Molecular Mechanisms of Trastuzumab Resistance in HER2 Overexpressing Breast Cancer

The epidermal growth factor receptor 2 (HER2) is a tyrosine kinase overexpressed in nearly 20% to 25% of invasive breast cancers. Trastuzumab is a humanized monoclonal antibody that targets HER2. The majority of patients with metastatic breast cancer initially respond to trastuzumab, however, within 1 year of treatment disease progresses. Several molecular mechanisms have been described as contributing to the development of trastuzumab resistance. They could be grouped as impaired access of trastuzumab to HER2, upregulation of HER2 downstream signaling pathways, signaling of alternative pathways, and impaired immune antitumor mechanisms. However, since many of them have overlapping effects, it would be of great clinical impact to identify the principal signaling pathways involved in drug resistance. Significant efforts are being applied to find other therapeutic modalities besides trastuzumab treatment to be used alone or in combination with current modalities

a touch of gastronomy

The last few years have seen a rapid growth of research interest in the study of the role of touch and oral-somatosensation in the experience of eating and drinking. The various ways in which the sense of touch can be used to enhance the diner's/consumer's experience in both everyday eating and drinking, as well as in the context of experiential dining, is also gaining ever more attention from professionals in a variety of disciplines. In this review, we highlight the importance that everything that we perceive via the sense of touch, from the weight of the menu to the feel of the tablecloth, tableware, cutlery, and even the food itself, has on our eating experience and food and beverage-related behaviors. Everything we feel, be it the weight, the temperature, or the texture of whatever we happen to come across while eating appears to matter. In addition, we also highlight the relevance of oral-somatosensory cues to our sensory and hedonic perception of foods. A number of examples are given to demonstrate some of the many ways in which chefs, designers, and artists are now exploiting these findings in order to change and, hopefully, to enhance the diner's eating experience in innovative ways

Suicide gene therapy on spontaneous canine melanoma: correlations between in vivo tumors and their derived multicell spheroids in vitro

To validate the use of multicellular spheroids to predict the efficacy of herpes simplex thymidine kinase/ganciclovir (HSVtk/GCV) suicide gene therapy in the respective in vivo tumors, we established and characterized 15 melanoma-derived cell lines from surgically excised melanoma tumors. Three HSVtk-lipofected cell lines were not sensitive to GCV in any culture configuration, other five displayed similar sensitivity as monolayers or spheroids, and only one resulted more sensitive when grown as spheroids. Other six cell lines manifested a relative multicellular resistance (MCR) phenotype growing as spheroids, compared with the same cells growing as monolayers. The reverse correlation between the MCR and the monolayers survival to HSVtk/GCV suggests that one of the main causes of MCR would be the rapid cell repopulation after suicide gene treatment. The high correlation of MCR with the spheroids radial growth and with the mitotic index of the respective originary tumors supported this re-growth involvement. A remarkable finding was the high correlation in HSVtk/GCV sensitivity between in vivo tumor and the corresponding derived cell lines growing as spheroids (R 2 0.85). This strongly encourages the implementation of spheroids as highly realistic experimental model for optimizing and predicting the in vivo response of the respective tumors to therapeutic strategies.Fil: Gil Cardeza, Maria Lourdes. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Dr. Ángel Roffo". Unidad de Transferencia Genética; ArgentinaFil: Villaverde, Marcela Solange. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Dr. Ángel Roffo". Unidad de Transferencia Genética; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Fiszman, Gabriel Leon. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Dr. Ángel Roffo". Unidad de Transferencia Genética; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Altamirano, Natalia Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Dr. Ángel Roffo". Unidad de Transferencia Genética; ArgentinaFil: Cwirenbaum, R. A.. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Dr. Ángel Roffo". Unidad de Transferencia Genética; ArgentinaFil: Glikin, Gerardo Claudio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Dr. Ángel Roffo". Unidad de Transferencia Genética; ArgentinaFil: Finocchiaro, Liliana Maria Elena. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Dr. Ángel Roffo". Unidad de Transferencia Genética; Argentin

Impact of texture TDS and flavour TDS tasks and of chocolate-chip biscuit characteristics on oral processing features

[EN] The objective of the present study was to investigate differences in oral activity when biscuits of the same type but with subtle composition differences are consumed and how performing a Temporal Dominance of Sensations (TDS) task modifies the way one eats. In addition, comparisons were made between performing a texture TDS (T-TDS) and a flavour TDS (F-TDS). Oral activity while eating biscuits with and without conducting a TDS task was recorded using a 3.dimensional motion capture system to monitor the evolution of jaw movements. The results showed that oral activity evolved over the consumption time, differed depending on the texture of the sample and was affected to a small but significant extent when a TDS task was performed simultaneously (the differences averaged < 4 cycles, 1 s in duration, 0.1 cycles/s in frequency, and 1 mm in lateral displacement). The biscuit samples were affected equally. Almost no differences were found on comparing oral activity during the execution of the T-TDS and the F-TDS tasks. Overall, the present results show differences in oral activity even for food products of the same category with subtle differences in composition. Performing TDS tasks (regardless of their modality) during sample consumption affected the total number, frequency and lateral amplitude of the chewing movements which should be taken into account for future research. However, these differences were small and affected both samples equally.The authors are grateful to the Spanish Ministry of the Economy and Competitiveness (AGL-2016-75403-R, Spain) and to the Regional Government of Valencia (Project Prometeo 2017/189, Spain) for financial support.Rizo, A.; Jimenez-Pérez, I.; Camacho-García, A.; Fiszman, S.; Pérez-Soriano, P.; Tarrega, A. (2019). Impact of texture TDS and flavour TDS tasks and of chocolate-chip biscuit characteristics on oral processing features. Food Quality and Preference. 76:109-117. https://doi.org/10.1016/j.foodqual.2019.04.005S1091177

Dynamic summarization of bibliographic-based data

<p>Abstract</p> <p>Background</p> <p>Traditional information retrieval techniques typically return excessive output when directed at large bibliographic databases. Natural Language Processing applications strive to extract salient content from the excessive data. Semantic MEDLINE, a National Library of Medicine (NLM) natural language processing application, highlights relevant information in PubMed data. However, Semantic MEDLINE implements manually coded schemas, accommodating few information needs. Currently, there are only five such schemas, while many more would be needed to realistically accommodate all potential users. The aim of this project was to develop and evaluate a statistical algorithm that automatically identifies relevant bibliographic data; the new algorithm could be incorporated into a dynamic schema to accommodate various information needs in Semantic MEDLINE, and eliminate the need for multiple schemas.</p> <p>Methods</p> <p>We developed a flexible algorithm named Combo that combines three statistical metrics, the Kullback-Leibler Divergence (KLD), Riloff's RlogF metric (RlogF), and a new metric called PredScal, to automatically identify salient data in bibliographic text. We downloaded citations from a PubMed search query addressing the genetic etiology of bladder cancer. The citations were processed with SemRep, an NLM rule-based application that produces semantic predications. SemRep output was processed by Combo, in addition to the standard Semantic MEDLINE genetics schema and independently by the two individual KLD and RlogF metrics. We evaluated each summarization method using an existing reference standard within the task-based context of genetic database curation.</p> <p>Results</p> <p>Combo asserted 74 genetic entities implicated in bladder cancer development, whereas the traditional schema asserted 10 genetic entities; the KLD and RlogF metrics individually asserted 77 and 69 genetic entities, respectively. Combo achieved 61% recall and 81% precision, with an F-score of 0.69. The traditional schema achieved 23% recall and 100% precision, with an F-score of 0.37. The KLD metric achieved 61% recall, 70% precision, with an F-score of 0.65. The RlogF metric achieved 61% recall, 72% precision, with an F-score of 0.66.</p> <p>Conclusions</p> <p>Semantic MEDLINE summarization using the new Combo algorithm outperformed a conventional summarization schema in a genetic database curation task. It potentially could streamline information acquisition for other needs without having to hand-build multiple saliency schemas.</p

Active compounds and distinctive sensory features provided by American ginseng (Panax quinquefolius L.) extract in a new functional milk beverage

American ginseng (Panax quinquefolius L.) has recognized neurocognitive effects, and a ginsenoside-rich extract of the root of the plant has been shown to improve cognitive functions in young adults. This study aimed at assessing the chemical and sensory profiles of a UHT-treated, low-lactose functional milk containing American ginseng. Individual ginsenosides in the milk were analyzed by HPLC. Descriptive sensory analysis was performed by a trained panel to quantitatively document sensory changes resulting from the addition of ginseng and the UHT process on flavored and unflavored milks. Consumer acceptance of the product was also investigated. Total ginsenoside content in the UHT-treated milk enriched with the ginseng extract after UHT process treatment was 7.52. mg/100. g of milk, corresponding to a recovery of 67.6% compared with the content in the unprocessed extract. The intake of 150 to 300. mL of this ginseng-enriched milk provides the amount of total ginsenosides (11.5 to 23. mg) necessary to improve cognitive function after its consumption. Both the presence of ginsenosides and their thermal treatment affected some sensory properties of the milk, most notably an increase in bitterness and metallic taste, the appearance of a brownish color, and a decrease in milky flavor. Levels of brown color, bitterness, and metallic taste were highest in the industrially processed ginseng-enriched milk. The bitterness attributable to ginseng extract was reduced by addition of vanilla flavor and sucralose. A consumer exploratory study revealed that a niche of consumers exists who are willing to consume this type of product.The financial support of the Ministry of Science and Innovation of Spain (Madrid, Spain) for the project SENIFOOD (CENIT Programme) and for the contract with A. Tárrega (Juan de la Cierva Programme) is acknowledged. We gratefully acknowledge Juan Duato Aguilar, from Naturex Spain S.L. (Quart de Poblet, Spain), for his valuable technical support

Clustering cliques for graph-based summarization of the biomedical research literature

BACKGROUND: Graph-based notions are increasingly used in biomedical data mining and knowledge discovery tasks. In this paper, we present a clique-clustering method to automatically summarize graphs of semantic predications produced from PubMed citations (titles and abstracts). RESULTS: SemRep is used to extract semantic predications from the citations returned by a PubMed search. Cliques were identified from frequently occurring predications with highly connected arguments filtered by degree centrality. Themes contained in the summary were identified with a hierarchical clustering algorithm based on common arguments shared among cliques. The validity of the clusters in the summaries produced was compared to the Silhouette-generated baseline for cohesion, separation and overall validity. The theme labels were also compared to a reference standard produced with major MeSH headings. CONCLUSIONS: For 11 topics in the testing data set, the overall validity of clusters from the system summary was 10% better than the baseline (43% versus 33%). While compared to the reference standard from MeSH headings, the results for recall, precision and F-score were 0.64, 0.65, and 0.65 respectively

Developing a reduced consumer-led lexicon to measure emotional response to beer

Previous researchers have recently recommended and utilised consumer-led lexicons to measure emotional response. This study further advances this approach by 1) making the lexicon generation process more efficient by using consumer focus groups as opposed to individual consumer interviews and 2) decreasing the number of responses required from each consumer by reducing the lexicon to categories of similar terms. In response to 10 lager samples which were manipulated in order to control selected sensory properties, focus groups generated a lexicon of 44 emotion terms. This lexicon was reduced to 12 distinct emotion categories using linguistic checks and cluster analysis. Naïve beer consumers (n = 113) used these 12 emotion categories to rate their emotional response to the 10 samples. The reduced consumer-led lexicon was validated through its ability to discriminate across samples as well as show differences in emotional response between genders and age groups. The 12 emotion categories were found to discriminate well between samples, although a number of categories grouped samples similarly. However, differences in responses to otherwise comparable emotion categories were identified between genders and age groups, highlighting the importance of including all emotion categories so as to not over-reduce the lexicon and risk missing out on valuable emotion data

Constructing a semantic predication gold standard from the biomedical literature

<p>Abstract</p> <p>Background</p> <p>Semantic relations increasingly underpin biomedical text mining and knowledge discovery applications. The success of such practical applications crucially depends on the quality of extracted relations, which can be assessed against a gold standard reference. Most such references in biomedical text mining focus on narrow subdomains and adopt different semantic representations, rendering them difficult to use for benchmarking independently developed relation extraction systems. In this article, we present a multi-phase gold standard annotation study, in which we annotated 500 sentences randomly selected from MEDLINE abstracts on a wide range of biomedical topics with 1371 semantic predications. The UMLS Metathesaurus served as the main source for conceptual information and the UMLS Semantic Network for relational information. We measured interannotator agreement and analyzed the annotations closely to identify some of the challenges in annotating biomedical text with relations based on an ontology or a terminology.</p> <p>Results</p> <p>We obtain fair to moderate interannotator agreement in the practice phase (0.378-0.475). With improved guidelines and additional semantic equivalence criteria, the agreement increases by 12% (0.415 to 0.536) in the main annotation phase. In addition, we find that agreement increases to 0.688 when the agreement calculation is limited to those predications that are based only on the explicitly provided UMLS concepts and relations.</p> <p>Conclusions</p> <p>While interannotator agreement in the practice phase confirms that conceptual annotation is a challenging task, the increasing agreement in the main annotation phase points out that an acceptable level of agreement can be achieved in multiple iterations, by setting stricter guidelines and establishing semantic equivalence criteria. Mapping text to ontological concepts emerges as the main challenge in conceptual annotation. Annotating predications involving biomolecular entities and processes is particularly challenging. While the resulting gold standard is mainly intended to serve as a test collection for our semantic interpreter, we believe that the lessons learned are applicable generally.</p

Subtle changes in the flavour and texture of a drink enhance expectations of satiety

Background: The consumption of liquid calories has been implicated in the development of obesity and weight gain. Energy-containing drinks are often reported to have a weak satiety value: one explanation for this is that because of their fluid texture they are not expected to have much nutritional value. It is important to consider what features of these drinks can be manipulated to enhance their expected satiety value. Two studies investigated the perception of subtle changes in a drink’s viscosity, and the extent to which thick texture and creamy flavour contribute to the generation of satiety expectations. Participants in the first study rated the sensory characteristics of 16 fruit yogurt drinks of increasing viscosity. In study two, a new set of participants evaluated eight versions of the fruit yogurt drink, which varied in thick texture, creamy flavour and energy content, for sensory and hedonic characteristics and satiety expectations. Results: In study one, participants were able to perceive small changes in drink viscosity that were strongly related to the actual viscosity of the drinks. In study two, the thick versions of the drink were expected to be more filling and have a greater expected satiety value, independent of the drink’s actual energy content. A creamy flavour enhanced the extent to which the drink was expected to be filling, but did not affect its expected satiety. Conclusions: These results indicate that subtle manipulations of texture and creamy flavour can increase expectations that a fruit yogurt drink will be filling and suppress hunger, irrespective of the drink’s energy content. A thicker texture enhanced expectations of satiety to a greater extent than a creamier flavour, and may be one way to improve the anticipated satiating value of energy-containing beverages