Typical Bronchial Carcinoid Metastasizing to the Brain: A Case Presentation

Introduction: Typicalbronchial carcinoid tumors are known for their relatively indolent behavior. There are only four reported cases in the medical literature describing typical bronchial carcinoids metastasizing to the brain. Little is known about the pathogenesis and presentation of this disease due to the very small patient population. CasePresentation: A 67-year-old Hispanic female presented to our hospital with a three-week history of right arm numbness and poor coordination. Computed tomography (CT) with intravenous contrast of the brain and subsequent magnetic resonance imaging demonstrated multiple enhancing nodular densities throughout the brain. CT with intravenous contrast of the chest, abdomen, and pelvis revealed a left hilar mass and a medial left upper lobe mass. Histopathological findings were consistent with a neuroendocrine neoplasm of bronchial origin. Conclusion: Although metastases to the central nervous system are very frequent with small cell carcinomas, their presence is very uncommon in well-differentiated neuroendocrine tumors such as the one we present here. This case raises questions about whether these tumors contain biomarkers that might predict a more aggressive behavior and if these patients might benefit from aggressive interventions similar to those taken in small cell carcinomas, such as prophylactic cranial radiation

Fibroblast Growth Factor Receptors (FGFRs) and Noncanonical Partners in Cancer Signaling

From MDPI via Jisc Publications RouterHistory: accepted 2021-05-09, pub-electronic 2021-05-14Publication status: PublishedFunder: Wellcome Trust; Grant(s): 107636/Z/15/ZFunder: Biotechnology and Biological Sciences Research Council; Grant(s): BB/R015864/1, BB/M011208/1Funder: Medical Research Council; Grant(s): MR/T016043/1Increasing evidence indicates that success of targeted therapies in the treatment of cancer is context-dependent and is influenced by a complex crosstalk between signaling pathways and between cell types in the tumor. The Fibroblast Growth Factor (FGF)/FGF receptor (FGFR) signaling axis highlights the importance of such context-dependent signaling in cancer. Aberrant FGFR signaling has been characterized in almost all cancer types, most commonly non-small cell lung cancer (NSCLC), breast cancer, glioblastoma, prostate cancer and gastrointestinal cancer. This occurs primarily through amplification and over-expression of FGFR1 and FGFR2 resulting in ligand-independent activation. Mutations and translocations of FGFR1-4 are also identified in cancer. Canonical FGF-FGFR signaling is tightly regulated by ligand-receptor combinations as well as direct interactions with the FGFR coreceptors heparan sulfate proteoglycans (HSPGs) and Klotho. Noncanonical FGFR signaling partners have been implicated in differential regulation of FGFR signaling. FGFR directly interacts with cell adhesion molecules (CAMs) and extracellular matrix (ECM) proteins, contributing to invasive and migratory properties of cancer cells, whereas interactions with other receptor tyrosine kinases (RTKs) regulate angiogenic, resistance to therapy, and metastatic potential of cancer cells. The diversity in FGFR signaling partners supports a role for FGFR signaling in cancer, independent of genetic aberration

Portacaval shunt causes apoptosis and liver atrophy in rats despite increases in endogenous levels of major hepatic growth factors

Background/Aims: The response to the liver damage caused by portacaval shunt (PCS) is characterized by low-grade hyperplasia and atrophy. To clarify mechanisms of this dissociation, we correlated the expression of 'hepatotrophic factors' and the antihepatotrophic and proapoptotic peptide, transforming growth factor (TGF)-β, with the pathologic changes caused by PCS in rats. Methods: PCS was created by side-to-side anastomosis between the portal vein and inferior vena cava, with ligation of the hilar portal vein. Hepatic growth mediators were measured to 2 months. Results: The decrease in the liver/body weight ratio during the first 7 days which stabilized by day 15, corresponded to parenchymal cell apoptosis and increases in hepatic TGF-β concentration that peaked at 1.4 × baseline at 15 days before returning to control levels by day 30. Variable increases in the concentrations of growth promoters (hepatocyte growth factor, TGF-α and augmenter of liver regeneration) also occurred during the period of hepatocellular apoptosis. Conclusions: The development of hepatic atrophy was associated with changes in TGF-β concentration, and occurred despite increased expression of multiple putative growth promoters. The findings suggest that apoptosis set in motion by TGF-β constrains the amount of hepatocyte proliferation independently from control of liver volume. © 2002 European Association for the Study of the Liver. Published by Elsevier Science B.V. All rights reserved

Discovery of a gatekeeper residue in the C terminal tail of the extracellular signal-regulated protein kinase 5 (ERK5)

The extracellular signal-regulated protein kinase 5 (ERK5) is a non-redundant mitogen-activated protein kinase (MAPK) that exhibits a unique C terminal extension which comprises distinct structural and functional properties. Here, we sought to elucidate the significance of phosphoacceptor sites in the C terminal transactivation domain of ERK5. We have found that Thr732 acted as a functional gatekeeper residue controlling C terminal-mediated nuclear translocation and transcriptional enhancement. Consistently, using a non-bias quantitative mass spectrometry approach, we demonstrated that phosphorylation at Thr732 conferred selectivity for binding interactions of ERK5 with proteins related to chromatin and RNA biology, whereas a number of metabolic regulators were associated with full-length wild type ERK5. Additionally, our proteomic analysis revealed that phosphorylation of the Ser730-Glu-Thr732-Pro motif could occur independently of dual phosphorylation at Thr218-Glu-Tyr220 in the activation loop. Together these results firmly establish the significance of C terminal phosphorylation in regulating ERK5 function, independently of MEK5. This novel mechanism may be of particular relevance in cancer cells where ERK5 has be found to be hyperphosphoryated on its C terminal tail

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Statins promote the regression of atherosclerosis via activation of the CCR7-dependent emigration pathway in macrophages.

HMG-CoA reductase inhibitors (statins) decrease atherosclerosis by lowering low-density-lipoprotein cholesterol. Statins are also thought to have additional anti-atherogenic properties, yet defining these non-conventional modes of statin action remains incomplete. We have previously developed a novel mouse transplant model of atherosclerosis regression in which aortic segments from diseased donors are placed into normolipidemic recipients. With this model, we demonstrated the rapid loss of CD68+ cells (mainly macrophages) in plaques through the induction of a chemokine receptor CCR7-dependent emigration process. Because the human and mouse CCR7 promoter contain Sterol Response Elements (SREs), we hypothesized that Sterol Regulatory Element Binding Proteins (SREBPs) are involved in increasing CCR7 expression and through this mechanism, statins would promote CD68+ cell emigration from plaques. We examined whether statin activation of the SREBP pathway in vivo would induce CCR7 expression and promote macrophage emigration from plaques. We found that western diet-fed apoE(-/-) mice treated with either atorvastatin or rosuvastatin led to a substantial reduction in the CD68+ cell content in the plaques despite continued hyperlipidemia. We also observed a significant increase in CCR7 mRNA in CD68+ cells from both the atorvastatin and rosuvastatin treated mice associated with emigration of CD68+ cells from plaques. Importantly, CCR7(-/-)/apoE(-/-) double knockout mice failed to display a reduction in CD68+ cell content upon statin treatment. Statins also affected the recruitment of transcriptional regulatory proteins and the organization of the chromatin at the CCR7 promoter to increase the transcriptional activity. Statins promote the beneficial remodeling of plaques in diseased mouse arteries through the stimulation of the CCR7 emigration pathway in macrophages. Therefore, statins may exhibit some of their clinical benefits by not only retarding the progression of atherosclerosis, but also accelerating its regression

Pre-treatment and extraction techniques for recovery of added value compounds from wastes throughout the agri-food chain

The enormous quantity of food wastes discarded annually force to look for alternatives for this interesting feedstock. Thus, food bio-waste valorisation is one of the imperatives of the nowadays society. This review is the most comprehensive overview of currently existing technologies and processes in this field. It tackles classical and innovative physical, physico-chemical and chemical methods of food waste pre-treatment and extraction for recovery of added value compounds and detection by modern technologies and are an outcome of the COST Action EUBIS, TD1203 Food Waste Valorisation for Sustainable Chemicals, Materials and Fuels