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Chung-Lin Lee,Ying-Hsu Chang,Chung-Yi Liu,Ming-Li Hsieh,Liang-Kang Huang,Yuan-Cheng Chu,Hung-Cheng Kan,Po-Hung Lin,Kai-Jie Yu,Cheng-Keng Chuang,Chun-Te Wu,See-Tong Pang,I-Hung Shao 대한비뇨의학회 2022 Investigative and Clinical Urology Vol.63 No.5
Purpose: Metastatic castration-resistant prostate cancer (mCRPC) has a poor prognosis. Abiraterone acetate (AA), enzalutamide, and chemotherapy are first-line treatments for patients with mCRPC. This study examined prognostic factors for AA response in the form of prostate-specific antigen (PSA) kinetics throughout androgen-deprivation therapy (ADT) in chemonaïve patients with mCRPC. Materials and Methods: We retrospectively included data from 34 chemonaïve patients with mCRPC who had received AA at some point between January 2017 and December 2018. We separated patients into two study arms according to the decrease in PSA percentages after use of AA for 3 months. We correlated PSA kinetics parameters with response and compared the two study groups with respect to PSA kinetics. Results: The patients’ median age was 77 years. In the total group of patients, 64% had a response to AA, whereas 35% did not. The ratio of the PSA level at nadir to the level during ADT was significantly higher in the AA-sensitive group (19.78 vs. 1.03, p=0.019). Conclusions: Patients who experienced a dramatic change in PSA level during ADT were more likely to be resistant to AA after progression to mCRPC. Chemotherapy rather than AA might be more suitable as a first-line treatment for these patients.
Peng Zhu,An-Qin Duan,Ting-Xian Deng,Xing-Rong Lu,Xiao-Ya Ma,Sha-Sha Liang,Chun-Ying Pang,Xian-Wei Liang 한국생물공학회 2017 Biotechnology and Bioprocess Engineering Vol.22 No.5
In recent years, CRISPR/Cas9 has rapidly become one of the most promising genome editing tools because it is simple and easy to use and cost effective. However, the large size of Cas9 sequences limits its application in clinically promising vectors and it also impacts non-viral transfection. In this study, CRISPR/Cas9 adenovirus vectors that target the buffalo 18s rDNA gene were constructed, transfected into 293 cells for adenovirus packaging, and the adenovirus was used to knockout the 18s rDNA gene in buffalo mammary epithelial cells. The results demonstrated that the CRISPR/Cas9 adenovirus vectors for the buffalo 18s rDNA gene could efficiently target the sites as revealed by the fluorescence reporter system. After amplification, the adenovirus titer of Sn458- 18s1 and Sn458-18s2 reached 1.03 × 109PFU/mL and 1.05 × 109 PFU/mL, respectively. For buffalo mammary epithelial cell infection, the efficiency was 100% when the multiplicity of infection (MOI) 100 PFU/mL. There were 9 mutational clones found in the 20 clones, and the gene mutagenesis rate reached 45%. Of these, 2 clones were 35-bp deleted and 7 clones were 12-bp deleted. These results suggested that the adenovirus system overcame the low transfection efficiency of the buffalo mammary epithelial cells associated with using lipid-based methods or electroporation. Moreover, we preliminary developed an efficient technique for multiple-locus gene targeting at repeated sequences of the buffalo genome.