RESUMEN
The aim of this study is to explore a cause-oriented therapy for patients with uterine cervical cancer that expresses erythropoietin (Epo) and its receptor (EpoR). Epo, by binding to EpoR, stimulates the proliferation and differentiation of erythroid progenitor cells into hemoglobin-containing red blood cells. In this study, we report that the HeLa cells in the xenografts expressed ε, γ, and α globins as well as myoglobin (Mb) to produce tetrameric α2ε2 and α2γ2 and monomeric Mb, most of which were significantly suppressed with an EpoR antagonist EMP9. Western blotting revealed that the EMP9 treatment inhibited the AKT-pAKT, MAPKs-pMAPKs, and STAT5-pSTAT5 signaling pathways. Moreover, the treatment induced apoptosis and suppression of the growth and inhibited the survival through disruption of the harmonized hemoprotein syntheses in the tumor cells concomitant with destruction of vascular nets in the xenografts. Furthermore, macrophages and natural killer (NK) cells with intense HIF-1α expression recruited significantly more in the degenerating foci of the xenografts. These findings were associated with the enhanced expressions of nNOS in the tumor cells and iNOS in macrophages and NK cells in the tumor sites. The treated tumor cells exhibited a substantial number of perforations on the cell surface, which indicates that the tumors were damaged by both the nNOS-induced nitric oxide (NO) production in the tumor cells as well as the iNOS-induced NO production in the innate immune cells. Taken together, these data suggest that HeLa cells constitutively acquire ε, γ and Mb synthetic capacity for their survival. Therefore, EMP9 treatment might be a cause-oriented and effective therapy for patients with squamous cell carcinoma of the uterine cervix.
Asunto(s)
Hemoglobinas/biosíntesis , Xenoinjertos/efectos de los fármacos , Neoplasias Experimentales/metabolismo , Péptidos/farmacología , Receptores de Eritropoyetina/antagonistas & inhibidores , Animales , Apoptosis/efectos de los fármacos , Western Blotting , Proliferación Celular/efectos de los fármacos , Eritropoyetina/química , Eritropoyetina/farmacología , Expresión Génica/efectos de los fármacos , Células HeLa , Hemoglobinas/genética , Xenoinjertos/metabolismo , Humanos , Masculino , Ratones Endogámicos BALB C , Ratones Desnudos , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Neoplasias Experimentales/genética , Neoplasias Experimentales/patología , Péptidos/síntesis química , Proteínas Proto-Oncogénicas c-akt/metabolismo , Receptores de Eritropoyetina/genética , Receptores de Eritropoyetina/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factor de Transcripción STAT5/metabolismo , Transducción de Señal/efectos de los fármacos , Trasplante HeterólogoAsunto(s)
Biomarcadores de Tumor/metabolismo , Herpesvirus Humano 4 , Linfoma Extranodal de Células NK-T/metabolismo , Linfoma Extranodal de Células NK-T/patología , Neoplasias Testiculares/metabolismo , Neoplasias Testiculares/patología , Anciano , Pueblo Asiatico , Humanos , Japón , Linfoma Extranodal de Células NK-T/cirugía , Masculino , Neoplasias Testiculares/cirugíaRESUMEN
Cytological diagnosis of adrenal cysts is becoming more important, with the increase in cases identified due to the widespread use of imaging modalities. Adrenal cysts have been classified into four main groups: endothelial, epithelial, parasitic, and pseudocyst, with endothelial cysts further classified as lymphangiomatous or angiomatous. We report on a case of adrenal lymphangioma with atypical lymphocytes found in the intraoperative aspirate, suggesting an inconclusive diagnosis, although immunohistochemical study led us to suppose their B-cell origin. This case provided important cytological findings that may assist in the prevention of cytological overdiagnosis.