Jonathan C. Cheng
University of Southern California
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Featured researches published by Jonathan C. Cheng.
Clinical Cancer Research | 2004
Martin G. Friedrich; Daniel J. Weisenberger; Jonathan C. Cheng; Shahin Chandrasoma; Kimberly D. Siegmund; Mark L. Gonzalgo; Marieta Toma; Hartwig Huland; Christine B. Yoo; Yvonne C. Tsai; Peter W. Nichols; Bernard H. Bochner; Peter A. Jones; Gangning Liang
Purpose: There is increasing evidence for a fundamental role for epigenetic silencing of apoptotic pathways in cancer. Changes in DNA methylation can be detected with a high degree of sensitivity, so we used the MethyLight assay to determine how methylation patterns of apoptosis-associated genes change during bladder carcinogenesis and whether DNA methylation could be detected in urine sediments. Experimental Design: We analyzed the methylation status of the 5′ regions of 12 apoptosis-associated genes (ARF, FADD, TNFRSF21, BAX, LITAF, DAPK, TMS-1, BCL2, RASSF1A, TERT, TNFRSF25, and EDNRB) in 18 bladder cancer cell lines, 127 bladder cancer samples, and 37 samples of adjacent normal bladder mucosa using the quantitative MethyLight assay. We also analyzed the methylation status in urine sediments of 20 cancer-free volunteers and 37 bladder cancer patients. Results: The 5′ regions of DAPK, BCL2, TERT, RASSFIA, and TNFRSF25 showed significant increases in methylation levels when compared with nonmalignant adjacent tissue (P ≤ 0.01). Methylation levels of BCL2 were significantly associated with tumor staging and grading (P ≤ 0.01), whereas methylation levels of RASSF1A and ARF were only associated with tumor stage (P ≤ 0.04), and TERT methylation and EDNRB methylation were predictors of tumor grade (P ≤ 0.02). To investigate clinical usefulness for noninvasive bladder cancer detection, we further analyzed the methylation status of the markers in urine samples of patients with bladder cancer. Methylation of DAPK, BCL2, and TERT in urine sediment DNA from bladder cancer patients was detected in the majority of samples (78%), whereas they were unmethylated in the urine sediment DNA from age-matched cancer-free individuals. Conclusions: Our results indicate that methylation of the 5′ region of apoptosis-associated genes is a common finding in patients with bladder carcinoma. The ability to detect methylation not only in bladder tissue, but also in urine sediments, suggests that methylation markers are promising tools for noninvasive detection of bladder cancers. Our results also indicate that some methylation markers, such as those in regions of RASSF1A and TNFRSF25, might be of limited use for detection because they are also methylated in normal bladder tissues.
Molecular and Cellular Biology | 2004
Jonathan C. Cheng; Daniel J. Weisenberger; Felicidad A. Gonzales; Gangning Liang; Guo-Liang Xu; Ye-Guang Hu; Victor E. Marquez; Peter A. Jones
ABSTRACT During tumorigenesis, tumor suppressor and cancer-related genes are commonly silenced by aberrant DNA methylation in their promoter regions. Recently, we reported that zebularine [1-(β-d-ribofuranosyl)-1,2-dihydropyrimidin-2-one] acts as an inhibitor of DNA methylation and exhibits chemical stability and minimal cytotoxicity both in vitro and in vivo. Here we show that continuous application of zebularine to T24 cells induces and maintains p16 gene expression and sustains demethylation of the 5′ region for over 40 days, preventing remethylation. In addition, continuous zebularine treatment effectively and globally demethylated various hypermethylated regions, especially CpG-poor regions. The drug caused a complete depletion of extractable DNA methyltransferase 1 (DNMT1) and partial depletion of DNMT3a and DNMT3b3. Last, sequential treatment with 5-aza-2′-deoxycytidine followed by zebularine hindered the remethylation of the p16 5′ region and gene resilencing, suggesting the possible combination use of both drugs as a potential anticancer regimen.
Annals of the New York Academy of Sciences | 2005
Victor E. Marquez; James A. Kelley; Riad Agbaria; Tisipi Ben‐Kasus; Jonathan C. Cheng; Christine B. Yoo; Peter A. Jones
1‐(β‐d‐ribofuranosyl)‐1,2‐dihydropyrimidin‐2‐one (zebularine) corresponds structurally to cytidine minus the exocyclic 4‐amino group. The increased electrophilic character of its simple aglycon endows the molecule with unique biologic properties as a potent inhibitor of both cytidine deaminase and DNA cytosine methyltransferase. The latter activity makes zebularine a promising antitumor agent that is hydrolytically stable, preferentially targets cancer cells, and shows activity both in vitro and in experimental animals, even after oral administration.
Nucleosides, Nucleotides & Nucleic Acids | 2005
Victor E. Marquez; Joseph J. Barchi; James A. Kelley; Kambhampati V. R. Rao; Riad Agbaria; Tsipi Ben-Kasus; Jonathan C. Cheng; Christine B. Yoo; Peter A. Jones
1-(β-D-ribofuranosyl)-1,2-dihydropyrimidin-2-one (zebularine) is structurally 4-deamino cytidine. The increased electrophilic character of this simple aglycon endows the molecule with unique chemical and biological properties, making zebularine a versatile starting material for the synthesis of complex nucleosides and an effective inhibitor of cytidine deaminase and DNA cytosine methyltransferase. Zebularine is a stable, antitumor agent that preferentially targets cancer cells and shows activity both in vitro and in experimental animals, even after oral administration.
Journal of the National Cancer Institute | 2003
Jonathan C. Cheng; Cindy B. Matsen; Felicidad A. Gonzales; Wei Ye; Sheldon Greer; Victor E. Marquez; Peter A. Jones; Eric U. Selker
Proceedings of the National Academy of Sciences of the United States of America | 2004
Gangning Liang; Joy C. Lin; Vivian Wei; Christine B. Yoo; Jonathan C. Cheng; Carvell T. Nguyen; Daniel J. Weisenberger; Gerda Egger; Daiya Takai; Felicidad A. Gonzales; Peter A. Jones
Cancer Cell | 2004
Jonathan C. Cheng; Christine B. Yoo; Daniel J. Weisenberger; Jody C. Chuang; Chandra Wozniak; Gangning Liang; Victor E. Marquez; Sheldon Greer; Torben F. Ørntoft; Thomas Thykjaer; Peter A. Jones
Biochemical Society Transactions | 2004
Christine B. Yoo; Jonathan C. Cheng; Peter A. Jones
Molecular Cancer Research | 2004
Daniel J. Weisenberger; Mihaela Velicescu; Jonathan C. Cheng; Felicidad A. Gonzales; Gangning Liang; Peter A. Jones
European Journal of Cancer | 2005
Martin G. Friedrich; Shahin Chandrasoma; Kimberly D. Siegmund; Daniel J. Weisenberger; Jonathan C. Cheng; Marieta Toma; Hartwig Huland; Peter A. Jones; Gangning Liang