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  1. Article ; Online: Analyses of single extracellular vesicles from non-small lung cancer cells to reveal effects of epidermal growth factor receptor inhibitor treatments

    Stridfeldt, Fredrik / Cavallaro, Sara / Haag, Petra / Lewensohn, Rolf / Linnros, J. / Viktorsson, Kristina / Dev, Apurba

    Talanta. 2023 July, v. 259 p.124553-

    2023  

    Abstract: Precision cancer medicine has changed the treatment landscape of non-small cell lung cancer (NSCLC) as illustrated by the introduction of tyrosine kinase inhibitors (TKIs) towards mutated epidermal growth factor receptor (EGFR). However, as responses to ... ...

    Abstract Precision cancer medicine has changed the treatment landscape of non-small cell lung cancer (NSCLC) as illustrated by the introduction of tyrosine kinase inhibitors (TKIs) towards mutated epidermal growth factor receptor (EGFR). However, as responses to EGFR-TKIs are heterogenous among NSCLC patients, there is a need for ways to early monitor changes in treatment response in a non-invasive way e.g., in patient's blood samples. Recently, extracellular vesicles (EVs) have been identified as a source of tumor biomarkers which could improve on non-invasive liquid biopsy-based diagnosis of cancer. However, the heterogeneity in EVs is high. Putative biomarker candidates may be hidden in the differential expression of membrane proteins in a subset of EVs hard to identify using bulk techniques. Using a fluorescence-based approach, we demonstrate that a single-EV technique can detect alterations in EV surface protein profiles. We analyzed EVs isolated from an EGFR-mutant NSCLC cell line, which is refractory to EGFR-TKIs erlotinib and responsive to osimertinib, before and after treatment with these drugs and after cisplatin chemotherapy. We studied expression level of five proteins; two tetraspanins (CD9, CD81), and three markers of interest in lung cancer (EGFR, programmed death-ligand 1 (PD-L1), human epidermal growth factor receptor 2 (HER2)). The data reveal alterations induced by the osimertinib treatment compared to the other two treatments. These include the growth of the PD-L1/HER2-positive EV population, with the largest increase in vesicles exclusively expressing one of the two proteins. The expression level per EV decreased for these markers. On the other hand, both the TKIs had a similar effect on the EGFR-positive EV population.
    Keywords biomarkers ; blood ; cell lines ; cisplatin ; drug therapy ; epidermal growth factor receptors ; erbB-2 receptor ; gene expression regulation ; landscapes ; liquids ; lung neoplasms ; medicine ; patients ; surface proteins ; tyrosine ; Extracellular vesicles ; Fluorescence microscopy ; Single EV analysis ; Immunostaining ; Non-small cell lung cancer ; EGFR-TKIs
    Language English
    Dates of publication 2023-07
    Publishing place Elsevier B.V.
    Document type Article ; Online
    Note Pre-press version ; Use and reproduction
    ZDB-ID 1500969-5
    ISSN 1873-3573 ; 0039-9140
    ISSN (online) 1873-3573
    ISSN 0039-9140
    DOI 10.1016/j.talanta.2023.124553
    Database NAL-Catalogue (AGRICOLA)

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  2. Article ; Online: Advances in molecular targeted therapies to increase efficacy of (chemo)radiation therapy.

    Viktorsson, Kristina / Rieckmann, Thorsten / Fleischmann, Maximilian / Diefenhardt, Markus / Hehlgans, Stephanie / Rödel, Franz

    Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al

    2023  Volume 199, Issue 12, Page(s) 1091–1109

    Abstract: Recent advances in understanding the tumor's biology in line with a constantly growing number of innovative technologies have prompted characterization of patients' individual malignancies and may display a prerequisite to treat cancer at its patient ... ...

    Abstract Recent advances in understanding the tumor's biology in line with a constantly growing number of innovative technologies have prompted characterization of patients' individual malignancies and may display a prerequisite to treat cancer at its patient individual tumor vulnerability. In recent decades, radiation- induced signaling and tumor promoting local events for radiation sensitization were explored in detail, resulting the development of novel molecular targets. A multitude of pharmacological, genetic, and immunological principles, including small molecule- and antibody-based targeted strategies, have been developed that are suitable for combined concepts with radiation (RT) or chemoradiation therapy (CRT). Despite a plethora of promising experimental and preclinical findings, however, so far, only a very limited number of clinical trials have demonstrated a better outcome and/or patient benefit when RT or CRT are combined with targeted agents. The current review aims to summarize recent progress in molecular therapies targeting oncogenic drivers, DNA damage and cell cycle response, apoptosis signaling pathways, cell adhesion molecules, hypoxia, and the tumor microenvironment to impact therapy refractoriness and to boost radiation response. In addition, we will discuss recent advances in nanotechnology, e.g., RNA technologies and protein-degrading proteolysis-targeting chimeras (PROTACs) that may open new and innovative ways to benefit from molecular-targeted therapy approaches with improved efficacy.
    MeSH term(s) Humans ; Molecular Targeted Therapy ; Neoplasms/radiotherapy ; Neoplasms/drug therapy ; Antineoplastic Agents/therapeutic use ; Signal Transduction ; Tumor Microenvironment
    Chemical Substances Antineoplastic Agents
    Language English
    Publishing date 2023-04-11
    Publishing country Germany
    Document type Journal Article ; Review
    ZDB-ID 84983-2
    ISSN 1439-099X ; 0179-7158 ; 0039-2073
    ISSN (online) 1439-099X
    ISSN 0179-7158 ; 0039-2073
    DOI 10.1007/s00066-023-02064-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Analyses of single extracellular vesicles from non-small lung cancer cells to reveal effects of epidermal growth factor receptor inhibitor treatments.

    Stridfeldt, Fredrik / Cavallaro, Sara / Hååg, Petra / Lewensohn, Rolf / Linnros, Jan / Viktorsson, Kristina / Dev, Apurba

    Talanta

    2023  Volume 259, Page(s) 124553

    Abstract: Precision cancer medicine has changed the treatment landscape of non-small cell lung cancer (NSCLC) as illustrated by the introduction of tyrosine kinase inhibitors (TKIs) towards mutated epidermal growth factor receptor (EGFR). However, as responses to ... ...

    Abstract Precision cancer medicine has changed the treatment landscape of non-small cell lung cancer (NSCLC) as illustrated by the introduction of tyrosine kinase inhibitors (TKIs) towards mutated epidermal growth factor receptor (EGFR). However, as responses to EGFR-TKIs are heterogenous among NSCLC patients, there is a need for ways to early monitor changes in treatment response in a non-invasive way e.g., in patient's blood samples. Recently, extracellular vesicles (EVs) have been identified as a source of tumor biomarkers which could improve on non-invasive liquid biopsy-based diagnosis of cancer. However, the heterogeneity in EVs is high. Putative biomarker candidates may be hidden in the differential expression of membrane proteins in a subset of EVs hard to identify using bulk techniques. Using a fluorescence-based approach, we demonstrate that a single-EV technique can detect alterations in EV surface protein profiles. We analyzed EVs isolated from an EGFR-mutant NSCLC cell line, which is refractory to EGFR-TKIs erlotinib and responsive to osimertinib, before and after treatment with these drugs and after cisplatin chemotherapy. We studied expression level of five proteins; two tetraspanins (CD9, CD81), and three markers of interest in lung cancer (EGFR, programmed death-ligand 1 (PD-L1), human epidermal growth factor receptor 2 (HER2)). The data reveal alterations induced by the osimertinib treatment compared to the other two treatments. These include the growth of the PD-L1/HER2-positive EV population, with the largest increase in vesicles exclusively expressing one of the two proteins. The expression level per EV decreased for these markers. On the other hand, both the TKIs had a similar effect on the EGFR-positive EV population.
    MeSH term(s) Humans ; Lung Neoplasms/pathology ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Carcinoma, Non-Small-Cell Lung/pathology ; B7-H1 Antigen/genetics ; B7-H1 Antigen/metabolism ; B7-H1 Antigen/therapeutic use ; Protein Kinase Inhibitors/pharmacology ; Protein Kinase Inhibitors/therapeutic use ; Mutation ; ErbB Receptors/genetics
    Chemical Substances osimertinib (3C06JJ0Z2O) ; B7-H1 Antigen ; Protein Kinase Inhibitors ; ErbB Receptors (EC 2.7.10.1)
    Language English
    Publishing date 2023-04-14
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 1500969-5
    ISSN 1873-3573 ; 0039-9140
    ISSN (online) 1873-3573
    ISSN 0039-9140
    DOI 10.1016/j.talanta.2023.124553
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Multi-marker profiling of extracellular vesicles using streaming current and sequential electrostatic labeling.

    Sahu, Siddharth S / Gevari, Moein T / Nagy, Ábel / Gestin, Maxime / Hååg, Petra / Lewensohn, Rolf / Viktorsson, Kristina / Karlström, Amelie E / Dev, Apurba

    Biosensors & bioelectronics

    2023  Volume 227, Page(s) 115142

    Abstract: High heterogeneity in the membrane protein expression of small extracellular vesicles (sEVs) means that bulk methods relying on antibody-based capture for expression analysis have a drawback that each type of antibody may capture a different sub- ... ...

    Abstract High heterogeneity in the membrane protein expression of small extracellular vesicles (sEVs) means that bulk methods relying on antibody-based capture for expression analysis have a drawback that each type of antibody may capture a different sub-population. An improved approach is to capture a representative sEV population, without any bias, and then perform a multiplexed protein expression analysis on this population. However, such a possibility has been largely limited to fluorescence-based methods. Here, we present a novel electrostatic labelling strategy and a microchip-based all-electric method for membrane protein analysis of sEVs. The method allows us to profile multiple surface proteins on the captured sEVs using alternating charge labels. It also permits the comparison of expression levels in different sEV-subtypes. The proof of concept was tested by capturing sEVs both non-specifically (unbiased) as well as via anti-CD9 capture probes (biased), and then profiling the expression levels of various surface proteins using the charge labelled antibodies. The method is the first of its kind, demonstrating an all-electrical and microchip based method that allows for unbiased analysis of sEV membrane protein expression, comparison of expression levels in different sEV subsets, and fractional estimation of different sEV sub-populations. These results were also validated in parallel using a single-sEV fluorescence technique.
    MeSH term(s) Static Electricity ; Biosensing Techniques ; Extracellular Vesicles ; Electricity ; Antibodies ; Membrane Proteins
    Chemical Substances Antibodies ; Membrane Proteins
    Language English
    Publishing date 2023-02-09
    Publishing country England
    Document type Journal Article
    ZDB-ID 1011023-9
    ISSN 1873-4235 ; 0956-5663
    ISSN (online) 1873-4235
    ISSN 0956-5663
    DOI 10.1016/j.bios.2023.115142
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Multi-marker profiling of extracellular vesicles using streaming current and sequential electrostatic labeling

    Sahu, Siddharth S. / Gevari, Moein T. / Nagy, Ábel / Gestin, Maxime / Haag, Petra / Lewensohn, Rolf / Viktorsson, Kristina / Karlström, Amelie E. / Dev, Apurba

    Biosensors and Bioelectronics. 2023 Feb. 09, p.115142-

    2023  , Page(s) 115142–

    Abstract: High heterogeneity in the membrane protein expression of small extracellular vesicles (sEVs) means that bulk methods relying on antibody-based capture for expression analysis have a drawback that each type of antibody may capture a different sub- ... ...

    Abstract High heterogeneity in the membrane protein expression of small extracellular vesicles (sEVs) means that bulk methods relying on antibody-based capture for expression analysis have a drawback that each type of antibody may capture a different sub-population. An improved approach is to capture a representative sEV population, without any bias, and then perform a multiplexed protein expression analysis on this population. However, such a possibility has been largely limited to fluorescence-based methods. Here, we present a novel electrostatic labelling strategy and a microchip-based all-electric method for membrane protein analysis of sEVs. The method allows us to profile multiple surface proteins on the captured sEVs using alternating charge labels. It also permits the comparison of expression levels in different sEV-subtypes. The proof of concept was tested by capturing sEVs both non-specifically (unbiased) as well as via anti-CD9 capture probes (biased), and then profiling the expression levels of various surface proteins using the charge labelled antibodies. The method is the first of its kind, demonstrating an all-electrical and microchip based method that allows for unbiased analysis of sEV membrane protein expression, comparison of expression levels in different sEV subsets, and fractional estimation of different sEV sub-populations. These results were also validated in parallel using a single-sEV fluorescence technique.
    Keywords antibodies ; biosensors ; fluorescence ; membrane proteins ; microchip technology ; protein synthesis ; Extracellular vesicles ; Streaming current ; Electrostatic labels
    Language English
    Dates of publication 2023-0209
    Publishing place Elsevier B.V.
    Document type Article ; Online
    Note Pre-press version
    ZDB-ID 1011023-9
    ISSN 1873-4235 ; 0956-5663
    ISSN (online) 1873-4235
    ISSN 0956-5663
    DOI 10.1016/j.bios.2023.115142
    Database NAL-Catalogue (AGRICOLA)

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  6. Article ; Online: Cytotoxic Alkylynols of the Sponge

    Kovalerchik, Dimitry / Zovko, Ana / Hååg, Petra / Sierakowiak, Adam / Viktorsson, Kristina / Lewensohn, Rolf / Ilan, Micha / Carmeli, Shmuel

    Marine drugs

    2022  Volume 20, Issue 4

    Abstract: A series of twenty-three linear and branched chain mono acetylene lipids were isolated from the Caribbean Sea ... ...

    Abstract A series of twenty-three linear and branched chain mono acetylene lipids were isolated from the Caribbean Sea sponge
    MeSH term(s) Acetylene/therapeutic use ; Alkanes ; Antineoplastic Agents/chemistry ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Carcinoma, Non-Small-Cell Lung/metabolism ; Humans ; Lung Neoplasms/drug therapy ; Lung Neoplasms/metabolism ; Structure-Activity Relationship
    Chemical Substances Alkanes ; Antineoplastic Agents ; Acetylene (OC7TV75O83)
    Language English
    Publishing date 2022-04-13
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2175190-0
    ISSN 1660-3397 ; 1660-3397
    ISSN (online) 1660-3397
    ISSN 1660-3397
    DOI 10.3390/md20040265
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Profiling of extracellular vesicles of metastatic urothelial cancer patients to discover protein signatures related to treatment outcome.

    Viktorsson, Kristina / Hååg, Petra / Shah, Carl-Henrik / Franzén, Bo / Arapi, Vasiliki / Holmsten, Karin / Sandström, Per / Lewensohn, Rolf / Ullén, Anders

    Molecular oncology

    2022  Volume 16, Issue 20, Page(s) 3620–3641

    Abstract: The prognosis of metastatic urothelial carcinoma (mUC) patients is poor, and early prediction of systemic therapy response would be valuable to improve outcome. In this exploratory study, we investigated protein profiles in sequential plasma-isolated ... ...

    Abstract The prognosis of metastatic urothelial carcinoma (mUC) patients is poor, and early prediction of systemic therapy response would be valuable to improve outcome. In this exploratory study, we investigated protein profiles in sequential plasma-isolated extracellular vesicles (EVs) from a subset of mUC patients treated within a Phase I trial with vinflunine combined with sorafenib. The isolated EVs were of exosome size and expressed exosome markers CD9, TSG101 and SYND-1. We found, no association between EVs/ml plasma at baseline and progression-free survival (PFS). Protein profiling of EVs, using an antibody-based 92-plex Proximity Extension Assay on the Oncology II<sup>®</sup> platform, revealed a heterogeneous protein expression pattern. Qlucore bioinformatic analyses put forward a protein signature comprising of SYND-1, TNFSF13, FGF-BP1, TFPI-2, GZMH, ABL1 and ERBB3 to be putatively associated with PFS. Similarly, a protein signature from EVs that related to best treatment response was found, which included FR-alpha, TLR 3, TRAIL and FASLG. Several of the markers in the PFS or best treatment response signatures were also identified by a machine learning classification algorithm. In conclusion, protein profiling of EVs isolated from plasma of mUC patients shows a potential to identify protein signatures that may associate with PFS and/or treatment response.
    MeSH term(s) Humans ; Carcinoma, Transitional Cell/metabolism ; Carcinoma, Transitional Cell/pathology ; Sorafenib/pharmacology ; Sorafenib/therapeutic use ; Toll-Like Receptor 3/metabolism ; Urinary Bladder Neoplasms/pathology ; Extracellular Vesicles/metabolism ; Biomarkers/metabolism ; Treatment Outcome
    Chemical Substances Sorafenib (9ZOQ3TZI87) ; Toll-Like Receptor 3 ; Biomarkers
    Language English
    Publishing date 2022-08-12
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2415106-3
    ISSN 1878-0261 ; 1574-7891
    ISSN (online) 1878-0261
    ISSN 1574-7891
    DOI 10.1002/1878-0261.13288
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: The prognostic implications of Notch1, Hes1, Ascl1, and DLL3 protein expression in SCLC patients receiving platinum-based chemotherapy.

    Tendler, Salomon / Kanter, Lena / Lewensohn, Rolf / Ortiz-Villalón, Cristian / Viktorsson, Kristina / De Petris, Luigi

    PloS one

    2020  Volume 15, Issue 10, Page(s) e0240973

    Abstract: Objectives: The aim was to analyse the tumor expression of Notch1, Hes1, Ascl1, and DLL3 in Small-Cell Lung Cancer (SCLC) and each such biomarker's potential association with clinical characteristics and prognosis after platinum-doublet chemotherapy ( ... ...

    Abstract Objectives: The aim was to analyse the tumor expression of Notch1, Hes1, Ascl1, and DLL3 in Small-Cell Lung Cancer (SCLC) and each such biomarker's potential association with clinical characteristics and prognosis after platinum-doublet chemotherapy (PDCT).
    Material and methods: The protein expression of the biomarkers was evaluated using immunohistochemistry. Patients were categorized according to their sensitivity to first line PDCT: with a Progression-free survival (PFS) ≥ 3 months after completion of treatment considered "sensitive" and < 3 months after completion of treatment considered "refractory". PFS and overall survival were computed using Kaplan-Meier curves with 95% confidence interval.
    Results and conclusion: The study included 46 patients, with 21 and 25 of the patients having "sensitive" and "refractory" disease, respectively. The majority of patients had a high DLL3 expression (n = 38), while a minority had Notch 1-high expression (n = 10). The chi-square test showed that there was a statistically significant negative association between Notch1 and Ascl1 expression (p = 0.013). The overall survival for patients with Notch1- high vs. low expression was 8.1 vs. 12.4 months, respectively (p = 0.036). Notch1 expression was an independent prognostic factor in the multivariate analysis (p = 0.02). No other biomarker showed any prognostic impact in this highly selected SCLC cohort. DLL3 is highly expressed in the majority of advanced staged SCLC cases, as expected. In the same patient population, Notch1 expression might have a potential prognostic implication, by driving a non-neuroendocrine differentiation process. Given the small number of cases with Notch1 high expression, the results of this study needs to be confirmed on a larger cohort.
    MeSH term(s) Aged ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Basic Helix-Loop-Helix Transcription Factors ; Biomarkers, Tumor/metabolism ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Intracellular Signaling Peptides and Proteins ; Lung Neoplasms/drug therapy ; Lung Neoplasms/metabolism ; Male ; Membrane Proteins ; Middle Aged ; Platinum/pharmacology ; Platinum/therapeutic use ; Prognosis ; Receptor, Notch1 ; Small Cell Lung Carcinoma/drug therapy ; Small Cell Lung Carcinoma/metabolism ; Survival Analysis ; Transcription Factor HES-1 ; Treatment Outcome
    Chemical Substances ASCL1 protein, human ; Antineoplastic Agents ; Basic Helix-Loop-Helix Transcription Factors ; Biomarkers, Tumor ; DLL3 protein, human ; Intracellular Signaling Peptides and Proteins ; Membrane Proteins ; NOTCH1 protein, human ; Receptor, Notch1 ; Transcription Factor HES-1 ; HES1 protein, human (149348-15-2) ; Platinum (49DFR088MY)
    Language English
    Publishing date 2020-10-26
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0240973
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Multiplex protein analysis and ensemble machine learning methods of fine needle aspirates from prostate cancer patients reveal potential diagnostic signatures associated with tumour grade.

    Röbeck, Pontus / Franzén, Bo / Cantera-Ahlman, Rafaele / Dragomir, Anca / Auer, Gert / Jorulf, Håkan / Jacobsson, Sven P / Viktorsson, Kristina / Lewensohn, Rolf / Häggman, Michael / Ladjevardi, Sam

    Cytopathology : official journal of the British Society for Clinical Cytology

    2023  Volume 34, Issue 4, Page(s) 286–294

    Abstract: Background: Improved molecular diagnosis is needed in prostate cancer (PC). Fine needle aspiration (FNA) is a minimally invasive biopsy technique, less traumatic compared to core needle biopsy, and could be useful for diagnosis of PC. Molecular ... ...

    Abstract Background: Improved molecular diagnosis is needed in prostate cancer (PC). Fine needle aspiration (FNA) is a minimally invasive biopsy technique, less traumatic compared to core needle biopsy, and could be useful for diagnosis of PC. Molecular biomarkers (BMs) in FNA-samples can be assessed for prediction, eg of immunotherapy efficacy before treatment as well as at treatment decision time points during disease progression.
    Methods: In the present pilot study, the expression levels of 151 BM proteins were analysed by proximity extension assay in FNA-samples from 16 patients, including benign prostate lesions (n = 3) and cancers (n = 13). An ensemble data analysis strategy was applied using several machine learning models.
    Results: Twelve potentially predictive BM proteins correlating with International Society of Urological Pathology grade groups were identified, among them vimentin, tissue factor pathway inhibitor 2, and integrin beta-5. The validity of the results was supported by network analysis that showed functional associations between most of the identified putative BMs. We also showed that multiple immune checkpoint targets can be assessed (eg PD-L1, CD137, and Galectin-9), which may support the selection of immunotherapy in advanced PC. Results are promising but need further validation in a larger cohort.
    Conclusions: Our pilot study represents a "proof of concept" and shows that multiplex profiling of potential diagnostic and predictive BM proteins is feasible on tumour material obtained by FNA sampling of prostate cancer. Moreover, our results demonstrate that an ensemble data analysis strategy may facilitate the identification of BM signatures in pilot studies when the patient cohort is limited.
    MeSH term(s) Male ; Humans ; Biopsy, Fine-Needle ; Pilot Projects ; Prostatic Neoplasms/pathology ; Prostate/pathology ; Biopsy, Large-Core Needle ; Biomarkers/metabolism
    Chemical Substances Biomarkers
    Language English
    Publishing date 2023-03-20
    Publishing country England
    Document type Journal Article
    ZDB-ID 1034190-0
    ISSN 1365-2303 ; 0956-5507 ; 1350-4037
    ISSN (online) 1365-2303
    ISSN 0956-5507 ; 1350-4037
    DOI 10.1111/cyt.13226
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Exploiting Electrostatic Interaction for Highly Sensitive Detection of Tumor-Derived Extracellular Vesicles by an Electrokinetic Sensor.

    Sahu, Siddharth Sourabh / Cavallaro, Sara / Hååg, Petra / Nagy, Ábel / Karlström, Amelie Eriksson / Lewensohn, Rolf / Viktorsson, Kristina / Linnros, Jan / Dev, Apurba

    ACS applied materials & interfaces

    2021  Volume 13, Issue 36, Page(s) 42513–42521

    Abstract: We present an approach to improve the detection sensitivity of a streaming current-based biosensor for membrane protein profiling of small extracellular vesicles (sEVs). The experimental approach, supported by theoretical investigation, exploits ... ...

    Abstract We present an approach to improve the detection sensitivity of a streaming current-based biosensor for membrane protein profiling of small extracellular vesicles (sEVs). The experimental approach, supported by theoretical investigation, exploits electrostatic charge contrast between the sensor surface and target analytes to enhance the detection sensitivity. We first demonstrate the feasibility of the approach using different chemical functionalization schemes to modulate the zeta potential of the sensor surface in a range -16.0 to -32.8 mV. Thereafter, we examine the sensitivity of the sensor surface across this range of zeta potential to determine the optimal functionalization scheme. The limit of detection (LOD) varied by 2 orders of magnitude across this range, reaching a value of 4.9 × 10
    MeSH term(s) Antibodies, Immobilized/immunology ; B7-H1 Antigen/analysis ; B7-H1 Antigen/metabolism ; Biosensing Techniques/methods ; Cell Line, Tumor ; Electrochemical Techniques ; ErbB Receptors/analysis ; ErbB Receptors/antagonists & inhibitors ; ErbB Receptors/metabolism ; Extracellular Vesicles/chemistry ; Extracellular Vesicles/drug effects ; Extracellular Vesicles/immunology ; Humans ; Limit of Detection ; Protein Kinase Inhibitors/pharmacology ; Static Electricity ; Tetraspanin 29/analysis ; Tetraspanin 29/metabolism
    Chemical Substances Antibodies, Immobilized ; B7-H1 Antigen ; CD274 protein, human ; CD9 protein, human ; Protein Kinase Inhibitors ; Tetraspanin 29 ; EGFR protein, human (EC 2.7.10.1) ; ErbB Receptors (EC 2.7.10.1)
    Language English
    Publishing date 2021-09-02
    Publishing country United States
    Document type Journal Article
    ISSN 1944-8252
    ISSN (online) 1944-8252
    DOI 10.1021/acsami.1c13192
    Database MEDical Literature Analysis and Retrieval System OnLINE

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