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BACKGROUND: Osteosarcoma patients often experience poor outcomes despite chemotherapy treatment, likely due in part to various mechanisms of tumor cell innate and/or acquired drug resistance. Exosomes, microvesicles secreted by cells, have been shown to play a role in drug resistance, but a comprehensive protein signature relating to osteosarcoma carboplatin resistance has not been fully characterized. METHODS: In this study, cell lysates and exosomes from two derivatives (HMPOS-2.5R and HMPOS-10R) of the HMPOS osteosarcoma cell line generated by repeated carboplatin treatment and recovery, were characterized proteomically by mass spectrometry. Protein cargos of circulating serum exosomes from dogs with naturally occurring osteosarcoma, were also assessed by mass spectrometry, to identify biomarkers that discriminate between good and poor responders to carboplatin therapy. RESULTS: Both cell lysates and exosomes exhibited distinct protein signatures related to drug resistance. Furthermore, exosomes from the resistant HMPOS-2.5R cell line were found to transfer drug resistance to drug-sensitive HMPOS cells. The comparison of serum exosomes from dogs with a favorable disease-free interval [DFI] of > 300 days, and dogs with < 100 days DFI revealed a proteomic signature that could discriminate between the two cohorts with high accuracy. Furthermore, when the patient's exosomes were compared to exosomes isolated from carboplatin resistant cell lines, several putative biomarkers were found to be shared. CONCLUSIONS: The findings of this study highlight the significance of exosomes in the potential transfer of drug resistance, and the discovery of novel biomarkers for the development of liquid biopsies to better guide personalized chemotherapy treatment.
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In collaboration with the American College of Veterinary Pathologists.
Assuntos
Patologia Veterinária , Médicos Veterinários , Animais , Humanos , Estados UnidosRESUMO
Mesotheliomas are uncommon neoplasms that arise from mesothelial cells in either the abdominal or thoracic cavities and are rarely diagnosed in cats. A 10-y-old spayed female domestic shorthair cat was presented to the Louisiana State University oncology service for evaluation of a large amount of abdominal effusion. Abdominal ultrasound identified a large mesenteric mass with numerous ill-defined nodules. An abdominocentesis was performed with cytologic and immunocytochemical findings consistent with a neoplastic effusion, with large clusters of epithelioid cells that exhibited strong cytoplasmic expression of pancytokeratin, vimentin, and Wilms tumor 1 antigens. Further testing was declined, and meloxicam was prescribed until the cat died 23 d after initial presentation. Upon postmortem examination, the omentum was contracted into a firm mass adhered to multiple organs and accompanied by numerous small white nodules throughout the abdominal cavity. On histopathology and immunohistochemistry, neoplastic cells were found throughout the abdominal cavity; 60-95% exhibited moderate-to-strong cytoplasmic immunoreactivity for cytokeratin, vimentin, and Wilms tumor 1 protein. The final diagnosis was an epithelioid mesothelioma. Our case illustrates the utility of cytology, immunocytochemistry, and its relation to histology and immunohistochemistry. We also reviewed the reported cases of feline mesothelioma.
Assuntos
Doenças do Gato/patologia , Imuno-Histoquímica/veterinária , Mesotelioma Maligno/veterinária , Animais , Biomarcadores Tumorais/metabolismo , Gatos , Feminino , Mesotelioma Maligno/diagnóstico , Mesotelioma Maligno/metabolismo , Mesotelioma Maligno/patologiaRESUMO
PCR-based approach was used to examine the rate of Chlamydia positivity in raptors from wild bird rehabilitation centers in Oregon. Three of 82 birds were identified as positive for Chlamydia with this PCR. Sequence analysis of 16S ribosomal DNA from 2 of these birds confirmed the presence of DNA from phylum Chlamydiae. One bird was positive for Chlamydia psittaci in both choanal and cloacal swabs. The second bird, a louse-infested red-tailed hawk, had evidence of choanal colonization by "Candidatus Rhabdochlamydia" spp. Our study describes evidence of this Chlamydia-like organism in the United States. This survey also suggests that the carriage rate of C. psittaci is low in raptors in Oregon wild bird rehabilitation centers, and that care must be taken in the design of PCR primers for phylum Chlamydiae such that colonization by insect endosymbionts is not mistaken for an infection by known chlamydial pathogens.