Genomic and transcriptomic characteristics of 12 novel primary cell lines derived from three patients with cholangiocarcinoma.

Cholangiocarcinoma (CCA) is an aggressive bile duct malignancy with poor prognosis. To improve our understanding of the biological characteristics of CCA and develop effective therapies, appropriate preclinical models are required. Here, we established and characterized 12 novel patient-derived primary cancer cell (PDPC) models using multi-region sampling.

Mechanistic insights into the allosteric inactivation mechanism of ZAP-70 induced by the hot spot W165C mutation.

Zeta chain-associated protein kinase 70 (ZAP-70) is a non-receptor tyrosine kinase that interacts with the activated T-cell receptor to transduce downstream signals, and thus plays an important role in the adaptive immune system. The biphosphorylated immunotyrosine-based activation motifs (ITAM-Y2P) binds to the N-SH2 and C-SH2 domains of ZAP-70 to promote the activation of ZAP-70. The present study explores molecular mechanisms of allosteric inactivation of ZAP-70 induced by the hot spot W165C mutation through atomically detailed molecular dynamics simulation approaches.

Surgical treatment of hilar cholangiocarcinoma: retrospective analysis.

Background: Achieving a better prognosis for patients and reducing the risk of complications are primary considerations in surgical decisions for hilar cholangiocarcinoma.

Methods: A retrospective analysis of the authors' clinical practice outcomes in the surgical management of patients with hilar cholangiocarcinoma following the planned-hepatectomy surgical treatment programme between 2009 and 2018.

Results: Some 473 patients were included, of whom 127 (26.

Totally laparoscopic associating simultaneous bile duct and portal vein ligation for planned hepatectomy for primary liver cancer: a case report.

Background: Some patients with liver cancer lose the chance to have surgical treatment due to insufficient future remnant liver. To address this problem, individual or occlusion of both the portal vein and the bile duct was used to achieve quick hypertrophy. This is the first study reported in which simultaneous ligation of the portal vein and the bile duct was applied as the first step of planned hepatectomy of primary liver cancer.

AXL Overexpression in Tumor-Derived Endothelial Cells Promotes Vessel Metastasis in Patients With Hepatocellular Carcinoma.

Portal vein tumor thrombus (PVTT) is one of the most serious forms of hepatocellular carcinoma (HCC) vessel metastasis and has a poor survival rate. However, the molecular mechanism of PVTT has not yet been elucidated. In this study, the molecular mechanism of AXL expressed in tumor-derived endothelial cells (TECs) in vessel metastasis was investigated.

Development and Evaluation of Nomograms to Predict the Cancer-Specific Mortality and Overall Mortality of Patients with Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the most common type among primary liver cancers (PLC). With its poor prognosis and survival rate, it is necessary for HCC patients to have a long-term follow-up. We believe that there are currently no relevant reports or literature about nomograms for predicting the cancer-specific mortality of HCC patients.

Screening and verification of long noncoding RNA promoter methylation sites in hepatocellular carcinoma.

Background: Long noncoding ribonucleic acid (lncRNA) promoter methylation is closely related to the occurrence and development of hepatocellular carcinoma (HCC). Thus, we aim to screen and verify the lncRNA promoter methylation sites associated with overall survival (OS), vascular invasion, pathological grade, and clinical stage in HCC.

Methods: Methylation-related data including clinical characteristic, transcriptome, methylation, and messenger RNA (mRNA) expression were taken from the Cancer Genome Atlas (TCGA) database.

A novel molecular-clinicopathologic nomogram to improve prognosis prediction of hepatocellular carcinoma.

Background: Emerging evidence suggests that long non-coding RNA (lncRNA) plays a crucial part in the development and progress of hepatocellular carcinoma (HCC). The objective was to develop novel molecular-clinicopathological prediction methods for overall survival (OS) and recurrence of HCC.

Results: An 8-lncRNA-based classifier for OS and a 14-lncRNA-based classifier for recurrence were developed by LASSO COX regression analysis, both of which had high accuracy.

FOXK1 Promotes Proliferation and Metastasis of Gallbladder Cancer by Activating AKT/mTOR Signaling Pathway.

Gallbladder cancer (GBC) is one of the most lethal malignancies worldwide, with extremely poor prognosis. Recently, forkhead box k1 (FOXK1), a member of the FOX transcription factor family, has been reported to be correlated with tumor progression in multiple malignancies. However, the role of FOXK1 in GBC has not been elucidated.

Screening and verification of microRNA promoter methylation sites in hepatocellular carcinoma.

The promoter methylation mode of microribonucleic acid (miRNA) plays a crucial role in the process of hepatocellular carcinoma (HCC). Therefore, the primary purpose of this study was to screen and verify the miRNA methylation sites associated with the overall survival (OS) and clinical characteristics of HCC patients. Methylation-related data were from the Cancer Genome Atlas (TCGA).

A novel genomic-clinicopathologic nomogram to improve prognosis prediction of hepatocellular carcinoma.

There is a lack of precise and clinical accessible model to predict the prognosis of hepatocellular carcinoma (HCC) in clinic practice currently. Here, an inclusive nomogram was developed by integrating genomic markers and clinicopathologic factors for predicting the outcome of patients with HCC. A total of 365 samples of HCC were obtained from the Cancer Genome Atlas (TCGA) database.

CD31 regulates metastasis by inducing epithelial-mesenchymal transition in hepatocellular carcinoma via the ITGB1-FAK-Akt signaling pathway.

Platelet endothelial cell adhesion molecule-1 (PECAM-1 or CD31) is a well-known marker of endothelial cells and a key factor for adhesion and accumulation of platelets. CD31 plays roles in cell proliferation, apoptosis, migration, and cellular immunity. CD31 is also expressed on tumor cells, such as breast cancer cells and non-Hodgkin's lymphomas, and contributes to tumor cell invasion.

Insufficient Radiofrequency Ablation Treated Hepatocellular Carcinoma Cells Promote Metastasis by Up-Regulation ITGB3.

Radiofrequency ablation (RFA) is one of the standards of care for early stage hepatocellular carcinoma (HCC). However, rapid progression of residual tumor after RFA has been confirmed. The aim of this study was to investigate the underlying mechanism of this phenomenon.

Colony-stimulating factor-1-induced AIF1 expression in tumor-associated macrophages enhances the progression of hepatocellular carcinoma.

M2-polarized (alternatively activated) macrophages play an important role in the progression of hepatocellular carcinoma (HCC). Allograft inflammatory factor 1 (AIF1) is overexpressed in M2-polarized macrophages. This study explored the role of AIF1 in tumor-associated macrophages in HCC.

Colony-Stimulating Factor 1 Receptor Blockade Inhibits Tumor Growth by Altering the Polarization of Tumor-Associated Macrophages in Hepatocellular Carcinoma.

Colony-stimulating factor-1 (CSF-1) and its receptor, CSF-1R, regulate the differentiation and function of macrophages and play an important role in macrophage infiltration in the context of hepatocellular carcinoma. The therapeutic effects of CSF-1R blockade in hepatocellular carcinoma remain unclear. In this study, we found that CSF-1R blockade by PLX3397, a competitive inhibitor with high specificity for CSF-1R tyrosine kinase, significantly delayed tumor growth in mouse models.

Reduced expression of CD109 in tumor-associated endothelial cells promotes tumor progression by paracrine interleukin-8 in hepatocellular carcinoma.

Tumor-associated endothelial cells (TEC) directly facilitate tumor progression, but little is known about the mechanisms. We investigated the function of CD109 in TEC and its clinical significance in hepatocellular carcinoma (HCC). The correlation between CD109 expressed on tumor vessels and the prognosis after surgical resection of HCC was studied.

Robo1 promotes angiogenesis in hepatocellular carcinoma through the Rho family of guanosine triphosphatases' signaling pathway.

Robo1 is a member of the Robo immunoglobulin superfamily of proteins, and it plays an important role in angiogenesis and cancer. In this study, we investigate the role of roundabout 1 (Robo1) in tumor angiogenesis in hepatocellular carcinoma (HCC). Firstly, the relationship between Robo1 expression on tumors and patient's survival and endothelial cells in tumor blood vessels and patient's survival was studied.

microRNA-26a suppresses recruitment of macrophages by down-regulating macrophage colony-stimulating factor expression through the PI3K/Akt pathway in hepatocellular carcinoma.

Background: microRNAs (miRNAs) have been reported to modulate macrophage colony-stimulating factor (M-CSF) and macrophages. The aim of this study was to find whether miR-26a can suppress M-CSF expression and the recruitment of macrophages.

Methods: Hepatocellular carcinoma (HCC) cell lines with decreased or increased expression of miR-26a were established in a previous study.

Incomplete radiofrequency ablation enhances invasiveness and metastasis of residual cancer of hepatocellular carcinoma cell HCCLM3 via activating β-catenin signaling.

Background: Radiofrequency ablation (RFA) is one of the curative therapies for hepatocellular carcinoma (HCC), however, accelerated progression of residual HCC after incomplete RFA has been reported more frequently. The underlying molecular mechanism of this phenomenon remains to be elucidated. In this study, we used an incomplete RFA orthotopic HCC nude mouse model to study the invasive and metastatic potential of residual cancer as well as the correlated mechanism.

Arsenic trioxide induces differentiation of CD133+ hepatocellular carcinoma cells and prolongs posthepatectomy survival by targeting GLI1 expression in a mouse model.

Background: Cancer stem cells (CSCs) play a key role in the posthepatectomy recurrence of hepatocellular carcinoma (HCC). CD133+ HCC cells exhibit liver CSC-like properties, and CSC differentiation-inducing therapy may lead these cells to lose their self-renewal ability and may induce terminal differentiation, which may in turn allow their malignant potential to be controlled. Because arsenic trioxide (As₂O₃) increases remission rates and prolongs survival among patients with acute promyelocytic leukemia by inducing differentiation and apoptosis of leukemic cells, we hypothesized that As₂O₃ might also inhibit HCC recurrence and prolong survival time after hepatectomy by inducing differentiation of HCC CSCs.

MicroRNA-26a inhibits angiogenesis by down-regulating VEGFA through the PIK3C2α/Akt/HIF-1α pathway in hepatocellular carcinoma.

Background & Aims: microRNAs (miRNAs) have been reported to regulate angiogenesis by down-regulating the expression of pro-angiogenic or anti-angiogenic factors. The aims of this study were to investigate whether miR-26a inhibited angiogenesis by down-regulating vascular endothelial growth factor A (VEGFA) and its clinical relevance in hepatocellular carcinoma (HCC).

Methods: The expression of miR-26a was modified in HepG2 and HCCLM3 cell lines respectively, and a panel of angiogenic factors was measured by real-time PCR in the cells.

Aspirin minimized the pro-metastasis effect of sorafenib and improved survival by up-regulating HTATIP2 in hepatocellular carcinoma.

Background Aims: We previously demonstrated the pro-metastasis effect of sorafenib in hepatocellular carcinoma (HCC), which is mediated by down-regulation of tumor suppressor HTATIP2. The aim of the present study was to determine whether aspirin minimizes this effect and improves survival.

Methods: The effects of sorafenib, aspirin, and combined sorafenib and aspirin were observed in HCCLM3 and HepG2 xenograft nude mice.