Dataset Information

Epigenetics in hepatocellular carcinoma development and therapy: The tip of the iceberg.

ABSTRACT: Hepatocellular carcinoma (HCC) is a deadly tumour whose causative agents are generally well known, but whose pathogenesis remains poorly understood. Nevertheless, key genetic alterations are emerging from a heterogeneous molecular landscape, providing information on the tumorigenic process from initiation to progression. Among these molecular alterations, those that affect epigenetic processes are increasingly recognised as contributing to carcinogenesis from preneoplastic stages. The epigenetic machinery regulates gene expression through intertwined and partially characterised circuits involving chromatin remodelers, covalent DNA and histone modifications, and dedicated proteins reading these modifications. In this review, we summarise recent findings on HCC epigenetics, focusing mainly on changes in DNA and histone modifications and their carcinogenic implications. We also discuss the potential drugs that target epigenetic mechanisms for HCC treatment, either alone or in combination with current therapies, including immunotherapies.

SUBMITTER: Fernandez-Barrena MG

PROVIDER: S-EPMC7585149 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Epigenetics in hepatocellular carcinoma development and therapy: The tip of the iceberg.

Fernández-Barrena Maite G MG Arechederra María M Colyn Leticia L Berasain Carmen C Avila Matias A MA

JHEP reports : innovation in hepatology 20200807 6

Hepatocellular carcinoma (HCC) is a deadly tumour whose causative agents are generally well known, but whose pathogenesis remains poorly understood. Nevertheless, key genetic alterations are emerging from a heterogeneous molecular landscape, providing information on the tumorigenic process from initiation to progression. Among these molecular alterations, those that affect epigenetic processes are increasingly recognised as contributing to carcinogenesis from preneoplastic stages. The epigenetic ...[more]

PMID: 33134907

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Project description:BackgroundRodents are among the most notorious invasive alien species worldwide. These invaders have substantially impacted native ecosystems, food production and storage, local infrastructures, human health and well-being. However, the lack of standardized and understandable estimation of their impacts is a serious barrier to raising societal awareness, and hampers effective management interventions at relevant scales.MethodsHere, we assessed the economic costs of invasive alien rodents globally in order to help overcome these obstacles. For this purpose, we combined and analysed economic cost data from the InvaCost database-the most up-to-date and comprehensive synthesis of reported invasion costs-and specific complementary searches within and beyond the published literature.ResultsOur conservative analysis showed that reported costs of rodent invasions reached a conservative total of US$ 3.6 billion between 1930 and 2022 (annually US$ 87.5 million between 1980 and 2022), and were significantly increasing through time. The highest cost reported was for muskrat Ondatra zibethicus (US$ 377.5 million), then unspecified Rattus spp. (US$ 327.8 million), followed by Rattus norvegicus specifically (US$ 156.6 million) and Castor canadensis (US$ 150.4 million). Of the total costs, 87% were damage-related, principally impacting agriculture and predominantly reported in Asia (60%), Europe (19%) and North America (9%). Our study evidenced obvious cost underreporting with only 99 documents gathered globally, clear taxonomic gaps, reliability issues for cost assessment, and skewed breakdowns of costs among regions, sectors and contexts. As a consequence, these reported costs represent only a very small fraction of the expected true cost of rodent invasions (e.g., using a less conservative analytic approach would have led to a global amount more than 80-times higher than estimated here).ConclusionsThese findings strongly suggest that available information represents a substantial underestimation of the global costs incurred. We offer recommendations for improving estimates of costs to fill these knowledge gaps including: systematic distinction between native and invasive rodents' impacts; monetizing indirect impacts on human health; and greater integrative and concerted research effort between scientists and stakeholders. Finally, we discuss why and how this approach will stimulate and provide support for proactive and sustainable management strategies in the context of alien rodent invasions, for which biosecurity measures should be amplified globally.

Project description:BackgroundCreating new therapies often involves drug companies paying healthcare professionals and institutions for research and development (R&D) activities, including clinical trials. However, industry sponsorship can create conflicts of interest (COIs). We analysed approaches to drug company R&D payment disclosure in European countries and the distribution of R&D payments at the country and company level.MethodsUsing documentary sources and a stakeholder survey we identified country- regulatory approaches to R&D payment disclosure. We reviewed company-level descriptions of disclosure practices in the United Kingdom, a country with a major role in Europe's R&D. We obtained country-level R&D payment data from industry trade groups and public authorities and company-level data from eurosfordocs.eu, a publicly available payments database. We conducted content analysis and descriptive statistical analysis.ResultsIn 32 of 37 studied countries, all R&D payments were reported without named recipients, following a self-regulatory approach developed by the industry. The methodological descriptions from 125 companies operating in the United Kingdom suggest that within the self-regulatory approach companies had much leeway in deciding what activities and payments were considered as R&D. In five countries, legislation mandated the disclosure of R&D payment recipients, but only in two were payments practically identifiable and analysable. In 17 countries with available data, R&D constituted 19%-82% of all payments reported, with self-regulation associated with higher shares. Available company-level data from three countries with self-regulation suggests that R&D payments were concentrated by big funders, and some companies reported all, or nearly all, payments as R&D.ConclusionThe lack of full disclosure of R&D payments in countries with industry self-regulation leaves considerable sums of money unaccounted for and potentially many COIs undetected. Disclosure mandated by legislation exists in few countries and rarely enhances transparency practically. We recommend a unified European approach to R&D payment disclosure, including clear definitions and a centralised database.

Dataset Information

Epigenetics in hepatocellular carcinoma development and therapy: The tip of the iceberg.

Publications

Epigenetics in hepatocellular carcinoma development and therapy: The tip of the iceberg.

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