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We have been developing a series of nonpeptidic, small molecule farnesyl protein transferase inhibitors that share a common tricyclic nucleus and compete with peptide/protein substrates for binding to farnesyl protein transferase. Here, we report on pharmacological and in vivo studies with SCH 66336, a lead compound in this structural class. SCH 66336(More)
  • L L Nielsen, P Lipari, J Dell, M Gurnani, G Hajian
  • 1998
Synergy (or antagonism) between two chemical agents is an in vitro empirical phenomenon, in which the observed effect of the combination is more (or less) than what would be predicted from the effects of each agent working alone. Although mathematical synergy is not directly provable in the clinical setting, it does predict a favorable outcome when the two(More)
A precise measurement of the proton flux in primary cosmic rays with rigidity (momentum/charge) from 1 GV to 1.8 TV is presented based on 300 million events. Knowledge of the rigidity dependence of the proton flux is important in understanding the origin, acceleration, and propagation of cosmic rays. We present the detailed variation with rigidity of the(More)
Knowledge of the precise rigidity dependence of the helium flux is important in understanding the origin, acceleration, and propagation of cosmic rays. A precise measurement of the helium flux in primary cosmic rays with rigidity (momentum/charge) from 1.9 GV to 3 TV based on 50 million events is presented and compared to the proton flux. The detailed(More)
An extensive 3-dimensional Monte Carlo calculation of the atmospheric neutrino flux is in progress with the FLUKA Monte Carlo code. The results are compared to those obtained under the 1-dimensional approximation, where secondary particles and decay products are assumed to be collinear to the primary cosmic ray, as usually done in most of the already(More)
PURPOSE Adenovirus-mediated p53 gene therapy for cancer is currently undergoing phase I/II clinical trials. The drug used in our clinical trials (p53 Ad; ACN53; SCH58500) consists of a replication-deficient, type 5 adenovirus vector expressing human wildtype p53 tumor suppressor under the control of the cytomegalovirus promoter. In preclinical models, p53(More)
SCH66336 is a p.o.-active, farnesyl protein transferase inhibitor. SCH66336 inhibits farnesylation of RAS and other proteins in tumor cells and suppresses tumor growth in human xenograft and transgenic mouse cancer models in vivo. SCH58500 is a replication-deficient, recombinant adenovirus, which expresses the human p53 tumor suppressor. In preclinical(More)
The products of the Ha-, Ki-, and N-ras proto-oncogenes comprise a family of 21 kDa guanine nucleotide-binding proteins which play a crucial role in growth factor signal transduction and in the control of cellular proliferation and differentiation. Activating mutations in the ras oncogenes occur in a wide variety of human tumors. Ras proteins undergo a(More)
A precision measurement by the Alpha Magnetic Spectrometer on the International Space Station of the positron fraction in primary cosmic rays in the energy range from 0.5 to 350 GeV based on 6.8 × 10(6) positron and electron events is presented. The very accurate data show that the positron fraction is steadily increasing from 10 to ∼ 250  GeV, but, from 20(More)
A Monte-Carlo calculation of the atmospheric neutrino fluxes [1, 2] has been extended to take account of the three-dimensional (3D) nature of the problem, including the bending of secondary particles in the geomagnetic field. Emphasis has been placed on minimizing the approximations when introducing the 3D considerations. In this paper, we describe the(More)