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Dartmouth, Lebanon

Kisselev A.F.,Norris Cotton Cancer Center | Van Der Linden W.A.,Leiden University | Overkleeft H.S.,Leiden University
Chemistry and Biology | Year: 2012

Proteasomes are large, multisubunit proteolytic complexes presenting multiple targets for therapeutic intervention. The 26S proteasome consists of a 20S proteolytic core and one or two 19S regulatory particles. The 20S core contains three types of active sites. Many structurally diverse inhibitors of these active sites, both natural product and synthetic, have been discovered in the last two decades. One, bortezomib, is used clinically for treatment of multiple myeloma, mantle cell lymphoma, and acute allograft rejection. Five more recently developed proteasome inhibitors are in trials for treatment of myeloma and other cancers. Proteasome inhibitors also have activity in animal models of autoimmune and inflammatory diseases, reperfusion injury, promote bone and hair growth, and can potentially be used as anti-infectives. In addition, inhibitors of ATPases and deubiquitinases of 19S regulatory particles have been discovered in the last decade. © 2012 Elsevier Ltd All rights reserved. Source

Sempere L.F.,Norris Cotton Cancer Center
Expert Review of Molecular Diagnostics | Year: 2011

The promise of personalized medicine is highly dependent on the identification of biomarkers that inform diagnostic decisions and treatment options, as well as on the accurate, rapid and cost-effective detection and interpretation of these biomarkers. miRNAs, which are short noncoding regulatory RNAs, are rapidly emerging as a novel class of biomarkers with a unique set of biological and chemical properties that makes them very appealing candidates for theranostic applications in cancer. Since the utility of some protein-encoding gene biomarkers is already exploited in routine clinical practice, it will be important to identify areas in which miRNAs provide complementary or superior information to these existing (and other translational) biomarkers to enhance the diagnostic, prognostic and predictive power of molecular characterization of tumors. In this article, the challenges and opportunities for integration of miRNA-based assays in the clinical toolkit to improve care and management of patients afflicted with solid tumors will be discussed. © 2011 Lorenzo F Sempere. Source

Compton D.A.,Norris Cotton Cancer Center
Current Opinion in Cell Biology | Year: 2011

Accurate chromosome segregation during cell division is essential for genome integrity. Errors in chromosome segregation are irreversible and lead to a state of aneuploidy where the number of chromosomes in a cell or organism is not a multiple of the haploid number of chromosomes. Aneuploidy reduces fecundity and is a frequent cause of inherited birth defects. In addition, aneuploidy is very common in solid tumors where it is associated with poor patient prognosis. Recent work has revealed the most common pathways by which chromosomes mis-segregate leading to aneuploidy. Moreover, answers to the key question of how cells respond to aneuploidy are beginning to emerge. © 2010 Elsevier Ltd. Source

Rolland S.G.,Norris Cotton Cancer Center | Conradt B.,Norris Cotton Cancer Center
Current Opinion in Cell Biology | Year: 2010

Mitochondria are highly dynamic organelles that constantly fuse and divide. Dynamin-related GTPases are the core components of the machineries that mediate mitochondrial fusion and fission. The role and regulation of these machineries are currently under intense investigation. Recently, members of the BCL2 family of proteins, conserved regulators of apoptosis, have been implicated in the regulation of mitochondrial dynamics. Here, we review the functions of mitochondrial fusion and fission in apoptotic and nonapoptotic cells and how members of the BCL2 family of proteins regulate these functions. © 2010 Elsevier Ltd. Source

Miller T.W.,Norris Cotton Cancer Center
Clinical Cancer Research | Year: 2014

Low estrogen receptor (ER) levels in breast tumors are associated with poorer response to antiestrogen therapy. Finn and colleagues identify low ER levels as a biomarker predicting benefit from the addition of the EGFR/HER2 dual inhibitor lapatinib to an antiestrogen treatment regimen in patients with metastatic ER+/HER2- breast cancer. © 2014 American Association for Cancer Research. Source

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