Development of an immune-related gene pairs index for the prognosis analysis of metastatic melanoma.

Melanoma is a skin cancer with great metastatic potential, which is responsible for the major deaths in skin cancer. Although the prognosis of melanoma patients has been improved with the comprehensive treatment, for patients with metastasis, the complexity and heterogeneity of diffuse diseases make prognosis prediction and systematic treatment difficult and ineffective. Therefore, we established a novel personalized immune-related gene pairs index (IRGPI) to predict the prognosis of patients with metastatic melanoma, which was conducive to provide new insights into clinical decision-making and prognostic monitoring for metastatic melanoma. Through complex analysis and filtering, we identified 24 immune-related gene pairs to build the model and obtained the optimal cut-off value from receiver operating characteristic curves, which divided the patients into high and low immune-risk groups. Meantime, the Kaplan-Meier analysis, Cox regression analysis and subgroup analysis showed that IRGPI had excellent prognostic value. Furthermore, IRGPI was shown that was closely associated with immune system in the subsequent tumor microenvironment analysis and gene set enrichment analysis. In addition, we broken through the data processing limitations of traditional researches in different platforms through the application of gene pairs, which would provide great credibility for our model. We believe that our research would provide a new perspective for clinical decision-making and prognostic monitoring in metastatic melanoma.

Ring synthetic chromosome V SCRaMbLE.

Structural variations (SVs) exert important functional impacts on biological phenotypic diversity. Here we show a ring synthetic yeast chromosome V (ring_synV) can be used to continuously generate complex genomic variations and improve the production of prodeoxyviolacein (PDV) by applying Synthetic Chromosome Recombination and Modification by LoxP-mediated Evolution (SCRaMbLE) in haploid yeast cells. The SCRaMbLE of ring_synV generates aneuploid yeast strains with increased PDV productivity, and we identify aneuploid chromosome I, III, VI, XII, XIII, and ring_synV. The neochromosome of SCRaMbLEd ring_synV generated more unbalanced forms of variations, including duplication, insertions, and balanced forms of translocations and inversions than its linear form. Furthermore, of the 29 novel SVs detected, 11 prompted the PDV biosynthesis; and the deletion of uncharacterized gene YER182W is related to the improvement of the PDV. Overall, the SCRaMbLEing ring_synV embraces the evolution of the genome by modifying the chromosome number, structure, and organization, identifying targets for phenotypic comprehension.

Hybrids of phenylsulfonylfuroxan and coumarin as potent antitumor agents.

Sixteen furoxan-based nitric oxide (NO) releasing coumarin derivatives (6a-c, 8a-g, 10a, 13a,b, 15, and 17a,b) were designed, synthesized, and evaluated against the A549, HeLa, A2780, A2780/CDDP, and HUVEC cell lines. Most derivatives displayed potent antiproliferation activities. Among them, 8b exhibited the strongest antiproliferation activity on the four sensitive cell lines mentioned above and three drug resistant tumor cell lines A2780/CDDP, MDA-MB-231/Gem, and SKOV3/CDDP with IC50 values from 14 to 53 nM and from 62 to 140 nM, respectively. Furthermore, 8b inhibited the growth of A2780 in vivo and displayed lower toxicity on nontumorigenesis T29, showing good selectivity against malignant cells in vitro. Preliminary pharmacological studies showed that 8b induces apoptosis, arrests the cell cycle at the G2/M phase in the A2780 cell line, and disrupts the phosphorylation of MEK1 and ERK1. Overall, the NO-releasing capacity and the inhibition of ERK/MAPK pathway signaling may explain the potent antineoplastic activity of these compounds.