Hyperoxic Treatment Induces Mesenchymal-to-Epithelial Transition in a Rat Adenocarcinoma Model

Tumor hypoxia is relevant for tumor growth, metabolism and epithelial-to-mesenchymal transition (EMT). We report that hyperbaric oxygen (HBO) treatment induced mesenchymal-to-epithelial transition (MET) in a dimetyl-α-benzantracene induced mammary rat adenocarcinoma model, and the MET was associated with extensive coordinated gene expression changes and less aggressive tumors. One group of tumor bearing rats was exposed to HBO (2 bar, pO2 = 2 bar, 4 exposures à 90 minutes), whereas the control group was housed under normal atmosphere (1 bar, pO2 = 0.2 bar). Treatment effects were determined by assessment of tumor growth, tumor vascularisation, tumor cell proliferation, cell death, collagen fibrils and gene expression profile. Tumor growth was significantly reduced (∼16%) after HBO treatment compared to day 1 levels, whereas control tumors increased almost 100% in volume. Significant decreases in tumor cell proliferation, tumor blood vessels and collagen fibrils, together with an increase in cell death, are consistent with tumor growth reduction and tumor stroma influence after hyperoxic treatment. Gene expression profiling showed that HBO induced MET. In conclusion, hyperoxia induced MET with coordinated expression of gene modules involved in cell junctions and attachments together with a shift towards non-tumorigenic metabolism. This leads to more differentiated and less aggressive tumors, and indicates that oxygen per se might be an important factor in the “switches” of EMT and MET in vivo. HBO treatment also attenuated tumor growth and changed tumor stroma, by targeting the vascular system, having anti-proliferative and pro-apoptotic effects

A new model for health care delivery

<p>Abstract</p> <p>Background</p> <p>The health care delivery system in the United States is facing cost and quality pressures that will require fundamental changes to remain viable. The optimal structures of the relationships between the hospital, medical school, and physicians have not been determined but are likely to have a large impact on the future of healthcare delivery. Because it is generally agreed that academic medical centers will play a role in the sustainability of this future system, a fundamental understanding of the relative contributions of the stakeholders is important as well as creativity in developing novel strategies to achieve a shared vision.</p> <p>Discussion</p> <p>Core competencies of each of the stakeholders (the hospital, the medical school and the physicians) must complement the others and should act synergistically. At the same time, the stakeholders should determine the common core values and should be able to make a meaningful contribution to the delivery of health care.</p> <p>Summary</p> <p>Health care needs to achieve higher quality and lower cost. Therefore, in order for physicians, medical schools, and hospitals to serve the needs of society in a gratifying way, there will need to be change. There needs to be more scientific and social advances. It is obvious that there is a real and urgent need for relationship building among the professionals whose duty it is to provide these services.</p

Metformin treatment response is dependent on glucose growth conditions and metabolic phenotype in colorectal cancer cells

Cancer cells exhibit altered metabolism, a phenomenon described a century ago by Otto Warburg. However, metabolic drug targeting is considered an underutilized and poorly understood area of cancer therapy. Metformin, a metabolic drug commonly used to treat type 2 diabetes, has been associated with lower cancer incidence, although studies are inconclusive concerning effectiveness of the drug in treatment or cancer prevention. The aim of this study was to determine how glucose concentration influences cancer cells’ response to metformin, highlighting why metformin studies are inconsistent. We used two colorectal cancer cell lines with different growth rates and clinically achievable metformin concentrations. We found that fast growing SW948 are more glycolytic in terms of metabolism, while the slower growing SW1116 are reliant on mitochondrial respiration. Both cell lines show inhibitory growth after metformin treatment under physiological glucose conditions, but not in high glucose conditions. Furthermore, SW1116 converges with SW948 at a more glycolytic phenotype after metformin treatment. This metabolic shift is supported by changed GLUT1 expression. Thus, cells having different metabolic phenotypes, show a clear differential response to metformin treatment based on glucose concentration. This demonstrates the importance of growth conditions for experiments or clinical studies involving metabolic drugs such as metformin

Metformin treatment response is dependent on glucose growth conditions and metabolic phenotype in colorectal cancer cells

Cancer cells exhibit altered metabolism, a phenomenon described a century ago by Otto Warburg. However, metabolic drug targeting is considered an underutilized and poorly understood area of cancer therapy. Metformin, a metabolic drug commonly used to treat type 2 diabetes, has been associated with lower cancer incidence, although studies are inconclusive concerning effectiveness of the drug in treatment or cancer prevention. The aim of this study was to determine how glucose concentration influences cancer cells’ response to metformin, highlighting why metformin studies are inconsistent. We used two colorectal cancer cell lines with different growth rates and clinically achievable metformin concentrations. We found that fast growing SW948 are more glycolytic in terms of metabolism, while the slower growing SW1116 are reliant on mitochondrial respiration. Both cell lines show inhibitory growth after metformin treatment under physiological glucose conditions, but not in high glucose conditions. Furthermore, SW1116 converges with SW948 at a more glycolytic phenotype after metformin treatment. This metabolic shift is supported by changed GLUT1 expression. Thus, cells having different metabolic phenotypes, show a clear differential response to metformin treatment based on glucose concentration. This demonstrates the importance of growth conditions for experiments or clinical studies involving metabolic drugs such as metformin

Cyclic production of biocompatible few-layer graphene ink with in-line shear-mixing for inkjet-printed electrodes and Li-ion energy storage

AbstractThe scalable production of two-dimensional (2D) materials is needed to accelerate their adoption to industry. In this work, we present a low-cost in-line and enclosed process of exfoliation based on high-shear mixing to create aqueous dispersions of few-layer graphene, on a large scale with a Yw ~ 100% yield by weight and throughput of ϕ ~ 8.3 g h−1. The in-line process minimises basal plane defects compared to traditional beaker-based shear mixing which we attribute to a reduced Reynolds number, Re ~ 105. We demonstrate highly conductive graphene material with conductivities as high as σ ∼ 1.5 × 104 S m−1 leading to sheet-resistances as low as Rs ∼ 2.6 Ω □−1 (t ∼ 25 μm). The process is ideal for formulating non-toxic, biocompatible and highly concentrated (c ∼ 100 mg ml−1) inks. We utilise the graphene inks for inkjet printable conductive interconnects and lithium-ion battery anode composites that demonstrate a low-rate lithium storage capability of 370 mAh g−1, close to the theoretical capacity of graphite. Finally, we demonstrate the biocompatibility of the graphene inks with human colon cells and human umbilical vein endothelial cells at high c ∼ 1 mg ml−1 facilitating a route for the use of the graphene inks in applications that require biocompatibility at high c such as electronic textiles.</jats:p