Estudio de la transferencia de calor en la etapa de cocido en la elaboración de aceitunas verdes al estilo sevillano

En este artículo se describe por primera vez a nivel industrial el aumento de temperatura que se produce en el interior de los tanques de elaboración durante la etapa de cocido. A partir del estudio de las características térmicas de la etapa de cocido se han podido determinar relaciones entre las variables que definen el proceso. Se ha demostrado que la temperatura al inicio del tratamiento de cocido influye en otras de las características del proceso como la duración de éste o la pendiente del aumento lineal de temperatura durante la etapa. El estudio establece que esta generación de calor puede provenir principalmente de las reacciones de hidrólisis alcalina que ocurren en el interior del fruto y, en menor proporción, de la dilución de la solución de hidróxido de sodio con el agua presente en la pulpa de las aceitunas

Study of the heat transfer during the alkaline treatment in the processing of Spanish Style green table olives

En este artículo se describe por primera vez a nivel industrial el aumento de temperatura que se produce en el interior de los tanques de elaboración durante la etapa de cocido. A partir del estudio de las características térmicas de la etapa de cocido se han podido determinar relaciones entre las variables que definen el proceso. Se ha demostrado que la temperatura al inicio del tratamiento de cocido influye en otras de las características del proceso como la duración de éste o la pendiente del aumento lineal de temperatura durante la etapa. El estudio establece que esta generación de calor puede provenir principalmente de las reacciones de hidrólisis alcalina que ocurren en el interior del fruto y, en menor proporción, de la dilución de la solución de hidróxido de sodio con el agua presente en la pulpa de las aceitunas

Oncogenic regulation of tumor metabolic reprogramming

Development of malignancy is accompanied by a complete metabolic reprogramming closely related to the acquisition of most of cancer hallmarks. In fact, key oncogenic pathways converge to adapt the metabolism of carbohydrates, proteins, lipids and nucleic acids to the dynamic tumor microenvironment, conferring a selective advantage to cancer cells. Therefore, metabolic properties of tumor cells are significantly different from those of non-transformed cells. In addition, tumor metabolic reprogramming is linked to drug resistance in cancer treatment. Accordingly, metabolic adaptations are specific vulnerabilities that can be used in different therapeutic approaches for cancer therapy. In this review, we discuss the dysregulation of the main metabolic pathways that enable cell transformation and its association with oncogenic signaling pathways, focusing on the effects of c-MYC, hypoxia inducible factor 1 (HIF1), phosphoinositide-3-kinase (PI3K), and the mechanistic target of rapamycin (mTOR) on cancer cell metabolism. Elucidating these connections is of crucial importance to identify new targets and develop selective cancer treatments that improve response to therapy and overcome the emerging resistance to chemotherapeutics

Use of 3D Prototypes for Complex Surgical Oncologic Cases

Introduction: Physical 3D models known by the industry as rapid prototyping involve the creation of a physical model from a 3D computer version. In recent years, there has been an increasing number of reports on the use of 3D models in medicine. Printing such 3D models with different materials integrating the many components of human anatomy is technically challenging. In this article, we report our technological developments along with our clinical implementation experience using high-fidelity 3D prototypes of tumors encasing major vessels in anatomically sensitive areas. Methods: Three patients with tumors encasing major vessels that implied complex surgery were selected for surgical planning using 3D prototypes. 3D virtual models were obtained from routine CT and MRI images. The models, with all their anatomical relations, were created by an expert pediatric radiologist and a surgeon, image by image, along with a computerized-aided design engineer. Results: Surgeons had the opportunity to practice on the model before the surgery. This allowed questions regarding surgical approach; feasibility and potential complications to be raised in advance of the actual procedure. All patients then successfully underwent surgery as planned. Conclusion: Having a tumor physically printed in its different main component parts with its anatomical relationships is technically feasible. Since a gross total resection is prognostic in a significant percentage of tumor types, refinements in planning may help achieve greater and safer resections therefore contributing to improve surgical management of complex tumors. In this early experience, 3D prototyping helped significantly in the many aspects of surgical oncology planning

Oxidative pentose phosphate pathway enzyme 6-phosphogluconate dehydrogenase plays a key role in breast cancer metabolism

The pentose phosphate pathway (PPP) plays an essential role in the metabolism of breast cancer cells for the management of oxidative stress and the synthesis of nucleotides. 6-phosphogluconate dehydrogenase (6PGD) is one of the key enzymes of the oxidative branch of PPP and is involved in nucleotide biosynthesis and redox maintenance status. Here, we aimed to analyze the functional importance of 6PGD in a breast cancer cell model. Inhibition of 6PGD in MCF7 reduced cell proliferation and showed a significant decrease in glucose consumption and an increase in glutamine consumption, resulting in an important alteration in the metabolism of these cells. No difference in reactive oxygen species (ROS) production levels was observed after 6PGD inhibition, indicating that 6PGD, in contrast to glucose 6-phosphate dehydrogenase, is not involved in redox balance. We found that 6PGD inhibition also altered the stem cell characteristics and mammosphere formation capabilities of MCF7 cells, opening new avenues to prevent cancer recurrance after surgery or chemotherapy. Moreover, inhibition of 6PGD via chemical inhibitor S3 resulted in an induction of senescence, which, together with the cell cycle arrest and apoptosis induction, might be orchestrated by p53 activation. Therefore, we postulate 6PGD as a novel therapeutic target to treat breast cancer

Glyceraldehyde-3-phosphate dehydrogenase is overexpressed in colorectal cancer onset

Background Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is an essential regulator of glycolysis used as a housekeeping marker for gene/protein normalisation. Given the pivotal role of GAPDH in tumour metabolism, our aim was to correlate its protein expression with tumour staging and prognosis of colorectal cancer. Methods GAPDH expression was immunohistochemically analysed in tumour tissues from 62 colorectal cancer (CRC) patients, and validated at mRNA level in an independent dataset comprising 98 paired stage II CRC and normal samples. Staining quantification was performed by computational image analysis, and correlations between GAPDH expression and tumour progression stage were assessed. Gene expression profiling was performed using Affymetrix microarrays. Probability of patient survival and disease-free survival were analysed by the univariate product-limit method of Kaplan-Meier. Groups were compared using Kruskal-Wallis tests. Results Overexpression of GAPDH is positively associated with early stage tumours without regional lymph node and distant metastases involved. These results were reinforced by those obtained at mRNA level. Conclusion Studying the role of GAPDH in malignant transformation can shed new light on the understanding of tumour onset and lead to the design of more efficient personalised therapies

Integrating systemic and molecular levels to infer key drivers sustaining metabolic adaptations

Metabolic adaptations to complex perturbations, like the response to pharmacological treatments in multifactorial diseases such as cancer, can be described through measurements of part of the fluxes and concentrations at the systemic level and individual transporter and enzyme activities at the molecular level. In the framework of Metabolic Control Analysis (MCA), ensembles of linear constraints can be built integrating these measurements at both systemic and molecular levels, which are expressed as relative differences or changes produced in the metabolic adaptation. Here, combining MCA with Linear Programming, an efficient computational strategy is developed to infer additional non-measured changes at the molecular level that are required to satisfy these constraints. An application of this strategy is illustrated by using a set of fluxes, concentrations, and differentially expressed genes that characterize the response to cyclin-dependent kinases 4 and 6 inhibition in colon cancer cells. Decreases and increases in transporter and enzyme individual activities required to reprogram the measured changes in fluxes and concentrations are compared with down-regulated and up-regulated metabolic genes to unveil those that are key molecular drivers of the metabolic response

De novo MYC addiction as an adaptive response of cancer cells to CDK4/6 inhibition

Cyclin‐dependent kinases (CDK) are rational cancer therapeutic targets fraught with the development of acquired resistance by tumor cells. Through metabolic and transcriptomic analyses, we show that the inhibition of CDK4/6 leads to a metabolic reprogramming associated with gene networks orchestrated by the MYC transcription factor. Upon inhibition of CDK4/6, an accumulation of MYC protein ensues which explains an increased glutamine metabolism, activation of the mTOR pathway and blunting of HIF‐1α‐mediated responses to hypoxia. These MYC‐driven adaptations to CDK4/6 inhibition render cancer cells highly sensitive to inhibitors of MYC, glutaminase or mTOR and to hypoxia, demonstrating that metabolic adaptations to antiproliferative drugs unveil new vulnerabilities that can be exploited to overcome acquired drug tolerance and resistance by cancer cells

Cysteine and Folate metabolism are targetable vulnerabilities of metastatic colorectal cancer

With most cancer-related deaths resulting from metastasis, the development of new therapeutic approaches against metastatic colorectal cancer (mCRC) is essential to increasing patient survival. The metabolic adaptations that support mCRC remain undefined and their elucidation is crucial to identify potential therapeutic targets. Here, we employed a strategy for the rational identification of targetable metabolic vulnerabilities. This strategy involved first a thorough metabolic characterisation of same-patient-derived cell lines from primary colon adenocarcinoma (SW480), its lymph node metastasis (SW620) and a liver metastatic derivative (SW620-LiM2), and second, using a novel multi-omics integration workflow, identification of metabolic vulnerabilities specific to the metastatic cell lines. We discovered that the metastatic cell lines are selectively vulnerable to the inhibition of cystine import and folate metabolism, two key pathways in redox homeostasis. Specifically, we identified the system xCT and MTHFD1 genes as potential therapeutic targets, both individually and combined, for combating mCRC