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1,091 results on '"Issa, Jean-Pierre J."'

206. Methylation of HIN-1, RASSF1A, RIL and CDH13 in breast cancer is associated with clinical characteristics, but only RASSF1A methylation is associated with outcome

Author

Xu Jia, Shetty Priya B, Feng Weiwei, Chenault Carol, Bast Robert C, Issa Jean-Pierre J, Hilsenbeck Susan G, and Yu Yinhua

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background Aberrant promoter CpG island hypermethylation is associated with transcriptional silencing. Tumor suppressor genes are the key targets of hypermethylation in breast cancer and therefore may lead to malignancy by deregulation of cell growth and division. Our previous pilot study with pairs of malignant and normal breast tissues identified correlated methylation of two pairs of genes - HIN-1/RASSFIA and RIL/CDH13 - with expression of estrogen receptors (ER), progesterone receptors (PR), and HER2 (HER2). To determine the impact of methylation on clinical outcome, we have conducted a larger study with breast cancers for which time to first recurrence and overall survival are known. Methods Tumors from 193 patients with early stage breast cancer who received no adjuvant systemic therapy were used to analyze methylation levels of RIL, HIN-1, RASSF1A and CDH13 genes for associations with known predictive and prognostic factors and for impact on time to first recurrence and overall survival. Results In this study, we found that ER was associated with RASSF1A methylation (p p = 0.002). PR was associated with RIL methylation (p = 0.012), HIN-1 (p = 0.002), and RASSF1A methylation (p = 0.019). Tumor size was associated with RIL and CDH13 methylation (both p = 0.002), and S-phase was associated with RIL methylation (p = 0.036). Only RASSF1A was associated with worse time to first recurrence (p = 0.045) and worse overall survival (p = 0.016) after adjusting for age, tumor size, S-phase, estrogen receptor and progesterone receptor. Conclusions Methylation of HIN-1, RASSF1A, RIL and CDH13 in breast cancers was associated with clinical characteristics, but only RASSF1A methylation was associated with time to first recurrence and overall survival. Our data suggest that RASSF1A methylation could be a potential prognostic biomarker.

Published
2012
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207. An Adverse Outcome Pathway Analysis Employing DNA Methylation Effects in Arsenic-Exposed Zebrafish Embryos Supports a Role of Epigenetic Events in Arsenic-Induced Chronic Disease

Author

van der Ven, Leo T.M., Jelinek, Jaroslav, Hodemaekers, Hennie M., Zwart, Edwin P., Ruiter, Sander, van den Brandhof, Evert-Jan, Issa, Jean-Pierre J., Pennings, Jeroen L.A., Luijten, Mirjam, Center for Health Protection, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands., Fels Institute for Cancer Research and Molecular Biology, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania., and Center for Environmental Quality, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.

Published
2018

208. DNA methylation aging clocks: challenges and recommendations

Author

Bell, Christopher G., primary, Lowe, Robert, additional, Adams, Peter D., additional, Baccarelli, Andrea A., additional, Beck, Stephan, additional, Bell, Jordana T., additional, Christensen, Brock C., additional, Gladyshev, Vadim N., additional, Heijmans, Bastiaan T., additional, Horvath, Steve, additional, Ideker, Trey, additional, Issa, Jean-Pierre J., additional, Kelsey, Karl T., additional, Marioni, Riccardo E., additional, Reik, Wolf, additional, Relton, Caroline L., additional, Schalkwyk, Leonard C., additional, Teschendorff, Andrew E., additional, Wagner, Wolfgang, additional, Zhang, Kang, additional, and Rakyan, Vardhman K., additional

Published
2019
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210. Engineering of Chimeric Antigen Receptor T Cells with integrin αEβ7 Results in Augmented Therapeutic Efficacy against E-cadherin positive tumor

Author

Sun, Hongxing, primary, He, Shan, additional, Meng, Lijun, additional, Wang, Ying, additional, Zhang, Hanghang, additional, Liu, Yongnian, additional, Wang, Jian, additional, Tao, Min, additional, Barta, Stefan K., additional, Dulaimi, Essel, additional, Fung, Henry, additional, Issa, Jean-Pierre J., additional, Zheng, Lei-Zhen, additional, and Zhang, Yi, additional

Published
2019
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213. Guadecitabine (SGI-110) in patients with intermediate or high-risk myelodysplastic syndromes: phase 2 results from a multicentre, open-label, randomised, phase 1/2 trial

Author

Garcia-Manero, Guillermo, primary, Roboz, Gail, additional, Walsh, Katherine, additional, Kantarjian, Hagop, additional, Ritchie, Ellen, additional, Kropf, Patricia, additional, O'Connell, Casey, additional, Tibes, Raoul, additional, Lunin, Scott, additional, Rosenblat, Todd, additional, Yee, Karen, additional, Stock, Wendy, additional, Griffiths, Elizabeth, additional, Mace, Joseph, additional, Podoltsev, Nikolai, additional, Berdeja, Jesus, additional, Jabbour, Elias, additional, Issa, Jean-Pierre J, additional, Hao, Yong, additional, Keer, Harold N, additional, Azab, Mohammad, additional, and Savona, Michael R, additional

Published
2019
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214. Abstract WP546: Changes in Promoter Methylation in AIRE1 and ALOX12: Novel Epigenetic Markers in Atherosclerotic Tissues

Author

Shin, Jong Wook, primary, Kim, Jee Yeon Kim, additional, Jelinek, Jaroslav, additional, Hwang, Junha, additional, Jeong, Hye Seon, additional, Kim, Dae Hyun, additional, Cho, Kwangjo, additional, Rha, Seo Hee, additional, Lee, Young Ho, additional, Kim, Geun-Eun, additional, Kwon, Sun U., additional, Cha, Jae Kwan, additional, Issa, Jean-Pierre J., additional, and Kim, Jei, additional

Published
2019
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217. Accelerated aging in normal breast tissue of women with breast cancer.

Author

Panjarian, Shoghag, Madzo, Jozef, Keith, Kelsey, Slater, Carolyn M., Sapienza, Carmen, Jelinek, Jaroslav, and Issa, Jean-Pierre J.

Subjects
BREAST cancer, CANCER treatment, CELL-free DNA, DNA methylation, ANOMALY detection (Computer security)
Abstract

Background: DNA methylation alterations have similar patterns in normal aging tissue and in cancer. In this study, we investigated breast tissue-specific age-related DNA methylation alterations and used those methylation sites to identify individuals with outlier phenotypes. Outlier phenotype is identified by unsupervised anomaly detection algorithms and is defined by individuals who have normal tissue age-dependent DNA methylation levels that vary dramatically from the population mean.Methods: We generated whole-genome DNA methylation profiles (GSE160233) on purified epithelial cells and used publicly available Infinium HumanMethylation 450K array datasets (TCGA, GSE88883, GSE69914, GSE101961, and GSE74214) for discovery and validation.Results: We found that hypermethylation in normal breast tissue is the best predictor of hypermethylation in cancer. Using unsupervised anomaly detection approaches, we found that about 10% of the individuals (39/427) were outliers for DNA methylation from 6 DNA methylation datasets. We also found that there were significantly more outlier samples in normal-adjacent to cancer (24/139, 17.3%) than in normal samples (15/228, 5.2%). Additionally, we found significant differences between the predicted ages based on DNA methylation and the chronological ages among outliers and not-outliers. Additionally, we found that accelerated outliers (older predicted age) were more frequent in normal-adjacent to cancer (14/17, 82%) compared to normal samples from individuals without cancer (3/17, 18%). Furthermore, in matched samples, we found that the epigenome of the outliers in the pre-malignant tissue was as severely altered as in cancer.Conclusions: A subset of patients with breast cancer has severely altered epigenomes which are characterized by accelerated aging in their normal-appearing tissue. In the future, these DNA methylation sites should be studied further such as in cell-free DNA to determine their potential use as biomarkers for early detection of malignant transformation and preventive intervention in breast cancer. [ABSTRACT FROM AUTHOR]

Published
2021
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222. Increased cytosine DNA-methyltransferase activity during colon cancer progression

Author

Issa, Jean-Pierre J., Vertino, Paula M., Wu Jianjun, Sazawal, Sudha, Celano, Paul, Nelkin, Barry D., Hamilton, Stanley R., and Baylin, Stephen B.

Subjects
Colorectal cancer -- Development and progression, Cytosine -- Measurement, Methyltransferases -- Measurement, Methylation -- Physiological aspects, Health
Abstract

Background. Molecular changes during progressive stages of colon cancer and other human tumors commonly involve altered regulation of DNA methylation. These changes include overall genomic hypomethylation, regional hypermethylation, and increased levels of messenger RNA (mRNA) for cytosine DNA-methyl-transferase (DNA-MTase), the enzyme that catalyzes DNA methylation at CpG (cytosine-phosphoguanine) sites. This increase in DNA-MTase transcripts (mRNA), if accompanied by increased DNA-MTase activity, could play a role in the abnormal DNA methylation patterns that appear early in colon tumor progression. Purpose: We sought to determine whether increased DNA-MTase mRNA levels during colon cancer progression are associated with increased cellular DNA-MTase enzymatic activity. Methods: We adapted a microassay for DNA-MTase and used it to measure activity in human colon carcinoma and in colon mucosa of normal control subjects and of patients with colon cancer or with familial adenomatous polyposis (FAP), which is a risk factor for colon cancer. Steady-state DNA-MTase gene transcripts were measured by a reverse transcriptase polymerase chain reaction assay. To compare DNA-MTase activity with mRNA levels, we determined both variables simultaneously for one colon cancer specimen, its adjacent mucosa, and the colon mucosa of a control patient and compared the values. Results: Compared with DNA-MTase activity in mucosa from normal control subjects, activity was elevated 1.4-fold in FAP mucosa, 1.6-fold in the uninvolved mucosa of patients with cancer, and 5.4-fold in the cancer specimens. All these differences were statistically significant. Fourteen of 15 cancer samples and 47% of the uninvolved adjacent mucosa samples had values that were higher than the highest value in normal mucosa. In one patient who had both a benign adenomatous polyp and a malignant adenocarcinoma, increasing DNA-MTase activity was observed at each stage of tumor progression. Conclusion: These results demonstrate that an increased DNA methylation capacity accompanies the increase in DNA-MTase transcripts observed during progressive stages of colon cancer. Implication: Further studies are needed to determine whether this abnormal methylation capacity plays a role in establishing the abnormal DNA methylation patterns seen in human malignancies. [J Natl Cancer Inst 85:1235-1240, 1993]

Published
1993

223. An Adverse Outcome Pathway analysis employing DNA methylation effects in arsenic-exposed zebrafish embryos supports a role of epigenetic events in arsenic-induced chronic disease

Author

van der Ven, Leo TM, Jelinek, Jaroslav, Hodemaekers, Hennie M, Zwart, Edwin P, Ruiter, Sander, Brandhof, Evert-Jan, Issa, Jean-Pierre J, Pennings, Jeroen LA, and Luijten, Mirjam

Abstract

Introduction There is a need to identify processes underlying development of chemically induced chronic disease in humans, preferably describing key events and their relationships in an Adverse Outcome Pathway analysis. Epigenetic modifications, and particularly DNA methylation effects, have been implicated as a major event in susceptibility to develop chronic disease. Arsenic is a known toxicant to which large human populations around the world are exposed through drinking water and industrial activities, and the role of epigenetic events in arsenic induced chronic disease has been suggested in multiple cases. Materials and Methods In this paper, arsenic was used as a case to design an epigenetics-based Adverse Outcome Pathway framework, and to provide further support through detecting effects on DNA methylation in zebrafish embryos, which have the advantage of an alternative whole organism model including the complete array of potential target tissues and their interactions. Four targets derived from literature, i.e. HOXB5, HOXB9, TP53, and PAPP2c, followed by a genome wide methylation analysis method, DREAM, and subsequent pyrosequencing verification. Results The four literature targets all showed very low baseline methylation, and notably HOXB5 and PAPP2c showed arsenic induced DNA methylation effects in extracts of 72 hpf arsenite exposed whole embryos. DREAM identified hypermethylation in four additional specific DNA sites, i.e. cbll1, cwc27, mvb12bb, and ybx1, which could all be related to specific cellular functions with relevance to carcinogenesis. Conclusion Altogether, through pathway analysis complemented with DNA methylation analysis in zebrafish embryos, the observations in this study adds to weight of evidence for the relation between arsenic-induced epigenetic effects and late-onset disease, specifically cancer.

Published
2017

226. Targeting CDK9 Reactivates Epigenetically Silenced Genes in Cancer

Author

Zhang, Hanghang, primary, Pandey, Somnath, additional, Travers, Meghan, additional, Sun, Hongxing, additional, Morton, George, additional, Madzo, Jozef, additional, Chung, Woonbok, additional, Khowsathit, Jittasak, additional, Perez-Leal, Oscar, additional, Barrero, Carlos A., additional, Merali, Carmen, additional, Okamoto, Yasuyuki, additional, Sato, Takahiro, additional, Pan, Joshua, additional, Garriga, Judit, additional, Bhanu, Natarajan V., additional, Simithy, Johayra, additional, Patel, Bela, additional, Huang, Jian, additional, Raynal, Noël J.-M., additional, Garcia, Benjamin A., additional, Jacobson, Marlene A., additional, Kadoch, Cigall, additional, Merali, Salim, additional, Zhang, Yi, additional, Childers, Wayne, additional, Abou-Gharbia, Magid, additional, Karanicolas, John, additional, Baylin, Stephen B., additional, Zahnow, Cynthia A., additional, Jelinek, Jaroslav, additional, Graña, Xavier, additional, and Issa, Jean-Pierre J., additional

Published
2018
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228. Abstract 2952: Targeting CDK9 reactivates epigenetically silenced genes in cancer

Author

Zhang, Hanghang, primary, Pandey, Somnath, additional, Travers, Meghan, additional, Khowsathit, Jittasak, additional, Morton, George, additional, Sum, Hongxing, additional, Barrero, Carlos A., additional, Merali, Carmen, additional, Okamoto, Yasuyuki, additional, Sato, Takahiro, additional, Garriga, Judit, additional, Bhanu, Natarajan V., additional, Simithy, Johayra, additional, Patel, Bela, additional, Madzo, Jozef, additional, Raynal, Noël, additional, Garcia, Benjamin A., additional, Jacobson, Marlene A., additional, Merali, Salim, additional, Zhang, Yi, additional, Childers, Wayne, additional, Abou-Gharbia, Magid, additional, Karanicolas, John, additional, Baylin, Stephen B., additional, Zahnow, Cynthia A., additional, Jelinek, Jaroslav, additional, Graña, Xavier, additional, and Issa, Jean-Pierre J., additional

Published
2018
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235. An Adverse Outcome Pathway Analysis Employing DNA Methylation Effects in Arsenic-Exposed Zebrafish Embryos Supports a Role of Epigenetic Events in Arsenic-Induced Chronic Disease

Author

van der Ven, Leo T.M., primary, Jelinek, Jaroslav, additional, Hodemaekers, Hennie M., additional, Zwart, Edwin P., additional, Ruiter, Sander, additional, van den Brandhof, Evert-Jan, additional, Issa, Jean-Pierre J., additional, Pennings, Jeroen L.A., additional, and Luijten, Mirjam, additional

Published
2017
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236. Guadecitabine (SGI-110) in treatment-naive patients with acute myeloid leukaemia: phase 2 results from a multicentre, randomised, phase 1/2 trial

Author

Kantarjian, Hagop M, primary, Roboz, Gail J, additional, Kropf, Patricia L, additional, Yee, Karen W L, additional, O'Connell, Casey L, additional, Tibes, Raoul, additional, Walsh, Katherine J, additional, Podoltsev, Nikolai A, additional, Griffiths, Elizabeth A, additional, Jabbour, Elias, additional, Garcia-Manero, Guillermo, additional, Rizzieri, David, additional, Stock, Wendy, additional, Savona, Michael R, additional, Rosenblat, Todd L, additional, Berdeja, Jesus G, additional, Ravandi, Farhad, additional, Rock, Edwin P, additional, Hao, Yong, additional, Azab, Mohammad, additional, and Issa, Jean-Pierre J, additional

Published
2017
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237. Caloric restriction delays age-related methylation drift

Author

Maegawa, Shinji, primary, Lu, Yue, additional, Tahara, Tomomitsu, additional, Lee, Justin T., additional, Madzo, Jozef, additional, Liang, Shoudan, additional, Jelinek, Jaroslav, additional, Colman, Ricki J., additional, and Issa, Jean-Pierre J., additional

Published
2017
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239. Abstract 5064: Identifying novel potential epigenetic anti-cancer drugs from natural compounds using a phenotypic-based screening

Author

Zhang, Hanghang, primary, Raynal, Noël J.-M, additional, Sato, Takahiro, additional, Okamoto, Yasuyuki, additional, Garriga, Judith, additional, Garcia, Benjamin, additional, Morton, George, additional, Childers, Wayne, additional, Jacobson, Marlene A., additional, Baylin, Stephen B., additional, Graña, Xavier, additional, Abou-Gharbia, Magid, additional, and Issa, Jean-Pierre J., additional

Published
2017
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246. Transcriptional Selectivity of Epigenetic Therapy in Cancer

Author

Sato, Takahiro, primary, Cesaroni, Matteo, additional, Chung, Woonbok, additional, Panjarian, Shoghag, additional, Tran, Anthony, additional, Madzo, Jozef, additional, Okamoto, Yasuyuki, additional, Zhang, Hanghang, additional, Chen, Xiaowei, additional, Jelinek, Jaroslav, additional, and Issa, Jean-Pierre J., additional

Published
2017
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248. Distinct genetic profiles in colorectal tumors with or without the CpG island methylator phenotype

Author

Toyota, Minoru, Ohe-Toyota, Mutsumi, Ahuja, Nita, and Issa, Jean-Pierre J.

Subjects
Colorectal cancer -- Causes of, Gene mutations -- Research, Oncogenes -- Research, Science and technology
Abstract

Colorectal cancers (CRCs) are characterized by multiple genetic (mutations) and epigenetic (CpG island methylation) alterations, but it is not known whether these evolve independently through stochastic processes. We have recently described a novel pathway termed CpG island methylator phenotype (CIMP) in CRC, which is characterized by the simultaneous methylation of multiple CpG islands, including several known genes, such as p16, hMLH1, and THBS1. We have now studied mutations in K-RAS, p53, DPC4, and TGF[bETA]JII in a panel of colorectal tumors with or without CIMP. We find that CIMP defines two groups of tumors with significantly different genetic lesions: frequent K-RAS mutations were found in [CIMP.sup.+] CRCs (28/41, 68%) compared with CIMP- cases (14/47, 30%, P = 0.0005). By contrast, p53 mutations were found in 24% (10/41) of [CIMP.sup.+] CRCs vs. 60% (30/46) of CIMP- cases (P = 0.002). Both of these differences were independent of microsatellite instability. These interactions between CIMP, K-RAS mutations, and p53 mutations were preserved in colorectal adenomas, suggesting that they occur early in carcinogenesis. The distinct combinations of epigenetic and genetic alterations in each group suggest that activation of oncogenes and inactivation of tumor suppressor genes is related to the underlying mechanism of generating molecular diversity in cancer, rather than simply accumulate stochastically during cancer development.

Published
2000

249. Epigenetics in cancer: what's the future?

Author

Boumber, Yanis and Issa, Jean-Pierre J.

Subjects
Gene expression, DNA, Methylation, Cancer -- Genetic aspects -- Development and progression -- Drug therapy -- Chemotherapy, Chemotherapy, Health, Zolinza (Medication), Dacogen (Medication), Vidaza (Medication), Istodax (Medication)
Abstract

Epigenetics is a rapidly expanding field that focuses on stable changes in gene expression that are not accompanied by changes in DNA sequence and that are mediated primarily by DNA methylation and histone modifications. Disruption of the epigenome is a fundamental mechanism in cancer, and several epigenetic drugs that have proved to prolong survival and to be less toxic than conventional chemotherapy were recently approved by the FDA for cancer treatment. These include azacitidine (Vidaza), decitabine (Dacogen), vorinostat (Zolinza), and romidepsin (Istodax). Promising results of combination clinical trials with DNA methylation inhibitors and histone deacetylase inhibitors have recently been reported, and data are emerging that describe molecular determinants of clinical responses. Despite significant advances, challenges remain, including a lack of predictive markers, unclear mechanisms of response and resistance, and rare responses in solid tumors. Preclinical studies are ongoing with novel classes of agents that target various components of the epigenetic machinery. In this review, we focus on recent clinical and translational data in the epigenetics field that have potential in cancer therapy., Epigenetics is defined as the study of stable changes in gene expression that are not accompanied by changes in DNA sequence. [1] Epigenetic changes are important biological processes with relevance [...]

Published
2011

250. Genome architecture marked by retrotransposons modulates predisposition to DNA methylation in cancer

Author

Estecio, Marcos R.H., Gallegos, Juan, Vallot, Celine, Castoro, Ryan J., Chung, Woonbok, Maegawa, Shinji, Oki, Yasuhiro, Kondo, Yutaka, Jelinek, Jaroslav, Lanlan Shen, Hartung, Helge, Aplan, Peter D., Czerniak, Bogdan A., Shoudan Liang, and Issa, Jean-Pierre J.

Subjects
DNA -- Structure, DNA -- Chemical properties, Gene silencing -- Analysis, Methylation -- Analysis, Retrotransposons -- Research, Cancer -- Genetic aspects, Cancer -- Research, Health
Published
2010

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