Introduction The detection of circulating tumor cells (CTC) is prognostic in several cancer types. This trial examines the incidence and prognostic value of CTCs in urothelial cancer (UC). Materials and Methods 44 subjects with UC were assessed for CTCs using CellSearch® Technology (Veridex, LLC, Raritan, NJ), using 7.5 ml of peripheral blood, sorted by magnetic separation (EpCaM positive, and immunofluorescent staining, (Cytokeratin 8, 18, or 19 positive, CD 45 negative, DAPI positive cells) to identify CTCs. Results Five of 30 (17%) subjects with clinically localized and 7 of 14 (50%) patients with metastatic UC had at least 1 detectable CTC, with a range of 1–177 CTCs. Six subjects had 5 or more CTCs. FISH analysis was performed in 20 samples from 18 unique subjects, using the UroVysion probe set. Copy number gains consistent with neoplasm were observed in cases with measurable CTCs, but not in any of the CTC-negative samples tested. With a median follow-up of 337 days, all 7 metastatic subjects with detectable CTCs had died, versus 3 of 7 (43%) metastatic subjects without detectable CTCs. Conclusions CTCs were observed in 50% of the metastatic UC patients tested. FISH analysis confirmed the aneusomic chromosomal content in the CTCs. The findings suggest measurable CTCs may be prognostic for shortened survival in metastatic UC patients, although the optimal threshold for a “positive” finding is unknown. CTCs were also detected in a subset of patients with clinically-localized disease, identifying a potential high-risk, pre-operative group for future study.

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HIV-associated neurocognitive disorders (HAND) continue to be a neurological complication of HIV infection in the era of combined antiretroviral therapy (cART). Hippocampal neurodegeneration and dysfunction occurs as a result of HIV infection, but few studies to date have assesses spatial learning and memory function in patients with HAND. We used the Memory Island (MI) Test to study the effects of HIV infection, Apolipoprotein E (ApoE) allele status, and CSF ApoE protein levels on spatial learning and memory in our cohort of Hispanic women. The MI Test is a virtual reality-based computer program that tests spatial learning and memory, and was designed to resemble the Morris Water Maze (MWM) test of hippocampal function widely used in rodent studies. In the current study, HIV-seropositive women (n=20) and controls (n=16) were evaluated with neuropsychological (NP) tests, the MI Test, ApoE, and CSF ApoE assays. On the MI, the HIV-seropositive group showed significant reduced learning and delayed memory performance compared with HIV-seronegative controls. When stratified by cognitive performance on NP tests, the HIV-seropositive, cognitively impaired group performed worse than HIV-seronegative controls in ability to learn and in the delayed memory trial. Interestingly, differences were observed in the results obtained by the NP tests and the MI Test for ε4 carriers and non-carriers: NP tests showed effects of the ε4 allele in HIV-seronegative women but not HIV-seropositive ones, whereas as the converse was true for the MI Test. Our findings suggest that the MI test is sensitive in detecting spatial deficits in HIV-seropositive women, and that these deficits may arise relatively early in the course of HAND.

YWHAE (14-3-3ε) protein levels are considered to be a reliable biomarker for neurodegeneration. The YWHAE protein interacts both directly and indirectly with human immunodeficiency virus (HIV) accessory proteins, leading to cell death. The purpose of this study was to examine the relationship between YWHAE polymorphisms and HIV-associated neurocognitive disorder (HAND) and the relationship between YWHAE protein levels and HAND. A cross-sectional study using random samples of HIV-seropositive (n=20) and HIV–seronegative (controls) (n=16) women from the Hispanic-Latino Longitudinal Cohort of Women was conducted. Individuals who are HIV-seropositive and heterozygous at the rs4790084/rs1204828 loci in the YWHAE gene were 3X more likely to display reduced cognitive functioning, to have received a HAND diagnosis, and to have less YHWAE protein expressed than homozygotes. Western blots from cerebral spinal fluid (CSF) indicate that the HIV-seropositive women with HAND expressed 4.5X less YWHAE compared to HIV-seropositive cognitively normal women (94% sensitivity, 84% specificity; HIV-seropositive vs. controls). Therefore, polymorphism in YWHAE may be a genetic risk factor for HAND and levels of YWHAE protein are a likely biomarker for neurocognitive status in HIV-seropositive women.