Exposure to a Glyphosate-based Herbicide Alters the Expression of Key Regulators of Mammary Gland Development on Pre-pubertal Male Rats.

We previously reported that exposure during gestation and lactation to a low dose of glyphosate-based herbicide (GBH) reduced the area and perimeter of male offspring mammary gland at postnatal day 60 (PND60), whereas a higher dose increased the longitudinal growth of the gland. Here, our aim was to assess whether perinatal exposure to GBH exhibits endocrine disruptive action in male mammary gland at an early time point (pre-puberty), which could be related to the changes observed after puberty. We also wanted to explore whether an early evaluation of the male rat mammary gland is appropriate to assess exposure to potential endocrine disrupting chemicals (EDCs). Pregnant rats were orally exposed, through the diet, to vehicle (saline solution), 3.5 or 350 mg/kg/day of GBH from gestational day 9 until weaning. At PND21, the male offspring were euthanized, and mammary gland samples were collected. The histology and proliferation index of the mammary glands were evaluated, and the mRNA expression of estrogen (ESR1) and androgen (AR) receptors, cyclin D1 (Ccnd1), amphiregulin (Areg), insulin-like growth factor 1 (IGF1), epidermal growth factor receptor (EGFR) and IGF1 receptor (IGF1R) were assessed. Moreover, the phosphorylated-Erk1/2 (p-ERK1/2) protein expression was determined. No differences were observed in mammary epithelial structures and AR expression between experimental groups; however, the proliferation index was reduced in GBH3.5-exposed males. This result was associated with decreased ESR1, Ccnd1, Areg, IGF1, EGFR and IGF1R mRNA expressions, as well as reduced p-Erk1/2 protein expression in these animals. ESR1, Ccnd1, IGF1R and EGFR expressions were also reduced in GBH350-exposed males. In conclusion, the mammary gland development of pre-pubertal male rats is affected by perinatal exposure to GBH. Although further studies are still needed to understand the molecular mechanisms involved in GBH350 exposure, the present results may explain the alterations observed in mammary gland growth of post-pubertal males exposed to low doses of GBH. Our results also suggest that early evaluation of the male rat mammary gland is useful in assessing exposure to potential EDCs. However, analysis of EDCs effects at later time points should not be excluded.

Immunoexpression of growth factors and receptors in polymorphous low-grade adenocarcinoma.

BACKGROUND: Polymorphous low-grade adenocarcinoma (PLGA) is a rare malignant tumor that usually arises in the minor salivary glands. Growth factors are cell-secreted peptides that regulate biological processes such as growth, proliferation, and differentiation. In salivary gland tumors, immunoexpression of growth factors and their receptors is associated with cell proliferation, malignant transformation, and tumor invasion. This study analyzed the expression of growth factors and receptors in PLGA, in other to better understand the mechanisms involved in the process of neoplastic cell proliferation and tumor progression. METHODS: The expression of growth factors FGF-2, PDGF-A, PDGF-B and receptors FGFR-1, FGFR-2, PDGFR-α, and EGFR was analyzed in 24 PLGA samples in comparison with normal salivary glands, by immunohistochemistry. A semi-quantitative analysis determined cell positivity in all stained sections. Scores were assigned according to percentage of reactive cells: score 0 < 10%; score 1-10 to 25%; score 2-25% to 50%; score 3->50%. The level of significance was set at 5%. RESULTS: Most of the growth factors and receptors, apart from FGFR-2, were significantly reactive in PLGA. Comparing to salivary acini, all of the reactive growth factors and receptors were significantly stronger in PLGA. Comparing to salivary ducts, the expression of FGF-2, PDGF-B, FGFR-1, and EGFR was significantly stronger in the nuclei and/or cytoplasm of the neoplastic cells. CONCLUSIONS: The increased expression of the growth factors and receptors in the PLGA, compared to normal salivary glands, may be related to cell proliferation, somehow participating in the oncogenic process.

[Role of the expression of c-Met receptor in the progression of gastric cancer]. / Papel de la expresión del receptor c-Met en la progresión del cancer gástrico.

The product of the proto-oncogene C-MET (the c-Met receptor) and its ligand, hepatocyte growth factor (HGF), have been implicated in the progression of gastric cancer. The aim of this study was to analyze the expression of c-Met receptor, HGF and proliferating cell nuclear antigen (PCNA) by the immunohistochemistry method of labeled streptavidin-biotin, as well as survival, and they were correlated with anatomopathological factors in stomach specimens of 40 patients, who underwent gastrectomy for gastric cancer in the Department of General Surgery, Hospital Central Universitario "Antonio María Pineda" in Barquisimeto, Venezuela, in 2001-2004. High expression of c-Met receptor and PCNA was observed in patients with advanced stages of gastric cancer (III and IV) compared with early stages (I and II) (p<0.01). There was also overexpression of the c-Met receptor in histologic variables with low degree of differentiation, deeper tumor invasion into the submucosa, liver metastases and it is reported a lower survival rate in patients with increased receptor expression (+++ and ++++) when compared with patients with the lowest expression (+ and ++) (p<0.01). The expression of HGF was constant in both, advanced and early groups. The c-Met receptor is associated with proliferation and cell migration in Venezuelan patients with gastric cancer and could be used as a prognostic factor in this pathology.

MET Is highly expressed in advanced stages of colorectal cancer and indicates worse prognosis and mortality.

UNLABELLED: The aim of the present study was to evaluate by immunohistochemistry the prognostic meaning of the tumor marker MET (hepatocyte growth factor) in patients submitted to surgical resection due to primary colorectal adenocarcinoma. PATIENTS AND METHODS: A retrospective study was carried out that included 286 consecutive patients with colorectal adenocarcinoma, submitted to surgical resection at Barretos Cancer Hospital, from 1993 to 2002. The histopathological expression of the MET tumor marker was evaluated using an anti-protein monoclonal antibody against MET by the streptavidin-biotin-peroxidase technique. The expression of the tumor marker was semi-quantitative, and the slide samples were independently analyzed by three pathologists unaware of patient clinical and histopathological data. RESULTS: The tumor marker expression was positive in 236 (79%) out of a total of 286 patients. This expression was statistically significantly different between stages I and IV (p=0.004), for overall survival (p=0.009), and for cancer-related mortality rates (p=0.022). However, no association between the tumor marker and recurrence (p=0.89) or disease-free interval (p=0.91) was observed. CONCLUSION: MET has shown significant expression at advanced stages of the disease, as well as for overall survival and cancer-related mortality rates demonstrating to be a valuable marker for poor prognosis in colorectal cancer patients.