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Dive into the research topics where Jonathan C. Cheng is active.

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Featured researches published by Jonathan C. Cheng.


Clinical Cancer Research | 2004

Detection of methylated apoptosis-associated genes in urine sediments of bladder cancer patients.

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

Continuous Zebularine Treatment Effectively Sustains Demethylation in Human Bladder Cancer Cells

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

Zebularine: A Unique Molecule for an Epigenetically Based Strategy in Cancer Chemotherapy

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

ZEBULARINE: A UNIQUE MOLECULE FOR AN EPIGENETICALLY BASED STRATEGY IN CANCER CHEMOTHERAPY. THE MAGIC OF ITS CHEMISTRY AND BIOLOGY

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

Inhibition of DNA Methylation and Reactivation of Silenced Genes by Zebularine

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

Distinct localization of histone H3 acetylation and H3-K4 methylation to the transcription start sites in the human genome

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

Preferential response of cancer cells to zebularine

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

Zebularine: a new drug for epigenetic therapy

Christine B. Yoo; Jonathan C. Cheng; Peter A. Jones


Molecular Cancer Research | 2004

Role of the DNA methyltransferase variant DNMT3b3 in DNA methylation.

Daniel J. Weisenberger; Mihaela Velicescu; Jonathan C. Cheng; Felicidad A. Gonzales; Gangning Liang; Peter A. Jones


European Journal of Cancer | 2005

Prognostic relevance of methylation markers in patients with non-muscle invasive bladder carcinoma

Martin G. Friedrich; Shahin Chandrasoma; Kimberly D. Siegmund; Daniel J. Weisenberger; Jonathan C. Cheng; Marieta Toma; Hartwig Huland; Peter A. Jones; Gangning Liang

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Gangning Liang

University of Southern California

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Daniel J. Weisenberger

University of Southern California

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Christine B. Yoo

University of Southern California

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Victor E. Marquez

National Institutes of Health

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Felicidad A. Gonzales

University of Southern California

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Kimberly D. Siegmund

University of Southern California

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