• Journal of Life Science
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• v.22 no.3
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• pp.398-406
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• 2012

This study aimed to examine whether the polygenic profile of ACE ID and ACTN3 R577X polymorphisms is associated with muscle power performance in Korean athletes. For this study, 106 top-class power athletes (top-class group), 158 elite power athletes (elite-class group), and 676 healthy adults (control) aged 18-39 yrs were recruited and their genotypes were analyzed. The top-class group showed higher frequencies of the II genotype and I allele in ACE, as well as higher frequencies of the RR genotype and R allele in ACTN3 (top-class vs. control: 41.4% vs. 32.1% for II genotype, 67.1% vs. 57.7% for I allele, p<0.05; 42.3% vs. 29.0% for RR genotype, 65.3% vs. 54.8% for I allele, p<0.05). In the polygenic profile, the top-class group had significantly higher frequencies of combined-II/ID+RR/RX genotype than the control group (top-class vs. control: 82.9% vs. 66.7% for II/ID+RR/RX, p<0.05), and there was even a sharp increase in total genotype score (TGS) in this group compared to the elite-class and control groups ($66{\pm}0.9$ vs. $58{\pm}1.9$ vs. $56{\pm}2.3$, p<0.05). The combined-II/ID+RR/RX genotype showed the possibility of succussion in the top-class muscle power performance with an odds ratio of 2.3 (CI:1.4-4.1, p<0.05). These results suggested that ACE and ACTN3 need to interact with each other to affect muscle-power performance in an additive form. Furthermore, the polygenic profile of ACE and ACTN3 can predict muscle performance with high success in a homogeneous dominant combined genotype (II/ID+RR/RX). A further study could identify and combine other genes into ACE and ACTN3 for muscle strength.

• Biomolecules & Therapeutics
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• v.32 no.1
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• pp.123-135
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• 2024

Although gemcitabine-based regimens are widely used as an effective treatment for pancreatic cancer, acquired resistance to gemcitabine has become an increasingly common problem. Therefore, a novel therapeutic strategy to treat gemcitabine-resistant pancreatic cancer is urgently required. Piceamycin has been reported to exhibit antiproliferative activity against various cancer cells; however, its underlying molecular mechanism for anticancer activity in pancreatic cancer cells remains unexplored. Therefore, the present study evaluated the antiproliferation activity of piceamycin in a gemcitabine-resistant pancreatic cancer cell line and patient-derived pancreatic cancer organoids. Piceamycin effectively inhibited the proliferation and suppressed the expression of alpha-actinin-4, a gene that plays a pivotal role in tumorigenesis and metastasis of various cancers, in gemcitabine-resistant cells. Long-term exposure to piceamycin induced cell cycle arrest at the G₀/G₁ phase and caused apoptosis. Piceamycin also inhibited the invasion and migration of gemcitabine-resistant cells by modulating focal adhesion and epithelial-mesenchymal transition biomarkers. Moreover, the combination of piceamycin and gemcitabine exhibited a synergistic antiproliferative activity in gemcitabine-resistant cells. Piceamycin also effectively inhibited patient-derived pancreatic cancer organoid growth and induced apoptosis in the organoids. Taken together, these findings demonstrate that piceamycin may be an effective agent for overcoming gemcitabine resistance in pancreatic cancer.