Differential stromal reprogramming in benign and malignant naturally occurring canine mammary tumours identifies disease-modulating stromal components

While cancer-associated stroma (CAS) in malignant tumours is well described, stromal changes in benign forms of naturally occurring tumours remain poorly characterized. Spontaneous canine mammary carcinomas (mCA) are viewed as excellent models of human mCA. We have recently reported highly conserved stromal reprogramming between canine and human mCA based on transcriptome analysis of laser-capture-microdissected FFPE specimen. To identify stromal changes between benign and malignant mammary tumours, we have analysed matched normal and adenoma-associated stroma (AAS) from 13 canine mammary adenomas and compared them to previous data from 15 canine mCA. Our analyses reveal distinct stromal reprogramming even in small benign tumours. While similarities between AAS and CAS exist, the stromal signature clearly distinguished adenomas from mCA. The distinction between AAS and CAS is further substantiated by differential enrichment in several hallmark signalling pathways as well as differential abundance in cellular composition. Finally, we identify COL11A1, VIT, CD74, HLA-DRA, STRA6, IGFBP4, PIGR, and TNIP1 as strongly discriminatory stromal genes between adenoma and mCA, and demonstrate their prognostic value for human breast cancer. Given the relevance of canine CAS as a model for the human disease, our approach identifies disease-modulating stromal components with implications for both human and canine breast cancer

Thyroglobulin as a negative marker for malignancy in canine and human breast tumors

Canine mammary gland tumors (CMTs) are the most common tumor type in female dogs. This study evaluated the expression pattern and role of thyroglobulin (Tg) in CMT and in human breast cancer (HBC). CMT samples were subjected to fine-needle aspiration, primary cell culture, and histopathology. The expression level of Tg was higher in benign CMT than in malignant CMT (mCMT) primary cells, particularly in the epithelial lineage. Moreover, treatment with Tg enhanced the sensitivity of doxorubicin in mCMT epithelial cells and mitigated proinflammatory response by increasing nuclear factor erythroid 2-related factor 2 (Nrf2). The proximal region of the Tg promoter was hypermethylated in mCMT epithelial cells, silencing Tg expression with concurrent downregulation of Nrf2-mediated antioxidant signaling. An identical pattern of Tg expression was observed in cytological and tissue samples. Tissue microarray analysis showed that Tg was highly expressed in normal and benign tissues when compared with their malignant counterparts, which was diminished along with higher histological grades. The survival rate was significantly higher in HBC patients with high Tg expression than those with low Tg expression. This study also showed that the progression of HBC is accompanied by the reduction of Tg expression along with augmentation of proinflammatory signaling. Our data suggested that Tg could be a negative indicator of malignancy in canine and human breast neoplasiaN

Feldspar, mica, beryl and tourmaline geochemistry and U-Pb geochronology in a monazite from fazenda Conc?rdia and S?o Domingos pegmatites - Esp?rito Santo, Brazil.

Os pegmatitos Fazenda Conc?rdia e S?o Domingos, inseridos no contexto geotect?nico do limite entre as faixas Ribeira e Ara?ua?, dentro da Prov?ncia Pegmat?tica Oriental do Brasil, est?o localizados, respectivamente, nos munic?pios de Mimoso do Sul e de Muqui ? sul do Esp?rito Santo. O objetivo principal deste trabalho ? estud?-los, a partir de aspectos geoqu?micos, a fi m de caracterizar a evolu??o desses corpos. As t?cnicas anal?ticas empregadas foram: microssonda eletr?nica (para a composi??o qu?mica dos feldspatos, micas, berilos e turmalina); LA-Q-ICP-MS (para a caracteriza??o dos elementos tra?os dos minerais citados); e LA-SF-ICP-MS (para a obten??o das idades pela raz?o U-Pb, em gr?os de monazita). Ambos os pegmatitos apresentam zoneamento simples e cont?m quartzo, feldspato e mica, por?m o pegmatito Fazenda Conc?rdia possui tamb?m turmalina, berilo e top?zio. Em rela??o ? geoqu?mica, foi poss?vel perceber que esses corpos apresentam um trend de evolu??o em que o pegmatito S?o Domingos ? menos diferenciado que o pegmatito Fazenda Conc?rdia. Quando comparados aos pegmatitos do Campo Marilac (Distrito Pegmat?tico de Governador Valadares), onde ocorrem pegmatitos simples a complexos, os pegmatitos Fazenda Conc?rdia e S?o Domingos n?o apresentam um grau de evolu??o elevado/complexo. A monazita do pegmatito S?o Domingos apresenta a mesma idade da rocha encaixante (Grupo Bom Jesus do Itabapoana), sendo assim produto da fus?o das rochas desse grupo.The Fazenda Conc?rdia and S?o Domingos pegmatites, inserted in the geotectonic context of the boundary between the Ribeira and Ara?ua? belts, within the Eastern Pegmatitic Province of Brazil, are located, respectively, in the Mimoso do Sul and Muqui municipalities ? southern Esp?rito Santo. The main objective of this work is to study them, through geochemical aspects, to characterize the evolution of these bodies. The analytical techniques employed were: electron microprobe (for the chemical composition of feldspars, micas, beryls and tourmaline); LA-Q-ICP-MS (for the characterization of trace elements of the mentioned minerals); and LA-SF-ICP-MS (to obtain ages by the U-Pb ratio in monazite grains). Both pegmatites present a simple zoning and contain quartz, feldspar and mica, however Fazenda Conc?rdia pegmatite has also tourmaline, beryl and topaz. About geochemistry, it was possible to notice that these bodies show an evolution trend in which S?o Domingos pegmatite is less diff erentiated than Fazenda Conc?rdia pegmatite. When compared to Campo Marilac pegmatites (Governador Valadares Pegmatitic District), where simple to complex pegmatites are found, the Fazenda Conc?rdia and S?o Domingos pegmatites don?t show a high degree of evolution/complexity. The S?o Domingos pegmatite monazite is as old as the country rock (Bom Jesus do Itabapoana Group), being, therefore, the product of this group rock fusion