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  1. Article: Inter and intra-tumor heterogeneity of paediatric type diffuse high-grade gliomas revealed by single-cell mass cytometry.

    Petrilli, Lucia Lisa / Fuoco, Claudia / Palma, Alessandro / Pasquini, Luca / Pericoli, Giulia / Grabovska, Yura / Mackay, Alan / Rossi, Sabrina / Carcaboso, Angel M / Carai, Andrea / Mastronuzzi, Angela / Jones, Chris / Cesareni, Gianni / Locatelli, Franco / Vinci, Maria

    Frontiers in oncology

    2022  Volume 12, Page(s) 1016343

    Abstract: Paediatric-type diffuse high-grade gliomas (PDHGG) are aggressive tumors affecting children and young adults, with no effective treatment. These highly heterogeneous malignancies arise in different sites of the Central Nervous System (CNS), carrying ... ...

    Abstract Paediatric-type diffuse high-grade gliomas (PDHGG) are aggressive tumors affecting children and young adults, with no effective treatment. These highly heterogeneous malignancies arise in different sites of the Central Nervous System (CNS), carrying distinctive molecular alterations and clinical outcomes (inter-tumor heterogeneity). Moreover, deep cellular and molecular profiling studies highlighted the coexistence of genetically and phenotypically different subpopulations within the same tumor mass (intra-tumor heterogeneity). Despite the recent advances made in the field, the marked heterogeneity of PDHGGs still impedes the development of effective targeted therapies and the identification of suitable biomarkers. In order to fill the existing gap, we used mass cytometry to dissect PDHGG inter- and intra-heterogeneity. This is one of the most advanced technologies of the "-omics" era that, using antibodies conjugated to heavy metals, allows the simultaneous measurement of more than 40 markers at single-cell level. To this end, we analyzed eight PDHGG patient-derived cell lines from different locational and molecular subgroups. By using a panel of 15 antibodies, directly conjugated to metals or specifically customized to detect important histone variants, significant differences were highlighted in the expression of the considered antigens. The single-cell multiparametric approach realized has deepened our understanding of PDHGG, confirming a high degree of intra- and inter-tumoral heterogeneity and identifying some antigens that could represent useful biomarkers for the specific PDHGG locational or molecular subgroups.
    Language English
    Publishing date 2022-12-08
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2649216-7
    ISSN 2234-943X
    ISSN 2234-943X
    DOI 10.3389/fonc.2022.1016343
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: J D Bernal (1901-1971) in perspective.

    Mackay, Alan L

    Journal of biosciences

    2003  Volume 28, Issue 5, Page(s) 539–546

    MeSH term(s) Crystallography, X-Ray/history ; History, 20th Century ; Humans ; Information Management ; Molecular Biology/history ; Politics ; Social Sciences ; USSR ; United Kingdom ; Warfare
    Language English
    Publishing date 2003-08-15
    Publishing country India
    Document type Biography ; Historical Article ; Portrait
    ZDB-ID 756157-x
    ISSN 0250-5991
    ISSN 0250-5991
    DOI 10.1007/bf02703329
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: The Long Non-Coding RNA H19 Drives the Proliferation of Diffuse Intrinsic Pontine Glioma with H3K27 Mutation.

    Roig-Carles, David / Jackson, Holly / Loveson, Katie F / Mackay, Alan / Mather, Rebecca L / Waters, Ella / Manzo, Massimiliano / Alborelli, Ilaria / Golding, Jon / Jones, Chris / Fillmore, Helen L / Crea, Francesco

    International journal of molecular sciences

    2021  Volume 22, Issue 17

    Abstract: Diffuse intrinsic pontine glioma (DIPG) is an incurable paediatric malignancy. Identifying the molecular drivers of DIPG progression is of the utmost importance. Long non-coding RNAs (lncRNAs) represent a large family of disease- and tissue-specific ... ...

    Abstract Diffuse intrinsic pontine glioma (DIPG) is an incurable paediatric malignancy. Identifying the molecular drivers of DIPG progression is of the utmost importance. Long non-coding RNAs (lncRNAs) represent a large family of disease- and tissue-specific transcripts, whose functions have not yet been elucidated in DIPG. Herein, we studied the oncogenic role of the development-associated
    MeSH term(s) Brain Stem Neoplasms/genetics ; Brain Stem Neoplasms/metabolism ; Brain Stem Neoplasms/pathology ; Cell Proliferation ; Cells, Cultured ; Gene Expression Regulation, Neoplastic ; Glioma/genetics ; Glioma/metabolism ; Glioma/pathology ; Histones/metabolism ; Humans ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Mutation ; RNA, Long Noncoding/genetics ; RNA, Long Noncoding/metabolism
    Chemical Substances H19 long non-coding RNA ; Histones ; MicroRNAs ; RNA, Long Noncoding ; mirnlet7 microRNA, human
    Language English
    Publishing date 2021-08-25
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms22179165
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Inhibition of exosome biogenesis affects cell motility in heterogeneous sub-populations of paediatric-type diffuse high-grade gliomas.

    Pericoli, Giulia / Galardi, Angela / Paolini, Alessandro / Petrilli, Lucia Lisa / Pepe, Gerardo / Palma, Alessandro / Colletti, Marta / Ferretti, Roberta / Giorda, Ezio / Levi Mortera, Stefano / Burford, Anna / Carai, Andrea / Mastronuzzi, Angela / Mackay, Alan / Putignani, Lorenza / Jones, Chris / Pascucci, Luisa / Peinado, Hector / Helmer-Citterich, Manuela /
    de Billy, Emmanuel / Masotti, Andrea / Locatelli, Franco / Di Giannatale, Angela / Vinci, Maria

    Cell & bioscience

    2023  Volume 13, Issue 1, Page(s) 207

    Abstract: Background: Paediatric-type diffuse High-Grade Gliomas (PDHGG) are highly heterogeneous tumours which include distinct cell sub-populations co-existing within the same tumour mass. We have previously shown that primary patient-derived and optical ... ...

    Abstract Background: Paediatric-type diffuse High-Grade Gliomas (PDHGG) are highly heterogeneous tumours which include distinct cell sub-populations co-existing within the same tumour mass. We have previously shown that primary patient-derived and optical barcoded single-cell-derived clones function as interconnected networks. Here, we investigated the role of exosomes as a route for inter-clonal communication mediating PDHGG migration and invasion.
    Results: A comprehensive characterisation of seven optical barcoded single-cell-derived clones obtained from two patient-derived cell lines was performed. These analyses highlighted extensive intra-tumour heterogeneity in terms of genetic and transcriptional profiles between clones as well as marked phenotypic differences including distinctive motility patterns. Live single-cell tracking analysis of 3D migration and invasion assays showed that the single-cell-derived clones display a higher speed and longer travelled distance when in co-culture compared to mono-culture conditions. To determine the role of exosomes in PDHGG inter-clonal cross-talks, we isolated exosomes released by different clones and characterised them in terms of marker expression, size and concentration. We demonstrated that exosomes are actively internalized by the cells and that the inhibition of their biogenesis, using the phospholipase inhibitor GW4689, significantly reduced the cell motility in mono-culture and more prominently when the cells from the clones were in co-culture. Analysis of the exosomal miRNAs, performed with a miRNome PCR panel, identified clone-specific miRNAs and a set of miRNA target genes involved in the regulation of cell motility/invasion/migration. These genes were found differentially expressed in co-culture versus mono-culture conditions and their expression levels were significantly modulated upon inhibition of exosome biogenesis.
    Conclusions: In conclusion, our study highlights for the first time a key role for exosomes in the inter-clonal communication in PDHGG and suggests that interfering with the exosome biogenesis pathway may be a valuable strategy to inhibit cell motility and dissemination for these specific diseases.
    Language English
    Publishing date 2023-11-13
    Publishing country England
    Document type Journal Article
    ZDB-ID 2593367-X
    ISSN 2045-3701
    ISSN 2045-3701
    DOI 10.1186/s13578-023-01166-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Cooperativity between H3.3K27M and PDGFRA poses multiple therapeutic vulnerabilities in human iPSC-derived diffuse midline glioma avatars.

    Skinner, Kasey R / Koga, Tomoyuki / Miki, Shunichiro / Gruener, Robert F / Grigore, Florina-Nicoleta / Torii, Emma H / Seelig, Davis M / Suzuki, Yuta / Kawauchi, Daisuke / Lin, Benjamin / Malicki, Denise M / Chen, Clark C / Benveniste, Etty N / Patel, Rakesh P / McFarland, Braden C / Huang, R Stephanie / Jones, Chris / Mackay, Alan / Miller, C Ryan /
    Furnari, Frank B

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Diffuse midline glioma (DMG) is a leading cause of brain tumor death in children. In addition to hallmark H3.3K27M mutations, significant subsets also harbor alterations of other genes, such ... ...

    Abstract Diffuse midline glioma (DMG) is a leading cause of brain tumor death in children. In addition to hallmark H3.3K27M mutations, significant subsets also harbor alterations of other genes, such as
    Language English
    Publishing date 2023-02-24
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.02.24.528982
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Beyond crystals: the dialectic of materials and information.

    Cartwright, Julyan H E / Mackay, Alan L

    Philosophical transactions. Series A, Mathematical, physical, and engineering sciences

    2012  Volume 370, Issue 1969, Page(s) 2807–2822

    Abstract: We argue for a convergence of crystallography, materials science and biology, that will come about through asking materials questions about biology and biological questions about materials, illuminated by considerations of information. The complex ... ...

    Abstract We argue for a convergence of crystallography, materials science and biology, that will come about through asking materials questions about biology and biological questions about materials, illuminated by considerations of information. The complex structures now being studied in biology and produced in nanotechnology have outstripped the framework of classical crystallography, and a variety of organizing concepts are now taking shape into a more modern and dynamic science of structure, form and function. Absolute stability and equilibrium are replaced by metastable structures existing in a flux of energy-carrying information and moving within an energy landscape of complex topology. Structures give place to processes and processes to systems. The fundamental level is that of atoms. As smaller and smaller groups of atoms are used for their physical properties, quantum effects become important; already we see quantum computation taking shape. Concepts move towards those in life with the emergence of specifically informational structures. We now see the possibility of the artificial construction of a synthetic living system, different from biological life, but having many or all of the same properties. Interactions are essentially nonlinear and collective. Structures begin to have an evolutionary history with episodes of symbiosis. Underlying all the structures are constraints of time and space. Through hierarchization, a more general principle than the periodicity of crystals, structures may be found within structures on different scales. We must integrate unifying concepts from dynamical systems and information theory to form a coherent language and science of shape and structure beyond crystals. To this end, we discuss the idea of categorizing structures based on information according to the algorithmic complexity of their assembly.
    MeSH term(s) Biopolymers/chemistry ; Crystallization/methods ; Models, Biological ; Models, Chemical ; Nanostructures/chemistry ; Nanostructures/ultrastructure
    Chemical Substances Biopolymers
    Language English
    Publishing date 2012-05-21
    Publishing country England
    Document type Introductory Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 208381-4
    ISSN 1471-2962 ; 1364-503X ; 0080-4614 ; 0264-3820 ; 0264-3952
    ISSN (online) 1471-2962
    ISSN 1364-503X ; 0080-4614 ; 0264-3820 ; 0264-3952
    DOI 10.1098/rsta.2012.0106
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Discussion of "Intangibles and research

    Mackay, Alan / Stark, Andrew W

    Accounting and business research : a research quarterly publ. by the Inst. of Chartered Accountants in England and Wales Vol. 38, No. 3 , p. 287-289

    an overview with a specific focus on the UK"

    2008  Volume 38, Issue 3, Page(s) 287–289

    Author's details Alan Mackay
    Language English
    Publisher Inst.
    Publishing place London
    Document type Article
    ZDB-ID 83112-8
    Database ECONomics Information System

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  8. Article: J D Bernal (1901–1971) in perspective

    Mackay, Alan L

    Journal of biosciences. 2003 Sept., v. 28, no. 5

    2003  

    Abstract: CONCLUSION: We must conclude that the sub-title of Bernal’s “The Social Function of Science” — “What science does: what science could do” is still the relevant challenge and indicates Bernal’s chief contribution, besides the foundation of molecular ... ...

    Abstract CONCLUSION: We must conclude that the sub-title of Bernal’s “The Social Function of Science” — “What science does: what science could do” is still the relevant challenge and indicates Bernal’s chief contribution, besides the foundation of molecular biology to our civilization. It is manifest that resources spent on armaments are a monstrous pathological symptom of our social structure. The ancient problem of “what is property” and what may be “owned” and by whom or by what organs of society is awakening.
    Keywords aggregation behavior ; molecular biology ; social behavior ; social structure
    Language English
    Dates of publication 2003-09
    Size p. 539-546.
    Publishing place Springer India
    Document type Article
    ZDB-ID 756157-x
    ISSN 0973-7138 ; 0250-5991
    ISSN (online) 0973-7138
    ISSN 0250-5991
    DOI 10.1007/BF02703329
    Database NAL-Catalogue (AGRICOLA)

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  9. Article ; Online: MRI and Molecular Characterization of Pediatric High-Grade Midline Thalamic Gliomas: The HERBY Phase II Trial.

    Rodriguez, Daniel / Calmon, Raphael / Aliaga, Esther Sanchez / Warren, Daniel / Warmuth-Metz, Monika / Jones, Chris / Mackay, Alan / Varlet, Pascale / Le Deley, Marie-Cécile / Hargrave, Darren / Cañete, Adela / Massimino, Maura / Azizi, Amedeo A / Saran, Frank / Zahlmann, Gudrun / Garcia, Josep / Vassal, Gilles / Grill, Jacques / Peet, Andrew /
    Dineen, Robert A / Morgan, Paul S / Jaspan, Timothy

    Radiology

    2022  Volume 304, Issue 1, Page(s) 174–182

    Abstract: Background Diffuse midline gliomas (DMG) are characterized by a high incidence ... ...

    Abstract Background Diffuse midline gliomas (DMG) are characterized by a high incidence of
    MeSH term(s) Brain Neoplasms/diagnostic imaging ; Brain Neoplasms/genetics ; Brain Neoplasms/pathology ; Child ; Female ; Glioma/diagnostic imaging ; Glioma/genetics ; Glioma/pathology ; Histones/genetics ; Humans ; Magnetic Resonance Imaging ; Mutation/genetics ; Prospective Studies ; Thalamus/pathology
    Chemical Substances Histones
    Language English
    Publishing date 2022-04-12
    Publishing country United States
    Document type Clinical Trial, Phase II ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80324-8
    ISSN 1527-1315 ; 0033-8419
    ISSN (online) 1527-1315
    ISSN 0033-8419
    DOI 10.1148/radiol.211464
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: Targeted therapy for pediatric diffuse intrinsic pontine glioma: a single-center experience.

    Del Baldo, Giada / Carai, Andrea / Abbas, Rachid / Cacchione, Antonella / Vinci, Mara / Di Ruscio, Valentina / Colafati, Giovanna Stefania / Rossi, Sabrina / Diomedi Camassei, Francesca / Maestro, Nicola / Temelso, Sara / Pericoli, Giulia / De Billy, Emmanuel / Giovannoni, Isabella / Carboni, Alessia / Rinelli, Martina / Agolini, Emanuele / Mackay, Alan / Jones, Chris /
    Chiesa, Silvia / Balducci, Mario / Locatelli, Franco / Mastronuzzi, Angela

    Therapeutic advances in medical oncology

    2022  Volume 14, Page(s) 17588359221113693

    Abstract: Background: Diffuse intrinsic pontine glioma (DIPG) is a fatal disease with a median overall survival (OS) of less than 12 months after diagnosis. Radiotherapy (RT) still remains the mainstay treatment. Several other therapeutic strategies have been ... ...

    Abstract Background: Diffuse intrinsic pontine glioma (DIPG) is a fatal disease with a median overall survival (OS) of less than 12 months after diagnosis. Radiotherapy (RT) still remains the mainstay treatment. Several other therapeutic strategies have been attempted in the last years without a significant effect on OS. Although radiological imaging is the gold standard for DIPG diagnosis, the urgent need to improve the survival has led to the reconsideration of biopsy with the aim to better understand the molecular profile of DIPG and support personalized treatment.
    Methods: In this study, we present a single-center experience in treating DIPG patients at disease progression combining targeted therapies with standard of care. Biopsy was proposed to all patients at diagnosis or disease progression. First-line treatment included RT and nimotuzumab/vinorelbine or temozolomide. Immunohistochemistry-targeted research included study of mTOR/p-mTOR pathway and
    Results: Based on the molecular profile, targeted therapy was administered in 9 out of 25 patients, while the remaining 16 patients were treated with standard of care. Personalized treatment included inhibition of the PI3K/AKT/mTOR pathway (5/9), PI3K/AKT/mTOR pathway and
    Conclusion: Despite the small simple size of our study, our data suggest a prognostic advantage and a safe profile of targeted therapies in DIPG patients, and we strongly advocate to reconsider the role of biopsy for these patients.
    Language English
    Publishing date 2022-09-06
    Publishing country England
    Document type Journal Article
    ZDB-ID 2503443-1
    ISSN 1758-8359 ; 1758-8340
    ISSN (online) 1758-8359
    ISSN 1758-8340
    DOI 10.1177/17588359221113693
    Database MEDical Literature Analysis and Retrieval System OnLINE

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