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The Korean Journal of Internal Medicine May 2019The Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) or European Organization for Research and Treatment of Cancer (EORTC) criteria are used to... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND/AIMS
The Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) or European Organization for Research and Treatment of Cancer (EORTC) criteria are used to assess metabolic tumor responses. However, tumor responses have shown considerable discrepancies between the morphologic criteria (Response Evaluation Criteria in Solid Tumors [RECIST]) and metabolic criteria. We performed this pooled study to compare the RECIST and metabolic criteria in the assessment of tumor responses.
METHODS
Electronic databases were searched for eligible articles with the terms "RECIST," "PERCIST," or "EORTC criteria." The level of concordance in the tumor responses between the two criteria was estimated using κ statistics.
RESULTS
A total of 216 patients were collected from eight studies comparing the RECIST and EORTC criteria. The agreement of tumor responses between the two criteria was moderate (κ = 0.447). Eighty-six patients (39.8%) showed disagreement: tumor response was upgraded in 70 patients and downgraded in 16 when adopting the EORTC criteria. The EORTC criteria significantly increased the overall response rate (53% vs. 28%, p < 0.0001). The agreement of tumor responses between the RECIST and PERCIST was deemed fair (κ = 0.389). Of 407 patients from nine studies, 181 (44.5%) showed a discrepancy: using the PERCIST, tumor response were upgraded in 151 patients and downgraded in 30. When adopting the PERCIST, the overall response rate was also significantly increased from 30% to 55% (p < 0.0001).
CONCLUSION
This pooled analysis demonstrates that the concordance of tumor responses between the morphologic criteria and metabolic criteria is not excellent. When adopting the metabolic criteria instead of the RECIST, overall response rates were significantly increased.
Topics: Fluorodeoxyglucose F18; Humans; Neoplasms; Outcome Assessment, Health Care; Positron-Emission Tomography
PubMed: 29334722
DOI: 10.3904/kjim.2017.063 -
Science Advances Mar 2022Muscle stem cells (MuSCs) are essential for tissue homeostasis and regeneration, but the potential contribution of MuSC morphology to in vivo function remains unknown....
Muscle stem cells (MuSCs) are essential for tissue homeostasis and regeneration, but the potential contribution of MuSC morphology to in vivo function remains unknown. Here, we demonstrate that quiescent MuSCs are morphologically heterogeneous and exhibit different patterns of cellular protrusions. We classified quiescent MuSCs into three functionally distinct stem cell states: responsive, intermediate, and sensory. We demonstrate that the shift between different stem cell states promotes regeneration and is regulated by the sensing protein Piezo1. Pharmacological activation of Piezo1 is sufficient to prime MuSCs toward more responsive cells. Piezo1 deletion in MuSCs shifts the distribution toward less responsive cells, mimicking the disease phenotype we find in dystrophic muscles. We further demonstrate that Piezo1 reactivation ameliorates the MuSC morphological and regenerative defects of dystrophic muscles. These findings advance our fundamental understanding of how stem cells respond to injury and identify Piezo1 as a key regulator for adjusting stem cell states essential for regeneration.
PubMed: 35302846
DOI: 10.1126/sciadv.abn0485 -
Glia May 2021Astrocytes fulfil many functions in the central nervous system (CNS), including contribution to the blood brain barrier, synapse formation, and trophic support. In...
Astrocytes fulfil many functions in the central nervous system (CNS), including contribution to the blood brain barrier, synapse formation, and trophic support. In addition, they can mount an inflammatory response and are heterogeneous in morphology and function. To extensively characterize astrocyte subtypes, we FACS-isolated and gene expression profiled distinct astrocyte subtypes from three central nervous system regions; forebrain, hindbrain and spinal cord. Astrocyte subpopulations were separated based on GLAST/SLC1A3 and ACSA-2/ATP1B2 cell surface expression. The local brain environment proved key in establishing different transcriptional programs in astrocyte subtypes. Transcriptional differences between subtypes were also apparent in experimental autoimmune encephalomyelitis (EAE) mice, where these astrocyte subtypes showed distinct responses. While gene expression signatures associated with blood-brain barrier maintenance were lost, signatures involved in neuroinflammation and neurotoxicity were increased in spinal cord astrocytes, especially during acute disease stages. In chronic stages of EAE, this reactive astrocyte signature was slightly decreased, while obtaining a more proliferative profile, which might be relevant for glia scar formation and tissue regeneration. Morphological heterogeneity of astrocytes previously indicated the presence of astrocyte subtypes, and here we show diversity based on transcriptome variation associated with brain regions and differential responsiveness to a neuroinflammatory insult (EAE).
Topics: Adenosine Triphosphatases; Animals; Astrocytes; Cation Transport Proteins; Cell Adhesion Molecules, Neuronal; Encephalomyelitis, Autoimmune, Experimental; Mice; Mice, Inbred C57BL; Neuroinflammatory Diseases; Spinal Cord
PubMed: 33332631
DOI: 10.1002/glia.23954 -
International Journal of Molecular... Dec 2022Salt stress is an unfavorable outcome of global climate change, adversely affecting crop growth and yield. It is the second-biggest abiotic factor damaging the... (Review)
Review
Salt stress is an unfavorable outcome of global climate change, adversely affecting crop growth and yield. It is the second-biggest abiotic factor damaging the morphological, physio-biochemical, and molecular processes during seed germination and plant development. Salt responses include modulation of hormonal biosynthesis, ionic homeostasis, the antioxidant defense system, and osmoprotectants to mitigate salt stress. Plants trigger salt-responsive genes, proteins, and metabolites to cope with the damaging effects of a high salt concentration. Enhancing salt tolerance among crop plants is direly needed for sustainable global agriculture. Novel protein markers, which are used for crop improvement against salt stress, are identified using proteomic techniques. As compared to single-technique approaches, the integration of genomic tools and exogenously applied chemicals offers great potential in addressing salt-stress-induced challenges. The interplay of salt-responsive proteins and genes is the missing key of salt tolerance. The development of salt-tolerant crop varieties can be achieved by integrated approaches encompassing proteomics, metabolomics, genomics, and genome-editing tools. In this review, the current information about the morphological, physiological, and molecular mechanisms of salt response/tolerance in crops is summarized. The significance of proteomic approaches to improve salt tolerance in various crops is highlighted, and an integrated omics approach to achieve global food security is discussed. Novel proteins that respond to salt stress are potential candidates for future breeding of salt tolerance.
Topics: Proteomics; Plant Breeding; Crops, Agricultural; Genomics; Salt Tolerance; Stress, Physiological
PubMed: 36613963
DOI: 10.3390/ijms24010518 -
Cancers Jan 2021The tyrosine kinase inhibitor (TKI) Lenvatinib represents one of the most effective therapeutic options in patients with advanced radioiodine refractory differentiated...
BACKGROUND
The tyrosine kinase inhibitor (TKI) Lenvatinib represents one of the most effective therapeutic options in patients with advanced radioiodine refractory differentiated thyroid carcinoma (DTC). We aimed to assess the role of 2-deoxy-2-[F] fluoro-D-glucose positron-emission-tomography/computed-tomography (F-FDG-PET/CT) in the monitoring of functional tumor response compared to morphological response.
METHODS
In 22 patients, a modified Positron Emission Tomography Response Criteria In Solid Tumors (mPERCIST) evaluation before treatment with Lenvatinib and at 3 and 6 month follow up was performed. Further PET-parameters and morphologic tumor response using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 were assessed and their prediction of progression-free survival (PFS) and disease-specific survival (DSS) was evaluated.
RESULTS
Most patients were rated stable in morphological evaluation and progressive using a metabolic response. All patients who responded to therapy through RECIST showed a decline in nearly all Positron Emission Tomography (PET)-parameters. For both time-points, non-responders according to mPERCIST showed significantly lower median PFS and DSS, whereas according to RECIST, only DSS was significantly lower.
CONCLUSION
Tumor response assessment by F-FDG-PET outperforms morphological response assessment by CT in patients with advanced radioiodine refractory DTC treated with Lenvatinib, which seems to be correlated with clinical outcomes.
PubMed: 33467085
DOI: 10.3390/cancers13020317 -
Frontiers in Plant Science 2022Rice () is a human staple food and serves as a model organism for genetic and molecular studies. Few studies have been conducted to determine the effects of...
Rice () is a human staple food and serves as a model organism for genetic and molecular studies. Few studies have been conducted to determine the effects of ultraviolet-B (UV-B) stress on rice. UV-B stress triggers morphological and physiological changes in plants. However, the underlying mechanisms governing these integrated responses are unknown. In this study, we conducted a proteomic response of rice leaves to UV-B stress using two-dimensional gel electrophoresis and identified the selected proteins by mass spectrometry analysis. Four levels of daily biologically effective UV-B radiation intensities were imposed to determine changes in protein accumulation in response to UV-B stress: 0 (control), 5, 10, and 15 kJ m din two cultivars, i.e., IR6 and REX. To mimic the natural environment, we conducted this experiment in Sunlit Soil-Plant-Atmosphere-Research (SPAR) chambers. Among the identified proteins, 11% of differentially expressed proteins were found in both cultivars. In the Rex cultivar, only 45% of proteins are differentially expressed, while only 27.5% were expressed in IR6. The results indicate that REX is more affected by UV-B stress than IR6 cultivars. The identified protein TSJT1 (spot 16) in both cultivars plays a crucial role in plant growth and development during stress treatment. Additionally, we found that UV-B stress altered many antioxidant enzymes associated with redox homeostasis and cell defense response. Another enzyme, the glyceraldehyde-3-phosphate dehydrogenase (GAPDH), has been identified as spot 15, which plays an essential role in glycolysis and cellular energy production. Another vital protein identified is glycosyl hydrolase (GH) as spot 9, which catalyzes the hydrolysis of glycosidic bonds in cell wall polymers and significantly affects cell wall architecture. Some identified proteins are related to photosynthesis, protein biosynthesis, signal transduction, and stress response. The findings of our study provide new insights into understanding how rice plants are tailored to UV-B stress modulating the expression of UV-B responsive proteins, which will help develop superior rice breeds in the future to combat UV-B stress. Data are available ProteomeXchange with identifier PXD032163.
PubMed: 36212327
DOI: 10.3389/fpls.2022.871331 -
Biomedicines Jan 2023MRI is undoubtedly the cornerstone of brain tumor imaging, playing a key role in all phases of patient management, starting from diagnosis, through therapy planning, to... (Review)
Review
MRI is undoubtedly the cornerstone of brain tumor imaging, playing a key role in all phases of patient management, starting from diagnosis, through therapy planning, to treatment response and/or recurrence assessment. Currently, neuroimaging can describe morphologic and non-morphologic (functional, hemodynamic, metabolic, cellular, microstructural, and sometimes even genetic) characteristics of brain tumors, greatly contributing to diagnosis and follow-up. Knowing the technical aspects, strength and limits of each MR technique is crucial to correctly interpret MR brain studies and to address clinicians to the best treatment strategy. This article aimed to provide an overview of neuroimaging in the assessment of adult primary brain tumors. We started from the basilar role of conventional/morphological MR sequences, then analyzed, one by one, the non-morphological techniques, and finally highlighted future perspectives, such as radiomics and artificial intelligence.
PubMed: 36830900
DOI: 10.3390/biomedicines11020364 -
Frontiers in Plant Science 2015Plants have evolved sophisticated genetic and epigenetic regulatory systems to respond quickly to unfavorable environmental conditions such as heat, cold, drought, and... (Review)
Review
Plants have evolved sophisticated genetic and epigenetic regulatory systems to respond quickly to unfavorable environmental conditions such as heat, cold, drought, and pathogen infections. In particular, heat greatly affects plant growth and development, immunity and circadian rhythm, and poses a serious threat to the global food supply. According to temperatures exposing, heat can be usually classified as warm ambient temperature (about 22-27°C), high temperature (27-30°C) and extremely high temperature (37-42°C, also known as heat stress) for the model plant Arabidopsis thaliana. The genetic mechanisms of plant responses to heat have been well studied, mainly focusing on elevated ambient temperature-mediated morphological acclimation and acceleration of flowering, modulation of circadian clock and plant immunity by high temperatures, and thermotolerance to heat stress. Recently, great progress has been achieved on epigenetic regulation of heat responses, including DNA methylation, histone modifications, histone variants, ATP-dependent chromatin remodeling, histone chaperones, small RNAs, long non-coding RNAs and other undefined epigenetic mechanisms. These epigenetic modifications regulate the expression of heat-responsive genes and function to prevent heat-related damages. This review focuses on recent progresses regarding the genetic and epigenetic control of heat responses in plants, and pays more attention to the role of the major epigenetic mechanisms in plant heat responses. Further research perspectives are also discussed.
PubMed: 25964789
DOI: 10.3389/fpls.2015.00267 -
BioRxiv : the Preprint Server For... Jun 2024A better understanding of nicotine neurobiology is needed to reduce or prevent chronic addiction, ameliorate the detrimental effects of nicotine withdrawal, and increase...
A better understanding of nicotine neurobiology is needed to reduce or prevent chronic addiction, ameliorate the detrimental effects of nicotine withdrawal, and increase successful cessation of use. Nicotine binds and activates two astrocyte-expressed nicotinic acetylcholine receptors (nAChRs), α4β2 and α7. We recently found that ( or ) expression is restricted to astrocytes in mice and humans. To determine if AKT2 plays a role in astrocytic nicotinic responses, we generated astrocyte-specific conditional knockout (cKO) and full KO mice for and experiments. For studies, we examined mice exposed to chronic nicotine for two weeks in drinking water (200 μg/mL) and following acute nicotine challenge (0.09, 0.2 mg/kg) after 24 hrs. Our studies used cultured mouse astrocytes to measure nicotine-dependent astrocytic responses. We validated our approaches using lipopolysaccharide (LPS) exposure inducing astrogliosis. Sholl analysis was used to measure glial fibrillary acidic protein responses in astrocytes. Our data show that wild-type (WT) mice exhibit increased astrocyte morphological complexity during acute nicotine exposure, with decreasing complexity during chronic nicotine use, whereas cKO mice showed increased astrocyte morphology complexity. In culture, we found that 100μM nicotine was sufficient for morphological changes and blocking α7 or α4β2 nAChRs prevented observed morphologic changes. Finally, we performed conditioned place preference (CPP) in cKO mice and found that astrocytic AKT2 deficiency reduced nicotine preference compared to controls. These findings show the importance of nAChRs and signaling in the astrocytic response to nicotine.
PubMed: 38854016
DOI: 10.1101/2024.05.31.596856 -
Plants (Basel, Switzerland) Nov 2023Rice ( L.) is one of the most significant staple foods worldwide. Carbohydrates, proteins, vitamins, and minerals are just a few of the many nutrients found in... (Review)
Review
Rice ( L.) is one of the most significant staple foods worldwide. Carbohydrates, proteins, vitamins, and minerals are just a few of the many nutrients found in domesticated rice. Ensuring high and constant rice production is vital to facilitating human food supplies, as over three billion people around the globe rely on rice as their primary source of dietary intake. However, the world's rice production and grain quality have drastically declined in recent years due to the challenges posed by global climate change and abiotic stress-related aspects, especially drought, heat, cold, salt, submergence, and heavy metal toxicity. Rice's reduced photosynthetic efficiency results from insufficient stomatal conductance and natural damage to thylakoids and chloroplasts brought on by abiotic stressor-induced chlorosis and leaf wilting. Abiotic stress in rice farming can also cause complications with redox homeostasis, membrane peroxidation, lower seed germination, a drop in fresh and dry weight, necrosis, and tissue damage. Frequent stomatal movements, leaf rolling, generation of reactive oxygen radicals (RORs), antioxidant enzymes, induction of stress-responsive enzymes and protein-repair mechanisms, production of osmolytes, development of ion transporters, detoxifications, etc., are recorded as potent morphological, biochemical and physiological responses of rice plants under adverse abiotic stress. To develop cultivars that can withstand multiple abiotic challenges, it is necessary to understand the molecular and physiological mechanisms that contribute to the deterioration of rice quality under multiple abiotic stresses. The present review highlights the strategic defense mechanisms rice plants adopt to combat abiotic stressors that substantially affect the fundamental morphological, biochemical, and physiological mechanisms.
PubMed: 38068585
DOI: 10.3390/plants12233948