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Wu Y.,Tsinghua University | Tan Y.,Tsinghua University | Wu J.,Tsinghua University | Chen S.,National University of Singapore | And 5 more authors.
ACS Applied Materials and Interfaces | Year: 2015

Array-based sensing offers several advantages for detecting a series of analytes with common structures or properties. In this study, four anionic conjugated polyelectrolytes (CPEs) with a common poly(p-pheynylene ethynylene) (PPE) backbone and varying pendant ionic side chains were designed. The conjugation length, repeat unit pattern, and ionic side chain composition were the main factors affecting the fluorescence patterns of CPE polymers in response to the addition of different metal ions. Eight metal ions, including Pb2+, Hg2+, Fe3+, Cr3+, Cu2+, Mn2+, Ni2+, and Co2+, categorized as water contaminants by the Environmental Protection Agency, were selected as analytes in this study. Fluorescence intensity response patterns of the four-PPE sensor array toward each of the metal ions were recorded, analyzed, and transformed into canonical scores using linear discrimination analysis (LDA), which permitted clear differentiation between metal ions using both two-dimensional and three-dimensional graphs. In particular, the array could readily differentiate between eight toxic metal ions in separate aqueous solutions at 100 nM. Our four-PPE sensor array also provides a practical application to quantify Pb2+ and Hg2+ concentrations in blind samples within a specific concentration range. © 2015 American Chemical Society. Source


Gao F.,Tsinghua University | Liu F.,Tsinghua University | Zheng J.,Tsinghua University | Zeng M.,Shenzhen Kivita Innovative Drug Discovery Institute | Jiang Y.,Tsinghua University
Analytical Sciences | Year: 2015

In vitro selection methods allow for isolation of DNAzymes (catalytic DNAs) from random DNA pools. Here we describe a fluorogenic DNAzyme, LYF5, isolated using a double-random selection approach: a random DNA pool was selected against a complex molecular mixture derived from a breast cancer cell line, T47D. LYF5 specifically indicates the T47D breast cancer cell line with high sensitivity. After sequence optimization, the second-generation DNAzyme, 2G-LYF5, exhibited an approximately 2-fold higher cleavage percentage. Finally, we have determined that the intramolecular stem-loop motif plays a crucial role in 2G-LYF5 activity. Our findings underscore the capability of singlestranded DNA molecules to perform highly sophisticated functions that are amenable to the development of diagnostic tests for early identification of breast cancer. 2015 © The Japan Society for Analytical Chemistry. Source


Jiang J.,Tsinghua University | Ding C.,Tsinghua University | Li L.,Shenzhen Kivita Innovative Drug Discovery Institute | Gao C.,Tsinghua University | And 3 more authors.
Tetrahedron Letters | Year: 2014

The synthesis of RITA and a variety of five-membered heterocyclic triads by the cyclocondensation of 1,4-bis(5-substituted-2-thienyl or 2-furyl)-1,3-butadiynes with water or Na2S·9H2O in the presence of KOH in DMSO is described. The study on the antiproliferative activities against K562, MCF-7, A549, and HCT116 tumor cells has revealed that some of the heterocyclic triads show higher antiproliferative activities than RITA, depending on the structures of substituents, the property of heteroatoms as well as their numbers. © 2014 Elsevier Ltd. All rights reserved. Source


He S.,Tsinghua University | Qu L.,Tsinghua University | Qu L.,McMaster University | Shen Z.,McMaster University | And 5 more authors.
Analytical Chemistry | Year: 2015

Breast cancer is one of the most commonly diagnosed cancers among females worldwide. Early detection of breast cancer is of vital importance to the reduction of the mortality rate. However, the lack of specific biomarkers that can effectively identify breast cancer cells limits the ability for early diagnosis of breast cancer. RNA-cleaving fluorogenic DNAzymes (RFDs), which can be produced through the systematic evolution of ligands by exponential enrichment (SELEX) process, are catalytic DNA molecules capable of generating a fluorescent signal when the appropriate target is bound. In this study, we carried out a SELEX experiment to select for RFDs that are active in the cell lysate of MDA-MB-231, a model breast cancer cell line. We obtained a RFD probe, named AAI2-5, that can detect MDA-MB-231 at a concentration of cell lysate proteins as low as 0.5 μg/mL (which is equivalent to ∼5000 cell/mL). AAI2-5 is capable of distinguishing MDA-MB-231 cells from normal cells as well as other types of tumor cells, including other subtypes of breast cancer cells. Moreover, AAI2-5 responded positively to more than 90% of malignant breast tumors. This report is the first study to explore the RFD system for the detection of cancer cells. The results suggest that RFD can be potentially applied for the diagnosis and treatment of breast cancer in the future. © 2014 American Chemical Society. Source


Chu B.,Tsinghua University | Liu F.,Tsinghua University | Li L.,Tsinghua University | Ding C.,Tsinghua University | And 6 more authors.
Cell death & disease | Year: 2015

Aberrant expression or function of epidermal growth factor receptor (EGFR) or the closely related human epidermal growth factor receptor 2 (HER2) can promote cell proliferation and survival, thereby contributing to tumorigenesis. Specific antibodies and low-molecular-weight tyrosine kinase inhibitors of both proteins are currently in clinical trials for cancer treatment. Benzimidazole derivatives possess diverse biological activities, including antitumor activity. However, the anticancer mechanism of 5a (a 2-aryl benzimidazole compound; 2-chloro-N-(2-p-tolyl-1H-benzo[d]imidazol-5-yl)acetamide, C(16)H(14)ClN(3)O, MW299), a novel 2-aryl benzimidazole derivative, toward breast cancer is largely unknown. Here, we demonstrate that 5a potently inhibited both EGFR and HER2 activity by reducing EGFR and HER2 tyrosine phosphorylation and preventing downstream activation of PI3K/Akt and MEK/Erk pathways in vitro and in vivo. We also show that 5a inhibited the phosphorylation of FOXO and promoted FOXO translocation from the cytoplasm into the nucleus, resulting in the G1-phase cell cycle arrest and apoptosis. Moreover, 5a potently induced apoptosis via the c-Jun N-terminal kinase (JNK)-mediated death receptor 5 upregulation in breast cancer cells. The antitumor activity of 5a was consistent with additional results demonstrating that 5a significantly reduced tumor volume in nude mice in vivo. Analysis of the primary breast cancer cell lines with HER2 overexpression further confirmed that 5a significantly inhibited Akt Ser473 and Bad Ser136 phosphorylation and reduced cyclin D3 expression. On the basis of our findings, further development of this 2-aryl benzimidazole derivative, a new class of multitarget anticancer agents, is warranted and represents a novel strategy for improving breast cancer treatment. Source

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