RESUMO
Peritoneal carcinomatosis (PC) is a complex manifestation of abdominal cancers, with a poor prognosis and limited treatment options. Recent work identifying high concentrations of the cytokine interleukin-6 (IL-6) and its soluble receptor (sIL-6-Rα) in the peritoneal cavity of patients with PC has highlighted this pathway as an emerging potential therapeutic target. This review article provides a comprehensive overview of the current understanding of the potential role of IL-6 in the development and progression of PC. We discuss mechansims by which the IL-6 pathway may contribute to peritoneal tumor dissemination, mesothelial adhesion and invasion, stromal invasion and proliferation, and immune response modulation. Finally, we review the prospects for targeting the IL-6 pathway in the treatment of PC, focusing on common sites of origin, including ovarian, gastric, pancreatic, colorectal and appendiceal cancer, and mesothelioma.
Assuntos
Interleucina-6 , Neoplasias Peritoneais , Humanos , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/secundário , Interleucina-6/metabolismo , Interleucina-6/antagonistas & inibidores , Animais , Terapia de Alvo Molecular , Transdução de SinaisRESUMO
Nationally reported greenhouse gas inventories are a core component of the Paris Agreement's transparency framework. Comparisons with emission estimates derived from atmospheric observations help identify improvements to reduce uncertainties and increase the confidence in reported values. To facilitate comparisons over the contiguous United States, we present a 0.1° × 0.1° gridded inventory of annual 2012-2018 anthropogenic methane emissions, allocated to 26 individual source categories, with scale-dependent error estimates. Our inventory is consistent with the U.S. Environmental Protection Agency (EPA) Inventory of U.S. Greenhouse Gas Emissions and Sinks (GHGI), submitted to the United Nations in 2020. Total emissions and patterns (spatial/temporal) reflect the activity and emission factor data underlying the GHGI, including many updates relative to a previous gridded version of the GHGI that has been extensively compared with observations. These underlying data are not generally available in global gridded inventories, and comparison to EDGAR version 6 shows large spatial differences, particularly for the oil and gas sectors. We also find strong regional variability across all sources in annual 2012-2018 spatial trends, highlighting the importance of understanding regional- and facility-level activities. Our inventory represents the first time series of gridded GHGI methane emissions and enables robust comparisons of emissions and their trends with atmospheric observations.