Biomedical subjects

Stephen Baylin

Publications and source records attributed to Stephen Baylin.

3 recordsLinked to original sources

PubMed2007

The sociobiologic integrative model (SBIM): enhancing the integration of sociobehavioral, environmental, and biomolecular knowledge in urban health and disparities research.

Disentangling the myriad determinants of disease, within the context of urban health or health disparities, requires a transdisciplinary approach. Transdisciplinary approaches draw on concepts from multiple scientific disciplines to develop a novel, integrated perspective from which to conduct scientific investigation. Most historic and contemporary conceptual models of health were derived either from the sociobehavioral sciences or the biomolecular sciences. Those models deriving from the sociobehavioral sciences generally lack detail on involved biological mechanisms whereas those derived from the biomolecular sciences largely do not consider socioenvironmental determinants. As such, advances in transdisciplinary characterizations of health in complex systems like the urban environment or health disparities may be impeded. This paper suggests a sociobiologic organizing model that encourages a multilevel, integrative perspective in the study of urban health and health disparities.

Causality↗

PubMed2006

Combined DNA methyltransferase and histone deacetylase inhibition in the treatment of myeloid neoplasms.

Optimal reexpression of most genes silenced through promoter methylation requires the sequential application of DNA methyltransferase inhibitors followed by histone deacetylase inhibitors in tumor cell cultures. Patients with myelodysplastic syndrome or acute myeloid leukemia (AML) were treated with the methyltransferase inhibitor 5-azacitidine (aza-CR) followed by the histone deacetylase inhibitor sodium phenylbutyrate. Major responses associated with cytogenetic complete response developed in patients receiving prolonged dosing schedules of aza-CR. Bisulfite sequencing of the p15 promoter in marrow DNA during the first cycle of treatment showed heterogeneous allelic demethylation in three responding patients, suggesting ongoing demethylation within the tumor clone, but no demethylation in two nonresponders. Six of six responding patients with pretreatment methylation of p15 or CDH-1 promoters reversed methylation during the first cycle of therapy (methylation-specific PCR), whereas none of six nonresponders showed any demethylation. Gene demethylation correlated with the area under the aza-CR plasma concentration-time curve. Administration of both drugs was associated with induction of acetylation of histones H3 and H4. This study provides the first demonstration that molecular mechanisms responsible for responses to DNA methyltransferase/histone deacetylase inhibitor combinations may include reversal of aberrant epigenetic gene silencing. The promising percentage of major hematologic responses justifies the testing of such combinations in prospective randomized trials.

Acetylation↗

PubMed2002

Altered methylation patterns in cancer cell genomes: cause or consequence?

CpG islands are associated with at least half of all cellular genes and are normally methylation-free. Dense methylation of cytosine residues within islands causes strong and heritable transcriptional silencing. Such silencing normally occurs almost solely at genes subject to genomic imprinting or to X chromosome inactivation. Aberrant methylation of CpG islands associated with tumor suppressor genes has been proposed to contribute to carcinogenesis. However, questions of mechanisms underlying the cancer changes and the precise consequences for tumorigenesis exist in the field, and must continue to be addressed before the importance of abnormalities in genomic methylation patterns in carcinogenesis can be fully understood. In this article, two workers in DNA methylation, one concentrating on cancer biology and the other on developmental biology, address recurrent questions about cancer epigenetics from different perspectives. The goal is to highlight important controversies in the field which can be productive targets of ongoing and future research.

Animals↗