No abstract

The tumor microenvironment is abundant with exosomes that are secreted by the cancer cells themselves. Exosomes are nanosized, organelle-like membranous structures that are increasingly being recognized as major contributors in the progression of malignant neoplasms. A critical element in melanoma progression is its propensity to metastasize, but little is known about how melanoma cell-derived exosomes modulate the microenvironment to optimize conditions for tumor progression and metastasis. Here, we provide evidence that melanoma cell-derived exosomes promote phenotype switching in primary melanocytes through paracrine/autocrine signaling. We found that the mitogen-activated protein kinase (MAPK) signaling pathway was activated during the exosome-mediated epithelial-to-mesenchymal transition (EMT)-resembling process, which promotes metastasis. Let-7i, an miRNA modulator of EMT, was also involved in this process. We further defined two other miRNA modulators of EMT (miR-191 and let-7a) in serum exosomes for differentiating stage I melanoma patients from non-melanoma subjects. These results provide the first strong molecular evidence that melanoma cell-derived exosomes promote the EMT-resembling process in the tumor microenvironment. Thus, novel strategies targeting EMT and modulating the tumor microenvironment may emerge as important approaches for the treatment of metastatic melanoma.

Plasma miRNAs provide reliable and noninvasive markers for CRC. Plasma miR-21 warrants study in larger cohorts. It seems uniquely promising as a plasma biomarker for CRC.

Plasma miRNAs are reliable, noninvasive, and inexpensive markers for CR adenomas. This miRNA panel warrants study in larger cohorts. Plasma-based assays could provide better screening compliance compared to fecal occult blood or endoscopic screening.

BACKGROUND:The number of long-term survivors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) is increasing; however, few studies have addressed their long-term pulmonary function. METHODS: The authors examined 660 baseline and follow-up pulmonary function tests in 89 long-term survivors of pediatric hematologic malignancies and allo-HSCT. RESULTS: At least 1 abnormal lung parameter was seen in 40.4% of baseline tests and developed in 64% of post-allo-HSCT tests (median follow-up: 8.9 years). Abnormal baseline values in ratio of forced expiratory volume in 1 second and forced vital capacity (FEV 1 /FVC), FEV 1 , residual volume (RV), functional residual capacity (FRC), and FVC were associated with abnormal post-allo-HSCT values. The following pulmonary function values declined significantly with time: FEV 1 /FVC, forced mid-expiratory flow (FEF 25%-75% ), total lung capacity (TLC), diffusion capacity corrected for hemoglobin (DLCO corr ), RV, FRC, and RV/TLC. Older age at the time of allo-HSCT was associated with lower FEV 1 /FVC, FEF 25%-75% , and DLCO corr and higher RV/TLC. Patients who experienced respiratory events within 1 year post-allo-HSCT had lower FEV 1 and FVC values and higher RV/TLC from their baseline pulmonary function tests. Female patients had reduced FVC, TLC, and RV values but higher FEV 1 /FVC. Pulmonary dysfunction was also associated with high-risk hematological malignancies and peripheral blood HSC product. CONCLUSIONS: Abnormal pulmonary functions in allo-HSCT survivors are prevalent, which underscore the need for risk-adapted continual monitoring and improved preventive and management strategies.

A quantitation study using reversed phase HPLC with UV and evaporative light-scattering detector (ELSD) was conducted on 90 library standards selected from 15 small molecule combinatorial libraries (six standards from each library). This study assessed the quantitation errors using a single calibration curve for rapid purity analysis of combinatorial libraries. The average quantitation error of six standards from one library at 200 microM by UV was 13. 4%, 20.6%, and 60.3%, at 214, 220, and 254 nm, respectively. By ELSD, the average quantitation error of these six standards at 200 micro was only 7.7%. Applying this ELSD calibration curve to 84 standards from 14 structurally diverse libraries, an average quantitation error of 16.4% was obtained. The average quantitation error of all 90 standards from 15 libraries using 15 calibration curves was 18.5%.

Epstein-Barr virus (EBV)infection is associated with a broad spectrum of disease. While quantification of EBV nucleic acid in the peripheral blood has been demonstrated to be useful for diagnosis and patient care, the optimal sample type and reporting format for such testing remain uncertain. Using quantitative real-time PCR (QRT-PCR), we evaluated EBV in whole blood (WB), peripheral blood mononuclear cells (PBMC), and plasma in 249 samples from 122 patients. In WB and PBMC, results were reported both in viral copies/ml and in copies/g of total DNA. Trendings of quantitative values over time among the different sample types were compared. The sensitivities of QRT-PCR using WB and that using PBMC did not differ significantly (P ‫؍‬ 0.33), and both were more sensitive than plasma alone (P < 0.0001). EBV viral load results from WB and PBMC paired sample types also showed a significant correlation (P < 0.05), as did results reported in copies/ml and copies/g DNA for both WB and PBMC (R 2 > 0.93). EBV viral loads detected using WB and PBMC trended very closely for the few patients who had multiple positive samples available for analysis. WB and PBMC show comparable sensitivities and a close quantitative correlation when assayed for EBV by QRT-PCR. The close correlation between copies/ml and copies/g DNA also suggests that normalization to cell number or genomic DNA in cellular specimens may not be necessary.

Intelligent stimuli-responsive molecularly imprinted polymers (SR-MIPs) have attracted considerable research interest in recent years due to the potential applications in drug delivery, biotechnology and separation sciences. This review comprehensively summarizes various SR-MIPs, including the design and applications of thermo-responsive MIPs, pH-responsive MIPs, photo-responsive MIPs, biomolecule-responsive MIPs and ion-responsive MIPs. Besides the development of current SR-MIPs, the advantages as well as the disadvantages of current SR-MIPs were also displayed from different angles, especially preparation methods and application fields. We believe this review will be helpful to guide the design, development and application of SR-MIPs.Polymers 2015, 7 1690