Learn More
Stem cells reside in specialized microenvironments or 'niches' that regulate their function. In vitro studies using hypoxic culture conditions (<5% O2) have revealed strong regulatory links between O2 availability and functions of stem and precursor cells. Although some stem cells are perivascular, others may occupy hypoxic niches and be regulated by O2(More)
Apicomplexan parasites are the cause of numerous important human diseases including malaria and AIDS-associated opportunistic infections. Drug treatment for these diseases is not satisfactory and is threatened by resistance. The discovery of the apicoplast, a chloroplast-like organelle, presents drug targets unique to these parasites. The(More)
Members of the phylum Apicomplexa include the causative agents of numerous important human and life-stock diseases. Apicomplexans are obligate intracellular pathogens and have adapted to a diverse range of hosts and host cells. A key component to the parasite's success is its ability to secure the supply of essential nutrients and metabolic building blocks.(More)
PURPOSE Dabrafenib (GSK2118436) is a potent inhibitor of mutated BRAF kinase. Our multicenter, single-arm, phase II study assessed the safety and clinical activity of dabrafenib in BRAF(V600E/K) mutation-positive metastatic melanoma (mut(+) MM). PATIENTS AND METHODS Histologically confirmed patients with stage IV BRAF(V600E/K) mut(+) MM received oral(More)
Non-small cell lung cancer (NSCLC) is the leading cause of cancer deaths worldwide. The oxygen-sensitive hypoxia inducible factor (HIF) transcriptional regulators HIF-1alpha and HIF-2alpha are overexpressed in many human NSCLCs, and constitutive HIF-2alpha activity can promote murine lung tumor progression, suggesting that HIF proteins may be effective(More)
Cellular properties are influenced by complex factors inherent to their microenvironments. While oxygen deprivation (hypoxia) occurs in tumours because of rapid cell proliferation and aberrant blood vessel formation, embryonic cells develop in a naturally occurring hypoxic environment. Cells respond to hypoxia by stabilizing hypoxia-inducible factors(More)
6506 Background: Signaling through the RAS/RAF/MEK pathway is activated in many human cancers. GSK212 is a potent, selective allosteric inhibitor of MEK1/2 that inhibits proliferation of myeloid cell lines in vitro. A phase I/II study of a single, daily, oral dosing regimen was conducted to define the recommended phase II dose (RP2D) and evaluate(More)
PURPOSE Tumor-derived circulating cell-free DNA (cfDNA) is a potential alternative source from which to derive tumor mutation status. cfDNA data from four clinical studies of the BRAF inhibitor (BRAFi) dabrafenib or the MEK inhibitor (MEKi) trametinib were analyzed to determine the association between BRAF mutation status in cfDNA and tumor tissue, and the(More)
In this era of more rational therapies, substantial efforts are being made to identify optimal targets. The discovery of translo-cations involving the anaplastic lymphoma kinase (ALK) receptor tyrosine kinase in a subset of non–small cell lung cancers has become a paradigm for precision medicine. Notably, ALK was initially discovered as the fusion gene in(More)
  • 1