ConferenceMed Phys · April 2025
BACKGROUND: Stereotactic radiosurgery (SRS) is widely used for managing brain metastases (BMs), but an adverse effect, radionecrosis, complicates post-SRS management. Differentiating radionecrosis from tumor recurrence non-invasively remains a major clinic ...
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Journal ArticleNeoplasia · April 2025
Diffuse midline gliomas (DMGs) are lethal brain tumors that arise in children and young adults, resulting in a median survival of less than two years. Genetically engineered mouse models (GEMMs) are critical to studying tumorigenesis and tumor-immune inter ...
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Journal ArticleNat Cancer · March 2025
FLASH radiotherapy holds promise for treating solid tumors given the potential lower toxicity in normal tissues but its therapeutic effects on tumor immunity remain largely unknown. Using a genetically engineered mouse model of medulloblastoma, we show tha ...
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Journal ArticleNeuro-Oncology Practice · January 13, 2025
AbstractA significant proportion of patients with brain metastases experience a seizure event during their disease course, which can impact morbidity and long-term outcomes. A host of factors elevate the ris ...
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Journal ArticleFront Oncol · 2025
PURPOSE: This work investigates the use of a spherical projection-based U-Net (SPU-Net) segmentation model to improve meningioma segmentation performance and allow for uncertainty quantification. METHODS: A total of 76 supratentorial meningioma patients tr ...
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Journal ArticleInt J Radiat Oncol Biol Phys · October 1, 2024
PURPOSE: To develop a novel deep ensemble learning model for accurate prediction of brain metastasis (BM) local control outcomes after stereotactic radiosurgery (SRS). METHODS AND MATERIALS: A total of 114 brain metastases (BMs) from 82 patients were evalu ...
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Journal ArticleNeuro Oncol · August 5, 2024
DNA damage response (DDR) mechanisms are critical to maintenance of overall genomic stability, and their dysfunction can contribute to oncogenesis. Significant advances in our understanding of DDR pathways have raised the possibility of developing therapie ...
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Journal ArticleNeuro Oncol · June 3, 2024
A majority of cancers (~85%) activate the enzyme telomerase to maintain telomere length over multiple rounds of cellular division. Telomerase-negative cancers activate a distinct, telomerase-independent mechanism of telomere maintenance termed alternative ...
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Journal ArticleAdv Radiat Oncol · June 2024
PURPOSE: Clinical and imaging surveillance of patients with brain metastases is important after stereotactic radiosurgery (SRS) because many will experience intracranial progression (ITCP) requiring multidisciplinary management. The prognostic significance ...
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Journal ArticleSci Data · May 15, 2024
Meningiomas are the most common primary intracranial tumors and can be associated with significant morbidity and mortality. Radiologists, neurosurgeons, neuro-oncologists, and radiation oncologists rely on brain MRI for diagnosis, treatment planning, and l ...
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Journal ArticleInt J Radiat Oncol Biol Phys · April 1, 2024
PURPOSE: The intracranial benefit of offering dual immune-checkpoint inhibition (D-ICPI) with ipilimumab and nivolumab to patients with melanoma or non-small cell lung cancer (NSCLC) receiving stereotactic radiosurgery (SRS) for brain metastases (BMs) is u ...
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Journal ArticleBrain Sci · January 30, 2024
Both glioblastoma (GBM) and dementia are devastating diseases with limited treatments that are usually not curative. Having clinically diagnosed dementia with an associated biopsy-proven etiology and a coexisting GBM diagnosis is a rare occurrence. The rel ...
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Journal ArticleJ Clin Invest · January 16, 2024
Since the discovery that cGAS/STING recognizes endogenous DNA released from dying cancer cells and induces type I interferon and antitumor T cell responses, efforts to understand and therapeutically target the STING pathway in cancer have ensued. Relative ...
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Journal ArticleCancer Cell · January 8, 2024
Recent clinical trials for H3K27-altered diffuse midline gliomas (DMGs) have shown much promise. We present a consensus roadmap and identify three major barriers: (1) refinement of experimental models to include immune and brain-specific components; (2) co ...
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Journal ArticleAdv Radiat Oncol · January 2024
PURPOSE: Genetic variants affecting the radiation response protein ataxia-telangiectasia mutated (ATM) have been associated with increased adverse effects of radiation but also with improved local control after conventional radiation therapy. However, it i ...
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Journal ArticleJ Radiosurg SBRT · 2024
PURPOSE: To investigate whether TP53 variants may be correlated with overall survival and local control following stereotactic radiosurgery (SRS) for brain metastases (BMs) from non-small cell lung cancer (NSCLC). METHODS: Patients undergoing an initial co ...
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Journal ArticleRadiat Res · December 1, 2023
Medulloblastoma is the most common malignant brain tumor of children. Although standard of care radiotherapy for pediatric medulloblastoma (PM) can lead to long-term remission or cure in many patients, it can also cause life-long cognitive impairment and o ...
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Journal ArticleCommun Biol · November 10, 2023
Enzymes with novel functions are needed to enable new organic synthesis techniques. Drawing inspiration from gain-of-function cancer mutations that functionally alter proteins and affect cellular metabolism, we developed METIS (Mutated Enzymes from Tumors ...
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Journal ArticleOncogene · October 2023
Pooled genetic screens represent a powerful approach to identify vulnerabilities in cancer. Here we used pooled CRISPR/Cas9-based approaches to identify vulnerabilities associated with telomerase reverse transcriptase (TERT) promoter mutations (TPMs) found ...
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Journal ArticleCancers (Basel) · July 31, 2023
Glioblastoma (GBM) is the most common malignant primary brain tumor in adults. Despite standard therapies, including resection and chemoradiation, recurrence is virtually inevitable. Current treatment for recurrent glioblastoma (rGBM) is rapidly evolving, ...
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Journal ArticleCancers (Basel) · April 24, 2023
Radiation necrosis, also known as treatment-induced necrosis, has emerged as an important adverse effect following stereotactic radiotherapy (SRS) for brain metastases. The improved survival of patients with brain metastases and increased use of combined s ...
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Journal ArticleActa Neuropathol Commun · March 25, 2023
Gangliogliomas are brain tumors composed of neuron-like and macroglia-like components that occur in children and young adults. Gangliogliomas are often characterized by a rare population of immature astrocyte-appearing cells expressing CD34, a marker expre ...
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Journal ArticleSTAR Protoc · March 17, 2023
Genetically engineered mice are commonly used to model brainstem gliomas in pre-clinical research. One technique for inducing primary tumors in these genetically engineered mice involves delivering viral vectors containing the code for gene-editing protein ...
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Journal ArticleAdv Radiat Oncol · 2023
PURPOSE: Hypofractionated stereotactic radiosurgery (HF-SRS) with or without surgical resection is potentially a preferred treatment for larger or symptomatic brain metastases (BMs). Herein, we report clinical outcomes and predictive factors following HF-S ...
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Journal ArticleAdv Radiat Oncol · 2023
PURPOSE: Existing brain metastasis prognostic models do not identify patients at risk of very poor survival after radiation therapy (RT). Identifying patient and disease risk factors for 30-day mortality (30-DM) after RT may help identify patients who woul ...
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Journal ArticleNeurooncol Adv · 2023
BACKGROUND: Primary central nervous system lymphoma (PCNSL) is an aggressive diffuse large B-cell lymphoma. Treatment approaches are historically associated with neurotoxicity, particularly with high-dose whole-brain radiotherapy (WBRT). We hypothesized th ...
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Journal ArticleNeurooncol Adv · 2023
BACKGROUND: Medulloblastoma is the most common malignant pediatric brain tumor, and leptomeningeal dissemination (LMD) of medulloblastoma both portends a poorer prognosis at diagnosis and is incurable at recurrence. The biological mechanisms underlying LMD ...
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Journal ArticleCancers (Basel) · October 22, 2022
Stereotactic radiosurgery (SRS) is a standard of care for many patients with brain metastases. To optimize post-SRS surveillance, this study aimed to validate a previously published nomogram predicting post-SRS intracranial progression (IP). We identified ...
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Journal ArticleCancers (Basel) · September 17, 2022
Diffuse midline gliomas arise in the brainstem and other midline brain structures and cause a large proportion of childhood brain tumor deaths. Radiation therapy is the most effective treatment option, but these tumors ultimately progress. Inhibition of th ...
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Journal ArticleInt J Radiat Oncol Biol Phys · March 1, 2022
PURPOSE: Diffuse intrinsic pontine gliomas (DIPGs) arise in the pons and are the leading cause of death from brain tumors in children. DIPGs are routinely treated with radiation therapy, which temporarily improves neurological symptoms but generally fails ...
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Journal ArticleNat Commun · February 1, 2022
The role of PPM1D mutations in de novo gliomagenesis has not been systematically explored. Here we analyze whole genome sequences of 170 pediatric high-grade gliomas and find that truncating mutations in PPM1D that increase the stability of its phosphatase ...
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Journal ArticleSemin Radiat Oncol · January 2022
Targeting the DNA damage response represents a promising approach to improve the efficacy of radiation therapy. One appealing target for this approach is the serine/threonine kinase ataxia telangiectasia mutated (ATM), which is activated by DNA double stra ...
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Journal ArticleClin Cancer Res · December 15, 2021
PURPOSE: To investigate the therapeutic role of a novel telomere-directed inhibitor, 6-thio-2'-deoxyguanosine (THIO) in gliomas both in vitro and in vivo. EXPERIMENTAL DESIGN: A panel of human and mouse glioma cell lines was used to test therapeutic effica ...
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ConferenceInternational journal of radiation oncology, biology, physics · November 2021
Purpose/objective(s)Improved survival for patients with brain metastases (BM) has been accompanied by a rise in tumor recurrence after stereotactic radiosurgery (SRS). Laser interstitial thermal therapy (LITT) has evolved as an effective treatment ...
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ConferenceInternational journal of radiation oncology, biology, physics · November 2021
Purpose/objective(s)To compare dosimetric results of two beam arrangement strategies and their robustness to setup uncertainties in fractionated thoracic spine Stereotactic Body Radiotherapy (SBRT) MATERIALS/METHODS: Fifteen patients who received ...
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Journal ArticleFront Oncol · 2021
As local disease control improves, the public health impact of brain metastases (BrM) continues to grow. Molecular features are frequently different between primary and metastatic tumors as a result of clonal evolution during neoplasm migration, selective ...
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Journal ArticleNat Commun · August 19, 2019
Pilocytic astrocytoma (PA), the most common childhood brain tumor, is a low-grade glioma with a single driver BRAF rearrangement. Here, we perform scRNAseq in six PAs using methods that enabled detection of the rearrangement. When compared to higher-grade ...
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Journal ArticleRadiother Oncol · March 2018
BACKGROUND: Pemetrexed is a folate antimetabolite used in the management of advanced adenocarcinoma of the lung. We sought to assess the impact of pemetrexed on intracranial disease control and radiation-related toxicity among patients with adenocarcinoma ...
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Journal ArticleBioorg Med Chem Lett · February 15, 2018
Mutations in the metabolic enzyme isocitrate dehydrogenase 1 (IDH1) are commonly found in gliomas. AGI-5198, a potent and selective inhibitor of the mutant IDH1 enzyme, was radiolabeled with radioiodine and fluorine-18. These radiotracers were evaluated as ...
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Journal ArticleSemin Neurol · February 2018
Glioblastoma (GBM) is the most common primary malignant tumor of the central nervous system. The current standard of care for GBM is maximal resection followed by postoperative radiation with concomitant and adjuvant temozolomide. Despite this multimodalit ...
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Journal ArticleEur J Med Chem · August 25, 2016
INTRODUCTION: Malignant gliomas frequently harbor mutations in the isocitrate dehydrogenase 1 (IDH1) gene. Studies suggest that IDH mutation contributes to tumor pathogenesis through mechanisms that are mediated by the neomorphic metabolite of the mutant I ...
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Journal ArticleR Soc Open Sci · August 2015
The Kolmogorov-Arnold stochasticity parameter technique is applied for the first time to the study of cancer genome sequencing, to reveal mutations. Using data generated by next-generation sequencing technologies, we have analysed the exome sequences of br ...
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Journal ArticleBlood · January 8, 2015
Gain-of-function mutations in nicotinamide adenine dinucleotide phosphate-dependent isocitrate dehydrogenase (IDH)1 and IDH2 frequently arise in human leukemias and other cancers and produce high levels of D-2-hydroxyglutarate (D-2HG). We expressed the R19 ...
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Journal ArticleJ Biol Chem · August 22, 2014
Mutations in the cytosolic NADP(+)-dependent isocitrate dehydrogenase (IDH1) occur in several types of cancer, and altered cellular metabolism associated with IDH1 mutations presents unique therapeutic opportunities. By altering IDH1, these mutations targe ...
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Journal ArticleNat Genet · July 2014
Gliomas arising in the brainstem and thalamus are devastating tumors that are difficult to surgically resect. To determine the genetic and epigenetic landscape of these tumors, we performed exomic sequencing of 14 brainstem gliomas (BSGs) and 12 thalamic g ...
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Journal ArticleNeuro Oncol · July 2014
Malignant cells must maintain their telomeres, but genetic mechanisms responsible for telomere maintenance in tumors have only recently been discovered. In particular, mutations of the telomere binding proteins alpha thalassemia/mental retardation syndrome ...
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Journal ArticleOncotarget · March 30, 2014
Frequent mutations in isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) and the promoter of telomerase reverse transcriptase (TERT) represent two significant discoveries in glioma genomics. Understanding the degree to which these two mutations co-occur or o ...
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Journal ArticleOncotarget · March 30, 2014
Anaplastic astrocytoma WHO grade III (A3) is a lethal brain tumor that often occurs in middle aged patients. Clinically, it is challenging to distinguish A3 from glioblastoma multiforme (GBM) WHO grade IV. To reveal the genetic landscape of this tumor type ...
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Journal ArticleNature Genetics · January 1, 2014
Gliomas arising in the brainstem and thalamus are devastating tumors that are difficult to surgically resect. To determine the genetic and epigenetic landscape of these tumors, we performed exomic sequencing of 14 brainstem gliomas (BSGs) and 12 thalamic g ...
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Journal ArticleCancer Cell · May 13, 2013
Hotspot mutations in IDH1 and IDH2 cause a differentiation block that can promote tumorigenesis. Two recent papers reported that small molecules targeting mutant IDH1 or mutant IDH2 release this differentiation block and/or impede tumor growth, providing a ...
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Journal ArticleProc Natl Acad Sci U S A · April 9, 2013
Malignant cells, like all actively growing cells, must maintain their telomeres, but genetic mechanisms responsible for telomere maintenance in tumors have only recently been discovered. In particular, mutations of the telomere binding proteins alpha thala ...
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Journal ArticleOncotarget · April 2013
A heterogeneous population of uncommon neoplasms of the central nervous system (CNS) cause significant morbidity and mortality. To explore their genetic origins, we sequenced the exomes of 12 pleomorphic xanthoastrocytomas (PXA), 17 non-brainstem pediatric ...
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Journal ArticleCancer Res · January 15, 2013
Point mutations at Arg132 of the cytoplasmic NADP(+)-dependent isocitrate dehydrogenase 1 (IDH1) occur frequently in gliomas and result in a gain of function to produce the "oncometabolite" D-2-hydroxyglutarate (D-2HG). The mutated IDH1 allele is usually a ...
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Journal ArticleNat Chem Biol · November 2012
Mutations in an enzyme can result in a neomorphic catalytic activity in cancers. We applied cancer-associated mutations from isocitrate dehydrogenases to homologous residues in the active sites of homoisocitrate dehydrogenases to derive enzymes that cataly ...
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Journal ArticleOncotarget · July 2012
Mutations in the critical chromatin modifier ATRX and mutations in CIC and FUBP1, which are potent regulators of cell growth, have been discovered in specific subtypes of gliomas, the most common type of primary malignant brain tumors. However, the frequen ...
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Journal ArticleJ Grad Med Educ · June 2012
BACKGROUND: Studies have shown that publication of work during medical school and residency is associated with higher numbers of later publications and citations of published research. However, it is unknown whether this association exists for non-PhD phys ...
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Journal ArticleProc Natl Acad Sci U S A · February 22, 2011
Point mutations of the NADP(+)-dependent isocitrate dehydrogenases 1 and 2 (IDH1 and IDH2) occur early in the pathogenesis of gliomas. When mutated, IDH1 and IDH2 gain the ability to produce the metabolite (R)-2-hydroxyglutarate (2HG), but the downstream e ...
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Journal ArticlePLoS One · February 4, 2011
BACKGROUND: Gliomas frequently contain mutations in the cytoplasmic NADP(+)-dependent isocitrate dehydrogenase (IDH1) or the mitochondrial NADP(+)-dependent isocitrate dehydrogenase (IDH2). Several different amino acid substitutions recur at either IDH1 R1 ...
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Journal ArticleBiochem Biophys Res Commun · July 30, 2010
Isocitrate dehydrogenase 1 (IDH1) and isocitrate dehydrogenase 2 (IDH2) are enzymes which convert isocitrate to alpha-ketoglutarate while reducing nicotinamide adenine dinucleotide phosphate (NADP+to NADPH). IDH1/2 were recently identified as mutated in a ...
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Journal ArticleJ Natl Cancer Inst · July 7, 2010
Dysregulation of metabolism is a common phenomenon in cancer cells. The NADP(+)-dependent isocitrate dehydrogenases 1 and 2 (IDH1 and IDH2) function at a crossroads of cellular metabolism in lipid synthesis, cellular defense against oxidative stress, oxida ...
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Journal ArticleCancer Cell · March 16, 2010
Oncogenes usually increase their normal function when activated. However, seemingly oncogenic mutations in IDH1 and IDH2 reduce their native enzyme activity. In this issue of Cancer Cell, Ward et al. pin down a neomorphic enzyme activity as a possible onco ...
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Journal ArticleJ Biol Chem · January 11, 2008
Picornaviruses have a peptide termed VPg covalently linked to the 5'-end of the genome. Attachment of VPg to the genome occurs in at least two steps. First, Tyr-3 of VPg, or some precursor thereof, is used as a primer by the viral RNA-dependent RNA polymer ...
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