Columbus, OH, United States
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Harshman S.W.,Ohio State University | Harshman S.W.,Arthur mes Comprehensive Cancer Center | Young N.L.,Florida State University | Parthun M.R.,Arthur mes Comprehensive Cancer Center | And 3 more authors.
Nucleic Acids Research | Year: 2013

H1 and related linker histones are important both for maintenance of higher-order chromatin structure and for the regulation of gene expression. The biology of the linker histones is complex, as they are evolutionarily variable, exist in multiple isoforms and undergo a large variety of posttranslational modifications in their long, unstructured, NH2-and COOH-terminal tails. We review recent progress in understanding the structure, genetics and posttranslational modifications of linker histones, with an emphasis on the dynamic interactions of these proteins with DNA and transcriptional regulators. We also discuss various experimental challenges to the study of H1 and related proteins, including limitations of immunological reagents and practical difficulties in the analysis of posttranslational modifications by mass spectrometry. © The Author(s) 2013. Published by Oxford University Press.

Blum K.A.,Arthur mes Comprehensive Cancer Center | Liu Z.,Ohio State University | Lucas D.M.,Arthur mes Comprehensive Cancer Center | Lucas D.M.,Ohio State University | And 16 more authors.
British Journal of Haematology | Year: 2010

Targeting aberrant DNA hypermethylation in chronic lymphocytic leukaemia (CLL) and non-Hodgkin lymphoma (NHL) with decitabine may reverse epigenetic silencing in B-cell malignancies. Twenty patients were enrolled in two phase I trials to determine the minimum effective pharmacological dose of decitabine in patients with relapsed/refractory CLL (n = 16) and NHL (n = 4). Patients received 1-3 cycles of decitabine. Dose-limiting toxicity (DLT) was observed in 2 of 4 CLL and 2 of 2 NHL patients receiving decitabine at 15 mg/m2 per d days 1-10, consisting of grade 3-4 thrombocytopenia and hyperbilirubinaemia. Six patients with CLL received decitabine at 10 mg/m 2 per d days 1-10 without DLT; however, re-expression of methylated genes or changes in global DNA methylation were not observed. Therefore, a 5-day decitabine schedule was examined. With 15 mg/m2 per d decitabine days 1-5, DLT occurred in 2 of 6 CLL and 2 of 2 NHL patients, consisting of grade 3-4 neutropenia, thrombocytopenia, and febrile neutropenia. Eight patients had stable disease. In 17 patients, there were no significant changes in genome-wide methylation or in target gene re-expression. In conclusion, dose-limiting myelosuppression and infectious complications prevented dose escalation of decitabine to levels associated with changes in global methylation or gene re-expression in CLL and NHL. © 2010 Blackwell Publishing Ltd.

Onesti J.K.,Ohio State University | Onesti J.K.,Arthur mes Comprehensive Cancer Center | Guttridge D.C.,Arthur mes Comprehensive Cancer Center | Guttridge D.C.,Ohio State University
BioMed Research International | Year: 2014

Cancer cachexia, consisting of significant skeletal muscle wasting independent of nutritional intake, is a major concern for patients with solid tumors that affects surgical, therapeutic, and quality of life outcomes. This review summarizes the clinical implications, background of inflammatory cytokines, and the origin and sources of procachectic factors including TNF- α, IL-6, IL-1, INF- γ, and PIF. Molecular mechanisms and pathways are described to elucidate the link between the immune response caused by the presence of the tumor and the final result of skeletal muscle wasting. © 2014 Jill K. Onesti and Denis C. Guttridge.

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