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- Göstring, Lovisa, et al.
(författare)
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Cellular Effects of HER3-Specific Affibody Molecules
- 2012
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:6, s. e40023-
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Tidskriftsartikel (refereegranskat)abstract
- Recent studies have led to the recognition of the epidermal growth factor receptor HER3 as a key player in cancer, and consequently this receptor has gained increased interest as a target for cancer therapy. We have previously generated several Affibody molecules with subnanomolar affinity for the HER3 receptor. Here, we investigate the effects of two of these HER3-specific Affibody molecules, Z05416 and Z05417, on different HER3-overexpressing cancer cell lines. Using flow cytometry and confocal microscopy, the Affibody molecules were shown to bind to HER3 on three different cell lines. Furthermore, the receptor binding of the natural ligand heregulin (HRG) was blocked by addition of Affibody molecules. In addition, both molecules suppressed HRG-induced HER3 and HER2 phosphorylation in MCF-7 cells, as well as HER3 phosphorylation in constantly HER2-activated SKBR-3 cells. Importantly, Western blot analysis also revealed that HRG-induced downstream signalling through the Ras-MAPK pathway as well as the PI3K-Akt pathway was blocked by the Affibody molecules. Finally, in an in vitro proliferation assay, the two Affibody molecules demonstrated complete inhibition of HRG-induced cancer cell growth. Taken together, our findings demonstrate that Z05416 and Z05417 exert an anti-proliferative effect on two breast cancer cell lines by inhibiting HRG-induced phosphorylation of HER3, suggesting that the Affibody molecules are promising candidates for future HER3-targeted cancer therapy.
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| 2. |
- Kronqvist, Nina, et al.
(författare)
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Combining phage and staphylococcal surface display for generation of ErbB3-specific Affibody molecules
- 2011
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Ingår i: Protein Engineering Design & Selection. - : Oxford University Press (OUP). - 1741-0126 .- 1741-0134. ; 24:4, s. 385-396
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Tidskriftsartikel (refereegranskat)abstract
- Emerging evidence suggests that the catalytically inactive ErbB3 (HER3) protein plays a fundamental role in normal tyrosine kinase receptor signaling as well as in aberrant functioning of these signaling pathways, resulting in several forms of human cancers. ErbB3 has recently also been implicated in resistance to ErbB2-targeting therapies. Here we report the generation of high-affinity ErbB3-specific Affibody molecules intended for future molecular imaging and biotherapeutic applications. Using a high-complexity phage-displayed Affibody library, a number of ErbB3 binders were isolated and specific cell-binding activity was demonstrated in immunofluorescence microscopic studies. Subsequently, a second-generation library was constructed based on sequences of the candidates from the phage display selection. By exploiting the sensitive affinity discrimination capacity of a novel bacterial surface display technology, the affinity of candidate Affibody molecules was further increased down to subnanomolar affinity. In summary, the demonstrated specific targeting of native ErbB3 receptor on human cancer cell lines as well as competition with the heregulin/ErbB3 interaction indicates that these novel biological agents may become useful tools for diagnostic and therapeutic targeting of ErbB3-expressing cancers. Our studies also highlight the powerful approach of combining the advantages of different display technologies for generation of functional high-affinity protein-based binders. Potential future applications, such as radionuclide-based diagnosis and treatment of human cancers are discussed.
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| 4. |
- Svenberg, Linus, et al.
(författare)
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Investigation of the Chemical Inhibition Effect of Ground Elder (Aegopodium podagraria) on Timothy (Phleum pratense)?Introducing High School Students to Analytical Chemistry and Chemical Ecology
- 2023
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Ingår i: Journal of Chemical Education. - : American Chemical Society (ACS). - 0021-9584 .- 1938-1328. ; 100:3, s. 1227-1236
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Tidskriftsartikel (refereegranskat)abstract
- The understanding of analytical chemistry and its application in different areas of life science is something that should be encouraged for students studying chemistry, and also something that appeals to many students. Life science includes a vast variety of areas, out of which some are more easily approached in student projects. The chemical communication between organisms, such as plants, as described in chemical ecology is one example. It is therefore beneficial to offer students inquiry-based project work that allows them to explore, and gain a deeper understanding of, this discipline within the grand context that is chemistry. Hence, the present work describes the application of analytical chemistry using gas chromatography-mass spectrometry, including sample preparation for the study of chemical inhibitory (allelopathic) properties of compounds found in the plant Aegopodium podagraria. The questions posed to the students performing this project work were "What compounds can be found in the extracts of the plant?", "Are the extracts allelopathic?", and "Can you determine which compounds contribute to the possible allelopathic properties?". The reported results indicate that the extracts might have allelopathic properties and showed that the extracts contained compounds such as alpha-pinene and beta-caryophyllene. The identified terpenes were shown to have minor allelopathic properties by themselves but displayed an impact on the germination of seeds and length of the sprouts when applied as a blend. This project, and its results, proposes a framework for investigation of other plants and can be adapted to suit students at different academic levels.
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