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  1. Article ; Online: A paradigm shift in how we treat pediatric low-grade glioma-Targeting the molecular drivers.

    Ziegler, David S / Lehmann, Rebecca / Eisenstat, David D

    Neuro-oncology

    2024  Volume 26, Issue 4, Page(s) 593–595

    MeSH term(s) Child ; Humans ; Glioma/genetics ; Glioma/therapy ; Brain Neoplasms/genetics ; Brain Neoplasms/therapy
    Language English
    Publishing date 2024-01-19
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2028601-6
    ISSN 1523-5866 ; 1522-8517
    ISSN (online) 1523-5866
    ISSN 1522-8517
    DOI 10.1093/neuonc/noae008
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 5307: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (2.OG)
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  2. Article ; Online: Development of Orthotopic Patient-Derived Xenograft Models of Pediatric Intracranial Tumors.

    Upton, Dannielle H / Ziegler, David S / Tsoli, Maria

    Methods in molecular biology (Clifton, N.J.)

    2024  Volume 2806, Page(s) 75–90

    Abstract: The development of clinically relevant and reliable models of central nervous system tumors has been instrumental in advancing the field of Neuro-Oncology. The orthotopic intracranial injection is widely used to study the growth, invasion, and spread of ... ...

    Abstract The development of clinically relevant and reliable models of central nervous system tumors has been instrumental in advancing the field of Neuro-Oncology. The orthotopic intracranial injection is widely used to study the growth, invasion, and spread of tumors in a controlled environment. Orthotopic models are performed to examine tumor cells isolated from a specific region in a patient in the same site or location in an animal model. Orthotopic brain tumor models are also utilized for preclinical testing of therapeutics as they closely recapitulate the behavior of such cancer and the brain environment of patients. Below, we describe our experiences in the development of murine models of pediatric brain tumors including diffuse midline glioma (DMG), glioblastoma (GBM), and medulloblastoma. The method provides an overview of intracranial stereotactic injections in mice.
    MeSH term(s) Animals ; Humans ; Mice ; Brain Neoplasms/pathology ; Disease Models, Animal ; Child ; Xenograft Model Antitumor Assays/methods ; Medulloblastoma/pathology ; Glioma/pathology ; Glioblastoma/pathology ; Heterografts
    Language English
    Publishing date 2024-04-27
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-3858-3_7
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Never say never.

    Ziegler, David S

    Journal of clinical oncology : official journal of the American Society of Clinical Oncology

    2015  Volume 33, Issue 5, Page(s) 518–520

    MeSH term(s) Communication ; Death ; Empathy ; Fear ; Hope ; Humans ; Neoplasms ; Parents/psychology ; Physician-Patient Relations ; Predictive Value of Tests ; Prognosis ; Statistics as Topic ; Truth Disclosure ; Uncertainty
    Language English
    Publishing date 2015-02-10
    Publishing country United States
    Document type Journal Article
    ZDB-ID 604914-x
    ISSN 1527-7755 ; 0732-183X
    ISSN (online) 1527-7755
    ISSN 0732-183X
    DOI 10.1200/JCO.2014.58.7717
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1847: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (1.OG)
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    Zs.MO 650: Show issues

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  4. Article ; Online: From cells to organoids: The evolution of blood-brain barrier technology for modelling drug delivery in brain cancer.

    Gonzales-Aloy, Estrella / Ahmed-Cox, Aria / Tsoli, Maria / Ziegler, David S / Kavallaris, Maria

    Advanced drug delivery reviews

    2023  Volume 196, Page(s) 114777

    Abstract: Brain cancer remains the deadliest cancer. The blood-brain barrier (BBB) is impenetrable to most drugs and is a complex 3D network of multiple cell types including endothelial cells, astrocytes, and pericytes. In brain cancers, the BBB becomes disrupted ... ...

    Abstract Brain cancer remains the deadliest cancer. The blood-brain barrier (BBB) is impenetrable to most drugs and is a complex 3D network of multiple cell types including endothelial cells, astrocytes, and pericytes. In brain cancers, the BBB becomes disrupted during tumor progression and forms the blood-brain tumor barrier (BBTB). To advance therapeutic development, there is a critical need for physiologically relevant BBB in vitro models. 3D cell systems are emerging as valuable preclinical models to accelerate discoveries for diseases. Given the versatility and capability of 3D cell models, their potential for modelling the BBB and BBTB is reviewed. Technological advances of BBB models and challenges of in vitro modelling the BBTB, and application of these models as tools for assessing therapeutics and nano drug delivery, are discussed. Quantitative, in vitro BBB models that are predictive of effective brain cancer therapies will be invaluable for accelerating advancing new treatments to the clinic.
    MeSH term(s) Humans ; Blood-Brain Barrier/metabolism ; Endothelial Cells ; Brain Neoplasms/pathology ; Brain/pathology ; Organoids/pathology
    Language English
    Publishing date 2023-03-16
    Publishing country Netherlands
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 639113-8
    ISSN 1872-8294 ; 0169-409X
    ISSN (online) 1872-8294
    ISSN 0169-409X
    DOI 10.1016/j.addr.2023.114777
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2241: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (1.OG)
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  5. Article ; Online: Preclinical evaluation of protein synthesis inhibitor omacetaxine in pediatric brainstem gliomas.

    Chen, Yongjuan / Khan, Aaminah / Katsinas, Christopher / Michniewicz, Filip / Goldberg, Jessie / Franshaw, Laura / Tsoli, Maria / Ziegler, David S

    Neuro-oncology advances

    2024  Volume 6, Issue 1, Page(s) vdae029

    Abstract: Background: Diffuse intrinsic pontine gliomas (DIPGs) pose a significant challenge as a highly aggressive and currently incurable form of pediatric brain cancer, necessitating the development of novel therapeutic strategies. Omacetaxine, an FDA-approved ...

    Abstract Background: Diffuse intrinsic pontine gliomas (DIPGs) pose a significant challenge as a highly aggressive and currently incurable form of pediatric brain cancer, necessitating the development of novel therapeutic strategies. Omacetaxine, an FDA-approved protein synthesis inhibitor for treating certain hematological malignancies, was investigated for its potential antitumor effects against preclinical DIPG models.
    Methods: We employed primary DIPG cultures to study omacetaxine's cytotoxicity and its impact on colony formation. Annexin V staining and flow cytometry assessed apoptosis. Wound healing assays evaluated migration, while western blotting determined inhibition of oncogenic proteins. We tested omacetaxine's therapeutic efficacy in an orthotopic DIPG model and assessed brain penetration using mass spectrometry.
    Results: We found a pronounced cytotoxic activity of omacetaxine against DIPG neurospheres, with low IC
    Conclusions: Despite these promising in vitro effects, omacetaxine's efficacy in an orthotopic DIPG model was limited due to inadequate penetration across the blood-brain barrier. As such, further research and advancements are crucial to improve the drug's brain penetration, thus enhancing its overall therapeutic potential.
    Language English
    Publishing date 2024-03-16
    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/vdae029
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  6. Article ; Online: Challenges and opportunities to penetrate the blood-brain barrier for brain cancer therapy.

    Upton, Dannielle H / Ung, Caitlin / George, Sandra M / Tsoli, Maria / Kavallaris, Maria / Ziegler, David S

    Theranostics

    2022  Volume 12, Issue 10, Page(s) 4734–4752

    Abstract: Despite significant advances in research, the prognosis for both primary and secondary brain cancers remains poor. The blood-brain barrier (BBB) is a complex and unique semi-permeable membrane that serves as a protective structure to maintain homeostasis ...

    Abstract Despite significant advances in research, the prognosis for both primary and secondary brain cancers remains poor. The blood-brain barrier (BBB) is a complex and unique semi-permeable membrane that serves as a protective structure to maintain homeostasis within the brain. However, it presents a significant challenge for the delivery of therapeutics into the brain and tumor. Some brain tumors are known to compromise BBB integrity, producing a highly heterogeneous vasculature known as the blood-tumor-barrier (BTB). Identifying strategies to bypass these obstacles to improve the penetrability of anticancer therapeutics has been the focus of research in this area. In this review, we discuss the strategies that have been investigated to evade or alter the cellular and molecular barriers of both the BBB and the BTB and detail the methods currently under preclinical or clinical investigation, including molecular, biological, and physical processes to overcome the BBB or BTB. Increased understanding of the BBB and BTB and the current methods of overcoming these barriers will enable the development of new and more effective treatment strategies for brain tumors.
    MeSH term(s) Biological Transport ; Blood-Brain Barrier/pathology ; Brain/pathology ; Brain Neoplasms/pathology ; Drug Delivery Systems ; Humans
    Language English
    Publishing date 2022-06-06
    Publishing country Australia
    Document type Journal Article ; Review
    ZDB-ID 2592097-2
    ISSN 1838-7640 ; 1838-7640
    ISSN (online) 1838-7640
    ISSN 1838-7640
    DOI 10.7150/thno.69682
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  7. Article ; Online: Ganglioglioma Arising From Desmoplastic Medulloblastoma: A Case Report and Review of Literature.

    Valvi, Santosh / Ziegler, David S

    Pediatrics

    2017  Volume 139, Issue 3

    Abstract: We describe a case of medulloblastoma maturating into ganglioglioma during therapy. A 10-month-old boy was diagnosed with a desmoplastic medulloblastoma and was treated with gross total resection followed by induction chemotherapy. A recurrence in the ... ...

    Abstract We describe a case of medulloblastoma maturating into ganglioglioma during therapy. A 10-month-old boy was diagnosed with a desmoplastic medulloblastoma and was treated with gross total resection followed by induction chemotherapy. A recurrence in the tumor bed during therapy was managed with focal radiation therapy and consolidation chemotherapy. After further progression, the recurrent tumor was resected completely. The histopathology revealed a benign ganglioglioma with no residual medulloblastoma. This case raises the possibility that a malignant medulloblastoma can differentiate into a benign tumor and suggests that differentiation therapy may have value in the treatment of medulloblastoma.
    MeSH term(s) Cerebellar Neoplasms/pathology ; Child ; Ganglioglioma/pathology ; Humans ; Infratentorial Neoplasms/pathology ; Male ; Medulloblastoma/pathology ; Neoplasms, Second Primary/pathology
    Language English
    Publishing date 2017-03
    Publishing country United States
    Document type Case Reports ; Journal Article ; Review
    ZDB-ID 207677-9
    ISSN 1098-4275 ; 0031-4005
    ISSN (online) 1098-4275
    ISSN 0031-4005
    DOI 10.1542/peds.2016-1403
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    Um IV Zs.131: Show issues Location:
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    ab Jg. 2022: Lesesaal (EG)
    Zs.MO 357: Show issues

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  8. Article ; Online: Microtubule-Targeting Combined with HDAC Inhibition Is a Novel Therapeutic Strategy for Diffuse Intrinsic Pontine Gliomas.

    Ehteda, Anahid / Khan, Aaminah / Rajakumar, Gayathiri / Vanniasinghe, Anne S / Gopalakrishnan, Anjana / Liu, Jie / Tsoli, Maria / Ziegler, David S

    Molecular cancer therapeutics

    2023  Volume 22, Issue 12, Page(s) 1413–1421

    Abstract: Diffuse intrinsic pontine gliomas (DIPG) are an incurable childhood brain cancer for which novel treatments are needed. DIPGs are characterized by a mutation in the H3 histone (H3K27M), resulting in loss of H3K27 methylation and global gene dysregulation. ...

    Abstract Diffuse intrinsic pontine gliomas (DIPG) are an incurable childhood brain cancer for which novel treatments are needed. DIPGs are characterized by a mutation in the H3 histone (H3K27M), resulting in loss of H3K27 methylation and global gene dysregulation. TRX-E-009-1 is a novel anticancer agent with preclinical activity demonstrated against a range of cancers. We examined the antitumor activity of TRX-E-009-1 against DIPG neurosphere cultures and observed tumor-specific activity with IC50s ranging from 20 to 100 nmol/L, whereas no activity was observed against normal human astrocyte cells. TRX-E-009-1 exerted its anti-proliferative effect through the induction of apoptotic pathways, with marked increases in cleaved caspase 3 and cleaved PARP levels, while also restoring histone H3K27me3 methylation. Co-administration of TRX-E-009-1 and the histone deacetylase (HDAC) inhibitor SAHA extended survival in DIPG orthotopic animal models. This antitumor effect was further enhanced with irradiation. Our findings indicate that TRX-E-009-1, combined with HDAC inhibition, represents a novel, potent therapy for children with DIPG.
    MeSH term(s) Child ; Animals ; Humans ; Histones/metabolism ; Diffuse Intrinsic Pontine Glioma/drug therapy ; Diffuse Intrinsic Pontine Glioma/genetics ; Diffuse Intrinsic Pontine Glioma/pathology ; Brain Stem Neoplasms/drug therapy ; Brain Stem Neoplasms/genetics ; Brain Stem Neoplasms/pathology ; Glioma/drug therapy ; Glioma/genetics ; Glioma/metabolism ; Histone Deacetylases/genetics ; Cell Line, Tumor ; Mutation ; Microtubules/metabolism
    Chemical Substances Histones ; Histone Deacetylases (EC 3.5.1.98)
    Language English
    Publishing date 2023-09-03
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2063563-1
    ISSN 1538-8514 ; 1535-7163
    ISSN (online) 1538-8514
    ISSN 1535-7163
    DOI 10.1158/1535-7163.MCT-23-0179
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 5750: Show issues Location:
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  9. Article ; Online: Communicating with families of young people with hard-to-treat cancers: Healthcare professionals' perspectives on challenges, skills, and training.

    Kelada, Lauren / Robertson, Eden G / McKay, Skye / McGill, Brittany C / Daly, Rebecca / Mazariego, Carolyn / Taylor, Natalie / Tyedmers, Elijah / Armitage, Nicole / Evans, Holly E / Wakefield, Claire E / Ziegler, David S

    Palliative & supportive care

    2024  , Page(s) 1–7

    Abstract: Objectives: Hard-to-treat childhood cancers are those where standard treatment options do not exist and the prognosis is poor. Healthcare professionals (HCPs) are responsible for communicating with families about prognosis and complex experimental ... ...

    Abstract Objectives: Hard-to-treat childhood cancers are those where standard treatment options do not exist and the prognosis is poor. Healthcare professionals (HCPs) are responsible for communicating with families about prognosis and complex experimental treatments. We aimed to identify HCPs' key challenges and skills required when communicating with families about hard-to-treat cancers and their perceptions of communication-related training.
    Methods: We interviewed Australian HCPs who had direct responsibilities in managing children/adolescents with hard-to-treat cancer within the past 24 months. Interviews were analyzed using qualitative content analysis.
    Results: We interviewed 10 oncologists, 7 nurses, and 3 social workers. HCPs identified several challenges for communication with families including: balancing information provision while maintaining realistic hope; managing their own uncertainty; and nurses and social workers being underutilized during conversations with families, despite widespread preferences for multidisciplinary teamwork. HCPs perceived that making themselves available to families, empowering them to ask questions, and repeating information helped to establish and maintain trusting relationships with families. Half the HCPs reported receiving no formal training for communicating prognosis and treatment options with families of children with hard-to-treat cancers. Nurses, social workers, and less experienced oncologists supported the development of communication training resources, more so than more experienced oncologists.
    Significance of results: Resources are needed which support HCPs to communicate with families of children with hard-to-treat cancers. Such resources may be particularly beneficial for junior oncologists and other HCPs during their training, and they should aim to prepare them for common challenges and foster greater multidisciplinary collaboration.
    Language English
    Publishing date 2024-01-24
    Publishing country England
    Document type Journal Article
    ZDB-ID 2454009-2
    ISSN 1478-9523 ; 1478-9515
    ISSN (online) 1478-9523
    ISSN 1478-9515
    DOI 10.1017/S1478951523001992
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    Zs.A 6697: Show issues Location:
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  10. Article ; Online: A Phase 1 Study of Intravenous EGFR-ErbituxEDVsMIT in Children with Solid or CNS Tumours Expressing Epidermal Growth Factor Receptor.

    Evans, Louise / Walker, Rick / MacDiarmid, Jennifer / Brahmbhatt, Himanshu / Anazodo, Antoinette / McCowage, Geoffrey / Gifford, Andrew J / Kavallaris, Maria / Trahair, Toby / Ziegler, David S

    Targeted oncology

    2024  

    Language English
    Publishing date 2024-03-28
    Publishing country France
    Document type Journal Article
    ZDB-ID 2222136-0
    ISSN 1776-260X ; 1776-2596
    ISSN (online) 1776-260X
    ISSN 1776-2596
    DOI 10.1007/s11523-024-01051-2
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