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- Paiva, J. S., et al.
(författare)
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iLoF: An intelligent Lab on Fiber Approach for Human Cancer Single-Cell Type Identification
- 2020
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- With the advent of personalized medicine, there is a movement to develop "smaller" and "smarter" microdevices that are able to distinguish similar cancer subtypes. Tumor cells display major differences when compared to their natural counterparts, due to alterations in fundamental cellular processes such as glycosylation. Glycans are involved in tumor cell biology and they have been considered to be suitable cancer biomarkers. Thus, more selective cancer screening assays can be developed through the detection of specific altered glycans on the surface of circulating cancer cells. Currently, this is only possible through time-consuming assays. In this work, we propose the "intelligent" Lab on Fiber (iLoF) device, that has a high-resolution, and which is a fast and portable method for tumor single-cell type identification and isolation. We apply an Artificial Intelligence approach to the back-scattered signal arising from a trapped cell by a micro-lensed optical fiber. As a proof of concept, we show that iLoF is able to discriminate two human cancer cell models sharing the same genetic background but displaying a different surface glycosylation profile with an accuracy above 90% and a speed rate of 2.3 seconds. We envision the incorporation of the iLoF in an easy-to-operate microchip for cancer identification, which would allow further biological characterization of the captured circulating live cells.
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| 2. |
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| 3. |
- Meghdadi, S., et al.
(författare)
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Synthesis, X-ray crystal structure, and electrochemistry of copper(II) complexes of a new tridentate unsymmetrical Schiff base ligand and its hydrolytically rearranged isomer
- 2012
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Ingår i: Inorganica Chimica Acta. - : Elsevier BV. - 0020-1693. ; 385, s. 31-38
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Tidskriftsartikel (refereegranskat)abstract
- A new unsymmetrical Schiff base ligand HL1, HBacabza, and its copper(II) complexes [Cu2L21(OAc)(2)] (1) and [Cu2L22(N-3)(2)]center dot 2H(2)O (2) with HBacabza = 3-(2- aminobenzylimino)-1-phenylbutan-1-one as HL1 and its hydrolytically rearranged isomer 3-(2-aminomethylphenyleneimino)-1-phenylbutan-1-one as HL2, have been synthesized and characterized by elemental analyses and spectroscopic methods. The rearrangement of HL1 to HL2 occurs in a hydrolysis-recondensation process in the reaction of HL1 with Cu(ClO4)(2)center dot 6H(2)O and NaN3. The crystal structures of the ligand and its complexes have been determined by single crystal X-ray diffraction. The deprotonated Bacabza coordinates to the metal center as a tridentate ligand. The acetate anion coordinates through one oxygen atom in complex 1 leading to a mono-atomic acetate oxygen-bridging dimeric copper(II) complex. Similarly, the azide anion coordinates through one nitrogen atom in complex 2 leading to a mono-atomic azide nitrogen-bridging dimeric copper(II) complex. The copper(II) ions adopt a distorted square pyramidal (4 + 1) coordination in these two complexes. The cyclic voltammetric studies of these complexes in N, N-dimethylformamide indicate that the reduction process corresponding to Cu-II/Cu-I is electrochemically irreversible in complex 1, presumably due to the structural changes during the course of redox reaction, and quasi-reversible in complex 2.
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| 5. |
- Mereiter, S., et al.
(författare)
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Glycomic analysis of gastric carcinoma cells discloses glycans as modulators of RON receptor tyrosine kinase activation in cancer
- 2016
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Ingår i: Biochimica Et Biophysica Acta-General Subjects. - : Elsevier BV. - 0304-4165. ; 1860:8, s. 1795-1808
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Tidskriftsartikel (refereegranskat)abstract
- Background: Terminal alpha 2-3 and alpha 2-6 sialylation of glycans precludes further chain elongation, leading to the biosynthesis of cancer relevant epitopes such as sialyl-Lewis X (SLe(X)). SLe(X) overexpression is associated with tumor aggressive phenotype and patients' poor prognosis. Methods: MKN45 gastric carcinoma cells transfected with the sialyltransferase ST3GAL4 were established as a model overexpressing sialylated terminal glycans. We have evaluated at the structural level the glycome and the sialoproteome of this gastric cancer cell line applying liquid chromatography and mass spectrometry. We further validated an identified target expression by proximity ligation assay in gastric tumors. Results: Our results showed that ST3GAL4 overexpression leads to several glycosylation alterations, including reduced O-glycan extension and decreased bisected and increased branched N-glycans. A shift from alpha 2-6 towards alpha 2-3 linked sialylated N-glycans was also observed. Sialoproteomic analysis further identified 47 proteins with significantly increased sialylated N-glycans. These included integrins, insulin receptor, carcinoembryonic antigens and RON receptor tyrosine kinase, which are proteins known to be key players in malignancy. Further analysis of RON confirmed its modification with SLe(X) and the concomitant activation. SLe(X) and RON co-expression was validated in gastric tumors. Conclusion: The overexpression of ST3GAL4 interferes with the overall glycophenotype of cancer cells affecting a multitude of key proteins involved in malignancy. Aberrant glycosylation of the RON receptor was shown as an alternative mechanism of oncogenic activation. General significance: This study provides novel targets and points to an integrative tumor glycomic/proteomic-profiling for gastric cancer patients' stratification. This article is part of a Special Issue entitled "Glycans in personalised medicine" Guest Editor: Professor Gordan Lauc.
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| 6. |
- Mereiter, S., et al.
(författare)
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The Thomsen-Friedenreich Antigen: A Highly Sensitive and Specific Predictor of Microsatellite Instability in Gastric Cancer
- 2018
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Ingår i: Journal of Clinical Medicine. - : MDPI AG. - 2077-0383. ; 7:9
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Tidskriftsartikel (refereegranskat)abstract
- Microsatellite instability (MSI) is a distinct molecular subtype of gastric cancer. In recent years, the clinical consequences of MSI and the therapeutic opportunities to target this peculiar cancer subtype became evident. However, despite the importance of MSI for the stratification of patients, the time and resources required for diagnosis still present an obstacle. In an attempt to identify a new marker for MSI in gastric cancer, we evaluated the expression of five cancer-associated glycan epitopes in a cohort of 13 MSI and 17 microsatellite stable (MSS) cases. Our analysis revealed a highly significant (p < 0.001) association between the expression of the Thomsen-Friedenreich (TF) antigen and MSI status. Hence, we present here the identification of the first single marker for MSI in gastric cancer, excelling with a specificity of 94% (16/17), sensitivity of 69.2% (9/13), negative predictive value of 80% (16/20), and positive predictive value of 90% (9/10). The TF antigen, detected by simple antibody-based assays, is highly specific for carcinoma being undetectable in gastric healthy and premalignant epithelia. This finding lays the basis for new studies and holds promise in improving the rapid identification of MSI in the clinical setting.
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