2H-NMR measurements of deuterated poly(dimethylsiloxane) [PDMS(d)] elastomers with systematically varied elastic and swelling properties are presented. 2H-NMR transverse dephasing data are compared to the predictions of a model describing elastomer deuterium transverse dephasing data as a linear superposition of contributions from elastic and pendant chains. Structural parameters obtained from the model for 2H-NMR transverse dephasing are compared to structural parameters inferred from swelling measurements using statistical and thermodynamic models. As predicted by the model for transverse dephasing data, dephasing time constants for elastic chains are directly proportional to number-average molecular weights of elastic chains obtained from swelling measurements.

Nasopharyngeal carcinoma (NPC) is a prevalent malignancy in Southeast Asia among the Chinese population. Aberrant regulation of transcripts has been implicated in many types of cancers including NPC. Herein, we characterized mRNA and miRNA transcriptomes by RNA sequencing (RNASeq) of NPC model systems. Matched total mRNA and small RNA of undifferentiated Epstein–Barr virus (EBV)-positive NPC xenograft X666 and its derived cell line C666, well-differentiated NPC cell line HK1, and the immortalized nasopharyngeal epithelial cell line NP460 were sequenced by Solexa technology. We found 2812 genes and 149 miRNAs (human and EBV) to be differentially expressed in NP460, HK1, C666 and X666 with RNASeq; 533 miRNA–mRNA target pairs were inversely regulated in the three NPC cell lines compared to NP460. Integrated mRNA/miRNA expression profiling and pathway analysis show extracellular matrix organization, Beta-1 integrin cell surface interactions, and the PI3K/AKT, EGFR, ErbB, and Wnt pathways were potentially deregulated in NPC. Real-time quantitative PCR was performed on selected mRNA/miRNAs in order to validate their expression. Transcript sequence variants such as short insertions and deletions (INDEL), single nucleotide variant (SNV), and isomiRs were characterized in the NPC model systems. A novel TP53 transcript variant was identified in NP460, HK1, and C666. Detection of three previously reported novel EBV-encoded BART miRNAs and their isomiRs were also observed. Meta-analysis of a model system to a clinical system aids the choice of different cell lines in NPC studies. This comprehensive characterization of mRNA and miRNA transcriptomes in NPC cell lines and the xenograft provides insights on miRNA regulation of mRNA and valuable resources on transcript variation and regulation in NPC, which are potentially useful for mechanistic and preclinical studies.

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Abstract. Hepatocellular carcinoma (HCC) shows low response to most conventional chemotherapies. To facilitate target identification for novel therapeutic development, we deployed gene expression profiling on 43 paired HCC tumors and adjacent non-tumoral liver, which is also considered as the pre-malignant liver lesion. In conjunction with ontology analysis, a major functional process found to play a role in the malignant transformation of HCC was microtubule-related cellular assembly. We further examined the potential use of microtubule targeting taxane drugs, including paclitaxel and docetaxel, and compared with findings to results from doxorubicin, a common chemotherapeutic agent used in HCC. Recent studies showed that drug delivery by nanoparticles have enhanced efficacy with reduced side effects. In this regard, the nanoparticle albumin-bound (nab)-paclitaxel was also examined. In a panel of HCC cell lines studied, a high sensitivity towards taxane drugs was generally found, although the effect from nab-paclitaxel was most profound. The nabpaclitaxel showed an effective IC 50 dose at 15-fold lower than paclitaxel alone or the derivative analogue docetaxel, and 450-fold less compared to doxorubicin. Flow cytometric analysis confirmed a cell cycle blockade at the G 2 /M phase and increased apoptosis following nab-paclitaxel treatment.In vivo animal studies also showed that nab-paclitaxel readily inhibited xenograft growth with less toxicity to host cells compared to other anti-microtubule drugs and doxorubicin. Gene silencing of the microtubule regulatory gene STMN1 by RNAi suggested a distinct synergistic effect in the combined treatment with nab-paclitaxel. Our findings in this study highly suggest that the microtubule assembly represents a promising therapeutic target development in HCC.