Tamaro Hudson

Fetal cell microchimerism, the presence of genetically distinct fetal cells in maternal tissues, arises naturally during pregnancy when fetal stem cells migrate into maternal circulation. These cells can engraft in damaged tissues, including malignancies, and may play a role in tumor biology. This study evaluated the association between fetal microchimerism—detected through Testis-Specific Protein Y-encoded (TSPY) expression—and clinicopathologic features of invasive breast cancer in African American women. We conducted a blinded case–case study using immunohistochemical analysis of TSPY expression in 202 archival breast cancer tissues. TSPY protein, a marker of microchimeric Y-chromosome DNA, was assessed in relation to clinical and pathological characteristics including estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) status, tumor grade, stage, size, and molecular subtype. Associations were examined using Chi-square tests. Survival outcomes were evaluated using Kaplan–Meier analysis. The results demonstrated that TSPY expression was not associated with patient age, receptor status, or triple-negative phenotype. However, TSPY positivity was significantly associated with higher tumor grade (p = 0.043), suggesting a relationship between fetal microchimerism and more aggressive disease features. Therefore, we concluded that microchimeric TSPY expression is enriched in higher-grade breast tumors among African American women. These findings suggest that fetal cell microchimerism may contribute to—or serve as a biomarker of—advanced breast cancer biology, although its mechanistic role requires further investigation.

Challenges to docetaxel use in prostate cancer treatment include several resistance mechanisms as well as toxicity. To overcome these challenges and to improve the therapeutic efficacy in heterogeneous prostate cancer, the use of multiple agents that can destroy different subpopulations of the tumor is required. Brusatol, a multitarget inhibitor, has been shown to exhibit potent anticancer activity and play an important role in drug response and chemoresistance. Thus, the combination of brusatol and docetaxel in a nanoparticle platform for the treatment of prostate cancer is expected to produce synergistic effects. In this study, we reported the development of polymeric nanoparticles for the delivery of brusatol and docetaxel in the treatment of prostate cancer. The one-factor-at-a-time method was used to screen for formulation and process variables that impacted particle size. Subsequently, factors that had modifiable effects on particle size were evaluated using a 2⁴ full factorial statistical experimental design followed by the optimization of drug loading. The optimization of blank nanoparticles gave a formulation with a mean size of 169.1 nm ± 4.8 nm, in agreement with the predicted size of 168.333 nm. Transmission electron microscopy showed smooth spherical nanoparticles. The drug release profile showed that the encapsulated drugs were released over 24 h. Combination index data showed a synergistic interaction between the drugs. Cell cycle analysis and the evaluation of caspase activity showed differences in PC-3 and LNCaP prostate cancer cell responses to the agents. Additionally, immunoblots showed differences in survivin expression in LNCaP cells after treatment with the different agents and formulations for 24 h and 72 h. Therefore, the nanoparticles are potentially suitable for the treatment of advanced prostate cancer.

ID 20175 Poster Board 342 Fragile X-associated tremor/ataxia syndrome (FXT/AS) is a late-onset neurodegenerative disease associated with movement and memory problems, affecting 1 in 3000 males over 50 years of age. This syndrome is characterized by excess CGG (55-200) repeats of a trinucleotide sequence in the DNA for the fragile X mental retardation 1 gene (FMR1). It is suspected to induce mitochondria dysfunction in the CNS. Currently, no effective pharmacological treatments exist for FXTAS. The goal of this research was to test the ability of synthetic macamides, which are endocannabinoid like-compound, to restore mitochondrial viability. Macamides were chosen as they have been shown to prevent mitochondrial membrane toxicity in Parkinson’s disease. To establish a rapid screening cell model to study the pharmacological efficacy of macamides, fibroblast baby hamster kidney (BHK-21) cell lines were treated with glucose oxidase (GluOx) at varying concentrations and times. Mitochondrial viability was assessed by the colorimetric Janus B Green Assay, which stains the mitochondria and enables assessment of cell numbers and the presence of oxygen in anchorage-dependent cell culture. GluOx treatment of BHK-21 cells caused a dose- and time-dependent increase in oxidative stress. There was a significant disruption in the morphology of BHK-21 cells at a high glucose concentration, i.e., 40 nM, between 2 and 24 hours post-exposure. The Janus B Green colorimetric assay confirmed the morphology data. In examining the effects of glucose on mitochondrial viability, we demonstrated that at 15, 30, 35, and 40 nM, glucose significantly decreased mitochondria viability compared to the untreated, with 40 nM having the most significant effect. Upon establishing this model of mitochondrial dysfunction, we next investigated the ability of three novel mitochondrial antioxidants (e.g., macamides) to protect mitochondrial viability. Macamides preserved the morphology of the BHK-21 cells at concentrations of 0.5uM, 1uM, and 5uM. Furthermore, in the presence of glucose, macamides at a low concentration of 0.5uM prevented the reduction of mitochondria viability. This study provides evidence of the efficacy of macamides as novel therapeutic candidates in the treatment of mitochondrial dysfunction associated with FXTAS. Support/Funding Information: Award Number TL1TR001431

Background: Although studies have observed several markers correlate with progression of prostate cancer (PCa), no specific markers have been identified that accurately predict the progression of this disease, even in African American (AA) men who are generally at higher risk than other ethnic groups. The primary goal of this study was to explore whether three markers could predict the progression of PCa.Method: We investigated protein expression of Annexin 2 (ANX2), serine peptidase inhibitor, kazal type 1(SPINK1)/tumor‐associated trypsin inhibitor (TATI), and heat shock protein 60 (Hsp60) in 79 archival human prostate trans‐rectal ultrasound (TRUS) biopsy tissues according to a modified World Health Organization (WHO) classification: normal (WHO1a), Gleason Score (GS6 (WHO1b), GS7 subgroups (WHO2 = 3 + 4, WHO3 = 4 + 3), GS8 (WHO4), and GS9‐10 (WHO5). AA men aged 41‐90 diagnosed from 1990 to 2013 at Howard University were included. Automated staining assessed expression of each biomarker. Spearman correlation assessed the direction and relationship between biomarkers, WHO and modified WHO GS, age, and 5‐year survival. A two‐tailed t‐test and ANOVA evaluated biomarkers expression in relationship to WHO normal and other GS levels, and between WHO GS levels. A logistic and linear regression analysis examined the relationship between biomarker score and WHO GS categories. Kaplan‐Meier curves graphed survival.Results: ANX2 expression decreased monotonically with the progression of PCa while expression of SPINK1/TATI and Hsp60 increased but had a more WHO GS‐specific effect; SPINK1/TATI differed between normal and GS 2‐6 and HSP60 differed between GS 7 and GS 2‐6. WHO GS was found to be significantly and negatively associated with ANX2, and positively with SPINK1/TATI and Hsp60 expression. High SPINK1/TATI expression together with the low ANX2 expression at higher GS exhibited a bi‐directional relationship that is associated with PCa progression and survival.Conclusion: Importantly, the data reveal that ANX2, and SPINK1/TAT1 highly associate with WHO GS and with the transition from one stage of PrCa to the next in AA men. Future research is needed in biracial and larger population studies to confirm this dynamic relationship between ANX2 and SPINK1 as independent predictors of PCa progression in all men.

Objective: Cancer imposes higher burden on men. Sex differences in healthcare utilization may contribute to this problem. We compared healthcare utilization among adults with and without a history of cancer as measured by having at least one physician visit within the previous 12 months. Material and methods: We analyzed data from 7,229 responders (weighted population size=211,722,892) enrolled in the 2007 Health Information and National Trends Survey (HINTS), a nationally representative sample of non-institutionalized adults in the United States. We used survey weights in all analyses and variance estimation procedures to account for the complex survey design and used logistic regression models to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Results: Study participants consisted of 2808 (48.6%) males and 4421 (51.4%) females. Overall, men were less likely to have seen a physician within the previous 12 months (OR=0.39; 95% CI: 0.31-0.48) regardless of their cancer status. Cancer survivors were more likely to visit a physician within the previous 12 months (OR=2.01; 95% CI: 1.28-3.19) regardless of sex. When stratified by personal history of cancer, men without a history of cancer were less likely to visit a physician (OR=0.38; 95% CI: 0.30-0.47) whereas men with a history of cancer were as likely to have seen a physician in the previous 12 months as women with similar cancer status (OR=1.24; 95% CI: 0.44-3.45). Conclusion: Men increase their healthcare utilization to that of women only after they receive diagnosis of cancer. Targeted interventions to promote utilization of preventive care services by men are needed to reduce the burden of chronic illnesses including cancer among men. Cite this article as: Burnside C, Hudson T, Williams C, Lawson W, Laiyemo AO. Sex differences in the use of healthcare services among US adults with and without a cancer diagnosis. Turk J Urol 2018; 44: 298-302.

Snail transcription factor can induce epithelial-mesenchymal transition (EMT), associated with decreased cell adhesion-associated molecules like E-cadherin, increased mesenchymal markers like vimentin, leading to increased motility, invasion and metastasis. Muscadine grape skin extract (MSKE) has been shown to inhibit prostate cancer cell growth and induce apoptosis without affecting normal prostate epithelial cells. We investigated novel molecular mechanisms by which Snail promotes EMT in prostate cancer cells via Reactive Oxygen Species (ROS) and whether it can be antagonized by MSKE.