-
Bech Fog posted an update 6 months ago
Hepatocytes are the primary functional cells of the liver that perform essential roles in homeostasis, regeneration, and injury. Most mammalian somatic cells are diploid and contain pairs of each chromosome, but there are also polyploid cells containing additional sets of chromosomes. Hepatocytes are among the best described polyploid cells, with polyploids comprising more than 25 and 90% of the hepatocyte population in humans and mice, respectively. Cellular and molecular mechanisms that regulate hepatic polyploidy have been uncovered, and in recent years, diploid and polyploid hepatocytes have been shown to perform specialized functions. Diploid hepatocytes accelerate liver regeneration induced by resection and may accelerate compensatory regeneration after acute injury. Polyploid hepatocytes protect the liver from tumor initiation in hepatocellular carcinoma and promote adaptation to tyrosinemia-induced chronic injury. This review describes how ploidy variations influence cellular activity and presents a model for context-specific functions for diploid and polyploid hepatocytes.Hepatoblastoma (HB) is the predominant primary liver tumor in children. While the prognosis is favorable when the tumor can be resected, the outcome is dismal for patients with progressed HB. Therefore, a better understanding of the molecular mechanisms responsible for HB is imperative for early detection and effective treatment. Sequencing analysis of human HB specimens unraveled the pivotal role of Wnt/β-catenin pathway activation in this disease. Nonetheless, β-catenin activation alone does not suffice to induce HB, implying the need for additional alterations. Perturbations of several pathways, including Hippo, Hedgehog, NRF2/KEAP1, HGF/c-Met, NK-1R/SP, and PI3K/AKT/mTOR cascades and aberrant activation of c-MYC, n-MYC, and EZH2 proto-oncogenes, have been identified in HB, although their role requires additional investigation. Here, we summarize the current knowledge on HB molecular pathogenesis, the relevance of the preclinical findings for the human disease, and the innovative therapeutic strategies that could be beneficial for the treatment of HB patients.Liver cancer is the second most lethal malignancy worldwide. Cell lines and murine models are the most common tools for modeling human liver carcinogenesis. Most recently, organoids with a three-dimensional structure derived from primary tissues or cells have been applied to liver cancer research. Organoids can be generated from induced pluripotent stem cells, embryonic or adult, healthy or diseased tissues. In particular, liver organoids have been widely employed in mechanistic studies aimed at delineating the molecular pathways responsible for hepatocarcinogenesis. The introduction of clustered regularly interspaced palindromic repeats (CRISPR)-associated protein 9 (Cas9) and microengineered miniorganoid technologies into liver organoids for cancer study has significantly accelerated these investigations. Translational advances have been made by utilizing liver tumor organoids for anticancer drug screening, biobanking, omics profiling, and biomarker discovery. This review summarizes the latest advances and the remaining challenges in the use of organoid models for the study of liver cancer.Tumor heterogeneity, a key hallmark of hepatocellular carcinomas (HCCs), poses a significant challenge to developing effective therapies or predicting clinical outcomes in HCC. Recent advances in next-generation sequencing-based multi-omic and single cell analysis technologies have enabled us to develop high-resolution atlases of tumors and pull back the curtain on tumor heterogeneity. By combining multiregion targeting sampling strategies with deep sequencing of the genome, transcriptome, epigenome, and proteome, several studies have revealed novel mechanistic insights into tumor initiation and progression in HCC. Epacadostat mouse Advances in multiparametric immune cell profiling have facilitated a deeper dive into the biological complexity of HCC, which is crucial in this era of immunotherapy. Moreover, studies using liquid biopsy have demonstrated their potential to circumvent the need for tissue sampling to investigate heterogeneity. In this review, we discuss how multi-omic and single-cell sequencing technologies have advanced our understanding of tumor heterogeneity in HCC.Despite advances in treatment options for hepatocellular carcinoma (HCC), 5-year survival for HCC remains below 20%. This poor survival is multifactorial but is partly related to underuse of curative treatment in clinical practice. In light of growing treatment options, delivered by different types of providers, optimal management requires input from multiple specialties. A multidisciplinary approach has been evolving over the past couple of decades, bringing different specialists together to develop a therapeutic plan to treat and manage HCC, which significantly increases timely guideline-concordant treatment and improves overall survival. The present review attempts to highlight the need for such a multimodal approach by providing insights on its potential structure and impact on the various aspects of HCC management.
To conduct a systematic review of randomized controlled trials about the safety (number and severity of adverse events) and efficacy (pain reduction and functional improvement) of mesotherapy in musculoskeletal disorders, and to compare them with other therapeutic options, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement.
A search of PubMed, Cochrane Library and Scopus database resulted in an initial total of 16,253 records. A total of 931 articles were included in the study. A final total of 7 articles, published from 1 Jan 1999 until 30 Apr 2020 were selected. Two independent reviewers selected potentially relevant studies based on the inclusion criteria for full-text reading. They evaluated the methodological quality of each study and included only studies of high methodological quality, according to the Physiotherapy Evidence Database scale.
Seven studies were included in the meta-analysis, and visual analogue scale scores before and after mesotherapy were considered.