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Biomarker Research Jul 2021Response Evaluation Criteria in Solid Tumors (RECIST) is the gold standard for assessment of treatment response in solid tumors. Morphologic change of tumor size... (Review)
Review
Response Evaluation Criteria in Solid Tumors (RECIST) is the gold standard for assessment of treatment response in solid tumors. Morphologic change of tumor size evaluated by RECIST is often correlated with survival length and has been considered as a surrogate endpoint of therapeutic efficacy. However, the detection of morphologic change alone may not be sufficient for assessing response to new anti-cancer medication in all solid tumors. During the past fifteen years, several molecular-targeted therapies and immunotherapies have emerged in cancer treatment which work by disrupting signaling pathways and inhibited cell growth. Tumor necrosis or lack of tumor progression is associated with a good therapeutic response even in the absence of tumor shrinkage. Therefore, the use of unmodified RECIST criteria to estimate morphological changes of tumor alone may not be sufficient to estimate tumor response for these new anti-cancer drugs. Several studies have reported the low reliability of RECIST in evaluating treatment response in different tumors such as hepatocellular carcinoma, lung cancer, prostate cancer, brain glioma, bone metastasis, and lymphoma. There is an increased need for new medical imaging biomarkers, considering the changes in tumor viability, metabolic activity, and attenuation, which are related to early tumor response. Promising imaging techniques, beyond RECIST, include dynamic contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI), diffusion-weight imaging (DWI), magnetic resonance spectroscopy (MRS), and F-fluorodeoxyglucose (FDG) positron emission tomography (PET). This review outlines the current RECIST with their limitations and the new emerging concepts of imaging biomarkers in oncology.
PubMed: 34215324
DOI: 10.1186/s40364-021-00306-8 -
Journal of Neuroinflammation Dec 2022Both resident microglia and invading peripheral immune cells can respond to injury and degeneration in the central nervous system. However, after dead and dying neurons...
BACKGROUND
Both resident microglia and invading peripheral immune cells can respond to injury and degeneration in the central nervous system. However, after dead and dying neurons have been cleared and homeostasis is re-established, it is unknown whether resident immune cells fully resume normal functions and to what degree the peripheral immune cells take up residence.
METHODS
Using flow cytometry, in vivo retinal imaging, immunohistochemistry, and single-cell mRNA sequencing, we assess resident microglia and monocyte-derived macrophages in the retina during and after the loss of photoreceptors in the Arr1 mouse model of inducible degeneration.
RESULTS
We find that photoreceptor loss results in a small, sustained increase in mononuclear phagocytes and, after degeneration wanes, these cells re-establish a spatial mosaic reminiscent of healthy retinas. Transcriptomic analysis revealed the population remained unusually heterogeneous, with several subpopulations expressing gene patterns consistent with mildly activated phenotypes. Roughly a third of "new resident" cells expressed markers traditionally associated with both microglial and monocytic lineages, making their etiology ambiguous. Using an inducible Cre-based fluorescent lineage tracing paradigm to confirm the origins of new resident immune cells, we found approximately equal numbers of microglia and monocyte-derived macrophages after degeneration had subsided. In vivo retinal imaging and immunohistochemical analysis showed that both subpopulations remained functionally responsive to sites of local damage, though on average the monocyte-derived cells had less morphological complexity, expressed higher levels of MHCII, and had less migratory activity than the native resident population.
CONCLUSIONS
Monocytic cells that infiltrate the retina during degeneration differentiate into monocyte-derived macrophages that can remain in the retina long-term. These monocyte-derived macrophages adopt ramified morphologies and microglia-like gene expression. However, they remain distinguishable in morphology and gene expression from resident microglia and appear to differ functionally, showing less responsiveness to subsequent retinal injuries. These findings support the idea that persistent changes in the local immune population that occur in response to cell loss in aging and progressive retinal diseases may include the establishment of subpopulations of bone marrow-derived cells whose ability to respond to subsequent insults wanes over time.
Topics: Mice; Animals; Retinal Degeneration; Microglia; Macrophages; Retina; Monocytes
PubMed: 36510226
DOI: 10.1186/s12974-022-02652-2 -
TheScientificWorldJournal Nov 2013Drought is one of the most important phenomena which limit crops' production and yield. Crops demonstrate various morphological, physiological, biochemical, and... (Review)
Review
Drought is one of the most important phenomena which limit crops' production and yield. Crops demonstrate various morphological, physiological, biochemical, and molecular responses to tackle drought stress. Plants' vegetative and reproductive stages are intensively influenced by drought stress. Drought tolerance is a complicated trait which is controlled by polygenes and their expressions are influenced by various environmental elements. This means that breeding for this trait is so difficult and new molecular methods such as molecular markers, quantitative trait loci (QTL) mapping strategies, and expression patterns of genes should be applied to produce drought tolerant genotypes. In wheat, there are several genes which are responsible for drought stress tolerance and produce different types of enzymes and proteins for instance, late embryogenesis abundant (lea), responsive to abscisic acid (Rab), rubisco, helicase, proline, glutathione-S-transferase (GST), and carbohydrates during drought stress. This review paper has concentrated on the study of water limitation and its effects on morphological, physiological, biochemical, and molecular responses of wheat with the possible losses caused by drought stress.
Topics: Adaptation, Physiological; Droughts; Gene Expression Regulation, Plant; Plant Diseases; Plant Proteins; Stress, Physiological; Triticum
PubMed: 24319376
DOI: 10.1155/2013/610721 -
ACS Nano Feb 2021Materials that respond to endogenous stimuli are being leveraged to enhance spatiotemporal control in a range of biomedical applications from drug delivery to diagnostic... (Review)
Review
Materials that respond to endogenous stimuli are being leveraged to enhance spatiotemporal control in a range of biomedical applications from drug delivery to diagnostic tools. The design of materials that undergo morphological or chemical changes in response to specific biological cues or pathologies will be an important area of research for improving efficacies of existing therapies and imaging agents, while also being promising for developing personalized theranostic systems. Internal stimuli-responsive systems can be engineered across length scales from nanometers to macroscopic and can respond to endogenous signals such as enzymes, pH, glucose, ATP, hypoxia, redox signals, and nucleic acids by incorporating synthetic bio-inspired moieties or natural building blocks. This Review will summarize response mechanisms and fabrication strategies used in internal stimuli-responsive materials with a focus on drug delivery and imaging for a broad range of pathologies, including cancer, diabetes, vascular disorders, inflammation, and microbial infections. We will also discuss observed challenges, future research directions, and clinical translation aspects of these responsive materials.
Topics: Drug Delivery Systems; Humans; Neoplasms; Oxidation-Reduction; Precision Medicine; Stimuli Responsive Polymers
PubMed: 33555171
DOI: 10.1021/acsnano.0c09115 -
The Journal of Comparative Neurology Jul 2021Astrocytes are a population of central nervous system (CNS) cells with distinctive morphological and functional characteristics that differ within specific areas of the... (Review)
Review
Astrocytes are a population of central nervous system (CNS) cells with distinctive morphological and functional characteristics that differ within specific areas of the brain and are widely distributed throughout the CNS. There are mainly two types of astrocytes, protoplasmic and fibrous, which differ in morphologic appearance and location. Astrocytes are important cells of the CNS that not only provide structural support, but also modulate synaptic activity, regulate neuroinflammatory responses, maintain the blood-brain barrier, and supply energy to neurons. As a result, astrocytic disruption can lead to widespread detrimental effects and can contribute to the pathophysiology of several neurological conditions. The characteristics of astrocytes in more common neuropathologies such as Alzheimer's and Parkinson's disease have significantly been described and continue to be widely studied. However, there still exist numerous rare neurological conditions in which astrocytic involvement is unknown and needs to be explored. Accordingly, this review will summarize functional and morphological changes of astrocytes in various rare neurological conditions based on current knowledge thus far and highlight remaining neuropathologies where astrocytic involvement has yet to be investigated.
Topics: Animals; Astrocytes; Humans; Nervous System Diseases
PubMed: 33496339
DOI: 10.1002/cne.25118 -
Respiratory Research Sep 2023Rhinovirus infections commonly evoke asthma exacerbations in children and adults. Recurrent asthma exacerbations are associated with injury-repair responses in the... (Review)
Review
BACKGROUND
Rhinovirus infections commonly evoke asthma exacerbations in children and adults. Recurrent asthma exacerbations are associated with injury-repair responses in the airways that collectively contribute to airway remodeling. The physiological consequences of airway remodeling can manifest as irreversible airway obstruction and diminished responsiveness to bronchodilators. Structural cells of the airway, including epithelial cells, smooth muscle, fibroblasts, myofibroblasts, and adjacent lung vascular endothelial cells represent an understudied and emerging source of cellular and extracellular soluble mediators and matrix components that contribute to airway remodeling in a rhinovirus-evoked inflammatory environment.
MAIN BODY
While mechanistic pathways associated with rhinovirus-induced airway remodeling are still not fully characterized, infected airway epithelial cells robustly produce type 2 cytokines and chemokines, as well as pro-angiogenic and fibroblast activating factors that act in a paracrine manner on neighboring airway cells to stimulate remodeling responses. Morphological transformation of structural cells in response to rhinovirus promotes remodeling phenotypes including induction of mucus hypersecretion, epithelial-to-mesenchymal transition, and fibroblast-to-myofibroblast transdifferentiation. Rhinovirus exposure elicits airway hyperresponsiveness contributing to irreversible airway obstruction. This obstruction can occur as a consequence of sub-epithelial thickening mediated by smooth muscle migration and myofibroblast activity, or through independent mechanisms mediated by modulation of the β agonist receptor activation and its responsiveness to bronchodilators. Differential cellular responses emerge in response to rhinovirus infection that predispose asthmatic individuals to persistent signatures of airway remodeling, including exaggerated type 2 inflammation, enhanced extracellular matrix deposition, and robust production of pro-angiogenic mediators.
CONCLUSIONS
Few therapies address symptoms of rhinovirus-induced airway remodeling, though understanding the contribution of structural cells to these processes may elucidate future translational targets to alleviate symptoms of rhinovirus-induced exacerbations.
Topics: Child; Adult; Humans; Rhinovirus; Airway Remodeling; Endothelial Cells; Bronchodilator Agents; Asthma; Airway Obstruction
PubMed: 37773065
DOI: 10.1186/s12931-023-02529-9 -
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 -
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 -
Srpski Arhiv Za Celokupno Lekarstvo 2007Performing vigorous physical activity means a multiorgan system engagement, but the cardiovascular system plays a critical role. In order to provide enough oxygen to... (Review)
Review
Performing vigorous physical activity means a multiorgan system engagement, but the cardiovascular system plays a critical role. In order to provide enough oxygen to activate muscles during repeated physical activity of high intensity, the heart undergoes profound morphologic, functional and electrophysiological alterations, which have been identified as the "athlete's heart syndrome". "The athlete's heart" is a complex, but not precisely defined concept, anatomically and functionally and in relation to health and disease. It means the whole heart enlargement and/or hypertrophy of the cardiac muscle, also increasing economy of cardiac performance at rest and during physical activity with higher maximal functional capacities, all that having an adaptive response to vigorous physical activity. For morphological changes called the "athlete's heart, full-time, programed and intensive physical activity at maximal levels is primarily responsible. But as there are different kinds of physical activities, the degree of those morphological changes is highly variable. Considering many sudden cardiac deaths in sports, it is needless to say how important it is to know where the borderline is between normal changes of the heart due to physical activity and pathological changes due to some cardiac diseases. As sport has a growing socio-economic significance, sudden cardiac death events have to be reduced.
Topics: Adaptation, Physiological; Cardiomegaly; Death, Sudden, Cardiac; Humans; Sports; Syndrome
PubMed: 17642467
DOI: No ID Found -
Physics and Imaging in Radiation... Jan 2019Adaptive radiation planning for pancreatic adenocarcinoma (PA) relies on accurate treatment response assessment, while traditional response evaluation criteria...
Combined morphologic and metabolic pipeline for Positron emission tomography/computed tomography based radiotherapy response evaluation in locally advanced pancreatic adenocarcinoma.
BACKGROUND AND PURPOSE
Adaptive radiation planning for pancreatic adenocarcinoma (PA) relies on accurate treatment response assessment, while traditional response evaluation criteria inefficiently characterize tumors with complex morphological features or intrinsically low metabolism. To better assess treatment response of PA, we quantify and compare regional morphological and metabolic features of the 3D pre- and post-radiation therapy (RT) tumor models.
MATERIALS AND METHODS
Thirty-one PA patients with pre and post-RT Positron emission tomography/computed tomography (PET/CT) scans were evaluated. 3D meshes of pre- and post-RT tumors were generated and registered to establish vertex-wise correspondence. To assess tumor response, Mahalanobis distances ( ∣) between pre- and post-RT tumor surfaces with anatomic and metabolic fused vectors were calculated for each patient. ∣ was evaluated by overall survival (OS) prediction and survival risk classification. As a comparison, the same analyses were conducted on traditional imaging/physiological predictors, and distances measurements based on metabolic and morphological features only.
RESULTS
Among all the imaging/physiological parameters, ∣ was shown to be the best predictor of OS (HR = 0.52, p = 0.008), while other parameters failed to reach significance. Moreover, ∣ outperformed traditional morphologic and metabolic measurements in patient risk stratification, either alone (HR = 11.51, p < 0.001) or combined with age (HR = 9.04, p < 0.001).
CONCLUSIONS
We introduced a PET/CT-based novel morphologic and metabolic pipeline for response evaluation in locally advanced PA. The fused ∣ outperformed traditional morphologic, metabolic, and physiological measurements in OS prediction and risk stratification. The novel fusion model may serve as a new imaging-marker to more accurately characterize the heterogeneous tumor RT response.
PubMed: 32190750
DOI: 10.1016/j.phro.2018.12.003