Despite the potential for adverse pathological features in anterior-based disease, there appears to be no demographic predilection, notable delay in diagnosis or significant difference in survival outcomes.

Mechanisms underlying progression to androgen-independent prostate cancer following radical ablation therapy remain poorly defined. Although intraprostatic infections have been highlighted as potential cofactors, pathogen influences on pathways that support tumor regrowth are not known. To explore this provocative concept, we derived androgen-sensitive and -insensitive prostate epithelial cells persistently infected with human herpesvirus 8 (HHV-8), an oncogenic herpesvirus that has been detected in normal prostate epithelium, prostate adenocarcinoma, and biologic fluids of patients with prostate cancer, to explore its effects on transition to hormone-refractory disease. Strikingly, we found that HHV-8 infection of androgen-sensitive prostate cancer cells conferred the capacity for androgen-independent growth. This effect was associated with altered expression and transcriptional activity of the androgen receptor (AR). However, HHV-8 infection bypassed AR signaling by promoting enhancer of zeste homolog 2 (EZH2)-mediated epigenetic silencing of tumor-suppressor genes, including MSMB and DAB2IP that are often inactivated in advanced disease. Furthermore, we found that HHV-8 triggered epithelial-to-mesenchymal transition. Although HHV-8 has not been linked etiologically to prostate cancer, virologic outcomes revealed by our study provide mechanistic insight into how intraprostatic infections could constitute risk for progression to androgen-independent metastatic disease where EZH2 has been implicated. Taken together, our findings prompt further evaluations of the relationship between HHV-8 infections and risk of advanced prostate cancer. Cancer Res; 73(18); 5695-708. Ó2013 AACR.

Background The relationship between race, prostate tumor location, and BCR‐free survival is inconclusive. This study examined the independent and joint roles of patient race and tumor location on biochemical recurrence‐free (BCR) survival. Methods A retrospective cohort study was conducted among men with newly diagnosed, biopsy‐confirmed, NCCN‐defined low risk CaP who underwent radical prostatectomy (RP) at the Walter Reed National Military Medical Center from 1996 to 2008. BCR‐free survival was modeled using Kaplan‐Meier estimation curves and multivariable Cox proportional hazards (PH) analyses. Results There were 539 eligible patients with low‐risk CaP (25% African American, AA; 75% Caucasian American, CA). Median age at CaP diagnosis and post‐RP follow‐up time was 59.2 and 8.1 years, respectively. Kaplan‐Meier analyses showed no significant association between race (P = .52) or predominant tumor location (P = .98) on BCR‐free survival. In Cox PH multivariable analysis, neither race (HR = 1.18; 95% CI = 0.68‐2.02; P = .56) nor predominant tumor location (HR = 1.13; 95% CI = 0.59‐2.15; P = .71) was an independent predictor of BCR‐free survival. Conclusions Neither race nor predominant tumor location was associated with adverse oncologic outcome.

KSHV is the etiologic agent for Kaposi's sarcoma (KS), a neoplasm that manifests most aggressively as multifocal lesions on parts of human skin with a propensity for inflammatory reactivity. However, mechanisms that control evolution of KS from a benign hyperplasia to the histologically complex cutaneous lesion remain unknown. In this study, we found that KSHV induces proteomic and morphological changes in melanocytes and melanoma-derived cell lines, accompanied by deregulation of the endogenous anti-inflammatory responses anchored by the MC1-R/α-MSH signaling axis. We also identified two skin-derived cell lines that displayed differences in ability to support long-term KSHV infection and mapped this dichotomy to differences in (a) NF-κB activation status, (b) processing and expression of KSHV latency-associated nuclear antigen isoforms putatively associated with the viral lytic cycle, and (c) susceptibility to virus-induced changes in expression of key anti-inflammatory response genes that antagonize NF-κB, including MC1-R, POMC, TRP-1, and xCT. Viral subversion of molecules that control the balance between latency and lytic replication represents a novel correlate of KSHV pathogenesis and tropism in skin and underscores the potential benefit of harnessing the endogenous anti-inflammatory processes as a therapeutic option for attenuating cutaneous KS and other proinflammatory outcomes of KSHV infection in high-risk individuals.

Hydrocarbons are a wide-ranging group of flammable chemicals and are often used in suicide attempts either by ingestion or as an accelerant in self-immolation. In this case study, we present a 37-year-old female who suffered 6% TBSA partial-thickness burns to her perineum and buttocks, which she claims resulted from diarrhea after ingesting a bottle of lighter fluid. The patient underwent decontamination and medical treatment for her burns and during her inpatient stay, it became apparent that the burns were more likely sustained from an intentional rectal administration of lighter fluid. To our knowledge, this is one of the first reported cases of hydrocarbon enema. We review hydrocarbon poisoning, including both ingestion and dermal exposure, and discuss medical management.