@article {3011, title = {Expression of the human telomerase reverse transcriptase gene is modulated by quadruplex formation in its first exon due to DNA methylation}, journal = {J Biol Chem.20859-2087}, volume = {292}, year = {2017}, pages = {20859-20870}, author = {Li PT and Wang ZF and Chu IT and Kuan YM and Li MH and Huang MC and Chiang PC and Chang TC and Chen CT} } @article {3009, title = {A novel transition pathway of ligand-induced topological conversion from hybrid forms to parallel forms of human telomeric G-quadruplexes.}, journal = {Nucleic Acids Res.}, volume = {44}, year = {2016}, pages = {3958-68}, author = {Wang ZF and Li MH and Chen WW and Hsu ST and Chang TC} } @article {3010, title = {Specific polyunsaturated fatty acids modulate lipid delivery and oocyte development in C. elegans revealed by molecular-selective label-free imaging.}, journal = {Sci Rep.}, volume = {6}, year = {2016}, pages = {32021}, author = {Chen WW and Yi YH and Chien CH and Hsiung KC and Ma TH and Lin YC and Lo SJ and Chang TC.} } @article {3007, title = {Conformational transition of a hairpin structure to G-quadruplex within the WNT1 gene promoter}, journal = {J Am Chem Soc}, volume = {137}, year = {2015}, pages = {210-8}, author = {Kuo MH and Wang ZF and Tseng TY and Li MH and Hsu ST and Lin JJ and Chang TC} } @article {3008, title = {Direct evidence of mitochondrial G-quadruplex DNA by using fluorescent anti-cancer agents}, journal = {Nucleic Acids Res.}, volume = {43}, year = {2015}, pages = {10102-13}, author = {Huang WC and Tseng TY and Chen YT and Chang CC and Wang ZF and Wang CL and Hsu TN and Li PT and Chen CT and Lin JJ and Lou PJ and Chang TC} } @article {3006, title = {A Fluorescent Anti-Cancer Agent, 3,6-bis(1-methyl-4-vinylpyridinium) Carbazole Diiodide, Stains G-Quadruplexes in Cells and Inhibits Tumor Growth}, journal = {Curr Top Med Chem.}, volume = {15}, year = {2015}, pages = {1964-70}, author = {Tseng TY and Chang CC and Lin JJ and Chang TC} } @article {2184, title = {BMVC test, an improved fluorescence assay for detection of malignant pleural effusions}, journal = {Cancer medicine}, volume = {3}, year = {2014}, pages = {162-173}, author = {Lin IT and Tsai YL and Kang CC and Huang WC and Wang CL and Lin MY and Lou PJ and Shih JY and Wang HC and Wu HD and Tsai TH and Jan ISang and Chang TC} } @article {2185, title = {Detection of cell carcinogenic transformation by a quadruplex DNA binding fluorescent probe}, journal = {PloS one}, volume = {9}, year = {2014}, pages = {e86143}, author = {Yang TL and Lin L and Lou PJ and Chang TC and Young TH} } @article {2186, title = {Inhibition of Cancer Cell Migration and Invasion through Suppressing the Wnt1-mediating Signal Pathway by G-quadruplex Structure Stabilizers}, journal = {The Journal of biological chemistry}, year = {2014}, author = {Wang JM and Huang FC and Kuo MH and Wang ZF and Tseng TY and Chang LC and Yen SJ and Chang TC and Lin JJ} } @article {2023, title = {Lipid droplet pattern and nondroplet-like structure in two fat mutants of Caenorhabditis elegans revealed by coherent anti-Stokes Raman scattering microscopy.}, journal = {Journal of biomedical optics}, volume = {19}, year = {2014}, pages = {11011}, abstract = {

ABSTRACT. Lipid is an important energy source and essential component for plasma and organelle membranes in all kinds of cells. Coherent anti-Stokes Raman scattering (CARS) microscopy is a label-free and nonlinear optical technique that can be used to monitor the lipid distribution in live organisms. Here, we utilize CARS microscopy to investigate the pattern of lipid droplets in two live Caenorhabditis elegans mutants (fat-2 and fat-3). The CARS images showed a striking decrease in the size, number, and content of lipid droplets in the fat-2 mutant but a slight difference in the fat-3 mutant as compared with the wild-type worm. Moreover, a nondroplet-like structure with enhanced CARS signal was detected for the first time in the uterus of fat-2 and fat-3 mutants. In addition, transgenic fat-2 mutant expressing a GFP fusion protein of vitellogenin-2 (a yolk lipoprotein) revealed that the enhanced CARS signal colocalized with the GFP signal, which suggests that the nondroplet-like structure is primarily due to the accumulation of yolk lipoproteins. Together, this study implies that CARS microscopy is a potential tool to study the distribution of yolk lipoproteins, in addition to lipid droplets, in live animals.

}, url = {http://www.ncbi.nlm.nih.gov/pubmed/23979461}, author = {Yi YH and Chien CH and Chen WW and Ma TH and Liu KY and Chang YS and Chang TC and Lo SJ} } @article {2188, title = {Structural basis of sodium-potassium exchange of a human telomeric DNA quadruplex without topological conversion}, journal = {Nucleic acids research,}, volume = {42}, year = {2014}, pages = {4723-4733}, author = {Wang ZF and Li MH and Hsu ST and Chang TC} } @article {2189, title = {Unfolding kinetics of human telomeric g-quadruplexes studied by NMR spectroscopy}, journal = {The journal of physical chemistry. B}, volume = {118}, year = {2014}, pages = {931-6}, author = {Li MH and Wang ZF and Kuo MH and Hsu ST and Chang TC} } @article {568, title = {A cis-element with mixed G-quadruplex structure of NPGPx promoter is essential for nucleolin-mediated transactivation on non-targeting siRNA stress}, journal = {Nucleic Acids Research}, volume = {41}, number = {3}, year = {2013}, note = {

109FMTimes Cited:0Cited References Count:33

}, month = {Feb}, pages = {1533-1543}, abstract = {

We reported that non-targeting siRNA (NT-siRNA) stress induces non-selenocysteine containing phospholipid hydroperoxide glutathione peroxidase (NPGPx) expression to cooperate with exoribonuclease XRN2 for releasing the stress [Wei,P.C., Lo,W.T., Su,M.I., Shew,J.Y. and Lee, W. H. (2011) Non-targeting siRNA induces NPGPx expression to cooperate with exoribonuclease XRN2 for releasing the stress. Nucleic Acids Res., 40, 323-332]. However, how NT-siRNA stress inducing NPGPx expression remains elusive. In this communication, we showed that the proximal promoter of NPGPx contained a mixed G-quadruplex (G4) structure, and disrupting the structure diminished NT-siRNA induced NPGPx promoter activity. We also demonstrated that nucleolin (NCL) specifically bonded to the G4-containing sequences to replace the originally bound Sp1 at the NPGPx promoter on NT-siRNA stress. Consistently, overexpression of NCL further increased NPGPx promoter activity, whereas depletion of NCL desensitized NPGPx promoter to NT-siRNA stress. These results suggest that the cis-element with mixed G4 structure at the NPGPx promoter plays an essential role for its transactivation mediated by NCL to release cells from NT-siRNA stress.

}, keywords = {c-myc, complex-formation, DNA structures, gene, initiation, myc g-quadruplex, protein, region, telomeric DNA, transcription}, isbn = {0305-1048}, url = {http://www.ncbi.nlm.nih.gov/pubmed/23241391}, author = {Wei, P. C. and Wang, Z. F. and Lo, W. T. and Su, M. I. and Shew, J. Y. and Chang, T. C. and Lee, W. H.} } @article {2022, title = {Aggregation induced photodynamic therapy enhancement based on linear and nonlinear excited FRET of fluorescent organic nanoparticles}, journal = {Journal of Materials Chemistry B,}, volume = {1}, year = {2013}, pages = {2350-2357}, abstract = {

A binary molecule can self-assemble to form fluorescent organic nanoparticles (FONs) based on the Aggregation-Induced Emission Enhancement (AIEE) property and subsequently, presents an efficient fluorescence resonance energy transfer (FRET) to generate singlet oxygen under linear and nonlinear light sources. Biologically, this FON-photosensitizer is much more phototoxic to cancer cells than to normal cells without significant dark toxicity. Eventually, a new approach, called FON FRET-PDT or AIEE FRET-PDT, to promote the PDT effect is expected.

}, url = {http://pubs.rsc.org/en/content/articlelanding/2013/TB/c3tb00345k$\#$!divAbstract}, author = {Meng-Chieh Hsieh and Cheng-Hao Chien and Cheng-Chung Chang and Ta-Chau Chan} } @article {1929, title = {Assaying the binding strength of G-quadruplex ligands using single-molecule TPM experiments}, journal = {Anal Biochem}, volume = {436}, year = {2013}, pages = {101-8}, abstract = {

G-quadruplexes are stable secondary structures formed by Hoogsteen base pairing of guanine-rich single-stranded DNA sequences in the presence of monovalent cations (Na(+) or K(+)). Folded G-quadruplex (G4) structures in human telomeres have been proposed as a potential target for cancer therapy. In this study, we used single-molecule tethered particle motion (TPM) experiments to assay the binding strength of possible G4 ligands. We found that individual single-stranded DNA molecules containing the human telomeric sequence d[AGGG(TTAGGG)3] fluctuated between the folded and the unfolded states in a 10 mM Na(+) solution at 37 {\textdegree}C. The durations of folded and unfolded states were single-exponentially distributed, and in return the folding and unfolding rate constants were 1.68 {\textpm} 0.01 and 1.63 {\textpm} 0.03 (s(-1)), respectively. In the presence of G4 ligands, such as TMPyP4, DODCI, BMVC, and BMVPA, the unfolding rate constant decreased appreciably. In addition, combining the Cu(2+)-induced G4 unfolding and TPM assay, we showed that BMVC and TMPyP4 are better G4 stabilizers than DODCI. The capability of monitoring the fluctuation between the folded and the unfolded state of G4 DNA in real time allows the determination of both kinetic and thermodynamic parameters in a single measurement and offers a simple way to assay binding strength under various conditions.

}, url = {http://www.ncbi.nlm.nih.gov/pubmed/23376016}, author = {Liu, S. W. and Chu, J. F. and Tsai, C. T. and Fang, H. C. and Chang, T. C. and Li, H. W.} } @article {2025, title = {Automated quantitative analysis of lipid accumulation and hydrolysis in living macrophages with label-free imaging.}, journal = {Analytical and bioanalytical chemistry}, year = {2013}, abstract = {

The accumulation of lipids in macrophages is a key factor that promotes the formation of atherosclerotic lesions. Several methods such as biochemical assays and neutral lipid staining have been used for the detection of lipids in cells. However, a method for real-time quantitative assessment of the lipid content in living macrophages has yet to be shown, particularly for its kinetic process with drugs, due to the lack of suitable tools for non-invasive chemical detection. Here we demonstrate label-free real-time monitoring of lipid droplets (LDs) in living macrophages by using coherent anti-Stokes Raman scattering (CARS) microscopy. In addition, we have established an automated image analysis method based on maximum entropy thresholding (MET) to quantify the cellular lipid content. The result of CARS image analysis shows a good correlation (R 2 \> 0.9) with the measurement of biochemical assay. Using this method, we monitored the processes of lipid accumulation and hydrolysis in macrophages. We further characterized the effect of a lipid hydrolysis inhibitor (diethylumbelliferyl phosphate, DEUP) and determined the kinetic parameters such as the inhibition constant, K i. Our work demonstrates that the automated quantitative analysis method is useful for the studies of cellular lipid metabolism and has potential for preclinical high-throughput screening of therapeutic agents related to atherosclerosis and lipid-associated disorders.

}, url = {http://www.ncbi.nlm.nih.gov/pubmed/23934396}, author = {Chen WW and Chien CH and Wang CL and Wang HH and Wang YL and Ding ST and Lee TS and Chang TC} } @article {2024, title = {Chemical principles for the design of a novel fluorescent probe with high cancer-targeting selectivity and sensitivity.}, journal = {Integrative biology : quantitative biosciences from nano to macro}, volume = {5}, year = {2013}, pages = {1217-28}, abstract = {

Understanding of principles governing selective and sensitive cancer targeting is critical for development of chemicals for cancer diagnostics and treatment. We determined the underlying mechanisms of how a novel fluorescent small organic molecule, 3,6-bis(1-methyl-4-vinylpyridinium)carbazole diiodide (BMVC), selectively labels cancer cells but not normal cells. We show that BMVC is retained in the lysosomes of normal cells. In cancer cells, BMVC escapes lysosomal retention and localizes to the mitochondria or to the nucleus, where DNA-binding dramatically increases BMVC fluorescence intensity, allowing it to light up only cancer cells. Structure-function analyses of BMVC derivatives show that hydrogen-bonding capacity is a key determinant of lysosomal retention in normal cells, whereas lipophilicity directs these derivatives to the mitochondria or the nucleus in cancer cells. In addition, drug-resistant cancer cells preferentially retain BMVC in their lysosomes compared to drug-sensitive cancer cells, and BMVC can be released from drug-resistant lysosomes using lysosomotropic agents. Our results further our understanding of how properties of cellular organelles differ between normal and cancer cells, which can be exploited for diagnostic and/or therapeutic use. We also provide physiochemical design principles for selective targeting of small molecules to different organelles. Moreover, our results suggest that agents which can increase lysosomal membrane permeability may re-sensitize drug-resistant cancer cells to chemotherapeutic agents.

}, url = {http://www.ncbi.nlm.nih.gov/pubmed/23970166}, author = {Kang CC and Huang WC and Kouh CW and Wang ZF and Cho CC and Chang CC and Wang CL and Chang TC and Seemann J and Huang LJ} } @article {2026, title = {In-cell optical imaging of exogenous G-quadruplex DNA by fluorogenic ligands.}, journal = {Nucleic acids research}, year = {2013}, abstract = {

Guanine-rich oligonucleotides (GROs) are promising therapeutic candidate for cancer treatment and other biomedical application. We have introduced a G-quadruplex (G4) ligand, 3,6-bis(1-methyl-4-vinylpyridinium) carbazole diiodide, to monitor the cellular uptake of naked GROs and map their intracellular localizations in living cells by using confocal microscopy. The GROs that form parallel G4 structures, such as PU22, T40214 and AS1411, are detected mainly in the lysosome of CL1-0 lung cancer cells after incubation for 2 h. On the contrary, the GROs that form non-parallel G4 structures, such as human telomeres (HT23) and thrombin binding aptamer (TBA), are rarely detected in the lysosome, but found mainly in the mitochondria. Moreover, the fluorescence resonant energy transfer studies of fluorophore-labeled GROs show that the parallel G4 structures can be retained in CL1-0 cells, whereas the non-parallel G4 structures are likely distorted in CL1-0 cells after cellular uptake. Of interest is that the distorted G4 structure of HT23 from the non-parallel G4 structure can reform to a probable parallel G4 structure induced by a G4 ligand in CL1-0 living cells. These findings are valuable to the design and rationale behind the possible targeted drug delivery to specific cellular organelles using GROs.

}, url = {http://www.ncbi.nlm.nih.gov/pubmed/24030712}, author = {Tseng TY and Wang ZF and Chien CH and Chang TC} } @article {569, title = {Photo-Induced Antitumor Effect of 3,6-Bis(1-methyl-4-vinylpyridinium) Carbazole Diiodide}, journal = {Biomed Research International}, year = {2013}, note = {

090CRTimes Cited:0Cited References Count:32

}, abstract = {

We have applied a fluorescent molecule 3,6-bis(1-methyl-4-vinylpyridinium) carbazole diiodide (BMVC) for tumor targeting and treatment. In this study, we investigated the photo-induced antitumor effect of BMVC. In vitro cell line studies showed that BMVC significantly killed TC-1 tumor cells at light dose greater than 40 J/cm(2). The fluorescence of BMVC in the tumor peaked at 3 hours and then gradually decreased to reach the control level a. er 24 hours. In vivo tumor treatment studies showed BMVC plus light irradiation (iPDT) significantly inhibited the tumor growth. At day 24 a. er tumor implantation, tumor volume was measured to be 225 +/- 79 mm(3), 2542 +/- 181 mm(3), 1533 +/- 766 mm(3), and 1317 +/- 108 mm(3) in the iPDT, control, light-only, and BMVC-only groups, respectively. Immunohistochemistry studies showed the microvascular density was significantly lower in the iPDT group. Taken together, our results demonstrated that BMVC may be a potent tumor-specific photosensitizer (PS) for PDT.

}, keywords = {bmvc, cancer, cells, DNA, light, photodynamic therapy, photosensitizer, quadruplex structure, telomerase, tumors}, isbn = {2314-6133}, url = {http://www.ncbi.nlm.nih.gov/pubmed/23509809}, author = {Chou, Y. S. and Chang, C. C. and Chang, T. C. and Yang, T. L. and Young, T. H. and Lou, P. J.} } @article {1932, title = {A specific fluorescent probe for visualizing G-quadruplex DNA by fluorescence lifetime imaging microscopy}, journal = {J Biomed Opt.}, volume = {18}, year = {2013}, pages = {101309}, abstract = {

ABSTRACT. The importance of guanine-quadruplex (G4) is not only in protecting the ends of chromosomes for human telomeres but also in regulating gene expression for several gene promoters. However, the existence of G4 structures in living cells is still in debate. A fluorescent probe, 3,6-bis(1-methyl-2-vinylpyridinium) carbazole diiodide (o-BMVC), for differentiating G4 structures from duplexes is characterized. o-BMVC has a large contrast in fluorescence decay time, binding affinity, and fluorescent intensity between G4 structures and duplexes, which makes it a good candidate for probing G4 DNA structures. The fluorescence decay time of o-BMVC upon interaction with G4 structures of telomeric G-rich sequences is \~{}2.8 ns and that of interaction with the duplex structure of a calf thymus is \~{}1.2 ns. By analyzing its fluorescence decay time and histogram, we were able to detect one G4 out of 1000 duplexes in vitro. Furthermore, by using fluorescence lifetime imaging microscopy, we demonstrated an innovative methodology for visualizing the localization of G4 structures as well as mapping the localization of different G4 structures in living cells.

}, url = {http://www.ncbi.nlm.nih.gov/pubmed/23839279}, author = {Ting-Yuan Tseng and Cheng-Hao Chien and Jen-Fei Chu and Wei-Chun Huang and Mei-Ying Lin and Cheng-Chung Chang and Ta-Chau Chang} } @article {570, title = {Molecular engineering of G-quadruplex ligands based on solvent effect of polyethylene glycol}, journal = {Nucleic Acids Res}, volume = {40}, number = {17}, year = {2012}, note = {

Wang, Zi-FuChang, Ta-ChauengResearch Support, Non-U.S. Gov{\textquoteright}tEngland2012/06/28 06:00Nucleic Acids Res. 2012 Sep 1;40(17):8711-20. Epub 2012 Jun 26.

}, month = {Sep 1}, pages = {8711-20}, abstract = {

Because various non-parallel G-quadruplexes of human telomeric sequences in K+ solution can be converted to a parallel G-quadruplex by adding polyethylene glycol (PEG) as a co-solvent, we have taken advantage of this property of PEG to study the covalent attachment of a PEG unit to a G-quadruplex ligand, 3,6-bis(1-methyl-4-vinylpyridinium) carbazole diiodide (BMVC). The hybrid ligand with the PEG unit, BMVC-8C3O or BMVC-6C2O by substituting either the tetraethylene glycol or the triethylene glycol terminated with a methyl-piperidinium cation in N-9 position of BMVC, not only induces structural change from different non-parallel G-quadruplexes to a parallel G-quadruplex but also increases the melting temperature of human telomeres in K+ solution by more than 45 degrees C. In addition, our ligand work provides further confidence that the local water structure plays the key to induce conformational change of human telomere.

}, keywords = {*G-Quadruplexes, Carbazoles/*chemistry, Circular Dichroism, Ligands, Nucleic Acid Denaturation, Polyethylene Glycols/chemistry, Pyridinium Compounds/*chemistry, Solvents/chemistry, Telomere/*chemistry}, isbn = {1362-4962 (Electronic)0305-1048 (Linking)}, url = {http://www.ncbi.nlm.nih.gov/pubmed/22735707}, author = {Wang, Z. F. and Chang, T. C.} } @article {571, title = {Induction of senescence in cancer cells by the G-quadruplex stabilizer, BMVC4, is independent of its telomerase inhibitory activity}, journal = {Br J Pharmacol}, volume = {167}, number = {2}, year = {2012}, note = {

Huang, Fong-ChunChang, Cheng-ChungWang, Jing-MinChang, Ta-ChauLin, Jing-JerengResearch Support, Non-U.S. Gov{\textquoteright}tEngland2012/04/19 06:00Br J Pharmacol. 2012 Sep;167(2):393-406. doi: 10.1111/j.1476-5381.2012.01997.x.

}, month = {Sep}, pages = {393-406}, abstract = {

BACKGROUND AND PURPOSE: Telomerase is the enzyme responsible for extending G-strand telomeric DNA and represents a promising target for treatment of neoplasia. Inhibition of telomerase can be achieved by stabilization of G-quadruplex DNA structures. Here, we characterize the cellular effects of a novel G-quadruplex stabilizing compound, 3,6-bis(4-methyl-2-vinylpyrazinium iodine) carbazole (BMVC4). EXPERIMENTAL APPROACH: The cellular effects of BMVC4 were characterized in both telomerase-positive and alternative lengthening of telomeres (ALT) cancer cells. The molecular mechanism of how BMVC4 induced senescence is also addressed. KEY RESULTS: BMVC4-treated cancer cells showed typical senescence phenotypes. BMVC4 induced senescence in both ALT and telomerase-overexpressing cells, suggesting that telomere shortening through telomerase inhibition might not be the cause for senescence. A large fraction of DNA damage foci was not localized to telomeres in BMVC4-treated cells and BMVC4 suppressed c-myc expression through stabilizing the G-quadruplex structure located at its promoter. These results indicated that the cellular targets of BMVC4 were not limited to telomeres. Further analyses showed that BMVC4 induced DNA breaks and activation of ataxia telangiectasia-mutated mediated DNA damage response pathway. CONCLUSIONS AND IMPLICATIONS: BMVC4, a G-quadruplex stabilizer, induced senescence by activation of pathways of response to DNA damage that was independent of its telomerase inhibitory activity. Thus, BMVC4 has the potential to be developed as a chemotherapeutic agent against both telomerase positive and ALT cancer cells.

}, keywords = {*G-Quadruplexes, Antineoplastic Agents/*pharmacology, Carbazoles/chemistry/*pharmacology, Cell Aging/*drug effects, Cell Line, Tumor, DNA Damage, Gene Expression Regulation, Neoplastic/drug effects, Genes, myc/genetics/physiology, Humans, Molecular Structure, Mutagenesis, Site-Directed, Pyrazines/chemistry/*pharmacology, Telomerase/*antagonists \& inhibitors/genetics/metabolism}, isbn = {1476-5381 (Electronic)0007-1188 (Linking)}, url = {http://www.ncbi.nlm.nih.gov/pubmed/22509942}, author = {Huang, F. C. and Chang, C. C. and Wang, J. M. and Chang, T. C. and Lin, J. J.} } @article {574, title = {Selective photodynamic therapy based on aggregation-induced emission enhancement of fluorescent organic nanoparticles}, journal = {Biomaterials}, volume = {33}, number = {3}, year = {2012}, note = {

Chang, Cheng-ChungHsieh, Meng-ChiehLin, Jung-ChihChang, Ta-ChauengResearch Support, Non-U.S. Gov{\textquoteright}tEngland2011/10/26 06:00Biomaterials. 2012 Jan;33(3):897-906. doi: 10.1016/j.biomaterials.2011.10.018. Epub 2011 Oct 22.

}, month = {Jan}, pages = {897-906}, abstract = {

Three binary molecule conjugates were designed and synthesized by conjugating a chromophore (3, 6-bis-(1-methyl-4-vinylpyridinium)-carbazole diiodide, BMVC) to mono-, bis- and trishydroxyl photosensitizers, respectively. BMVC plays the role of cancer cells recognizer; AIEE (aggregation-induced emission enhancement) generator and FRET (Fluorescence Resonance Energy Transfer) donor. The self assembling properties of these binary conjugates result in different degrees of AIEE and then achieve the formations of FONs (fluorescent organic nanoparticles), which present efficient FRET and singlet oxygen generations. Biologically, FONs-photosensitizers from these compounds were much more phototoxicities to cancer cell than to normal cell without significant dark toxicity. In addition, their intracellular fluorescent colors switching upon photo-excitation are expected to be used for further cell death biomarker applications. This improved photodynamic activity might be due to the aggregation of compounds in the cell that form FONs which can promote PDT (photodynamic therapy) and are observed in cancer cell but not normal cell.

}, keywords = {Cell Line, Drug Design, Fluorescence Resonance Energy Transfer, HeLa Cells, Humans, Nanoparticles/*chemistry, Photochemotherapy/*methods, Photosensitizing Agents/chemical synthesis/chemistry}, isbn = {1878-5905 (Electronic)0142-9612 (Linking)}, url = {http://www.ncbi.nlm.nih.gov/pubmed/22024361}, author = {Chang, C. C. and Hsieh, M. C. and Lin, J. C. and Chang, T. C.} } @article {572, title = {Investigation of lipid homeostasis in living Drosophila by coherent anti-Stokes Raman scattering microscopy}, journal = {J Biomed Opt}, volume = {17}, number = {12}, year = {2012}, note = {

Chien, Cheng-HaoChen, Wei-WenWu, June-TaiChang, Ta-ChauengResearch Support, Non-U.S. Gov{\textquoteright}t2012/12/05 06:00J Biomed Opt. 2012 Dec;17(12):126001. doi: 10.1117/1.JBO.17.12.126001.

}, month = {Dec}, pages = {126001}, abstract = {

To improve our understanding of lipid metabolism, Drosophila is used as a model animal, and its lipid homeostasis is monitored by coherent anti-Stokes Raman scattering microscopy. We are able to achieve in vivo imaging of larval fat body (analogous to adipose tissue in mammals) and oenocytes (analogous to hepatocytes) in Drosophila larvae at subcellular level without any labeling. By overexpressing two lipid regulatory proteins--Brummer lipase (Bmm) and lipid storage droplet-2 (Lsd-2)--we found different phenotypes and responses under fed and starved conditions. Comparing with the control larva, we observed more lipid droplet accumulation by approximately twofold in oenocytes of fat-body-Bmm-overexpressing (FB-Bmm-overexpressing) mutant under fed condition, and less lipid by approximately fourfold in oenocytes of fat-body-Lsd-2-overexpressing (FB-Lsd-2-overexpressing) mutant under starved condition. Moreover, together with reduced size of lipid droplets, the lipid content in the fat body of FB-Bmm-overexpressing mutant decreases much faster than that of the control and FB-Lsd-2-overexpressing mutant during starvation. From long-term starvation assay, we found FB-Bmm-overexpressing mutant has a shorter lifespan, which can be attributed to faster consumption of lipid in its fat body. Our results demonstrate in vivo observations of direct influences of Bmm and Lsd-2 on lipid homeostasis in Drosophila larvae.

}, isbn = {1560-2281 (Electronic)1083-3668 (Linking)}, url = {http://www.ncbi.nlm.nih.gov/pubmed/23208212}, author = {Chien, C. H. and Chen, W. W. and Wu, J. T. and Chang, T. C.} } @article {573, title = {Structure conversion and structure separation of G-quadruplexes investigated by carbazole derivatives}, journal = {Curr Pharm Des}, volume = {18}, number = {14}, year = {2012}, note = {

Chang, Ta-ChauChu, Jen-FeiTsai, Yu-LinWang, Zi-FuengResearch Support, Non-U.S. Gov{\textquoteright}tReviewNetherlands2012/03/02 06:00Curr Pharm Des. 2012;18(14):2002-13.

}, pages = {2002-13}, abstract = {

The challenge of G-quadruplexes is that the G-rich sequences can adopt various G4 structures and possibly interconvert among them, particularly under the change of environmental conditions. Both NMR and circular dichroism (CD) show the spectral conversion of d[AG3(T2AG3)3] (HT22) from Na-form to K-form after Na+/K+ ion exchange. No appreciable change on the induced CD spectra of BMVC molecule and the single molecule tethered particle motion of HT22 in Na+ solution upon K+ titration suggests that the spectral conversion is unlikely due to the structural conversion via fully unfolded intermediate. Although a number of mechanisms were proposed for the spectral change induced by the Na+/K+ ion exchange, determining the precise structures of HT22 in K+ solution may be essential to unravel the mechanism of the structural conversion. Thus, development of a new method for separating different structures is of critical importance for further individual verification. In the second part of this review, we describe a new approach based on "micelle-enhanced ultrafiltration" method for DNA structural separation. The BMVC, a G-quadruplex ligand, is first modified and then forms a large size of emulsion after ultrasonic emulsification, together with its different binding affinities to various DNA structures; for the first time, we are able to separate different DNA structures after membrane filtration. Verification of the possible structural conversion and investigation of structural diversity among various G4 structures are essential for exploring their potential biological roles and for developing new anticancer drugs.

}, keywords = {*Drug Discovery, *G-Quadruplexes, Antineoplastic Agents/*pharmacology, Carbazoles/*chemistry, Circular Dichroism, DNA/*chemistry, Emulsions, Fluorescence Resonance Energy Transfer, Ligands, Magnetic Resonance Spectroscopy, Micelles, Temperature, Ultrafiltration}, isbn = {1873-4286 (Electronic)1381-6128 (Linking)}, url = {http://www.ncbi.nlm.nih.gov/pubmed/22376106}, author = {Chang, T. C. and Chu, J. F. and Tsai, Y. L. and Wang, Z. F.} } @article {557, title = {Emulsified BMVC derivative induced filtration for G-quadruplex DNA structural separation}, journal = {Nucleic Acids Res}, volume = {39}, number = {17}, year = {2011}, note = {

Tsai, Yu-LinWang, Zi-FuChen, Wei-WenChang, Ta-ChauEnglandNucleic Acids Res. 2011 Sep 1;39(17):e114. doi: 10.1093/nar/gkr499. Epub 2011 Jun 28.

}, month = {Sep 1}, pages = {e114}, type = {Research Support, Non-U.S. Gov{\textquoteright}t}, edition = {2011/07/01}, abstract = {

A novel method based on emulsion/filtration is introduced for G-quadruplex DNA structural separation. We first synthesized a lipophilic analogue of BMVC, 3,6-Bis(1-methyl-4-vinylpyridinium)-9-(12{\textquoteright}-bromododecyl) carbazole diiodide (BMVC-12C-Br), which can form an oil-in-water (o/w) phase emulsion. Due to the binding preferences of BMVC-12C-Br emulsion to some specific DNA structures, the large emulsion ( approximately 2 microm) bound DNA was separated from the small free DNA in the filtrate by a 0.22 microm pore size MCE membrane. This method is able to isolate the non-parallel G-quadruplexes from the parallel G-quadruplexes and the linear duplexes from both G-quadruplexes. In addition, this method allows us not only to determine the absence of the parallel G-quadruplexes of d(T(2)AG(3))(4) and the presence of the parallel G-quadruplexes of d(T(2)AG(3))(2) in K(+) solution, but also to verify structural conversion from antiparallel to parallel G-quadruplexes of d[AG(3)(T(2)AG(3))(3)] in K(+) solution under molecular PEG condition. Moreover, this emulsion can separate the non-parallel G-quadruplexes of d(G(3)CGCG(3)AGGAAG(5)CG(3)) monomer from the parallel G-quadruplexes of its dimer in K(+) solution. Together with NMR spectra, one can simplify the spectra for both the free DNA and the bound DNA to establish a spectrum-structure correlation for further structural analysis.

}, keywords = {*G-Quadruplexes, Carbazoles/*chemistry, DNA/*chemistry/*isolation \& purification, Emulsions, Filtration/*methods, Fluorescence, Fluorescent Dyes/*chemistry, Hydrocarbons, Brominated/*chemistry, Microscopy, Fluorescence, Potassium/chemistry, Pyridinium Compounds/*chemistry}, isbn = {1362-4962 (Electronic)0305-1048 (Linking)}, url = {http://www.ncbi.nlm.nih.gov/pubmed/21715373}, author = {Tsai, Y. L. and Wang, Z. F. and Chen, W. W. and Chang, T. C.} } @article {576, title = {Structural Conversion of Intramolecular and Intermolecular G-Quadruplexes of bcl2mid: The Effect of Potassium Concentration and Ion Exchange}, journal = {Journal of Physical Chemistry B}, volume = {115}, number = {10}, year = {2011}, note = {

731NFTimes Cited:6Cited References Count:50

}, month = {Mar 17}, pages = {2360-2370}, abstract = {

The gel assay, circular dichroism, and differential scanning calorimetry results all demonstrate that a major monomer component of bcl2mid exists at low [K(+)] and an additional dimer component appears at high [K(+)]. This implies that bcl2mid is a good candidate for elucidating the mechanisms of structural conversion between different G-quadruplexes. We further discovered that the conversion between the monomer and dimer forms of bcl2mid does not occur at room temperature but is detected when heated above the melting point. In addition, the use of the lithium cation to keep the same ionic strength in a K(+) solution favors the formation of the bcl2mid dimer. We also found that the bcl2mid dimer is more stable than the monomer. However, after the bcl2mid monomer is formed in a K(+) solution, there is no appreciable structural conversion from the monomer to the dimer detected with addition of Li(+) at room temperature. Furthermore, the spectral changes of bcl2mid when transitioning from sodium form to potassium form take place upon K(+) titration. The absence of the dimer form for bcl2mid after the direct addition of 150 mM [K(+)] at room temperature suggests that the spectral changes are not due to rapid unfolding and refolding. In addition, this work reveals the conditions that would be useful for NMR studies of G-quadruplexes.

}, keywords = {arrangements, c-myc promoter, DNA g-quadruplexes, human genome, human telomeric sequence, k+ solution, molecule, region, STABILITY, transcription}, isbn = {1520-6106}, url = {://WOS:000288113300026}, author = {Lin, C. T. and Tseng, T. Y. and Wang, Z. F. and Chang, T. C.} } @article {577, title = {A Novel Method for Screening G-quadruplex Stabilizers to Human Telomeres}, journal = {Journal of the Chinese Chemical Society}, volume = {58}, number = {3}, year = {2011}, note = {

804QCTimes Cited:0Cited References Count:37

}, month = {Jun}, pages = {296-300}, abstract = {

We present a simple method based on the Cu(2+) induced unfolding of G-quadruplex (G4) of human telomere sequence d[AG(3)(T(2)AG(3))(3)] to screen a number of 3,6-bis(1-methyl-4-vinylpyridinium)carbazole diiodide (BMVC) analogues for better G4 stabilizers. Using circular dichroism (CD), the screening results suggest that the tri-cations of 9-substituted BMVC derivatives are better G4 stabilizers than the bi-cations of BMVC. In addition, 3,6-bis(1-methyl-4-vinylpyrazinium)carbazole diiodide (BMVC4) is likely a better core molecule than BM VC for G4 stabilizers.

}, keywords = {bmvc derivatives, cancer, cells, conformational switch, copper induced unfolding, DNA, Drug Design, g-quadruplex, inhibition, molecule, stabilizer, target, terminal transferase, yeast telomere}, isbn = {0009-4536}, url = {://WOS:000293668100005}, author = {Chu, J. F. and Wang, Z. F. and Tseng, T. Y. and Chang, T. C.} } @article {578, title = {Label-free imaging of Drosophila in vivo by coherent anti-Stokes Raman scattering and two-photon excitation autofluorescence microscopy}, journal = {Journal of Biomedical Optics}, volume = {16}, number = {1}, year = {2011}, note = {

725HWTimes Cited:7Cited References Count:36

}, month = {Jan}, abstract = {

Drosophila is one of the most valuable model organisms for studying genetics and developmental biology. The fat body in Drosophila, which is analogous to the liver and adipose tissue in human, stores lipids that act as an energy source during its development. At the early stages of metamorphosis, the fat body remodeling occurs involving the dissociation of the fat body into individual fat cells. Here we introduce a combination of coherent anti-Stokes Raman scattering (CARS) and two-photon excitation autofluorescence (TPE-F) microscopy to achieve label-free imaging of Drosophila in vivo at larval and pupal stages. The strong CARS signal from lipids allows direct imaging of the larval fat body and pupal fat cells. In addition, the use of TPE-F microscopy allows the observation of other internal organs in the larva and autofluorescent globules in fat cells. During the dissociation of the fat body, the findings of the degradation of lipid droplets and an increase in autofluorescent globules indicate the consumption of lipids and the recruitment of proteins in fat cells. Through in vivo imaging and direct monitoring, CARS microscopy may help elucidate how metamorphosis is regulated and study the lipid metabolism in Drosophila. (C) 2011 Society of Photo-Optical Instrumentation Engineers (SPIE). [DOI: 10.1117/1.3528642]

}, keywords = {caenorhabditis-elegans, cars microscopy, coherent anti-stokes raman scattering microscopy, drosophila, ENERGY, fat body, flies, in vivo, kynurenine, label-free imaging, melanogaster, metabolism, quantitative-analysis, tissues, two-photon excitation autofluorescence microscopy}, isbn = {1083-3668}, url = {://WOS:000287636800030}, author = {Chien, C. H. and Chen, W. W. and Wu, J. T. and Chang, T. C.} } @article {579, title = {Single-Molecule TPM Studies on the Conversion of Human Telomeric DNA}, journal = {Biophysical Journal}, volume = {98}, number = {8}, year = {2010}, note = {

586UTTimes Cited:5Cited References Count:42

}, month = {Apr 21}, pages = {1608-1616}, abstract = {

Human telomere contains guanine-rich (G-rich) tandem repeats of single-stranded DNA sequences at its 3{\textquoteright} tail. The G-rich sequences can be folded into various secondary structures, termed G-quadruplexes (G4s), by Hoogsteen basepairing in the presence of monovalent cations (such as Na(+) and K(+)). We developed a single-molecule tethered particle motion (TPM) method to investigate the unfolding process of G4s in the human telomeric sequence AGGG(TTAGGG)3 in real time. The TPM method monitors the DNA tether length change caused by formation of the G4, thus allowing the unfolding process and structural conversion to be monitored at the single-molecule level. In the presence of its antisense sequence, the folded G4 structure can be disrupted and converted to the unfolded conformation, with apparent unfolding time constants of 82 s and 3152 s. We also observed that the stability of the G4 is greatly affected by different monovalent cations. The folding equilibrium constant of G4 is strongly dependent on the salt concentration, ranging from 1.75 at 5 mM Na(+) to 3.40 at 15 mM Na(+). Earlier spectral studies of Na(+)- and K(+)-folded states suggested that the spectral conversion between these two different folded structures may go through a structurally unfolded intermediate state. However, our single-molecule TPM experiments did not detect any totally unfolded intermediate within our experimental resolution when sodium-folded G4 DNA molecules were titrated with high-concentration, excess potassium ions. This observation suggests that a totally unfolding pathway is likely not the major pathway for spectral conversion on the timescale of minutes, and that interconversion among folded states can be achieved by the loop rearrangement. This study also demonstrates that TPM experiments can be used to study conformational changes in single-stranded DNA molecules.

}, keywords = {BINDING, conformational switch, g-quadruplex structures, k+ solution, kinetics, potassium solution, quartet structures, sequence, tethered particle motion, translocation}, isbn = {0006-3495}, url = {://WOS:000276939800028}, author = {Chu, J. F. and Chang, T. C. and Li, H. W.} } @article {558, title = {Detection of G-quadruplexes in cells and investigation of G-quadruplex structure of d(T2AG3)4 in K+ solution by a carbazole derivative: BMVC}, journal = {Methods Mol Biol}, volume = {608}, year = {2010}, note = {

Chang, Ta-ChauChang, Cheng-ChungClifton, N.J.Methods Mol Biol. 2010;608:183-206. doi: 10.1007/978-1-59745-363-9_12.

}, pages = {183-206}, type = {Research Support, Non-U.S. Gov{\textquoteright}t}, edition = {2009/12/17}, abstract = {

Verification of the existence of quadruplex structure in native human telomeres and determination of the major structure of d(T(2)AG(3))(4) (H24) in K(+) solution are the major questions regarding the structure of human telomeres. We have synthesized a fluorescent probe of 3,6-bis(1-methyl-4-vinylpyridinium)carbazole diiodide (BMVC) that has a very high binding affinity for G-quadruplex H24. BMVC stabilizes quadruplex structures and acts as a sensitive probe to the local environment. Although the circular dichroism patterns of H24 are different in Na(+) and K(+) solutions, similar binding behaviors of BMVC to H24 in these solutions led us to suggest that the major G-quadruplex structure of H24 in K(+) solution is very likely similar to that in Na(+) solution. Of particular interest is the fluorescent band detected at -575 nm in quadruplex H24 and at -545 nm in duplex DNA. In addition, the intensity of BMVC fluorescence increases by two orders of magnitudes upon interaction with either duplex or G-quadruplex DNA. BMVC has a greater binding preference for G-quadruplex H24 than for duplex DNA. Analyzing the BMVC fluorescence at the ends of metaphase chromosomes and other regions of chromosomes allowed us to verify the presence of G-quadruplex structure in human telomeres for the first time. Using fluorescence lifetime imaging microscopy, the longer decay time of BMVC in G-quadruplex H24 than in duplex DNA allowed us to map the G-quadruplex structure in human metaphase chromosomes.

}, keywords = {*G-Quadruplexes, Adenocarcinoma/genetics/pathology, Carbazoles/*chemistry, Computer Simulation, DNA/*chemistry/ultrastructure, Fluorescent Dyes, Guanine/*chemistry, Humans, Lung Neoplasms/genetics/pathology, Potassium/*chemistry, Pyridinium Compounds/*chemistry, Solutions, Telomere/*chemistry/ultrastructure, Tumor Cells, Cultured}, isbn = {1940-6029 (Electronic)1064-3745 (Linking)}, url = {http://www.ncbi.nlm.nih.gov/pubmed/20012423}, author = {Chang, T. C. and Chang, C. C.} } @article {580, title = {Improved diagnostic accuracy of malignant neck lumps by a simple BMVC staining assay}, journal = {Analyst}, volume = {134}, number = {4}, year = {2009}, note = {

423FNTimes Cited:1Cited References Count:12

}, pages = {708-711}, abstract = {

A handheld device based on fluorescence of 3,6-bis(1-methyl-4-vinylpyridinium) carbazole diiodide (BMVC) staining was established for the rapid, point-of-care screening of cancer cells (see Chang and co-workers, Analyst, 2007, 132, 745). Offering instant screening of cancer at low cost, here we apply this simple assay in clinical tests on fine needle aspirates of neck masses from 114 outpatients (115 specimens). The diagnostic accuracy of this simple method alone is ca. 80\% (80/99). The combination of the BMVC test and the fine needle aspiration (FNA) cytology reduced the non-diagnosis from 17 cases in FNA cytology to 6 cases in the combined method. Moreover, an algorithm is proposed to improve the diagnostic accuracy of malignant neck lumps up to nearly 100\%.

}, keywords = {biopsy, cancer, limitations, needle-aspiration-cytology, tool}, isbn = {0003-2654}, url = {://WOS:000264482300010}, author = {Liao, L. J. and Kang, C. C. and Jan, I. S. and Chen, H. C. and Wang, C. L. and Lou, P. J. and Chang, T. C.} } @article {582, title = {A dual selective antitumor agent and fluorescence probe: the binary BMVC-porphyrin photosensitizer}, journal = {Chemmedchem}, volume = {3}, number = {5}, year = {2008}, note = {

305MUTimes Cited:3Cited References Count:22

}, month = {May}, pages = {725-728}, abstract = {n/a}, keywords = {cancer, cell death markers, cytotoxicity, fret, lifetime, localization, photodynamic therapy, photoinduced translocation, series, singlet oxygen}, isbn = {1860-7179}, url = {://WOS:000256183300003}, author = {Kang, C. C. and Chen, C. T. and Cho, C. C. and Lin, Y. C. and Chang, C. C. and Chang, T. C.} } @article {583, title = {G-quadruplex stabilizer 3,6-bis(1-methyl-4-vinylpyridinium)carbazole diiodide induces accelerated senescence and inhibits tumorigenic properties in cancer cells}, journal = {Molecular Cancer Research}, volume = {6}, number = {6}, year = {2008}, note = {

318NHTimes Cited:14Cited References Count:50

}, month = {Jun}, pages = {955-964}, abstract = {

Carbazole derivatives that stabilized G-quadruplex DNA structure formed by human telomeric sequence have been designed and synthesized. Among them, 3,6-bis(1-methyl-4-vinylpyridinium)carbazole diiodide (BMVC) showed an increase in G-quadruplex melting temperature by 13 degrees C and has a potent inhibitory effect on telomerase activity. Treatment of H1299 cancer cells with 0.5 mu mol/L BMVC did not cause acute toxicity and affect DNA replication; however, the BMVC-treated cells ceased to divide after a lag period. Hallmarks of senescence, including morphologic changes, detection of senescence-associated beta-galactosidase activity, and decreased bromodeoxyuridine incorporation, were detected in BMVC-treated cancer cells. The BMVC-induced senescence phenotype is accompanied by progressive telomere shortening and detection of the DNA damage foci, indicating that BMVC caused telomere uncapping after long-term treatments. Unlike other telomerase inhibitors, the BMVC-treated cancer cells showed a fast telomere shortening rate and a lag period of growth before entering senescence. Interestingly, BMVC also suppressed the tumor-related properties of cancer cells, including cell migration, colony-forming ability, and anchorage-independent growth, indicating that the cellular effects of BMVC were not limited to telomeres. Consistent with the observations from cellular experiments, the tumorigenic potential of cancer cells was also reduced in mouse xenografts after BMVC treatments. Thus, BMVC repressed tumor progression through both telomere-dependent and telomere-independent pathways.

}, keywords = {DNA structures, Drug Design, human genome, human telomerase, Ligands, proliferation, promoter region, small-molecule, target, transcription}, isbn = {1541-7786}, url = {://WOS:000257098200008}, author = {Huang, F. C. and Chang, C. C. and Lou, P. J. and Kuo, I. C. and Chien, C. W. and Chen, C. T. and Shieh, F. Y. and Chang, T. C. and Lin, J. J.} } @article {581, title = {Isolation, purification and characterization of hemerythrin from Methylococcus capsulatus (Bath)}, journal = {Journal of Inorganic Biochemistry}, volume = {102}, number = {8}, year = {2008}, note = {

331KVTimes Cited:13Cited References Count:23

}, month = {Aug}, pages = {1607-1614}, abstract = {

Earlier work from our laboratory has indicated that a hemerythrin-like protein was over-produced together with the particulate methane monooxygenase (pMMO) when Methylococcus capsulatus (Bath) was grown under high copper concentrations. A homologue of hemerythrin had not previously been found in any prokaryote. To confirm its identity as a hemerythrin, we have isolated and purified this protein by ion-exchange, gel-filtration and hydrophobic interaction chromatography, and characterized it by mass spectrometry, UV-visible, CD, EPR and resonance Raman spectroscopy. On the basis of biophysical and multiple sequence alignment analysis, the protein isolated from M. capsulatus (Bath) is in accord with hemerythrins previously reported from higher organisms. Determination of the Fe content in conjunction with molecular-weight estimation and mass analysis indicates that the native hemerythrin in M. capsulatus (Bath) is a monomer with molecular mass 14.8 kDa, in contrast to hemerythrins from other eukaryotic organisms, where they typically exist as a tetramer or higher oligomers. (c) 2008 Elsevier Inc. All rights reserved.

}, keywords = {bacterial chemotaxis protein, domain, electron paramagnetic resonance, hemerythrin, methane monooxygenase, methylococcus capsulatus (bath), multiple sequence alignment, particulate methane monooxygenase, protein purification, resonance raman spectroscopy}, isbn = {0162-0134}, url = {://WOS:000258012000007}, author = {Kao, W. C. and Wang, V. C. C. and Huang, Y. C. and Yu, S. S. F. and Chang, T. C. and Chan, S. I.} } @article {584, title = {Interaction between human telomere and a carbazole derivative: A molecular dynamics simulation of a quadruplex stabilizer and telomerase inhibitor}, journal = {Journal of Physical Chemistry A}, volume = {111}, number = {38}, year = {2007}, note = {

213GTTimes Cited:17Cited References Count:54

}, month = {Sep 27}, pages = {9224-9232}, abstract = {

The mechanism of inhibition of telomerase by drugs is a key factor in an understanding of guanine-quadruplex complex stabilization during human cancer. This study describes a simulated annealing docking and molecular dynamics simulation to investigate a synthesized potent inhibitor, 3,6-bis(1-methyl-4-vinylpyridinium iodine) carbazole (BMVC), which stabilizes the quadruplex structure of the human telomeric DNA sequence d[AG(3)(T(2)AG(3))(3)] and inhibits telomerase activity. The compound was predicted to selectively interact with the quadruplex structure. During our simulation, the binding affinities were calculated and used to predict the best drug-binding sites as well as enhanced selectivity compared with other compounds. Our studies suggest that the simulation results quite coincide with the experimental results. In addition, molecular modeling shows that a 2:1 binding model involving the external binding of BMVC to both ends of the G-quartet of d[AG(3)(T(2)AG(3))(3)] is the most stable binding mode and this agrees with the absorbance titration results that show two binding sites. Of particular interest is that one pyridinium ring and carbazole moiety of the BMVC can stack well at the end of G-quartet. This implies that BMVC is a good human quadruplex stabilizer and also a good telomerase inhibitor.

}, keywords = {bmvc, cancer-cells, DNA structures, Drug Design, fluorescence probe, human fibroblasts, potent, target, terminal transferase, tumor-cells}, isbn = {1089-5639}, url = {://WOS:000249655600006}, author = {Yang, D. Y. and Chang, T. C. and Sheu, S. Y.} } @article {585, title = {Effect of different electronic properties on 9-aryl-substituted BMVC derivatives for new fluorescence probes}, journal = {Journal of Luminescence}, volume = {127}, number = {1}, year = {2007}, note = {

180AKTimes Cited:8Cited References Count:22

}, month = {Nov}, pages = {41-47}, abstract = {

We have previously illustrated that the electron donor of carbazole moiety and the electron acceptor of methyl pyridinium cation in 3,6-bis(1-methyl-4-vinylpyridinium) carbazole diiodide (BMVC) molecule could form an intramolecular charge-transfer state. The intramolecular twist of the vinyl group in bridging the donor and acceptor plays an important role in the BMVC fluorescence. Here, we have synthesized three 9-aryl-substituted BMVC derivatives with different electronic properties for the design of the second generation of fluorescence probes. The steady-state solvatochromic studies show no appreciable change to the charge transfer of BMVC by substituting an anisole electron-donating group at 9-position of BMVC. However, substituting a 9-nitrobenzyl electron-withdrawing group in BMVC could restrict the charge transfer in the excited state. Moreover, the increase of the fluorescence yields of 9-anisole BMVC and 9-phenyl BMVC upon interaction with DNA is even higher than that in glycerol, while the fluorescence yield of 9-nitrobenzyl BMVC upon interaction with DNA is much lower than that in glycerol. Although 9-nitrobenzyl BMVC is a good G-quadruplex stabilizer, substituting an electron-withdrawing group at 9-position of BMVC is not recommended for the design of fluorescence probes. On the other hand, colocalization between 9-phenyl BMVC and MitoTracker Red in the merged image of cells indicates that the 9-phenyl BMVC is a potential fluorescent mitochondrial probe. (C) 2007 Elsevier B.V. All rights reserved.

}, keywords = {DNA, florescence probe, human telomeres, intramolecular charge transfer, laser-dyes, molecular rotor, molecular rotors, photophysical properties, quadruplex structure, sensitivity, SYSTEMS, torsional relaxation, viscosity dependence}, isbn = {0022-2313}, url = {://WOS:000247332000009}, author = {Tsai, Y. L. and Chang, C. C. and Kang, C. C. and Chang, T. C.} } @article {587, title = {Investigation of spectral conversion of d(TTAGGG)(4) and d(TTAGGG)(13) upon potassium titration by a G-quadruplex recognizer BMVC molecule}, journal = {Nucleic Acids Research}, volume = {35}, number = {9}, year = {2007}, note = {

180GKTimes Cited:43Cited References Count:45

}, month = {May}, pages = {2846-2860}, abstract = {

We have introduced a G- quadruplex- binding ligand, 3,6- bis( 1- methyl- 4- vinylpyridinium) carbazole diiodide ( BMVC), to verify the major structure of d( T(2)AG(3))(4) ( H24) in potassium solution and examine the structural conversion of H24 in sodium solution upon potassium titration. The studies of circular dichroism, induced circular dichroism, spectral titration and gel competition have allowed us to determine the binding mode and binding ratio of BMVC to the H24 in solution and eliminate the parallel form as the major G- quadruplex structure. Although the mixed- type form could not be eliminated as a main component, the basket and chair forms are more likely the main components of H24 in potassium solution. In addition, the circular dichroism spectra and the job plots reveal that a longer telomeric sequence d( T(2)AG(3))(13) ( H78) could form two units of G4 structure both in sodium or potassium solutions. Of particular interest is that no appreciable change on the induced circular dichroism spectra of BMVC is found during the change of the circular dichroism patterns of H24 upon potassium titration. Considering similar spectral conversion detected for H24 and a long sequence H78 together with the G4 structure stabilized by BMVC, it is therefore unlikely that the rapid spectral conversion of H24 and H78 is due to structural change between different types of the G4 structures. With reference to the circular dichroism spectra of d( GAA)(7) and d( GAAA)(5), we suggest that the spectral conversion of H24 upon potassium titration is attributed to fast ion exchange resulting in different loop base interaction and various hydrogen bonding effects.

}, keywords = {antiparallel, BINDING, circular-dichroism, crystal-structure, d(g(4)t(4)g(4)), DNA quadruplexes, human telomere, parallel, sequence forms, tetraplex}, isbn = {0305-1048}, url = {://WOS:000247350800004}, author = {Chang, C. C. and Chien, C. W. and Lin, Y. H. and Kang, C. C. and Chang, T. C.} } @article {586, title = {A handheld device for potential point-of-care screening of cancer}, journal = {Analyst}, volume = {132}, number = {8}, year = {2007}, note = {

192UUTimes Cited:14Cited References Count:15

}, pages = {745-749}, abstract = {

A simple handheld device based on the fluorescence analysis of 3,6-bis(1-methyl-4-vinylpyridinium) carbazole diiodide ( BMVC) stained cells was established for routine screening and potentially for early detection of cancer cells at extremely low cost. Flow cytometry assay further supported the utility of this simple device, where a preliminary study of tissue biopsy showed highly encouraging results.

}, keywords = {bmvc, cells, DNA, flow-cytometry, human telomeres, quadruplex structure, SPECTROSCOPY}, isbn = {0003-2654}, url = {://WOS:000248229700014}, author = {Kang, C. C. and Chang, C. C. and Chang, T. C. and Liao, L. J. and Lou, P. J. and Xie, W. and Yeung, E. S.} } @article {561, title = {Investigation of spectral conversion of d(TTAGGG)4 and d(TTAGGG)13 upon potassium titration by a G-quadruplex recognizer BMVC molecule}, journal = {Nucleic Acids Res}, volume = {35}, number = {9}, year = {2007}, note = {

Chang, Cheng-ChungChien, Chih-WeiLin, Yi-HsuehKang, Chi-ChihChang, Ta-ChauEnglandNucleic Acids Res. 2007;35(9):2846-60. Epub 2007 Apr 11.

}, pages = {2846-60}, type = {Research Support, Non-U.S. Gov{\textquoteright}t}, edition = {2007/04/14}, abstract = {

We have introduced a G-quadruplex-binding ligand, 3,6-bis(1-methyl-4-vinylpyridinium)carbazole diiodide (BMVC), to verify the major structure of d(T2AG3)4 (H24) in potassium solution and examine the structural conversion of H24 in sodium solution upon potassium titration. The studies of circular dichroism, induced circular dichroism, spectral titration and gel competition have allowed us to determine the binding mode and binding ratio of BMVC to the H24 in solution and eliminate the parallel form as the major G-quadruplex structure. Although the mixed-type form could not be eliminated as a main component, the basket and chair forms are more likely the main components of H24 in potassium solution. In addition, the circular dichroism spectra and the job plots reveal that a longer telomeric sequence d(T2AG3)13 (H78) could form two units of G4 structure both in sodium or potassium solutions. Of particular interest is that no appreciable change on the induced circular dichroism spectra of BMVC is found during the change of the circular dichroism patterns of H24 upon potassium titration. Considering similar spectral conversion detected for H24 and a long sequence H78 together with the G4 structure stabilized by BMVC, it is therefore unlikely that the rapid spectral conversion of H24 and H78 is due to structural change between different types of the G4 structures. With reference to the circular dichroism spectra of d(GAA)7 and d(GAAA)5, we suggest that the spectral conversion of H24 upon potassium titration is attributed to fast ion exchange resulting in different loop base interaction and various hydrogen bonding effects.

}, keywords = {Binding Sites, Carbazoles/*chemistry, Circular Dichroism, DNA/*chemistry, Electrophoresis, Polyacrylamide Gel, G-Quadruplexes, Guanine/chemistry, Humans, Nucleic Acid Conformation, Potassium/chemistry, Pyridinium Compounds/*chemistry, Sodium/chemistry, Spectrophotometry, Telomere/*chemistry}, isbn = {1362-4962 (Electronic)0305-1048 (Linking)}, url = {http://www.ncbi.nlm.nih.gov/pubmed/17430965}, author = {Chang, C. C. and Chien, C. W. and Lin, Y. H. and Kang, C. C. and Chang, T. C.} } @article {589, title = {Detection of quadruplex DNA structures in human telomeres by using a fluorescence probe BMVC molecule}, journal = {Abstracts of Papers of the American Chemical Society}, volume = {232}, year = {2006}, note = {

V15db109-BIOLTimes Cited:0Cited References Count:0

}, month = {Sep 10}, pages = {805-805}, abstract = {n/a}, isbn = {0065-7727}, url = {://WOS:000207781600708}, author = {Chang, T. C. and Chang, C. C. and Chu, J. F. and Kao, F. J. and Lou, P. J.} } @article {590, title = {G-quadruplex structure of d(TTAGGG)4 in potassium solution investigated by BMVC molecule}, journal = {Abstracts of Papers of the American Chemical Society}, volume = {232}, year = {2006}, note = {

V15db119-BIOLTimes Cited:0Cited References Count:0

}, month = {Sep 10}, pages = {803-803}, abstract = {n/a}, isbn = {0065-7727}, url = {://WOS:000207781600706}, author = {Chang, T. C. and Chang, C. C.} } @article {591, title = {Solvent effect on photophysical properties of a fluorescence probe: BMVC}, journal = {Journal of Luminescence}, volume = {119}, year = {2006}, note = {

034JRTimes Cited:21Cited References Count:17

}, month = {Jul-Oct}, pages = {84-90}, abstract = {

Fluorescence studies of 3,6-bis(1-methyl-4-vinylpyridinium) carbazole diiodide (BMVC) in glycerol/water mixtures allow us to elucidate the photophysical behavior of BMVC upon interaction with different DNA structures. The very weak fluorescence emission of BMVC in highly polar solvents of water is attributed to an increase in nonradiative decay due to the intramolecular twist of the vinyl group induced by charge transfer. Increasing the solvent viscosity and rigidity could lead to large changes in the barrier height and substantial effects on relaxation processes, and result in an enhancement of the fluorescence quantum yield. Similarly, different binding interactions of BMVC with various DNA could perturb the frictions of the reorientation of the vinyl group. We suggest that the intramolecular twist of the vinyl group of BMVC is mainly responsible for the distinct fluorescence emissions under different local environments. (c) 2006 Elsevier B.V. All rights reserved.

}, keywords = {bmvc, carbazole, chromophores, DYNAMICS, Fluorescence, laser-dyes, photoluminescence, photophysical properties, quadruplex DNA, relaxation, sensitivity, viscosity}, isbn = {0022-2313}, url = {://WOS:000236925800019}, author = {Chang, C. C. and Chu, J. F. and Kuo, H. H. and Kang, C. C. and Lin, S. H. and Chang, T. C.} } @article {588, title = {A new approach for the detection of a nonfluorescent compound by CE-resonance Raman spectroscopy based on the sweeping-MEKC mode}, journal = {Electrophoresis}, volume = {27}, number = {23}, year = {2006}, note = {

117WCTimes Cited:9Cited References Count:27

}, month = {Dec}, pages = {4688-4693}, abstract = {

A CE-resonance Raman spectroscopy (CE-RRS) method based on MEKC and sweeping-MEKC modes is described. A nonfluorescent compound, malachite green (MG), and a doubled Nd:YAG laser (532 nm, 300 mW) were selected as model compound and light source, respectively. In order to carry out a quantitative analysis of MG, a monochromator (effective bandwidth, 0.4 nm) was used to collect the specific Raman line at 1616 cm(-1) (N-phi and C-C stretch, corresponding to 582 nm when the wavelength of the exciting source was 532 nm). As a result, the LOD for MG was 10 ppm, based on the MEKC/RRS mode. This could be improved to 5 ppb when the sweeping-MEKC/RRS mode was applied. Furthermore, with the addition of nano-size silver colloids to the CE buffer the detection limits can be further improved, but the data obtained with surface-enhanced resonance Raman spectroscopy (SERRS) are less useful for quantitative purposes.

}, keywords = {capillary-electrophoresis, ce, dynamic ph junction, fluorescence detection, identification, leucomalachite green, malachite green, mass-spectrometry, performance liquid-chromatography, raman spectroscopy, SCATTERING, stacking, surface enhanced-resonance raman spectroscopy, sweeping-mekc}, isbn = {0173-0835}, url = {://WOS:000242903000011}, author = {Tsai, C. H. and Chan, P. H. and Lin, C. H. and Chang, T. C. and Chia, C. T.} } @article {592, title = {Verification of antiparallel G-quadruplex structure in human telomeres by using two-photon excitation fluorescence lifetime imaging microscopy of the 3,6-bis(1-methyl-4-vinylpyridinium)carbazole diiodide molecule}, journal = {Analytical Chemistry}, volume = {78}, number = {8}, year = {2006}, note = {

034RMTimes Cited:48Cited References Count:26

}, month = {Apr 15}, pages = {2810-2815}, abstract = {

Different G-quadruplex structures for the human telomeric sequence d(T(2)AG(3))(4) in vitro have been documented in the presence of sodium and potassium. Verification of the G-quadruplex structures in human telomeres in vivo is the main issue in establishing the biological function of the G-quadruplex structures in telomeres as well as the development of anticancer agents. Here we have applied two-photon excitation fluorescence lifetime imaging microscopy to measure the fluorescence lifetime of the BMVC molecule upon interaction with various DNA structures. The distinction in lifetime measured with submicrometer spatial resolution in two-photon excitation fluorescence lifetime imaging microscopy provides a powerful approach not only to verify the existence of the antiparallel G-quadruplex structure in human telomeres but also to map its localizations in metaphase chromosomes.

}, keywords = {c-myc promoter, carbazole, DNA, Drug Design, DYNAMICS, region, target}, isbn = {0003-2700}, url = {://WOS:000236948300046}, author = {Chang, C. C. and Chu, J. F. and Kao, F. J. and Chiu, Y. C. and Lou, P. J. and Chen, H. C. and Chang, T. C.} } @article {594, title = {Thionin in a cyclodextrin nanocavity: Measuring local compressibilities by pressure tuning hole burning spectroscopy}, journal = {Chemical Physics Letters}, volume = {413}, number = {4-6}, year = {2005}, note = {

967MBTimes Cited:3Cited References Count:24

}, month = {Sep 26}, pages = {335-341}, abstract = {

We present pressure tuning hole burning experiments on thionin with alpha-cyclodextrin (alpha-CD) and beta-cyclodextrin (beta-CD) in a glycerol/water glass. The low temperature absorption spectra do not show the formation of a caging complex. The pressure tuning data, however, show that the compressibility of the sample with beta-CD, where the formation of an inclusion complex is not restricted due to geometrical reasons increases as compared to the other samples. This is just the opposite of what one would expect. This increase is interpreted in terms of a reduced solvent density around the chromophore due to the hydrophobic effect. (c) 2005 Elsevier B.V. All rights reserved.

}, keywords = {beta-cyclodextrin, COMPLEXES, dye, globular-proteins}, isbn = {0009-2614}, url = {://WOS:000232094200017}, author = {Hecht, C. and Hermann, P. and Friedrich, J. and Chang, C. C. and Chang, T. C.} } @article {595, title = {Investigation of thionin-DNA interaction by satellite hole spectroscopy}, journal = {Optics and Spectroscopy}, volume = {98}, number = {5}, year = {2005}, note = {

937ULTimes Cited:2Cited References Count:25

}, month = {May}, pages = {655-660}, abstract = {

The interactions of the two tautomers of thionin dye with DNA have been investigated by using satellite hole burning spectroscopy. Similar features in the absorption and satellite hole spectra of thionin in the presence of calf thymus (CT) DNA and polynucleotides [d(GC)(6)](2) (GC) suggested that thionin preferentially binds to GC rather than polynucleotides [d(AT)(6)](2) (AT). Different binding effects of the two tautomers to DNA could be observed. While the imino form fully intercalates into the DNA base pairs, the amino form is only partially intercalated. In addition, a broad hole associated with an antihole appeared in the presence of DNA, particularly in GC base pairs. The coincidence of the antihole with the absorption band of the amino form showed that the amino form is the photoproduct of the imino form. An increase in intensity of the broad hole and its antihole and the loss of nonresonant hole intensity upon interaction with CT DNA could be described by rapid ground state recovery resulting from fast charge transfer between the intercalated thionin and a guanine base quenching the internal conversion. (c) 2005 Pleiades Publishing, Inc.

}, keywords = {9-aminoacridine, absorption-spectra, acids, burning spectra, COMPLEXES, glasses, methylene-blue, organic-molecules, polynucleotides, proteins}, isbn = {0030-400X}, url = {://WOS:000229951200003}, author = {Chang, T. C. and Yang, Y. P. and Huang, K. H. and Chang, C. C. and Hecht, C.} } @article {593, title = {Simple method in diagnosing cancer cells by a novel fluorescence probe BMVC}, journal = {Journal of the Chinese Chemical Society}, volume = {52}, number = {6}, year = {2005}, note = {

000EYTimes Cited:4Cited References Count:8

}, month = {Dec}, pages = {1069-1072}, abstract = {

Different cellular accumulations with distinct fluorescence properties of BMVC in cancer cells from normal cells allow us to establish a simple and economic method for the diagnosis of cancer cells. With using a light emitting diode to excite the BMVC molecule, microarray fluorescence analysis of a cell-based glass chip provides an easy method towards the detection of a limited number of cancer cells.

}, keywords = {bmvc, cell-based microarray, detection limit, diagnosis of cancer cells, led, quadruplex DNA}, isbn = {0009-4536}, url = {://WOS:000234444900001}, author = {Kang, C. C. and Chang, C. C. and Cheng, J. Y. and Chang, T. C.} } @article {596, title = {Simple method in diagnosing cancer cells by a novel fluorescence probe BMVC}, journal = {Abstracts of Papers of the American Chemical Society}, volume = {230}, year = {2005}, note = {

032TJ137-ANYLTimes Cited:0Cited References Count:0

}, month = {Aug 28}, pages = {U241-U241}, abstract = {n/a}, isbn = {0065-7727}, url = {://WOS:000236797300460}, author = {Chang, T. C. and Chang, C. C. and Kang, C. C.} } @article {562, title = {A novel carbazole derivative, BMVC: a potential antitumor agent and fluorescence marker of cancer cells}, journal = {Chem Biodivers}, volume = {1}, number = {9}, year = {2004}, note = {

Chang, Cheng-ChungKuo, I-ChunLin, Jing-JerLu, Yu-ChengChen, Chin-TinBack, Hong-TsunLou, Pei-JenChang, Ta-ChauSwitzerlandChem Biodivers. 2004 Sep;1(9):1377-84.

}, month = {Sep}, pages = {1377-84}, type = {Comparative StudyResearch Support, Non-U.S. Gov{\textquoteright}t}, edition = {2006/12/29}, abstract = {

We have investigated a novel compound, 3,6-bis[2-(1-methylpyridinium)vinyl]carbazole diiodide (BMVC), for inhibiting telomerase activity and distinguishing human lung H1299 and oral Ca9-22 cancer cells from lung IMR90 and skin Detroit-551 normal fibroblast cells. The telomeric repeat amplification protocol (TRAP) assay shows that the concentration of BMVC that inhibits 50\% of the telomerase activity (IC50) is ca. 0.05 microM. On the other hand, the cell-viability assay indicates that the cytotoxicity was less than 15\% to the H1299 and Ca9-22 cancer cells, and almost negligible to the MRC-5 and Detroit-551 normal cells after incubation with 0.5 microM BMVC for 72 h. The low concentration of 0.05 microM of BMVC can inhibit telomerase activity but does not have general toxic effects to normal cells, implying that BMVC is a promising telomerase inhibitor. Moreover, wide-field fluorescence images of 0.1 microM BMVC-treated cells show bright fluorescence spots in the nuclei of the most H1299 and Ca9-22 cancer cells. Interestingly, similar fluorescence spots are hardly observed in the nuclei of the IMR90 and Detroit-551 normal cells, implying that BMVC might be a useful marker to distinguish tumor cells and normal cells.

}, keywords = {Antineoplastic Agents/*chemistry/diagnostic use/pharmacology, Biological Markers/chemistry, Carbazoles/*chemistry/diagnostic use/pharmacology, Cell Line, Tumor, Cells, Cultured, Drug Screening Assays, Antitumor/methods, Drugs, Investigational/chemistry/diagnostic use/pharmacology, Fluorescent Dyes/chemistry, Humans, Microscopy, Fluorescence/methods, Pyridinium Compounds/*chemistry/diagnostic use/pharmacology}, isbn = {1612-1880 (Electronic)1612-1872 (Linking)}, url = {http://www.ncbi.nlm.nih.gov/pubmed/17191915}, author = {Chang, C. C. and Kuo, I. C. and Lin, J. J. and Lu, Y. C. and Chen, C. T. and Back, H. T. and Lou, P. J. and Chang, T. C.} }