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1.
Prostate ; 77(6): 617-624, 2017 May.
Article in English | MEDLINE | ID: mdl-28117495

ABSTRACT

BACKGROUND: Serum-prostate specific antigen (PSA) levels have been used for many years as a biomarker for prostate cancer. This usage is under scrutiny due to the fact that elevated PSA levels can be caused by other conditions such as benign prostatic hyperplasia and infections of or injury to the prostate. As a result, the identification of specific pathogens capable of increasing serum levels of PSA is important. A potential candidate responsible for elevated PSA is human herpesvirus 8 (HHV-8). We have reported previously that HHV-8 is capable of infecting and establishing a latent infection in the prostate. In this current study we test the hypothesis that HHV-8 infection is associated with elevated PSA levels. Circulating cytokine levels between men with elevated PSA and controls are also compared. METHODS: HHV-8 serostatus was determined among men with elevated serum PSA (≥4 ng/ml; n = 168, no prostate cancer on biopsy) and age-matched controls (PSA <4 ng/ml; n = 234), Circulating cytokine levels were determined among a subset of each group (116 with elevated PSA and 85 controls). RESULTS: Men with an elevated serum PSA were significantly more likely to be HHV-8 seropositive (42.9%) than the age-matched cancer-free men (22.2%; OR 2.51; 95%CI 1.48-4.29, P = 00001). Comparison of circulating cytokine levels between men with elevated serum PSA and controls indicated that elevated serum PSA is associated with a pro-inflammatory response with a mixed Th1/Th2 response while HHV-8 infection was associated with significantly higher levels of IL12p70, IL-10, and IL-13 indicating a Th2 immune response. CONCLUSIONS: We found a significant association between HHV-8 infection and increased levels of serum PSA. In an age of patient-centered medicine, men with an elevated serum PSA should be considered for HHV-8 serology testing to determine if HHV-8 is responsible for the elevated PSA. Prostate 77: 617-624, 2017. © 2017 Wiley Periodicals, Inc.


Subject(s)
Cytokines/blood , Herpesviridae Infections/blood , Herpesviridae Infections/epidemiology , Herpesvirus 8, Human , Prostate-Specific Antigen/blood , Aged , Biomarkers/blood , Herpesviridae Infections/diagnosis , Humans , Male , Middle Aged , Prostatic Neoplasms/blood , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/epidemiology , Trinidad and Tobago/epidemiology
2.
Int J Urol ; 24(1): 64-68, 2017 01.
Article in English | MEDLINE | ID: mdl-27734534

ABSTRACT

OBJECTIVES: To compare the cytokine profile between human herpesvirus 8 seropositive and seronegative men with and without prostate cancer. METHODS: The study sample was obtained from the Tobago Prostate Survey, an ongoing study of prostate cancer in the Caribbean island of Tobago. Participants in the study were recruited mostly by public service announcement and by word of mouth. For analyses of circulating levels of pro-inflammatory cytokines, participants with biopsy-confirmed prostate cancer (n = 79) were compared with control participants (n = 87). RESULTS: Cytokine analyses showed a T helper 2 response with suppressed T helper 1 response in prostate cancer patients, as evidenced by significantly increased levels of interleukin-13 and reduced levels of interleukin-12p70. Herpesvirus 8 seropositive men showed significantly increased levels of interleukin-13 and interleukin-10. At logistic regression analyses, interleukin-12p70 predicted prostate cancer in 94.4% of human herpesvirus 8 seropositive men. CONCLUSIONS: These findings show that prostate cancer elicits an antitumor, T helper 2 response with a suppressed T helper 1 response. Human herpesvirus 8 infection results in a similar immune response supporting the hypothesis that in Tobago, human herpesvirus 8 establishes a chronic infection that can contribute to an immune response favoring the formation and survival of prostate cancer.


Subject(s)
Herpesviridae Infections/immunology , Herpesvirus 8, Human/immunology , Prostatic Neoplasms/immunology , Th2 Cells/immunology , Tumor Microenvironment/immunology , Aged , Case-Control Studies , Herpesviridae Infections/blood , Herpesviridae Infections/virology , Herpesvirus 8, Human/isolation & purification , Humans , Interleukin-10/blood , Interleukin-12/blood , Interleukin-13/blood , Lymphocyte Activation , Male , Middle Aged , Prostate/immunology , Prostate/virology , Prostatic Neoplasms/blood , Prostatic Neoplasms/virology , Trinidad and Tobago
3.
PLoS One ; 9(8): e106013, 2014.
Article in English | MEDLINE | ID: mdl-25153315

ABSTRACT

Angiogenesis, the formation of new blood vessels, is important for the survival of ovarian transplants and the restoration of ovarian functions. Without angiogenesis, transplanted ovarian tissue becomes more susceptible to tissue damage and necrosis. Administration of analgesics for pain management has been shown to decrease angiogenesis, which can influence transplant success especially in aged animals. Aging and the effects of hypoxia after transplantation decrease reproductive viability of the ovarian transplant; therefore, it is important to understand the additional effects of analgesics on aged animal models. The present study investigated the effects of two analgesics, buprenorphine, an opiate, and meloxicam, a non-steroidal anti-inflammatory drug (NSAID), on the reproductive indicators related to estrous cyclicity and follicular integrity after ovarian transplantation of young ovaries into aged CBA/J mice. These aged females did not show any different reproductive responses when treated with either buprenorphine or meloxicam. No significant differences were observed in estrous cycle length, the onset of estrous cycling, the regularity of estrous cycles, and the proportion of viable follicles and total number of follicles per ovarian sample across treatment groups.


Subject(s)
Buprenorphine/pharmacology , Estrous Cycle/drug effects , Ovarian Follicle/drug effects , Thiazines/pharmacology , Thiazoles/pharmacology , Transplants/drug effects , Animals , Estrus/drug effects , Female , Meloxicam , Mice , Mice, Inbred CBA , Neovascularization, Physiologic/drug effects , Reproduction/drug effects
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