Pichia pastoris is an efficient host for the expression and secretion of heterologous proteins and the most important feature of P. pastoris is the existence of a strong and tightly regulated promoter from the alcohol oxidase I (AOX1) gene. The AOX1 promoter (pAOX1) has been used to express foreign genes and to produce a variety of recombinant proteins in P. pastoris. However, some efforts have been made to develop new alternative promoters to pAOX1 to avoid the use of methanol. The glyceraldehyde-3-phosphate dehydrogenase promoter (pGAP) has been used for constitutive expression of many heterologous proteins. The pGAP-based expression system is more suitable for large-scale production because the hazard and cost associated with the storage and delivery of large volume of methanol are eliminated. Some important developments and features of this expression system will be summarized in this review.
The purpose of this study was to evaluate the importance of diffusion-weighted magnetic resonance imaging (DW-MRI) apparent diffusion coefficient (ADC) values to predict treatment response to neoadjuvant chemotherapy (NCT) in patients with locally advanced breast cancer (LABC). Thirty-two patients with LABC underwent 2-4 cylces of NCT (docetaxel and epirubicin). The DW-MRI scans were performed within one week prior to chemotherapy and after the first course of treatment, respectively. Accordingly, tumor volumes, changes in tumor ADC values, and their degree of correlation were analyzed. The overall response (OR) was observed in 62.5% (95% CI, 45.7-79.3%) of patients after 2 cycles of NCT. The clinical complete response (CR) rate and pathological CR (pCR) rate were 15.6 and 9.4%, respectively. The stable disease (SD) rate was 34.4% (11 patients), and progressive disease (PD) was observed in only one patient (3.1%). After the first cycle of NCT, the ADC values in the CR + PR group significantly increased (P < 0.001). The initial ADC values before chemotherapy in the OR group were significantly lower than those in the SD + PD group (P < 0.001). The initial ADC values and the changes in tumor volume after chemotherapy were negatively correlated (r = -0.58, P = 0.02). The lower the initial tumor ADC value was the more obvious the decrease in tumor volume after chemotherapy. The changes in ADC values of tumors after chemotherapy and the changes in tumor volume were positively correlated (r = 0.96, P < 0.001). After chemotherapy, the greater the change in ADC value, the more the tumor volume was reduced. Using the initial ADC values of breast cancer tumors and the early changes in ADC values after NCT, we may be able to predict tumor response to chemotherapy. Tumors with low initial ADC values may be sensitive to chemotherapy; tumors with significantly increasing ADC values early after chemotherapy may be sensitive to chemotherapy.
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