Article

Histopathological evidence for an association of inflammation with ductal pin-like lesions but not with ductal adenocarcinoma in the prostate of the noble rat.

Institute of Biomedicine, Department of Anatomy, University of Turku, Turku, Finland.
The Prostate (Impact Factor: 3.84). 06/2008; 68(7):728-39. DOI: 10.1002/pros.20719
Source: PubMed

ABSTRACT Chronic inflammation may contribute to the development of prostate cancer. The goal of this study was to determine the possible association of prostatic inflammation, prostatic intraepithelial neoplasia (PIN)-like lesion, and prostate cancer, and to assess the androgen and estrogen dependency of the early steps of carcinogenesis.
Noble rats were treated with testosterone and estradiol implants for 13, 18, or 26 weeks. Hormone dependency of the lesions was studied in a subset of animals by removing hormone implants for 3 weeks after 15 weeks treatment time.
After treatment for 13 weeks, acute and chronic inflammation was found in the dorsolateral prostate lobes and both inflammation and PIN-like lesions were present in the periurethal area of the prostate in all animals (n = 8). Following hormone exposure for 18 and 26 weeks, inflammation in the prostate remained, and adenocarcinomas in the periurethal prostate area with no adjacent inflammation were observed in all 18 animals studied. When both hormone implants were removed after 15 weeks, PIN-like lesions progressed further to adenocarcinoma only in two of seven animals. When only the estradiol implants were removed, three of five animals developed adenocarcinomas.
Even though adenocarcinomas were not morphologically associated with inflammation, PIN-like lesions preceding adenocarcinoma were found in close association with inflammation, pointing towards a possible initiator role of inflammation in the early steps of prostatic carcinogenesis. Further, these results indicate that both androgens and estrogens together play a significant role in the induction of inflammation and prostatic cancer in this model.

0 Bookmarks
 · 
53 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: Characterization of novel rodent models for prostate cancer studies requires evaluation of either spontaneous and carcinogen-induced tumors as well as tumor incidence in different prostatic lobes. We propose a new short-term rodent model of chemically induced prostate carcinogenesis in which prostate cancer progression occurs differentially in the dorsolateral and ventral lobes. METHODS: Adult gerbils were treated with MNU alone or associated with testosterone for 3 or 6 months of treatment. Tumor incidence, latency, localization, and immunohistochemistry (AR, PCNA, smooth muscle α-actin, p63, MGMT, and E-cadherin) were studied in both lobes. RESULTS: Comparisons between both lobes revealed that lesions developed first in the DL while the VL presented longer tumor latency. However, after 6 months, there was a dramatic increase in tumor multiplicity in the VL, mainly in MNU-treated groups. Lesions clearly progressed from a premalignant to a malignant phenotype over time and tumor latency was decreased by MNU + testosterone administration. Three-dimensional reconstruction of the prostatic complex showed that the DL developed tumors exclusively in the periurethral area and showed intense AR, PCNA, and MGMT immunostaining. Moreover, VL lesions emerged throughout the entire lobe. MNU-induced lesions presented markers indicative of an aggressive phenotype: lack of basal cells, rupture of the smooth muscle cell layer, loss of E-cadherin, and high MGMT staining. CONCLUSIONS: There are distinct pathways involved in tumor progression in gerbil prostate lobes. This animal provides a good model for prostate cancer since it allows the investigation of advanced steps of carcinogenesis with shorter latency periods in both lobes. Prostate © 2013 Wiley Periodicals, Inc.
    The Prostate 04/2013; · 3.84 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: The prostate is considered to be an androgen dependent organ. On the other hand, the presence of estrogen receptors among different tissue components of the prostate indicates the direct effect of estrogen on the prostate, beside the known indirect effect through the hypothalamo-gonadal axis. Estrogen has been incriminated in the pathogenesis of certain prostatic diseases, namely, cancer prostate, benign prostatic hyperplasia and prostatitis. Methods: 57 adult male albino rats were used in this study. The rats were divided into two groups. Control groups (normal and sham) and experimental groups which were exposed to different estrogen treatments and were further subdivided into 3 subgroups: group LA (repeated low doses group), group TA (Therapeutic dose group) and group HA (single high dose group). The animals were sacrificed and the prostatic specimen were collected and prepared for light, electron microscopically and immunohistological studies. Results: The histological examination revealed the presence of epithelial and stromal hyperplasia in all the experimental groups in a dose dependant manner, the signs of epithelial hyperplasia included papillary projections, vesicular nuclei, marginated nucleoli and double nucleoli. Other common changes included inflammatory infiltration, apoptosis and acinar dilatation. Only the (TA) and (HA) groups showed signs of dysplasia in the form of pleomorphism and hyperchromatism. The ultrastructure examination of different experimental groups revealed variable degrees of degenerative changes. The changes included irregular cell membranes, poor cytoplasmic organelles, proliferated rough endoplasmic reticulum and the appearance of cytoplasmic vacuolations and fatty like inclusions. Nuclear changes included irregular nuclear membranes and pyknotic nuclei. Again, the profound degenerative changes were marked in both the (TA) and (HA) groups. Immunohistological examination revealed decreased immunostaining reactivity in all the experimental groups compared to the control groups. A further decrease was noted in both the (TA) and (HA) groups accompanying the severe dysplasia of these groups. Conclusion: It was concluded that estrogen induces prostatic hyperplasia and prostatic inflammation. Only therapeutic or high doses of estrogen produce dysplastic changes. Within certain limits, estrogen acts in a dose dependent manner. Recommendation: It could be recommended that estrogen treatment for cancer prostate should be restricted to specific cases. Maximum attention to serious side effects has to be ensured during estrogen treatments. Further investigations are needed to prove or exclude the role of estrogen in different prostatic diseases.
    Australian Journal of Basic and Applied Sciences. 01/2011; 5:59-73.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Previous studies with selenium and/or vitamin E in prostate carcinogenesis animal models have been negative, but these models may not involve oxidative stress mechanisms. In this study, we examined the potential of selenomethionine and alpha-tocopherol to modulate prostate cancer development in the testosterone plus estradiol-treated NBL rat, a model that does involve sex hormone-induced oxidative stress mechanisms and prostatic inflammation. One week following the implantation with hormone-filled Silastic implants, rats were fed diets containing l-selenomethionine (1.5 or 3.0 mg/kg), DL-alpha-tocopherol acetate (2,000 or 4,000 mg/kg), or a natural ingredient control diet (NIH-07). The development of prostate carcinomas was not affected by dietary treatment with either agent. Food intake, body weight, and mortality were also not affected. The high dose of selenomethionine reduced the severity of epithelial dysplasia in the lateral prostate that was not associated with inflammation, and alpha-tocopherol reduced in a dose-related fashion the incidence of marked inflammation and marked epithelial dysplasia in the lateral prostate, regardless of whether these lesions were associated with inflammation. alpha-Tocopherol significantly increased the incidence of adenocarcinomas of the mammary glands at both dietary concentrations. Collectively, our findings suggest that selenomethionine and alpha-tocopherol supplementation does not prevent prostate cancer in rats fed diets with nutritionally adequate levels of selenium and vitamin E. Importantly, the results of the current animal studies and those reported previously were fully predictive of the outcome of the Selenium and Vitamin E Cancer Prevention Trial.
    Cancer Prevention Research 02/2010; 3(3):371-80. · 4.89 Impact Factor