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Neurosurgery Sep 2017Neuroimaging plays an ever evolving role in the diagnosis, treatment planning, and post-therapy assessment of brain tumors. This review provides an overview of current... (Review)
Review
Neuroimaging plays an ever evolving role in the diagnosis, treatment planning, and post-therapy assessment of brain tumors. This review provides an overview of current magnetic resonance imaging (MRI) methods routinely employed in the care of the brain tumor patient. Specifically, we focus on advanced techniques including diffusion, perfusion, spectroscopy, tractography, and functional MRI as they pertain to noninvasive characterization of brain tumors and pretreatment evaluation. The utility of both structural and physiological MRI in the post-therapeutic brain evaluation is also reviewed with special attention to the challenges presented by pseudoprogression and pseudoresponse.
Topics: Brain; Brain Neoplasms; Humans; Magnetic Resonance Imaging; Neuroimaging
PubMed: 28486641
DOI: 10.1093/neuros/nyx103 -
Journal of Clinical Oncology : Official... Jul 2017Development of novel therapies for CNS tumors requires reliable assessment of response and progression. This requirement has been particularly challenging in... (Review)
Review
Development of novel therapies for CNS tumors requires reliable assessment of response and progression. This requirement has been particularly challenging in neuro-oncology for which contrast enhancement serves as an imperfect surrogate for tumor volume and is influenced by agents that affect vascular permeability, such as antiangiogenic therapies. In addition, most tumors have a nonenhancing component that can be difficult to accurately quantify. To improve the response assessment in neuro-oncology and to standardize the criteria that are used for different CNS tumors, the Response Assessment in Neuro-Oncology (RANO) working group was established. This multidisciplinary international working group consists of neuro-oncologists, medical oncologists, neuroradiologists, neurosurgeons, radiation oncologists, neuropsychologists, and experts in clinical outcomes assessments, working in collaboration with government and industry to enhance the interpretation of clinical trials. The RANO working group was originally created to update response criteria for high- and low-grade gliomas and to address such issues as pseudoresponse and nonenhancing tumor progression from antiangiogenic therapies, and pseudoprogression from radiochemotherapy. RANO has expanded to include working groups that are focused on other tumors, including brain metastases, leptomeningeal metastases, spine tumors, pediatric brain tumors, and meningiomas, as well as other clinical trial end points, such as clinical outcomes assessments, seizures, corticosteroid use, and positron emission tomography imaging. In an effort to standardize the measurement of neurologic function for clinical assessment, the Neurologic Assessment in Neuro-Oncology scale was drafted. Born out of a workshop conducted by the Jumpstarting Brain Tumor Drug Development Coalition and the US Food and Drug Administration, a standardized brain tumor imaging protocol now exists to reduce variability and improve reliability. Efforts by RANO have been widely accepted and are increasingly being used in neuro-oncology trials, although additional refinements will be needed.
Topics: Central Nervous System Neoplasms; Clinical Trials as Topic; Disease Progression; Humans; Neuroimaging; Outcome and Process Assessment, Health Care; Practice Guidelines as Topic; Quality of Life; Tumor Burden
PubMed: 28640707
DOI: 10.1200/JCO.2017.72.7511 -
Neurotherapeutics : the Journal of the... Apr 2017Radiographic endpoints including response and progression are important for the evaluation of new glioblastoma therapies. The current RANO criteria was developed to... (Review)
Review
Radiographic endpoints including response and progression are important for the evaluation of new glioblastoma therapies. The current RANO criteria was developed to overcome many of the challenges identified with previous guidelines for response assessment, however, significant challenges and limitations remain. The current recommendations build on the strengths of the current RANO criteria, while addressing many of these limitations. Modifications to the current RANO criteria include suggestions for volumetric response evaluation, use contrast enhanced T1 subtraction maps to increase lesion conspicuity, removal of qualitative non-enhancing tumor assessment requirements, use of the post-radiation time point as the baseline for newly diagnosed glioblastoma response assessment, and "treatment-agnostic" response assessment rubrics for identifying pseudoprogression, pseudoresponse, and a confirmed durable response in newly diagnosed and recurrent glioblastoma trials.
Topics: Brain; Brain Neoplasms; Clinical Trials as Topic; Disease Progression; Glioblastoma; Humans; Image Enhancement; Image Interpretation, Computer-Assisted; Magnetic Resonance Imaging; Treatment Outcome
PubMed: 28108885
DOI: 10.1007/s13311-016-0507-6 -
The Plant Cell Jan 2023Maize (Zea mays) originated in southern Mexico and has spread over a wide latitudinal range. Maize expansion from tropical to temperate regions has necessitated a...
Maize (Zea mays) originated in southern Mexico and has spread over a wide latitudinal range. Maize expansion from tropical to temperate regions has necessitated a reduction of its photoperiod sensitivity. In this study, we cloned a quantitative trait locus (QTL) regulating flowering time in maize and show that the maize ortholog of Arabidopsis thaliana EARLY FLOWERING3, ZmELF3.1, is the causal locus. We demonstrate that ZmELF3.1 and ZmELF3.2 proteins can physically interact with ZmELF4.1/4.2 and ZmLUX1/2, to form evening complex(es; ECs) in the maize circadian clock. Loss-of-function mutants for ZmELF3.1/3.2 and ZmLUX1/2 exhibited delayed flowering under long-day and short-day conditions. We show that EC directly represses the expression of several flowering suppressor genes, such as the CONSTANS, CONSTANS-LIKE, TOC1 (CCT) genes ZmCCT9 and ZmCCT10, ZmCONSTANS-LIKE 3, and the PSEUDORESPONSE REGULATOR (PRR) genes ZmPRR37a and ZmPRR73, thus alleviating their inhibition, allowing florigen gene expression and promoting flowering. Further, we identify two closely linked retrotransposons located in the ZmELF3.1 promoter that regulate the expression levels of ZmELF3.1 and may have been positively selected during postdomestication spread of maize from tropical to temperate regions during the pre-Columbian era. These findings provide insights into circadian clock-mediated regulation of photoperiodic flowering in maize and new targets of genetic improvement for breeding.
Topics: Zea mays; Flowers; Plant Proteins; Adaptation, Physiological; Acclimatization; Photoperiod; Arabidopsis; Gene Expression Regulation, Plant
PubMed: 36173348
DOI: 10.1093/plcell/koac296 -
The Plant Cell Oct 2020Circadian clocks regulate growth and development in plants and animals, but the role of circadian regulation in crop production is poorly understood. Rice () grain yield...
Circadian clocks regulate growth and development in plants and animals, but the role of circadian regulation in crop production is poorly understood. Rice () grain yield is largely determined by tillering, which is mediated by physiological and genetic factors. Here we report a regulatory loop that involves the circadian clock, sugar, and strigolactone (SL) pathway to regulate rice tiller-bud and panicle development. Rice () positively regulates expression of (, also known as ), (), and (, also known as ) to repress tiller-bud outgrowth. Downregulating and overexpressing increases and reduces tiller numbers, respectively, whereas manipulating () expression results in the opposite effects. also regulates expression to mediate panicle and grain development. Genetic analyses using double mutants and overexpression in the mutants show that , , and act downstream of Sugars repress expression in roots and tiller buds to promote tiller-bud outgrowth. The circadian clock integrates sugar responses and the SL pathway to regulate tiller and panicle development, providing insights into improving plant architecture and yield in rice and other cereal crops.
Topics: Circadian Clocks; Gene Expression Regulation, Plant; Heterocyclic Compounds, 3-Ring; Lactones; Mutation; Oryza; Plant Proteins; Plants, Genetically Modified; Promoter Regions, Genetic; Signal Transduction; Sugars
PubMed: 32796126
DOI: 10.1105/tpc.20.00289 -
The EMBO Journal Feb 2021The roles of clock components in salt stress tolerance remain incompletely characterized in rice. Here, we show that, among OsPRR (Oryza sativa Pseudo-Response...
The roles of clock components in salt stress tolerance remain incompletely characterized in rice. Here, we show that, among OsPRR (Oryza sativa Pseudo-Response Regulator) family members, OsPRR73 specifically confers salt tolerance in rice. Notably, the grain size and yield of osprr73 null mutants were significantly decreased in the presence of salt stress, with accumulated higher level of reactive oxygen species and sodium ions. RNA sequencing and biochemical assays identified OsHKT2;1, encoding a plasma membrane-localized Na transporter, as a transcriptional target of OsPRR73 in mediating salt tolerance. Correspondingly, null mutants of OsHKT2;1 displayed an increased tolerance to salt stress. Immunoprecipitation-mass spectrometry (IP-MS) assays further identified HDAC10 as nuclear interactor of OsPRR73 and co-repressor of OsHKT2;1. Consistently, H3K9ac histone marks at OsHKT2;1 promoter regions were significantly reduced in osprr73 mutant. Together, our findings reveal that salt-induced OsPRR73 expression confers salt tolerance by recruiting HDAC10 to transcriptionally repress OsHKT2;1, thus reducing cellular Na accumulation. This exemplifies a new molecular link between clock components and salt stress tolerance in rice.
Topics: CLOCK Proteins; Cell Membrane; Gene Expression Regulation, Plant; Histone Deacetylases; Homeostasis; Loss of Function Mutation; Oryza; Plant Proteins; Promoter Regions, Genetic; Salt Tolerance; Sodium
PubMed: 33347628
DOI: 10.15252/embj.2020105086 -
Contrast Media & Molecular Imaging 2018Glioblastoma (GBM) is the most common primary malignant type of brain neoplasm in adults and carries a dismal prognosis. The current standard of care for GBM is surgical... (Review)
Review
Glioblastoma (GBM) is the most common primary malignant type of brain neoplasm in adults and carries a dismal prognosis. The current standard of care for GBM is surgical excision followed by radiation therapy (RT) with concurrent and adjuvant temozolomide-based chemotherapy (TMZ) by six additional cycles. In addition, antiangiogenic therapy with an antivascular endothelial growth factor (VEGF) agent has been used for recurrent glioblastoma. Over the last years, new posttreatment entities such as pseudoprogression and pseudoresponse have been recognized, apart from radiation necrosis. This review article focuses on the role of different imaging techniques such as conventional magnetic resonance imaging (MRI), diffusion-weighted imaging (DWI), diffusion tensor imaging (DTI), dynamic contrast enhancement (DCE-MRI) and dynamic susceptibility contrast (DSE-MRI) perfusion, magnetic resonance spectroscopy (MRS), and PET/SPECT in differentiation of such treatment-related changes from tumor recurrence.
Topics: Diagnostic Imaging; Disease Progression; Glioblastoma; Glioma; Humans; Neoplasm Recurrence, Local
PubMed: 30627060
DOI: 10.1155/2018/6828396 -
AJNR. American Journal of Neuroradiology Dec 2011The current standard of care for newly diagnosed cases of high-grade glioma is surgical resection followed by RT with concurrent chemotherapy. The most widely used... (Review)
Review
The current standard of care for newly diagnosed cases of high-grade glioma is surgical resection followed by RT with concurrent chemotherapy. The most widely used criteria for assessing treatment response are based on a 2D measurement of the enhancing area on MR imaging known as the Macdonald Criteria. Recently, nontumoral increases (pseudoprogression) and decreases (pseudoresponse) in enhancement have been found, and these can confuse outcome evaluation. Here we review pseudoprogression and pseudoresponse and describe how better understanding of these phenomena can aid interpretation.
Topics: Brain; Brain Neoplasms; Disease Progression; Glioma; Humans; Magnetic Resonance Imaging; Prognosis; Treatment Outcome
PubMed: 21393407
DOI: 10.3174/ajnr.A2397 -
Neuro-oncology Advances 2022Glioblastoma (GBM) is the most common primary adult intracranial malignancy and carries a dismal prognosis despite an aggressive multimodal treatment regimen that... (Review)
Review
Glioblastoma (GBM) is the most common primary adult intracranial malignancy and carries a dismal prognosis despite an aggressive multimodal treatment regimen that consists of surgical resection, radiation, and adjuvant chemotherapy. Radiographic evaluation, largely informed by magnetic resonance imaging (MRI), is a critical component of initial diagnosis, surgical planning, and post-treatment monitoring. However, conventional MRI does not provide information regarding tumor microvasculature, necrosis, or neoangiogenesis. In addition, traditional MRI imaging can be further confounded by treatment-related effects such as pseudoprogression, radiation necrosis, and/or pseudoresponse(s) that preclude clinicians from making fully informed decisions when structuring a therapeutic approach. A myriad of novel imaging modalities have been developed to address these deficits. Herein, we provide a clinically oriented review of standard techniques for imaging GBM and highlight emerging technologies utilized in disease characterization and therapeutic development.
PubMed: 35821676
DOI: 10.1093/noajnl/vdac080 -
Neuro-oncology Oct 2014Over the past 20 years, very few agents have been approved for the treatment of brain tumors. Recent studies have highlighted some of the challenges in assessing... (Review)
Review
Over the past 20 years, very few agents have been approved for the treatment of brain tumors. Recent studies have highlighted some of the challenges in assessing activity in novel agents for the treatment of brain tumors. This paper reviews some of the key challenges related to assessment of tumor response to therapy in adult high-grade gliomas and discusses the strengths and limitations of imaging-based endpoints. Although overall survival is considered the "gold standard" endpoint in the field of oncology, progression-free survival and response rate are endpoints that hold great value in neuro-oncology. Particular focus is given to advancements made since the January 2006 Brain Tumor Endpoints Workshop, including the development of Response Assessment in Neuro-Oncology criteria, the value of T2/fluid-attenuated inversion recovery, use of objective response rates and progression-free survival in clinical trials, and the evaluation of pseudoprogression, pseudoresponse, and inflammatory response in radiographic images.
Topics: Brain Neoplasms; Glioma; Humans; Magnetic Resonance Imaging; Neuroimaging; Response Evaluation Criteria in Solid Tumors
PubMed: 25313235
DOI: 10.1093/neuonc/nou224