Browsing by Author "Lin, Yi-Jan"

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Development of a Mucin4-Targeting SPIO Contrast Agent for Effective Detection of Pancreatic Tumor Cells in Vitro and in Vivo
(2013-11-28)
Wu, Shou-Cheng
;
Chen, Yu-Jen
;
Lin, Yi-Jan
;
Wu, Tung-Ho
;
Wang, Yun-Ming
In search of a unique and reliable contrast agent targeting pancreatic adenocarcinoma, new multifunctional nanoparticles (MnMEIO-silane-NH2-(MUC4)-mPEG NPs) were successfully developed in this study. Mucin4-expression levels were determined through different imaging studies in a panel of pancreatic tumor cells (HPAC, BxPC-3, and Panc-1) both in vitro and in vivo studies. The in vitro T-2-weighted MR imaging study in HPAC and Panc-1 tumor cells treated with NPs showed -89.1 +/- 5.7% and -0.9 +/- 0.2% contrast enhancement, whereas in in vivo study, it is found to be -81.5 +/- 4.5% versus -19.6 +/- 5.2% (24 h postinjection, 7.0 T), respectively. The T-2-weighted MR and optical imaging studies revealed that the novel agent can specifically and effectively target to mucin4-expressing tumors in nude mice. Hence, it is suggested that MnMEIO-silane-NH2-(MUC4)-mPEG NPs are able to provide an efficient and targeted delivery of MUC4 antibodies to mucin4-expressing pancreatic tumors.
The First Residue of the PWWP Motif Modulates HATH Domain Binding, Stability, and Protein-Protein Interaction
(2015-07-07)
Hung, Yi-Lin
;
Lee, Hsia-Ju
;
Jiang, Ingjye
;
Lin, Shang-Chi
;
Lo, Wei-Cheng
Hepatoma-derived growth factor (hHDGF) and HDGF-related proteins (HRPs) contain conserved N-terminal HATH domains with a characteristic structural motif; namely the PWWP motif. The HATH domain has attracted attention because of its ability to bind with heparin/heparan sulfate, DNA, and methylated histone peptide. Depending on the sequence of the PWWP motif, HRP HATHs are classified into P-type (Pro-His-Trp-Pro) and A-type (Ala-His-Trp-Pro) forms. A-type HATH is highly unstable and tends to precipitate in solution. We replaced the Pro residue in P-type HATH(HDGF) with Ala and evaluated the influence on structure, dynamics, and ligand binding. Nuclear magnetic resonance (NMR) hydrogen/deuterium exchange and circular dichroism (CD) measurements revealed reduced stability. Analysis of NMR backbone N-15 relaxations (R-1, R-2, and nuclear Overhauser effect) revealed additional backbone dynamics in the interface between the beta-barrel and the C-terminal helix bundle. The beta 1-beta 2 loop, where the AHWP sequence is located, has great structural flexibility, which aids HATH-HATH interaction through the loop. A-type HATH, therefore, shows a stronger tendency to aggregate when binding with heparin and DNA oligomers. This study defines the role of the first residue of the PWWP motif in modulating HATH domain stability and oligomer formation in binding.