Death rate from HCC is increasing and liver cancer is the second leading cause of cancer-related mortality worldwide. Most patients with HCC have underlying liver cirrhosis and compromised liver function, limiting treatment options. Cirrhosis is associated with cell dedifferentiation and expansion of hepatocholangiolar progenitor cells. We identified a miRNA signature associated with HCC and hepatocytic differentiation of progenitor cells. We further identified miR-148a as an inducer of hepatocytic differentiation that is downregulated in HCC. MiR-148a-mimetic treatment in vivo suppressed tumor growth, reduced tumor malignancy and liver fibrosis, and prevented tumor development. These effects were associated with an increased differentiated phenotype and were mediated by IKKα/NUMB/NOTCH signaling. Conclusion our results identified miR-148a as an inhibitor of the IKKα/NUMB/NOTCH pathway and an inducer of hepatocytic differentiation that when deregulated promotes HCC initiation and progression. This study represents the first evidence that differentiation-targeted therapy is a promising strategy to treat and prevent HCC.

Bismuth oxyhalides with layered structures have emerged as an important class of photocatalysts but usually suffer from low activity largely due to their unfavorable band structures. Although point defects as typical electronic structure modifiers have been actively used to modify electronic structures of photocatalysts for high photocatalytic activity, the underlying role of halogen vacancies in improving activity of bismuth oxyhalides has been overlooked. In this study, we demonstrate the substantial role of iodine vacancies in enabling photocatalytic activity of BiOI as a model oxyhalide photocatalyst. It is found that iodine vacancies cause a 0.23 eV downward shift of the valence band maximum of BiOI but not much change in the bandgap. Such band structure modification leads to the formation of photogenerated holes with a stronger oxidative ability, which is favorable for photocatalysis with the holes induced half reaction as a rate-determining step. The results obtained might provide an important implication in designing highly efficient oxyhalide-based photocatalysts by controlling halogen vacancies.

Purpose: Liver cancer, one of the most common cancers in China, is reported to feature relatively high morbidity and mortality. Curcumin (Cum) is considered as a drug possessing anti-angiogenic, anti-inflammation and anti-oxidation effect. Previous research has demonstrated antitumor effects in a series of cancers. Materials and Methods: In this study the in vitro cytotoxicity of Cum was measured by MTT assay and pro-apoptotic effects were assessed by DAPI staining and measurement of caspase-3 activity. In vivo anti-hepatoma efficacy of Cum was assessed with HepG2 xenografts. Results: It is found that Cum dose-dependently inhibited cell growth in HepG2 cells with activation of apoptosis. Moreover, Cum delayed the growth of liver cancer in a dose-dependent manner in nude mice. Conclusions: Cum might be a promising phytomedicine in cancer therapy and further efforts are needed to explore this therapeutic strategy.

Granulocyte-colony-stimulating factor (G-cSF) is a member of the hematopoietic growth factor family that primarily affects the neutrophil lineage. G-cSF serves as a powerful mobilizer of peripheral blood stem cells and recombinant human G-cSF (rhG-cSF) has been used to treat granulocytopenia and neutropenia after chemotherapy for cancer patients. However, recent studies have found that G-cSF plays an important role in cancer progression. G-cSF expression is increased in different types of cancer cells, such as lung cancer, gastric cancer, colorectal cancer, invasive bladder carcinoma, glioma and breast cancer. However, it is unclear whether treatment with G-cSF has an adverse effect. The current review provides an overview of G-cSF in malignant breast cancer development and the data presented in this review are expected to provide new ideas for cancer therapy. Contents 1. introduction 2. Structure of the G-cSF gene 3. regulation of G-cSF gene expression 4. The G-cSF receptor 5. G-cSF expression in breast cancer 6. direct effects of G-cSF on breast cancer 7. role of tumor microenvironment in the effect of G-cSF on breast cancer 8. conclusions

MicroRNA expression profiling in human liver progenitor cells following hepatocytic differentiation identified miR-122 and miR-194 as the microRNAs most strongly upregulated during hepatocytic differentiation of progenitor cells. MiR-194 was also highly upregulated following hepatocytic differentiation of human embryonic stem cells (hESCs). Overexpression of miR-194 in progenitor cells accelerated their differentiation into hepatocytes, as measured by morphological features such as canaliculi and expression of hepatocytic markers. Overexpression of miR-194 in hESCs induced their spontaneous differentiation, a phenotype accompanied with accelerated loss of the pluripotent factors OCT4 and NANOG and decrease in mesoderm marker HAND1 expression. We then identified YAP1 as a direct target of miR-194. Inhibition of YAP1 strongly induced hepatocytic differentiation of progenitor cells and YAP1 over expression reversed the miR-194-induced hepatocytic differentiation of progenitor cells. In conclusion, we identified miR-194 as a potent inducer of hepatocytic differentiation of progenitor cells and further identified YAP1 as a mediator of miR-194's effects on hepatocytic differentiation and liver progenitor cell fate.

Adipocyte is the most predominant cell type in the tumor microenvironment of breast cancer and plays a pivotal role in cancer progression, yet the underlying mechanisms and functional mediators remain elusive. We isolated primary preadipocytes from mammary fat pads of human breast cancer patients and generated mature adipocytes and cancer-associated adipocytes (CAAs) in vitro. The CAAs exhibited significantly different gene expression profiles as assessed by transcriptome sequencing. One of the highly expressed genes in CAAs is granulocyte colony-stimulating factor (G-CSF). Recombinant human G-CSF treatment or stably expression of human G-CSF in triple-negative breast cancer (TNBC) cell lines enhanced EMT, migration, and invasion of cancer cells, by activating Stat3. Accordantly, targeting G-CSF/Stat3 signaling with G-CSF-neutralizing antibody, a chemical inhibitor, or siRNAs for Stat3 could abrogate CAAs- or G-CSF-induced migration and invasion of breast cancer cells. The pro-invasive genes MMP2 and MMP9 were identified as target genes of G-CSF in TNBC cells. Furthermore, in human breast cancer tissues, elevated G-CSF expression in adipocytes is well correlated with activated Stat3 signal in cancer cells. Together, our results suggest a novel strategy to intervene with invasive breast cancers by targeting CAAs-derived G-CSF.

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Circulating tumor cells (CTCs) are defined as tumor cells circulating in the peripheral blood of patients, shed from either the primary tumors or its metastases. Many techniques have been developed in the recent years to identify CTCs in breast cancer patients, and trials have proved the prognostic significance of CTCs. In this study, we validated the CTC detection method of combining cell filtration and laser scanning cytometry (LSC), which was highly reproducible with increased sensitivity and accuracy. In 134 non-metastatic breast cancer patients analyzed, HER2 was found to be the only primary tumor characteristics that correlated with the presence of CTCs. 85 patients with definitive stage information were selected for association study between the disease stages and CTC numbers. The detection rate and the number of CTCs were correlated with the disease stages. Moreover, assessment of CTCs in 92 metastatic breast cancer patients was found to be able to predict the efficacy of chemotherapy. Increase in CTC numbers was an independent prognostic factor for treatment outcomes. Our results suggested that CTC assessment could be an indication of the disease progression and analysis of the properties of CTCs is likely to provide new insights into the biology of breast cancer and contribute to defining novel treatments and better prediction of clinical outcomes.