Phase II study of intravenous TZT‐1027 in patients with advanced or metastatic soft‐tissue sarcomas with prior exposure to anthracycline‐based chemotherapy

Abstract

Auditory information is important for social and reproductive behaviors in birds generally, but is crucial for oscine species (songbirds), in particular because in these species auditory feedback ensures the learning and accurate maintenance of song. While there is considerable information on the auditory projections through the forebrain of songbirds, there is no information available for projections through the brainstem. At the latter levels the prevalent model of auditory processing in birds derives from an auditory specialist, the barn owl, which uses time and intensity parameters to compute the location of sounds in space, but whether the auditory brainstem of songbirds is similarly functionally organized is unknown. To examine the songbird auditory brainstem we charted the projections of the cochlear nuclei angularis (NA) and magnocellularis (NM) and the third‐order nucleus laminaris (NL) in zebra finches using standard tract‐tracing techniques. As in other avian species, the projections of NM were found to be confined to NL, and NL and NA provided the ascending projections. Here we report on differential projections of NA and NL to the torus semicircularis, known in birds as nucleus mesencephalicus lateralis, pars dorsalis (MLd), and in mammals as the central nucleus of the inferior colliculus (ICc). Unlike the case in nonsongbirds, the projections of NA and NL to MLd in the zebra finch showed substantial overlap, in agreement with the projections of the cochlear nuclei to the ICc in mammals. This organization could suggest that the “what” of auditory stimuli is as important as “where.” J. Comp. Neurol. 518:2109–2134, 2010. © 2010 Wiley‐Liss, Inc.

Targeting Microtubules to Inhibit Angiogenesis and Disrupt Tumour Vasculature:Implications for Cancer Treatment

“…When administered to patients with advanced non-small cell lung cancer, who had previously received treatment with platinum-based chemotherapy, TZT-1027 demonstrated no anti-cancer activity [194]. Similarly, although TZT-1027 was found to be safe and well tolerated when given to 29 patients with advanced or metastatic softtissue sarcomas, no objective response was observed and the most commonly reported toxicities were neutropenia, fatigue, and constipation [195]. Lastly, three phase I trials have been conducted to set the MTD of ABT-751, a novel orally bioavailable sulphonamide.…”

Filamentous tropical marine cyanobacteria: a rich source of natural products for anticancer drug discovery

“…Due to the promising data from phase I studies of TZT-1027 against soft tissue sarcoma, phase II trials were conducted in patients with advanced or metastatic soft tissue sarcomas. Phase II study revealed that TZT-1027 was safe and well tolerated (Patel et al 2006). However, in another phase II study conducted on patients with advanced nonsmall-cell lung cancer after treatment with platinum-based chemotherapy, TZT-1027 was found inactive as an anticancer drug (Riely et al 2007).…”

Marine Peptide Secondary Metabolites

“…These favorable results have resulted in TZT-1027 reaching Phase II clinical trials stage for different types of cancer (Patel et al, 2006;Riely et al, 2007).…”