 and the number of cells with CSC properties indicating that JAK–STAT signalling controlled the number of cells with CSC features. We also show that phosphorylated STAT3 interacted with the SWI/SNF complex. We conclude that MLS contains JAK–STAT-regulated subpopulations of cells with CSC features. Combined doxorubicin and ruxolitinib treatment targeted both proliferating cells as well as cells with CSC features, providing new means to circumvent chemotherapy resistance in treatment of MLS patients. © 2019 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC
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| 57. |
- Ekberg, Jenny, et al.
(författare)
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Expression of cyclin A1 and cell cycle proteins in hematopoietic cells and acute myeloid leukemia and links to patient outcome
- 2005
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Ingår i: European Journal of Haematology. - : Wiley-Blackwell Publishing Inc.. - 0902-4441 .- 1600-0609. ; 75:2, s. 106-115
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Tidskriftsartikel (refereegranskat)abstract
- Abnormal expression of several key regulators essential for G1/S transitions has been implicated in tumorigenesis. A critical role of cyclin A1 in the development of acute myeloid leukemia (AML) has previously been demonstrated in transgenic mice. Our present study focused on the expression and prognostic significance of cyclin A1 and a panel of cell cycle regulatory proteins including cyclin A2, cyclin B1, cyclin E, CDK1, CDK2, p21 and p27 in bone marrow samples from 40 patients with AML. Freshly isolated CD34+ hematopoietic cells and bone marrow samples from 10 healthy donors were also assessed for cell type- and subcellular-specific expression of the cell cycle regulatory proteins. The level of cyclin A1 expression was the only factor that showed a significant correlation with patient outcome. In log-rank test stratified by levels of cyclin A1 expression, patients with high levels of cyclin A1 had significantly worse overall survival (OS) (P = 0.012) compared to those with low levels. Further, patients with high levels of cyclin A1 had significantly lower disease-free survival (DFS) (P = 0.028). Multivariate analysis indicated that cyclin A1 protein expression was an independent prognostic factor for predicting DFS (P = 0.035) and OS (P = 0.045). No correlation between cyclin A1 expression and age was found. However, expression of cyclin A2, cyclin B1, cyclin E, CDK1, CDK2, p21 and p27 did not show prognostic significance in these AML patients.
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| 58. |
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| 59. |
- Ekberg, Jenny, et al.
(författare)
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Regulation of the cyclin A1 protein is associated with its differential subcellular localization in hematopoietic and leukemic cells
- 2004
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Ingår i: Oncogene. - : Nature Publishing Group. - 0950-9232 .- 1476-5594. ; 23:56, s. 9082-9089
-
Tidskriftsartikel (refereegranskat)abstract
- An important role of the cell cycle regulatory protein cyclin A1 in the development of acute myeloid leukemia (AML) was previously demonstrated in a transgenic mouse model. We have now turned our attention to study specific aspects of the activity and subcellular distribution of cyclin A1 using bone marrow samples from normal donors and patients with AML, as well as leukemic cell lines. We show that the localization of cyclin A1 in normal hematopoietic cells is nuclear, whereas in leukemic cells from AML patients and cell lines, it is predominantly cytoplasmic. In leukemic cell lines treated with all-trans retinoic acid (ATRA), cyclin A1 localized to the nucleus. Further, there was a direct interaction between cyclin A1 and cyclin-dependent kinase 1, as well as a major ATRA receptor, RARalpha, in ATRA-treated cells but not in untreated leukemic cells. Our results indicate that the altered intracellular distribution of cyclin A1 in leukemic cells correlates with the status of the leukemic phenotype.
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| 60. |
- Ekberg, Lars, et al.
(författare)
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What margins should be added to the clinical target volume in radiotherapy treatment planning for lung cancer?
- 1988
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Ingår i: Radiotherapy and Oncology. - 1879-0887. ; 48:1, s. 71-77
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The planning target volume in radiotherapy treatment planning takes into account both movements of the clinical target volume (CTV) and set-up deviations. MATERIALS AND METHODS: A group of patients who received radiotherapy for lung cancer were studied. In order to measure the CTV movements due to respiration and other internal organ motions, fluoroscopy was performed for 20 patients. To study the accuracy and reproducibility of patient and beam set-up, 553 electronic portal images from 20 patients were evaluated. Discrepancies between planned and actual field positions were measured and the systematic and random errors were identified. The combined effect of these geometrical variations was evaluated. RESULTS: The average CTV movement with quiet respiration was about 2.4 mm in the medio-lateral and dorso-ventral directions. Movement in the cranio-caudal direction was on average 3.9 mm with a range of 0-12 mm. The systematic set-up errors were on average 2.0 mm in the transversal plane and 3.0 mm in the cranio-caudal direction. The random errors can be described by their standard deviations of 3.2 and 2.6 mm. In this study, the combined effect of the two parameters (CTV movement and set-up deviations) varied between 7.5 and 10.3 mm in different anatomical directions. CONCLUSIONS: In our daily clinical routine, we use a margin of 11 mm in the transversal plane and 15 mm cranially and caudally, also taking into account other unquantified variations and uncertainties.
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