Comprehensive evaluation of the anti-angiogenic and anti-neoplastic effects of Endostar on liver cancer through optical molecular imaging.

Molecular imaging enables non-invasive monitoring of tumor growth, progression, and drug treatment response, and it has become an important tool to promote biological studies in recent years. In this study, we comprehensively evaluated the in vivo anti-angiogenic and anti-neoplastic effects of Endostar on liver cancer based on the optical molecular imaging systems including micro-computer tomography (Micro-CT), bioluminescence molecular imaging (BLI) and fluorescence molecular tomography (FMT). Firefly luciferase (fLuc) and green fluorescent protein (GFP) dual labeled human hepatocellular carcinoma cells (HCC-LM3-fLuc-GFP cells) were used to establish the subcutaneous and orthotopic liver tumor model. After the tumor cells were implanted 14∼18 days, Endostar (5 mg/kg/day) was administered through an intravenous tail vein injection for continuous 14 days. The computer tomography angiography (CTA) and BLI were carried out for the subcutaneous tumor model. FMT was executed for the orthotopic tumor model. The CTA data showed that tumor vessel formation and the peritumoral vasculature of subcutaneous tumor in the Endostar treatment group was significantly inhibited compared to the control group. The BLI data exhibited the obvious tumor inhibition day 8 post-treatment. The FMT detected the tumor suppression effects of Endostar as early as day 4 post-treatment and measured the tumor location. The above data confirmed the effects of Endostar on anti-angiogenesis and tumor suppression on liver cancer. Our system combined CTA, BLI, and FMT to offer more comprehensive information about the effects of Endostar on the suppression of vessel and tumor formation. Optical molecular imaging system enabled the non-invasive and reliable assessment of anti-tumor drug efficacy on liver cancer

Use of indocyanine green for detecting the sentinel lymph node in breast cancer patients: from preclinical evaluation to clinical validation.

Assessment of the sentinel lymph node (SLN) in patients with early stage breast cancer is vital in selecting the appropriate surgical approach. However, the existing methods, including methylene blue and nuclides, possess low efficiency and effectiveness in mapping SLNs, and to a certain extent exert side effects during application. Indocyanine green (ICG), as a fluorescent dye, has been proved reliable usage in SLN detection by several other groups. In this paper, we introduce a novel surgical navigation system to detect SLN with ICG. This system contains two charge-coupled devices (CCD) to simultaneously capture real-time color and fluorescent video images through two different bands. During surgery, surgeons only need to follow the fluorescence display. In addition, the system saves data automatically during surgery enabling surgeons to find the registration point easily according to image recognition algorithms. To test our system, 5 mice and 10 rabbits were used for the preclinical setting and 22 breast cancer patients were utilized for the clinical evaluation in our experiments. The detection rate was 100% and an average of 2.7 SLNs was found in 22 patients. Our results show that the usage of our surgical navigation system with ICG to detect SLNs in breast cancer patients is technically feasible

The enhanced chemotherapeutic effects of doxorubicin loaded PEG coated TiO2 nanocarriers in an orthotopic breast tumor bearing mouse model

Many chemotherapeutics used for cancer treatments encounter issues during delivery to tumors in vivo and have high levels of systemic toxicity. One of the most prominent progresses in improving drug delivery efficiency is through exploring various types of nanoparticles (NPs) as drug carriers. Recent studies have demonstrated that titanium dioxide (TiO2) nanocarriers have potential for drug delivery and therapy even in multidrug resistant cancers in vitro. Moreover, it was proved that the anticancer activity of doxorubicin (DOX) was enhanced by loading onto TiO2 nanoparticles in breast cancer cells in vitro. However, there is no evidence from the animal model in vivo, which is a critical step for their further clinical applications. The aim of this study was to explore novel TiO2-PEG-DOX nanoparticles, the DOX loaded polyethylene glycol (PEG) coated TiO2 nanocarriers, and investigate their potential application in enabling controlled drug release and enhancing the chemotherapeutic efficacy of DOX in the orthotopic breast tumor bearing mice. The tumor growth and drug treatment efficacy were dynamically monitored by bioluminescence imaging (BLI), and the safety of NPs for in vivo usage was also evaluated. It was found that TiO2-PEG-DOX nanoparticles possessed improved antitumor efficacy without observable side effects compared to the free DOX treatment. Our study suggested that the PEG coated TiO2 nanocarrier is a safe and potential platform for the efficient drug delivery and minimizing the systemic toxicity of chemotherapeutic agents. It has been proved for the first time that TiO2-based nanocarriers enhance the chemotherapeutic effects of doxorubicin in vivo

Analytical and experimental evaluation of SiC-inverter nonlinearites for traction drives used in electric vehicles

This paper investigates the inverter nonlinearities in a drive system based on silicon carbide metal-oxide-semiconductor field-effect transistor (SiC-mosfets) and compares its performance with that of an equivalent silicon insulated-gate bipolar transistor (Si-IGBT) system. Initially, a novel comprehensive analytical model of the inverter voltage distortion is developed. Not only voltage drops, dead time, and output capacitance, but also switching delay times and voltage overshoot of the power devices are taken into account in the model. Such a model yields a more accurate prediction of the inverter's output voltage distortion, and is validated by experimentation. Due to inherent shortcomings of the commonly used double pulse test, the switching characteristics of both SiC-mosfets and Si-IGBTs in the pulse width modulation inverter are tested instead, such that the actual performances of the SiC and Si devices in the motor drive system are examined. Then, the switching performance is incorporated into the physical model to quantify the distorted voltages of both the SiC-based and Si-based systems. The results show that, despite its existing nonlinearities, the SiC-based drive has lower voltage distortion compared to the conventional Si-based drive as a result of its shorter switching times and smaller voltage drop, as well as a higher efficiency. Finally, the overriding operational advantages of the SiC-based drive over its Si-based counterpart is fully demonstrated by comprehensive performance comparisons

Monitoring Tumor Targeting and Treatment Effects of IRDye 800CW and GX1-Conjugated Polylactic Acid Nanoparticles Encapsulating Endostar on Glioma by Optical Molecular Imaging

Molecular imaging used in cancer diagnosis and therapeutic response monitoring is important for glioblastoma (GBM) research. Antiangiogenic therapy currently is one of the emerging approaches for GBM treatment. In this study, a multifunctional nanoparticle was fabricated that can facilitate the fluorescence imaging of tumor and deliver a therapeutic agent to the tumor region in vivo and therefore possesses broad application in cancer diagnosis and treatment. This particle was polylactic acid (PLA) nanoparticles encapsulating Endostar, which was further conjugated with GX1 peptide and the near-infrared (NIR) dye IRDye 800CW (IGPNE). We demonstrated noninvasive angiogenesis targeting and therapy of IGPNE on U87MG xenografts in vivo using dual-modality optical molecular imaging including NIR fluorescence molecular imaging (FMI) and bioluminescence imaging (BLI). The NIR FMI results demonstrated that IGPNE had more accumulation to the tumor site compared to free IRDye 800CW. To further evaluate the antitumor treatment efficacy of IGPNE, BLI and immunohistochemistry analysis were performed on tumor-bearing mice. With the aid of molecular imaging, the results confirmed that IGPNE enhanced antitumor treatment efficacy compared to free Endostar. In conclusion, IGPNE realizes real-time imaging of U87MG tumors and improves the antiangiogenic therapeutic efficacy in vivo

Molecular imaging of vulnerable atherosclerotic plaques in vivo with osteopontin-specific upconversion nanoprobes

Owing to the high mortality rate of cardiovascular diseases, developing novel noninvasive diagnostic methods becomes urgent and mandatory. It is well-known that the rupture of vulnerable plaques directly leads to deadly consequences. However, differentiating vulnerable plaques from stable plaques remains challenging in the clinic. In the current study, osteopontin (OPN), a secreted biomarker associated with macrophages and foamy macrophages, was selected as a target for identifying the vulnerable plaques. A dual modality imaging probe was constructed by covalently attaching an OPN antibody to NaGdF:Yb,Er@NaGdF upconversion nanoparticles. Upon intravenous injection of the resulting probes, upconversion optical imaging was performed to visualize the plaques induced by altering the shear stress in carotid arteries of a mouse model. The imaging studies revealed that the signals of vulnerable and stable plagues induced by lowered shear stress and oscillatory shear stress, respectively, presented significantly different signal intensities, implying that the current probe and imaging strategy are potentially useful for a precise diagnosis of atherosclerosis plaques

The mouse body weight and tumor volume.

<p>A. The mouse body weight of the subcutaneous tumor model. B. The mouse tumor volume of the subcutaneous tumor model.</p

The quantitative FMT light intensity of the orthotopic tumor.

<p>The quantitative FMT light intensity of the orthotopic tumor.</p

The FMT of the orthotopic tumor model.

<p>The coronal degree view of the orthotopic tumor progression and drug response was monitored by the FMT system.</p