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| 2. |
- Aguilar, Helena, et al.
(författare)
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VAV3 mediates resistance to breast cancer endocrine therapy
- 2014
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Ingår i: Breast Cancer Research. - : BioMed Central. - 1465-5411 .- 1465-542X. ; 16:3, s. R53-
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Endocrine therapies targeting cell proliferation and survival mediated by estrogen receptor alpha (ERalpha) are among the most effective systemic treatments for ERalpha-positive breast cancer. However, most tumors initially responsive to these therapies acquire resistance through mechanisms that involve ERalpha transcriptional regulatory plasticity. Here, we identify VAV3 as a critical component in this process.METHODS: A cell-based chemical compound screen was carried out to identify therapeutic strategies against resistance to endocrine therapy. Binding to ERalpha was evaluated by molecular docking analyses, an agonist fluoligand assay, and short-hairpin (sh) RNA-mediated protein depletion. Microarray analyses were performed to identify altered gene expression. Western blot of signaling and proliferation markers and shRNA-mediated protein depletion in viability and clonogenic assays were performed to delineate the role of VAV3. Genetic variation in VAV3 was assessed for association with the response to tamoxifen. Immunohistochemical analyses of VAV3 were carried out to determine the association with therapy response and different tumor markers. An analysis of gene expression association with drug sensitivity was carried out to identify a potential therapeutic approach based on differential VAV3 expression.RESULTS: The compound YC-1 was found to comparatively reduce the viability of cell models of acquired resistance. This effect was probably not due to activation of its canonical target (soluble guanylyl cyclase) but instead a result of binding to ERalpha. VAV3 was selectively reduced upon exposure to YC-1 or ERalpha depletion and, accordingly, VAV3 depletion comparatively reduced the viability of cell models of acquired resistance. In the clinical scenario, germline variation in VAV3 was associated with response to tamoxifen in Japanese breast cancer patients (rs10494071 combined P value = 8.4 x 10-4). The allele association combined with gene expression analyses indicated that low VAV3 expression predicts better clinical outcome. Conversely, high nuclear VAV3 expression in tumor cells was associated with poorer endocrine therapy response. Based on VAV3 expression levels and the response to erlotinib in cancer cell lines, targeting EGFR signaling may be a promising therapeutic strategy.CONCLUSIONS: This study proposes VAV3 as a biomarker and rationale signaling target to prevent and/or overcome resistance to endocrine therapy in breast cancer.
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| 3. |
- Mantero, Juan, et al.
(författare)
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NORM and heavy metal levels in pit lakes in Sweden
- 2018
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Ingår i: Environmental radioactivity –experience from Japan and Sweden. JSPS Alumni Club in Sweden (SAC) Activity Seminar . 15-16 November, Gothenburg, Sweden.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 4. |
- Garcia-Tenorio, Rafael, et al.
(författare)
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Journal of Environmental Radioactivity special issue: II International Conference on Radioecological Concentration Processes. (50 years later).
- 2018
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Ingår i: Journal of environmental radioactivity. - : Elsevier BV. - 1879-1700 .- 0265-931X. ; 186, s. 1-2
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- An international conference on Radioecological Concentration Processes was held in Seville, Spain, 6-9 November 2016 at the Centro Nacional de Aceleradores. It was attended by 160 participants from 35 different countries. This was the 2nd conference on this item since 1966, 50 years ago. The conference covered aspects of radiological important radionuclides on terrestrial, marine and freshwater environments and has allowed obtaining a clear picture of the status of the Radioecology as a consolidated discipline in the 21st century.
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| 6. |
- Mantero, Juan, et al.
(författare)
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Elementary characterization of environmental samples from pit lakes in Sweden
- 2016
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Ingår i: EXRS2016 European Conference on X-ray Spectrometry, Gothenburg, June 19-24, 2016.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The effect of mining activities in a country as Sweden (the major metal mining country in the European Union) implies enormous quantities of generated mining wastes. Historically, more than 2700 mines gather around 30000 sites that have been minor mines and quarries (according to the database of Geological Survey of Sweden, SGU). In 1950, there were around 100 active mines while nowadays no more than 15 active mines still remains with ongoing extractions. Many of these sites had opencast mines. During exploitation by open-pit mining, the water table is suppressed to avoid the flooding of active mines. However, when mining activity ceases, the water table recovers its original position, flooding the open pits and giving rise to mine pit lakes. The environmental problem arise because these waters can be affected by Acidic Mine Drainage (AMD), having high/very high concentration of heavy metals in solution. Apart from the impact to the ecosystem, these places are nearby populated areas and most of them are usually used for recreation purposes (swimming, fishing, diving) by inhabitant of these former mining areas. In this work, a survey on 30 different abandoned pit lakes was performed. Superficial waters and sediments from the shoreline were sampled to check the levels of metals (major elements and traces) at these sites. Water samples were doubly analysed: via TXRF with a S2 PICOFOX (equipped with Mo tube) and via ICP-MS. The aim was to compare and cross-check both measurement systems pointing out the advantages/disadvantages between them. Also physico-chemical parameters as pH, T, ORP, DO or salinity were measured in water samples and will be correlated with the chemical behaviour of some elements. The elementary characterization of sediments was carried out by WDXRF with an AXIOS system. The concentration levels of Fe, Mn, Cu, Zn, S, Mg, Ca, Cr among others metals will be shown. In Waters, levels of Fe ranges from 0.01 to 235 mg/l, for S (0.9 to 8600 mg/l), Mn (0.02 to 8400 ppm), Cu (0.9 to 6400 ppm) or Zn (35 to 32000 ppm) as some examples. Regarding sediments, Fe ranges from 0.18 to 55 %, S (0.01 to 8.5%), Mn (0.01 to 0.85%), Cu (6 to 2125 ppm) or Zn (65 to 2000 ppm) with traces in Ba (35 to 7100 ppm) or Pb (1.3 to 2800 ppm) as more relevant elements. The main conclusion is that during this survey, some places with high levels of heavy metals were identified both in water and sediment samples.
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| 9. |
- Mantero, Juan, et al.
(författare)
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Pit lakes from Southern Sweden: natural radioactivity and elementary characterization
- 2020
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Natural radioactivity in the environment is a field gaining more attention in last decades. This work is focused on the study of natural radioactivity complemented with elementary characterization at former non-uraniferous mining areas in Sweden. This aim is addressed through the study of mining lakes, called pit lakes, which are water bodies generated after opencast mining. Environmental matrices (water, sediments and rocks) from 32 Swedish pit lakes, commonly used for recreational purposes were radiometrically characterized via alpha (238U, 234U, 232Th, 230Th, 210Po isotopes) and gamma spectrometry (238U and 232Th series radionuclides). Additionally, ambient dose rate equivalent in the immediate surrounding of each pit lake was quantified. Physico-chemical parameters (pH, specific conductivity, dissolved oxygen, oxidation–reduction potential) and elemental composition (major and trace elements by ICP-MS) were analysed in water samples and elementary composition of sediments/rocks was measured by XRF and SEM–EDX in some specific cases. A non-negligible number of pit lakes (26%) with enhanced U levels in water was found. At some sites, rocks contained up to 4% of U in areas with high degree of interaction with local population. Concerning the elementary perspective, another popular site (due to its turquoise water) was found to have elevated dissolved heavy metal levels. Results obtained in this work prove that measurement of natural radioactivity is another component that should be included in routine analysis of characterization in mining areas, especially if restauration of post-mining sites is intended for human recreational.
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| 10. |
- Mantero, Juan, et al.
(författare)
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Quality assurance via internal tests in a newly setup laboratory for environmental radioactivity
- 2019
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Ingår i: Journal of Radioanalytical and Nuclear Chemistry. - : Springer Science and Business Media LLC. - 0236-5731 .- 1588-2780. ; 322:2, s. 891-900
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Tidskriftsartikel (refereegranskat)abstract
- The present work shows one way to apply inner Control Tests to produce reliable results based on (a) the combination of different techniques (alpha vs. Gamma spectrometry, alpha spectrometry vs. ICP-MS or gamma spectrometry vs. XRF) and (b) on the performance of inter-comparison exercises with another laboratory with a wider experience in the field.
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