Targeting myeloid regulators by paclitaxel-loaded enzymatically degradable nanocups.

Tumor microenvironment is characterized by immunosuppressive mechanisms associated with the accumulation of immune regulatory cells - myeloid-derived suppressor cells (MDSC). Therapeutic depletion of MDSC has been associated with inhibition of tumor growth and therefore represents an attractive approach to cancer immunotherapy. MDSC in cancer are characterized by enhanced enzymatic capacity to generate reactive oxygen and nitrogen species (RONS) which have been shown to effectively degrade carbonaceous materials. We prepared enzymatically openable nitrogen-doped carbon nanotube cups (NCNC) corked with gold nanoparticles and loaded with paclitaxel as a therapeutic cargo. Loading and release of paclitaxel was confirmed through electron microscopy, Raman spectroscopy and LC-MS analysis. Under the assumption that RONS generated by MDSCs can be utilized as a dual targeting and oxidative degradation mechanism for NCNC, here we report that systemic administration of paclitaxel loaded NCNC delivers paclitaxel to circulating and lymphoid tissue MDSC resulting in the inhibition of growth of tumors (B16 melanoma cells inoculated into C57BL/6 mice) in vivo. Tumor growth inhibition was associated with decreased MDSC accumulation quantified by flow cytometry that correlated with bio-distribution of gold-corked NCNC resolved by ICP-MS detection of residual gold in mouse tissue. Thus, we developed a novel immunotherapeutic approach based on unique nanodelivery vehicles, which can be loaded with therapeutic agents that are released specifically in MDSC via NCNC selective enzymatic "opening" affecting change in the tumor microenvironment.

Median nerve changes following steroid injection for carpal tunnel syndrome.

INTRODUCTION: Neuromuscular ultrasound is a painless, radiation-free, high-resolution imaging modality for assessment of the peripheral nervous system. The purpose of this study was to use neuromuscular ultrasound to assess the changes that occur in the median nerve after steroid injection for carpal tunnel syndrome (CTS). METHODS: Ultrasound and nerve conduction studies were performed at baseline and 1 week, 1 month, and 6 months after steroid injection in 19 individuals (29 wrists) with CTS. RESULTS: Significant changes were noted in median nerve cross-sectional area (P < 0.001), mobility (P = 0.001), and vascularity (P = 0.042) at the distal wrist crease after steroid injection, and the nerve cross-sectional area correlated with symptom score and electrodiagnostic parameters. Changes in the ultrasonographic parameters were seen within 1 week of injection. CONCLUSIONS: These findings suggest neuromuscular ultrasound is potentially helpful for the assessment of individuals undergoing treatment for CTS, as typical changes can be expected after successful treatment injection.

Multispectral analysis of bone lesions in the hands of patients with rheumatoid arthritis.

Quantitative measures of rheumatoid arthritis (RA) disease progression can provide valuable tools for evaluation of new treatments during clinical trials. In this study, a novel multispectral (MS) MRI analysis method is presented to quantify changes in bone lesion volume (DeltaBLV) in the hands of RA patients. Image registration and MS analysis were employed to identify MS tissue class transitions between two serial MRI exams. DeltaBLV was determined from MS class transitions between two time points. The following three classifiers were investigated: (a) multivariate Gaussian (MVG), (b) k-nearest neighbor (k-NN), and (c) K-means (KM). Unlike supervised classifiers (MVG, k-NN), KM, an unsupervised classifier, does not require labeled training data, resulting in potentially greater clinical utility. All MS estimates of DeltaBLV were linearly correlated (r(p)) with manual estimates. KM and k-NN estimates also exhibited a significant rank-order correlation (r(s)) with manual estimates. For KM, r(p) = 0.94 p < 0.0001, r(s) = 0.76 p = 0.002; for k-NN, r(p) = 0.86 p = 0.0001, r(s) = 0.69 p = 0.009; and for MVG, r(p) = 0.84 p = 0.0003, r(s) = 0.49 p = 0.09. Temporal classification rates were as follows: for KM, 90.1%; for MVG, 89.5%; and for k-NN, 86.7%. KM matched the performance of k-NN, offering strong potential for use in multicenter clinical trials. This study demonstrates that MS tissue class transitions provide a quantitative measure of DeltaBLV.