Browsing by Author "Liao, Wei-Neng"

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Prorenin receptor acts as a potential molecular target for pancreatic ductal adenocarcinoma diagnosis
(2016-08-23)
Arundhathi, Arivajiagane
;
Chuang, Wen-Han
;
Chen, Jen-Kun
;
Wang, Shin-E
;
Shyr, Yi-Ming
Recent studies have implicated the prorenin receptor (PRR) is associated with pancreatic tumorigenesis. We therefore investigated the role of PRR in pancreatic tumorigenesis and assessed whether PRR can serve as a target for imaging diagnosis at early stages of PDAC. Here we show that aberrant expression of PRR in premalignant PanIN lesions, and human PDAC samples, and PDAC cell lines, particularly in Panc-1 cells. Interestingly, PRR expression was positively associated with PDAC progression. Moreover, overexpression of human PRR resulted in increased cell proliferation and decreased apoptosis, while knockdown of human PRR caused decreased cell proliferation and enhanced apoptosis in pancreatic cancer cells. We also observed that overexpression of human PRR enhanced MAPK and PI3K/Akt signaling pathways in PDAC cells, while knockdown of human PRR suppressed both of pathways. The confocal imaging analysis showed that human PRR was highly expressed in Panc-1, ASPC, and Miapaca cells, whereas BXPC-3, and HPAC cells had a significantly lower fluorescent signals. Consistently, the single-photon emission computed tomography (SPET/CT) showed that the uptake of anti-PRR labelled with I-125 was higher in Panc-1 and ASPC tumors-bearing mice after 96 hours injection. Importantly, tumors in pancreas of Pdx1-cre; LSL-Kras(G12D) mice had a significant increased PRR expression and accumulation of radioactivity at 96 h after injection. These data suggest that I-125-anti-PRR can detect the orthotopic tumors in Pdx1-cre; LSL-Kras(G12D) mice. Therefore, anti-PRR labelled with I-125 is a promising radiotracer for imaging diagnosis at early stages of pancreatic cancer.
Synthesis and Evaluation of Aminothiazole-Paeonol Derivatives as Potential Anticancer Agents
(2016-02-01)
Tsai, Chia-Ying
;
Kapoor, Mohit
;
Huang, Ying-Pei
;
Lin, Hui-Hsien
;
Liang, Yu-Chuan
In this study, novel aminothiazole-paeonol derivatives were synthesized and characterized using H-1-NMR, C-13-NMR, IR, mass spectroscopy, and high performance liquid chromatography. All the new synthesized compounds were evaluated according to their anticancer effect on seven cancer cell lines. The experimental results indicated that these compounds possess high anticancer potential regarding human gastric adenocarcinoma (AGS cells) and human colorectal adenocarcinoma (HT-29 cells). Among these compounds, N-[4-(2-hydroxy-4-methoxyphenyl)thiazol-2-yl]-4-methoxybenzenesulfonamide (13c) had the most potent inhibitory activity, with IC50 values of 4.0 mu M to AGS, 4.4 mu M to HT-29 cells and 5.8 mu M to HeLa cells. The 4-fluoro-N-[4-(2-hydroxy-4-methoxyphenyl)thiazol-2-yl]benzenesulfonamide (13d) was the second potent compound, showing IC50 values of 7.2, 11.2 and 13.8 mu M to AGS , HT-29 and HeLa cells, respectively. These compounds are superior to 5-fluorouracil (5-FU) for relatively higher potency against AGS and HT-29 human cancer cell lines along with lower cytotoxicity to fibroblasts. Novel aminothiazole-paeonol derivatives in this work might be a series of promising lead compounds to develop anticancer agents for treating gastrointestinal adenocarcinoma.