| 61. |
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| 62. |
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| 63. |
- Hedenfalk, I, et al.
(författare)
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Gene-expression profiles in hereditary breast cancer
- 2001
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Ingår i: New England Journal of Medicine. - 0028-4793. ; 344:8, s. 48-539
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Many cases of hereditary breast cancer are due to mutations in either the BRCA1 or the BRCA2 gene. The histopathological changes in these cancers are often characteristic of the mutant gene. We hypothesized that the genes expressed by these two types of tumors are also distinctive, perhaps allowing us to identify cases of hereditary breast cancer on the basis of gene-expression profiles.METHODS: RNA from samples of primary tumor from seven carriers of the BRCA1 mutation, seven carriers of the BRCA2 mutation, and seven patients with sporadic cases of breast cancer was compared with a microarray of 6512 complementary DNA clones of 5361 genes. Statistical analyses were used to identify a set of genes that could distinguish the BRCA1 genotype from the BRCA2 genotype.RESULTS: Permutation analysis of multivariate classification functions established that the gene-expression profiles of tumors with BRCA1 mutations, tumors with BRCA2 mutations, and sporadic tumors differed significantly from each other. An analysis of variance between the levels of gene expression and the genotype of the samples identified 176 genes that were differentially expressed in tumors with BRCA1 mutations and tumors with BRCA2 mutations. Given the known properties of some of the genes in this panel, our findings indicate that there are functional differences between breast tumors with BRCA1 mutations and those with BRCA2 mutations.CONCLUSIONS: Significantly different groups of genes are expressed by breast cancers with BRCA1 mutations and breast cancers with BRCA2 mutations. Our results suggest that a heritable mutation influences the gene-expression profile of the cancer.
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| 64. |
- Kallioniemi, I., et al.
(författare)
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Characterization of random rough surfaces from scattered intensities by neural networks
- 2001
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Ingår i: Journal of Modern Optics. - 0950-0340 .- 1362-3044. ; 48:9, s. 1447-1453
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Tidskriftsartikel (refereegranskat)abstract
- Optical scatterometry, a non-invasive characterization method, is used to infer the statistical properties of random rough surfaces. The Gaussian model with rms-roughness sigma and correlation length Lambda is considered in this paper but the employed technique is applicable to any representation of random rough surfaces. Surfaces with wide ranges of Lambda and sigma, up to 5 wavelengths (lambda), are characterized with neural networks. Two models are used: self-organizing map (SOM) for rough classification and multi-layer perceptron (MLP) for quantitative estimation with nonlinear regression. Models infer Lambda and sigma from scattering, thus involving the inverse problem. The intensities are calculated with the exact electromagnetic theory, which enables a wide range of parameters. The most widely known neural network model in practise is SOM, which we use to organize samples into discrete classes with resolution Delta Lambda = Delta sigma = 0.5 lambda. The more advanced MLP model is trained for optimal behaviour by providing it with known parts of input (scattering) and output (surface parameters). We show that a small amount of data is sufficient for an excellent accuracy on the order of 0.3 lambda and 0.15 lambda for estimating Lambda and sigma, respectively.
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| 65. |
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| 66. |
- Karvonen, H, et al.
(författare)
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Crosstalk between ROR1 and BCR pathways defines novel treatment strategies in mantle cell lymphoma
- 2017
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Ingår i: Blood advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 1:24, s. 2257-2268
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Tidskriftsartikel (refereegranskat)abstract
- Targeting ROR1 downregulates NF-κB p65 expression and sensitizes MCL cells to BCR- or Bcl-2–targeted drugs. Inhibition of BCR signaling by BTK-specific inhibitors such as ibrutinib impairs ROR1 levels and consecutively ROR1-targeted therapies.
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| 67. |
- Karvonen, H, et al.
(författare)
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Glucocorticoids induce differentiation and chemoresistance in ovarian cancer by promoting ROR1-mediated stemness
- 2020
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Ingår i: Cell death & disease. - : Springer Science and Business Media LLC. - 2041-4889. ; 11:9, s. 790-
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Tidskriftsartikel (refereegranskat)abstract
- Glucocorticoids are routinely used in the clinic as anti-inflammatory and immunosuppressive agents as well as adjuvants during cancer treatment to mitigate the undesirable side effects of chemotherapy. However, recent studies have indicated that glucocorticoids may negatively impact the efficacy of chemotherapy by promoting tumor cell survival, heterogeneity, and metastasis. Here, we show that dexamethasone induces upregulation of ROR1 expression in ovarian cancer (OC), including platinum-resistant OC. Increased ROR1 expression resulted in elevated RhoA, YAP/TAZ, and BMI-1 levels in a panel of OC cell lines as well as primary ovarian cancer patient-derived cells, underlining the translational relevance of our studies. Importantly, dexamethasone induced differentiation of OC patient-derived cells ex vivo according to their molecular subtype and the phenotypic expression of cell differentiation markers. High-throughput drug testing with 528 emerging and clinical oncology compounds of OC cell lines and patient-derived cells revealed that dexamethasone treatment increased the sensitivity to several AKT/PI3K targeted kinase inhibitors, while significantly decreasing the efficacy of chemotherapeutics such as taxanes, as well as anti-apoptotic compounds such as SMAC mimetics. On the other hand, targeting ROR1 expression increased the efficacy of taxane drugs and SMAC mimetics, suggesting new combinatorial targeted treatments for patients with OC.
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| 68. |
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| 69. |
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| 70. |
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