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1.
Sci Rep ; 8(1): 679, 2018 01 12.
Article in English | MEDLINE | ID: mdl-29330439

ABSTRACT

Citrullination, or the post-translational deimination of polypeptide-bound arginine, is involved in several pathological processes in the body, including autoimmunity and tumorigenesis. Recent studies have shown that nanomaterials can trigger protein citrullination, which might constitute a common pathogenic link to disease development. Here we demonstrated auto-antibody production in serum of nanomaterials-treated mice. Citrullination-associated phenomena and PAD levels were found to be elevated in nanomaterials -treated cell lines as well as in the spleen, kidneys and lymph nodes of mice, suggesting a systemic response to nanomaterials injection, and validated in human pleural and pericardial malignant mesothelioma (MM) samples. The observed systemic responses in mice exposed to nanomaterials support the evidence linking exposure to environmental factors with the development of autoimmunity responses and reinforces the need for comprehensive safety screening of nanomaterials. Furthermore, these nanomaterials induce pathological processes that mimic those observed in Pleural MM, and therefore require further investigations into their carcinogenicity.


Subject(s)
Autoantibodies/blood , Hydrolases/metabolism , Nanowires/administration & dosage , Nickel/chemistry , Proteins/metabolism , A549 Cells , Animals , Antibody Formation , Cell Line, Tumor , Citrullination , Female , Humans , Hydrolases/immunology , Kidney/metabolism , Kidney/pathology , Lymph Nodes/metabolism , Lymph Nodes/pathology , Mesothelioma/metabolism , Mesothelioma/pathology , Mice , Mice, Inbred C57BL , Nanowires/chemistry , Spleen/metabolism , Spleen/pathology
2.
ACS Nano ; 8(6): 5682-95, 2014 Jun 24.
Article in English | MEDLINE | ID: mdl-24873349

ABSTRACT

Despite the widespread availability of immunohistochemical and other methodologies for screening and early detection of lung and breast cancer biomarkers, diagnosis of the early stage of cancers can be difficult and prone to error. The identification and validation of early biomarkers specific to lung and breast cancers, which would permit the development of more sensitive methods for detection of early disease onset, is urgently needed. In this paper, ultra-small and bright nanoprobes based on quantum dots (QDs) conjugated to single domain anti-HER2 (human epidermal growth factor receptor 2) antibodies (sdAbs) were applied for immunolabeling of breast and lung cancer cell lines, and their performance was compared to that of anti-HER2 monoclonal antibodies conjugated to conventional organic dyes Alexa Fluor 488 and Alexa Fluor 568. The sdAbs-QD conjugates achieved superior staining in a panel of lung cancer cell lines with differential HER2 expression. This shows their outstanding potential for the development of more sensitive assays for early detection of cancer biomarkers.


Subject(s)
Biomarkers, Tumor/metabolism , Breast Neoplasms/metabolism , Lung Neoplasms/metabolism , Quantum Dots , Receptor, ErbB-2/metabolism , Antibodies/chemistry , Antibodies, Monoclonal/chemistry , Cell Line, Tumor , Coculture Techniques , Flow Cytometry , Fluorescent Dyes/chemistry , Humans , Immunohistochemistry , Macrophages/metabolism , Microscopy, Confocal
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