No abstract

Hepatolithiasis is the presence of calculi within the intrahepatic bile duct specifically located proximal to the confluence of the left and right hepatic ducts. The ultimate goal of hepatolithiasis treatment is the complete removal of the stone, the correction of the associated strictures and the prevention of recurrent cholangitis. Although hepatectomy could effectively achieve the above goals, it can be restricted by the risk of insufficient residual liver volume, and has a 15.6% rate of residual hepatolithiasis. With improvements in minimally invasive surgery, post-operative cholangioscopy (POC), provides an additional option for hepatolithiasis treatment with higher clearance rate and fewer severe complications. POC is very safe, and can be performed repeatedly until full patient benefit is achieved. During POC three main steps are accomplished: first, the analysis of the residual hepatolithiasis distribution indirectly by imaging methods or directly endoscopic observation; second, the establishment of the surgical pathway to relieve the strictures; and third, the removal of the stone by a combination of different techniques such as simple basket extraction, mechanical fragmentation, electrohydraulic lithotripsy or laser lithotripsy, among others. In summary, a step-by-step strategy of POC should be put forward to standardize the procedures, especially when dealing with complicated residual hepatolithiasis. This review briefly summarizes the classification, management and complications of hepatolithiasis during the POC process.

BackgroundHomeobox B7 (HOXB7) has been identified associated with poor prognosis of hepatocellular carcinoma (HCC). However, the specific mechanism by which HOXB7 promotes the malignant progression of HCC remains to be determined.MethodsImmunohistochemistry (IHC) was used to detect the expression level of HOXB7 in 77-paired HCC tissue samples, and the correlation between HOXB7 and HCC prognosis was assessed. The location of HOXB7 was confirmed by immunofluorescence. Cell Titer-Blue assay was used to assess the proliferation of hepatoma cells. The stem-like properties of hepatoma cells were analysed by sphere formation and clone formation assays. The effect of HOXB7 on expression of cancer stem cell markers was evaluated. Transwell and wound-healing assays were performed to estimate the invasion and migration abilities of hepatoma cells. A xenograft tumor model was established in nude mice to assess the role of HOXB7 in tumor growth. Bioluminescence imaging was used to survey the effect of HOXB7 on the metastatic ability of hepatoma cells in vivo.ResultsHigher expression of HOXB7 was detected in HCC tissues compared with noncancerous tissues and significantly associated with poor prognosis of HCC. In addition, HOXB7 knockdown suppressed the cell proliferation, clone formation, sphere formation, invasion and migration of hepatoma cells in vitro; conversely, these biological abilities of hepatoma cells were enhanced by HOXB7 overexpression. Moreover, the cancer stem cell markers EPCAM and NANOG were up-regulated by HOXB7. The role of HOXB7 in promoting tumor growth and metastasis was verified in vivo. Further investigation revealed that c-Myc and Slug expression was elevated by HOXB7 and the AKT pathway was activated.ConclusionOverexpression of HOXB7 was significantly correlated with poor prognosis of HCC. HOXB7 up-regulated c-Myc and Slug expression via the AKT pathway to promote the acquisition of stem-like properties and facilitate epithelial-mesenchymal transition of hepatoma cells, accelerating the malignant progression of HCC.

Our study verifies the potential benefit and safety of adjuvant sorafenib for both decreasing HCC recurrence and extending disease-free and overall survival rates for patients with BCLC-stage C HCC after curative resection.

Colorectal cancer (CRC) is the third most diagnosed cancer worldwide. Progesterone is associated with a decreased risk of CRC and leads to a favourable prognosis. However, the specific mechanism by which progesterone suppresses malignant progression remains to be elucidated. In the present study, the level of progesterone was first analysed in 77 patients with CRC, and immunohistochemistry was performed to detect the expression of progesterone receptor (PGR) in the paired specimens. The correlations between progesterone, PGR and CRC prognosis were assessed. A Cell Counting Kit-8 assay was then used to detect proliferation of the CRC cells. Flow cytometry was performed to estimate apoptosis and to evaluate the cycle of the CRC cells. A xenograft tumour model was established in nude mice to assess the role of progesterone in tumour growth. Finally, a PCR microarray was used to screen differentially expressed genes to further interpret the mechanism by which progesterone inhibits the malignant progression of CRC. It was found that low expression of progesterone and PGR were significantly associated with poor prognosis of CRC. In addition, progesterone suppressed CRC cell proliferation by arresting the cell cycle and inducing apoptosis in vitro . Moreover, the inhibitory role of progesterone in tumour growth was verified in vivo . Further investigation showed that the level of growth arrest and DNA damage-inducible protein α (GADD45α) was up-regulated by progesterone, and this was followed by the activation of the JNK pathway. Progesterone increased the activity of the JNK pathway via GADD45α to inhibit proliferation by arresting the cell cycle and inducing apoptosis, thereby suppressing the malignant progression of CRC. Therefore, it can be concluded that progesterone and PGR might act as inhibiting factors for poor prognosis of CRC.

Hepatocellular carcinoma is associated with high mortality, and tumor metastasis is an important reason for poor prognosis. However, metastasis has not been effectively prevented in clinical therapy and the mechanisms underlying metastasis have not been fully characterized. CCAAT/enhancer-binding protein-α (C/EBPα) is a transcriptional regulator with an essential role in tumor metastasis. We used short-activating RNAs (saRNA) to enhance expression of C/EBPα. Intravenous injection of C/EBPα-saRNA in a nude mouse liver orthotopic xenograft tumor model inhibited intrahepatic and distant metastasis. C/EBPα-saRNA-treated mice showed increased serum levels of albumin and decreased alanine aminotransferase (ALT), glutamic-oxalacetic transaminase (AST), indicating a role of C/EBPα in improving liver function. Migration and invasion were inhibited in hepatoma cell lines transfected with C/EBPα-saRNA. We also observed an inhibition of epithelial-mesenchymal transition (EMT) and suppression of epidermal growth factor receptor (EGFR), EGFR phosphorylation, and β-catenin in C/EBPa-saRNA-transfected cells. Our results suggested that C/EBPα-saRNA successfully inhibited HCC metastasis by inhibiting EGFR/β-catenin signaling pathway mediated EMT in vitro and in vivo.

Cancer is a major public health problem around the world and the key leading cause of death in the world. It is well-known that glucolipid metabolism, immunoreaction, and growth/death pattern of cancer cells are markedly different from normal cells. Recently, acyl-CoA synthetase long-chain family 4 (ACSL4) is found be participated in the activation of long chain fatty acids metabolism, immune signaling transduction, and ferroptosis, which can be a promising potential target and biomarker for anticancer. Specifically, ACSL4 inhibits the progress of lung cancer, estrogen receptor (ER) positive breast cancer, cervical cancer and the up-regulation of ACSL4 can improve the sensitivity of cancer cells to ferroptosis by enhancing the accumulation of lipid peroxidation products and lethal reactive oxygen species (ROS). However, it is undeniable that the high expression of ACSL4 in ER negative breast cancer, hepatocellular carcinoma, colorectal cancer, and prostate cancer can also be related with tumor cell proliferation, migration, and invasion. In the present review, we provide an update on understanding the controversial roles of ACSL4 in different cancer cells.

Summary Diabetic cardiomyopathy (DCM) is one of the most common complications of diabetes without effective treatment options. Its pathogenesis is complex and remains unclear. Long non-coding RNA (lncRNA) MIAT allele has been reported to be enriched in DCM patients and activate a pyroptosis program in hypoxia-induced H9c2 cells. Thus, whether MIAT played a role in DCM pyroptosis remains to be clarified. In the study, the expression of MIAT was found elevated in the serum of diabetic patients, as well as in high-glucose induced cardiomyocytes and diabetic mice. Further, the expression levels of CASP1 and pyroptosis correlation factors (IL-1 and IL-18) were downregulated after silencing MIAT. Through modeling and validation experiments, we then confirmed that the MIAT-miR-214-3p-CASP1 axis serves as an essential point in pyroptosis of DCM mice. These results suggested that silencing MIAT would be a potential treatment strategy for DCM.