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BJR Open 2020Inaccurate assessment of surveillance imaging to assess response to glioma therapy may have life-changing consequences. Varied management plans including chemotherapy,... (Review)
Review
Inaccurate assessment of surveillance imaging to assess response to glioma therapy may have life-changing consequences. Varied management plans including chemotherapy, radiotherapy or immunotherapy may all contribute to heterogeneous post-treatment appearances and the overlap between the morphological features of pseudoprogression, pseudoresponse and radiation necrosis can make their discrimination very challenging. Therefore, there has been a drive to develop objective strategies for post-treatment assessment of brain gliomas. This review discusses the most important of these approaches such as the RANO "Response Assessment in Neuro-Oncology", iRANO "Immunotherapy Response Assessment in Neuro-Oncology" and RAPNO "Response Assessment in Paediatric Neuro-Oncology" models. In addition to these systematic approaches for glioma surveillance, the relatively limited information provided by conventional imaging modalities alone has motivated the development of novel advanced magnetic resonance (MR) and metabolic imaging methods for further discrimination between viable tumour and treatment induced changes. Multiple clinical trials and meta-analyses have investigated the diagnostic performance of these novel techniques in the follow up of brain gliomas, including both single modality descriptive studies and comparative imaging assessment. In this manuscript, we review the literature and discuss the promises and pitfalls of frequently studied modalities in glioma surveillance imaging, including MR perfusion, MR diffusion and MR spectroscopy. In addition, we evaluate other promising MR techniques such as chemical exchange saturation transfer as well as fludeoxyglucose and non-FDG positron emission tomography techniques.
PubMed: 33178973
DOI: 10.1259/bjro.20200009 -
International Journal of Molecular... Oct 2020Abscisic acid (ABA) is involved in regulating drought tolerance, and pyrabactin resistance-like (PYL) proteins are known as ABA receptors. To elucidate the role of one...
Precise Editing of the Gene by RNA-Guided Cas9 Nuclease Confers Enhanced Drought Tolerance and Grain Yield in Rice ( L.) by Regulating Circadian Rhythm and Abiotic Stress Responsive Proteins.
Abscisic acid (ABA) is involved in regulating drought tolerance, and pyrabactin resistance-like (PYL) proteins are known as ABA receptors. To elucidate the role of one of the ABA receptors in rice, was mutagenized through CRISPR/Cas9 in rice. Homozygous and heterozygous mutant plants lacking any off-targets and T-DNA were screened based on site-specific sequencing and used for morpho-physiological, molecular, and proteomic analysis. Mutant lines appear to accumulate higher ABA, antioxidant activities, chlorophyll content, leaf cuticular wax, and survival rate, whereas a lower malondialdehyde level, stomatal conductance, transpiration rate, and vascular bundles occur under stress conditions. Proteomic analysis found a total of 324 differentially expressed proteins (DEPs), out of which 184 and 140 were up and downregulated, respectively. The mutants showed an increase in grain yield under both drought and well watered field conditions. Most of the DEPs related to circadian clock rhythm, drought response, and reactive oxygen species were upregulated in the mutant plants. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that DEPs were only involved in circadian rhythm and Gene Ontology (GO) analysis showed that most of the DEPs were involved in response to abiotic stimulus, and abscisic acid-activated signaling pathways. Protein GIGANTEA, Adagio-like, and Pseudo-response regulator proteins showed higher interaction in protein-protein interaction (PPI) network. Thus, the overall results showed that CRISPR/Cas9-generated mutants have potential to improve both drought tolerance and the yield of rice. Furthermore, global proteome analysis provides new potential biomarkers and understandings of the molecular mechanism of rice drought tolerance.
Topics: Abscisic Acid; CRISPR-Cas Systems; Chlorophyll; Circadian Rhythm; Droughts; Gene Editing; Gene Expression Regulation, Plant; Intracellular Signaling Peptides and Proteins; Oryza; Plant Proteins; Plants, Genetically Modified; Proteomics; Reactive Oxygen Species; Stress, Physiological
PubMed: 33113937
DOI: 10.3390/ijms21217854 -
PeerJ 2020The circadian clock not only participates in regulating various stages of plant growth, development and metabolism, but confers plant environmental adaptability to...
BACKGROUND
The circadian clock not only participates in regulating various stages of plant growth, development and metabolism, but confers plant environmental adaptability to stress such as drought. Pseudo-Response Regulators (PRRs) are important component of the central oscillator (the core of circadian clock) and play a significant role in plant photoperiod pathway. However, no systematical study about this gene family has been performed in cotton.
METHODS
genes were identified in diploid and tetraploid cotton using bioinformatics methods to investigate their homology, duplication and evolution relationship. Differential gene expression, KEGG enrichment analysis and qRT-PCR were conducted to analyze gene expression patterns under diurnal changes and their response to drought stress.
RESULTS
A total of 44 PRR family members were identified in four species, with 16 in , 10 in , and nine in as well as in . Phylogenetic analysis indicated that PRR proteins were divided into five subfamilies and whole genome duplication or segmental duplication contributed to the expansion of PRR gene family. Gene structure analysis revealed that members in the same clade are similar, and multiple cis-elements related to light and drought stress response were enriched in the promoters of genes. qRT-PCR results showed that genes transcripts presented four expression peaks (6 h, 9 h, 12 h, 15 h) during 24 h and form obvious rhythmic expression trend. Transcriptome data with PEG treatment, along with qRT-PCR verification suggested that members of clade III () and clade V ( and ) may be involved in drought response. This study provides an insight into understanding the function of genes in circadian rhythm and in response to drought stress in cotton.
PubMed: 33033660
DOI: 10.7717/peerj.9936 -
Clinical Cancer Research : An Official... Jan 2021To explore a prognostic or predictive role of MRI and O-(2-F-fluoroethyl)-L-tyrosine (FET) PET parameters for outcome in the randomized multicenter trial ARTE that... (Randomized Controlled Trial)
Randomized Controlled Trial
MRI and FET-PET Predict Survival Benefit from Bevacizumab Plus Radiotherapy in Patients with Isocitrate Dehydrogenase Wild-type Glioblastoma: Results from the Randomized ARTE Trial.
PURPOSE
To explore a prognostic or predictive role of MRI and O-(2-F-fluoroethyl)-L-tyrosine (FET) PET parameters for outcome in the randomized multicenter trial ARTE that compared bevacizumab plus radiotherapy with radiotherpay alone in elderly patients with glioblastoma.
PATIENTS AND METHODS
Patients with isocitrate dehydrogenase wild-type glioblastoma ages 65 years or older were included in this analysis. Tumor volumetric and apparent diffusion coefficient (ADC) analyses of serial MRI scans from 67 patients and serial FET-PET tumor-to-brain intensity ratios (TBRs) from 31 patients were analyzed blinded for treatment arm and outcome. Multivariate Cox regression analysis was done to account for established prognostic factors and treatment arm.
RESULTS
Overall survival benefit from bevacizumab plus radiotherapy compared with radiotherapy alone was observed for larger pretreatment MRI contrast-enhancing tumor [HR per cm 0.94; 95% confidence interval (CI), 0.89-0.99] and for higher ADC (HR 0.18; CI, 0.05-0.66). Higher FET-TBR on pretreatment PET scans was associated with inferior overall survival in both arms. Response assessed by standard MRI-based Response Assessment in Neuro-Oncology criteria was associated with overall survival in the bevacizumab plus radiotherapy arm by trend only ( = 0.09). High FET-TBR of noncontrast-enhancing tumor portions during bevacizumab therapy was associated with inferior overall survival on multivariate analysis (HR 5.97; CI, 1.16-30.8).
CONCLUSIONS
Large pretreatment contrast-enhancing tumor mass and higher ADCs identify patients who may experience a survival benefit from bevacizumab plus radiotherapy. Persistent FET-PET signal of no longer contrast-enhancing tumor after concomitant bevacizumab plus radiotherapy suggests pseudoresponse and predicts poor outcome.
Topics: Aged; Aged, 80 and over; Bevacizumab; Brain; Brain Neoplasms; Chemoradiotherapy; Female; Glioblastoma; Humans; Isocitrate Dehydrogenase; Magnetic Resonance Imaging; Male; Positron-Emission Tomography; Progression-Free Survival; Radiopharmaceuticals; Tyrosine
PubMed: 32967939
DOI: 10.1158/1078-0432.CCR-20-2096 -
Frontiers in Oncology 2020Imaging-based monitoring of disease burden in glioma patients is frequently confounded by treatment effects. Circulating biomarkers could theoretically augment...
Imaging-based monitoring of disease burden in glioma patients is frequently confounded by treatment effects. Circulating biomarkers could theoretically augment imaging-based response monitoring. This systematic review aimed to present and evaluate evidence for differential expression and diagnostic accuracy of circulating biomarkers with respect to outcomes of tumor response, progression, stable disease, and treatment effects (pseudoprogression, radionecrosis, pseudoresponse, and pseudolesions) in patients undergoing treatment for World Health Organization grades II-IV diffuse astrocytic and oligodendroglial tumors. MEDLINE, EMBASE, Web Of Science, and SCOPUS databases were searched until August 18, 2019, for observational or diagnostic studies on multiple circulating biomarker types: extracellular vesicles, circulating nucleic acids, circulating tumor cells, circulating proteins, and metabolites, angiogenesis related cells, immune cells, and other cell lines. Methodological quality of included studies was assessed using an adapted Quality Assessment of Diagnostic Accuracy Studies-2 tool, and level of evidence (IA-IVD) for individual biomarkers was evaluated using an adapted framework from the National Comprehensive Cancer Network guidelines on evaluating tumor marker utility. Of 13,202 unique records, 58 studies met the inclusion criteria. One hundred thirty-three distinct biomarkers were identified in a total of 1,853 patients across various treatment modalities. Fifteen markers for response, progression, or stable disease and five markers for pseudoprogression or radionecrosis reached level IB. No biomarkers reached level IA. Only five studies contained data for diagnostic accuracy measures. Overall methodological quality of included studies was low. While extensive data on biomarker dysregulation in varying response categories were reported, no biomarkers ready for clinical application were identified. Further assay refinement and evaluation in larger cohorts with diagnostic accuracy study designs are required. : CRD42018110658.
PubMed: 32923382
DOI: 10.3389/fonc.2020.01191 -
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 -
Neuro-oncology Advances 2019
PubMed: 32642667
DOI: 10.1093/noajnl/vdz038 -
Physiologia Plantarum Jul 2020Hypocotyl elongation relies on directional cell expansion, a process under light and circadian clock control. Under short photoperiods (SD), hypocotyl elongation in...
Hypocotyl elongation relies on directional cell expansion, a process under light and circadian clock control. Under short photoperiods (SD), hypocotyl elongation in Arabidopsis thaliana follows a rhythmic pattern, a process in which circadian morning-to-midnight waves of the transcriptional repressors PSEUDO-RESPONSE REGULATORS (PRRs) jointly gate PHYTOCHROME-INTERACTING FACTOR (PIF) activity to dawn. Previously, we described CYCLING DOF FACTOR 5 (CDF5) as a target of this antagonistic PRR/PIF dynamic interplay. Under SD, PIFs induce CDF5 accumulation specifically at dawn, when it promotes the expression of positive cell elongation regulators such as YUCCA8 to induce growth. In contrast to SD, hypocotyl elongation under long days (LD) is largely reduced. Here, we examine whether CDF5 is an actor in this photoperiod specific regulation. We report that transcription of CDF5 is robustly induced in SD compared to LD, in accordance with PIFs accumulating to higher levels in SD, and in contrast to other members of the CDF family, whose expression is mainly clock regulated and have similar waveforms in SD and LD. Notably, when CDF5 was constitutively expressed under LD, CDF5 protein accumulated to levels comparable to SD but was inactive in promoting cell elongation. Similar results were observed for CDF1. Our findings indicate that both CDFs can promote cell elongation specifically in shorter photoperiods, however, their activity in LD is inhibited at the post-translational level. These data not only expand our understanding of the biological role of CDF transcription factors, but also identify a previously unrecognized regulatory layer in the photoperiodic response of hypocotyl elongation.
Topics: Arabidopsis Proteins; Basic Helix-Loop-Helix Transcription Factors; Gene Expression Regulation, Plant; Hypocotyl; Light; Photoperiod
PubMed: 32379360
DOI: 10.1111/ppl.13119 -
Frontiers in Plant Science 2020Timing of flowering is crucial for the transformation from vegetative to reproductive growth in the important food crop, wheat ( L.). The circadian clock is a central...
Timing of flowering is crucial for the transformation from vegetative to reproductive growth in the important food crop, wheat ( L.). The circadian clock is a central part of photoperiod regulation, with Pseudo-Response Regulators (PRRs) representing key components of circadian networks. However, little is known about the effects of PRR family members on yield-related traits in crop plants. In this study, we identified polymorphisms and haplotypes of , demonstrating that natural variations in are associated with significant differences in yield-related traits including heading date, plant height and thousand grain weight. showed an earlier heading date, advanced by 0.9 to 1.7%. and displayed reduced plant height and increased thousand grain weight of up to 13.3 to 26.4% and 6.3 to 17.3%, respectively. Subcellular localization and transcriptional activity analysis showed that TaPRR1 is a nuclear localization protein with transcriptional activity controlled by an IR domain. The expression profiles of genes over a 48-h period were characterized by circadian rhythms, which had two peaks under both short- and long- day conditions. In addition, geographical distribution analysis indicated higher distribution frequencies of , , and in different agro-ecological production zones. Furthermore, analysis of molecular variance of the distribution frequency of haplotypes suggested significant differences in haplotype distribution frequency between landraces and modern cultivars. Our study provides a basis for in-depth understanding of function on yield-related traits in wheat, as well as establishing theoretical guidance for wheat molecular marker-assisted breeding.
PubMed: 32226438
DOI: 10.3389/fpls.2020.00285 -
Cancer Biotherapy & Radiopharmaceuticals Aug 2020An α particle-emitting nanodrug that is a potent and specific antitumor agent and also prompts significant remodeling of local immunity in the tumor microenvironment...
An α particle-emitting nanodrug that is a potent and specific antitumor agent and also prompts significant remodeling of local immunity in the tumor microenvironment (TME) has been developed and may impact the treatment of melanoma. Biocompatible ultrasmall fluorescent core-shell silica nanoparticles (C' dots, diameter ∼6.0 nm) have been engineered to target the melanocortin-1 receptor expressed on melanoma through α melanocyte-stimulating hormone peptides attached to the C' dot surface. Actinium-225 is also bound to the nanoparticle to deliver a densely ionizing dose of high-energy α particles to cancer. Nanodrug pharmacokinetic properties are optimal for targeted radionuclide therapy as they exhibit rapid blood clearance, tumor-specific accumulation, minimal off-target localization, and renal elimination. Potent and specific tumor control, arising from the α particles, was observed in a syngeneic animal model of melanoma. Surprisingly, the C' dot component of this drug initiates a favorable pseudopathogenic response in the TME generating distinct changes in the fractions of naive and activated CD8 T cells, Th1 and regulatory T cells, immature dendritic cells, monocytes, MΦ and M1 macrophages, and activated natural killer cells. Concomitant upregulation of the inflammatory cytokine genome and adaptive immune pathways each describes a macrophage-initiated pseudoresponse to a viral-shaped pathogen. This study suggests that therapeutic α-particle irradiation of melanoma using ultrasmall functionalized core-shell silica nanoparticles potently kills tumor cells, and at the same time initiates a distinct immune response in the TME.
Topics: Actinium; Alpha Particles; Animals; Cell Line, Tumor; Computational Biology; Disease Models, Animal; Dose-Response Relationship, Radiation; Drug Carriers; Female; Gene Expression Regulation, Neoplastic; Humans; Immunity, Cellular; Male; Maximum Tolerated Dose; Melanoma, Experimental; Mice; Molecular Targeted Therapy; Nanoparticles; RNA-Seq; Radiopharmaceuticals; Receptor, Melanocortin, Type 1; Silicon Dioxide; Skin Neoplasms; Tissue Distribution; Tumor Microenvironment
PubMed: 32013538
DOI: 10.1089/cbr.2019.3150