Learn More
Second-generation nuclear medicine markers of tumour hypoxia have been synthesised and screened for hypoxic marking activity in cell cultures and in mouse tumours (EMT-6). Markers of the iodinated azomycin nucleoside class with greater water solubility and faster plasma clearance rates relative to iodoazomycin arabinoside (IAZA) were of particular interest.(More)
Tumor cells at low oxygen tension are relatively radioresistant. The hypoxic fraction of individual tumors before, during and after radiotherapy is likely to have prognostic value but its diagnosis still awaits an accurate and acceptable assay. The recent indications that hypoxia can also induce the expression of specific genes and promote a more aggressive(More)
Tumor hypoxia, present in many human cancers, can lead to resistance to radiation and chemotherapy, is associated with a more aggressive tumor phenotype and is an independent prognostic factor of clinical outcome. It is therefore important to identify and localize tumor hypoxia in cancer patients. In the current study, serial microPET imaging was used to(More)
UNLABELLED Molecular imaging allows the noninvasive assessment of cancer progression and response to therapy. The aim of this study was to investigate molecular and cellular determinants of 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) PET and diffusion-weighted (DW) MR imaging in lung carcinoma xenografts. METHODS Four lung cancer cell lines (A549,(More)
Radiotherapy prescription can now be customized to target the major mechanism(s) of resistance of individual tumors. In that regard, functional imaging techniques should be exploited to identify the dominant mechanism(s). Tumor biology research has identified several mechanisms of tumor resistance that may be unique to radiation treatments. These fall into(More)
There is unmet need for chemical tools to explore the role of the Mediator complex in human pathologies ranging from cancer to cardiovascular disease. Here we determine that CCT251545, a small-molecule inhibitor of the WNT pathway discovered through cell-based screening, is a potent and selective chemical probe for the human Mediator complex-associated(More)
A variety of radioactive agents, injected directly intravenously have demonstrated foci of inflammation by gamma camera imaging, avoiding the in vitro preparation of labeled leukocytes. This study sought to find out if any of these agents mimicked the biodistribution in abscesses and non-target organs of labeled mixed leukocyte suspensions. Eight different(More)
Cationic dyes of the cyanine type have been observed to specifically inhibit NAD-linked respiration in rat liver mitochondria, with 50% inhibition occurring at about 0.2 mumol/g of mitochondrial protein. The dyes show no effect on succinate oxidation or coupled phosphorylation in the range which completely inhibits NADH oxidation. This specific inhibition(More)
The Mediator complex-associated cyclin-dependent kinase CDK8 has been implicated in human disease, particularly in colorectal cancer where it has been reported as a putative oncogene. Here we report the discovery of 109 (CCT251921), a potent, selective, and orally bioavailable inhibitor of CDK8 with equipotent affinity for CDK19. We describe a(More)
PURPOSE To assess the ability of vascular endothelial growth factor receptor type 2 (VEGFR2)-targeted and nontargeted ultrasonography (US) to depict antiangiogenic therapy effects and to investigate whether first-pass kinetics obtained with VEGFR2-targeted microbubbles provide independent data about tumor vascularization. MATERIALS AND METHODS(More)