VFA T1 mapping may become a noninvasive imaging tool for the diagnosis of liver fibrosis.

Gene therapy is one of the frontiers of modern medicine. Adeno-associated virus (AAV)-mediated gene therapy is becoming a promising approach to treat a variety of diseases and cancers. AAV-mediated cancer gene therapies have rapidly advanced due to their superiority to other gene-carrying vectors, such as the lack of pathogenicity, the ability to transfect both dividing and non-dividing cells, low host immune response, and long-term expression. This article reviews and provides up to date knowledge on AAV-mediated cancer gene therapy.

Among pharmacokinetic parameters of DCE-MRI in our study, K(trans) was an excellent predictor for differentiating fibrotic livers from normal livers, and differentiating normal livers from nonadvanced or advanced fibrosis livers. J. Magn. Reson. Imaging 2016;44:98-104.

Breast cancer is the most common malignancy in women worldwide. Recent developments in minimally invasive interventional radiology techniques have significantly improved breast cancer treatment. This study aimed to develop a novel technique for the local management of breast cancers using radiofrequency heat (RFH). We performed both in vitro experiments using human breast cancer cells and in vivo validation in xenograft animal models with magnetic resonance imaging (MRI) and pathological correlation to investigate the feasibility of our approach. Four treatment groups, including (1) no treatment (control), (2) RFH-only, (3) chemo (doxorubicin)-only, and (4) combination therapy with both doxorubicin and RFH, were conducted in each experiment. In vitro combination therapy significantly decreased breast cancer cell proliferation while increased their apoptosis index compared to the other three groups. MRI demonstrated a significant tumor size reduction in animals treated with combination therapy compared to those receiving other treatments in vivo. Such result was further confirmed by pathological examination. In conclusion, our findings suggests that RFH can enhance the therapeutic efficiency of doxorubicin on breast cancers, thus establishing the basis for future development of interventional molecular image-guided local chemotherapy for breast malignancies.

BackgroundNeurovascular compression (NVC) of the trigeminal nerve is associated with trigeminal neuralgia (TN). Some arteries that compress the trigeminal nerve are large, while others are small. This study evaluated the influence of diameter of compression arteries (DCA) on NVC with and without TN using axial diffusivity (AD) and radial diffusivity (RD) of magnetic resonance (MR) imaging.MethodsFifty TN patients with unilateral NVC, 50 asymptomatic patients with unilateral NVC, and 50 healthy controls (HC) were divided into three groups (NVC with TN, NVC without TN, and HC). The three groups were imaged with a 3.0-T MR system using three-dimensional fast imaging employing steady-state acquisition (3D FIESTA) and diffusion tensor imaging (DTI). We compared the mean size of DCA between NVC with and without TN. The mean values of AD and RD at the site of NVC were compared between the three groups. Correlation analyses were performed between the DCA and the diffusion metrics (AD and RD) in NVC patients with and without TN.ResultsThe mean DCA in NVC patients with TN (1.58 ± 0.34 mm) was larger than that without TN (0.89 ± 0.29 mm). Compared with NVC without TN and HC, the mean values of RD at the site of NVC with TN were significantly increased; however, no significant changes of AD were found between the groups. Correlation analysis showed that DCA positively correlated with RD in NVC patients with and without TN (r = 0.830, p = 0.000). No significant correlation was found between DCA and AD (r = 0.178, p = 0.077).ConclusionsLarger-diameter compression arteries may increase the chances of TN, and may be a possible facilitating factor for TN.

Background Clinical management of triple-negative breast cancer (TNBC) patients remain challenging because of the development of chemo-resistance. Identification of biomarkers for risk stratification of chemo-resistance and therapeutic decision-making to overcome such resistance is thus necessary. Methods Retrospective analysis was performed to identify potential stratification biomarkers. The levels of ceramide kinase (CERK) was determined in breast cancer patients. The roles of CERK and its downstream signaling pathways were analysed using cellular and biochemical assays. Results CERK upregulation was identified as a biomarker for chemotherapeutic response in TNBC. A > 2-fold change in CERK (from tumor)/CERK (from normal counterpart) was significantly associated with chemo-resistance (OR = 2.66, 95% CI 1.18–7.34), P = 0.04. CERK overexpression was sufficient to promote TNBC growth and migration, and confer chemo-resistance in TNBC cell lines, although this resistance could be overcome via CERK inhibition. Mechanistic studies suggest that CERK mediates intrinsic resistance and inferior response to chemotherapy in TNBC by regulating multiple oncogenic pathways such as Ras/ERK, PI3K/Akt/mTOR, and RhoA. Conclusions Our work provides an explanation for the heterogeneity of chemo-response across TNBC patients and demonstrates that CERK inhibition offers a therapeutic strategy to overcome treatment resistance.

A new facile approach, namely chemical-assisted sol-gel growth (CASGG), was successfully developed to induce the formation of fine CaF2:Yb3+, Tm3+ nanocrytals within the pore channels of mesoporous silica (mSiO2) nanoparticles. A series of upconversion photoluminescent crystalline CaF2:Yb3+,Tm3+@mSiO2 nanospheres with controlled diameters from ~65 nm to ~290 nm were fabricated. All nanospheres presented sound cyto-compatibility and unique ratiometric spectral monitoring functionalities for drug release kinetics. The nanospheres with smallest dimension (UCNP-2.5, ~65nm) induced the most sustained DOX release kinetics. More importantly, the in-vitro study demonstrated that the DOX loaded UCNP-2.5 nanopheres presented the strongest anti-cancer efficacy to MCF-7 human breast cancer cells due to its stronger penetration ability to cell nuclei due to the size effect.

Daunting challenges in investigating the controlled release of drugs in complicated intracellular microenvironments demand the development of stimuli-responsive drug delivery systems. Here, a nanoparticle system, CaF2:Tm,Yb@mSiO2, made of a mesoporous silica (mSiO2) nanosphere with CaF2:Tm,Yb upconversion nanoparticles (UCNPs) is developed, filling its mesopores and with its surface-modified with polyacrylic acid for binding the anticancer drug molecules (doxorubicin, DOX). The unique design of CaF2:Tm,Yb@mSiO2 enables us to trigger the drug release by two mechanisms. One is the pH-triggered mechanism, where drug molecules are preferentially released from the nanoparticles at acidic conditions unique for the intracellular environment of cancer cells compared to normal cells. Another is the 808 nm near infrared (NIR)-triggered mechanism, where 808 nm NIR induces the heating of the nanoparticles to weaken the electrostatic interaction between drug molecules and nanoparticles. In addition, luminescence resonance energy transfer occurs from the UCNPs (the energy donor) to the DOX drug (the energy acceptor) in the presence of 980 nm NIR irradiation, allowing us to monitor the drug release by detecting the vanishing blue emission from the UCNPs. This study demonstrates a new multifunctional nanosystem for dual-triggered and optically monitored drug delivery, which will facilitate the rational design of personalized cancer therapy.