Infection with high risk Human papillomavirus (HR-HPV) is necessary but not sufficient to cause cervical carcinoma. This study explored whether multiple HR-HPV or coinfection with Epstein-Barr virus (EBV) influence the integration status of HPV16 genome. The presence and typing of HPV in a series of 125 cervical specimens were assessed by polymerase chain reaction (PCR) using the specific primers for the HPV L1 region. As for EBV infection, the viral EBNA1 gene was used for its detection through PCR amplification. Disruption of the HPV E2 gene was assessed by amplification of the entire E2 gene with single set of primers, while E2 transcripts were evaluated by a reverse transcription PCR method (RT-PCR). The overall prevalence of HPVDNA was of 81.8% in cervical cancers versus 26.9% in benign lesions. In HPV positive cases, HPV16 and HPV18 were the most prevalent types, followed by HPV types 33, 31. EBV EBNA1 prevalence was statistically more frequent in cervical carcinomas than in benign lesions (29.5%, vs 9.6%; P=0.01). No viral infection was detected in healthy control women. The uninterrupted E2 gene was correlated with the presence of E2 transcripts originating from the HPV episomal forms. It was observed that integration was more common in HPV18 and EBV coinfection. The presence of EBV caused a five-fold [OR= 5; CI= 1.15-21.8; P = 0.04] increase in the risk of HPV16 genome integration in the host genome. This study indicates that EBV infection is acting as a cofactor for induction of cervical cancer by favoring HPVDNA integration.

Objectives: Cancer is a complex process in which cytokines play an important role. Cytokines are low-molecular weight soluble proteins involved in cellular transmission signals and several disorders. Pro-inflammatory cytokines (IL-1, TNF-alpha and IL-6) are involved in prostate cancer development. The aim of this study was to relate the expression (analyzed by Western blot and immuno-histochemistry) of several pro-inflammatory cytokines (IL-1, TNF-alpha and IL-6) with serum levels of prostate-specific antigen (PSA) in normal (no pathological samples) as pathological samples (hyperplasia and cancer), in order to elucidate their possible role in tumor progression. We are also discussing the possible use of these cytokines as a potential therapeutic target. Methods: This study was carried out in 5 normal, 25 benign prostatic hyperplastic (BPH) and 17 prostate cancer (PC) human prostates. Immunohistochemical and Western blot analysis were performed. Serum levels of PSA were assayed by a PSA DPC immulite assays (Diagnostics Products Corporation, Los Angeles, CA) Results: In BPH, IL-1alpha, IL-6 and TNF-alpha were only expressed in patients with PSA serum levels of 0-4 ng/ml or 4-20 ng/ml, but not in the group >20 ng/ml. In PC these cytokines were only expressed in patients with PSA serum levels >4 ng/ml, although the expression of these cytokines was elevated when PSA levels were >20 ng/ml. Conclusions: In PC there might be an association between high expression of pro-inflammatory cytokines (IL-1, TNFalpha and IL-6), elevated serum levels of PSA and cancer progression. A better understanding of the biologic mechanism of this association may improve the finding of new targets for therapy in these patients.

Objetivo: El cáncer es un proceso complejo en el cual las citoquinas juegan un importante papel. Las citoquinas son proteínas solubles de bajo peso molecular, que participan en la transmisión celular y en diferentes patologías. Las citoquinas pro-inflamatorias (IL-1, TNF-alfa e IL-6) están muy relacionadas con el desarrollo del cáncer de próstata. El objetivo de nuestro trabajo consistió en relacionar la expresión (mediante inmunocitoquímica y Western blot) de diferentes citoquinas pro-inflamatorias (IL-1, TNF-alfa e IL-6) con los niveles de antígeno prostático específico (PSA) en suero, tanto en pacientes normales (sin patología prostática) como en condiciones patológicas (hiperplasia y cáncer), así como su posible papel en la progresión tumoral. Se discutirá el posible uso de estas citoquinas como diana terapéutica. Métodos: Este estudio se ha realizado en 5 pacientes normales, 25 pacientes diagnosticados de hiperplasia benigna de próstata (HBP) y 17 pacientes de cáncer (CP). Se han realizado análisis de Western blot e inmunocitoquímica. Los niveles séricos de PSA se midieron mediante un "PSA DPC immulite assays" (Diagnostics Products Corporation, Los Angeles, CA). Resultados: En HBP, IL-1alfa, IL-6 y TNF-alfa, solo se expresan en pacientes con niveles séricos de PSA de 0-4 ng/ml ó 4-20 ng/ml, pero no en el grupo >20 ng/ml. En cáncer, estas citoquinas se expresan en pacientes con niveles séricos de PSA >4 ng/ml, aunque la expresión de estas citoquinas se eleva considerablemente cuando los niveles de PSA son >20 ng/ml. Conclusiones: En cáncer, podría existir una asociación entre elevada expresión de citoquinas pro-inflamatorias (IL-1, TNF-alfa e IL-6), elevados niveles séricos de PSA y progresión del cáncer. Un mejor conocimiento de los mecanismos biológicos de esta asociación, podrían ayudarnos a encontrar una posible diana terapéutica para los pacientes con patología prostática.