Correlations between alterations of T-helper 17 cells and treatment efficacy after concurrent radiochemotherapy in locally advanced cervical cancer (stage IIB-IIIB): a 3-year prospective study.

BACKGROUND: Recently, T-helper 17 (Th17) cells have been proved to play an important role in promoting cervical cancer. But, till now, few study has been carried out to understand the involvement of these cells in efficacy of anti-tumor treatments. This study aimed to investigate the alterations in the percentage of circulating Th17 cells and related cytokines in locally advanced cervical cancer (LACC) patients before and after concurrent chemoradiotherapy (cCRT) and to analyze the correlations between the alterations in Th17 cells and treatment efficacy. METHODS: A prospective study with 49 LACC (International federation of gynecology and obstetrics [FIGO] stage IIB-IIIB) patients and 23 controls was conducted. Patients received the same cCRT schedule and were followed up for 3 years. Circulating Th17 cells (CD3+CD8- interleukin [IL]-17+ T cells) and related cytokines IL-17, transforming growth factor-ß (TGF-ß), IL-10, IL-23, IL-6, and IL-22 were detected before and after cCRT. Correlations between alterations of circulating Th17 cells and treatment efficacy were analyzed. Kaplan-Meier analysis was used for overall survival (OS) and progression-free survival (PFS). RESULTS: We found that 40 patients finished the entire cCRT schedule and met the endpoint of this study. The percentage of circulating Th17 cells in the LACC patients was higher than that in the controls, and it significantly decreased after cCRT (P < 0.05). After cCRT, patients were divided into two groups based on the average of the Th17 cells declined. The subgroup of patients with a prominent decrease in circulating Th17 cells after cCRT had a higher treatment efficacy and longer PFS and OS times. Compared with the control patients, LACC patients had higher IL-6, IL-10, IL-22, TGF-ß levels and a lower IL-23 level (P < 0.05). After cCRT, IL-6, IL-10, IL-17, IL-23 level significantly increased and TGF-ß level significantly decreased compared with the levels before cCRT (P < 0.05). CONCLUSION: Circulating Th17 cells in the LACC patients (FIGO stage IIB-IIIB) were higher than those in the controls, but they generally decreased after cCRT. A more pronounced decrease in circulating Th17 cells after cCRT was correlated with better therapeutic effect and longer PFS and OS times.

Efficient access to a designed phosphapalladacycle catalyst via enantioselective catalytic asymmetric hydrophosphination.

A chiral phosphine auxiliary was generated with excellent ee via catalytic asymmetric hydrophosphination of 3-(naphthalen-1-ylmethylene)pentane-2,4-dione. The subsequent metal complexation of the monophosphine yielded two different coordination complexes depending on the reaction conditions. The ortho-palladation of both coordination complexes resulted in the formation of a single dimeric phosphapalladacycle complex that could be further converted to the monomeric bisacetonitrile derivative. Moreover, the palladium complex exhibits interesting oxophilicity as the stable bisaquo derivative could be isolated and characterized crystallographically. The catalytic potential of the phosphapalladacycle was also demonstrated.

Pd-catalyzed enantiodivergent and regiospecific phospha-Michael addition of diphenylphosphine to 4-oxo-enamides: efficient access to chiral phosphinocarboxamides and their analogues.

The palladacycle-catalyzed asymmetric P-H addition of 4-oxo-enamides has been developed, which provides efficient access to phosphinocarboxamides and their analogues. Solvent-mediated reversal of stereoselectivity (ee from +96% to -92%) was observed, and the underlying mechanism that allows facile access to both enantiomers of the product by judicious choice of solvents is revealed.

[Production of myostatin gene knockout Wuzhishan miniature pig fibroblasts with zinc-finger nucleases].

Disruption of myostatin (MSTN) gene in pigs may improve porcine lean meat percentage (LMP), and create an animal model for certain human diseases. Using zinc-finger nucleases (ZFNs) technology, MSTN gene was deleted in Wuzhishan miniature pig fibroblasts by transfection of either ZFNs plasmids or ZFNs mRNA in high efficiency. Strikingly, ZFNs encoding mRNA could produce MSTN+/-and MSTN-/- cell colonies with single or double allele deletion by single transfection. Sequencing results demonstrated that 92.18% of the mutations were short fragment deletions or insertions (≤10 bp). Prediction of amino acids sequences indicated that more than half of the mutations cause premature transla-tional-termination codon. MSTN+/+, MSTN+/-, and MSTN-/- cell colonies were used as nuclear donor for somatic cell nuclear transfer (SCNT), and developmental potential of SCNT embryos were measured by the blastocyst rate. The results revealed no significant difference in development competence among the three kinds of reconstructed embryos (14.29% vs. 19.64% vs. 16.13%), which provides the possibility of making myostatin knock out pigs in the future.