Transcription factors (TFs) control the levels as well as the sites and times of expression of a discrete set of target genes by binding to specific cis-regulatory elements in the corresponding promoter regions. They ...
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Transcription factors (TFs) control the levels as well as the sites and times of expression of a discrete set of target genes by binding to specific cis-regulatory elements in the corresponding promoter regions. They can function as master control switches for the regulation of metabolic pathways, cell differentiation and the cell cycle. Thus, the state of a living cell is the result of regulated transcription of thousands of genes in which TFs are major players. A first step in the discovering the regulatory networks is to establish the organization of cis-elements in promoters and the direct targets of TFs. Towards this goal, our lab has developed two publicly available TF and promoter databases. AGRIS (***) is dedicated to reveal regulatory networks in Arabidopsis and is currently composed of databases of putative cis-elements (AtcisDB) and TFs (AtTFDB). The regulatory network in Arabidopsis is constructed based on available data by linking cis-regulatory elements and transcription factors, interactions that are visualized by *** (***) provides regulatory information gathered from computational and experimental sources for the grasses, initially including maize, rice, sorghum and sugarcane. Promoter sequences across these grasses and cis-elements important for gene expression are gathered in GrassPROMDB. GrassTFDB contains information on TFs, their DNA-binding properties and the genes that they have been experimentally demonstrated to bind/regulate. GrassREGNET is the ultimate component of GRASSIUS, currently under development, and will provide a dynamic relationship between the contents of GrassTFDB and GrassPROMDB in the light of experimentally verified interactions, helping visualize spatio-temporal gene regulation and regulatory networks.
Background: The TGF-β/SMAD pathway is part of a broader signaling network in which crosstalk between pathways occurs. While the molecular mechanisms of TGF-β/SMAD signaling pathway have been studied in detail, the g...
There is increasing evidence that Darwin’s theory of evolution by natural selection provides insights into the etiology and treatment of cancer. On a microscopic scale, neoplastic cells meet the conditions for evolut...
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There is increasing evidence that Darwin’s theory of evolution by natural selection provides insights into the etiology and treatment of cancer. On a microscopic scale, neoplastic cells meet the conditions for evolution by Darwinian selection: cell reproduction with heritable variability that affects cell survival and replication. This suggests that, like other areas of biological and biomedical research, Darwinian theory can provide a general framework for understanding many aspects of cancer, including problems of great clinical importance. With the availability of raw molecular data increasing rapidly, this theory may provide guidance in translating data into understanding and progress. Several conceptual and analytical tools from evolutionary biology can be applied to cancer biology. Two clinical problems may benefit most from the application of Darwinian theory: neoplastic progression and acquired therapeutic resistance. The Darwinian theory of cancer has especially profound implications for drug development, both in terms of explaining past difficulties, and pointing the way toward new approaches. Because cancer involves complex evolutionary processes, research should incorporate both tractable (simplified) experimental systems, and also longitudinal observational studies of the evolutionary dynamics of cancer in laboratory animals and in human patients. Cancer biology will require new tools to control the evolution of neoplastic cells.
Although multiple genetic lesions and dysregulated signaling pathways have been identified in melanoma as potential pharmacological targets, currently no treatments exist that can effectively combat disseminated melan...
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The article provides information on a workshop on the development of imaging systems for cancer prevention and preemption convened by the U.S. National Cancer Institute (NCI) Cancer Imaging program held in Gaithersbur...
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The article provides information on a workshop on the development of imaging systems for cancer prevention and preemption convened by the U.S. National Cancer Institute (NCI) Cancer Imaging program held in Gaithersburg, Maryland. Doctor Katherine Ferrara of the University of California discussed the function of ultrasound in breast tumor imaging. Ways to close the gap between development and application of imaging approaches were tackled in a roundtable discussion on cervix and skin cancer.
Resistance to targeted and immune-based therapies limits cures in patients with metastatic melanoma. A growing number of reports have identified nongenetic primary resistance mechanisms including intrinsic microenviro...
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Resistance to targeted and immune-based therapies limits cures in patients with metastatic melanoma. A growing number of reports have identified nongenetic primary resistance mechanisms including intrinsic microenvironment- and lineage plasticity–mediated processes serving critical functions in the persistence of disease throughout therapy. There is a temporally shifting spectrum of cellular identities fluidly occupied by therapy-persisting melanoma cells responsible for driving therapeutic resistance and metastasis. The key epigenetic, metabolic, and phenotypic reprogramming events requisite for the manifestation and maintenance of so-called persister melanoma populations remain poorly understood and underscore the need to comprehensively investigate actionable vulnerabilities. Here we attempt to integrate the field's observations on nongenetic mechanisms of drug resistance in melanoma. We postulate that the future design of therapeutic strategies specifically addressing therapy-persisting subpopulations of melanoma will improve the curative potential of therapy for patients with metastatic disease.
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