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1.
Int J Mol Sci ; 20(19)2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31574948

RESUMO

Partially hydrolyzed guar gum (PHGG) has received considerable attention for its various bioactive functions. The injection of d-galactose can cause aging-related injury which is usually resulted from oxidative stress on tissues and cells. In this study, d-galactose (200 mg/kg/day) was injected into rats, and the protective effects of PHGG (500, 1000, and 1500 mg/kg/day) against oxidative damages, as well as its probiotic functions, were analyzed. The results showed that PHGG treatment at a concentration of 1500 mg/kg/day greatly reduced the levels of lactic acid, nitric oxide, inducible nitric oxide synthase, advanced glycation end products, and increased the telomerase activity, by 7.60%, 9.25%, 12.28%, 14.58%, and 9.01%, respectively. Moreover, PHGG significantly elevated the activities of antioxidant enzymes and decreased the content of malondialdehyde in rat serum and brain. The oxidative damage was also significantly alleviated in the liver and hippocampus and the expressions of brain-derived neurotrophic factor and choline acetyltransferase also increased. Furthermore, PHGG treatment could significantly regulated the expression of sirtuin 1, forkhead box O1, and tumor protein p53 in the hippocampus. It also increased the levels of organic acids and improved the composition of intestinal microbiota. These findings demonstrated that PHGG treatment could effectively alleviate the oxidative damage and dysbacteriosis.

2.
Nutrients ; 11(5)2019 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-31035540

RESUMO

Natural polysaccharides, particularly galactomannans, are potential candidates for treatment of alcoholic liver diseases (ALD). However, applications are restricted due to the physicochemical properties associated with the high molecular weight. In this work, guar gum galactomannans were partially hydrolyzed by ß-mannanase, and the molecular mechanisms of hepatoprotective effects were elucidated both in vitro and in vivo. Release of lactate dehydrogenase and cytochrome C were attenuated by partially hydrolyzed guar gum (PHGG) in HepG2 cells, due to protected cell and mitochondrial membrane integrity. PHGG co-administration decreased serum amino transaminases and cholinesterase levels of acute alcohol intoxicated mice, while hepatic pathologic morphology was depleted. Activity of superoxide dismutase, catalase, and glutathione peroxidase was recovered to 198.2, 34.5, 236.0 U/mg protein, respectively, while malondialdehyde level was decreased by 76.3% (PHGG, 1000 mg/kg∙day). Co-administration of PHGG induced a 4.4-fold increment of p-AMPK expression, and lipid metabolism was mediated. PHGG alleviated toll-like-receptor-4-mediated inflammation via the signaling cascade of MyD88 and IκBα, decreasing cytokine production. Moreover, mediated expression of Bcl-2 and Bax was responsible for inhibited acute alcohol-induced apoptosis with suppressed cleavage of caspase 3 and PARP. Findings gained suggest that PHGG can be used as functional food supplement for the treatment of acute alcohol-induced liver injury.


Assuntos
Etanol/toxicidade , Galactanos/química , Galactanos/farmacologia , Hepatopatias Alcoólicas/prevenção & controle , Mananas/química , Mananas/farmacologia , Gomas Vegetais/química , Gomas Vegetais/farmacologia , Animais , Apoptose/efeitos dos fármacos , Membrana Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Células Hep G2 , Humanos , Inflamação/metabolismo , Peroxidação de Lipídeos , Potencial da Membrana Mitocondrial , Camundongos , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo
3.
Carbohydr Polym ; 213: 59-69, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30879690

RESUMO

Immunostimulatory activity of the flaxseed gum neutral fraction (NFG) was investigated. NFG was characterized as a xylose rich heteroglycan through monosaccharide composition analysis, FT-IR, methylation/GC-MS, and 1D/2D-NMR. NFG stimulated NO production and phagocytic activity of macrophages. Secretion of interleukin-6, interleukin-1ß, and tumor necrosis factor-α (254.7 pg/mL, 2.5 ng/mL, and 42.9 pg/mL, respectively) was significantly induced by NFG. Mitogen-activated protein kinases of JNK and P38 were activated by NFG with increased phosphorylation of JNK and P38, while NO production was reduced to 6.05 and 4.42 µM by JNK and P38 inhibitor, respectively. Nuclear factor-κB signaling pathway was also activated by NFG with the suppression of IκBα and up-regulation of phosphorylation of IκBα and nuclear factor-κB P65. Toll like receptor-2 was the molecular target of NFG and responsible for the activation of down-stream signaling pathways. Thus, NFG from flaxseed gum may potentially be used as a natural immunomodulator in functional foods.


Assuntos
Adjuvantes Imunológicos/farmacologia , Linho/química , Macrófagos/efeitos dos fármacos , Polissacarídeos/farmacologia , Receptor 2 Toll-Like/antagonistas & inibidores , Xilose/farmacologia , Adjuvantes Imunológicos/química , Adjuvantes Imunológicos/isolamento & purificação , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Citocinas/antagonistas & inibidores , Citocinas/biossíntese , Relação Dose-Resposta a Droga , Camundongos , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Células RAW 264.7 , Relação Estrutura-Atividade , Receptor 2 Toll-Like/metabolismo , Xilose/química , Xilose/isolamento & purificação
5.
Int J Cancer ; 141(7): 1445-1457, 2017 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-28643325

RESUMO

Tumor antigens is at the core of cancer immunotherapy, however, the ideal antigen selection is difficult especially in poorly immunogenic tumors. In this study, we designed a strategy to modify hepatocellular carcinoma (HCC) cells by surface expressing anti-CD3scfv within the tumor site strictly, which depended on the E1A-engineered human umbilical cord mesenchymal stem cells (HUMSC.E1A) delivery system. Subsequently, membrane-bound anti-CD3scfv actived the lymphocytes which lysed HCC cells bypassing the expression of antigens or MHC restriction. First, we constructed the anti-CD3scfv gene driven by human α-fetoprotein (AFP) promoter into an adenoviral vector and the E1A gene into the lentiviral vector. Our results showed that anti-CD3scfv could specifically express on the surface of HCC cells and activate the lymphocytes to kill target cells effectively in vitro. HUMSC infected by AdCD3scfv followed by LentiR.E1A could support the adenoviral replication and packaging in vitro 36 h after LentiR.E1A infection. Using a subcutaneous HepG2 xenograft model, we confirmed that AdCD3scfv and LentiR.E1A co-transfected HUMSC could migrate selectively to the tumor site and produce considerable adenoviruses. The new generated AdCD3scfv infected and modified tumor cells successfully. Mice injected with the MSC.E1A.AdCD3scfv and lymphocytes significantly inhibited the tumor growth compared with control groups. Furthermore, 5-fluorouracil (5-FU) could sensitize adenovirus infection at low MOI resulting in improved lymphocytes cytotoxicity in vitro and in vivo. In summary, this study provides a promising strategy for solid tumor immunotherapy.


Assuntos
Complexo CD3/imunologia , Carcinoma Hepatocelular/terapia , Imunoterapia/métodos , Neoplasias Hepáticas/terapia , Anticorpos de Cadeia Única/imunologia , Cordão Umbilical/citologia , Adenoviridae/genética , Adenoviridae/fisiologia , Animais , Citotoxicidade Celular Dependente de Anticorpos , Antimetabólitos Antineoplásicos/farmacologia , Complexo CD3/genética , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/virologia , Membrana Celular/imunologia , Movimento Celular , Fluoruracila/farmacologia , Vetores Genéticos , Xenoenxertos , Humanos , Lentivirus/genética , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/virologia , Linfócitos/imunologia , Células-Tronco Mesenquimais/imunologia , Camundongos , Anticorpos de Cadeia Única/genética , Anticorpos de Cadeia Única/metabolismo , Fatores de Tempo , Replicação Viral , Ensaios Antitumorais Modelo de Xenoenxerto/métodos , alfa-Fetoproteínas/genética
6.
Eur J Med Chem ; 124: 417-427, 2016 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-27597417

RESUMO

[Pd(L)(DMSO)Cl2] (1) and [Pt(L)(DMSO)Cl2] (2) with 9-amino-oxoisoaporphine (L), were synthesized and characterized. 1 and 2 are more selectively cytotoxic to Hep-G2 cells versus normal liver cells (HL-7702). Various experiments showed that 2 acted as telomerase inhibitors targeting G4-DNA and triggered cell apoptosis by interacting with c-myc G4-DNA. Furthermore, 2 significantly induced cell cycle arrest at both G2/M and S phase, which leading to the down-regulation of cdc25 A, cyclin D, cyclin B, cyclin A and CDK2 and the up-regulation of p53, p27, p21,chk1 and chk2. In addition, 2 also caused mitochondrial dysfunction. Taken together, we found that 2 exerted its cytotoxic activity mainly via inhibiting telomerase by interaction with c-myc G4-DNA and disruption of mitochondrial function.


Assuntos
Apoptose/efeitos dos fármacos , DNA/química , Quadruplex G/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Compostos Organometálicos/farmacologia , Proteínas Proto-Oncogênicas c-myc/genética , Telomerase/antagonistas & inibidores , Antineoplásicos/química , Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Aporfinas/química , Transporte Biológico , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , DNA/metabolismo , Regulação para Baixo/efeitos dos fármacos , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/patologia , Compostos Organometálicos/química , Compostos Organometálicos/metabolismo , Platina/química , Espécies Reativas de Oxigênio/metabolismo , Solubilidade , Relação Estrutura-Atividade , Transcrição Genética/efeitos dos fármacos
7.
Mol Med Rep ; 14(1): 995-1001, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27222229

RESUMO

Ewing's sarcoma, the second most common type of malignant bone tumor, generally occurs in children and young adults. The current treatment of Ewing's sarcoma comprises systemic anti­cancer chemotherapy with complete surgical resection. However, the majority of patients with Ewing's sarcoma develop resistance to chemotherapy. The present study revealed an oncogenic role of lactate dehydrogenase­A (LDHA) in the resistance of Ewing's sarcoma to cetuximab. LDHA was shown to be upregulated at the protein and mRNA level in cetuximab­resistant Ewing's sarcoma tissues and a cell line. In addition, a link between LDHA­induced glycolysis and cetuximab resistance in Ewing's sarcoma cells was revealed. Of note, inhibition of LDHA by either small interfering RNA or LDHA inhibitor oxamate significantly re­sensitized cetuximab­resistant cells to cetuximab. Combined treatment with LDHA inhibitor and cetuximab synergistically reduced the viability of cetuximab-resistant cells through the suppression of LDHA. The present study revealed a novel mechanism of cetuximab resistance from the perspective of cancer­cell metabolism and provided a sensitization approach, which may aid in the development of anti-chemoresistance strategies for the treatment of cetuximab-resistant Ewing's sarcoma.


Assuntos
Antineoplásicos/farmacologia , Cetuximab/farmacologia , Resistencia a Medicamentos Antineoplásicos , L-Lactato Desidrogenase/antagonistas & inibidores , Sarcoma de Ewing/metabolismo , Adolescente , Adulto , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Expressão Gênica , Glicólise , Humanos , Isoenzimas/antagonistas & inibidores , Isoenzimas/genética , L-Lactato Desidrogenase/genética , Masculino , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Interferente Pequeno , Sarcoma de Ewing/genética , Adulto Jovem
8.
Hepatology ; 64(2): 456-72, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-26990897

RESUMO

UNLABELLED: Hepatocellular carcinoma (HCC) remains a global challenge due to high morbidity and mortality rates and poor response to treatment. Immunotherapy, based on introduction of dendritic cells (DCs) activated by tumor cell lysates as antigens ex vivo, shows limited response rates in HCC patients. Here, we demonstrate that tumor cell-derived exosomes (TEXs), displaying an array of HCC antigens, can elicit a stronger immune response than cell lysates in vitro and in vivo. Significant tumor growth inhibition was achieved in ectopic and orthotopic HCC mice treated with TEX-pulsed DCs. Importantly, the tumor immune microenvironment was significantly improved in orthotopic HCC mice treated by TEX-pulsed DCs, demonstrated by increased numbers of T lymphocytes, elevated levels of interferon-γ, and decreased levels of interleukin-10 and tumor growth factor-ß in tumor sites. As expected, T cells played an essential role in the TEX-pulsed DC-mediated immune response. Notably, exosomes from HCC cells not only promoted HCC-specific cytolysis but also provided cross-protective effects against pancreatic cancer cells. Moreover, HCC-specific cytolysis, elicited by DCs pulsed with human HepG2 cell-derived exosomes, was observed across different human HCC cells irrespective of human leukocyte antigen types. CONCLUSION: HCC TEXs can potently carry HCC antigens, trigger a strong DC-mediated immune response, and improve the HCC tumor microenvironment. (Hepatology 2016;64:456-472).


Assuntos
Carcinoma Hepatocelular/terapia , Exossomos , Imunoterapia/métodos , Neoplasias Hepáticas Experimentais/terapia , Animais , Carcinoma Hepatocelular/imunologia , Linhagem Celular , Estudos de Viabilidade , Humanos , Neoplasias Hepáticas Experimentais/imunologia , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Nus , Chaperonas Moleculares , Linfócitos T , Microambiente Tumoral
9.
PLoS One ; 11(1): e0148263, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26824903

RESUMO

Mouse models are commonly used for studying hepatocellular carcinoma (HCC) biology and exploring new therapeutic interventions. Currently three main modalities of HCC mouse models have been extensively employed in pre-clinical studies including chemically induced, transgenic and transplantation models. Among them, transplantation models are preferred for evaluating in vivo drug efficacy in pre-clinical settings given the short latency, uniformity in size and close resemblance to tumors in patients. However methods used for establishing orthotopic HCC transplantation mouse models are diverse and fragmentized without a comprehensive comparison. Here, we systemically evaluate four different approaches commonly used to establish HCC mice in preclinical studies, including intravenous, intrasplenic, intrahepatic inoculation of tumor cells and intrahepatic tissue implantation. Four parameters--the latency period, take rates, pathological features and metastatic rates--were evaluated side-by-side. 100% take rates were achieved in liver with intrahepatic, intrasplenic inoculation of tumor cells and intrahepatic tissue implantation. In contrast, no tumor in liver was observed with intravenous injection of tumor cells. Intrahepatic tissue implantation resulted in the shortest latency with 0.5 cm (longitudinal diameter) tumors found in liver two weeks after implantation, compared to 0.1cm for intrahepatic inoculation of tumor cells. Approximately 0.1cm tumors were only visible at 4 weeks after intrasplenic inoculation. Uniform, focal and solitary tumors were formed with intrahepatic tissue implantation whereas multinodular, dispersed and non-uniform tumors produced with intrahepatic and intrasplenic inoculation of tumor cells. Notably, metastasis became visible in liver, peritoneum and mesenterium at 3 weeks post-implantation, and lung metastasis was visible after 7 weeks. T cell infiltration was evident in tumors, resembling the situation in HCC patients. Our study demonstrated that orthotopic HCC mouse models established via intrahepatic tissue implantation authentically reflect clinical manifestations in HCC patients pathologically and immunologically, suggesting intrahepatic tissue implantation is a preferable approach for establishing orthotopic HCC mouse models.


Assuntos
Carcinoma Hepatocelular/secundário , Neoplasias Hepáticas/patologia , Neoplasias Pulmonares/secundário , Neoplasias Peritoneais/secundário , Células Tumorais Cultivadas/transplante , Animais , Modelos Animais de Doenças , Histocitoquímica , Humanos , Injeções Intravenosas , Fígado/patologia , Pulmão/patologia , Imagem por Ressonância Magnética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Nus , Transplante de Neoplasias/métodos , Peritônio/patologia , Baço/patologia
10.
Int J Genomics ; 2015: 197603, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26425543

RESUMO

This study has analyzed the gene expression patterns of an IPMN microarray dataset including normal pancreatic ductal tissue (NT), intraductal papillary mucinous adenoma (IPMA), intraductal papillary mucinous carcinoma (IPMC), and invasive ductal carcinoma (IDC) samples. And eight clusters of differentially expressed genes (DEGs) with similar expression pattern were detected by k-means clustering. Then a survey map of functional disorder in IPMN progression was established by functional enrichment analysis of these clusters. In addition, transcription factors (TFs) enrichment analysis was used to detect the key TFs in each cluster of DEGs, and three TFs (FLI1, ERG, and ESR1) were found to significantly regulate DEGs in cluster 1, and expression of these three TFs was validated by qRT-PCR. All these results indicated that these three TFs might play key roles in the early stages of IPMN progression.

11.
Biochem Biophys Res Commun ; 427(3): 666-70, 2012 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-23026048

RESUMO

Toll-like receptors (TLRs) play a key role in innate immune response and inflammation, especially in periodontitis. Meanwhile, hyperglycemia can induce inflammation in diabetes complications. However, the activity of TLRs in periodontitis complicated with hyperglycemia is still unclear. In the present study, high glucose (25 mmol/l) significantly induced TLR2 expression in gingival fibroblasts (p<0.05). Also, high glucose increased nuclear factor kappa B (NF-κB) p65 nuclear activity, tumor necrosis factor-α (TNF-α) and interleukin-lß (IL-1ß) levels. Protein kinase C (PKC)-α and δ knockdown with siRNA significantly decreased TLR2 and NF-κB p65 expression (p<0.05), whereas inhibition of PKC-ß had no effect on TLR2 and NF-κB p65 under high glucose (p<0.05). Additional studies revealed that TLR2 knockdown significantly abrogated high-glucose-induced NF-κB expression and inflammatory cytokine secretion. Collectively, these data suggest that high glucose stimulates TNF-α and IL-1ß secretion via inducing TLR2 through PKC-α and PKC-δ in human gingival fibroblasts.


Assuntos
Gengiva/imunologia , Hiperglicemia/imunologia , Interleucina-1beta/biossíntese , Proteína Quinase C-alfa/metabolismo , Proteína Quinase C/metabolismo , Receptor 2 Toll-Like/biossíntese , Fator de Necrose Tumoral alfa/biossíntese , Núcleo Celular/metabolismo , Células Cultivadas , Fibroblastos/efeitos dos fármacos , Fibroblastos/imunologia , Técnicas de Silenciamento de Genes , Gengiva/efeitos dos fármacos , Glucose/farmacologia , Humanos , Proteína Quinase C beta , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Receptor 2 Toll-Like/genética , Fator de Transcrição RelA/metabolismo
12.
Cell Immunol ; 271(1): 118-23, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21745658

RESUMO

Interaction of costimulatory molecules and their receptors is crucial for tumor lysate-pulsed dendritic cells (sensitized DC, sDC) to promote T cell activation, clonal expansion and its antitumor immunity. To augment the costimulatory signal may regulate the interaction between DC and cytotoxic T lymphocyte (CTL) and consequently enhance the antitumor response. The costimulatory ligand and receptor pair of 4-1BB/4-1BBL is one of the main factors in the costimulation of CTL. We explored the adjuvant role of a recombinant human 4-1BBL extracellular domain (ex4-1BBL) in modulating CTL activation induced by HepG2 antigen-loaded DC (sDC). The augment effects of sDC in combination with ex4-1BBL on the proliferation, activation, cell survival and cytotoxicity against HepG2 cells of CTL were examined. In the presence of ex4-1BBL, sDC exhibited markedly augmented effects on the above four functions of CTL. These results demonstrate that ex4-1BBL plays an important role in the costimulation pathway for DC-mediated CTL's activation, which might be a useful adjuvant factor for DC-based cancer biotherapy.


Assuntos
Ligante 4-1BB/imunologia , Células Dendríticas/imunologia , Linfócitos T Citotóxicos/imunologia , Linfócitos T/imunologia , Ligante 4-1BB/metabolismo , Sítios de Ligação/imunologia , Proliferação de Células , Sobrevivência Celular/imunologia , Células Cultivadas , Técnicas de Cocultura , Citotoxicidade Imunológica/imunologia , Células Dendríticas/metabolismo , Citometria de Fluxo , Células Hep G2 , Humanos , Interferon gama/imunologia , Interferon gama/metabolismo , Interleucina-2/imunologia , Interleucina-2/metabolismo , Células K562 , Ativação Linfocitária/imunologia , Linfócitos T/metabolismo , Linfócitos T Citotóxicos/metabolismo , Fatores de Tempo , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/imunologia , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/metabolismo
13.
Asia Pac J Clin Nutr ; 20(2): 154-60, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21669582

RESUMO

OBJECTIVE: To determine the effects of total parenteral nutrition (TPN) and enteral nutrition (EN) on biochemical and clinical outcomes in pancreatic cancer patients who underwent pancreaticoduodenectomy. METHODS: From the year 2006 to 2008, 60 patients who underwent pancreaticoduodenectomy in Tianjin Third Central Hospital were enrolled in this study. They were randomly divided into the EN group and the TPN group. The biochemical and clinical parameters were recorded and analyzed between the two groups. RESULTS: There was no significant difference in the nutritional status, liver and kidney function, and blood glucose levels between the TPN and EN groups on the preoperative day, the 1st and 3 rd postoperative days. However, on the 7th postoperative day, there was significant difference between the two groups in 24 h urinary nitrogen, serum levels of, total protein (TP), transferrin (TF), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and γ-glutamyl transpeptadase (GGT), blood urea nitrogen (BUN) and creatinine (Cr). On the 14th postoperative day, there was a significant difference between the two groups in terms of urinary levels of 24 h nitrogen, TP, TF, retinol binding protein, ALT, AST, ALP, GGT, total bilirubin, direct bilirubin, BUN, Cr, and glucose. The incidence of delayed gastric emptying in the EN and TPN groups was 0% and 20%, respectively. Moreover, the incidence of pancreatic fistulas and hemorrhages in the EN group were 3.6% and 3.6%, versus 26.7% and 30% in the TPN group, respectively. CONCLUSIONS: EN is better than TPN for pancreatic cancer patients who received pancreaticoduodenectomy.


Assuntos
Nutrição Enteral/métodos , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia , Nutrição Parenteral Total/métodos , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Aspartato Aminotransferases/sangue , Bilirrubina/metabolismo , Biomarcadores/sangue , Biomarcadores/urina , Proteínas Sanguíneas/metabolismo , Nitrogênio da Ureia Sanguínea , Creatinina/sangue , Creatinina/urina , Feminino , Esvaziamento Gástrico , Glucose/metabolismo , Hemorragia/prevenção & controle , Humanos , Rim/metabolismo , Fígado/metabolismo , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Nitrogênio/urina , Fístula Pancreática/prevenção & controle , Neoplasias Pancreáticas/metabolismo , Complicações Pós-Operatórias , Transferrina/metabolismo , Resultado do Tratamento , gama-Glutamiltransferase/sangue
14.
World J Gastroenterol ; 15(12): 1506-11, 2009 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-19322926

RESUMO

AIM: To evaluate the effect of intrahepatic trans-plantation of hepatic oval cells (HOC) on fulminant hepatic failure (FHF) in rats. METHODS: HOC obtained from rats were labeled with green fluocescent protein (GFP) or 5, 6-carboxyfluorescein diacetate succinmidyl ester (CFDA-SE). Cell fluorescence was observed under fluorescent microscope at 6, 24, 48 and 72 h after labeling. CFDA-SE labeled HOC (5 x 10(6) cells each rat) were injected into livers of rats with FHF induced by D-galactosamine. Serum albumin (ALB), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBil) levels were measured at different time points. Liver function of rats was examined on days 3, 7, 14 and 21 after HOC transplantation. RESULTS: The positive rate of GFP and CFDA-SE labeled HOC was 10% and 90%, respectively, with no significant change in cell viabilities. The survival rate was higher in HOC transplantation group than in control group, especially 48 (9/15 vs 6/15) and 72 h (9/15 vs 4/15) after HOC transplantation. The serum ALT, AST and TBil levels were decreased while the serum Alb level was increased after HOC transplantation. Fluorescence became faded and diffused in liver tissues, suggesting that proliferation and differentiation occur in transplanted HOC. CONCLUSION: CFDA-SE is superior to GFP in labeling HOC, although fluorescence intensity is decreased progressively with cell division. HOC transplantation can improve the liver function and increase the survival rate of recipients.


Assuntos
Transplante de Células/métodos , Hepatócitos/transplante , Falência Hepática Aguda/cirurgia , 2-Acetilaminofluoreno/toxicidade , Animais , Carcinógenos/toxicidade , Divisão Celular/efeitos dos fármacos , Hepatócitos/citologia , Hepatócitos/efeitos dos fármacos , Hepatócitos/ultraestrutura , Falência Hepática Aguda/induzido quimicamente , Ratos , Ratos Wistar , Sobreviventes
15.
Zhonghua Zhong Liu Za Zhi ; 30(10): 759-63, 2008 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-19173806

RESUMO

OBJECTIVE: To investigate the practical possibility of inducing dendritic cells (DCs) from mononuclear cells in the lost blood during operation of hepatocellular carcinoma (HCC) patients, and attempted to find a new source of precursor cells for the personalized immunotherapy based on DCs. METHODS: Collected lost blood during hepatectomy from 9 HCC patients and human cord blood from 8 cases of healthy donors undergoing caesarean section. Their mononuclear cells were divided into monocytes and nonadherent lymphocytes. RhGM-CSF and rhIL-4 were administered to induce the monocytes differentiation into DCs, and then loaded with different antigens (lysate antigen of autologous liver cancer cells and cell line SMMC-7721 cells). The lymphocytes were induced into cytokine-induced killer cells (CIK) with IL-2, CD3-Ab, gamma-IFN and PHA. MTT assay was performed to detect the proliferation rate of T lymphocytes mediated by DC and the cytotoxicity of CIK to liver cancer cells. RESULTS: DCs induced from monocytes of the intra-operative lost blood possessed typical morphology and phenotypes. Compared with the DCs from cord blood, the DCs from intra-operative lost blood expressed lower level of surface markers, but both could effectively induce proliferation of CIK and enhance the cytotoxicity of activated CIK against liver cancer cells at similar levels. When the DCs from lost blood and their counterpart from cord blood were both loaded with autologous tumor cell antigen, the proliferation rates of CIK were (388.9 +/- 137.3)% and (315.1 +/- 44.5)%, respectively, and the killing rates against tumor cells were (87.1 +/- 8.0)% and (90.0 +/- 5.1)%, respectively. When the two similar DC groups were loaded with lysate antigen of SMMC-7721 cells, the proliferation rates of CIK were (239.9 +/- 48.7)% and (226.3 +/- 32.3)%, respectively, and the killing rates against tumor cells were (76.4 +/- 7.9)% and (81.1 +/- 4.3)%, respectively. There were no significant differences between those two DC groups. The data also showed that the proliferation and cytotoxicity of CIK induced by DCs loaded with autologous antigen were higher than that of DCs loaded with SMMC-7721 antigen. CONCLUSION: Mononuclear cells separated from intra-operative lost blood of HCC patients can be induced into mature DCs, which can effectively activate CIK and significantly increase its killing effect on the liver cancer cells, and may become a new source of DCs to study and develop vaccines for clinical application.


Assuntos
Células Matadoras Induzidas por Citocinas/imunologia , Citocinas/metabolismo , Células Dendríticas/imunologia , Neoplasias Hepáticas/imunologia , Perda Sanguínea Cirúrgica , Morte Celular , Linhagem Celular Tumoral , Proliferação de Células , Células Matadoras Induzidas por Citocinas/citologia , Células Matadoras Induzidas por Citocinas/metabolismo , Citotoxicidade Imunológica/imunologia , Células Dendríticas/citologia , Células Dendríticas/metabolismo , Sangue Fetal , Humanos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Células Tumorais Cultivadas
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