Publications

Abstract The genomic profiling of circulating tumor cells (CTCs) in the bloodstream should provide clinically relevant information on therapeutic efficacy and help predict cancer survival. However, the molecular characterization of CTCs has so far proven extremely difficult. A variety of technologies have been developed for CTC isolation, but so far the impact on the genomic assessment of CTCs has not been fully evaluated. To fill this gap, here we contrasted the genomic profiles of CTC pools recovered from blood samples obtained from four metastatic colorectal cancer (mCRC) patients using three different enrichment strategies (CellSearch, Parsortix, and FACS). Our results suggest clear differences in the mutational burden of CTC pools depending on the enrichment method used, with all evaluated methods returning a somewhat limited representation of the mutational spectrum of individual tumors, potentially due to allelic dropout during whole-genome amplification. Nevertheless, the CTC pools from Parsortix, and in part, CellSearch, showed diversity estimates, mutational signatures and drug-suitability scores remarkably close to the ones found in matching primary tumor samples. In contrast, FACS CTC pools were substantially enriched in apparent sequencing artifacts, which led to much higher estimates of genomic diversity. Although CTC genomics still faces technical challenges, our results suggest that CTC-derived metrics can reflect the diversity scores seen in primary tumor lesions thus highlighting the utility of CTCs to assess the heterogeneity status of individual tumors, and to help clinicians prioritize drugs in mCRC.

Conclusions: An analysis showed that in appendicular abscesses content gram-negatives were predominant. Gram-positive bacteria dominated in paravesical abscesses with 65 % isolates from gallbladder and 66.7 % from the affected tissue samples. In liver abscesses gram-positive cocci were isolated in 57.1 %. In multiple abdominal abscesses due to bowel perforation rod-shaped microflora was predominant (76 %) and represented by either obligate aerobes or obligate and facultative anaerobes.

Abstract Treatment for tumors depends on host immune system. The antitumor and immunoregulatory activities of Ulva lactuca polysaccharide (ULP) were evaluated in H22 tumor‐bearing mice and cyclophosphamide‐induced immunosuppressed mice, respectively. The structural properties of ULP were identified through multi‐angle laser light scattering, high‐performance liquid chromatography, Fourier‐transformed infrared, and nuclear magnetic resonance. It was composed of α‐D‐Man p ‐(1→, →2,4)‐β‐L‐Rha p ‐(1→, β‐D‐Glc p A‐(1→, β‐Gal p A‐(1→, →2,4)‐α‐D‐Glc p ‐(1→, and →6)‐β‐D‐Gal p ‐(1→ with the molecular weight of 1.46 × 10 5 Da. Its antioxidant, anti‐inflammatory, and antitumor effects were determined. Liver and tumor tissues were collected for histopathological, immunohistochemical, and western blotting analysis. ULP showed the great tumor growth inhibition of 74.41% compared with cyclophosphamide, which has side effects on immune system. ULP enhanced the expression of p53 to inhibit tumorigenesis, promoted the activation of IKKα , and inhibited the activation of p65 within the NF‐κB pathway. ULP inhibited the tumor growth through downregulating the expressions of PI3K / Akt and mTOR , and promoting BAX / Bcl‐2 ratio. The inhibition of TRAF2 / TNF‐α and CD31 / VEGF achieved a direct killing effect on tumor cells and inhibited tumor proliferation by inhibiting angiogenesis, respectively. Moreover, ULP increased the levels of immunoglobulin M and total superoxide dismutase, decreased the level of methane dicarboxylic aldehyde, and inhibited the activation of PI3K / AKT / mTOR / p70S6k pathways. The results showed that ULP exhibited pronounced antitumor activity and immunoregulatory effect.

Microbes produce bioactive chemical compounds to influence the physiology and growth of their neighbors, and our understanding of their biological activities may be enhanced by our ability to visualize such molecules in vivo. We demonstrate here the application of surface-enhanced Raman scattering spectroscopy for simultaneous detection of quorum-sensing-regulated pyocyanin and violacein, produced respectively by Pseudomonas aeruginosa and Chromobacterium violaceum bacterial colonies, grown as a coculture on agar-based plasmonic substrates. Our plasmonic approach allowed us to visualize the expression and spatial distribution of the microbial metabolites in the coculture taking place as a result of interspecies chemical interactions. By combining surface-enhanced Raman scattering spectroscopy with analysis of gene expression we provide insight into the chemical interplay occurring between the interacting bacterial species. This highly sensitive, cost-effective, and easy to implement approach allows spatiotemporal imaging of cellular metabolites in live microbial colonies grown on agar with no need for sample preparation, thereby providing a powerful tool for the analysis of microbial chemotypes.