Fumarate drives EMT in renal cancer

Medical Research Counci

Metabolic reprogramming and epithelial-to-mesenchymal transition in cancer

Several lines of evidence indicate that during transformation epithelial cancer cells can acquire mesenchymal features via a process called epithelial-to-mesenchymal transition (EMT). This process endows cancer cells with increased invasive and migratory capacity, enabling tumour dissemination and metastasis. EMT is associated with a complex metabolic reprogramming, orchestrated by EMT transcription factors, which support the energy requirements of increased motility and growth in harsh environmental conditions. The discovery that mutations in metabolic genes such as FH, SDH and IDH activate EMT provided further evidence that EMT and metabolism are intertwined. In this review, we discuss the role of EMT in cancer and the underpinning metabolic reprogramming. We also put forward the hypothesis that, by altering chromatin structure and function, metabolic pathways engaged by EMT are necessary for its full activation.MS and CF are funded by an MRC Core Funding to the MRC Cancer Unit

Fumarate drives EMT in renal cancer

Medical Research Counci

CSP plants with thermocline thermal energy storage and integrated steam generator – Techno-economic modeling and design optimization

Although CSP has reached technological maturity, high capital investment and specific electricity cost remain the major development barriers. To reduce them, highly efficient, integrated, and cheaper CSP components are urgently needed. In this paper, we investigate a novel CSP plant configuration with a single-tank Thermal Energy Storage (TES) fully integrated with the steam generator. The objective of this research is twofold: i) provide a reliable model of single-tank thermal storages with integrated steam generator; ii) identify two optimized CSP plant designs to achieve best energetic and economic performances. To achieve these aims we developed a numerical model of the main system components and validated it against experimental data. This model was then integrated in a full simulation and heuristic design optimization of the plant. The results revealed that the system proposed can generate electricity in middle-Italy (Rome) at a cost of 230.25 $/MWh with a 15% reduction compared to the double tank option. Furthermore, if cogeneration is used to recover the waste heat, this system is an interesting option for users such as small districts, university campuses and hospitals. In the latter case, the optimized system pays off in 6 years and covers 80% of the heating and cooling requirements

Exploiting tumour addiction with a serine and glycine-free diet.

Understanding cancer metabolism is key to unveil the Achilles’ heel of cancer cells and provide novel therapeutic interventions for patients. While the rerouting of metabolic pathways during development1 or cancer transformation and progression2, 3, 4 has been extensively characterised, the exact dynamic of these events, their distribution and frequency in the different tumour types, and the correlation with genetic background remain largely unknown. In a recent article published in Nature, Karen Vousden’s team assesses the effect of serine and glycine dietary restriction in autochthonous mouse tumour models driven by different oncogenes (Maddocks et al, 2017)5, leading to potential area of therapeutic intervention

Improved melting of latent heat storage via porous medium and uniform Joule heat generation

© 2020 To enhance the rate of heat transfer in phase change materials (PCM), high conductivity porous materials have been widely used recently as a promising method. This study introduces a novel approach for improving melting of PCM by incorporating uniform Joule heat generation with the porous structure compared to central heat generation. Different cases based on the heater-in foam configuration under the same heat generation rate are numerically verified and compared with the case of using the central heating element, which the heat transfer in the domain enhances by the porous medium. The effects of pore density and rate of heat generation are explored using the thermal non-equilibrium model to better deal with the interstitial heat transfer between the internal heat-generated-in-foam and the PCM. For the case with the central heating element, the effects of heater dimensions as well as the rate of heat generation are also investigated. The results show that the uniform heat generation from the porous structure can substantially reduce the melting time. Applying 100 kW/m3 for the rate of heat generation reduces the melting time by 21% compared with the best case of the localised heater. Meanwhile, applying higher pore-density foam does not bring any significant effect due to the uniform distribution of the heat generation. The results also show a small effect of localized heater size on the melting time with the same rate of heat generation density from the porous structure. However, for an identical volumetric heat source power of the localised heater, the rate of heat generation per volume is more effective compared with the heating element size due to the presence of the porous medium

Basal and one-month differed neutrophil, lymphocyte and platelet values and their ratios strongly predict the efficacy of checkpoint inhibitors immunotherapy in patients with advanced BRAF wild-type melanoma

Background To evaluate the capability of basal and one-month differed white blood cells (WBC), neutrophil, lymphocyte and platelet values and their ratios (neutrophils-to-lymphocytes ratio, NLR, and platelets-to-lymphocytes ratio, PLR) in predicting the response to immune checkpoint inhibitors (ICI) in metastatic melanoma (MM). Methods We performed a retrospective study of 272 BRAF wild-type MM patients treated with first line ICI. Bivariable analysis was used to correlate patient/tumor characteristics with clinical outcomes. Variations between time 1 and time 0 (Delta) of blood parameters were also calculated and dichotomized using cut-off values assessed by ROC curve. Results At baseline, higher neutrophils and NLR negatively correlated with PFS, OS and disease control rate (DCR). Higher PLR was also associated with worse OS. In multivariable analysis, neutrophils (p = 0.003), WBC (p = 0.069) and LDH (p = 0.07) maintained their impact on PFS, while OS was affected by LDH (p < 0.001), neutrophils (p < 0.001) and PLR (p = 0.022), while DCR by LDH (p = 0.03) and neutrophils (p = 0.004). In the longitudinal analysis, PFS negatively correlated with higher Delta platelets (p = 0.039), Delta WBC (p < 0.001), and Delta neutrophils (p = 0.020), and with lower Delta lymphocytes (p < 0.001). Moreover, higher Delta NLR and Delta PLR identified patients with worse PFS, OS and DCR. In the multivariable model, only Delta NLR influenced PFS (p = 0.004), while OS resulted affected by higher Delta WBC (p < 0.001) and lower Delta lymphocytes (p = 0.038). Higher Delta WBC also affected the DCR (p = 0.003). When clustering patients in 4 categories using basal LDH and Delta NLR, normal LDH/lower Delta NLR showed a higher PFS than high LDH/higher Delta NLR (20 vs 5 months). Moreover, normal LDH/higher Delta lymphocytes had a higher OS than high LDH/lower Delta lymphocytes (50 vs. 10 months). Conclusions Baseline and early variations of blood cells, together with basal LDH, strongly predict the efficacy of ICI in MM. Our findings propose simple, inexpensive biomarkers for a better selection of patient treatments. Prospective multicenter studies are warranted to confirm these data. © 2022, The Author(s)

A Case of Paediatric Sudden Visual Loss

Optic neuromyelitis (NMO) is a demienilizing disease traditionally characterized by optic neuritis and transverse myelitis..

Seventh Cranial Nerve Palsy: The First Sign of Multiple Sclerosis in A Young Children

Multiple sclerosis (MS) is a chronic autoimmune inflammatory disease of the central nervous system characterized pathologically by demyelination and subsequent axonal degeneration..