N-acetyl-L-aspartyl-L-glutamate peptidase-like 2 is overexpressed in cancer and promotes a pro-migratory and pro-metastatic phenotype.

N-acetyl-L-aspartyl-L-glutamate peptidase-like 2 (NAALADL2) is a member of the glutamate carboxypeptidase II family, best characterized by prostate-specific membrane antigen (PSMA/NAALAD1). Using immunohistochemistry (IHC), we have shown overexpression of NAALADL2 in colon and prostate tumours when compared with benign tissue. In prostate cancer, NAALADL2 expression was associated with stage and Grade, as well as circulating mRNA levels of the NAALADL2 gene. Overexpression of NAALADL2 was shown to predict poor survival following radical prostatectomy. In contrast to PSMA/NAALAD1, NAALADL2 was localized at the basal cell surface where it promotes adhesion to extracellular matrix proteins. Using stable knockdown and overexpression cell lines, we have demonstrated NAALADL2-dependent changes in cell migration, invasion and colony-forming potential. Expression arrays of the knockdown and overexpression cell lines have identified nine genes that co-expressed with NAALADL2, which included membrane proteins and genes known to be androgen regulated, including the prostate cancer biomarkers AGR2 and SPON2. Androgen regulation was confirmed in a number of these genes, although NAALADL2 itself was not found to be androgen regulated. NAALADL2 was also found to regulate levels of Ser133 phosphorylated C-AMP-binding protein (CREB), a master regulator of a number of cellular processes involved in cancer development and progression. In combination, these data suggest that changes in expression of NAALADL2 can impact upon a number of pro-oncogenic pathways and processes, making it a useful biomarker for both diagnosis and prognosis.

Effect of age on interaural asymmetry of event-related potentials in a dichotic listening task.

Three groups of subjects, children, young adults, and elderly persons with presbyacusis, were tested in a directed attention, quasidichotic paradigm in which continuous speech was monitored for syntactically and/or semantically anomalous words. The task evoked an event-related potential (ERP) characterized by a positive peak in the latency region of 600 to 1,000 msec. ERPs were separately averaged for target-word-right and target-word-left conditions. Amplitude and latency measures at the peak of the global field power waveform were calculated. Amplitude was significantly larger in children than in either adult group. In children and young adults, both amplitude and latency measures were equivalent for target-right and target-left conditions, but in elderly persons, latency was significantly greater in the target-left than in the target-right condition. Topographic maps of amplitude at the peak of the ERP waveform showed maximal positivity symmetrically distributed around the midline centroparietal area in both right-attended and left-attended conditions. In elderly persons, however, maximal positivity in the left-attended condition was significantly delayed relative to maximal positivity in the right-attended condition. Results are consistent with previous findings of interaural asymmetry in a dichotic listening task in elderly persons.

Toward a more ecologically valid measure of speech understanding in background noise.

In an attempt to develop a more ecologically valid measure of speech understanding in a background of competing speech, we constructed a quasidichotic procedure based on the monitoring of continuous speech from loudspeakers placed directly to the listener's right and left sides. The listener responded to the presence of incongruous or anomalous words imbedded within the context of two children's fairy tales. Attention was directed either to the right or to the left side in blocks of 25 utterances. Within each block, there were target (anomalous) and nontarget (nonanomalous) words. Responses to target words were analyzed separately for attend-right and attend-left conditions. Our purpose was twofold: (1) to evaluate the feasibility of such an approach for obtaining electrophysiologic performance measures in the sound field and (2) to gather normative interaural symmetry data for the new technique in young adults with normal hearing. Event-related potentials to target and nontarget words at 30 electrode sites were obtained in 20 right-handed young adults with normal hearing. Waveforms and associated topographic maps were characterized by a slight negativity in the region of 400 msec (N400) and robust positivity in the region of 900 msec (P900). Norms for interaural symmetry of the P900 event-related potential in young adults were derived.