EZH2 is a key component of hepatoblastoma tumor cell growth.

Background: Enhancer of zeste homolog 2 (EZH2) catalyzes the trimethylation of histone H3 at lysine 27 via the polycomb recessive complex 2 (PRC2) and plays a time-specific role in normal fetal liver development. EZH2 is overexpressed in hepatoblastoma (HB), an embryonal tumor. EZH2 can also promote tumorigenesis via a noncanonical, PRC2-independent mechanism via proto-oncogenic, direct protein interaction, including β-catenin.

Liver Transplantation for Colorectal Liver Metastases.

Colorectal cancer is one of the most common malignancies worldwide. Approximately half of the patients diagnosed will develop colorectal liver metastases (CRLM). Liver resection has a 50% 5-year survival; however, only a fourth of cases are resectable.

Quality of Life Outcomes for Patients Who Underwent Conventional Resection and Liver Transplantation for Locally Advanced Hepatoblastoma.

Hepatoblastoma is the most common malignant liver tumor of childhood, with liver transplant and extended resection used as surgical treatments for locally advanced tumors. Although each approach has well-described post-operative complications, quality-of-life outcomes have not been described following the two interventions. Long-term pediatric survivors of hepatoblastoma who underwent conventional liver resection or liver transplantation at a single institution from January 2000-December 2013 were recruited to complete quality-of-life surveys.

Structural and Functional Impact of Posttranslational Modification of Glypican-3 on Liver Carcinogenesis.

Glypican-3 (GPC3) is a cell-surface glycoprotein that is frequently overexpressed in hepatocellular carcinoma (HCC). GPC3 undergoes extensive posttranslational modification (PTM) including cleavage and glycosylation. This review focuses on the structure and function of GPC3 in liver cancer, highlighting the PTM of the tertiary and quaternary structures of GPC3 as a potential oncogenic regulatory mechanism.

Inhibition of Glypican-3 Cleavage Results in Reduced Cell Proliferation in a Liver Cancer Cell Line.

Introduction: Glypican-3 (GPC3) is a surface-bound proteoglycan overexpressed in pediatric liver cancer and utilized clinically as an immunohistochemical tumor marker. Furin is a proprotein convertase that is ubiquitously expressed and shown to modify GPC3 post-translationally. In experimental models of epithelial-based cancers, furin inhibition decreased tumor cell migration and proliferation representing a potential therapeutic target.

β-catenin cancer-enhancing genomic regions axis is involved in the development of fibrolamellar hepatocellular carcinoma.

Fibrolamellar hepatocellular carcinoma (FLC) is a disease that occurs in children and young adults. The development of FLC is associated with creation of a fusion oncoprotein DNAJB1-PKAc kinase, which activates multiple cancer-associated pathways. The aim of this study was to examine the role of human genomic regions, called cancer-enhancing genomic regions or aggressive liver cancer domains (CEGRs/ALCDs), in the development of FLC.

Minimally Invasive Surgery for Resectable Adrenocortical Carcinoma: A Nationwide Analysis.

Introduction: The utilization of minimally invasive surgery (MIS) for adrenocortical carcinoma (ACC) remains controversial due to concerns regarding the quality of surgical resection and subsequent oncologic risks. Current guidelines recommend open resections for all cases of suspected ACC independent of size; however, there has been increased adoption of MIS for ACC over time. We sought to determine whether the rise in the utilization of MIS is associated with worse survival outcomes for ACC.

The volume-outcomes relationship in donation after circulatory death liver transplantation.

Background: Donation after circulatory death (DCD) liver transplantation (LT) has become an effective mechanism for expanding the donor pool and decreasing waitlist mortality. However, it is unclear if low-volume DCD centers can achieve comparable outcomes to high-volume centers.

Methods: From 2011 to 2019 utilizing the United Network for Organ Sharing (UNOS) database, liver transplant centers were categorized into tertiles based on their annual volume of DCD LTs.

An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis.

The absence of a clinically relevant animal model addressing the typical immune characteristics of hepatocellular cancer (HCC) has significantly impeded elucidation of the underlying mechanisms and development of innovative immunotherapeutic strategies. To develop an ideal animal model recapitulating human HCC, immunocompetent male C57BL/6J mice first receive a carbon tetrachloride (CCl4) injection to induce liver fibrosis, then receive histologically-normal oncogenic hepatocytes from young male SV40 T antigen (TAg)-transgenic mice (MTD2) by intra-splenic (ISPL) inoculation. Androgen generated in recipient male mice at puberty initiates TAg expression under control of a liver-specific promoter.

Inhibition of the Receptor Tyrosine Kinase AXL Restores Paclitaxel Chemosensitivity in Uterine Serous Cancer.

Uterine serous cancer (USC) is aggressive, and the majority of recurrent cases are chemoresistant. Because the receptor tyrosine kinase AXL promotes invasion and metastasis of USC and is implicated in chemoresistance in other cancers, we assessed the role of AXL in paclitaxel resistance in USC, determined the mechanism of action, and sought to restore chemosensitivity by inhibiting AXL and We used short hairpin RNAs and BGB324 to knock down and inhibit AXL. We assessed sensitivity of USC cell lines to paclitaxel and measured paclitaxel intracellular accumulation in the presence or absence of AXL.