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The circadian clock in the suprachiasmatic nucleus (SCN) is thought to drive daily rhythms of behavior by secreting factors that act locally within the hypothalamus. In a systematic screen, we identified transforming growth factor-alpha (TGF-alpha) as a likely SCN inhibitor of locomotion. TGF-alpha is expressed rhythmically in the SCN, and when infused into(More)
PURPOSE The present studies evaluated the ability of injectable, biodegradable microspheres releasing carboplatin, doxorubicin, or 5-fluorouracil to suppress the growth of solid tumors implanted subcutaneously or intramuscularly. METHODS Seven to 10 days after implantation of MATB-III cells, rats received systemic chemotherapy, intratumoral bolus(More)
PURPOSE Delivery of chemotherapeutics using implantable, biodegradable polymers provides a potentially powerful method of treating brain tumors. The present studies examined the ability of injectable microspheres, formulated to release carboplatin or BCNU for 2-3 weeks, to enhance survival in a rodent model of deep, inoperable glioma. METHODS Rat glioma(More)
The bradykinin analog, Cereport (RMP-7), was designed to increase permeability of the blood brain barrier (BBB). Over the past several years it has been developed primarily as a means of increasing permeability of the blood brain tumor barrier, where early evidence indicated a particularly robust and reliable effect. The present series of experiments were(More)
Delivery of chemotherapeutic agents to solid peripheral tumors is compromised because the impaired microvasculature within and surrounding tumors limits diffusion and convection of agents from the vasculature to the tumor. Using a variety of rat tumor models, we show that intravenous administration of a vasoactive bradykinin B2 receptor agonist (Cereport,(More)
Previous studies have shown that the bradykinin agonist, RMP-7, can safely permeabilize the blood brain barrier (BBB) by activation of constitutive B2 receptors on endothelial cells. The paper describes a series of studies using quantitative autoradiography and intracarotid infusions of RMP-7 to further elucidate the effect on BBB permeability. Because(More)
Several experiments studied the effects of i.v. infusions of the bradykinin agonist, Cereport (RMP-7), on permeability of the blood-brain tumor barrier in rat gliomas. First, the ability of Cereport to increase uptake of two poorly blood-brain barrier-penetrating drugs (lypophilic paclitaxel and hydrophilic carboplatin) was directly compared to provide new(More)
Cereport (RMP-7) is a selective bradykinin B2 receptor agonist which increases the permeability of the 'blood-brain tumour barrier' (BBTB) to increase delivery of chemotherapeutic agents to brain tumours. A series of experiments was performed in an RG2 rodent model of glioma to evaluate and refine intravenous (i.v.) parameters to optimize Cereport's(More)
Cereport (RMP-7) enhances delivery of chemotherapeutics into brain tumors by increasing the permeability of the glioma vasculature (i.e. , the blood-brain tumor barrier; BBTB). Its effect on brain tumors has consistently been more robust than that on normal brain. The present experiments tested the hypothesis that the ability of Cereport to increase the(More)