Cancer is a disease of complex genetic alterations, and comprehensive genetic diagnosis is beneficial to match each patient to appropriate therapy. However, acquisition of representative tumor samples is invasive and sometimes impossible. Circulating tumor DNA (ctDNA) is a promising tool to use as a non-invasive biomarker for cancer mutation profiling. Here we implemented targeted next generation sequencing (NGS) with a customized gene panel of 382 cancer-relevant genes on 605 ctDNA samples in multiple cancer types. Overall, tumor-specific mutations were identified in 87% of ctDNA samples, with mutation spectra highly concordant with their matched tumor tissues. 71% of patients had at least one clinically-actionable mutation, 76% of which have suggested drugs approved or in clinical trials. In particular, our study reveals a unique mutation spectrum in Chinese lung cancer patients which could be used to guide treatment decisions and monitor drug-resistant mutations. Taken together, our study demonstrated the feasibility of clinically-useful targeted NGS-based ctDNA mutation profiling to guide treatment decisions in cancer.

The results of the present study define a novel mechanism of action of ACEI treatment in patients with stable CAD: the augmentation of circulating EPCs with enhanced functional activity. Given the well-established role of EPCs of participating in repair after ischemic injury, stimulation of EPCs by ACEI may contribute to the clinical benefit of ACEI therapy in patients with CAD.

Skin rash, diarrhea and hepatotoxicity are the most common toxicities of Gefitinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor. The present study investigated the effects of genetic polymorphisms of drug target, metabolizing enzymes and transporters on Gefitinib toxicities. Thirty single-nucleotide polymorphisms, including EGFR, cytochromes P450 and ATP-binding cassette (ABC), were genotyped by matrix-assisted laser desorption/ionization time-of-flight platform in 59 non-small cell lung cancer patients treated with Gefitinib. Correlation analyses were performed to evaluate their effects on Gefitinib-induced toxicities. ABCB1 rs1128503 TT genotype was a significant high-risk determinant of both skin rash and diarrhea, with 15.78- and 10.78-fold of incident risk increased, respectively. (odds ratio (OR)=15.78, 95% confidence interval (CI) 2.01-124.1, P=0.0087; OR=10.78, 95% CI 1.54-75.40, P=0.0166 vs non-TT genotypes). Patients with ABCB1 rs1128503 TT genotype had greater risk of skin rash and diarrhea. Therefore, polymorphism analyses of ABCB1 might be beneficial to optimize Gefitinib treatment.

Pleural effusions (PE) are the most common complications that may be produced by a wide variety of diseases. A large number of studies exploring the role of carcinoembryonic antigen (CEA) and cytokeratin fragment 19 (CYFRA 21-1) marker in differential diagnosis of PE have been published, employing differing methodologies with sometimes conflicting results. A comprehensive systematic review would be useful to synthesize the currently available bulk of information. The objective of this work was to assess and compare the overall value of pleural fluid CEA and CYFRA 21-1 in differential diagnosis of PEs with a meta-analysis. All the English and Chinese published studies for differential diagnosis of PEs by pleural fluid CEA and CYFRA 21-1 were collected. Methodological quality of the included studies was evaluated. Pooled sensitivity and specificity were calculated, the threshold effect and the possible sources of heterogeneity were also analyzed. Summary receiver operating characteristic (SROC) curve analysis was used to compare the differential diagnostic ability of pleural fluid CEA and CYFRA 21-1. A total of 19 studies were included in the meta-analysis, with a total of 3,228 subjects. Pooled sensitivity and specificity of CEA and CYFRA 21-1 were 45.9% (43.2-48.5%) and 97.0% (96.0-97.8%), and 47.3% (44.0-50.6%) and 91.8% (89.5-93.7%), respectively. Both CEA and CYFRA 21-1 have a threshold effect, the main source of heterogeneity was from variable assay methods. The areas under the SROC curve (AUCs) of CEA and CYFRA 21-1 were 0.7691 and 0.8213, respectively. There was no statistical significance between the AUC of CEA and CYFRA 21-1 (P>0.05). Both CEA and CYFRA 21-1 have good performance in the differential diagnosis of PE, when compared with CEA, CYFRA 21-1 has no advantage.

Our previous studies have shown that Ginkgo biloba extract increased endothelial progenitor-cell (EPC) numbers and functional activity. However, the mechanisms remain to be determined. Recent studies have demonstrated that increased EPC numbers and activity were associated with the inhibition of EPC senescence, which involved activation of telomerase. Therefore, we investigated whether Ginkgo biloba extract inhibited the onset of EPC senescence through telomerase activation, leading to potentiation of cellular activity. After ex vivo cultivation, EPCs became senescent as determined by acidic ss-galactosidase staining. Ginkgo biloba extract dose-dependently prevented the onset of EPC senescence in culture. Moreover, Ginkgo biloba extract increased proliferation of EPCs as assessed by MTT assay and colony-forming capacity. To get further insights into the underlying mechanisms of these effects, we measured telomerase activity and determined the phosphorylation of Akt by Western blotting. Ginkgo biloba extract significantly increased telomerase activity and phosphorylation of the serine/threonine protein kinase Akt, a downstream effector of phosphoinositide 3-kinase (PI3K). Moreover, pretreatment with PI3K inhibitor, LY294002, significantly attenuated the Ginkgo biloba extract-induced telomerase activity. Taken together, the results indicated that Ginkgo biloba extract delayed the onset of EPC senescence, which may be related to activation of telomerase through the PI3k/Akt signaling pathway. The inhibition of EPC senescence by Ginkgo biloba extract in vitro may improve the functional activity of EPCs in a way that is important for potential cell therapy.