RESUMEN
We established two patient derived tumor cells (PDCs) from right and left pulmonary metastatic lesions respectively of a patient with giant cell tumor. At that time, patient-derived tumor cells from right and left surgical specimens were collected and cultured. High-throughput screening (HTS) for 24 drugs was conducted with a micropillar/microwell chip platform using giant cell tumor PDCs. Using 6 doses per drug in 6 replicates for giant cell tumor PDCs, the dose response curves and corresponding IC50 values were calculated from the scanned images using the S+ Chip Analyzer. A sensitive response was more significantly achieved for AZD4547 (FGFR2 inhibitor) in giant cell tumor PDCs originated from the right pulmonary nodule under the micropillar/microwell chip platform using 3D culture. This sensitivity was consistent with the target expression patterns of giant cell tumor PDCs (FGFR2-IIIC mRNA expression in giant cell tumor PDCs originated from the right pulmonary nodule was increased significantly as compared to those originated from left). However, in a conventional 2D cultured MTT assay, there was no difference for IC50 values of AZD4547 between giant cell tumor PDCs originated from right and left pulmonary nodules. An HTS platform based on 3D culture on micropillar/microwell chips and PDC models could be applied as a useful preclinical tool to evaluate the intrapatient tumor/response heterogeneity. This platform based on 3D culture might reflect far better the relation between the tumor-biology and the matched targeted agent as compared to a conventional 2D cultured MTT assay.
Asunto(s)
Expresión Génica , Tumores de Células Gigantes/genética , Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos/genética , Adulto , Antineoplásicos/farmacología , Técnicas de Cultivo de Célula , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Evaluación Preclínica de Medicamentos/métodos , Ensayos de Selección de Medicamentos Antitumorales/métodos , Tumores de Células Gigantes/diagnóstico , Tumores de Células Gigantes/tratamiento farmacológico , Ensayos Analíticos de Alto Rendimiento , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/secundario , Masculino , Metástasis de la Neoplasia , Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos/antagonistas & inhibidores , Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos/metabolismoRESUMEN
BACKGROUND: Oncogenic osteomalacia is a rare paraneoplastic syndrome characterized by osteomalacia, which occurs as a result of excess renal phosphate excretion caused by fibroblast growth factor-23 secreted by mesenchymal tumors. This entity is rare in head and neck cancers. We report a rare case of oncogenic osteomalacia in a patient with an anterior skull base giant cell tumor. METHODS AND RESULTS: A 34-year-old woman presented with a 5-year history of progressive weakness in both lower limbs and the trunk. Hypophosphatemia and hypocalcemia had been noted by a local physician, but her symptoms persisted despite receiving calcium and vitamin D supplements. A recent onset of epistaxis and nasal blockage led to referral to the head and neck services. Nasal endoscopy revealed a left nasal cavity mass. Further evaluation with imaging studies revealed a mass in the nasal cavity with intracranial extension. Biopsy of the lesion suggested a neurogenic tumor. A putative diagnosis of anterior skull base neurogenic tumor with paraneoplastic hypophosphatemia was made. After the biochemical parameters were corrected, the patient underwent craniofacial resection. The final histopathologic study suggested the lesion as a "giant cell tumor." During the postoperative period the patient's biochemical and clinical symptoms improved dramatically, allowing her to regain normal mobility. CONCLUSIONS: Clinicians and pathologists must be aware of the clinical symptoms, laboratory abnormalities, and pathologic features of oncogenic osteomalacia, which may be caused by tumors in the head and neck and thus make an exhaustive effort to diagnose the same.
Asunto(s)
Tumores de Células Gigantes/complicaciones , Cavidad Nasal , Neoplasias de Tejido Conjuntivo/diagnóstico , Neoplasias de Tejido Conjuntivo/etiología , Neoplasias Nasales/complicaciones , Adulto , Femenino , Tumores de Células Gigantes/diagnóstico , Tumores de Células Gigantes/terapia , Humanos , Neoplasias de Tejido Conjuntivo/terapia , Neoplasias Nasales/diagnóstico , Neoplasias Nasales/terapia , Osteomalacia , Síndromes ParaneoplásicosRESUMEN
OBJECTIVE: To study the characteristic changes of 31P-MR spectroscopy of bone and soft tissue tumors. METHODS: 41 patients were examined by phosphorus surface coil of 3 tesla MR machine, including 18 benign tumor foci and 28 malignant foci, and adjacent normal muscles. The areas under the peaks of various metabolites in the spectra were measured, including phosphomonoester (PME), inorganic phosphours (Pi), phosphodiester (PDE), phosphocreatine (Pcr), adenosine triphosphate (ATP) gamma, alpha, beta. The ratios of the metabolites to beta-ATP, NTP and Pcr were calculated. Intracellular pH was calculated according to the chemical shift change of Pi relative to Pcr. RESULTS: The ratios of Pcr/PME and PME/NTP in benign and malignant tumor groups were significantly different from those of the normal group (P<0.05). Between benign and malignant tumor groups, the ratios of PME/beta-ATP and PME/NTP were significantly different (P<0.05). CONCLUSION: Pcr/PME and PME/NTP are potential diagnostic indexes of bone and soft tissue tumors. PME/beta-ATP and PME/NTP are potential indexes of differential diagnosis of bone and soft tissue tumors.