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  1. Article ; Online: Innovative strategies for measuring kinase activity to accelerate the next wave of novel kinase inhibitors.

    Veth, Tim S / Kannegieter, Nynke M / de Graaf, Erik L / Ruijtenbeek, Rob / Joore, Jos / Ressa, Anna / Altelaar, Maarten

    Drug discovery today

    2024  Volume 29, Issue 3, Page(s) 103907

    Abstract: The development of protein kinase inhibitors (PKIs) has gained significance owing to their therapeutic potential for diseases like cancer. In addition, there has been a rise in refining kinase activity assays, each possessing unique biological and ... ...

    Abstract The development of protein kinase inhibitors (PKIs) has gained significance owing to their therapeutic potential for diseases like cancer. In addition, there has been a rise in refining kinase activity assays, each possessing unique biological and analytical characteristics crucial for PKI development. However, the PKI development pipeline experiences high attrition rates and approved PKIs exhibit unexploited potential because of variable patient responses. Enhancing PKI development efficiency involves addressing challenges related to understanding the PKI mechanism of action and employing biomarkers for precision medicine. Selecting appropriate kinase activity assays for these challenges can overcome these attrition rate issues. This review delves into the current obstacles in kinase inhibitor development and elucidates kinase activity assays that can provide solutions.
    MeSH term(s) Humans ; Antineoplastic Agents/pharmacology ; Neoplasms/drug therapy ; Protein Kinase Inhibitors/pharmacology ; Protein Kinase Inhibitors/therapeutic use
    Chemical Substances Antineoplastic Agents ; Protein Kinase Inhibitors
    Language English
    Publishing date 2024-01-30
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 1324988-5
    ISSN 1878-5832 ; 1359-6446
    ISSN (online) 1878-5832
    ISSN 1359-6446
    DOI 10.1016/j.drudis.2024.103907
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Gluten-Free Bread Enriched with Artichoke Leaf Extract In Vitro Exerted Antioxidant and Anti-Inflammatory Properties.

    Vacca, Mirco / Pinto, Daniela / Annunziato, Alessandro / Ressa, Arianna / Calasso, Maria / Pontonio, Erica / Celano, Giuseppe / De Angelis, Maria

    Antioxidants (Basel, Switzerland)

    2023  Volume 12, Issue 4

    Abstract: Due to its high nutritional value and broad beneficial effects, the artichoke plant ( ...

    Abstract Due to its high nutritional value and broad beneficial effects, the artichoke plant (
    Language English
    Publishing date 2023-04-01
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2704216-9
    ISSN 2076-3921
    ISSN 2076-3921
    DOI 10.3390/antiox12040845
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Novel kinome profiling technology reveals drug treatment is patient and 2D/3D model dependent in glioblastoma.

    Fabro, Federica / Kannegieter, Nynke M / de Graaf, Erik L / Queiroz, Karla / Lamfers, Martine L M / Ressa, Anna / Leenstra, Sieger

    Frontiers in oncology

    2022  Volume 12, Page(s) 1012236

    Abstract: Glioblastoma is the deadliest brain cancer. One of the main reasons for poor outcome resides in therapy resistance, which adds additional challenges in finding an effective treatment. Small protein kinase inhibitors are molecules that have become widely ... ...

    Abstract Glioblastoma is the deadliest brain cancer. One of the main reasons for poor outcome resides in therapy resistance, which adds additional challenges in finding an effective treatment. Small protein kinase inhibitors are molecules that have become widely studied for cancer treatments, including glioblastoma. However, none of these drugs have demonstrated a therapeutic activity or brought more benefit compared to the current standard procedure in clinical trials. Hence, understanding the reasons of the limited efficacy and drug resistance is valuable to develop more effective strategies toward the future. To gain novel insights into the method of action and drug resistance in glioblastoma, we established in parallel two patient-derived glioblastoma 2D and 3D organotypic multicellular spheroids models, and exposed them to a prolonged treatment of three weeks with temozolomide or either the two small protein kinase inhibitors enzastaurin and imatinib. We coupled the phenotypic evidence of cytotoxicity, proliferation, and migration to a novel kinase activity profiling platform (QuantaKinome™) that measured the activities of the intracellular network of kinases affected by the drug treatments. The results revealed a heterogeneous inter-patient phenotypic and molecular response to the different drugs. In general, small differences in kinase activation were observed, suggesting an intrinsic low influence of the drugs to the fundamental cellular processes like proliferation and migration. The pathway analysis indicated that many of the endogenously detected kinases were associated with the ErbB signaling pathway. We showed the intertumoral variability in drug responses, both in terms of efficacy and resistance, indicating the importance of pursuing a more personalized approach. In addition, we observed the influence derived from the application of 2D or 3D models in
    Language English
    Publishing date 2022-11-03
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2649216-7
    ISSN 2234-943X
    ISSN 2234-943X
    DOI 10.3389/fonc.2022.1012236
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: PaDuA: A Python Library for High-Throughput (Phospho)proteomics Data Analysis

    Ressa, Anna / Fitzpatrick, Martin / van den Toorn, Henk / Heck, Albert J. R / Altelaar, Maarten

    Journal of proteome research. 2018 Dec. 10, v. 18, no. 2

    2018  

    Abstract: The increased speed and sensitivity in mass spectrometry-based proteomics has encouraged its use in biomedical research in recent years. Large-scale detection of proteins in cells, tissues, and whole organisms yields highly complex quantitative data, the ...

    Abstract The increased speed and sensitivity in mass spectrometry-based proteomics has encouraged its use in biomedical research in recent years. Large-scale detection of proteins in cells, tissues, and whole organisms yields highly complex quantitative data, the analysis of which poses significant challenges. Standardized proteomic workflows are necessary to ensure automated, sharable, and reproducible proteomics analysis. Likewise, standardized data processing workflows are also essential for the overall reproducibility of results. To this purpose, we developed PaDuA, a Python package optimized for the processing and analysis of (phospho)proteomics data. PaDuA provides a collection of tools that can be used to build scripted workflows within Jupyter Notebooks to facilitate bioinformatics analysis by both end-users and developers.
    Keywords bioinformatics ; biomedical research ; computer software ; information processing ; mass spectrometry ; phosphoproteins ; proteome ; proteomics
    Language English
    Dates of publication 2018-1210
    Size p. 576-584.
    Publishing place American Chemical Society
    Document type Article
    ZDB-ID 2078618-9
    ISSN 1535-3907 ; 1535-3893
    ISSN (online) 1535-3907
    ISSN 1535-3893
    DOI 10.1021/acs.jproteome.8b00576
    Database NAL-Catalogue (AGRICOLA)

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  5. Article ; Online: Effect of Seasonality on Microbiological Variability of Raw Cow Milk from Apulian Dairy Farms in Italy.

    Celano, Giuseppe / Calasso, Maria / Costantino, Giuseppe / Vacca, Mirco / Ressa, Arianna / Nikoloudaki, Olga / De Palo, Pasquale / Calabrese, Francesco Maria / Gobbetti, Marco / De Angelis, Maria

    Microbiology spectrum

    2022  Volume 10, Issue 5, Page(s) e0051422

    Abstract: Raw cow milk is one of the most complex and unpredictable food matrices shaped by the interaction between biotic and abiotic factors. Changes in dairy farming conditions impact the quality and safety of milk, which largely depend on seasonality. Changes ... ...

    Abstract Raw cow milk is one of the most complex and unpredictable food matrices shaped by the interaction between biotic and abiotic factors. Changes in dairy farming conditions impact the quality and safety of milk, which largely depend on seasonality. Changes in microbiome composition and relative metabolic pathways are derived from microbial interactions, as well as from seasonality, mammary, and extramammary conditions (e.g., farm management and outdoor environment). Breeding data from >600 Apulian farms were examined, and the associated physicochemical parameters were processed by a reductionist approach to obtain a raw cow milk sample subset. We investigated the microbiological variability in cultivable and 16S rRNA sequencing microbiota as affected by seasonal fluctuations at two time points (winter and summer seasons). We identified families (
    MeSH term(s) Cattle ; Female ; Animals ; Milk/metabolism ; Milk/microbiology ; Farms ; Dairying/methods ; RNA, Ribosomal, 16S/genetics ; Seasons
    Chemical Substances RNA, Ribosomal, 16S
    Language English
    Publishing date 2022-08-16
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2807133-5
    ISSN 2165-0497 ; 2165-0497
    ISSN (online) 2165-0497
    ISSN 2165-0497
    DOI 10.1128/spectrum.00514-22
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: PaDuA: A Python Library for High-Throughput (Phospho)proteomics Data Analysis.

    Ressa, Anna / Fitzpatrick, Martin / van den Toorn, Henk / Heck, Albert J R / Altelaar, Maarten

    Journal of proteome research

    2018  Volume 18, Issue 2, Page(s) 576–584

    Abstract: The increased speed and sensitivity in mass spectrometry-based proteomics has encouraged its use in biomedical research in recent years. Large-scale detection of proteins in cells, tissues, and whole organisms yields highly complex quantitative data, the ...

    Abstract The increased speed and sensitivity in mass spectrometry-based proteomics has encouraged its use in biomedical research in recent years. Large-scale detection of proteins in cells, tissues, and whole organisms yields highly complex quantitative data, the analysis of which poses significant challenges. Standardized proteomic workflows are necessary to ensure automated, sharable, and reproducible proteomics analysis. Likewise, standardized data processing workflows are also essential for the overall reproducibility of results. To this purpose, we developed PaDuA, a Python package optimized for the processing and analysis of (phospho)proteomics data. PaDuA provides a collection of tools that can be used to build scripted workflows within Jupyter Notebooks to facilitate bioinformatics analysis by both end-users and developers.
    MeSH term(s) Computational Biology/methods ; Data Analysis ; Databases, Genetic ; Phosphoproteins/analysis ; Proteomics/methods ; Reference Standards ; Software ; Workflow
    Chemical Substances Phosphoproteins
    Language English
    Publishing date 2018-12-21
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2078618-9
    ISSN 1535-3907 ; 1535-3893
    ISSN (online) 1535-3907
    ISSN 1535-3893
    DOI 10.1021/acs.jproteome.8b00576
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Measurement of the 2νββ Decay Half-Life of ^{82}Se with the Global CUPID-0 Background Model.

    Azzolini, O / Beeman, J W / Bellini, F / Beretta, M / Biassoni, M / Brofferio, C / Bucci, C / Capelli, S / Caracciolo, V / Cardani, L / Carniti, P / Casali, N / Celi, E / Chiesa, D / Clemenza, M / Colantoni, I / Cremonesi, O / Cruciani, A / D'Addabbo, A /
    Dafinei, I / Di Domizio, S / Dompè, V / Fantini, G / Ferroni, F / Gironi, L / Giuliani, A / Gorla, P / Gotti, C / Keppel, G / Kotila, J / Martinez, M / Nagorny, S S / Nastasi, M / Nisi, S / Nones, C / Orlandi, D / Pagnanini, L / Pallavicini, M / Pattavina, L / Pavan, M / Pessina, G / Pettinacci, V / Pirro, S / Pozzi, S / Previtali, E / Puiu, A / Ressa, A / Rusconi, C / Schäffner, K / Tomei, C / Vignati, M / Zolotarova, A S

    Physical review letters

    2023  Volume 131, Issue 22, Page(s) 222501

    Abstract: We report on the results obtained with the global CUPID-0 background model, which combines the data collected in the two measurement campaigns for a total exposure of 8.82  kg×yr of ^{82}Se. We identify with improved precision the background sources ... ...

    Abstract We report on the results obtained with the global CUPID-0 background model, which combines the data collected in the two measurement campaigns for a total exposure of 8.82  kg×yr of ^{82}Se. We identify with improved precision the background sources within the 3 MeV energy region, where neutrinoless double β decay of ^{82}Se and ^{100}Mo is expected, making more solid the foundations for the background budget of the next-generation CUPID experiment. Relying on the excellent data reconstruction, we measure the two-neutrino double β-decay half-life of ^{82}Se with unprecedented accuracy: T_{1/2}^{2ν}=[8.69±0.05(stat)_{-0.06}^{+0.09}(syst)]×10^{19}  yr.
    Language English
    Publishing date 2023-12-15
    Publishing country United States
    Document type Journal Article
    ZDB-ID 208853-8
    ISSN 1079-7114 ; 0031-9007
    ISSN (online) 1079-7114
    ISSN 0031-9007
    DOI 10.1103/PhysRevLett.131.222501
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Multiomics profiling of paired primary and recurrent glioblastoma patient tissues.

    Dekker, Lennard J M / Kannegieter, Nynke M / Haerkens, Femke / Toth, Emma / Kros, Johan M / Steenhoff Hov, Dag Are / Fillebeen, Julien / Verschuren, Lars / Leenstra, Sieger / Ressa, Anna / Luider, Theo M

    Neuro-oncology advances

    2020  Volume 2, Issue 1, Page(s) vdaa083

    Abstract: Background: Despite maximal therapy with surgery, chemotherapy, and radiotherapy, glioblastoma (GBM) patients have a median survival of only 15 months. Almost all patients inevitably experience symptomatic tumor recurrence. A hallmark of this tumor type ...

    Abstract Background: Despite maximal therapy with surgery, chemotherapy, and radiotherapy, glioblastoma (GBM) patients have a median survival of only 15 months. Almost all patients inevitably experience symptomatic tumor recurrence. A hallmark of this tumor type is the large heterogeneity between patients and within tumors itself which relates to the failure of standardized tumor treatment. In this study, tissue samples of paired primary and recurrent GBM tumors were investigated to identify individual factors related to tumor progression.
    Methods: Paired primary and recurrent GBM tumor tissues from 8 patients were investigated with a multiomics approach using transcriptomics, proteomics, and phosphoproteomics.
    Results: In the studied patient cohort, large variations between and within patients are observed for all omics analyses. A few pathways affected at the different omics levels partly overlapped if patients are analyzed at the individual level, such as synaptogenesis (containing the SNARE complex) and cholesterol metabolism. Phosphoproteomics revealed increased STMN1(S38) phosphorylation as part of ERBB4 signaling. A pathway tool has been developed to visualize and compare different omics datasets per patient and showed potential therapeutic drugs, such as abobotulinumtoxinA (synaptogenesis) and afatinib (ERBB4 signaling). Afatinib is currently in clinical trials for GBM.
    Conclusions: A large variation on all omics levels exists between and within GBM patients. Therefore, it will be rather unlikely to find a drug treatment that would fit all patients. Instead, a multiomics approach offers the potential to identify affected pathways on the individual patient level and select treatment options.
    Language English
    Publishing date 2020-07-04
    Publishing country England
    Document type Journal Article
    ZDB-ID 3009682-0
    ISSN 2632-2498 ; 2632-2498
    ISSN (online) 2632-2498
    ISSN 2632-2498
    DOI 10.1093/noajnl/vdaa083
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: The GB4.0 Platform, an All-In-One Tool for CRISPR/Cas-Based Multiplex Genome Engineering in Plants.

    Vazquez-Vilar, Marta / Garcia-Carpintero, Víctor / Selma, Sara / Bernabé-Orts, Joan M / Sanchez-Vicente, Javier / Salazar-Sarasua, Blanca / Ressa, Arianna / de Paola, Carmine / Ajenjo, María / Quintela, Jose Carlos / Fernández-Del-Carmen, Asun / Granell, Antonio / Orzáez, Diego

    Frontiers in plant science

    2021  Volume 12, Page(s) 689937

    Abstract: CRISPR/Cas ability to target several loci simultaneously (multiplexing) is a game-changer in plant breeding. Multiplexing not only accelerates trait pyramiding but also can unveil traits hidden by functional redundancy. Furthermore, multiplexing enhances ...

    Abstract CRISPR/Cas ability to target several loci simultaneously (multiplexing) is a game-changer in plant breeding. Multiplexing not only accelerates trait pyramiding but also can unveil traits hidden by functional redundancy. Furthermore, multiplexing enhances dCas-based programmable gene expression and enables cascade-like gene regulation. However, the design and assembly of multiplex constructs comprising tandemly arrayed guide RNAs (gRNAs) requires scarless cloning and is still troublesome due to the presence of repetitive sequences, thus hampering a more widespread use. Here we present a comprehensive extension of the software-assisted cloning platform GoldenBraid (GB), in which, on top of its multigene cloning software, we integrate new tools for the Type IIS-based easy and rapid assembly of up to six tandemly-arrayed gRNAs with both Cas9 and Cas12a, using the gRNA-tRNA-spaced and the crRNA unspaced approaches, respectively. As stress tests for the new tools, we assembled and used for Agrobacterium-mediated stable transformation a 17 Cas9-gRNAs construct targeting a subset of the Squamosa-Promoter Binding Protein-Like (SPL) gene family in
    Language English
    Publishing date 2021-07-01
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2613694-6
    ISSN 1664-462X
    ISSN 1664-462X
    DOI 10.3389/fpls.2021.689937
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Tumour kinome re-wiring governs resistance to palbociclib in oestrogen receptor positive breast cancers, highlighting new therapeutic modalities.

    Pancholi, Sunil / Ribas, Ricardo / Simigdala, Nikiana / Schuster, Eugene / Nikitorowicz-Buniak, Joanna / Ressa, Anna / Gao, Qiong / Leal, Mariana Ferreira / Bhamra, Amandeep / Thornhill, Allan / Morisset, Ludivine / Montaudon, Elodie / Sourd, Laura / Fitzpatrick, Martin / Altelaar, Maarten / Johnston, Stephen R / Marangoni, Elisabetta / Dowsett, Mitch / Martin, Lesley-Ann

    Oncogene

    2020  Volume 39, Issue 25, Page(s) 4781–4797

    Abstract: Combination of CDK4/6 inhibitors and endocrine therapy improves clinical outcome in advanced oestrogen receptor (ER)-positive breast cancer, however relapse is inevitable. Here, we show in model systems that other than loss of RB1 few gene-copy number ( ... ...

    Abstract Combination of CDK4/6 inhibitors and endocrine therapy improves clinical outcome in advanced oestrogen receptor (ER)-positive breast cancer, however relapse is inevitable. Here, we show in model systems that other than loss of RB1 few gene-copy number (CN) alterations are associated with irreversible-resistance to endocrine therapy and subsequent secondary resistance to palbociclib. Resistance to palbociclib occurred as a result of tumour cell re-wiring leading to increased expression of EGFR, MAPK, CDK4, CDK2, CDK7, CCNE1 and CCNE2. Resistance altered the ER genome wide-binding pattern, leading to decreased expression of 'classical' oestrogen-regulated genes and was accompanied by reduced sensitivity to fulvestrant and tamoxifen. Persistent CDK4 blockade decreased phosphorylation of tuberous sclerosis complex 2 (TSC2) enhancing EGFR signalling, leading to the re-wiring of ER. Kinome-knockdown confirmed dependency on ERBB-signalling and G2/M-checkpoint proteins such as WEE1, together with the cell cycle master regulator, CDK7. Noteworthy, sensitivity to CDK7 inhibition was associated with loss of ER and RB1 CN. Overall, we show that resistance to CDK4/6 inhibitors is dependent on kinase re-wiring and the redeployment of signalling cascades previously associated with endocrine resistance and highlights new therapeutic networks that can be exploited upon relapse after CDK4/6 inhibition.
    MeSH term(s) Animals ; Antineoplastic Combined Chemotherapy Protocols/pharmacology ; Breast Neoplasms/genetics ; Breast Neoplasms/metabolism ; Breast Neoplasms/therapy ; Cell Line, Tumor ; Cyclin-Dependent Kinase 4/genetics ; Cyclin-Dependent Kinase 4/metabolism ; Cyclin-Dependent Kinase 6/genetics ; Cyclin-Dependent Kinase 6/metabolism ; Drug Resistance, Neoplasm/drug effects ; Drug Resistance, Neoplasm/genetics ; Female ; Fulvestrant/administration & dosage ; Humans ; MCF-7 Cells ; Mice, Inbred BALB C ; Mice, Nude ; Piperazines/pharmacology ; Protein Kinase Inhibitors/pharmacology ; Pyridines/pharmacology ; RNA Interference ; Receptors, Estrogen/genetics ; Receptors, Estrogen/metabolism ; Retinoblastoma Protein/genetics ; Retinoblastoma Protein/metabolism ; Tamoxifen/administration & dosage ; Xenograft Model Antitumor Assays/methods
    Chemical Substances Piperazines ; Protein Kinase Inhibitors ; Pyridines ; Receptors, Estrogen ; Retinoblastoma Protein ; Tamoxifen (094ZI81Y45) ; Fulvestrant (22X328QOC4) ; Cyclin-Dependent Kinase 4 (EC 2.7.11.22) ; Cyclin-Dependent Kinase 6 (EC 2.7.11.22) ; palbociclib (G9ZF61LE7G)
    Language English
    Publishing date 2020-04-19
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 639046-8
    ISSN 1476-5594 ; 0950-9232
    ISSN (online) 1476-5594
    ISSN 0950-9232
    DOI 10.1038/s41388-020-1284-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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