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Cancer Management and Research 2021Complete tumor response can be achieved in a certain proportion of patients with locally advanced rectal cancer, who achieve maximal response to neoadjuvant therapy... (Review)
Review
Complete tumor response can be achieved in a certain proportion of patients with locally advanced rectal cancer, who achieve maximal response to neoadjuvant therapy (NAT). For these patients, a watch-and-wait (WW) or nonsurgical strategy has been proposed and is becoming widely practiced in order to avoid unnecessary surgical complications. Therefore, a non-invasive, reliable diagnostic tool for accurately evaluating complete tumor response is needed. Magnetic resonance imaging (MRI) plays a crucial role in both primary staging and restaging tumor response to NAT in rectal cancer without relying on resected specimen. In recent years, numerous efforts have been made to research the value of MRI in predicting and evaluating complete response in rectal cancer. Current MRI evaluation is mainly based on morphological and functional images. Morphologic MRI yields high soft tissue resolution, multiplanar images, and provides detailed depictions of rectal cancer and its surrounding structures. Functional MRI may help to distinguish residual tumor from fibrosis, therefore improving the diagnostic performance of morphologic MRI in identifying complete tumor response. Both morphologic and functional MRI have several promising parameters that may help accurately evaluate and/or predict complete response of rectal cancer. However, these parameters still have limitations and the results remain inconsistent. Recent development of new techniques, such as textural analysis, radiomics analysis and deep learning, demonstrate great potential based on MRI-derived parameters. This article aimed to review and help better understand the strengths, limitations, and future trends of these MRI-derived methods in evaluating complete response in rectal cancer.
PubMed: 34103987
DOI: 10.2147/CMAR.S309252 -
Annual Review of Physiology Feb 2024Tuft cells are a rare and morphologically distinct chemosensory cell type found throughout many organs, including the gastrointestinal tract. These cells were identified... (Review)
Review
Tuft cells are a rare and morphologically distinct chemosensory cell type found throughout many organs, including the gastrointestinal tract. These cells were identified by their unique morphologies distinguished by large apical protrusions. Ultrastructural data have begun to describe the molecular underpinnings of their cytoskeletal features, and tuft cell-enriched cytoskeletal proteins have been identified, although the connection of tuft cell morphology to tuft cell functionality has not yet been established. Furthermore, tuft cells display variations in function and identity between and within tissues, leading to the delineation of distinct tuft cell populations. As a chemosensory cell type, they display receptors that are responsive to ligands specific for their environment. While many studies have demonstrated the tuft cell response to protists and helminths in the intestine, recent research has highlighted other roles of tuft cells as well as implicated tuft cells in other disease processes including inflammation, cancer, and viral infections. Here, we review the literature on the cytoskeletal structure of tuft cells. Additionally, we focus on new research discussing tuft cell lineage, ligand-receptor interactions, tuft cell tropism, and the role of tuft cells in intestinal disease. Finally, we discuss the implication of tuft cell-targeted therapies in human health and how the morphology of tuft cells may contribute to their functionality.
Topics: Humans; Intestinal Mucosa; Tuft Cells; Intestines; Gastrointestinal Tract; Cell Lineage
PubMed: 37863104
DOI: 10.1146/annurev-physiol-042022-030310 -
Cancer Cell International Jul 2022Glioblastoma is a highly aggressive brain tumor. A big effort is required to find novel molecules which can cross the blood-brain barrier and efficiently kill these...
BACKGROUND
Glioblastoma is a highly aggressive brain tumor. A big effort is required to find novel molecules which can cross the blood-brain barrier and efficiently kill these tumor cells. In this perspective, trehalose (α-glucopyranosyl-[1→1]-α-D-glucopyranoside), found in various dietary sources and used as a safe nutrient supplement, attracted our attention for its pleiotropic effects against tumor cells.
METHODS
Human glioblastoma cell lines U373-MG and T98G were exposed to trehalose and analyzed at different time points. Cell proliferation was evaluated at medium term, and clonogenic capacity and cell morphology were evaluated at long term. Western blot was used to evaluate biochemical markers of autophagy (also measured in cells co-treated with EIPA or chloroquine), and mTOR, AMPK and ERK 1/2 signalling. Macropinocytosis was evaluated morphologically by bright-field microscopy; in cells loaded with the fluorescein-conjugated fluid-phase tracer dextran, macropinocytic vacuoles were also visualized by fluorescence microscopy, and the extent of macropinocytosis was quantified by flow cytometry.
RESULTS
The long-term effect of trehalose on U373-MG and T98G cell lines was impressive, as indicated by a dramatic reduction in clonogenic efficiency. Mechanistically, trehalose proved to be an efficient autophagy inducer in macropinocytosis-deficient T98G cells and an efficient inducer of macropinocytosis and eventual cell death by methuosis in U373-MG glioblastoma cells, proved to be poorly responsive to induction of autophagy. These two processes appeared to act in a mutually exclusive manner; indeed, co-treatment of U373-MG cells with the macropinocytosis inhibitor, EIPA, significantly increased the autophagic response. mTOR activation and AMPK inhibition occurred in a similar way in the two trehalose-treated cell lines. Interestingly, ERK 1/2 was activated only in macropinocytosis-proficient U373-MG cells harbouring loss-of-function mutations in the negative RAS regulator, NF1, suggesting a key role of RAS signalling.
CONCLUSIONS
Our results indicate that trehalose is worthy of further study as a candidate molecule for glioblastoma therapy, due to its capacity to induce a sustained autophagic response, ultimately leading to loss of clonogenic potential, and more interestingly, to force macropinocytosis, eventually leading to cell death by methuosis, particularly in tumor cells with RAS hyperactivity. As a further anticancer strategy, stimulation of macropinocytosis may be exploited to increase intracellular delivery of anticancer drugs.
PubMed: 35864494
DOI: 10.1186/s12935-022-02652-5 -
Frontiers in Behavioral Neuroscience 2022Stress exposure has been shown to induce a variety of molecular and functional alterations associated with anxiety and depression. Some studies suggest that microglia,...
Stress exposure has been shown to induce a variety of molecular and functional alterations associated with anxiety and depression. Some studies suggest that microglia, the immune cells of the brain, play a significant role in determining neuronal and behavioral responses to chronic stress and also contribute to the development of stress-related psychopathologies. However, little is known about the impact of the duration of stress exposure upon microglia and neurons morphology, particularly considering sex differences. This issue deserves particular investigation, considering that the process of morphologic remodeling of neurons and microglia is usually accompanied by functional changes with behavioral expression. Here, we examine the effects of short and long unpredictable chronic mild stress (uCMS) protocols on behavior, evaluating in parallel microglia and neurons morphology in the dorsal hippocampus (dHIP) and in the (NAc), two brain regions involved in the etiology of depression. We report that long-term uCMS induced more behavioral alterations in males, which present anxiety and depression-like phenotypes (anhedonia and helplessness behavior), while females only display anxiety-like behavior. After short-term uCMS, both sexes presented anxiety-like behavior. Microglia cells undergo a process of morphologic adaptation to short-term uCMS, dependent on sex, in the NAc: we observed a hypertrophy in males and an atrophy in females, transient effects that do not persist after long-term uCMS. In the dHIP, the morphologic adaptation of microglia is only observed in females (hypertrophy) and after the protocol of long uCMS. Interestingly, males are more vulnerable to neuronal morphological alterations in a region-specific manner: dendritic atrophy in granule neurons of the dHIP and hypertrophy in the medium spiny neurons of the NAc, both after short- or long-term uCMS. The morphology of neurons in these brain regions were not affected in females. These findings raise the possibility that, by differentially affecting neurons and microglia in dHIP and NAc, chronic stress may contribute for differences in the clinical presentation of stress-related disorders under the control of sex-specific mechanisms.
PubMed: 35330844
DOI: 10.3389/fnbeh.2022.834821 -
Proceedings of the National Academy of... Mar 2021Patterns and morphology develop in living systems such as embryos in response to chemical signals. To understand and exploit the interplay of chemical reactions with...
Patterns and morphology develop in living systems such as embryos in response to chemical signals. To understand and exploit the interplay of chemical reactions with mechanical transformations, chemomechanical polymer systems have been synthesized by attaching chemicals into hydrogels. In this work, we design autonomous responsive elastic shells that undergo morphological changes induced by chemical reactions. We couple the local mechanical response of the gel with the chemical processes on the shell. This causes swelling and deswelling of the gel, generating diverse morphological changes, including periodic oscillations. We further introduce a mechanical instability and observe buckling-unbuckling dynamics with a response time delay. Moreover, we investigate the mechanical feedback on the chemical reaction and demonstrate the dynamic patterns triggered by an initial deformation. We show the chemical characteristics that account for the shell morphology and discuss the future designs for autonomous responsive materials.
PubMed: 33649242
DOI: 10.1073/pnas.2025717118 -
Frontiers in Aging Neuroscience 2022The levodopa challenge test (LCT) has been routinely used in Parkinson disease (PD) evaluation and predicts the outcome of deep brain stimulation (DBS). Guidelines...
BACKGROUND
The levodopa challenge test (LCT) has been routinely used in Parkinson disease (PD) evaluation and predicts the outcome of deep brain stimulation (DBS). Guidelines recommend that patients with an improvement in Unified Parkinson's Disease Rating Scale (UPDRS)-III score > 33% in the LCT receive DBS treatment. However, LCT results are affected by many factors, and only provide information on the immediate effectiveness of dopamine. The aim of the present study was to investigate the relationship between LCT outcome and brain imaging features of PD patients to determine whether the latter can be used to identify candidates for DBS.
METHODS
A total of 38 PD patients were enrolled in the study. Based on improvement in UPDRS-III score in the LCT, patients were divided into low improvement (PD-LCT-L) and high improvement (PD-LCT-H) groups. Each patient's neural network was reconstructed based on T1-weighted magnetic resonance imaging data using the Jensen-Shannon divergence similarity estimation method. The network was established with the multiple kernel support vector machine technique. We analyzed differences in individual morphologic brain networks and their global and local metrics to determine whether there were differences in the connectomes of PD-LCT-L and PD-LCT-H groups.
RESULTS
The 2 groups were similar in terms of demographic and clinical characteristics. Mean ± SD levodopa responsiveness was 26.52% ± 3.47% in the PD-LCT-L group (N = 13) and 58.66% ± 4.09% in the PD-LCT-H group ( = 25). There were no significant differences between groups in global and local metrics. There were 43 consensus connections that were affected in both groups; in PD-LCT-L patients, most of these connections were decreased whereas those related to the dorsolateral superior frontal gyrus and left cuneus were significantly increased.
CONCLUSION
Morphologic brain network assessment is a valuable method for predicting levodopa responsiveness in PD patients, which can facilitate the selection of candidates for DBS.
PubMed: 36688150
DOI: 10.3389/fnagi.2022.990913 -
Psychonomic Bulletin & Review Dec 2022We investigated the processing of morphologically complex words adopting an approach that goes beyond estimating average effects and allows testing predictions about...
We investigated the processing of morphologically complex words adopting an approach that goes beyond estimating average effects and allows testing predictions about variability in performance. We tested masked morphological priming effects with English derived ('printer') and inflected ('printed') forms priming their stems ('print') in non-native speakers, a population that is characterized by large variability. We modeled reaction times with a shifted-lognormal distribution using Bayesian distributional models, which allow assessing effects of experimental manipulations on both the mean of the response distribution ('mu') and its standard deviation ('sigma'). Our results show similar effects on mean response times for inflected and derived primes, but a difference between the two on the sigma of the distribution, with inflectional priming increasing response time variability to a significantly larger extent than derivational priming. This is in line with previous research on non-native processing, which shows more variable results across studies for the processing of inflected forms than for derived forms. More generally, our study shows that treating variability in performance as a direct object of investigation can crucially inform models of language processing, by disentangling effects which would otherwise be indistinguishable. We therefore emphasize the importance of looking beyond average performance and testing predictions on other parameters of the distribution rather than just its central tendency.
Topics: Humans; Bayes Theorem; Language; Reaction Time
PubMed: 35715685
DOI: 10.3758/s13423-022-02109-w -
International Journal of Molecular... Feb 2023In acute myeloid leukemia (AML) many patients experience relapse, despite the achievement of morphological complete remission; therefore, conventional morphologic... (Review)
Review
In acute myeloid leukemia (AML) many patients experience relapse, despite the achievement of morphological complete remission; therefore, conventional morphologic criteria are currently considered inadequate for assessing the quality of the response after treatment. Quantification of measurable residual disease (MRD) has been established as a strong prognostic marker in AML and patients that test MRD negative have lower relapse rates and better survival than those who test positive. Different techniques, varying in their sensitivity and applicability to patients, are available for the measurement of MRD and their use as a guide for selecting the most optimal post-remission therapy is an area of active investigation. Although still controversial, MRD prognostic value promises to support drug development serving as a surrogate biomarker, potentially useful for accelerating the regulatory approval of new agents. In this review, we will critically examine the methods used to detect MRD and its potential role as a study endpoint.
Topics: Humans; Leukemia, Myeloid, Acute; Remission Induction; Biomarkers; Neoplasm, Residual; Recurrence
PubMed: 36834477
DOI: 10.3390/ijms24043062 -
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 -
Physiologia Plantarum Dec 2019Drought is the primary limitation to plant growth and yield in agricultural systems. Cucumber (Cucumis sativus) is one of the most important vegetables worldwide and has...
Drought is the primary limitation to plant growth and yield in agricultural systems. Cucumber (Cucumis sativus) is one of the most important vegetables worldwide and has little tolerance for water deficit. To understand the drought stress response strategy of this plant, the responses of cucumber to short-term drought and rewatering were determined in this study by morphological structure and proteomic analyses. The leaf relative water content was significantly decreased under drought, and the cell structure was altered, while rewatering obviously alleviated the symptoms of water shortage and cell damage. A total of 320 and 246 proteins exhibiting significant abundance changes in response to drought and recovery, respectively, were identified. Our proteome analysis showed that 63 co-regulated proteins were shared between drought and rewatering, whereas most of the responsive proteins were unique. The proteome is adjusted through a sequence of regulatory processes including the biosynthesis of secondary metabolites and the glutathione metabolism pathway, which showed a high correlation between protein abundance profile and corresponding enzyme activity. Drought and recovery regulated different types of proteins, allowing plants to adapt to environmental stress or restore growth, respectively, which suggests that short-term drought and recovery are almost fully uncoupled processes. As an important component of the antioxidant system in plants, glutathione metabolism may be one of the main strategies for regulating antioxidant capacity during drought recovery. Our results provide useful information for further analyses of drought adaptability in cucumber plants.
Topics: Cucumis sativus; Droughts; Plant Leaves; Plant Proteins; Proteome; Stress, Physiological; Water
PubMed: 30663056
DOI: 10.1111/ppl.12926