Role of PPAR alpha in the mechanism of action of the nongenotoxic carcinogen and peroxisome proliferator Wy-14,643

Chronic administration of peroxisome proliferators to mice and rats results in hepatomegaly and ultimately carcinogenesis. The mechanism underlying the carcinogenic effect of nongenotoxic peroxisome proliferators is not well understood. To determine whether nongenotoxic carcinogenesis is receptor mediated, we evaluated the effect of the prototypical peroxisome proliferator Wy-14,643 on replicative DNA synthesis and carcinogenesis in the PPAR alpha-null mouse line. Male mice (F4, Sv/129 ter) of both genotypes (+/+) and (-/-) were fed either a control diet or one containing 0.1% Wy-14,643 for either 1 week, 5 weeks, or 11 months. Wild-type mice fed the Wy-14,643 diet for 1 or 5 weeks showed increased hepatic labeling by bromodeoxyuridine (BrDU) compared to untreated controls. In contrast, there was no increase in hepatic BrDU labeling index in (-/-) mice fed the Wy-14,643 diet for the same time periods compared to controls. After 11 months, 100% of the (+/+) mice fed the Wy-14,643 diet had multiple hepatocellular neoplasms, including adenomas and carcinomas, while the (-/-) mice fed the Wy-14,643 diet were unaffected. This work demonstrates that the effects of Wy-14,643 on replicative DNA synthesis and hepatocarcinogenesis are mediated by PPAR alpha.      

Immunogenicity of an Intranasally Administered Modified Live Canine Parvovirus Type 2b Vaccine in Pups with Maternally Derived Antibodies

The ability of a modified live canine parvovirus type 2b vaccine to elicit active immunization in pups with maternally derived antibodies (MDA) by intranasal administration was evaluated. The vaccine induced seroconversion in 100% of pups with MDA titers of ≤80 and in 51.6% of pups with titers between 160 and 320.     

Ocular adnexal MALT lymphoma: an intriguing model for antigen-driven lymphomagenesis and microbial-targeted therapy.

Non-Hodgkin's lymphomas constitute one half of malignancies arising in the orbit and the ocular adnexae. Mucosa-associated lymphoid tissue (MALT)-type lymphoma is the most common histological category in this anatomic region. The incidence of ocular adnexal lymphoma of mucosa-associated lymphoid tissue-type (OAML) is increasing and recent studies offered new relevant insights in molecular, pathogenetic and therapeutic issues on these neoplasms. A pathogenetic model of antigen-driven lymphoproliferation similar to that reported for Helicobacter pylori-related gastric MALT lymphomas has been hypothesized for OAML. This notion is supported by the association between OAML and Chlamydophila psittaci infection, an association that is of likely pathogenetic relevance and may influence both the biological behavior and the therapeutic management of these neoplasms. However, this association displays evident geographical variability indicating that other etiopathogenic agents could be involved. These recent acquisitions coupled with the occurrence of chromosomal translocations and other genetic alterations, as well as additional risk factors like autoimmune disorders have contributed to render OAML an exciting challenge for a broad group of physicians and scientists. OAML is an indolent and rarely lethal malignancy that, in selected patients, can be managed with observation alone. Lymphomatous lesions are frequently responsible for symptoms affecting patient's quality of life, requiring, therefore, immediate treatment. Several therapeutic strategies are available, often associated with relevant side-effects. However, the therapeutic choice in OAML is not supported by consolidated evidence due to the lack of prospective trials. In this review, we analyze the most relevant biological, molecular, pathological and clinical features of OAML and propose some therapeutic guidelines for patients affected by this malignancy.     

HER-2, p53, p21 and hormonal receptors proteins expression as predictive factors of response and prognosis in locally advanced breast cancer treated with neoadjuvant docetaxel plus epirubicin combination

Background  

Neoadjuvant chemotherapy has been considered the standard care in locally advanced breast cancer. However, about 20% of the patients do not benefit from this clinical treatment and, predictive factors of response were not defined yet. This study was designed to evaluate the importance of biological markers to predict response and prognosis in stage II and III breast cancer patients treated with taxane and anthracycline combination as neoadjuvant setting.