RESUMO
DERL2 (derlin 2) is a critical component of the endoplasmic reticulum quality control pathway system whose mutations play an important role in carcinogenesis, including cholangiocarcinoma (CHOL). However, its role and its underlying mechanism have yet to be elucidated. Herein, we revealed that DERL2 was highly expressed in CHOL and considered as an independent prognostic indicator for inferior survival in CHOL. DERL2 ectopically expressed in CHOL cells promoted cell proliferation and colony formation rates, and depleting DERL2 in CHOL cells curbed tumor growth in vitro and in vivo. More interestingly, the knockout of DERL2 augmented the growth-inhibitory effect of gemcitabine chemotherapy on CHOL cells by inducing cell apoptosis. Mechanistically, we discovered that DERL2 interacted with BAG6 (BAG cochaperone 6), thereby extending its half-life and reinforcing the oncogenic role of BAG6 in CHOL progression. (AU)
Assuntos
Colangiocarcinoma , Resistencia a Medicamentos Antineoplásicos , Carcinogênese , Tratamento FarmacológicoRESUMO
DERL2 (derlin 2) is a critical component of the endoplasmic reticulum quality control pathway system whose mutations play an important role in carcinogenesis, including cholangiocarcinoma (CHOL). However, its role and its underlying mechanism have yet to be elucidated. Herein, we revealed that DERL2 was highly expressed in CHOL and considered as an independent prognostic indicator for inferior survival in CHOL. DERL2 ectopically expressed in CHOL cells promoted cell proliferation and colony formation rates, and depleting DERL2 in CHOL cells curbed tumor growth in vitro and in vivo. More interestingly, the knockout of DERL2 augmented the growth-inhibitory effect of gemcitabine chemotherapy on CHOL cells by inducing cell apoptosis. Mechanistically, we discovered that DERL2 interacted with BAG6 (BAG cochaperone 6), thereby extending its half-life and reinforcing the oncogenic role of BAG6 in CHOL progression. (AU)
Assuntos
Colangiocarcinoma , Resistencia a Medicamentos Antineoplásicos , Carcinogênese , Tratamento FarmacológicoRESUMO
DERL2 (derlin 2) is a critical component of the endoplasmic reticulum quality control pathway system whose mutations play an important role in carcinogenesis, including cholangiocarcinoma (CHOL). However, its role and its underlying mechanism have yet to be elucidated. Herein, we revealed that DERL2 was highly expressed in CHOL and considered as an independent prognostic indicator for inferior survival in CHOL. DERL2 ectopically expressed in CHOL cells promoted cell proliferation and colony formation rates, and depleting DERL2 in CHOL cells curbed tumor growth in vitro and in vivo. More interestingly, the knockout of DERL2 augmented the growth-inhibitory effect of gemcitabine chemotherapy on CHOL cells by inducing cell apoptosis. Mechanistically, we discovered that DERL2 interacted with BAG6 (BAG cochaperone 6), thereby extending its half-life and reinforcing the oncogenic role of BAG6 in CHOL progression.
Assuntos
Apoptose , Colangiocarcinoma , Humanos , Colangiocarcinoma/tratamento farmacológico , Colangiocarcinoma/metabolismo , Colangiocarcinoma/patologia , Chaperonas Moleculares/genética , Chaperonas Moleculares/metabolismo , Proteínas de Membrana/metabolismo , Resistencia a Medicamentos Antineoplásicos/genéticaRESUMO
Objectives: To provide data on the safety and efficacy of renal arterial embolization (RAE) in patients with high-grade blunt renal injury. Materials and methods: Fifteen patients with high-grade blunt renal injury (AAST grades IV-V) admitted to our hospital from July 2014 to December 2019 were retrospectively reviewed in this study. Their clinical success rate and complications were investigated accordingly. Results: Fifteen patients with high-grade blunt renal injury, 13 men and 2 women with an average age of 41.6 years, including 11 hemodynamically unstable patients and 4 stable patients, were treated with RAE. Among these patients, 73.3% (11 of 15) had grade IV, and 26.7% (4 of 15) had grade V injuries, while 53.3% (8 of 15) patients had concomitant injuries. One patient received main RAE and 14 patients received selective RAE. The clinical success rate after the first embolization was 93.3% (14 of 15). RAE was repeated and was successfully performed in one patient with sustained hematuria. No significant difference in creatinine levels was found before and after embolization. During the follow-up period of 2-82 months, two patients required tube drainage due to urine leaks, one patient developed renal failure requiring renal replacement therapy, and one patient developed secondary hypertension. Conclusions: RAE can provide a high success rate of hemostasis for both hemodynamically stable and unstable patients with high-grade blunt renal injury, and only minor complications are observed with this procedure.
