NeuroPharmacology: As Applied to Designing New Chemotherapeutic Agents

Neurooncology anticancer drugs are no exception—their distribution and tissue interactions follow the general rules of classical pharmacology. In an attempt to assist with the new therapeutic approaches to manage cancers involving the central nervous system, classical chemobiodynamic compartment and pharmacokinetic models are discussed and illustrated. In addition, strategies and approaches for penetrating the blood brain barrier (BBB) are reviewed and modeled. Finally, in support of classical pharmacology, a new anticancer agent in clinical trial for brain tumors is reviewed as an example of clinical onco-neuropharmacology

New Approaches in the Treatment of Glioblastoma Multiforme

Central nervous system (CNS) malignancies are rare, but commonly fatal and glioblastoma (GBM) is the most common of the primary brain tumors. In contrast to metastatic malignancies involving the CNS, which have external blood supplies that develop when the malignant cells penetrate the blood-brain-barrier (BBB), GBM generates its own intracerebral neovascular support system. Thus, the therapeutic issues as discussed herein review the development of drugs and therapeutics that will penetrate the BBB and are cytotoxic to GBM and other brain tumors. Since GBM is a CNS malignancy with minimal effective therapeutic options available, designing drugs and therapeutics as treatment for this malignancy that penetrate, but do not disrupt the BBB is the goal of this chapter. 4-Demethylcholesteryl-4-penclomedine (DM-CHOC-PEN) was designed and developed because of its lipophilic properties that would potentiate crossing the BBB and penetrate brain tumors. The drug has now completed Phase I/II clinical trial in humans with primary brain malignancies demonstrating objective responses in GBM. In addition, preliminary experiences with naturally occurring polyphenols—curcumin, quercetin, catechins and phloretin and derivatives—are reviewed as potential naturally occurring anti-glioblastoma agents

Comparative Anticancer Activity in Human Tumor Xenograft Models, Preclinical Pharmacology and Toxicology for 4- Hydroperoxyifosfamide (HOOI): A Potential Neuro-Alkylating Agent for Primary and Metastatic Cancers Involving the Central Nervous System

Background: 4-Hydropeoxyifosfamide (HOOI) is a hydroperoxy derivative of ifosfamide that was developed as an anticancer agent that can penetrate the blood-brain barrier (BBB), which can be potentially useful in the management of brain tumors

The decay tau -> 3 pi + nu(tau) as a probe of the mechanism of dynamical chiral symmetry breaking

The decays tau -> 3 pi + nu(tau) are analyzed at one loop order in the framework of Generalized Chiral Perturbation Theory, in order to test the sensitivity to the size of spontaneous chiral symmetry breaking parameters, contained in the S-wave. The latter, due to a kinematical suppression, at threshold, of the P-wave, is relatively large enough to be detectable at high energy machines, through azimuthal left-right asymmetries. This quantity (for the pi- pi- pi+ mode), integrated from threshold to Q^2 = 0.35 GeV^2, varies from (17 +- 3) % in the standard case of large condensate up to (40 +- 5) % in the extreme case of tiny condensate. The feasibility of such measurement at high luminosity colliders (e.g. CLEO) is discussed. This method provides a completely independent cross-check of forthcoming experimental determination of the quark condensate, based on low energy pi-pi scattering.Comment: 29 pages, Latex, using JHEP.cls (included), 7 PS figure

AKARI and BLAST Observations of the Cassiopeia A Supernova Remnant and Surrounding Interstellar Medium

We use new large area far infrared maps ranging from 65 - 500 microns obtained with the AKARI and the Balloon-borne Large Aperture Submillimeter Telescope (BLAST) missions to characterize the dust emission toward the Cassiopeia A supernova remnant (SNR). Using the AKARI high resolution data we find a new "tepid" dust grain population at a temperature of ~35K and with an estimated mass of 0.06 solar masses. This component is confined to the central area of the SNR and may represent newly-formed dust in the unshocked supernova ejecta. While the mass of tepid dust that we measure is insufficient by itself to account for the dust observed at high redshift, it does constitute an additional dust population to contribute to those previously reported. We fit our maps at 65, 90, 140, 250, 350, and 500 microns to obtain maps of the column density and temperature of "cold" dust (near 16 K) distributed throughout the region. The large column density of cold dust associated with clouds seen in molecular emission extends continuously from the surrounding interstellar medium to project on the SNR, where the foreground component of the clouds is also detectable through optical, X-ray, and molecular extinction. At the resolution available here, there is no morphological signature to isolate any cold dust associated only with the SNR from this confusing interstellar emission. Our fit also recovers the previously detected "hot" dust in the remnant, with characteristic temperature 100 K.Comment: Accepted for publication in the Astrophysical Journal. Maps and related data are available at http://blastexperiment.info