Manuel Scimeca, Elena Giannini, Chiara Antonacci, Chiara Adriana Pistolese, Luigi Giusto Spagnoli and Elena Bonanno, Apr 23, 2014
Background: Mammary microcalcifications have a crucial role in breast cancer detection, but the p... more Background: Mammary microcalcifications have a crucial role in breast cancer detection, but the processes that induce their formation are unknown. Moreover, recent studies have described the occurrence of the epithelial–mesenchymal transition (EMT) in breast cancer, but its role is not defined. In this study, we hypothesized that epithelial cells acquire mesenchymal characteristics and become capable of producing breast microcalcifications.
Methods: Breast sample biopsies with microcalcifications underwent energy dispersive X-ray microanalysis to better define the elemental composition of the microcalcifications. Breast sample biopsies without microcalcifications were used as controls. The ultrastructural phenotype of breast cells near to calcium deposits was also investigated to verify EMT in relation to breast microcalcifications. The mesenchymal phenotype and tissue mineralization were studied by
immunostaining for vimentin, BMP-2, β2-microglobulin, β-catenin and osteopontin (OPN).
Results: The complex formation of calcium hydroxyapatite was strictly associated with malignant lesions whereas calcium-oxalate is mainly reported in benign lesions. Notably, for the first time, we observed the presence of magnesium-substituted hydroxyapatite, which was frequently noted in breast cancer but never found in benign lesions.
Morphological studies demonstrated that epithelial cells with mesenchymal characteristics were significantly increased in infiltrating carcinomas with microcalcifications and in cells with ultrastructural features typical of osteoblasts close to microcalcifications. These data were strengthened by the rate of cells expressing molecules typically involved during physiological mineralization (i.e. BMP-2, OPN) that discriminated infiltrating carcinomas with microcalcifications from those without microcalcifications.
Conclusions: We found significant differences in the elemental composition of calcifications between benign and malignant lesions. Observations of cell phenotype led us to hypothesize that under specific stimuli, mammary cells, which despite retaining a minimal epithelial phenotype (confirmed by cytokeratin expression), may acquire some mesenchymal characteristics transforming themselves into cells with an osteoblast-like phenotype, and are able to contribute to the production of breast microcalcifications."
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Papers by manuel scimeca
Methods: Breast sample biopsies with microcalcifications underwent energy dispersive X-ray microanalysis to better define the elemental composition of the microcalcifications. Breast sample biopsies without microcalcifications were used as controls. The ultrastructural phenotype of breast cells near to calcium deposits was also investigated to verify EMT in relation to breast microcalcifications. The mesenchymal phenotype and tissue mineralization were studied by
immunostaining for vimentin, BMP-2, β2-microglobulin, β-catenin and osteopontin (OPN).
Results: The complex formation of calcium hydroxyapatite was strictly associated with malignant lesions whereas calcium-oxalate is mainly reported in benign lesions. Notably, for the first time, we observed the presence of magnesium-substituted hydroxyapatite, which was frequently noted in breast cancer but never found in benign lesions.
Morphological studies demonstrated that epithelial cells with mesenchymal characteristics were significantly increased in infiltrating carcinomas with microcalcifications and in cells with ultrastructural features typical of osteoblasts close to microcalcifications. These data were strengthened by the rate of cells expressing molecules typically involved during physiological mineralization (i.e. BMP-2, OPN) that discriminated infiltrating carcinomas with microcalcifications from those without microcalcifications.
Conclusions: We found significant differences in the elemental composition of calcifications between benign and malignant lesions. Observations of cell phenotype led us to hypothesize that under specific stimuli, mammary cells, which despite retaining a minimal epithelial phenotype (confirmed by cytokeratin expression), may acquire some mesenchymal characteristics transforming themselves into cells with an osteoblast-like phenotype, and are able to contribute to the production of breast microcalcifications."
disposal of these molecules that, yet pharmacologically active, are excreted by humans
and animals. These compounds contaminate soil, water and plants. Many studies have
reported the bioaccumulation of antibiotics in plants and their negative effects on
photosynthesis, cell growth and oxidative balance. Therefore, the principal objective
of this paper was the study of antibiotic accumulation sites in plants and its uptake
modality. Iberis sempervirens L., grown in soil and in agar in the presence or absence
of tetracycline, were used as a model system. Using confocal and transmission electron
microscopy, we demonstrated that tetracycline was absorbed and propagated in plants
through apoplastic transport and also accumulated in intercellular spaces. Tetracycline
was rarely detected inside cells (in cytoplasm and mitochondria where, coherent
to its pharmacological activity, it probably affected ribosomes), except in stomata.
Moreover, we verified and clarified further the phytotoxic effects of tetracycline on
plants. We observed that the antibiotic induced a large reduction in plant growth and
development and inhibition of photosynthetic activity. As tetracycline may lead to
oxidative stress in plants, plant cells tried to balance this disequilibrium by increasing
the amount and activity of some endogenous enzyme antioxidant agents (superoxide
dismutase 1 and catalase) and levels of antiradical secondary metabolites.
a subcutaneous nodular lesion localized on her right upper arm.
Conventional histological examination revealed a lesion characterized
by a necrotic center surrounded by palisading epithelioid histiocytes
embedded into the fibroadipous and skeletal muscle tissue.
Transmission electron microscopy analysis confirmed the histological
observations in terms of cellular composition of the granuloma.
The ultrastructural microanalysis shed light on the elemental composition
of the examined granulomatous formation since it clearly
detected metallic deposits with an emission pick at EDX for aluminum
within the hystocites’s granules. Our results support previous
published data on the reactive nature of granulomatous reaction at
the site of vaccine. The presence of aluminum inside the cytoplasm
of macrophages proved by microanalysis gives strength to the
etiopatogenic hypothesis of the granuloma formation.
Methods: Breast sample biopsies with microcalcifications underwent energy dispersive X-ray microanalysis to better define the elemental composition of the microcalcifications. Breast sample biopsies without microcalcifications were used as controls. The ultrastructural phenotype of breast cells near to calcium deposits was also investigated to verify EMT in relation to breast microcalcifications. The mesenchymal phenotype and tissue mineralization were studied by
immunostaining for vimentin, BMP-2, β2-microglobulin, β-catenin and osteopontin (OPN).
Results: The complex formation of calcium hydroxyapatite was strictly associated with malignant lesions whereas calcium-oxalate is mainly reported in benign lesions. Notably, for the first time, we observed the presence of magnesium-substituted hydroxyapatite, which was frequently noted in breast cancer but never found in benign lesions.
Morphological studies demonstrated that epithelial cells with mesenchymal characteristics were significantly increased in infiltrating carcinomas with microcalcifications and in cells with ultrastructural features typical of osteoblasts close to microcalcifications. These data were strengthened by the rate of cells expressing molecules typically involved during physiological mineralization (i.e. BMP-2, OPN) that discriminated infiltrating carcinomas with microcalcifications from those without microcalcifications.
Conclusions: We found significant differences in the elemental composition of calcifications between benign and malignant lesions. Observations of cell phenotype led us to hypothesize that under specific stimuli, mammary cells, which despite retaining a minimal epithelial phenotype (confirmed by cytokeratin expression), may acquire some mesenchymal characteristics transforming themselves into cells with an osteoblast-like phenotype, and are able to contribute to the production of breast microcalcifications."
disposal of these molecules that, yet pharmacologically active, are excreted by humans
and animals. These compounds contaminate soil, water and plants. Many studies have
reported the bioaccumulation of antibiotics in plants and their negative effects on
photosynthesis, cell growth and oxidative balance. Therefore, the principal objective
of this paper was the study of antibiotic accumulation sites in plants and its uptake
modality. Iberis sempervirens L., grown in soil and in agar in the presence or absence
of tetracycline, were used as a model system. Using confocal and transmission electron
microscopy, we demonstrated that tetracycline was absorbed and propagated in plants
through apoplastic transport and also accumulated in intercellular spaces. Tetracycline
was rarely detected inside cells (in cytoplasm and mitochondria where, coherent
to its pharmacological activity, it probably affected ribosomes), except in stomata.
Moreover, we verified and clarified further the phytotoxic effects of tetracycline on
plants. We observed that the antibiotic induced a large reduction in plant growth and
development and inhibition of photosynthetic activity. As tetracycline may lead to
oxidative stress in plants, plant cells tried to balance this disequilibrium by increasing
the amount and activity of some endogenous enzyme antioxidant agents (superoxide
dismutase 1 and catalase) and levels of antiradical secondary metabolites.
a subcutaneous nodular lesion localized on her right upper arm.
Conventional histological examination revealed a lesion characterized
by a necrotic center surrounded by palisading epithelioid histiocytes
embedded into the fibroadipous and skeletal muscle tissue.
Transmission electron microscopy analysis confirmed the histological
observations in terms of cellular composition of the granuloma.
The ultrastructural microanalysis shed light on the elemental composition
of the examined granulomatous formation since it clearly
detected metallic deposits with an emission pick at EDX for aluminum
within the hystocites’s granules. Our results support previous
published data on the reactive nature of granulomatous reaction at
the site of vaccine. The presence of aluminum inside the cytoplasm
of macrophages proved by microanalysis gives strength to the
etiopatogenic hypothesis of the granuloma formation.