Change in Neurocognitive Functioning After Treatment With Cranial Radiation in Childhood

Spiegler, Brenda J.; Bouffet, Éric; Greenberg, Mark; Rutka, James T.; Mabbott, Donald

doi:10.1200/jco.2004.05.186

Cited by 347 publications

(295 citation statements)

References 29 publications

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“…Following surgical resection, these patients require aggressive multimodal therapy, resulting in long-term treatment-related complications, including developmental, neurological, neuroendocrine, and psychosocial deficits (1)(2)(3). Variants of MB have been defined (e.g., classic, desmoplastic, anaplastic, and extremely nodular) pathologically and by gene expression profiling (4)(5)(6)(7).…”

mentioning

confidence: 99%

T-cell TGF-β signaling abrogation restricts medulloblastoma progression

Gate

Danielpour

Rodríguez

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Cancer cell secretion of TGF-β is a potent mechanism for immune evasion. However, little is known about how central nervous system tumors guard against immune eradication. We sought to determine the impact of T-cell TGF-β signaling blockade on progression of medulloblastoma (MB), the most common pediatric brain tumor. Genetic abrogation of T-cell TGF-β signaling mitigated tumor progression in the smoothened A1 (SmoA1) transgenic MB mouse. T regulatory cells were nearly abolished and antitumor immunity was mediated by CD8 cytotoxic T lymphocytes. To define the CD8 T-cell subpopulation responsible, primed CD8 T cells were adoptively transferred into tumor-bearing immunocompromised SmoA1 recipients. This led to generation of CD8 + / killer cell lectin-like receptor G1 high (KLRG1 hi )/IL-7R lo short-lived effector cells that expressed granzyme B at the tumor. These results identify a cellular immune mechanism whereby TGF-β signaling blockade licenses the T-cell repertoire to kill pediatric brain tumor cells.cancer immunology | neuroimmunology | neuro-oncology

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mentioning

confidence: 99%

T-cell TGF-β signaling abrogation restricts medulloblastoma progression

Gate

Danielpour

Rodríguez

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…Improved survival rates and longevity of juvenile cancer patients now reveal debilitating late effects of radiation therapy for brain health (1)(2)(3), including significant attention deficits and learning problems in later life (4,5).…”

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confidence: 99%

Voluntary running rescues adult hippocampal neurogenesis after irradiation of the young mouse brain

Naylor

Bull²,

Nilsson

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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Cranial radiation therapy is commonly used in the treatment of childhood cancers. It is associated with cognitive impairments tentatively linked to the hippocampus, a neurogenic region of the brain important in memory function and learning. Hippocampal neurogenesis is positively regulated by voluntary exercise, which is also known to improve hippocampal-dependent cognitive functions. In this work, we irradiated the brains of C57/BL6 mice on postnatal day 9 and evaluated both the acute effects of irradiation and the effects of voluntary running on hippocampal neurogenesis and behavior 3 months after irradiation. Voluntary running significantly restored precursor cell and neurogenesis levels after a clinically relevant, moderate dose of irradiation. We also found that irradiation perturbed the structural integration of immature neurons in the hippocampus and that this was reversed by voluntary exercise. Furthermore, irradiation-induced behavior alterations observed in the open-field test were ameliorated. Together, these results clearly demonstrate the usefulness of physical exercise for functional and structural recovery from radiation-induced injury to the juvenile brain, and they suggest that exercise should be evaluated in rehabilitation therapy of childhood cancer survivors.exercise ͉ juvenile ͉ open field ͉ radiotherapy ͉ stem cell

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“…This is of particular relevance in pediatric neuro-oncology because therapies toxic to the developing brain cause irreversible and continuous loss of cognition and changes in other aspects of human behavior (41).…”

Section: Identification Of Cscs In Adult and Pediatric Tumorsmentioning

confidence: 99%