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1.
J Biomed Nanotechnol ; 15(9): 1867-1880, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31387675

RESUMO

The present study aims to evaluate the effect of the ethyl acetate extract of Cichorium (EAEC) as a novel photosensitizer in photodynamic therapy (PDT) of colorectal carcinoma (CRC) HCT116 and SW620 cells. The absorption and fluorescence spectra of EAEC were measured using a UV-vis spectrophotometer and fluorescence spectrophotometer, respectively. EAEC-induced reactive oxygen species (ROS) production in HCT116 and SW620 cells was detected using 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) and glutathione/glutathione disulfide (GSH/GSSG). The photo- and dark toxicities of EAEC were estimated using the Cell Counting Kit-8 (CCK-8) assay. Cellular uptake and localization of EAEC were detected by confocal laser fluorescence microscopy. Annexin V-FITC/PI staining, Western blotting and immunofluorescence staining were used to assess apoptosis and autophagy. The antitumor activity of EAEC was confirmed in a xenograft model. Finally, effects on the PERK pathway were verified using qRT-PCR and Western blotting. EAEC displayed absorption and fluorescence emission peaks at 660 nm and 678 nm, respectively. EAEC induced ROS production in CRC cells. Assessment of dark toxicity showed that treatment with EAEC alone induced little cytotoxicity in CRC or normal cells but that EAEC-PDT induced significant photocytotoxicity in CRC cells in a time- and dose-dependent manner. After cellular uptake, EAEC was located in the mitochondria. Treatment with EAEC-PDT reduced xenograft tumor size. Further evaluation suggested that activation of the PERK pathway mediates these effects, as the apoptotic rate and autophagy flux increased markedly after EAEC-PDT. EAEC, a natural photosensitizer extracted from Cichorium, displays potential utility in PDT of CRC by targeting the PERK pathway.


Assuntos
Autofagia , Neoplasias Colorretais , Fotoquimioterapia , Acetatos , Apoptose , Linhagem Celular , Linhagem Celular Tumoral , Estresse do Retículo Endoplasmático , Humanos , Fármacos Fotossensibilizantes , Proteínas Quinases , Espécies Reativas de Oxigênio
2.
J Gastrointest Surg ; 2019 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-31066014

RESUMO

BACKGROUND AND AIMS: The Child-Pugh (CP) score is a widely used method to assess liver function and predict postoperative outcomes in patients with hepatocellular carcinoma (HCC). Recently, the fibrosis index (FIB-4) has been demonstrated to be closely associated with liver fibrosis and cirrhosis. This study aimed to compare the capability of FIB-4 index with CP score in predicting the outcomes for HCC patients after hepatectomy. METHODS: A total of 495 HCC patients who underwent hepatectomy were enrolled. The performance of the FIB-4 index in predicting postoperative liver failure (PHLF) and overall survival was compared with that of the CP score. RESULTS: Of them, 9.3% (46/495) patients developed PHLF. The area under the receiver operating characteristic (ROC) curve of the FIB-4 index for predicting PHLF was greater than that of the CP score (0.744 versus 0.621; P = 0.044). The optimal cutoff value of the FIB-4 index for predicting PHLF was 4.16. Multivariable analyses revealed that the FIB-4 index was an independent predictor of PHLF regardless of the hepatectomy subgroups, but the CP grade was only a significant predictor of PHLF in the minor hepatectomy subgroup. The FIB-4 index (4.16) stratified patients into two distinct overall survival cohorts (P = 0.006). The FIB-4 index also classified patients with the Barcelona Clinical Liver Cancer (BCLC) stages 0 and A into two distinct overall survival cohorts (P = 0.001 and P = 0.034, respectively). CONCLUSION: The FIB-4 index may be a better predictor of PHLF and overall survival in HCC patients with hepatectomy than CP score.

3.
Medicine (Baltimore) ; 98(15): e15168, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30985698

RESUMO

A precise and noninvasive method to predict posthepatectomy liver failure (PHLF) in clinical practice is still lacking. Liver fibrosis or cirrhosis accompanied with varying degrees of portal hypertension plays an important role in the occurrence of PHLF in hepatocellular carcinoma (HCC) patients. This study aims to compare the predictive ability of the albumin-bilirubin score to spleen thickness ratio (ALBI/ST) versus fibrosis-4 index (FIB-4) and aspartate aminotransferase to platelet count ratio index (ARPI) for the occurrence of PHLF. We retrospectively enrolled 932 patients who underwent liver resection for HCC between 2010 and 2017. The predictive accuracy of ALBI/ST ratio, FIB-4, and APRI for occurrence of PHLF was evaluated by receiver operating characteristic curve analysis. PHLF was diagnosed in 69 (7.4%) patients. The ALBI/ST ratio was found to be a significant predictor of PHLF. The AUC of ALBI/ST (AUC = 0.774; 95% CI, 0.731-0.817; P <.001) was larger than that of FIB-4 (AUC = 0.696; 95% CI, 0.634-0.759; P <.001) and APRI (AUC = 0.697; 95% CI, 0.629-0.764; P <.001). Multivariate analysis demonstrated that ALBI/ST ratio was a strong risk factor of PHLF in all hepatectomy subgroups. In conclusion, the ALBI/ST ratio has a superior predictive ability for PHLF compared with APRI and FIB-4.


Assuntos
Carcinoma Hepatocelular/cirurgia , Hepatectomia , Falência Hepática/diagnóstico , Neoplasias Hepáticas/cirurgia , Complicações Pós-Operatórias/diagnóstico , Biomarcadores/sangue , Carcinoma Hepatocelular/diagnóstico , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Prognóstico , Curva ROC , Estudos Retrospectivos , Baço/diagnóstico por imagem , Baço/patologia
4.
Scand J Gastroenterol ; 53(12): 1562-1568, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30572742

RESUMO

BACKGROUND AND AIMS: The impact of portal hypertension (PH) on postoperative short-term outcomes and long-term survival in hepatocellular carcinoma (HCC) patients has lately been discussed controversially. This study aimed to explore the influence of PH on postoperative outcomes in HCC patients undergoing surgical resection. METHODS: Patients undergoing hepatectomy for HCC from 2010 to 2014 were enrolled. The impact of PH on postoperative complications, posthepatectomy liver failure (PHLF) and overall survival (OS) was evaluated. RESULTS: A total of 355 HCC patients were enrolled; 129 (36.3%) experienced postoperative complications and 21 (5.9%) developed PHLF. PH was identified as an independent predictor of PHLF. Patients with PH experienced a higher incidence of complications and PHLF than patients without PH. On the Cox proportional hazards regression model, PH was verified as a risk factor of OS for BCLC stage 0/A and B patients. Patients without PH had significantly better long-term survival compared to patients with PH both in the total cohort and in cirrhosis subgroup. CONCLUSION: Liver resection in HCC patients with PH showed a significantly increased postoperative complications and PHLF, and revealed a decreasing long-term survival than non-PH patients. Besides, tumor burden also played an important role in determining the OS. However, due to the improvement in surgical technique and perioperative management, surgery was feasible in carefully selected HCC patients with PH.


Assuntos
Carcinoma Hepatocelular/cirurgia , Hipertensão Portal/complicações , Falência Hepática/epidemiologia , Neoplasias Hepáticas/cirurgia , Complicações Pós-Operatórias/epidemiologia , Adulto , Carcinoma Hepatocelular/mortalidade , China/epidemiologia , Feminino , Hepatectomia , Mortalidade Hospitalar , Humanos , Incidência , Cirrose Hepática/complicações , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida
5.
Photodiagnosis Photodyn Ther ; 24: 349-357, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30385297

RESUMO

BACKGROUND: Inflammatory bowel disease (IBD) is a group of inflammatory conditions characterized by chronic inflammation of the gastrointestinal (GI) tract. Recent preclinical and clinical studies have shown the therapeutic value of photodynamic therapy with low doses of photosensitizer and/or light in colitis treatment, but the detailed mechanism is unclear. METHODS: We examined 5-aminolevulinic acid (5-ALA) mediated photodynamic therapy (PDT) in dextran sulfate sodium (DSS)-induced colitis in mice. Endoscopic and macroscopic observations as well as the Disease Activity Index score (DAI) was used to monitor the disease. Cytokine expression was measured by quantitative RT-PCR analysis to evaluate the efficacy of PDT. We applied the Clariom™ D bioinformatics analysis to investigate the differentially expressed genes after PDT. Finally, we used quantitative RT-PCR analysis and Western blotting to validate the targets of differentially expressed genes. RESULTS: 5-ALA-PDT improved the DAI score and decreased the expression of various inflammatory cytokines. The Clariom™ D bioinformatics analysis identified 2043 diff ;erentially expressed genes (702 up-regulated and 1341 down-regulated). We confirmed the down-regulation of lncRNA-Neat1, lncRNA-Snhg5 and lncRNA-Gm9926 and the up-regulation of miRNA-204-5p, miRNA-218-5p, miRNA-200a-3p and miRNA-466h-5p. Additionally, the decreased expression level of the AKT3, p-AKT3, PI3K, p-PI3K protein were confirmed. CONCLUSIONS: This study provides in vivo comprehensive lncRNA and miRNA microarray analysis after 5-ALA-PDT treatment in DSS-induced colitis, and it may help to develop novel lncRNA-miRNA-related therapeutic approaches, such as the Neat1-miRNA204-5p-PI3K-AKT axis, to further increase the efficiency of PDT in IBD.

6.
World J Surg Oncol ; 16(1): 208, 2018 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-30326907

RESUMO

BACKGROUND: Underlying liver function is a major concern when applying surgical resection for hepatocellular carcinoma (HCC). We aimed to explore the capability of the albumin-bilirubin (ALBI) grade to predict post-hepatectomy liver failure (PHLF) and long-term survival after hepatectomy for HCC patients with different Barcelona Clinic Liver Cancer (BCLC) stages. METHODS: Between January 2010 and December 2014, 338 HCC patients who were treated with liver resection were enrolled. The predictive accuracy of ALBI grade system for PHLF and long-term survival across different BCLC stages was examined. RESULTS: A total of 26 (7.7%) patients developed PHLF. Patients were divided into BCLC 0/A and BCLC B/C categories. ALBI score was found to be a strong independent predictor of PHLF across different BCLC stages by multivariate analysis. In terms of overall survival (OS), it exhibited high discriminative power in the total cohort and in BCLC 0/A subgroup. However, differences in OS between ALBI grade 1 and 2 patients in BCLC B/C subgroup were not significant (P = 0.222). CONCLUSION: The ALBI grade showed good predictive ability for PHLF in HCC patients across different BCLC stages. However, the ALBI grade was only a significant predictor of OS in BCLC stage 0/A patients and failed to predict OS in BCLC stage B/C patients.

7.
J Exp Clin Cancer Res ; 35(1): 115, 2016 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-27440153

RESUMO

BACKGROUND: Synaptojanin 2 Binding Protein (SYNJ2BP) is essential to cell proliferation. Previous studies show that SYNJ2BP participates in sprouting angiogenesis, which plays an important part in several abnormal conditions including cancer. However, the activity of SYNJ2BP in hepatocellular carcinoma (HCC) has not been elucidated yet. METHODS: Firstly, real-time PCR and western blotting (WB) were adopted to evaluate SYNJ2BP expressions in HCC tissues and HCC cell lines. Secondly, we did follow-up and prognostic study to explore the association of SYNJ2BP expression and HCC patients prognosis. Thirdly, we induced or silenced SYNJ2BP expression on selected HCC cell lines and explored the function of SYNJ2BP in vitro and in vivo. Lastly, we conducted Cignal Finder Cancer 10-Pathway Reporter Array in combination with loss- and gain-of-function assay to investigate potential mechanisms. RESULTS: Through various techniques we found that SYNJ2BP was decreased in HCC tissues and HCC cell lines. The subsequent analysis showed that low expression of SYNJ2BP was associated with tumor size, tumor nodule number, vascular invasion, TNM stage and BCLC stage, and was an independent risk factor for survival of HCC. Later, the in vitro experiments demonstrated that SYNJ2BP inhibited HCC cells invasion, migration and proliferation, also the in vivo testing revealed that SYNJ2BP inhibited tumor growth and metastasis. Finally, we also uncovered that SYNJ2BP inhibited HCC growth and metastasis through activating DLL4-mediated Notch signaling pathway. CONCLUSIONS: Collectively, our data provide evidence that SYNJ2BP may act as a tumor suppressor during HCC development and could serve as a potential therapeutic target.


Assuntos
Carcinoma Hepatocelular/patologia , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Neoplasias Hepáticas/patologia , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Animais , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Masculino , Camundongos , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Transdução de Sinais
8.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 39(1): 102-8, 2014 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-24473379

RESUMO

Despite its more than 100-year history in experimental and clinical use, photodynamic therapy (PDT) is only starting to be appreciated for its full potential. PDT combines a photosensitizer and light in the presence of oxygen to treat cancer and other disorders. This paper reviews the molecular mechanism of PDT at the cellular level as well as in therapeutic settings in vivo. The availability of multiple photosensitizers with different structures and functional properties makes PDT an extremely versatile and, conversely, a challenging approach to cancer therapy. The advancing understanding of molecular pathways helps to design improved regimens. As most cancers are being treated with combined therapies, PDT is being integrated into rationally designed regimens that exploit molecular responses to PDT for improved efficacy.


Assuntos
Neoplasias/tratamento farmacológico , Fotoquimioterapia , Fármacos Fotossensibilizantes/uso terapêutico , Humanos
9.
World J Gastroenterol ; 19(33): 5590-2, 2013 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-24023506

RESUMO

When a distal common bile duct neoplasm is at the stage of carcinoma in situ or high-grade dysplasia, it is difficult for the surgeon to decide whether to perform pancreaticoduodenectomy. Here we describe a patient with a progressive dysplastic lesion in the common bile duct, which developed from moderate-high to high-grade dysplasia in approximately 2 mo. The patient refused major surgery. Therefore, endoscopic-assisted photodynamic therapy was performed. The result at follow-up using a trans-T-tube choledochoscope showed that the lesion was completely necrotic. This report is the first to describe the successful treatment of high-grade dysplasia of the distal bile duct using photodynamic therapy via a choledochoscope.


Assuntos
Neoplasias do Ducto Colédoco/tratamento farmacológico , Fotoquimioterapia/métodos , Hematoporfirinas/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Fármacos Fotossensibilizantes/uso terapêutico
10.
Zhonghua Zhong Liu Za Zhi ; 35(2): 132-4, 2013 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-23714669

RESUMO

OBJECTIVE: To investigate retrospectively the relationship between clinicopathological factors and lymph node matastasis of pancreatic adenocarcinoma. METHODS: The clinicopathological factors, including gender, age, preoperative CA-19-9 level etc. of 71 patients with pancreatic adenocarcinoma were summarized to analyze the relationship between those factors and lymph node matastasis. RESULTS: Among the 71 cases, there were 49 males (69.0%) and 22 females (31.0%). Forty-eight were ≥ 60 (67.6%) and 23 were < 60 (32.4%) years old. Twenty patients had normal preoperative CA-19-9 level (28.2%) and 51 had elevated level (71.8%). The tumor in 43 (60.6%) cases located in the pancreatic head and neck, and 28 (39.4%) in the body and tail. The tumors in 8 patients were well-differentiated (11.3%), 27 were moderately differentiated (38.0%), and 36 were poorly differentiated (50.7%). The maximum diameter of the tumor was ≤ 2 cm in 11 cases (15.5%), 2 - 5 cm in 45 cases (63.4%), and > 5 cm in 15 cases (21.1%). Ten patients had tumor confined to the pancreas (14.1%), and 61 invaded peripancreatic tissues (85.9%). Vascular tumor thrombus was found in 48 cases (67.6%), and 23 cases were absent (32.4%). Thirty-six cases had lymph node matastasis (50.7%). Univariate chi-square test revealed that differentiation and range of local infiltration were significantly associated with lymph node meatstasis (P < 0.05). Multivariate logistic regression analysis also showed that differentiation and range of local infiltration were significantly associated with lymph node meatstasis (P < 0.05). CONCLUSIONS: The differentiation of tumor and range of local infiltration of pancreatic adenocarcinoma are significantly associated with lymph node metastasis. There is no significant relationship of location of the tumor, maximum diameter, presence or absence of vascular tumor thrombus with lymph node metastasis. Therefore, special attention should be paid to lymph node dissection in cases with a poorly differentiated pancreatic adenocarcinoma invading into peripancreatic tissues.


Assuntos
Adenocarcinoma/patologia , Neoplasias Pancreáticas/patologia , Adenocarcinoma/imunologia , Adenocarcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno CA-19-9/metabolismo , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Células Neoplásicas Circulantes , Pancreatectomia , Neoplasias Pancreáticas/imunologia , Neoplasias Pancreáticas/cirurgia , Estudos Retrospectivos , Carga Tumoral
11.
World J Gastroenterol ; 18(43): 6341-4, 2012 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-23180959

RESUMO

An isolated parenchymal gastric metastasis from ovarian carcinoma without any other sites of recurrence is extremely rare. Only two cases have been reported, both of which were symptomatic. We herein report such a case without any symptoms. A 61-year-old woman presented with a high cancer antigen-125 level without any other clinical manifestation. A subsequent ¹8F-fluorodeoxyglucose (¹8F-FDG) positron emission tomography/computed tomography scan revealed a submucosal mass with hypermetabolism of ¹8F-FDG (standardized uptake value: 5.36) in the gastric antrum. The final pathology after gastric antrectomy showed a metastatic gastric tumor from a primary ovarian carcinoma. We also performed an extensive literature review about gastric metastasis from ovarian carcinoma published until recently, and this is the first case of an isolated parenchymal gastric metastasis from ovarian carcinoma without any symptoms.


Assuntos
Adenocarcinoma/secundário , Neoplasias Ovarianas/patologia , Antro Pilórico/patologia , Neoplasias Gástricas/secundário , Adenocarcinoma/cirurgia , Adulto , Idoso , Feminino , Gastrectomia , Humanos , Pessoa de Meia-Idade , Imagem Multimodal , Neoplasias Ovarianas/cirurgia , Tomografia por Emissão de Pósitrons , Valor Preditivo dos Testes , Antro Pilórico/diagnóstico por imagem , Antro Pilórico/cirurgia , Neoplasias Gástricas/cirurgia , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento
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