Progression through dissemination to tumor-surrounding tissues and metastasis development is a hallmark of cancer that requires continuous cell-to-cell interactions and tissue remodeling. In fact, ...metastization can be regarded as a tissue disease orchestrated by cancer cells, leading to neoplastic colonization of new organs. Collagen is a major component of the extracellular matrix (ECM), and increasing evidence suggests that it has an important role in cancer progression and metastasis. Desmoplasia and collagen biomarkers have been associated with relapse and death in cancer patients. Despite the increasing interest in ECM and in the desmoplastic process in tumor microenvironment as prognostic factors and therapeutic targets in cancer, further research is required for a better understanding of these aspects of cancer biology. In this review, published evidence correlating collagen with cancer prognosis is retrieved and analyzed, and the role of collagen and its fragments in cancer pathophysiology is discussed.
Ranking among the most lethal tumour entities, pancreatic duct adenocarcinoma cells invade neighbouring tissue resulting in high incidence of metastasis. They are supported by tumour stroma ...fibroblasts which have undergone differentiation into cancer-associated fibroblasts (CAFs). Stiffness of cell substratum, cytokines, such as transforming growth factor-β (TGF-β), and stromal matrix proteins, such as laminin-332, are factors which promote CAF differentiation. In a spheroid culture system, differentiation of CAFs was analysed for laminin-332 production, laminin-binding integrin repertoire, adhesion and migration behaviour, and, in heterospheroids, for their interplay with the pancreatic duct adenocarcinoma AsPC-I cells. Our data reveal that CAFs produce laminin-332 thus contributing to its ectopic deposition within the tumour stroma. Moreover, CAF differentiation correlates with an increased expression of α3β1 integrin, the principal laminin-332-receptor. Beyond its role as novel CAF marker protein, integrin α3β1 crucially determines differentiation and maintenance of the CAF phenotype, as knock-out of the integrin α3 subunit reversed the CAF differentiated state. AsPC-I cells co-cultured in heterospheroids with integrin α3-deficient CAFs invaded less than from heterospheroids with wild-type CAFs. This study highlights the role of integrin α3β1 integrin-laminin-332 interaction of CAFs which promotes and sustains differentiation of CAFs and promotes carcinoma invasion.
•Prediction of Internal quality and browing disorders in pears with VIS-NIR.•Experiment mimics conditions for VIS-NIR fruit sorter in packinghouses.•Benchmark of regression models for SSC, firmness, ...weight and size in pears.•Benchmark of classification models for browning disorder detection in pears.
This study explores the possibility of predicting the soluble solids content (SSC), firmness and the presence of internal browning disorders in ‘Rocha’ pear (Pyrus communis L.) using a single VIS-NIR spectroscopic measurement in semi-transmittance mode. The spectroscopic measurement setup was developed to mimic real world conditions and takes into account geometry and technical requirements of a commercial fruit sorting optical module. The randomness of the fruit position during the spectra acquisition was simulated by sampling each fruit on four sides. Calibration models for internal quality properties were built using individual and/or average side spectra. The results show that models using the spectrum of each side as an individual sample only under-perform slightly relatively to the models based on spectra averages, which are common in the laboratory but very difficult to implement on an automated grading line. The performance of PLS, SVM and Ridge Regression models was compared for the prediction of SSC and firmness. Multiple types of spectra pre-processing were computed and the best combination of model and pre-processing method identified. The lowest RMSEP results for SSC and firmness were 0.7% (R2 = 0.71) and 7.66 N (R2 = 0.68) respectively, achieved using SVM on data pre-processed with Standard Normal Variate corrected 2nd derivative. For the internal disorder detection (browning), a classification benchmark composed by five different models (PLS-LDA, PCA-Logistic Regression, PCA-Extremely Randomized Trees, Extremely Randomized Trees and SVC) was implemented. PLS-LDA applied to the raw spectra presented the highest sensitivity, 76%. The results confirm that simultaneously achieving viable firmness and SSC predictions and internal disorder detection levels in pears is possible using a single VIS-NIR spectral measurement.
Despite significant advances in the treatment of thrombogenic diseases, antiplatelet therapies are still associated with a high bleeding risk. Consequently, potential benefits of preventing ...thromboembolic events by pharmacological agents need to be balanced with the potential harm of inducing hemorrhage. Glycoprotein VI (GPVI) is a platelet-specific receptor, which plays a crucial role in thrombus formation. GPVI deficiency has been identified in patients who suffer from significant reduction of collagen-induced thrombus formation, with a slight tendency for mild bleeding. However, an isolated GPVI deficiency can reduce thrombus formation while not resulting in severe bleeding. Together, these observations strongly suggest that physiological hemostasis does not require GPVI, but pharmacological GPVI modulation may provide novel "bleeding-free" antithrombotic therapies. In this review, we discuss recent findings regarding the biological role of GPVI in platelet-related disorders and highlight the efforts to develop potential therapeutic strategies based on its structure, signaling pathways, and biological effects.
Visible/near infrared spectroscopy (Vis-NIRS) was used to monitor the yellow-fleshed kiwifruit (Actinidia chinensis Planch ‘Jintao’) ripening on two selected orchards along 13 weeks, from pre-harvest ...to the late harvest. Calibration models for several Internal Quality Attibutes (IQA) were built from the spectral data of 375 individual kiwifruit. The analyzed IQA were L*, a* and b* from the CIELAB color space, hue angle, chroma, firmness, dry matter (DM), soluble solids content (SSC), juice pH and titratable acidity (TA). Different pre-processing methods were tested for the construction of PLS calibration models. SSC and Hue were the best performing models with a correlation coefficient of 0.81 and 0.88, and root mean square error of prediction (RMSEP) of 1.27% and 1.95∘, respectively. The interpretation of the models in terms of the known absorption bands and the impact of signal to noise ratio (SNR) in them is discussed. The calibration models were used to perform average predictions of the IQA on orchard subareas, for each day of the experiment. These average predictions were compared with the IQA’s average reference values on the same subareas and days. The model’s metrics improved significantly through the averaging procedure, with RMSEP = 0.26–0.36% and R2 = 0.99 for SSC; and RMSEP = 0.42∘ – 0.56∘ and R2 ≈ 1 for Hue. Since orchard management is done essentially through averages and not individual values, this result reinforces the applicability of the NIR technology for follow-up of fruit ripening in the tree.
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•‘Jintao’ ripening followed on tree, in two orchards, along a period > 12 weeks.•Good Vis-NIR calibration models (SDR> 2) were obtained for SSC, hue and a*.•Average predictions from those models, for each day and orchard yield SDR > 8.•Average predictions allow for efficient follow-up of ripening.•Signal-to-noise ratio > 200 important to establish good models.
Cadherins mediate cohesive contacts between isotypic cells by homophilic interaction and prevent contact between heterotypic cells. Breast cancer cells neighboring endothelial cells (ECs) atypically ...express vascular endothelial (VE)-cadherin. To understand this EC-induced VE-cadherin expression in breast cancer cells, MCF7 and MDA-MB-231 cells expressing different endogenous cadherins were co-cultured with ECs and analyzed for VE-cadherin at the transcriptional level and by confocal microscopy, flow cytometry, and immunoblotting. After losing their endogenous cadherins and neo-expression of VE-cadherin, these cells integrated into an EC monolayer without compromising the barrier function instantly. However, they induced the death of nearby ECs. EC-derived extracellular vesicles (EVs) contained soluble and membrane-anchored forms of VE-cadherin. Only the latter was re-utilized by the cancer cells. In a reporter gene assay, EC-adjacent cancer cells also showed a juxtacrine but no paracrine activation of the endogenous VE-cadherin gene. This cadherin switch enabled intimate contact between cancer and endothelial cells in a chicken chorioallantoic membrane tumor model showing vasculogenic mimicry (VM). This EV-mediated, EC-induced cadherin switch in breast cancer cells and the neo-expression of VE-cadherin mechanistically explain the mutual communication in the tumor microenvironment. Hence, it may be a target to tackle VM, which is often found in breast cancers of poor prognosis.
Platelets play a crucial role in the immunological response and are involved in the pathological settings of vascular diseases, and their adhesion to the extracellular matrix is important to bring ...leukocytes close to the endothelial cells and to form and stabilize the thrombus. Currently there are several methods to study platelet adhesion; however, the optimal parameters to perform the assay vary among studies, which hinders their comparison and reproducibility. Here, a standardization and validation of a fluorescence-based quantitative adhesion assay to study platelet-ECM interaction in a high-throughput screening format is proposed. Our study confirms that fluorescence-based quantitative assays can be effectively used to detect platelet adhesion, in which BCECF-AM presents the highest sensitivity in comparison to other dyes.
In this paper we report a method to determine the soluble solids content (SSC) of 'Rocha' pear (
L. cv. Rocha) based on their short-wave NIR reflectance spectra (500-1100 nm) measured in conditions ...similar to those found in packinghouse fruit sorting facilities. We obtained 3300 reflectance spectra from pears acquired from different lots, producers and with diverse storage times and ripening stages. The macroscopic properties of the pears, such as size, temperature and SSC were measured under controlled laboratory conditions. For the spectral analysis, we implemented a computational pipeline that incorporates multiple pre-processing techniques including a feature selection procedure, various multivariate regression models and three different validation strategies. This benchmark allowed us to find the best model/preproccesing procedure for SSC prediction from our data. From the several calibration models tested, we have found that Support Vector Machines provides the best predictions metrics with an RMSEP of around 0.82 ∘ Brix and 1.09 ∘ Brix for internal and external validation strategies respectively. The latter validation was implemented to assess the prediction accuracy of this calibration method under more 'real world-like' conditions. We also show that incorporating information about the fruit temperature and size to the calibration models improves SSC predictability. Our results indicate that the methodology presented here could be implemented in existing packinghouse facilities for single fruit SSC characterization.
•SW-NIRS was used to build PLS calibration models for 'Ortanique' quality attributes.•The best calibration models were obtained for MI and TA and the worse for glucose.•Coarse predictive models were ...obtained for ascorbic acid, sucrose and total sugars.•Models’ robustness was tested externally with datasets from two orchards.•Model updating was implemented through bias correction and spiking.
The aim of this study was the non-destructive assessment of ‘Ortanique’ (Citrus reticulata Blanco x Citrus sinensis (L) Osbeck) ripening, based on the prediction of internal quality attributes (IQA) by short-wave near-infrared reflectance spectroscopy (SW-NIRS) calibration models. Spectra from fruit of 50 trees located in two different orchards, were acquired on tree using a customized portable visible near-infrared (vis-NIR) system. Partial least squares (PLS) was used to build the various IQA calibration models. The models were tested through internal validation (IV) and external validation (EV). Generally, the IV results were always superior to those of EV: regarding IV, a high regression coefficient (R2) and low root mean square error of prediction (RMSEP) were achieved, revealing a good predictive performance for juice pH (R2 = 0.80; RMSEP = 0.10; SDR = 2.23), soluble solids content (SSC) (R2 = 0.79; RMSEP = 0.75 %; SDR = 2.27), titratable acidity (TA) (R² = 0.73; RMSEP = 0.24 % citric acid; SDR = 1.94) and the maturation index (MI) (R2 = 0.80; RMSEP = 1.38; SDR = 2.2). The best EV predictions were obtained for TA (R2 = 0.69; RMSEP = 0.38 % citric acid; SDR = 1.24), and MI (R2 = 0.69; RMSEP = 2.07; SDR = 1.49). Calibration models for glucose, fructose and sucrose showed medium-coarse predictions for both validation strategies. A detailed investigation of MI models was performed, to understand the causes of their poor EV results. In the context of EV, model updating strategies were explored by using some validation samples to improve the calibration model. The methods of bias correction and spiking were tested, showing a clear improvement in the predictions.
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