The response evaluation and predictive value of Ki67 expression in neoadjuvant chemotherapy for breast cancer / 中华内分泌外科杂志

Objective To explore the expression of Ki 67 in 72 cases of breast cancer and to analyze the correlation of Ki67 expression with clinicopathological factors and efficacy of neo-adjuvant chemotherapy .To as-sess the prediction value of Ki 67 in selecting neo-adjuvant chemotherapy .Methods Ki67 expression in tumor tissues of 72 cases of breast cancer was detected before and after neo-adjuvant chemotherapy .Tumor tissues are a-chieved by core needle biopsy .Results Ki67 overexpression was found in those with axillary lymph node ( ALN) metastasis, in pathological stage III and tumor diameter >2 cm(P＜0.05).Ki67 expression was not significantly associated with age(P>0.05).Objective response(OR)rate of neo-adjuvant chemotherapy was 84.2%(61/72). Patients with Ki67 over-expression were more sensitive than those with lower-expression(P>0.05).Positive ex-pression rate of Ki67 was reduced significantly by neo-adjuvant chemotherapy(P＜0.05).Positive expression rate of Ki67 was reduced significantly in pathological complete response ( PCR ) group, clinical complete remission (CCR)group and partial response(PR)group.Conclusion The expression of Ki67 may be a potential predictive biomarker for neo-adjuvant therapy response in patients of breast cancer and can provide the basis for individual therapy for breast cancer .

Developing controllable hypermutable Clostridium cells through manipulating its methyl-directed mismatch repair system

Development of controllable hypermutable cells can greatly benefit understanding and harnessing microbial evolution. However, there have not been any similar systems developed for Clostridium, an important bacterial genus. Here we report a novel two-step strategy for developing controllable hypermutable cells of Clostridium acetobutylicum, an important and representative industrial strain. Firstly, the mutS/L operon essential for methyldirected mismatch repair (MMR) activity was inactivated from the genome of C. acetobutylicum to generate hypermutable cells with over 250-fold increased mutation rates. Secondly, a proofreading control system carrying an inducibly expressed mutS/L operon was constructed. The hypermutable cells and the proofreading control system were integrated to form a controllable hypermutable system SMBMutC, of which the mutation rates can be regulated by the concentration of anhydrotetracycline (aTc). Duplication of the miniPthl-tetR module of the proofreading control system further significantly expanded the regulatory space of the mutation rates, demonstrating hypermutable Clostridium cells with controllable mutation rates are generated. The developed C. acetobutylicum strain SMBMutC2 showed higher survival capacities than the control strain facing butanol-stress, indicating greatly increased evolvability and adaptability of the controllable hypermutable cells under environmental challenges.

Direct secretory expression of active microbial transglutaminase in Pichia pastoris / 生物工程学报

Direct secretory expression of active microbial transglutaminase (MTG) using heterologous hosts is a promising strategy, although its production level still needs to be improved for industrial production. Pichia pastoris is one of the most efficient expression systems developed in recent years. In this study, secretory expression of active MTG was successfully achieved by co-expressing the pro sequence and mature MTG genes in P. pastoris. Furthermore, we optimized the copy number of pro/MTG expression cassettes and the fermentation conditions. MTG production level reached 7.3 U/mL in 1-liter fermentor through high density fermentation, providing the feasiblity for industrial scale preparation of MTG.