Activation of Sphingomyelin Phosphodiesterase 3 in Liver Regeneration Impedes the Progression of Colorectal Cancer Liver Metastasis Via Exosome-Bound Intercellular Transfer of Ceramides.

Background & Aims: The machinery that prevents colorectal cancer liver metastasis (CRLM) in the context of liver regeneration (LR) remains elusive. Ceramide (CER) is a potent anti-cancer lipid involved in intercellular interaction. Here, we investigated the role of CER metabolism in mediating the interaction between hepatocytes and metastatic colorectal cancer (CRC) cells to regulate CRLM in the context of LR.

Tumor-derived exosomal miR-1247-3p induces cancer-associated fibroblast activation to foster lung metastasis of liver cancer.

The communication between tumor-derived elements and stroma in the metastatic niche has a critical role in facilitating cancer metastasis. Yet, the mechanisms tumor cells use to control metastatic niche formation are not fully understood. Here we report that in the lung metastatic niche, high-metastatic hepatocellular carcinoma (HCC) cells exhibit a greater capacity to convert normal fibroblasts to cancer-associated fibroblasts (CAFs) than low-metastatic HCC cells.

Aldehyde dehydrogenase-2 (ALDH2) opposes hepatocellular carcinoma progression by regulating AMP-activated protein kinase signaling in mice.

Unlabelled: Potential biomarkers that can be used to determine prognosis and perform targeted therapies are urgently needed to treat patients with hepatocellular carcinoma (HCC). To meet this need, we performed a screen to identify functional genes associated with hepatocellular carcinogenesis and its progression at the transcriptome and proteome levels. We identified aldehyde dedydrogenase-2 (ALDH2) as a gene of interest for further study.

Musashi 2 contributes to the stemness and chemoresistance of liver cancer stem cells via LIN28A activation.

Accumulating evidence suggests that cancer stem cells (CSCs), a small subset of cancer cells, are responsible for tumor initiation, progression, relapse and metastasis. Musashi 2 (MSI2), a RNA-binding protein, was proposed to be a potent oncogene playing key roles in myeloid leukemia and gastrointestinal malignancies. However, it remains elusive how MSI2 regulates stem cell features in HCC.

Bif-1 promotes tumor cell migration and metastasis via Cdc42 expression and activity.

Tumor metastasis is the process by which tumor cells disseminate from tumors and enter nearby and distant microenvironments for new colonization. Bif-1 (BAX-interacting factor 1), which has a BAR domain and an SH3 domain, has been reported to be involved in cell growth, apoptosis and autophagy. However, the influence of Bif-1 on metastasis has been less studied.

ADRB2 signaling promotes HCC progression and sorafenib resistance by inhibiting autophagic degradation of HIF1α.

Background & Aims: Considerable evidence suggests that adrenergic signaling played an essential role in tumor progression. However, its role in hepatocellular carcinoma (HCC) and the underlying mechanisms remain unknown.

Methods: The effect of adrenaline in hepatocarcinogenesis was observed in a classical diethylnitrosamine-induced HCC mouse model.

Interferon-microRNA signalling drives liver precancerous lesion formation and hepatocarcinogenesis.

Objective: Precancerous lesion, a well-established histopathologically premalignant tissue with the highest risk for tumourigenesis, develops preferentially from activation of DNA damage checkpoint and persistent inflammation. However, little is known about the mechanisms by which precancerous lesions are initiated and their physiological significance.

Design: Laser capture microdissection was used to acquire matched normal liver, precancerous lesion and tumour tissues.

HBx regulates fatty acid oxidation to promote hepatocellular carcinoma survival during metabolic stress.

Due to a high rate of nutrient consumption and inadequate vascularization, hepatocellular carcinoma (HCC) cells constantly undergo metabolic stress during tumor development. Hepatitis B virus (HBV) X protein (HBx) has been implicated in the pathogenesis of HBV-induced HCC. In this study, we investigated the functional roles of HBx in HCC adaptation to metabolic stress.

A20 suppresses hepatocellular carcinoma proliferation and metastasis through inhibition of Twist1 expression.

Background: Aberrant expression of A20 has been reported in several human malignancies including hepatocellular carcinoma (HCC). However, its clinical relevance and potential role in HCC remain unknown.

Methods: Quantitative PCR, Western blots and immunohistochemistry analyses were used to quantify A20 expression in HCC samples and cell lines.

MiR-429 increases the metastatic capability of HCC via regulating classic Wnt pathway rather than epithelial-mesenchymal transition.

Epigenetic modification of miR-429 can manipulate liver T-ICs via targeting the RBBP4/E2F1/Oct4 axis, which might be crucial for hepatocarcinogenesis. However, whether miR-429 plays a role in regulating metastasis of hepatocellular carcinoma is still unclear. Using quantitative methylation analysis and real-time PCR, we have identified the hypomethylated status and upregulation of miR-429 in portal vein metastasis samples in comparison with their matched primary tumor.

p28GANK inhibits endoplasmic reticulum stress-induced cell death via enhancement of the endoplasmic reticulum adaptive capacity.

It has been shown that oncoprotein p28(GANK), which is consistently overexpressed in human hepatocellular carcinoma (HCC), plays a critical role in tumorigenesis of HCC. However, the underlying mechanism remains unclear. Here, we demonstrated that p28(GANK) inhibits apoptosis in HCC cells induced by the endoplasmic reticulum (ER) stress.

p28GANK knockdown-derived reactive oxygen species induces apoptosis through mitochondrial dysfunction mediated by p38 in HepG2 cells.

Oncoprotein p28GANK knockdown by RNA interference (RNAi) can induce hepatoma cells apoptosis. However, the mechanisms have not been well defined yet. In the present study the p28GANK knockdown-induced apoptosis in HepG2 cells was prevented by caspase-9 inhibitor (Z-LEHD-FMK).

[Preparation of plastic nano-hydroxyapatite/poly (3-hydroxybutyrate-hydroxyvalerate)-polymethyl lene glycol gentamicin drug delivery system].

Objective: To develop the plastic nano-hydroxyapatite (nano-HA)/poly (3-hydroxybutyrate-hydroxyvalerate)-polyethylene glycol (PHBV-PEG) gentamicin (GM) drug delivery system (DDS) (nano-HA/PHBV-PEG-GM-DDS) for treating osteomyelitis and find its releasing character in vivo.

Methods: The plastic nano-HA/PHBV-PEG-GM-DDS was prepared using nano-HA as the core carrier of GM, nano-HA with PHBV and PEG as coating and plastic fibrin glue(FG) as microsphere scaffold. The morphological features of nano-HA, drug loaded nano-HA and drug loaded nano-HA/PHBV-PEG microsphere were examined by electron microscope.

[Development of an anti-infection nano-hydroxypatite drug delivery microsphere and its drug-release in vitro].

Objective: To develop an anti-infection nano-hydroxypatite (nano-HA) microsphere for local drug delivery for treating osteomyelitis.

Methods: The nano-HA was used as the core carrier to load gentamicin (GM) and coated with poly(-hydroxybutyrate-co- hydroxyvalerate)/polyethylene glycol (PHBV/PEG), which was degradable and biocompatible, to prepare nano-HA-PHBV/PEG-GM microsphere. The surface structure and in vitro drug-release of the microsphere were studied.