Improving early prostate cancer (PCa) detection in African-American (AA) men is fundamental for reducing racial disparities in PCa mortality. PCa detection and management relies mainly on PSA screening. While the use of this test has improved the eariy diagnosis and management of PCa, its limitations in regards to specificity, particularly among obese AA men, demands complementary non-invasive approaches for enhancing early PCa detection, monitoring disease progression, and evaluating therapeutic responses. The implementation of these novel approaches will depend on the identification of more specific and sensitive biomarkers that could be tailored to AA men. We will use an immunoseroproteomics approach focused on profiling serum auto-antibodies to tumor-associated antigens (TAAs) and serum exosomes in AA and Caucasian (CC) PCa patients. The project fills the gap of the lack of systematic immunoseroproteomics studies for biomarker identification in AA patients with PCa. It builds on our key observations indicating that: 1) PCa sera contain auto-antibodies to TAAs involved in tumor stress survival such as LEDGF/p75 and Survivin, and could act as sensors of inflammation and an augmented state of cellular oxidative stress (ASCOS);2) TAA mini-arrays enhance antibody detection in PCa patients and distinguish between cancer and normal populations;3) customized mini-arrays of PCa-specific TAAs are most effective in enhancing immunoserological diagnosis of PCa;4) PCa patient sera have exosomes that contain stress survival proteins such Survivin and PRDX3;and 5) there might be ethnic differences in the protein profiles or levels of serum exosomes. Our central hypothesis is that proteomic profiling of serum anti-TAA antibodies and exosomes in AA and CC PCa patients will yield novel biomarkers for enhancing early PCa detection and management, leading to the implementation of evidence-based interventions tailored to AA men.
The aims are to: 1) profile anfi-TAA antibodies in sera from AA and CC PCa patients using immunoproteomics and customized TAA mini-arrays;2) profile tumor-derived exosomal proteins in sera from AA and CC PCa patients by proteomics approaches;and 3) To determine in a comparative case-controlled pilot study if young AA men with no PCa diagnosis have increased serum levels of anti-TAA autoantibodies and tumorderived exosomal proteins, compared to AA men with PCa. Our goal is to identify and validate novel serum biomarkers that could be tailored to AA men to enhance the serological diagnosis of PCa, monitor disease progression, and guide personalized therapies.
The proposed study is responsive to the goals of the RFA-MD-11-002 because it addresses a specific theme identified by the NIMHD: Approaches for improvement of techniques for diagnosis, prevention, and treatment. The study is also highly significant and translational because knowledge of ethnic differences in the serobiology of PCa can be used for the design of early detecfion strategies that could be tailored to AA men, and more effective therapeutic interventions that would reduce racial disparities in PCa mortality.
|Liu, Jo-Wen; Montero, Manuel; Bu, Liming et al. (2015) Epidermal fatty acid-binding protein protects nerve growth factor-differentiated PC12 cells from lipotoxic injury. J Neurochem 132:85-98|
|Spencer-Hwang, Rhonda; Montgomery, Susanne; Dougherty, Molly et al. (2014) Experiences of a rail yard community: life is hard. J Environ Health 77:8-17|
|Payne, Kimberly J; Dovat, Sinisa (2014) G0S2--a new player in leukemia. Leuk Res 38:147-8|
|Salto, Lorena M; Riggs, Matt L; Delgado De Leon, Daisy et al. (2014) Underrepresented minority high school and college students report STEM-pipeline sustaining gains after participating in the Loma Linda University Summer Health Disparities Research Program. PLoS One 9:e108497|
|Weldon, David J; Saulsbury, Marilyn D; Goh, Joshua et al. (2014) One-pot synthesis of cinnamylideneacetophenones and their in vitro cytotoxicity in breast cancer cells. Bioorg Med Chem Lett 24:3381-4|
|Pacheco, Fabio J; Almaguel, Frankis G; Evans, Whitney et al. (2014) Docosahexanoic acid antagonizes TNF-?-induced necroptosis by attenuating oxidative stress, ceramide production, lysosomal dysfunction, and autophagic features. Inflamm Res 63:859-71|
|Salud, Margaret C; Marshak, Helen Hopp; Natto, Zuhair S et al. (2014) Exploring HIV-testing intentions in young Asian/Pacific Islander (API) women as it relates to acculturation, theory of gender and power (TGP), and the AIDS risk reduction model (ARRM). AIDS Care 26:642-7|
|Galloway, Nicholas R; Diaz Osterman, Carlos J; Reiber, Karl et al. (2014) Yin Yang 1 regulates the transcriptional repression of Survivin. Biochem Biophys Res Commun 445:208-13|
|Figueroa, Johnny D; De Leon, Marino (2014) Neurorestorative targets of dietary long-chain omega-3 fatty acids in neurological injury. Mol Neurobiol 50:197-213|
|Dai, Liping; Li, Jitian; Ortega, Rosalia et al. (2014) Preferential autoimmune response in prostate cancer to cyclin B1 in a panel of tumor-associated antigens. J Immunol Res 2014:827827|
Showing the most recent 10 out of 14 publications