RESUMEN
Background: Adrenocortical carcinoma (ACC) is a rare malignant tumor that occurs in the adrenal cortex. It has a high degree of malignancy and comparatively poor overall prognosis. Surgery is the standard curative therapy for localized ACC patients. The combination regimen of etoposide, doxorubicin, cisplatin (EDP) plus mitotane has been considered as the standardized chemotherapy regimen for advanced ACC. However, new effective regimens are emerging for specific conditions in metastatic ACC. Case presentation: We report a case of a 66-year-old man diagnosed with metastatic ACC who had a large left adrenal mass (110 mm × 87 mm) and multiple metastases in both lungs. The patient was treated with EP and sintilimab for six cycles; anlotinib was introduced after the third cycle. Follow-ups after the second to fourth cycles found significantly reduced lung metastases with all imaging examinations indicating partial response (PR) status. The patient received maintenance therapy thereafter with sintilimab plus anlotinib. Until recently, the patient's lung metastases and the left adrenal gland area mass (39mm × 29mm) have disappeared, and no disease progression has been observed. The progression-free survival of this patient has been extended to approximately 31 months, in sharp contrast to a median survival time of 12 months for majority of advanced ACC. The main adverse events during treatment were appetite loss and grade I myelosuppression and revealed only grade I hypertension and grade I hypothyroidism. Conclusion: This case highlights the remarkable response of our patient's ACC to treatment with a novel combination of EP and sintilimab combined with anlotinib. Our findings suggest a safe and more effective combination therapeutic option for patients with adrenocortical carcinoma.
RESUMEN
Abnormal Transmembrane protein 9 (TMEM9) expression has been identified in various human tumors. However, the prognostic potential and mechanistic role of TMEM9 in lung adenocarcinoma (LUAD) remain unclear. Here, we first found a significant upregulation of TMEM9 in LUAD tissues, and TMEM9 expression was positively correlated with microvessel density (MVD), T stage, and clinical stage. Survival analysis demonstrated TMEM9 was an independent indicator of poor prognosis in LUAD patients. In addition, downregulation of TMEM9 suppressed tumor growth and metastasis in vitro and in vivo models, and reduced HUVEC proliferation, migration, and tube formation in a cancer cell/HUVEC coculture model. Furthermore, TMEM9 upregulated VEGF expression, and VEGF-neutralizing antibodies reversed HUVEC angiogenesis and cancer cell migration ability caused by overexpression of TMEM9. In contrast, recombinant VEGF (rVEGF) abolished the inhibitory effect of TMEM9-knockdown LUAD cells on HUVEC angiogenesis and tumor cell migration. Moreover, we showed that TMEM9 upregulated VEGF expression by activating the mitogen-activated protein kinase/extracellular signal-regulated kinase/STAT3 (MEK/ERK/STAT3) pathway. Together, our study provides mechanistic insights into the role of TMEM9 in LUAD and highlights the potential of targeting the TMEM9/MEK/ERK/STAT3/VEGF pathway as a novel therapy for preventing LUAD progression.
Asunto(s)
Adenocarcinoma del Pulmón , Progresión de la Enfermedad , Neoplasias Pulmonares , Sistema de Señalización de MAP Quinasas , Proteínas de la Membrana , Factor de Transcripción STAT3 , Factor A de Crecimiento Endotelial Vascular , Animales , Femenino , Humanos , Masculino , Ratones , Persona de Mediana Edad , Células A549 , Adenocarcinoma del Pulmón/patología , Adenocarcinoma del Pulmón/metabolismo , Adenocarcinoma del Pulmón/genética , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/genética , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Ratones Endogámicos BALB C , Ratones Desnudos , Neovascularización Patológica/metabolismo , Neovascularización Patológica/genética , Factor de Transcripción STAT3/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
BACKGROUND: Epiplakin1 (EPPK1) has been associated with disease progression and unfavorable prognosis of many cancers, but its functional involvement in esophageal squamous cell carcinoma (ESCC) remains to be uncovered. METHODS: The Quantitative Real-time PCR (qPCR) assay was employed to determine the expression of EPPK1 in ESCC tissues and cells. CCK-8 assay, colony forming assay, wound healing assay, and transwell invasion assay were utilized to evaluate the effects of EPPK1 on cell proliferation, migration, and invasion capacity in ESCC cells using small interfering ribonucleic acids. Flow cytometry was performed to estimate the cell apoptotic rate caused by silencing of EPPK1. The proteins related to epithelial-to-mesenchymal transition (EMT), apoptosis, and activation of the phosphatidylinositol 3-kinase/serine threonine protein kinase 1 (PI3K/AKT) signaling pathway were measured by western blot. RESULTS: The expression of EPPK1 was dramatically increased in ESCC tissues and cells compared to that in relative controls. Additionally, silencing of EPPK1 suppressed ESCC cell growth, colony formation, migration, invasion, and EMT, while promoting ESCC cell apoptosis. Furthermore, EPPK1 induced ESCC cell progression via mediating the PI3K/AKT signaling pathway. CONCLUSION: EPPK1 promotes ESCC progression by modulating the PI3K/AKT signaling pathway and could serve as a potential target for ESCC treatment.
