92-Gene Molecular Profiling in Identification of Cancer Origin: A Retrospective Study in Chinese Population and Performance within Different Subgroups

BACKGROUND: After cancer diagnosis, therapy for the patient is largely dependent on the tumor origin, especially when a metastatic tumor is being treated. However, cases such as untypical metastasis, poorly differentiated tumors or even a limited number of tumor cells may lead to challenges in identifying the origin. Moreover, approximately 3% to 5% of total solid tumor patients will not have to have their tumor origin identified in their lifetime. The THEROS CancerTYPE ID® is designed for identifying the tumor origin with an objective, rapid and standardized procedure. METHODOLOGY AND PRINCIPAL FINDINGS: This is a blinded retrospective study to evaluate performance of the THEROS CancerTYPE ID® in a Chinese population. In total, 184 formalin-fixed paraffin-embedded (FFPE) samples of 23 tumor origins were collected from the tissue bank of Fudan University Shanghai Cancer Center (FDUSCC). A standard tumor cell enrichment process was used, and the prediction results were compared with reference diagnosis, which was confirmed by two experienced pathologists at FDUSCC. All of the 184 samples were successfully analyzed, and no tumor specimens were excluded because of sample quality issues. In total, 151 samples were correctly predicted. The agreement rate was 82.1%. A Pearson Chi-square test shows that there is no difference between this study and the previous evaluation test performed by bioTheranostics Inc. No statistically significant decrease was observed in either the metastasis group or tumors with high grades. CONCLUSIONS: A comparable result with previous work was obtained. Specifically, specimens with a high probability score (>0.85) have a high chance (agreement rate = 95%) of being correctly predicted. No performance difference was observed between primary and metastatic specimens, and no difference was observed among three tumor grades. The use of laser capture micro-dissection (LCM) makes the THEROS CancerTYPE ID® accessible to almost all of the cancer patients with different tumor statuses

Electrical resistance of CNT-PEEK composites under compression at different temperatures

Electrically conductive polymers reinforced with carbon nanotubes (CNTs) have generated a great deal of scientific and industrial interest in the last few years. Advanced thermoplastic composites made of three different weight percentages (8%, 9%, and 10%) of multiwalled CNTs and polyether ether ketone (PEEK) were prepared by shear mixing process. The temperature- and pressure-dependent electrical resistance of these CNT-PEEK composites have been studied and presented in this paper. It has been found that electrical resistance decreases significantly with the application of heat and pressure

The Reform of Employee Compensation in China’s Industrial Enterprises

Although employee compensation reform in Chinese industrial sector has been discussed in the literature, the real changes in compensation system and pay practices have received insufficient attention and warrant further examination. This paper briefly reviews the pre- and post-reform compensation system, and reports the results of a survey of pay practices in the four major types of industrial enterprises in China. The research findings indicate that the type of enterprise ownership has little influence on general compensation practices, adoption of profit-sharing plans, and subsidy and allowance packages. In general, pay is linked more to individual performance and has become an important incentive to Chinese employees. However, differences are found across the enterprise types with regard to performance-related pay. Current pay practices are positively correlated to overall effectiveness of the enterprise

Functional Divergence among Silkworm Antimicrobial Peptide Paralogs by the Activities of Recombinant Proteins and the Induced Expression Profiles

Antimicrobial peptides are small-molecule proteins that are usually encoded by multiple-gene families. They play crucial roles in the innate immune response, but reports on the functional divergence of antimicrobial peptide gene families are rare. In this study, 14 paralogs of antimicrobial peptides belonging to cecropin, moricin and gloverin families were recombinantly expressed in pET expression systems. By antimicrobial activity tests, peptides representing paralogs in the same family of cecropin and moricin families, displayed remarkable differences against 10 tested bacteria. The evolutionary rates were relatively fast in the two families, which presented obvious functional divergence among paralogs of each family. Four peptides of gloverin family had similar antimicrobial spectrum and activity against tested bacteria. The gloverin family showed similar antimicrobial function and slow evolutionary rates. By induced transcriptional activity, genes encoding active antimicrobial peptides were upregulated at obviously different levels when silkworm pupae were infected by three types of microbes. Association analysis of antimicrobial activities and induced transcriptional activities indicated that the antimicrobial activities might be positively correlated with induced transcriptional activities in the cecropin and moricin families. These results suggest that representative BmcecB6, BmcecD and Bmmor as the major effector genes have broad antimicrobial spectrum, strong antimicrobial activity and high microbe-induced expression among each family and maybe play crucial roles in eliminating microbial infection

Apolipoprotein M Gene (APOM) Polymorphism Modifies Metabolic and Disease Traits in Type 2 Diabetes

This study aimed at substantiating the associations of the apolipoproein M gene (APOM) with type 2 diabetes (T2D) as well as with metabolic traits in Hong Kong Chinese. In addition, APOM gene function was further characterized to elucidate its activity in cholesterol metabolism. Seventeen APOM SNPs documented in the NCBI database were genotyped. Five SNPs were confirmed in our study cohort of 1234 T2D and 606 control participants. Three of the five SNPs rs707921(C+1871A), rs707922(G+1837T) and rs805264(G+203A) were in linkage disequilibrium (LD). We chose rs707922 to tag this LD region for down stream association analyses and characterized the function of this SNP at molecular level. No association between APOM and T2D susceptibility was detected in our Hong Kong Chinese cohort. Interestingly, the C allele of rs805297 was significantly associated with T2D duration of longer than 10 years (OR = 1.245, p = 0.015). The rs707922 TT genotype was significantly associated with elevated plasma total- and LDL- cholesterol levels (p = 0.006 and p = 0.009, respectively) in T2D patients. Molecular analyses of rs707922 lead to the discoveries of a novel transcript APOM5 as well as the cryptic nature of exon 5 of the gene. Ectopic expression of APOM5 transcript confirmed rs707922 allele-dependent activity of the transcript in modifying cholesterol homeostasis in vitro. In conclusion, the results here did not support APOM as a T2D susceptibility gene in Hong Kong Chinese. However, in T2D patients, a subset of APOM SNPs was associated with disease duration and metabolic traits. Further molecular analysis proved the functional activity of rs707922 in APOM expression and in regulation of cellular cholesterol content

Get Phases from Arsenic Anomalous Scattering: de novo SAD Phasing of Two Protein Structures Crystallized in Cacodylate Buffer

The crystal structures of two proteins, a putative pyrazinamidase/nicotinamidase from the dental pathogen Streptococcus mutans (SmPncA) and the human caspase-6 (Casp6), were solved by de novo arsenic single-wavelength anomalous diffraction (As-SAD) phasing method. Arsenic (As), an uncommonly used element in SAD phasing, was covalently introduced into proteins by cacodylic acid, the buffering agent in the crystallization reservoirs. In SmPncA, the only cysteine was bound to dimethylarsinoyl, which is a pentavalent arsenic group (As (V)). This arsenic atom and a protein-bound zinc atom both generated anomalous signals. The predominant contribution, however, was from the As anomalous signals, which were sufficient to phase the SmPncA structure alone. In Casp6, four cysteines were found to bind cacodyl, a trivalent arsenic group (As (III)), in the presence of the reducing agent, dithiothreitol (DTT), and arsenic atoms were the only anomalous scatterers for SAD phasing. Analyses and discussion of these two As-SAD phasing examples and comparison of As with other traditional heavy atoms that generate anomalous signals, together with a few arsenic-based de novo phasing cases reported previously strongly suggest that As is an ideal anomalous scatterer for SAD phasing in protein crystallography