RESUMO
Sarcomas are mesenchymal cancers which often show an aggressive behavior and patient survival largely depends on an early detection. In last years, much attention has been given to the fact that cancer patients release specific odorous volatile organic compounds (VOCs) that can be efficiently detected by properly trained sniffer dogs. Here, we have evaluated for the first time the ability of sniffer dogs (n = 2) to detect osteosarcoma cell cultures and patient samples. One of the two dogs was successfully trained to discriminate osteosarcoma patient-derived primary cells from mesenchymal stem/stromal cells (MSCs) obtained from healthy individuals. After the training phase, the dog was able to detect osteosarcoma specific odor cues in a different panel of 6 osteosarcoma cell lines with sensitivity and specificity rates between 95 and 100%. Moreover, the same VOCs were also detected by the sniffer dog in saliva samples from osteosarcoma patients (n = 2) and discriminated from samples from healthy individuals with a similar efficacy. Altogether, these results indicate that there are common odor profiles shared by cultures of osteosarcoma cells and body fluid samples from patients and provide a first proof of concept about the potential of canine odor detection as a non-invasive screening method to detect osteosarcomas.
Assuntos
Neoplasias Ósseas , Osteossarcoma , Sarcoma , Compostos Orgânicos Voláteis , Animais , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/veterinária , Cães , Humanos , Odorantes , Osteossarcoma/diagnóstico , Osteossarcoma/veterinária , Olfato , Cães TrabalhadoresRESUMO
For the cancer genomics era, there is a need for clinically annotated close-to-patient cell lines suitable to investigate altered pathways and serve as high-throughput drug-screening platforms. This is particularly important for drug-resistant tumors like chondrosarcoma which has few models available. Here we established and characterized new cell lines derived from two secondary (CDS06 and CDS11) and one dedifferentiated (CDS-17) chondrosarcomas as well as another line derived from a CDS-17-generated xenograft (T-CDS17). These lines displayed cancer stem cell-related and invasive features and were able to initiate subcutaneous and/or orthotopic animal models. Different mutations in Isocitrate Dehydrogenase-1 (IDH1), Isocitrate Dehydrogenase-2 (IDH2), and Tumor Supressor P53 (TP53) and deletion of Cyclin Dependent Kinase Inhibitor 2A (CDKN2A) were detected both in cell lines and tumor samples. In addition, other mutations in TP53 and the amplification of Mouse Double Minute 2 homolog (MDM2) arose during cell culture in CDS17 cells. Whole exome sequencing analysis of CDS17, T-CDS17, and matched patient samples confirmed that cell lines kept the most relevant mutations of the tumor, uncovered new mutations and revealed structural variants that emerged during in vitro/in vivo growth. Altogether, this work expanded the panel of clinically and genetically-annotated chondrosarcoma lines amenable for in vivo studies and cancer stem cell (CSC) characterization. Moreover, it provided clues of the genetic drift of chondrosarcoma cells during the adaptation to grow conditions.
RESUMO
AIM: The aim of this study was to evaluate effective bone regeneration using an autologous serum scaffold (alone or seeded with autologous bone marrow-mesenchymal stem cells, BM-MSCs), when implanted in a 30 mm length segmental mandibular defect in sheep. MATERIALS AND METHODS: The bone defect was filled either with serum scaffold alone (control group; n = 5) or combined with BM-MSCs (experimental group; n = 10). Bone regeneration was determined at 12 (T12; 2 control sheep and 4 experimental sheep) and 32 weeks (T32; 3 control and 6 experimental sheep), as measured by computed and microcomputed tomography and histological examination. RESULTS: Two sheep of the Experimental group died after surgery. While complete bone union in the control group was only observed at T32, it was observed both at T12 (1/4 sheep) and T32 (3/4 sheep) in the experimental group. When properties/characteristics of new bone where compared, a better bone quality, similar to native bone, was observed in the scaffold combined with BM-MSCs. CONCLUSIONS: Based on these results, we conclude that the serum scaffold can promote efficient repair of large bone defects, but the combination with BM-MSCs accelerates this process, increasing significantly the amount and quality of bone formed.
Assuntos
Mandíbula , Animais , Células da Medula Óssea , Células-Tronco Mesenquimais , Projetos Piloto , Ovinos , Engenharia Tecidual , Alicerces Teciduais , Microtomografia por Raio-XRESUMO
Whole-body irradiation has been associated with liver function alterations. Ionizing radiation exposure increases oxidative stress and antioxidants can activate transcription of antioxidant target genes. In the present study, modifications of the liver antioxidant system were evaluated at 7 and 30 days following sub-lethal whole-body X-irradiation in male Wistar rats, which were intragastrically supplemented with quercetin or control solvent for 4 days prior to and 6 days following irradiation. Animal groups were as follows: CS, control, solvent-supplemented; CQ, control, quercetin-supplemented; RS, irradiated, solvent-supplemented; and RQ, irradiated, quercetin-supplemented. After 7 days, liver tissue from RS animals demonstrated marked hydropic panlobular degeneration with Mallory bodies in ballooning hepatocytes. These changes were mostly reversed in RQ rats. Lipid peroxidation in addition to copper/zinc superoxide dismutase (Cu/Zn-SOD), nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and Kelch-like ECH-associated protein 1 (Keap1) protein expression levels were all increased by X-irradiation, but significantly decreased by quercetin supplementation. Catalase (CAT) and NAD(P)H: quinone oxidoreductase 1 (NQO1) expression levels remained high in irradiated rats regardless of quercetin supplementation. After 30 days, the liver from RS animals had small portal infiltrates and diffuse cytoplasmic vacuolization, with reduced lipid peroxidation and reduced expression levels of CAT, NQO1, Nrf2 and Keap1, but consistently elevated Cu/Zn-SOD expression. RQ animals indicated reduced expression levels of Nrf2 and Keap1 30 days after irradiation. The present study demonstrated a quercetin-induced reduction of the oxidative stress-associated increase in Nrf2 expression that may be useful for preventing cancer cell survival in response to ionizing radiation exposure.
Assuntos
Antioxidantes/farmacologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fator 2 Relacionado a NF-E2/genética , Quercetina/farmacologia , Animais , Antioxidantes/administração & dosagem , Biomarcadores , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos da radiação , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch , Peroxidação de Lipídeos , Fígado/patologia , Fígado/efeitos da radiação , Masculino , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Quercetina/administração & dosagem , RatosRESUMO
PURPOSE: The aims of this study were to quantify bone mineral density (BMD) and trabecular architecture of sequestra in patients with bisphosphonate-related osteonecrosis of the jaw (BRONJ) associated with dental implants and to assess if there are differences between trabecular bone in "implant loading-triggered" and "implant surgery-triggered" BRONJ. MATERIALS AND METHODS: Bone sequestra of 2 patients diagnosed with BRONJ associated with dental implants were scanned using high-resolution microcomputed tomography (microCT). Images were obtained at a voltage of 50 kV and 800 µA, and the specimens were scanned at 180 degrees with a single rotation step of 0.3, 1-mm aluminum filter, and a pixel size of 12 µm. The morphometric parameters examined were: BMD, ratio of bone volume/tissue volume (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), trabecular separation (Tb.Sp), connectivity density (Conn.D, mm), degree of anisotropy, and the structural model index. RESULTS: BMD and BV/TV were higher in bone sequestration than in healthy bone. Tb.Sp was lower and Tb.N and Tb.Th were higher in the BRONJ group. Conn.D and Tb.N values were significantly high in implant surgery-triggered sequestrum but substantially low in sequestra caused by loading as compared with those of the control sample. CONCLUSIONS: MicroCT is useful for assessing bone sequestration of BRONJ associated to dental implants. The necrotic bone is similar to that described in conventional BRONJ.
Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/etiologia , Implantes Dentários/efeitos adversos , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/diagnóstico por imagem , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/patologia , Densidade Óssea , Humanos , Masculino , Mandíbula/diagnóstico por imagem , Mandíbula/patologia , Pessoa de Meia-Idade , Microtomografia por Raio-XRESUMO
Osteogenesis imperfecta (OI), is a heterogeneous group of inherited disorders of connective tissue characterized by bone fragility. Patients with this disease frequently suffer fractures, over 80% of the extremities due to the more intensive mechanical load. Fractures of the facial bones occur very infrequently. Several studies have proved that bisphosphonate therapy may be effective in reducing fracture risk in OI patients. We report here an unusual case of pathological mandibular fracture following simple molar extraction in an adult patient with OI type I and oral alendronic acid treatment. Extraction was atraumatical and without bone removal. Fracture was treated by internal fixation by plate osteosynthesis and additional mandibulomaxillary fixation (MMF). Bone healing after fracture treatment was completely normal and no clinical signs of osteoneocrosis were observed. To the best of our knowledge, this is an unusual complication even in this type of patients. Particular care is necessary is these patients during oral surgery, even when they have been treated and controlled.
Assuntos
Fraturas Espontâneas/etiologia , Fraturas Mandibulares/etiologia , Dente Molar/cirurgia , Osteogênese Imperfeita/complicações , Extração Dentária/efeitos adversos , Adulto , Alendronato/uso terapêutico , Difosfonatos/uso terapêutico , Humanos , Masculino , Osteogênese Imperfeita/tratamento farmacológicoRESUMO
Carcinoid tumours of the thymus are rare. The case of a 57-year-old asymptomatic man with a carcinoid tumour of the thymus, who showed a widened mediastinum by chest x-ray, is presented. Fine needle aspiration suggested the diagnosis, which was confirmed by biopsy.