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9 results on '"Szyf, Moshe"'

2. Preclinical optimization of a broad-spectrum anti-bladder cancer tri-drug regimen via the Feedback System Control (FSC) platform.

Author

Liu, Qi, Zhang, Cheng, Ding, Xianting, Deng, Hui, Zhang, Daming, Cui, Wei, Xu, Hongwei, Wang, Yingwei, Xu, Wanhai, Lv, Lei, Zhang, Hongyu, He, Yinghua, Wu, Qiong, Szyf, Moshe, Ho, Chih-Ming, and Zhu, Jingde

Subjects
Cell Line, Tumor, Animals, Humans, Mice, Disease Models, Animal, Antineoplastic Agents, Antineoplastic Combined Chemotherapy Protocols, Drug Therapy, Combination, Tumor Burden, Drug Evaluation, Preclinical, Xenograft Model Antitumor Assays, Signal Transduction, Cell Survival, Drug Resistance, Neoplasm, Models, Theoretical, Urinary Bladder Neoplasms, Cancer, Breast Cancer, Biotechnology, Urologic Diseases, 5.1 Pharmaceuticals, Cell Line, Tumor, Disease Models, Animal, Drug Therapy, Combination, Drug Evaluation, Preclinical, Drug Resistance, Neoplasm, Models, Theoretical, Biochemistry and Cell Biology, Other Physical Sciences
Abstract

Therapeutic outcomes of combination chemotherapy have not significantly advanced during the past decades. This has been attributed to the formidable challenges of optimizing drug combinations. Testing a matrix of all possible combinations of doses and agents in a single cell line is unfeasible due to the virtually infinite number of possibilities. We utilized the Feedback System Control (FSC) platform, a phenotype oriented approach to test 100 options among 15,625 possible combinations in four rounds of assaying to identify an optimal tri-drug combination in eight distinct chemoresistant bladder cancer cell lines. This combination killed between 82.86% and 99.52% of BCa cells, but only 47.47% of the immortalized benign bladder epithelial cells. Preclinical in vivo verification revealed its markedly enhanced anti-tumor efficacy as compared to its bi- or mono-drug components in cell line-derived tumor xenografts. The collective response of these pathways to component drugs was both cell type- and drug type specific. However, the entire spectrum of pathways triggered by the tri-drug regimen was similar in all four cancer cell lines, explaining its broad spectrum killing of BCa lines, which did not occur with its component drugs. Our findings here suggest that the FSC platform holds promise for optimization of anti-cancer combination chemotherapy.

Published
2015

6. Rescue of Early bace-1 and Global DNA Demethylation by S-Adenosylmethionine Reduces Amyloid Pathology and Improves Cognition in an Alzheimer’s Model

Author

Do Carmo, Sonia, primary, Hanzel, Cecilia E., additional, Jacobs, Marie L., additional, Machnes, Ziv, additional, Iulita, M. Florencia, additional, Yang, Jingyun, additional, Yu, Lei, additional, Ducatenzeiler, Adriana, additional, Danik, Marc, additional, Breuillaud, Lionel S., additional, Bennett, David A., additional, Szyf, Moshe, additional, and Cuello, A. Claudio, additional

Published
2016
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7. Human leukocyte telomere length is associated with DNA methylation levels in multiple subtelomeric and imprinted loci

Author

Buxton, Jessica L., Suderman, Matthew, Pappas, Jane J., Borghol, Nada, McArdle, Wendy, Blakemore, Alexandra I. F., Hertzman, Clyde, Power, Christine, Szyf, Moshe, and Pembrey, Marcus

Subjects
Adult, Male, TISSUES, Adolescent, Article, DISEASE, Genomic Imprinting, Young Adult, Leukocytes, Cluster Analysis, Humans, OXIDATIVE STRESS, SHORTENS TELOMERES, POSITION, Child, Promoter Regions, Genetic, health care economics and organizations, Binding Sites, Science & Technology, MULTIDISCIPLINARY SCIENCES, Infant, Newborn, Infant, Telomere Homeostasis, DNA Methylation, Middle Aged, Telomere, VIABILITY, DYSFUNCTION, DNA-Binding Proteins, Repressor Proteins, INSIGHTS, SENESCENCE, Child, Preschool, CELLS, Science & Technology - Other Topics, CpG Islands, Transcription Initiation Site, biological, Protein Binding, Signal Transduction, Transcription Factors
Abstract

In humans, leukocyte telomere length (LTL) is positively correlated with lifespan, and shorter LTL is associated with increased risk of age-related disease. In this study we tested for association between telomere length and methylated cytosine levels. Measurements of mean telomere length and DNA methylation at .450,000 CpG sites were obtained for both blood (N 5 24) and EBV-transformed cell-line (N 5 36) DNA samples from men aged 44–45 years. We identified 65 gene promoters enriched for CpG sites at which methylation levels are associated with leukocyte telomere length, and 36 gene promoters enriched for CpG sites at which methylation levels are associated with telomere length in DNA from EBV-transformed cell-lines.Weobserved significant enrichment of positively associated methylated CpG sites in subtelomeric loci (within 4 Mb of the telomere) (P , 0.01), and also at loci in imprinted regions (P , 0.001). Our results pave the way for further investigations to help elucidate the relationships between telomere length, DNA methylation and gene expression in health and disease. The Section of Investigative Medicine at Imperial College London is funded by grants from the MRC, BBSRC, NIHR, an Integrative Mammalian Biology (IMB) Capacity Building Award, and FP7- HEALTH- 2009- 241592 EuroCHIP grant and is supported by the NIHR www.nature.com/scientificreports SCIENTIFIC REPORTS | 4 : 4954 | DOI: 10.1038/srep04954 7 Imperial Biomedical Research Centre Funding Scheme. For the 1958 Birth Cohort samples, venous blood collection was funded by the UK Medical Research Council (G0000934) and cell-line production, DNA extraction and processing by the Wellcome Trust (068545/Z/ 02). MS was supported by a grant from the Canadian Institute for Health Research MOP-42411. This work was also funded by aWellcome Trust programme grant 072937/Z/ 03/Z awarded to MP, and a Wellcome Trust fellowship grant, WT088431MA, held by JLB.

Published
2014
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