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  1. Article ; Online: Characterization of recurrence patterns and outcomes of medulloblastoma in adults: The University of Texas MD Anderson Cancer Center experience.

    Gregory, Timothy A / Mastall, Maximilian / Lin, Heather / Hess, Kenneth R / Yuan, Ying / Martin-Bejarano Garcia, Manuela / Fuller, Gregory N / Alfaro, Kristin D / Gule-Monroe, Maria K / Huse, Jason T / Khatua, Soumen / Rao, Ganesh / Sandberg, David I / Wefel, Jeffrey S / Yeboa, Debra N / Paulino, Arnold C / McGovern, Susan L / Zaky, Wafik / Mahajan, Anita /
    Suki, Dima / Weathers, Shiao-Pei / Harrison, Rebecca A / de Groot, John F / Puduvalli, Vinay K / Penas-Prado, Marta / Majd, Nazanin K

    Neuro-oncology advances

    2023  Volume 5, Issue 1, Page(s) vdad032

    Abstract: Background: Medulloblastoma in adults is rare and treatment decisions are largely driven from pediatric literature. We sought to characterize recurrent medulloblastoma in adults.: Methods: From a single-institution dataset of 200 adult patients ... ...

    Abstract Background: Medulloblastoma in adults is rare and treatment decisions are largely driven from pediatric literature. We sought to characterize recurrent medulloblastoma in adults.
    Methods: From a single-institution dataset of 200 adult patients diagnosed with medulloblastoma during 1978-2017, those with recurrence were analyzed for clinical features, treatment, and outcome.
    Results: Of the 200 patients, 82 (41%) with median age of 29 years (18-59) had recurrence after a median follow-up time of 8.4 years (95% CI = 7.1, 10.3). Of these, 30 (37%) were standard-risk, 31 (38%) were high-risk, and 21 (26%) had unknown-risk diseases at the time of initial diagnosis. Forty-eight (58%) presented with recurrence outside the posterior fossa, of whom 35 (43%) had distant recurrence only. Median Progression-free survival (PFS) and OS from initial surgery were 33.5 and 62.4 months, respectively. Neither PFS nor OS from initial diagnosis differed between the standard-risk and high-risk groups in those who experience recurrence (
    Conclusions: Recurrent medulloblastoma in adults has a poor prognosis irrespective of initial risk stratification. Recurrence commonly arises outside the posterior fossa years after initial diagnosis.
    Language English
    Publishing date 2023-04-13
    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/vdad032
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Clinical characterization of adult medulloblastoma and the effect of first-line therapies on outcome; The MD Anderson Cancer Center experience.

    Majd, Nazanin K / Mastall, Maximilan / Lin, Heather / Dibaj, Seyede Shiva / Hess, Kenneth R / Yuan, Ying / Garcia, Manuela Martin-Bejarano / Fuller, Gregory N / Alfaro, Kristin D / Gule-Monroe, Maria K / Huse, Jason T / Khatua, Soumen / Rao, Ganesh / Sandberg, David I / Wefel, Jeffrey S / Yeboa, Debra N / Paulino, Arnold C / McGovern, Susan L / Zaky, Wafik /
    Mahajan, Anita / Suki, Dima / Weathers, Shiao-Pei / Harriso, Rebecca A / De Groo, John F / Puduvalli, Vinay K / Penas-Prado, Marta

    Neuro-oncology advances

    2021  Volume 3, Issue 1, Page(s) vdab079

    Abstract: Background: Adult medulloblastoma (MB) is rare, and management guidelines are largely based on pediatric clinical trials and retrospective series. Limited data exist with respect to clinical characteristics, prognostic factors, and outcomes based on ... ...

    Abstract Background: Adult medulloblastoma (MB) is rare, and management guidelines are largely based on pediatric clinical trials and retrospective series. Limited data exist with respect to clinical characteristics, prognostic factors, and outcomes based on first-line treatments.
    Methods: Two hundred adults with MB seen at a single institution from January 1978 to April 2017 were identified and followed for a median of 8.4 y (7.1, 10.3).
    Results: Patient's median age at diagnosis was 29 y (18, 63). One hundred eleven (55.5%) were standard-risk, 59 (29.5%) were high-risk, and 30 (15.0%) were indeterminate. Most received post-operative radiation (RT) (184 [92.0%]), and 105 (52.5%) received first-line chemotherapy. Median overall survival (OS) was 8.8 y (7.2, 12.2) and median progression-free survival (PFS) was 6.6 y (4.9, 11.2). High-risk patients had inferior OS (Hazard ratio [HR] = 2.5 [1.5, 4.2],
    Conclusion: This is the largest single-institution retrospective study of adult MB to our knowledge and identifies standard-risk status, first-line RT and adjuvant chemotherapy as factors associated with improved outcomes.
    Language English
    Publishing date 2021-06-22
    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/vdab079
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Glioma progression is shaped by genetic evolution and microenvironment interactions

    Varn, Frederick S. / Johnson, Kevin C. / Martínek, Jan / Huse, Jason T. / Nasrallah, MacLean P. / Wesseling, Pieter / Cooper, Lee A.D. / Malta, Tathiane M. / Wade, Taylor E. / Sabedot, Thais S. / Brat, Daniel / Gould, Peter V. / Wöehrer, Adelheid / Aldape, Kenneth / Ismail, Azzam / Sivajothi, Santhosh K. / Barthel, Floris P. / Kim, Hun / Kocakavuk, Emre /
    Ahmed, Nazia / White, Kieron / Datta, Indrani / Moon, Hyo-Eun / Pollock, Steven / Goldfarb, Christine / Lee, Ga-Hyun / Garofano, Luciano / Anderson, Kevin J. / Nehar-Belaid, Djamel / Barnholtz-Sloan, Jill S. / Bakas, Spyridon / Byrne, Annette T. / D’Angelo, Fulvio / Gan, Hui K. / Khasraw, Mustafa / Migliozzi, Simona / Ormond, D. Ryan / Paek, Sun Ha / Van Meir, Erwin G. / Walenkamp, Annemiek M.E. / Watts, Colin / Weiss, Tobias / Weller, Michael / Palucka, Karolina / Stead, Lucy F. / Poisson, Laila M. / Noushmehr, Houtan / Iavarone, Antonio / Verhaak, Roel G.W. / Martinek, Jan / Ryan Ormond, D. / Ha Paek, Sun / Alfaro, Kristin D. / Amin, Samirkumar B. / Ashley, David M. / Bock, Christoph / Brodbelt, Andrew / Bulsara, Ketan R. / Castro, Ana Valeria / Connelly, Jennifer M. / Costello, Joseph F. / de Groot, John F. / Finocchiaro, Gaetano / French, Pim J. / Golebiewska, Anna / Hau, Ann C. / Hong, Chibo / Horbinski, Craig / Kannan, Kasthuri S. / Kouwenhoven, Mathilde CM. / Lasorella, Anna / LaViolette, Peter S. / Ligon, Keith L. / Lowman, Allison K. / Mehta, Shwetal / Miletic, Hrvoje / Molinaro, Annette M. / Ng, Ho Keung / Niclou, Simone P. / Niers, Johanna M. / Phillips, Joanna J. / Rabadán, Raúl / Rao, Ganesh / Reifenberger, Guido / Sanai, Nader / Short, Susan C. / Sillevis Smitt, Peter / Sloan, Andrew E. / Smits, Marion / Snyder, James M. / Suzuki, Hiromichi / Tabatabai, Ghazaleh / Tanner, Georgette / Tomaszewski, William H. / Wells, Michael / Westerman, Bart A. / Wheeler, Helen / Xie, Jichun / Alfred Yung, W.K. / Zadeh, Gelareh / Zhao, Junfei / Verhaak, Roel GW.

    Elsevier Inc. Cell. 2022 June 09, v. 185, no. 12 p.2184-2199.e16

    2022  

    Abstract: The factors driving therapy resistance in diffuse glioma remain poorly understood. To identify treatment-associated cellular and genetic changes, we analyzed RNA and/or DNA sequencing data from the temporally separated tumor pairs of 304 adult patients ... ...

    Institution The GLASS Consortium
    Abstract The factors driving therapy resistance in diffuse glioma remain poorly understood. To identify treatment-associated cellular and genetic changes, we analyzed RNA and/or DNA sequencing data from the temporally separated tumor pairs of 304 adult patients with isocitrate dehydrogenase (IDH)-wild-type and IDH-mutant glioma. Tumors recurred in distinct manners that were dependent on IDH mutation status and attributable to changes in histological feature composition, somatic alterations, and microenvironment interactions. Hypermutation and acquired CDKN2A deletions were associated with an increase in proliferating neoplastic cells at recurrence in both glioma subtypes, reflecting active tumor growth. IDH-wild-type tumors were more invasive at recurrence, and their neoplastic cells exhibited increased expression of neuronal signaling programs that reflected a possible role for neuronal interactions in promoting glioma progression. Mesenchymal transition was associated with the presence of a myeloid cell state defined by specific ligand-receptor interactions with neoplastic cells. Collectively, these recurrence-associated phenotypes represent potential targets to alter disease progression.
    Keywords DNA ; RNA ; adults ; disease progression ; evolution ; glioma ; histology ; isocitrate dehydrogenase ; mutation ; neurons ; therapeutics ; glioblastoma ; genomics ; treatment resistance ; microenvironment ; hypermutation ; macrophages ; single-cell ; spatial imaging
    Language English
    Dates of publication 2022-0609
    Size p. 2184-2199.e16.
    Publishing place Elsevier Inc.
    Document type Article ; Online
    ZDB-ID 187009-9
    ISSN 1097-4172 ; 0092-8674
    ISSN (online) 1097-4172
    ISSN 0092-8674
    DOI 10.1016/j.cell.2022.04.038
    Database NAL-Catalogue (AGRICOLA)

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  4. Article ; Online: The molecular landscape of glioma in patients with Neurofibromatosis 1.

    D'Angelo, Fulvio / Ceccarelli, Michele / Tala / Garofano, Luciano / Zhang, Jing / Frattini, Véronique / Caruso, Francesca P / Lewis, Genevieve / Alfaro, Kristin D / Bauchet, Luc / Berzero, Giulia / Cachia, David / Cangiano, Mario / Capelle, Laurent / de Groot, John / DiMeco, Francesco / Ducray, François / Farah, Walid / Finocchiaro, Gaetano /
    Goutagny, Stéphane / Kamiya-Matsuoka, Carlos / Lavarino, Cinzia / Loiseau, Hugues / Lorgis, Véronique / Marras, Carlo E / McCutcheon, Ian / Nam, Do-Hyun / Ronchi, Susanna / Saletti, Veronica / Seizeur, Romuald / Slopis, John / Suñol, Mariona / Vandenbos, Fanny / Varlet, Pascale / Vidaud, Dominique / Watts, Colin / Tabar, Viviane / Reuss, David E / Kim, Seung-Ki / Meyronet, David / Mokhtari, Karima / Salvador, Hector / Bhat, Krishna P / Eoli, Marica / Sanson, Marc / Lasorella, Anna / Iavarone, Antonio

    Nature medicine

    2018  Volume 25, Issue 1, Page(s) 176–187

    Abstract: Neurofibromatosis type 1 (NF1) is a common tumor predisposition syndrome in which glioma is one of the prevalent tumors. Gliomagenesis in NF1 results in a heterogeneous spectrum of low- to high-grade neoplasms occurring during the entire lifespan of ... ...

    Abstract Neurofibromatosis type 1 (NF1) is a common tumor predisposition syndrome in which glioma is one of the prevalent tumors. Gliomagenesis in NF1 results in a heterogeneous spectrum of low- to high-grade neoplasms occurring during the entire lifespan of patients. The pattern of genetic and epigenetic alterations of glioma that develops in NF1 patients and the similarities with sporadic glioma remain unknown. Here, we present the molecular landscape of low- and high-grade gliomas in patients affected by NF1 (NF1-glioma). We found that the predisposing germline mutation of the NF1 gene was frequently converted to homozygosity and the somatic mutational load of NF1-glioma was influenced by age and grade. High-grade tumors harbored genetic alterations of TP53 and CDKN2A, frequent mutations of ATRX associated with Alternative Lengthening of Telomere, and were enriched in genetic alterations of transcription/chromatin regulation and PI3 kinase pathways. Low-grade tumors exhibited fewer mutations that were over-represented in genes of the MAP kinase pathway. Approximately 50% of low-grade NF1-gliomas displayed an immune signature, T lymphocyte infiltrates, and increased neo-antigen load. DNA methylation assigned NF1-glioma to LGm6, a poorly defined Isocitrate Dehydrogenase 1 wild-type subgroup enriched with ATRX mutations. Thus, the profiling of NF1-glioma defined a distinct landscape that recapitulates a subset of sporadic tumors.
    MeSH term(s) Adolescent ; Adult ; Antigens, Neoplasm/metabolism ; Brain Neoplasms/complications ; Brain Neoplasms/genetics ; Brain Neoplasms/immunology ; Child ; Child, Preschool ; Cohort Studies ; DNA Methylation/genetics ; Female ; Germ-Line Mutation/genetics ; Glioma/complications ; Glioma/genetics ; Glioma/immunology ; Humans ; Male ; Middle Aged ; Neurofibromatosis 1/complications ; Neurofibromatosis 1/genetics ; Neurofibromin 1/genetics ; Reproducibility of Results ; T-Lymphocytes/immunology ; Transcriptome/genetics ; X-linked Nuclear Protein/genetics ; Young Adult
    Chemical Substances Antigens, Neoplasm ; NF1 protein, human ; Neurofibromin 1 ; ATRX protein, human (EC 3.6.4.12) ; X-linked Nuclear Protein (EC 3.6.4.12)
    Language English
    Publishing date 2018-12-10
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1220066-9
    ISSN 1546-170X ; 1078-8956
    ISSN (online) 1546-170X
    ISSN 1078-8956
    DOI 10.1038/s41591-018-0263-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 4212: Show issues Location:
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  5. Article ; Online: Longitudinal molecular trajectories of diffuse glioma in adults.

    Barthel, Floris P / Johnson, Kevin C / Varn, Frederick S / Moskalik, Anzhela D / Tanner, Georgette / Kocakavuk, Emre / Anderson, Kevin J / Abiola, Olajide / Aldape, Kenneth / Alfaro, Kristin D / Alpar, Donat / Amin, Samirkumar B / Ashley, David M / Bandopadhayay, Pratiti / Barnholtz-Sloan, Jill S / Beroukhim, Rameen / Bock, Christoph / Brastianos, Priscilla K / Brat, Daniel J /
    Brodbelt, Andrew R / Bruns, Alexander F / Bulsara, Ketan R / Chakrabarty, Aruna / Chakravarti, Arnab / Chuang, Jeffrey H / Claus, Elizabeth B / Cochran, Elizabeth J / Connelly, Jennifer / Costello, Joseph F / Finocchiaro, Gaetano / Fletcher, Michael N / French, Pim J / Gan, Hui K / Gilbert, Mark R / Gould, Peter V / Grimmer, Matthew R / Iavarone, Antonio / Ismail, Azzam / Jenkinson, Michael D / Khasraw, Mustafa / Kim, Hoon / Kouwenhoven, Mathilde C M / LaViolette, Peter S / Li, Meihong / Lichter, Peter / Ligon, Keith L / Lowman, Allison K / Malta, Tathiane M / Mazor, Tali / McDonald, Kerrie L / Molinaro, Annette M / Nam, Do-Hyun / Nayyar, Naema / Ng, Ho Keung / Ngan, Chew Yee / Niclou, Simone P / Niers, Johanna M / Noushmehr, Houtan / Noorbakhsh, Javad / Ormond, D Ryan / Park, Chul-Kee / Poisson, Laila M / Rabadan, Raul / Radlwimmer, Bernhard / Rao, Ganesh / Reifenberger, Guido / Sa, Jason K / Schuster, Michael / Shaw, Brian L / Short, Susan C / Smitt, Peter A Sillevis / Sloan, Andrew E / Smits, Marion / Suzuki, Hiromichi / Tabatabai, Ghazaleh / Van Meir, Erwin G / Watts, Colin / Weller, Michael / Wesseling, Pieter / Westerman, Bart A / Widhalm, Georg / Woehrer, Adelheid / Yung, W K Alfred / Zadeh, Gelareh / Huse, Jason T / De Groot, John F / Stead, Lucy F / Verhaak, Roel G W

    Nature

    2019  Volume 576, Issue 7785, Page(s) 112–120

    Abstract: The evolutionary processes that drive universal therapeutic resistance in adult patients with diffuse glioma remain ... ...

    Abstract The evolutionary processes that drive universal therapeutic resistance in adult patients with diffuse glioma remain unclear
    MeSH term(s) Adult ; Chromosomes, Human, Pair 1 ; Chromosomes, Human, Pair 19 ; Disease Progression ; Glioma/genetics ; Glioma/pathology ; Humans ; Isocitrate Dehydrogenase/genetics ; Mutation ; Polymorphism, Single Nucleotide ; Recurrence
    Chemical Substances Isocitrate Dehydrogenase (EC 1.1.1.41)
    Language English
    Publishing date 2019-11-20
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 120714-3
    ISSN 1476-4687 ; 0028-0836
    ISSN (online) 1476-4687
    ISSN 0028-0836
    DOI 10.1038/s41586-019-1775-1
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