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During pregnancy, the energy requirements of the fetus impose changes in maternal metabolism. Increasing insulin resistance in the mother maintains nutrient flow to the growing fetus, while prolactin and placental lactogen counterbalance this resistance and prevent maternal hyperglycemia by driving expansion of the maternal population of insulin-producing(More)
Despite many refinements in current therapeutic strategies, the overall prognosis for a patient with glioblastoma is dismal. Neural precursor cells (NPCs) are capable of tracking glioma tumors and thus could be used to deliver therapeutic molecules. We have engineered mouse NPCs to deliver a secreted form of tumor necrosis factor-related apoptosis-inducing(More)
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can selectively kill neoplastic cells and control of its activity could enhance tumor therapy. We have developed means to control the secretion of a novel recombinant (r) TRAIL fusion protein using a viral protease. This system uses the endoplasmic reticulum (ER) as a storage depot for rTRAIL,(More)
Therapeutic nanoparticles (TNPs) aim to deliver drugs more safely and effectively to cancers, yet clinical results have been unpredictable owing to limited in vivo understanding. Here we use single-cell imaging of intratumoral TNP pharmacokinetics and pharmacodynamics to better comprehend their heterogeneous behaviour. Model TNPs comprising a fluorescent(More)
The hepatocyte growth factor receptor (MET) is a receptor tyrosine kinase (RTK) that has emerged as an important cancer target. Consequently, a number of different inhibitors varying in specificity are currently in clinical development. However, to date, it has been difficult to visualize MET expression, intracellular drug distribution and small molecule(More)
Targeting DNA repair pathways is a powerful strategy to treat cancers. To gauge efficacy in vivo, typical response markers include late stage effects such as tumor shrinkage, progression free survival, or invasive repeat biopsies. These approaches are often difficult to answer critical questions such as how a given drug affects single cell populations as a(More)
The vitamin A metabolite, all-trans retinoic acid (atRA), is a regulator of nervous system development. Using a subtracted cDNA library constructed from neuroblastoma cells, the atRA-responsive gene calmin (Clmn) was identified (Merrill et al. [2004] Biol Chem 385:605-614). The Clmn transcript is detected very early in rat embryonic development and is(More)
The surface of the cornea contains the highest density of nociceptive nerves of any tissue in the body. These nerves are responsive to a variety of modalities of noxious stimuli and can signal pain even when activated by low threshold stimulation. Injury of corneal nerves can lead to altered nerve morphology, including neuropathic changes which can be(More)
Mitochondria, which are essential organelles in resting and replicating cells, can vary in number, mass and shape. Past research has primarily focused on short-term molecular mechanisms underlying fission/fusion. Less is known about longer-term mitochondrial behavior such as the overall makeup of cell populations' morphological patterns and whether these(More)
Therapeutic nanoparticles (TNPs) aim to deliver drugs more safely and effectively to cancers, yet clinical results have been unpredictable owing to limited in vivo understanding. Here we use single-cell imaging of intratumoral TNP pharmacokinetics and pharmacodynamics to better comprehend their heterogeneous behavior. Model TNPs comprised of a fluorescent(More)