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1.
Cell Death Dis ; 7(10): e2400, 2016 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-27711074

RESUMO

Aberrant autophagic processes have been found to have fundamental roles in the pathogenesis of different kinds of tumors, including hepatocellular carcinoma (HCC). P300/CBP-associated factor (PCAF), a histone acetyltransferase (HAT), performs its function by acetylating both histone and non-histone proteins. Our previous studies showed that PCAF was downregulated in HCC tissues and its high expression was significantly associated with patient survival after surgery, serving as a prognostic marker. In this study we found that overexpression of PCAF induced autophagy of HCC cells and its knockdown depressed autophagy. As type II programmed cell death, autophagy induced by PCAF-elicited cell death in HCC cells. In vivo experiments confirmed that PCAF-induced autophagy inhibited tumor growth. Subsequent in vitro experiments showed that PCAF promoted autophagy by inhibiting Akt/mTOR signaling pathway. Our findings show that PCAF is a novel modulator of autophagy in HCC, and can serve as an attractive therapeutic strategy of HCC treatment.


Assuntos
Autofagia , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Fatores de Transcrição de p300-CBP/metabolismo , Adenina/análogos & derivados , Adenina/farmacologia , Animais , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Feminino , Técnicas de Silenciamento de Genes , Humanos , Macrolídeos/farmacologia , Camundongos Endogâmicos BALB C , Camundongos Nus , Oligopeptídeos/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
2.
Chin Med J (Engl) ; 128(22): 3043-9, 2015 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-26608984

RESUMO

BACKGROUND: Intraperitoneal lymphangioma (IL) used to be thought of as a benign lymphatic malformation with a low rate of preoperative diagnosis. This retrospective study aimed to explore the connection between the cysts and clinical manifestation and imaging characteristics, and to study diagnostic confusion, therapeutic principles and potential recurrent reasons, to further enhance the comprehension of this rare disease. METHODS: Here, we retrospectively reviewed 21 patients diagnosed with IL. Age, sex, complaints, physical findings, and imaging features of each patient were documented. The therapies, postoperative complications and treatments were discussed. RESULTS: Symptomatology included eight patients (38%) with intermittent dull pain in the abdomen, and three patients (14%) complained of abdominal persistent pain. The physical examination revealed an abdominal mass in 16 patients (76%), and eight (38%) were reported no discomfort. IL was correctly established preoperatively in 19 patients (90%). Patients were treated using laparotomy, except one who was treated with laparoscopy. Two recurrences were noted during follow-up. CONCLUSIONS: IL should be suspected in any patient with a mobile abdominal mass and surgery is required immediately after discovery of the tumor.


Assuntos
Linfangioma/diagnóstico , Abdome/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Diagnóstico Diferencial , Feminino , Humanos , Laparoscopia , Linfangioma/cirurgia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Estudos Retrospectivos , Adulto Jovem
3.
World J Gastroenterol ; 21(18): 5719-34, 2015 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-25987799

RESUMO

AIM: To investigate whether prophylactic abdominal drainage is necessary after pancreatic resection. METHODS: PubMed, Web of Science, and the Cochrane Library were systematically searched to obtain relevant articles published before January 2014. Publications were retrieved if they met the selection criteria. The outcomes of interest included: mortality, morbidity, postoperative pancreatic fistula (POPF), clinically relevant pancreatic fistula (CR-PF), abdominal abscess, reoperation rate, the rate of interventional radiology drainage, and the length of hospital stay. Subgroup analyses were also performed for pancreaticoduodenectomy (PD) and for distal pancreatectomy. Begg's funnel plot and the Egger regression test were employed to assess potential publication bias. RESULTS: Nine eligible studies involving a total of 2794 patients were identified and included in this meta-analysis. Of the included patients, 1373 received prophylactic abdominal drainage. A fixed-effects model meta-analysis showed that placement of prophylactic drainage did not have beneficial effects on clinical outcomes, including morbidity, POPF, CR-PF, reoperation, interventional radiology drainage, and length of hospital stay (Ps > 0.05). In addition, prophylactic drainage did not significantly increase the risk of abdominal abscess. Overall analysis showed that omitting prophylactic abdominal drainage resulted in higher mortality after pancreatectomy (OR = 1.56; 95%CI: 0.93-2.92). Subgroup analysis of PD showed similar results to those in the overall analysis. Elimination of prophylactic abdominal drainage after PD led to a significant increase in mortality (OR = 2.39; 95%CI: 1.22-4.69; P = 0.01). CONCLUSION: Prophylactic abdominal drainage after pancreatic resection is still necessary, though more evidence from randomized controlled trials assessing prophylactic drainage after PD and distal pancreatectomy are needed.


Assuntos
Abscesso Abdominal/prevenção & controle , Drenagem , Pancreatectomia , Fístula Pancreática/prevenção & controle , Pancreaticoduodenectomia , Abscesso Abdominal/diagnóstico , Abscesso Abdominal/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Distribuição de Qui-Quadrado , Drenagem/efeitos adversos , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Razão de Chances , Pancreatectomia/efeitos adversos , Fístula Pancreática/diagnóstico , Fístula Pancreática/etiologia , Pancreaticoduodenectomia/efeitos adversos , Reoperação , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
4.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 28(12): 1303-6, 2012 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-23232523

RESUMO

AIM: To observe the expression of Fbxw7 and explore its correlation with cell proliferation of hepatocellular carcinoma (HCC). METHODS: The expression of Fbxw7 in paired tumor and tumor-adjacent normal tissues from 40 patients with HCC were assessed using RT-PCR and immunohistochemistry. The expression level of Fbxw7 mRNA in normal liver cell line (LO2) and HCC cell lines (Hep3B and SMMC-7721) were detected by real-time RT-PCR. Colony formation assay and tumor xenograft assay were performed in different cell lines with different Fbxw7 expression respectively to investigate the ability of cell proliferation in vitro and in vivo. RESULTS: The expression of Fbxw7 at both mRNA and protein levels in HCC tissues were significantly down-regulated compared to tumor-adjacent normal tissues (P<0.05). Down-regulation of Fbxw7 was found apparently associated with high Edmonson-Steiner classification and advanced TNM stage (P<0.05). The expression of Fbxw7 mRNA in LO2 was significantly higher than that in Hep3B or SMMC-7721 (P<0.05). Cell lines with less Fbxw7 expression had not only more colonies in colony formation assay (P<0.05), but also bigger xenografts in vitro (P<0.05). CONCLUSION: The low expression of Fbxw7 correlates with the poor clinicopathological characteristics and cell proliferation of HCC.


Assuntos
Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/fisiopatologia , Proteínas de Ciclo Celular/genética , Proliferação de Células , Proteínas F-Box/genética , Neoplasias Hepáticas/genética , Ubiquitina-Proteína Ligases/genética , Adulto , Idoso , Animais , Carcinoma Hepatocelular/metabolismo , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Proteínas F-Box/metabolismo , Proteína 7 com Repetições F-Box-WD , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/fisiopatologia , Masculino , Camundongos , Camundongos SCID , Pessoa de Meia-Idade , Ubiquitina-Proteína Ligases/metabolismo
5.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 28(9): 933-6, 2012 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-22980656

RESUMO

AIM: To investigate the effect of nimesulide on cell apoptosis and possible mechanism in human hepatocellular carcinoma SMMC-7721 cells. METHODS: SMMC-7721 cells were treated with nimesulide at different concentrations. Cell viability was assessed by MTT assay. Cell apoptosis rate was determined with flow cytometry. The cleavage activity of PARP and caspase-9 and the expression of HSP70 were evaluated using RT-PCR and Western blotting. The influence of HSP70 on cell apoptosis was observed using RNA interference silencing HSP70 expression. RESULTS: Nimesulide significantly inhibited cell growth in SMMC-7721 cells in a time- and concentration-dependent manner, and induced cell apoptosis in a concentration-dependent manner. Moreover, nimesulide promoted the cleavage of caspase-9 and PARP and inhibited the mRNA and protein expression of HSP70. Through the specific inhibition on HSP70 gene with siRNA, cell apoptosis increased, and the apoptosis was enhanced by the cleavage activity of caspase-9 and PARP. CONCLUSION: Nimesulide could inhibit cell growth and induce apoptosis in human hepatocellular carcinoma SMMC-7721 cells via the downregulation of HSP70.


Assuntos
Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/tratamento farmacológico , Proteínas de Choque Térmico HSP70/antagonistas & inibidores , Neoplasias Hepáticas/tratamento farmacológico , Sulfonamidas/farmacologia , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Regulação para Baixo , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico HSP70/fisiologia , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia
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