Search results for "Warburg"
showing 10 items of 25 documents
Metabolic Cooperation and Competition in the Tumor Microenvironment: Implications for Therapy
2017
The tumor microenvironment (TME) is an ensemble of non-tumor cells comprising fibroblasts, cells of the immune system, and endothelial cells, besides various soluble secretory factors from all cellular components (including tumor cells). The TME forms a pro-tumorigenic cocoon around the tumor cells where reprogramming of the metabolism occurs in tumor and non-tumor cells that underlies the nature of interactions as well as competitions ensuring steady supply of nutrients and anapleoretic molecules for the tumor cells that fuels its growth even under hypoxic conditions. This metabolic reprogramming also plays a significant role in suppressing the immune attack on the tumor cells and in resis…
Lactate and Acidity in the Cancer Microenvironment
2020
Fermentative glycolysis, an ancient evolved metabolic pathway, is exploited by rapidly growing tissues and tumors but also occurs in response to the nutritional and energetic demands of differentiated tissues. The lactic acid it produces is transported across cell membranes through reversible H+/lactate−symporters (MCT1 and MCT4) and is recycled in organs as a major metabolic precursor of gluconeogenesis and an energy source. Concentrations of lactate in the tumor environment, investigated utilizing an induced metabolic bioluminescence imaging (imBI) technique, appear to be dominant biomarkers of tumor response to irradiation and resistance to treatment. Suppression of lactic acid formation…
Cancer Acidity and Hypertonicity Contribute to Dysfunction of Tumor-Associated Dendritic Cells: Potential Impact on Antigen Cross-Presentation Machin…
2020
Macrophages (M) and dendritic cells (DC), major players of the mononuclear phagocyte system (MoPh), are potent antigen presenting cells that steadily sense and respond to signals from the surrounding microenvironment, leading to either immunogenic or tolerogenic outcomes. Next to classical MHC-I/MHC-II antigen-presentation pathways described in the vast majority of cell types, a subset of MoPh (CD8+, XCR1+, CLEC9A+, BDCA3+ conventional DCs in human) is endowed with a high competence to cross-present external (engulfed) antigens on MHC-I molecules to CD8+ T-cells. This exceptional DC function is thought to be a crucial crossroad in cytotoxic antitumor immunity and has been extensively studie…
Revisiting the Warburg effect: historical dogma versus current understanding
2020
Contrary to Warburg's original thesis, accelerated aerobic glycolysis is not a primary, permanent and universal consequence of dysfunctional or impaired mitochondria compensating for poor ATP yield per mole of glucose. Instead, in most tumours the Warburg effect is an essential part of a 'selfish' metabolic reprogramming, which results from the interplay between (normoxic/hypoxic) hypoxia-inducible factor-1 (HIF-1) overexpression, oncogene activation (cMyc, Ras), loss of function of tumour suppressors (mutant p53, mutant phosphatase and tensin homologue (PTEN), microRNAs and sirtuins with suppressor functions), activated (PI3K-Akt-mTORC1, Ras-Raf-MEK-ERK-cMyc, Jak-Stat3) or deactivated (LKB…
Lactate—An Integrative Mirror of Cancer Metabolism
2016
The technique of induced metabolic bioluminescence imaging (imBI) has been developed to obtain a “snapshot” of the momentary metabolic status of biological tissues. Using cryosections of snap-frozen tissue specimens, imBI combines highly specific and sensitive in situ detection of metabolites with a spatial resolution on a microscopic level and with metabolic imaging in relation to tissue histology. Here, we present the application of imBI in human colorectal cancer. Comparing the metabolic information of one biopsy with that of 2 or 3 biopsies per individual cancer, the classification into high versus low lactate tumors, reflecting different glycolytic activities, based on a single biopsy …
Congenital muscular dystrophy: from muscle to brain.
2016
Congenital muscular dystrophies (CMDs) are a wide group of muscular disorders that manifest with very early onset of muscular weakness, sometime associated to severe brain involvement. The histologic pattern of muscle anomalies is typical of dystrophic lesions but quite variable depending on the different stages and on the severity of the disorder. Recent classification of CMDs have been reported most of which based on the combination of clinical, biochemical, molecular and genetic findings, but genotype/phenotype correlation are in constant progression due to more diffuse utilization of the molecular analysis. In this article, the Authors report on CMDs belonging to the group of dystroglyc…
Una visión integral del cáncer (II). Campos de estudio y biomarcadores emergentes
2019
Pathology and clinical oncology work hand in hand so that techniques and treatments, biomarkers and antibodies share the common goal of identifying integral new treatment regimens that are more effective and less aggressive. Evidence shows how tissue mechanics affect carcinogenesis and that tumor heterogeneity depends on metabolic stromal alteration and the Warburg effect of malignant cells, regulated directly by PD-1, becoming a target for immunotherapy. Proliferation and apoptosis depend on mitochondrial dysfunction in tumor cells, determining the grade of chemo/radio-resistance. The status of intestinal microbiota regulates immune response, tumor microenvironment structure and oncologic …
Single-Cell Transcriptional Profiling of Cells Derived From Regenerating Alveolar Ducts
2020
Lung regeneration occurs in a variety of adult mammals after surgical removal of one lung (pneumonectomy). Previous studies of murine post-pneumonectomy lung growth have identified regenerative “hotspots” in subpleural alveolar ducts; however, the cell-types participating in this process remain unclear. To identify the single cells participating in post-pneumonectomy lung growth, we used laser microdissection, enzymatic digestion and microfluidic isolation. Single-cell transcriptional analysis of the murine alveolar duct cells was performed using the C1 integrated fluidic circuit (Fluidigm) and a custom PCR panel designed for lung growth and repair genes. The multi-dimensional data set was …
María Magdalena. Continuidad y variación en la cultura audiovisual (1897-2014)
2017
El objetivo principal de esta tesis consiste en analizar la presencia de María Magdalena en las producciones audiovisuales del periodo comprendido entre 1897 y 2014. Dichas producciones proceden de Europa, Estados Unidos, Canadá y México. El marco metodológico general a partir del que se plantea el análisis es la iconología, entendida como Zwichenraum o tierra de confluencias. En concreto, la noción de continuidad y variación, iniciada por Aby Warburg y continuada por Fritz Saxl, es la principal cuestión teórica en la que se basa la aproximación. El estudio se lleva a cabo en perspectiva diacrónica con el objetivo de detectar dichas fases de continuidad y variación del personaje a lo largo …
L’esperienza dell’immagine: il Denkraum der Besonnenheit di Aby Warburg
2014
Il lavoro si fonda sull’idea che il periodo del ricovero (1921-1924) di Aby Warburg nella clinica di Bellevue (Kreuzlingen), allora diretta da Ludwig Binswanger, debba essere considerato centrale per lo sviluppo teorico dello studioso amburghese. Piuttosto che liquidare come lungo momento di buio gli anni della malattia, si è ritenuto utile riflettere sulle connessioni tra l’esperienza e l’attitudine esistenziale di Warburg e gli sviluppi della sua ricerca. Prendendo in esame la celebre conferenza sul rituale del serpente (A lecture on Serpent Ritual) che lo storico dell’arte tedesco tenne nel 1923 a Kreuzlingen, con il consenso di Binswanger, per attestare la sua guarigione davanti a un pu…