Publications

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Journal Article
MH, K, ZF W, TY T, MH L, ST H, JJ L, TC C.  2015.  Conformational transition of a hairpin structure to G-quadruplex within the WNT1 gene promoter. J Am Chem Soc. 137(1):210-8.
WC, H, TY T, YT C, CC C, ZF W, CL W, TN H, PT L, CT C, JJ L, PJ L, TC C.  2015.  Direct evidence of mitochondrial G-quadruplex DNA by using fluorescent anti-cancer agents. Nucleic Acids Res.. 43(21):10102-13.
IT, L, YL T, CC K, WC H, CL W, MY L, PJ L, JY S, HC W, HD W, TH T, ISang J, TC C.  2014.  BMVC test, an improved fluorescence assay for detection of malignant pleural effusions. Cancer medicine. 3(1):162-173.
JM, W, FC H, MH K, ZF W, TY T, LC C, SJ Y, TC C, JJ L.  2014.  Inhibition of Cancer Cell Migration and Invasion through Suppressing the Wnt1-mediating Signal Pathway by G-quadruplex Structure Stabilizers. The Journal of biological chemistry.
CC, K, WC H, CW K, ZF W, CC C, CC C, CL W, TC C, J S, LJ H.  2013.  Chemical principles for the design of a novel fluorescent probe with high cancer-targeting selectivity and sensitivity.. Integrative biology : quantitative biosciences from nano to macro. 5(10):1217-28. AbstractWebsite

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.

Liao, LJ, Kang CC, Jan IS, Chen HC, Wang CL, Lou PJ, Chang TC.  2009.  Improved diagnostic accuracy of malignant neck lumps by a simple BMVC staining assay. Analyst. 134:708-711., Number 4 AbstractWebsite

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%.