Distinct Merkel Cell Polyomavirus Molecular Features in Tumour and Non Tumour Specimens from Patients with Merkel Cell Carcinoma

Merkel Cell Polyomavirus (MCPyV) is associated with Merkel Cell carcinoma (MCC), a rare, aggressive skin cancer with neuroendocrine features. The causal role of MCPyV is highly suggested by monoclonal integration of its genome and expression of the viral large T (LT) antigen in MCC cells. We investigated and characterized MCPyV molecular features in MCC, respiratory, urine and blood samples from 33 patients by quantitative PCR, sequencing and detection of integrated viral DNA. We examined associations between either MCPyV viral load in primary MCC or MCPyV DNAemia and survival. Results were interpreted with respect to the viral molecular signature in each compartment. Patients with MCC containing more than 1 viral genome copy per cell had a longer period in complete remission than patients with less than 1 copy per cell (34 vs 10 months, P = 0.037). Peripheral blood mononuclear cells (PBMC) contained MCPyV more frequently in patients sampled with disease than in patients in complete remission (60% vs 11%, P = 0.00083). Moreover, the detection of MCPyV in at least one PBMC sample during follow-up was associated with a shorter overall survival (P = 0.003). Sequencing of viral DNA from MCC and non MCC samples characterized common single nucleotide polymorphisms defining 8 patient specific strains. However, specific molecular signatures truncating MCPyV LT were observed in 8/12 MCC cases but not in respiratory and urinary samples from 15 patients. New integration sites were identified in 4 MCC cases. Finally, mutated-integrated forms of MCPyV were detected in PBMC of two patients with disseminated MCC disease, indicating circulation of metastatic cells. We conclude that MCPyV molecular features in primary MCC tumour and PBMC may help to predict the course of the disease

Pre-Micro RNA Signatures Delineate Stages of Endothelial Cell Transformation in Kaposi Sarcoma

MicroRNAs (miRNA) have emerged as key regulators of cell lineage differentiation and cancer. We used precursor miRNA profiling by a novel real-time QPCR method (i) to define progressive stages of endothelial cell transformation cumulating in Kaposi sarcoma (KS) and (ii) to identify specific miRNAs that serve as biomarkers for tumor progression. We were able to compare primary patient biopsies to well-established culture and mouse tumor models. Loss of mir-221 and gain of mir-15 expression demarked the transition from merely immortalized to fully tumorigenic endothelial cells. Mir-140 and Kaposi sarcoma–associated herpesvirus viral miRNAs increased linearly with the degree of transformation. Mir-24 emerged as a biomarker specific for KS

MECHANISMS OF PCBS MIXTURE TOXICITY ON ISOLATED RAT HEPATOCYTES

Exposure of isolated hepatocytes to a polychlorinated biphenyl mixture induced a rapid loss of cell viability. The effect was not dose-dependent. The biochemical effects in the cellular toxicity did not involve glutathione content, protein sulfhydryl groups and lipid peroxidation. A transient increase in cytosolic Ca2+ was observed after exposing the hepatocytes to the polychlorinated biphenyl mixture. Our findings indicate that polychlorinated biphenyls are able to kill hepatocytes and suggest that elevation of cytosolic Ca2+ concentration could be responsable of the toxicity

Nutritional composition of ultra-processed plant-based foods in the out-of-home environment: a multi-country survey with plant-based burgers.

Ultra-processed plant-based foods, such as plant-based burgers have gained in popularity. Particularly in the out-of-home (OOH) environment, evidence regarding their nutritional profile and environmental sustainability is still evolving. Plant-based burgers available at selected OOH sites were randomly sampled in cities of four WHO European Member States; Amsterdam, Copenhagen, Lisbon, and London. Plant-based burgers (patty, bread and condiment) (n=41) were lab-analysed for their energy, macronutrients, amino acids, and minerals content per 100g and serving, and were compared with reference values. For the plant-based burgers, the median values per 100g were: 234 kcal, 20.8g carbohydrates, 3.5g dietary fibre, and 12.0g fat, including 0.08g TFA and 2.2g SFA. Protein content was 8.9g/100g, with low protein quality according to amino acid composition. Median sodium content was 389mg/100g, equivalent to 1g salt. Compared with references, the median serving of plant-based burgers provided 31% of energy intake based on a 2,000 kcal per day, and contributed to carbohydrates(17-28%), dietary fibre(42%), protein(40%), total fat(48%), SFA(26%), and sodium(54%). One serving provided 15-23% of the reference values for calcium, potassium, and magnesium, while higher contributions were found for zinc(30%), manganese(38%), phosphorus(51%), and iron(67%). The ultra-processed plant-based burgers, provide protein, dietary fibre and essential minerals, but also contain relatively high levels of energy, sodium, and total fats. The amino acid composition of the plant-based burgers indicated low protein quality. The multifaceted nutritional profile of plant-based burgers highlights the need for manufacturers to implement improvements to better support healthy dietary habits. These improvements should include reducing energy, sodium and total fats