ABSTRACT
Medical imaging is a critical tool in the detection, staging, and treatment planning of upper urinary tract urothelial carcinoma (UTUC). This article reviews the strengths and weaknesses of the different imaging techniques and modalities available clinically. This includes multidetector computed tomography (CT), multiparametric magnetic resonance imaging (MRI), ultrasound (US), and positron emission tomography (PET) for the detection, staging, and management of UTUC. In addition, we review the imaging techniques that are being developed and are on the horizon but have not yet made it to clinical practice. Firstly, we review the imaging findings of primary UTUC and the techniques across multiple modalities. We then discuss imaging findings of metastatic disease. Lastly, we describe the role of imaging in the surveillance after resection of primary UTUC based upon current guidelines.
ABSTRACT
We report that heat shock protein 90 (Hsp90) inhibitors selectively kill diffuse large B cell lymphomas (DLBCLs) that depend on the BCL-6 transcriptional repressor. We found that endogenous Hsp90 interacts with BCL-6 in DLBCL cells and can stabilize BCL-6 mRNA and protein. Hsp90 formed a complex with BCL-6 at its target promoters, and Hsp90 inhibitors derepressed BCL-6 target genes. A stable mutant of BCL-6 rescued DLBCL cells from Hsp90 inhibitor-induced apoptosis. BCL-6 and Hsp90 were almost invariantly coexpressed in the nuclei of primary DLBCL cells, suggesting that their interaction is relevant in this disease. We examined the pharmacokinetics, toxicity and efficacy of PU-H71, a recently developed purine-derived Hsp90 inhibitor. PU-H71 preferentially accumulated in lymphomas compared to normal tissues and selectively suppressed BCL-6-dependent DLBCLs in vivo, inducing reactivation of key BCL-6 target genes and apoptosis. PU-H71 also induced cell death in primary human DLBCL specimens.
Subject(s)
DNA-Binding Proteins/antagonists & inhibitors , HSP90 Heat-Shock Proteins/antagonists & inhibitors , Lymphoma, B-Cell/metabolism , DNA-Binding Proteins/metabolism , Humans , Lymphoma, B-Cell/pathology , Protein Binding , Proto-Oncogene Proteins c-bcl-6ABSTRACT
Research with dopamine D(1) receptor antagonists or neuronal inactivating agents suggests that there is dissociable regulation of cocaine-seeking behavior by the rostral and caudal basolateral amygdala. In the present study, discrete infusions of the D(1) receptor agonist SKF 81297 (0.0-0.8 microg per side) were compared with those of the D(1) receptor antagonist SCH 23390 (0.0-2.0 microg per side) to demonstrate directly the importance of D(1) receptor mechanisms within the rostral and caudal basolateral amygdala for their functional heterogeneity in regulating cocaine-seeking behavior. Under a second-order schedule, cocaine-seeking behavior was studied during maintenance (cocaine and cocaine cues present) and reinstatement (only cocaine cues present). Food-maintained responding was used to examine the specificity of maximal behaviorally effective doses of SKF 81297 and SCH 23390. The results demonstrated that the D(1) agonist (0.4 or 0.8 microg) increased and the D(1) antagonist (1.0 microg) decreased cocaine-seeking behavior during maintenance when infused into the caudal but not the rostral basolateral amygdala. Cocaine intake was not affected by the agonist, and was decreased by the antagonist. During reinstatement, the D(1) agonist (0.4 microg) increased and the D(1) antagonist (1.0 microg) decreased cocaine-seeking behavior when infused into the rostral but not the caudal basolateral amygdala. In tests for behavioral specificity, the above effective doses of SKF 81297 and SCH 23390 used in self-administration experiments did not alter food-maintained responding. However, the 2.0-microg dose of SCH 23390 suppressed drug-maintained and food-maintained responding after infusion into both subregions. Collectively, these findings indicate dissociable sensitivity to D(1) receptor ligands within the caudal and rostral basolateral amygdala for altering cocaine-seeking behavior under different conditions that model phases of addiction.