RESUMO
A 46-year-old Dominican man, known to have HIV, presented with constitutional symptoms of two week's duration. The patient was found to have cytopenias, significantly elevated ferritin level and lymphadenopathy. Biopsies and laboratory studies met the criteria for hemophagocytic lymphohistiocytosis (HLH). A concomitant diagnosis of histoplasmosis was confirmed as the trigger for HLH and treatment resulted in clinical improvement and resolution of symptoms.
Assuntos
Anfotericina B/uso terapêutico , Soropositividade para HIV/diagnóstico , Histoplasmose/diagnóstico , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Antifúngicos/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Soropositividade para HIV/tratamento farmacológico , Histoplasmose/tratamento farmacológico , Humanos , Itraconazol/uso terapêutico , Linfo-Histiocitose Hemofagocítica/diagnóstico , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
Paragangliomas are tumors of the sympathetic and parasympathetic paraganglia. While most paraganglioma are of parasympathetic origin and present as benign palpable masses of the neck, sympathetic paraganglioma are often secretory, presenting with symptoms related to excess catecholamines. Such symptoms include hypertension, headache, palpitations, and diaphoresis. Most sympathetic paraganglioma form within the adrenal medulla, the largest sympathetic paraganglia, and are commonly known as pheochromocytomas. However, sympathetic paragangliomas may present extra-adrenally, carrying a significantly higher risk of malignancy. In this manuscript, we examine a case of a young man with an extra-adrenal sympathetic paraganglioma of the Organ of Zuckerkandl. Furthermore, we discuss appropriate diagnostic workup and treatment of pheochromocytomas and sympathetic paragangliomas.
Assuntos
Catecolaminas , Glomos Para-Aórticos , Paraganglioma , Aorta Abdominal/diagnóstico por imagem , Catecolaminas/sangue , Catecolaminas/metabolismo , Dissecação/métodos , Humanos , Masculino , Monitorização Fisiológica , Glomos Para-Aórticos/diagnóstico por imagem , Glomos Para-Aórticos/metabolismo , Glomos Para-Aórticos/patologia , Paraganglioma/diagnóstico por imagem , Paraganglioma/metabolismo , Paraganglioma/patologia , Paraganglioma/cirurgia , Cuidados Pré-Operatórios/métodos , Prognóstico , Radiografia , Resultado do Tratamento , Adulto JovemRESUMO
Development of drug resistance is one of the major causes of breast cancer treatment failure. The goal of this study was to understand the chemoresistance mechanism using the highly metastatic 4T1 breast cancer model, which emulates stage IV breast cancer in humans. The metastatic 4T1 breast cancer cell line treated with either doxorubicin or 5-FU showed a concentration-dependent reduced cell proliferation, with induced G2-phase growth arrest (doxorubicin) or G1-phase growth arrest (5-FU). Doxorubicin treatment partially suppressed the multiorgan metastasis of 4T1 breast cancer cells in the lung, heart, liver, and bone, compared with either 5-FU or cyclophosphamide. We isolated and characterized 4T1 breast cancer cells from doxorubicin-resistant metastatic tumors (cell line 4T1-R). Multiorgan metastasis of drug-resistant 4T1 breast tumors was totally resistant to doxorubicin treatment. Our results indicate that doxorubicin is localized exclusively in the cytoplasm of resistant 4T1 breast cancer cells and that it cannot reach the nucleus because of increased nuclear expression of P-glycoprotein. Pretreatment of doxorubicin-resistant 4T1-R breast cancer cells with verapamil, a general inhibitor of P-glycoprotein, increased nuclear translocation of doxorubicin and cellular cytotoxicity. Thus, impaired nuclear translocation of doxorubicin due to increased expression of P-glycoprotein is associated with doxorubicin resistance of highly metastatic 4T1 breast cancer.
