Yong Peng

The Ohio State University, Columbus, OH, United States

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Publications (9)63.04 Total impact

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    ABSTRACT: Traditional macroscopic and microscopic identification methods of medicinal materials are economical and practical, but usually experience-based due to few chemical supports. Here histochemical evaluation on bioactive components of Coptidis Rhizoma (CR) in anatomic sections using laser microdissection and liquid chromatography-mass spectrometry (LMD-LC-MS) was developed to correlate the inner quality and outer features of materials from different growing areas. Results of a total 33 peaks representing potential different alkaloids were detected and 8 common peaks were identified as the major alkaloids, namely magnoflorine, thalifendine, columbamine, epiberberine, jatrorrhizine, coptisine, palmatine, and berberine. Six major alkaloids were quantified in the top and middle sections of raw materials and in their tissues and cells at the same time. Histochemical analyses showed consistent results with direct determination in raw materials and explained the reason why top sections of all samples contained higher contents of alkaloids by giving out attributions of each alkaloid in different anatomic sections. Besides, results manifested the distribution and accumulation rules of alkaloids in diverse tissues and cells of CR. This study demonstrates an effective and scientific way to correlate bioactive components and morphological features of medicinal materials, which is beneficial to future research, agriculture and application. Copyright © 2014 John Wiley & Sons, Ltd.
    Drug Testing and Analysis 09/2014; · 3.17 Impact Factor
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    ABSTRACT: Our goal is to test if CS1 could be targeted by CAR T cells to treat MM. We generated a retroviral construct of a CS1-specific CAR and engineered primary human T cells expressing the CAR. We then tested the capacity of CS1-CAR T cells to eradicate human multiple myeloma tumor cells in vitro, ex vivo and in vivo using orthotopic MM xenograft mouse models. In vitro, compared to mock-transduced T cells, upon recognizing CS1 positive MM cells, CS1-CAR-tranduced T cells secreted more IFN-γ as well as IL-2, expressed higher levels of the activation marker CD69, showed higher capacity for degranulation, and displayed enhanced cytotoxicity. Ectopically forced expression of CS1 in MM cells with low CS1 expression enhanced recognition and killing by CAR T cells. Ex vivo, CS1-CAR T cells also showed similarly enhanced activities when responding to primary MM cells. More importantly, in orthotopic MM xenograft mouse models, adoptive transfer of human primary T cells expressing CS1-CAR efficiently suppressed the growth of human MM.1S and IM9 myeloma cells and significantly prolonged mouse survival. CS1 is a promising antigen that can be targeted by CAR-expressing T cells for treatment of MM.
    Clinical Cancer Research 03/2014; · 7.84 Impact Factor
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    ABSTRACT: The mechanism by which the 8q24 MYC enhancer region, including cancer-associated variant rs6983267, increases cancer risk is unknown due to the lack of protein-coding genes at 8q24.21. Here we report the identification of long noncoding RNAs named cancer-associated region long noncoding RNAs (CARLos) in the 8q24 region. The expression of one of the long noncoding RNAs, CARLo-5, is significantly correlated with the rs6983267 allele associated with increased cancer susceptibility. We also found the MYC enhancer region physically interacts with the active regulatory region of the CARLo-5 promoter, suggesting long-range interaction of MYC enhancer with the CARLo-5 promoter regulates CARLo-5 expression. Finally, we demonstrate that CARLo-5 has a function in cell-cycle regulation and tumor development. Overall, our data provide a key of the mystery of the 8q24 gene desert.
    Proceedings of the National Academy of Sciences 03/2014; · 9.81 Impact Factor
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    ABSTRACT: MicroRNAs (miRNAs) are small 19- to 24-nt noncoding RNAs that have the capacity to regulate fundamental biological processes essential for cancer initiation and progression. In cancer, miRNAs may function as oncogenes or tumor suppressors. Here, we conducted global profiling for miRNAs in a cohort of stage 1 nonsmall cell lung cancers (n = 81) and determined that miR-486 was the most down-regulated miRNA in tumors compared with adjacent uninvolved lung tissues, suggesting that miR-486 loss may be important in lung cancer development. We report that miR-486 directly targets components of insulin growth factor (IGF) signaling including insulin-like growth factor 1 (IGF1), IGF1 receptor (IGF1R), and phosphoinositide-3-kinase, regulatory subunit 1 (alpha) (PIK3R1, or p85a) and functions as a potent tumor suppressor of lung cancer both in vitro and in vivo. Our findings support the role for miR-486 loss in lung cancer and suggest a potential biological link to p53.
    Proceedings of the National Academy of Sciences 08/2013; · 9.81 Impact Factor
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    ABSTRACT: MicroRNAs (miRNAs) bind to complementary sequences of target mRNAs, resulting in translational repression or target degradation and thus gene silencing. MiRNAs are abundantly found in circulating blood, yet whether, as a class of regulatory molecules, they may interact with human natural killer (NK) cells has not been explored. Here we found that the treatment of human NK cells with several mature miRNAs, in the presence of a low concentration of IL-12, induced CD69 expression, IFN-γ production, and degranulation marker CD107a expression. In vivo, infusion of several miRNAs alone in murine peripheral blood also resulted in comparable NK but not T cell activation. Furthermore, miRNA administration significantly protected mice from tumor development in an NK cell-dependent manner. Mechanistically, we found that miRNA stimulation led to downstream activation of NF-κB, an effect that was blunted by a block in Toll-like receptor (TLR) 1 signaling and was attenuated in lymphoma patients. Knockdown of TLR1 resulted in less activation by miRNAs. Collectively, we show that miRNAs have a capacity to selectively activate innate immune effector cells that is at least in part via the TLR1-NF-κB signaling pathway. This may be important in the normal host defense against infection and/or malignant transformation.
    Blood 04/2013; · 9.78 Impact Factor
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    ABSTRACT: Bioactive components from dietary supplements such as curcumin may represent attractive agents for cancer prevention or treatment. DNA methylation plays a critical role in acute myeloid leukemia (AML) development, and presents an excellent target for treatment of this disease. However, it remains largely unknown how curcumin, a component of the popular Indian spice turmeric, plays a role in DNA hypomethylation to reactivate silenced tumor suppressor genes and to present a potential treatment option for AML. Here we show that curcumin down-regulates DNMT1 expression in AML cell lines, both and , and in primary AML cells . Mechanistically, curcumin reduced the expression of positive regulators of DNMT1, p65 and Sp1, which correlated with a reduction in binding of these transcription factors to the DNMT1 promoter in AML cell lines. This curcumin-mediated down-regulation of DNMT1 expression was concomitant with tumor suppressor gene reactivation, hypomethylation of the promoter, G1 cell cycle arrest, and induction of tumor cell apoptosis in vitro. In mice implanted with the human AML MV4-11 cell line, administration of curcumin resulted in remarkable suppression of AML tumor growth. Collectively, our data indicate that curcumin shows promise as a potential treatment for AML, and our findings provide a basis for future studies to test the clinical efficacy of curcumin - whether used as a single agent or as an adjuvant - for AML treatment.
    PLoS ONE 01/2013; 8(2):e55934. · 3.73 Impact Factor
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    ABSTRACT: T cell leukemia/ lymphoma 1 (TCL1) is an oncogene over-expressed in T-cell prolymphocytic leukemia (T-PLL) and in B-cell malignancies including B-CLL and lymphomas. To date, only a limited number of Tcl1 interacting proteins that regulate its oncogenic function have been identified. Prior studies utilized a proteomic approach to identify a novel interaction between Tcl1 with Atm (Ataxia Telangiectasia Mutated). The association of Tcl1 and Atm leads to activation of the NF-κB pathway. Here, we demonstrate that Tcl1 also interacts with Hsp70. The Tcl1-Hsp70 complex was validated by co-immunoprecipitation experiments. Also, we report that heat shock protein 70 (Hsp70), which plays a critical role in the folding and maturation of several oncogenic proteins, associates with Tcl1 protein and stabilizes its expression. The inhibition of the ATPase activity of Hsp70 results in ubiquitination and proteasome-dependent degradation of Tcl1. The inhibition of Hsp70 significantly reduced the growth of lymphoma xenografts in vivo and down-regulated the expression of Tcl1 protein. Our findings reveal a functional interaction between Tcl1 and Hsp70 and identify Tcl1 as a novel Hsp70 client protein. These findings suggest that inhibition of Hsp70 may represent an alternative effective therapy for CLL and lymphomas via its ability to inhibit the oncogenic functions of Tcl1.
    Blood 11/2012; · 9.78 Impact Factor
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    ABSTRACT: Antisense oligonucleotide G3139 is designed for Bcl-2 downregulation and is known to induce toll-like receptor activation. Novel stabilized lipid-polycation-DNA (sLPD) nanoparticles were constructed and evaluated for the delivery of G3139 to human carcinoma KB cells and for bioactivity in vivo. Polyethylenimine (PEI) was incorporated as a DNA condensing agent. The lipid composition used was DOTAP/DDAB/Chol/TPGS/linoleic acid/hexadecenal at molar ratios of 30/30/34/1/5/0.2. The nanoparticles were stabilized by the formation of a reversible covalent bond between the aldehyde group on the cis-11-hexadecenal and amines on the PEI. When sLPDs were used to transfect KB cells, 90.4% Bcl-2 downregulation was observed, compared to no significant downregulation by free G3139 and 54.6% downregulation by nonstabilized LPD-G3139. The sLPDs were then evaluated for therapeutic efficacy in mice bearing KB subcutaneous tumors and were found to trigger a strong antitumor response, inhibiting tumor growth and prolonging survival with 72% increase in lifespan (ILS). Consistent with previous reports on other G3139 nanoparticles, the increased antitumor activities of sLPDs in vivo were found to be associated with increased cytokine induction rather than Bcl-2 downregulation, suggesting an immunological mechanism.
    Molecular Pharmaceutics 03/2011; 8(3):709-15. · 4.57 Impact Factor
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    ABSTRACT: Antisense oligonucleotide G3139-mediated down-regulation of Bcl-2 is a potential strategy for overcoming chemoresistance in leukemia. However, the limited efficacy shown in recent clinical trials calls attention to the need for further development of novel and more efficient delivery systems. In order to address this issue, transferrin receptor (TfR)-targeted, protamine-containing lipid nanoparticles (Tf-LNs) were synthesized as delivery vehicles for G3139. The LNs were produced by an ethanol dilution method, and lipid-conjugated Tf ligand was then incorporated by a postinsertion method. The resulting Tf-LNs had a mean particle diameter of approximately 90 nm and G3139 loading efficiency of 90.4%. Antisense delivery efficiency of Tf-LNs was evaluated in K562, MV4-11, and Raji leukemia cell lines. The results showed that Tf-LNs were more effective than nontargeted LNs and free G3139 (p < 0.05) in decreasing Bcl-2 expression (by up to 62% at the mRNA level in K562 cells) and in inducing caspase-dependent apoptosis. In addition, Bcl-2 down-regulation and apoptosis induced by Tf-LN G3139 were shown to be blocked by excess free Tf and thus were TfR-dependent. Cell lines with higher TfR expression also showed greater Bcl-2 down-regulation. Furthermore, up-regulation of TfR expression in leukemia cells by iron chelator deferoxamine resulted in a further increase in antisense effect (up to 79% Bcl-2 reduction in K562 at the mRNA level) and in caspase-dependent apoptosis (by approximately 3-fold) by Tf-LN. Tf-LN-mediated delivery combined with TfR up-regulation by deferoxamine appears to be a potentially promising strategy for enhancing the delivery efficiency and therapeutic efficacy of antisense oligonucleotides.
    Molecular Pharmaceutics 02/2009; 6(1):221-30. · 4.57 Impact Factor