All-trans retinoic acid(ATRA)inhibits insufficient radiofrequency ablation(IRFA)-induced enrichment of tumor-initiating cells in hepatocellular carcinoma

Objective:Local recurrence of hepatocellular carcinoma(HCC)after radiofrequency ablation(RFA)treatment remains a serious problem.Tumor-initiating cells(TICs)are thought to be responsible for tumor relapse.Here,we investigated the effect of the TIC differentiation inducer,all-trans retinoic acid(ATRA),on RFA and explored the potential molecular mechanisms.Methods:The proportions of CD133+and epithelial cell adhesion molecule(Ep CAM);TICs in recurrent HCC after RFA and primary HCC were first determined in clinic.Then,the effect of heat intervention or insufficient RFA(IRFA)on the malignant potential of HCC cells,including cell migration,sphere formation ability,tumor growth,the proportion of CD133+and Ep CAM+TICs and expression of stem cell-related genes,was evaluated in vitro and in vivo.Finally,the effect of ATRA on the tumor growth and the proportion of TICs was evaluated.Results:In clinical data,a higher proportion of CD133+and Ep CAM+TICs was found in recurrent tumors than in primary tumors.In vitro heat intervention promoted the cell migration and sphere formation ability.Additionally,it increased the proportion of CD133+and Ep CAM+TICs and the expression of stem cell-related genes.In addition,after IRFA the residual tumors in xenografts grew faster and had more TICs than untreated tumors.ATRA remarkably inhibited residual tumor growth after IRFA by elimination of TICs though the PI3 K/AKT pathway.Combination treatment with ATRA resulted in longer survival outcomes in mouse xenografts than RFA alone.Conclusions:ATRA,as a TIC differentiation inducer,could help to improve the effect of RFA treatment,which was partially attributed to its effect against TICs.The data indicated its potential as an alternative drug in the development of better therapeutic strategies for use in combination with RFA.

Inhibition of growth and metastasis of triple-negative breast cancer targeted by Traditional Chinese Medicine Tubeimu in orthotopic mice models

Objective： Triple-negative breast cancer（TNBC） is highly invasive and metastatic, which is in urgent need of transformative therapeutics. Tubeimu（TBM）, the rhizome of Bolbostemma paniculatum（Maxim.） Franquet, is one of the Chinese medicinal herbs used for breast diseases since the ancient times. The present study evaluated the efficacy, especially the anti-metastatic effects of the dichloromethane extract of Tubeimu（ETBM） on TNBC orthotopic mouse models and cell lines.Methods： We applied real-time imaging on florescent orthotopic TNBC mice model and tested cell migration and invasion abilities with MDA-MB-231 cell line. Digital gene expression sequencing was performed and Kyoto Encyclopedia of Genes and Genomes（KEGG） analysis applied to explore the pathways influenced by ETBM.Moreover, quantitative real-time polymerase chain reactions（q RT-PCR） and Western blot were delivered to confirm the gene expression changes.Results： ETBM exhibited noticeable control on tumor metastasis and growth of TNBC tumors with no obvious toxicity. In compliance with this, it also showed inhibition of cell migration and invasion in vitro. Its impact on the changed biological behavior in TNBC may be a result of decreased expression of integrin β1（ITGβ1）, integrin β8（ITGβ8） and Rho GTPase activating protein 5（ARHGAP5）, which disabled the focal adhesion pathway and caused change in cell morphology.Conclusions： This study reveals that ETBM has anti-metastatic effects on MDA-MB-231-GFP tumor and may lead to a new therapeutic agent for the integrative treatment of highly invasive TNBC.

Effect of boron doping on waterproof and dielectric properties of polyborosiloxane coating on SiO2f/SiO2 composites

A hydrophobic coating of the silica fiber reinforced silica composites(SiO2f/SiO2) was synthesized by sol-gel method using methyltriethoxy-silane(MTES) and boric acid(B(OH)3) as raw materials. The relationship among boron doping, chemical structure of precursors and durability of hydrophobic coatings was discussed. The Si-O-B and methyl groups were successfully introduced in the gel precursors according to the FT-IR and XPS results. The resins were filled in the internal and surface holes of the SiO2f/SiO2 composites partially or completely, which is beneficial to reduce the physical adsorption of the moisture. In addition, hydroxyl groups of the SiO2f/SiO2 composites reacted with the resins and hydrophobic methyl groups were introduced, leading to the reduction of the chemical adsorption of water. Also, the boron doping was beneficial to enhancing the physical cross-linking between the coating and the SiO2f/SiO2 composites, and improved the adhesion of the coating to the substrate. The results show that the optimal hydrophobic coating with contact angle 130.33°, moisture absorption 0.33% and adhesion level 1 is obtained when the molar ratio of MTES to B(OH)3 is 10:4. The real permittivity of M10B4 is constant in the range of 2.32–2.51 and the dielectric tangent loss is constant in the range of 5.5 × 10-4–8.7 × 10-3. The hydrophobic coating has excellent dielectric properties.