Subacute cadmium exposure disrupts the hypothalamic-pituitary-gonadal axis, leading to polycystic ovarian syndrome and premature ovarian failure features in female rats.

Cadmium (Cd), a toxic heavy metal, is a known endocrine disruptor that is associated with reproductive complications. However, few studies have explored the effects of Cd exposure on features of polycystic ovary syndrome (PCOS) and premature ovary failure (POF). In this study, we assessed whether doses found in workers occupationally exposed to Cd and subacute exposure result in hypothalamic-pituitary-gonadal (HPG) axis and other irregularities. We administered CdCl2 to female rats (100 ppm in drinking water for 30 days) and then assessed Cd levels in the blood, HPG axis and uterus. Metabolic features, HPG axis function, reproductive tract (RT) morphophysiology, inflammation, oxidative stress (OS), and fibrosis were evaluated. Cd exposure increased Cd levels in the serum, HPG axis, and uterus. Cd rats displayed metabolic impairments, such as a reduction in adiposity, dyslipidemia, and insulin resistance (IR). Cd exposure also caused improper functioning in the HPG. Specifically, Cd exposure caused irregular estrous cyclicity, abnormal hypothalamic gene expression (upregulated - Kiss1, AR and mTOR; downregulated - Kiss1R, LepR and TNF-α), high LH levels, low AMH levels and abnormal ovarian follicular development, coupled with a reduction in ovarian reserve and antral follicle number was observed, suggesting ovarian depletion. Further, Cd exposure caused a reduction in corpora lutea (CL) and granulosa layer thickness together with an increase in cystic/atretic follicles. In addition, Cd exposure caused RT inflammation, OS and fibrosis. Finally, strong positive correlations were observed between serum, RT Cd levels, IR, dyslipidemia and estrous cycle length, cystic, atretic follicles, LH levels, and RT inflammation. Thus, these data suggest that subacute Cd exposure using doses found in workers occupationally exposed to Cd disrupt the HPG axis function, leading to PCOS and POF features and other abnormalities in female rats.

Osteopontin expression and its relationship with prognostic biomarkers in canine mammary carcinomas / Expressão de osteopontina e sua relação com biomarcadores prognóstico nos carcinomas mamários caninos

Osteopontin is a glycophosphoprotein implicated in different physiologic and pathologic processes and is known to be involved in progression and metastasis of various cancers in humans, but this relation is still little explored in the veterinary. The aim was to evaluate the expression of osteopontin in canine mammary carcinomas and its relation with well-established canine mammary tumor biomarkers. For that, expression of OPN, EGFR, HER2, and c-Kit were evaluated along with Ki67 rate in 43 mammary carcinomas. Osteopontin was demonstrated to be expressed by neoplastic epithelial cells in all carcinomas as well as in stromal cells from the tumor microenvironment. Relation between high osteopontin expression and EGFR positivity (P<0.001) and HER2 overexpression (P=0.012) was demonstrated. In conclusion, high OPN expression seems to be related to poor prognosis and MAPK pathway activation, given the association with EGFR and HER2, members of the MAPK signaling pathway.(AU)

A osteopontina é uma glicofosfoproteina implicada em diferentes processos fisiológicos e patológicos, sendo conhecida por estar envolvida na progressão e metástase de vários cânceres nos humanos, no entanto, essa relação é ainda pouco explorada na veterinária. O objetivo deste trabalho foi avaliar a expressão da osteopontina nos carcinomas mamários caninos e sua relação com biomarcadores bem estabelecidos para esta neoplasia. Para isto, foi avaliada a expressão de OPN, EGRH, HER2 e c-Kit juntamente com a taxa de Ki67 em 43 carcinomas mamários. A osteopontina foi expressa pelas células epiteliais neoplásicas em todos os carcinomas, assim como, nas células estromais do microambiente tumoral. Foi demonstrada uma relação entre uma alta expressão de osteopontina e positividade para EGFR (P<0.001) e superexpressão de HER2 (P=0.012). Em conclusão, alta expressão de OPN parece estar relacionada com mau prognóstico e ativação da via MAPK, devido a sua associação com EGRF e HER2, os quais são membros desta via de sinalização.(AU)

Feasibility study with 99mTc-HYNIC-ßAla-Bombesin(7-14) as an agent to early visualization of lung tumour cells in nude mice.

AIM: More sensitive and accurate imaging approaches for early detection and therapy monitoring of lung tumours are needed to ameliorate prognosis and outcome. Lung tumours are known to overexpress receptors for bombesin-like peptides. However, thus far, no study has demonstrated the potential role of bombesin-like peptides in identifying A549 lung tumour cells in xenograft animal models. Thus, we evaluate the feasibility of Tc-HYNIC-ßAla-Bombesin(7-14) as an imaging probe in lung cancer. METHODS AND RESULTS: Xenograft lung tumours were implanted in nude mice and evaluated by histopathological analysis. Tumours were easily visualized by Tc-HYNIC-ßAla-Bombesin(7-14) within 30 days after inoculation of the A549 cell line into mice. Scintigraphic images showed high tumour-to-background ratio. DISCUSSION: The data obtained in this study indicate that Tc-HYNIC-ßAla-Bombesin(7-14) may be useful as an imaging probe to detect A549 lung cancer cells. To our knowledge, this is the first time that this specific radiocompound has been used to visualize non-small-cell lung cancer A549 in mice. Further translational research in humans is required to establish the potential role of this radiocompound in clinical practice.

Clinical, cytologic, and histologic features of a mammary micropapillary carcinoma in a dog.

Mammary invasive micropapillary carcinoma is a rare variant of mammary carcinoma that was recently recognized in dogs. The cytologic features and biologic behavior of such neoplasms in dogs have not yet been widely discussed in the veterinary literature. We report the clinical, cytologic, and histologic features of a canine micropapillary carcinoma in a 13-year-old female mongrel dog. The mammary region presented with extreme local pain, severe edema and erythema, and multifocal epidermal ulceration, which is typical for an inflammatory mammary carcinoma. Fine-needle aspirates were highly cellular and consisted of individual cells and papillary cell clusters with characteristics of malignant epithelial cells. Histologic examination revealed neoplastic cells arranged in small papillae without fibrovascular cores, sometimes inside clear lymphatic spaces, indicating lymphovascular invasion. Regional lymph node evaluation revealed metastatic cells. Due to deteriorating clinical condition the dog was euthanatized 5 months after mastectomy. At necropsy, metastatic neoplastic mammary cells were found in popliteal and mediastinal lymph nodes, the right femoral biceps muscle, liver, heart, lungs, and urinary bladder.

Adenocarcinoma of the parotid salivary gland in a cow.

A 6-year-old Girolando dairy cow was presented for evaluation of a large subcutaneous facial mass. Fine-needle aspirates of the mass contained many neoplastic cells with high nuclear:cytoplasmic ratios arranged in sheets and loosely cohesive clusters with streaming erythrocytes and neutrophils in the background. Neoplastic cells were 13-25 µm in diameter and were round to cuboidal with variably distinct borders. Based on the signalment, anatomic location, and cytologic findings, differential diagnoses included salivary adenocarcinoma, squamous cell carcinoma, and mucoepidermoid carcinoma. The cow was euthanized and a necropsy was performed. The primary neoplasm arose from the left parotid salivary gland and meastatic tumor was found in the regional lymph nodes and lung. Histologically, the tumor was composed of anastomosing and irregular solid islets surrounded by scant stroma. Cells were negative for periodic acid-Schiff (PAS), PAS-diastase, and Alcian blue pH 2.5 stains, used to detect mucin. On immunohistochemical analysis, neoplastic luminal salivary gland cells expressed cytokeratin, but not S100, α-smooth muscle actin, or vimentin. Peripheral cells of neoplastic islets were immunoreactive for p63. The final diagnosis was nonsecretory adenocarcinoma of the parotid salivary gland.

Ocular melanoma and mammary mucinous carcinoma in an African lion.

BACKGROUND: Reports of neoplasms in Panthera species are increasing, but they are still an uncommon cause of disease and death in captive wild felids. The presence of two or more primary tumor in large felids is rarely reported, and there are no documented cases of ocular melanoma and mammary mucinous carcinoma in African lions. CASE PRESENTATION: An ocular melanoma and a mammary mucinous carcinoma are described in an African lion (Panthera leo). The first tumour was histologically characterized by the presence of epithelioid and fusiform melanocytes, while the latter was composed of mucus-producing cells with an epithelial phenotype that contained periodic acid-Schiff (PAS) and Alcian blue staining mucins. Metastases of both tumor were identified in various organs and indirect immunohistochemistry was used to characterize them. Peribiliary cysts were observed in the liver. CONCLUSIONS: This is the first description of these tumor in African lions.

Ectopic ossification presenting as osteoid metaplasia in a salivary mucocele in a Shih Tzu dog.

BACKGROUND: Salivary mucocele is an accumulation of saliva in a single or multiloculated cavity lined by connective tissue that is contiguous to a salivary gland-duct complex and is the most common condition affecting the salivary glands in dogs. Occasionally, different types of metaplastic lesions, such as squamous and osseous metaplasia - which are rare lesions in animals - can be observed in association with salivary mucocele. CASE PRESENTATION: A right facial enlargement was suddenly observed in a 4-year-old non-spayed female Shih-Tzu dog. The lesion presented itself as a soft and fluctuant mass located in the right side of the face near to the neck. Histologically, the mass consisted of a cavitary formation without an epithelial lining. Additionally, microscopic examination revealed the presence of osteoid-producing cells which gave rise to areas of bone formation, probably induced by irritation due to the presence sialoliths. Such cells and bone formations were also present in the cavity wall, consequently leading us to classify the condition as a salivary mucocele with osseous metaplasia. CONCLUSIONS: In the present case, the pathogenesis was probably associated with the presence of sialoliths, which can behave as etiological agents for the metaplastic lesion. The occurrence of osteoid metaplasia is a rare peculiar condition in the canine salivar y gland, and due to the rarity and lack of information about this specific disease, no clinical data can yet be associated with the development of salivary mucocele with osseous metaplasia in dogs.

Ovarian mucinous cystadenoma in a gray brocket deer (Mazama gouazoupira).

An ovarian mucinous cystadenoma is described in a gray brocket deer (Mazama gouazoupira). The tumor was histologically characterized by the presence of cysts and proliferation of papillae, both lined by single- or multi-layered pleomorphic epithelial cells that contained alcian blue-positive mucins.