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1.
Infect Immun ; 85(6)2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28348052

RESUMO

In addition to their chemical antimicrobial nature, bile acids are thought to have other functions in the homeostatic control of gastrointestinal immunity. However, those functions have remained largely undefined. In this work, we used ileal explants and mouse models of bile acid administration to investigate the role of bile acids in the regulation of the intestinal antimicrobial response. Mice fed on a diet supplemented with 0.1% chenodeoxycholic acid (CDCA) showed an upregulated expression of Paneth cell α-defensins as well as an increased synthesis of the type-C lectins Reg3b and Reg3g by the ileal epithelium. CDCA acted on several epithelial cell types, by a mechanism independent from farnesoid X receptor (FXR) and not involving STAT3 or ß-catenin activation. CDCA feeding did not change the relative abundance of major commensal bacterial groups of the ileum, as shown by 16S analyses. However, administration of CDCA increased the expression of ileal Muc2 and induced a change in the composition of the mucosal immune cell repertoire, decreasing the proportion of Ly6G+ and CD68+ cells, while increasing the relative amount of IgGκ+ B cells. Oral administration of CDCA to mice attenuated infections with the bile-resistant pathogens Salmonella enterica serovar Typhimurium and Citrobacter rodentium, promoting lower systemic colonization and faster bacteria clearance, respectively. Our results demonstrate that bile acid signaling in the ileum triggers an antimicrobial program that can be potentially used as a therapeutic option against intestinal bacterial infections.


Assuntos
Ácido Quenodesoxicólico/administração & dosagem , Infecções por Enterobacteriaceae/imunologia , Íleo/microbiologia , Imunidade nas Mucosas , Infecções por Salmonella/imunologia , alfa-Defensinas/imunologia , Animais , Carga Bacteriana , Citrobacter rodentium/efeitos dos fármacos , Íleo/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Celulas de Paneth/imunologia , Celulas de Paneth/microbiologia , Salmonella typhimurium/efeitos dos fármacos
2.
Bioelectromagnetics ; 36(2): 149-61, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25639237

RESUMO

A previous study found that incident magnetic field exposure from pulsed magnetic field therapy (PMFT) mats can exceed ICNIRP 1998 reference levels. Due to the popularity of PMFT mats for private therapeutic use, regulators need to know if the products are compliant with the basic restrictions and how overexposure can be determined. This case study's objective was to test if such products are intrinsically compliant with ICNIRP 1998 and ICNIRP 2010 basic restrictions by evaluating three different commercially-available PMFT products. In the first step, experimentally validated numerical models of these mats were developed. As a second step, the induced fields were evaluated in high-resolution anatomical models of the IT'IS Virtual Population for various lying positions and compared to the safety guidelines. As expected, a strong influence of exposure on the PMFT design, anatomy, lying position and body orientation was found. The maximum exposure of one PMFT exceeds 3.1 times the basic restrictions of ICNIRP 1998 for the central nervous system tissues and 1.36 times the limit of ICNIRP 2010 for the peripheral tissues. Body loops can significantly increase the electric fields close to the skin, e.g., when the hand and thigh are in contact during mat use. In conclusion, PMFT products are not intrinsically compliant with ICNIRP 1998 and ICNIRP 2010 basic restrictions and therefore require special considerations.


Assuntos
Campos Eletromagnéticos/efeitos adversos , Exposição Ambiental/análise , Magnetoterapia/instrumentação , Adulto , Criança , Exposição Ambiental/normas , Feminino , Fidelidade a Diretrizes , Guias como Assunto , Humanos , Magnetoterapia/efeitos adversos , Exposição Materna , Modelos Anatômicos , Modelos Teóricos , Postura , Gravidez , Reprodutibilidade dos Testes , Suíça
3.
Hepatogastroenterology ; 62(140): 790-3, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26902002

RESUMO

BACKGROUND/AIMS: Intraoperative blood loss is an independent predictor of recurrence and survival after resection of hepatocellular carcinoma (HCC). The aim of this study was to identify the risk factors associated with intraoperative major blood loss in patients undergoing liver resection for HCC. METHODOLOGY: Clinicopathologic data and perioperative outcomes of 386 patients who underwent liver resection for HCC were retrospectively reviewed. The patients were divided into high (> 1,000 mL) and low (51,000 mL) blood loss groups according to the intraoperative blood loss. Intraoperative blood loss,more than 1,000 mL was defined as major blood loss. The risk factors associated with intraoperative major blood loss were analyzed by univariate and multivariate analyses. RESULTS: Vascular invasion, major hepatectomy and prolonged operation time were risk factors associated with intraoperative major blood loss during resection of HCC on multivariate analysis. Moreover, HCC patients with intraoperative major blood loss had prolonged hospital stay, higher incidence of postoperative complication and mortality compared with patients' with blood loss 1,000 mL. CONCLUSIONS: Vascular invasion, major hepatectomy and prolonged operation time are independent predictors of intraoperative major blood loss during resection of HCC.


Assuntos
Perda Sanguínea Cirúrgica/estatística & dados numéricos , Carcinoma Hepatocelular/cirurgia , Hepatectomia , Neoplasias Hepáticas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Fosfatase Alcalina/sangue , Aspartato Aminotransferases/sangue , Transfusão de Sangue , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/patologia , Estudos de Coortes , Feminino , Hemorragia/epidemiologia , Hemorragia/terapia , Artéria Hepática/patologia , Veias Hepáticas/patologia , Humanos , Complicações Intraoperatórias/epidemiologia , Complicações Intraoperatórias/terapia , Tempo de Internação , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Invasividade Neoplásica , Duração da Cirurgia , Estudos Retrospectivos , Fatores de Risco , Carga Tumoral
4.
Mol Cell Biochem ; 393(1-2): 283-91, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24792036

RESUMO

Glioma-associated oncogene homolog-1 (Gli-1) is considered a marker of Hedgehog pathway activation and is associated with the progression of several cancers. We have previously reported that Gli-1 was correlated with invasion and metastasis in hepatocellular carcinoma (HCC). However, the exact roles and mechanisms of Gli-1 in HCC invasion are unclear. In this study, we found that small interfering RNA mediated down-regulation of Gli-1 expression significantly suppressed adhesion, motility, migration, and invasion of both SMMC-7721 and SK-Hep1 cells. Furthermore, down-regulation of Gli-1 significantly reduced expressions and activities of both matrix metalloproteinase (MMP)-2 and MMP-9. In addition, we found that down-regulation of Gli-1 resulted in up-regulation of E-cadherin and concomitant down-regulation of Snail and Vimentin, consistent with inhibition of epithelial-mesenchymal transition (EMT). Taken together, our results suggest that down-regulation of Gli-1 suppresses HCC cell migration and invasion likely through inhibiting expressions and activations of MMP-2, 9 and blocking EMT.


Assuntos
Carcinoma Hepatocelular/genética , Movimento Celular/genética , Neoplasias Hepáticas/genética , Fatores de Transcrição/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/patologia , Metaloproteinase 2 da Matriz/biossíntese , Metaloproteinase 9 da Matriz/biossíntese , Invasividade Neoplásica/genética , RNA Interferente Pequeno , Transdução de Sinais/genética , Fatores de Transcrição/antagonistas & inibidores , Proteína GLI1 em Dedos de Zinco
5.
Biochem J ; 449(2): 353-64, 2013 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-23098229

RESUMO

Mature T-lymphocytes undergo spontaneous apoptosis in the biobreeding diabetes-prone strain of rats due to the loss of the functional GIMAP5 (GTPase of the immune-associated nucleotide-binding protein 5) protein. The mechanisms underlying the pro-survival function of GIMAP5 in T-cells have not yet been elucidated. We have previously shown that GIMAP5 deficiency in T-cells impairs Ca2+ entry via plasma membrane channels following exposure to thapsigargin or stimulation of the T-cell antigen receptor. In the present study we report that this reduced Ca2+ influx in GIMAP5-deficient T-cells is associated with the inability of their mitochondria to sequester Ca2+ following capacitative entry, which is required for sustained Ca2+ influx via the plasma membrane channels. Consistent with a role for GIMAP5 in regulating mitochondrial Ca2+, overexpression of GIMAP5 in HEK (human embryonic kidney)-293 cells resulted in increased Ca2+ accumulation within the mitochondria. Disruption of microtubules, but not the actin cytoskeleton, abrogated mitochondrial Ca2+ sequestration in primary rat T-cells, whereas both microtubules and actin cytoskeleton were needed for the GIMAP5-mediated increase in mitochondrial Ca2+ in HEK-293 cells. Moreover, GIMAP5 showed partial colocalization with tubulin in HEK-293 cells. On the basis of these findings, we propose that the pro-survival function of GIMAP5 in T-lymphocytes may be linked to its requirement to facilitate microtubule-dependent mitochondrial buffering of Ca2+ following capacitative entry.


Assuntos
Cálcio/metabolismo , Proteínas de Ligação ao GTP/metabolismo , Mitocôndrias/metabolismo , Linfócitos T/metabolismo , Animais , Western Blotting , Membrana Celular/metabolismo , Células Cultivadas , Citoesqueleto/metabolismo , Proteínas de Ligação ao GTP/genética , Células HEK293 , Humanos , Transporte de Íons , Microscopia Confocal , Mutação , Ratos , Receptores de Antígenos de Linfócitos T/metabolismo , Linfócitos T/citologia , Tubulina (Proteína)/metabolismo
6.
J Radiol Prot ; 34(2): N31-9, 2014 06.
Artigo em Inglês | MEDLINE | ID: mdl-24705441

RESUMO

This article discusses technical issues related to compliance assessment of ICNIRP 2010 basic restrictions. Several difficulties are identified in this study when assessing the spatial average and 99th percentile value of the electric field. These issues are mainly attributed to the lack of clarity in the guideline specifications, which leads to inadequate or irreproducible results. Effects on compliance results due to such ambiguous procedures are hereby investigated, with particular focus on technical issues rather than biological ones. Examples spanning from simple canonical test cases to realistic applications have been selected to highlight the strong variability in dosimetry results. Based on our findings, revisiting the ICNIRP 2010 guidelines is strongly recommended, and proposed alternative solutions are outlined.


Assuntos
Eletricidade , Campos Eletromagnéticos , Exposição Ambiental/análise , Fidelidade a Diretrizes/organização & administração , Monitoramento de Radiação/normas , Proteção Radiológica/normas , Algoritmos , Simulação por Computador , Interpretação Estatística de Dados , Agências Internacionais/normas , Internacionalidade , Modelos Estatísticos , Doses de Radiação
7.
J Huazhong Univ Sci Technolog Med Sci ; 34(3): 363-369, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24939300

RESUMO

LncRNAH19 has been implicated as having both oncogenic and tumor suppression properties in cancer. LncRNAH19 transcripts also serve as a precursor for miR-675. However, it is unknown whether LncRNAH19 and miR-675 are involved in the migration and invasion of hepatocellular carcinoma (HCC) cells. The purpose of this study was to investigate the effect and mechanism of LncRNAH19 and miR-675 on migration and invasion of HCC cells. The migration and invasion of HCC cells were measured by Transwell migration and invasion assays after transfection of HCC cells with miR-675 inhibitors and LncRNAH19siRNA. The levels of LncRNAH19 and miR-675 were detected by quantitative reverse transcriptase real-time polymerase chain reaction (qRT-PCR), and the protein expression of AKT, GSK-3ß and Cdc25A by Western blotting analysis. The expression levels of LncRNAH19 and miR-675 were higher in MHCC-97H cells than in L02, Huh-7 and HepG2 cells. Transwell migration assay revealed that the miR-675 inhibitor and LncRNAH19siRNA could significantly increase the migration of HCC cells (P<0.01) as compared with the control group. Transwell invasion assay demonstrated that the miR-675 inhibitor and LncRNAH19siRNA could significantly increase the invasion of HCC cells (P<0.01) as compared with the control group. Western blotting analysis showed that the expression levels of AKT and Cdc25A were significantly increased (P<0.05), and the expression level of GSK-3ß was significantly decreased (P<0.05) after treatment with miR-675 inhibitors and LncRNAH19siRNA as compared with the control group. These findings suggested that inhibition of LncRNAH19 and miR-675 expression can promote migration and invasion of HCC cells via AKT/GSK-3ß/Cdc25A signaling pathway.


Assuntos
Movimento Celular/genética , Quinase 3 da Glicogênio Sintase/metabolismo , MicroRNAs/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Longo não Codificante/genética , Transdução de Sinais , Fosfatases cdc25/metabolismo , Western Blotting , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Linhagem Celular , Linhagem Celular Tumoral , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Glicogênio Sintase Quinase 3 beta , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Invasividade Neoplásica , Interferência de RNA , Reação em Cadeia da Polimerase Via Transcriptase Reversa
9.
Front Psychol ; 15: 1285792, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38348255

RESUMO

Previous research has indicated that natural landscapes exhibit a greater capacity for ameliorating negative emotional states in individuals when compared to urban landscapes. Nevertheless, significant scientific inquiries, such as the uniformity of the rejuvenating effect across distinct categories of natural landscapes on college students and the choice of the optimal plant community for achieving the most potent restorative effect, remain unexplored. This study aimed to address these questions by selecting four plant communities (single-layer grassland, single-layer woodland, tree-grass composite woodland, tree-shrub-grass composite woodland) and using an electroencephalography method to capture the neuroelectric activity of the participants in combination with the Positive and Negative Affect Schedule score to explore the effects of plant community types on emotional recovery. The results showed that all four plant communities significantly increased positive emotions and significantly reduced negative emotions. There was no significant difference in the recovery effect of positive emotions among the four plant community types, but there was a significant difference in the recovery effect of negative emotions. The effect of tree-shrub-grass composite woodland on the negative emotion recovery effect is the best; the EEG results found that the alpha wave amplitude induced by the tree-shrub-grass composite woodland was significantly higher than that of the other three groups of plant communities, and the EEG and behavioral results were consistent. The results show that the tree-shrub-grass composite woodland has the best restoration effect and has stronger planning and design significance.

10.
Carcinogenesis ; 34(1): 10-9, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22948179

RESUMO

The aberrant activation of sonic hedgehog (SHH) pathway contributes to initiation and progression of various malignancies. However, the roles and underlying mechanisms of SHH signaling pathway in invasion and metastasis of liver cancer have not been well understood. In this study, we found that SHH signaling was activated and correlated with invasion and metastasis in hepatocellular carcinoma (HCC). Enhanced SHH signaling by recombinant human SHH N-terminal peptide (rSHH-N) promoted hepatoma cell adhesion, migration and invasion, whereas blockade of SHH signaling with SHH neutralizing antibody or cyclopamine suppressed hepatoma cell adhesion, migration and invasion. Furthermore, matrix metalloproteinase (MMP)-2 and MMP-9 expressions and activities were upregulated and downregulated by rSHH-N and SHH signaling inhibitor, respectively. The rSHH-N-mediated hepatoma cell migration and invasion was blocked by MMP-specific inhibitors or neutralizing antibodies to MMP-2 and MMP-9. In addition, phosphorylations of AKT and focal adhesion kinase (FAK) were increased and decreased by rSHH-N and SHH signaling inhibitor, respectively. Further investigations showed that activation of AKT and FAK were required for rSHH-N-mediated upregulation of MMP-2 and MMP-9, cell migration and invasion. Finally, we found that SHH protein expression was positively correlated with phosphorylatd FAK Tyr397, phosphorylatd AKT Ser473, MMP-2 and MMP-9 protein expressions in HCC samples. Taken together, our findings suggest that SHH pathway induces cell migration and invasion through FAK/AKT signaling-mediated MMP-2 and MMP-9 production and activation in liver cancer.


Assuntos
Movimento Celular , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Proteínas Hedgehog/metabolismo , Neoplasias Hepáticas/patologia , Invasividade Neoplásica , Peptídeo Hidrolases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ativação Enzimática , Humanos , Neoplasias Hepáticas/enzimologia
11.
J Immunol ; 186(9): 5131-41, 2011 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-21430227

RESUMO

Autoreactive CD8(+) T lymphocytes play a key role in the pathogenesis of several autoimmune diseases. It is not yet well understood how autoreactive CD8(+) T cells, which express TCRs with low reactivity toward self-Ags, gain the ability to respond to autoantigens to cause disease. Previously, we have shown that prior stimulation of CD8(+) T cells with synergistic combinations of cytokines produced by the innate immune response, such as IL-21 and IL-15, induces Ag-independent proliferation. Such "cytokine-primed" CD8 T cells displayed increased responsiveness to limiting quantities of the cognate Ag. In this paper, we report that prior stimulation with IL-15 and IL-21 also enables CD8(+) T cells to respond to weakly agonistic TCR ligands, resulting in proliferation, cytokine secretion, and cytolytic activity. Using a transgenic mouse model of autoimmune diabetes, we show that cytokine-primed autoreactive CD8(+) T cells induce disease following stimulation by weak TCR ligands, but their diabetogenic potential is dependent on continuous availability of IL-15 in vivo. These findings suggest that inflammatory cytokines could facilitate the triggering of autoreactive CD8(+) T cells by weak autoantigens, and this mechanism may have important implications for autoimmune diseases associated with microbial infections and chronic inflammation.


Assuntos
Autoantígenos/imunologia , Autoimunidade/imunologia , Linfócitos T CD8-Positivos/imunologia , Diabetes Mellitus Tipo 1/imunologia , Interleucina-15/imunologia , Interleucinas/imunologia , Animais , Separação Celular , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Ativação Linfocitária/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/imunologia
12.
Bioelectromagnetics ; 34(5): 375-84, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23404214

RESUMO

Compliance with the established exposure limits for the electric field (E-field) induced in the human brain due to low-frequency magnetic field (B-field) induction is demonstrated by numerical dosimetry. The objective of this study is to investigate the dependency of dosimetric compliance assessments on the applied methodology and segmentations. The dependency of the discretization uncertainty (i.e., staircasing and field singularity) on the spatially averaged peak E-field values is first determined using canonical and anatomical models. Because spatial averaging with a grid size of 0.5 mm or smaller sufficiently reduces the impact of artifacts regardless of tissue size, it is a superior approach to other proposed methods such as the 99th percentile or smearing of conductivity contrast. Through a canonical model, it is demonstrated that under the same uniform B-field exposure condition, the peak spatially averaged E-fields in a heterogeneous model can be significantly underestimated by a homogeneous model. The frequency scaling technique is found to introduce substantial error if the relative change in tissue conductivity is significant in the investigated frequency range. Lastly, the peak induced E-fields in the brain tissues of five high-resolution anatomically realistic models exposed to a uniform B-field at ICNIRP and IEEE reference levels in the frequency range of 10 Hz to 100 kHz show that the reference levels are not always compliant with the basic restrictions. Based on the results of this study, a revision is recommended for the guidelines/standards to achieve technically sound exposure limits that can be applied without ambiguity.


Assuntos
Encéfalo/efeitos da radiação , Campos Eletromagnéticos , Exposição Ambiental , Campos Magnéticos , Adolescente , Adulto , Estatura , Peso Corporal , Pré-Escolar , Condutividade Elétrica , Feminino , Análise de Elementos Finitos , Humanos , Processamento de Imagem Assistida por Computador/métodos , Masculino , Modelos Anatômicos , Modelos Biológicos , Obesidade/fisiopatologia , Doses de Radiação , Incerteza
13.
Zhen Ci Yan Jiu ; 48(7): 658-65, 2023 Jul 25.
Artigo em Zh | MEDLINE | ID: mdl-37518959

RESUMO

OBJECTIVE: To observe the effect of acupotomy on the expressions of p16Ink4a and p21Waf1/Cip1 in knee osteoarthritis (KOA) rabbits,so as to analyze whether acupotomy can treat KOA by inhibiting the cellular senescence of chondrocytes. METHODS: Twenty-four New Zealand male rabbits were randomly divided into normal, model, acupotomy and electroacupuncture (EA) groups, with 6 rabbits in each group. The KOA model was established by left hindlimb straightening fixation. After modeling, rabbits in the acupotomy group were treated with acupotomy loosening therapy on high stress points around the affected knee joints such as tendons attachment points of vastus medialis, vastus lateralis, rectus femoris, biceps femoris and pes anserine bursa, once a week for 3 weeks. In the EA group, "Xuehai"(SP10), "Liangqiu" (ST34),"Neixiyan" (EX-LE4) and "Waixiyan" (ST35) on the affected hindlimb were selected for EA treatment (3 mA, 2 Hz/100 Hz), 20 min each time, once every other day for 3 weeks. Before and after treatments, the knee Lequesne MG score and passive range of motion (PROM) of the affected knee joint were evaluated. After the treatments, the expressions of p16Ink4a and p21Waf1/Cip1 in the cartilage tissue of the affected knee joint were detected by immunohistochemistry and Western blot respectively. RESULTS: Before and after treatment, compared with the normal group, the Lequesne MG score was significantly increased (P<0.01), the PROM was significantly decreased (P<0.01) in the model group. After treatment, compared with the normal group, the positive expression and protein expression levels of p16Ink4a and p21Waf1/Cip1 were significantly increased (P<0.01) in the model group; compared with the model group, the Lequesne MG score was significantly decreased (P<0.01), the PROM was significantly increased (P<0.01), the positive expression and protein expression levels of p16Ink4a and p21Waf1/Cip1 were significantly decreased (P<0.01,P<0.05) in the acupo-tomy and EA groups; compared with the EA group, the Lequesne MG score was decreased (P<0.05), the PROM was increased (P<0.05), the positive expression and protein expression levels of p16Ink4a and p21Waf1/Cip1 were decreased (P<0.05,P<0.01) in the acupotomy group. CONCLUSION: Acupotomy intervention can down-regulate the expressions of cellular senescence markers p16Ink4a and p21Waf1/Cip1 in chondrocytes, indicating that acupotomy therapy may alleviate cartilage degeneration by inhibiting chondrocyte premature cellular senescence to treat KOA.


Assuntos
Terapia por Acupuntura , Eletroacupuntura , Osteoartrite do Joelho , Coelhos , Masculino , Animais , Osteoartrite do Joelho/genética , Osteoartrite do Joelho/terapia , Inibidor p16 de Quinase Dependente de Ciclina/genética , Cartilagem/metabolismo
14.
J Surg Res ; 175(2): 243-50, 2012 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-21601221

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) has a high predilection for portal vein invasion. Furthermore, the treatment of HCC with portal vein tumor thrombosis (PVTT) is controversial. The objective of this study was to investigate clinicopathologic characteristics and surgical outcomes of HCC patients with PVTT. METHODS: The clinicopathologic data and surgical outcomes of 88 patients HCC with PVTT and 211 patients without PVTT who underwent surgery were retrospectively reviewed. The risk factors and the prognosis of HCC patients with PVTT were determined. RESULTS: Cirrhosis, serum alkaline phosphatase (ALP) > 100 IU/L, tumor size > 8 cm, incomplete tumor capsule, and adjacent organ invasion were risk factors for PVTT in HCC on multivariate analysis. Furthermore, HCC patients with PVTT received more major hepatectomies, had more intraoperative blood loss and greater blood transfusion requirements, and higher incidence of postoperative mortality compared with HCC patients without PVTT. The median overall survival of HCC patients with PVTT after surgery was 9 mo, with the 1-, 2-, and 3-y overall survival rates of 31.1%, 18.3%, and 15.2 %, respectively. AFP level, adjacent organ invasion, and PVTT location predicted overall survival of HCC patients with PVTT. CONCLUSIONS: High serum ALP level, cirrhosis, large tumor, incomplete tumor capsule and adjacent organ invasion are predictors of PVTT in HCC. Surgery is a valid therapy for selected HCC patients with PVTT.


Assuntos
Carcinoma Hepatocelular/cirurgia , Hepatectomia , Neoplasias Hepáticas/cirurgia , Veia Porta , Trombectomia , Trombose/cirurgia , Adulto , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/mortalidade , Comorbidade , Feminino , Humanos , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Trombose/epidemiologia , Trombose/mortalidade , Resultado do Tratamento
15.
J Surg Oncol ; 105(1): 71-80, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21815147

RESUMO

BACKGROUND AND OBJECTIVES: Nidogen-2 is a ubiquitous component of basement membrane (BM), which is modified by tumor cells to facilitate tumor invasion. However, the expression and function of nidogen-2 in hepatocellular carcinoma (HCC) remains unknown at present. In this study, we sought to investigate the potential role of nidogen-2 in HCC. METHODS: Nidogen-2 expression in HCC tissues, cell lines, and serum was evaluated by immunohistochemistry, immunoassay, and real-time PCR assays. The regulation of nidogen-2 expression was investigated using doxycycline induction and small interfering RNA analyses. RESULTS: Nidogen-2 was significantly decreased in both HCC tissues and serum (P < 0.001). The decreased expression of nidogen-2 in HCC tissues was significantly correlated with tumor progression factors (P < 0.05). Inhibition of matrix metalloproteinase (MMP)-9 led to significantly upregulate nidogen-2 expression in vitro assays. Moreover, patients with HCC had lowest serum nidogen-2 levels compared with patients with benign liver diseases and normal volunteers. Furthermore, the receiver operating characteristic curve analysis revealed a good diagnostic performance of nidogen-2 for HCC. CONCLUSIONS: These findings suggest that decreased expression of nidogen-2 may have a potential pathogenetic role in the development of HCC and may also have potential diagnostic value for HCC.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/metabolismo , Moléculas de Adesão Celular/metabolismo , Neoplasias Hepáticas/metabolismo , Adulto , Idoso , Proteínas de Ligação ao Cálcio , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Estudos de Casos e Controles , Moléculas de Adesão Celular/genética , Linhagem Celular Tumoral , Feminino , Humanos , Técnicas Imunoenzimáticas , Fígado/metabolismo , Fígado/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/secundário , Masculino , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Inibidores de Metaloproteinases de Matriz , Pessoa de Meia-Idade , Prognóstico , RNA Mensageiro/genética , RNA Interferente Pequeno/genética , Curva ROC , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise Serial de Tecidos
16.
J Pathol ; 225(3): 463-72, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21671467

RESUMO

MicroRNAs are involved in human carcinogenesis and cancer progression. Our previous study has shown that loss of miR-338-3p expression is associated with clinical aggressiveness of hepatocellular carcinoma (HCC). However, the exact roles and mechanisms of miR-338-3p remain unknown in HCC. To determine whether and how miR-338-3p influences liver cancer cell invasion, we studied miR-338-3p in the liver cancer cell lines, and we found that miR-338-3p is down-regulated in treated cells. Forced expression of miR-338-3p in SK-HEP-1 cells suppressed cell migration and invasion, whereas inhibition of miR-338-3p in SMMC-7721 cells induced cell migration and invasion. Furthermore, smoothened (SMO) was identified as a direct target of miR-338-3p. Forced expression of miR-338-3p down-regulated SMO and matrix metalloproteinase (MMP)-9 expression, but inhibition of miR-338-3p up-regulated SMO and MMP9 expression. However, small interfering RNA targeted SMO reversed the effects induced by blockade of miR-338-3p. SMO and MMP9 were overexpressed and associated with invasion and metastasis in HCC tissues. These data indicate that miR-338-3p suppresses cell invasion by targeting the smoothened gene in liver cancer in vitro and miR-338-3p might be a novel potential strategy for liver cancer treatment.


Assuntos
Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , MicroRNAs/fisiologia , Receptores Acoplados a Proteínas G/biossíntese , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Movimento Celular/genética , Regulação Neoplásica da Expressão Gênica , Marcação de Genes , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Metaloproteinase 9 da Matriz/metabolismo , MicroRNAs/genética , Invasividade Neoplásica , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/genética , RNA Mensageiro/genética , RNA Neoplásico/genética , Receptores Acoplados a Proteínas G/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Receptor Smoothened , Células Tumorais Cultivadas
17.
Artigo em Inglês | MEDLINE | ID: mdl-34335838

RESUMO

Subchondral bone lesions, as the crucial inducement for accelerating cartilage degeneration, have been considered as the initiating factor and the potential therapeutic target of knee osteoarthritis (KOA). Acupotomy, the biomechanical therapy guided by traditional Chinese meridians theory, alleviates cartilage deterioration by correcting abnormal mechanics. Whether this mechanical effect of acupotomy inhibits KOA subchondral bone lesions is indistinct. This study aimed to investigate the effects of acupotomy on inhibiting subchondral bone resorption and to define the possible mechanism in immobilization-induced KOA rabbits. After KOA modeling, 8 groups of rabbits (4w/6w acupotomy, 4w/6w electroacupuncture, 4w/6w model, and 4w/6w control groups) received the indicated intervention for 3 weeks. Histological and bone histomorphometry analyses revealed that acupotomy prevented both cartilage surface erosion and subchondral bone loss. Further, acupotomy suppressed osteoclast activity and enhanced osteoblast activity in KOA subchondral bone, showing a significantly decreased expression of tartrate-resistant acid phosphatase (TRAP), matrix metalloproteinases-9 (MMP-9), and cathepsin K (Ctsk) and a significantly increased expression of osteocalcin (OCN); this regulation may be mediated by blocking the decrease in osteoprotegerin (OPG) and the increase in NF-κB receptor activated protein ligand (RANKL). These findings indicated that acupotomy inhibited osteoclast activity and promoted osteoblast activity to ameliorate hyperactive subchondral bone resorption and cartilage degeneration in immobilization-induced KOA rabbits, which may be mediated by the OPG/RANKL signaling pathway. Taken together, our results indicate that acupotomy may have therapeutic potential in KOA by restoring the balance between bone formation and bone resorption to attenuate subchondral bone lesions.

18.
Zhonghua Yi Xue Za Zhi ; 90(16): 1097-9, 2010 Apr 27.
Artigo em Zh | MEDLINE | ID: mdl-20646425

RESUMO

OBJECTIVE: To investigate the clinicopathological features and the safety of surgical treatment of large hepatocellular carcinoma (HCC). METHODS: A total of 316 HCC patients undergoing hepatectomy at our hospital from December 2005 to December 2008 were divided into HCC > 10 cm (large HCC) group (n = 119) and HCC < or = 10 cm group (n = 197). The clinicopathological data and surgical outcomes were compared between two groups. RESULTS: The HCC > 10 cm group had a higher rate of symptoms and physical findings than the HCC < or = 10 cm group. Compared with HCC < or = 10 cm group, intrahepatic metastasis, vascular invasion, adjacent organ invasion and poorly differentiated tumor were more common in HCC > 10 cm group. The preoperative serum levels of alpha-fetoprotein, aspartate aminotransferase and alkaline phosphatase were higher in HCC > 10 cm group. The patients with HCC > 10 cm received more major hepatectomies, suffered more intraoperative blood loss, had greater blood transfusion requirements and needed a longer operative duration. However, the incidences of postoperative complications and mortality rate were similar in two groups. CONCLUSION: Large HCC is characterized by more clinical manifestations, higher incidences of vascular invasion and adjacent organ invasion, and worse histological grades. Surgical resection for large HCC is both safe and feasible.


Assuntos
Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Adulto , Feminino , Hepatectomia , Humanos , Masculino , Pessoa de Meia-Idade
19.
Inflamm Res ; 58(8): 513-21, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19277846

RESUMO

OBJECTIVE AND DESIGN: To investigate the effects of sulforaphane on endothelial inflammatory gene expression in endothelial cells. MATERIALS AND METHODS: Human aortic endothelial cells were used in the study. RESULTS: One-hour pretreatment of endothelial cells (EC) with sulforaphane (1-4 muM) suppressed TNF-alpha-induced MCP-1 and VCAM-1 mRNA and protein levels, but had no effect on TNF-alpha-induced ICAM-1 expression. Sulforaphane also inhibited TNF-alpha-induced activation of p38 MAP kinase, but not c-Jun-N-terminal kinase. Sulforaphane had no effect on TNF-alpha-induced NF-kappaB nuclear binding activity, IkappaB-alpha degradation or activation of NF-kappaB-driven transcriptional activity. Expression of dominant negative Nrf2 inhibited sulforaphane-induced antioxidant response element (ARE)-driven promoter activity, but had no effect on sulforaphane-mediated inhibition of VCAM-1 and MCP-1 expression. CONCLUSION: These data suggest that sulforaphane may be useful as a therapeutic agent for the treatment of inflammatory diseases.


Assuntos
Anticarcinógenos/farmacologia , Autoantígenos/biossíntese , Células Endoteliais/metabolismo , Tiocianatos/farmacologia , Fator de Necrose Tumoral alfa/farmacologia , Molécula 1 de Adesão de Célula Vascular/biossíntese , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Antioxidantes/metabolismo , Western Blotting , Células Cultivadas , DNA/genética , Células Endoteliais/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , Ensaio de Imunoadsorção Enzimática , Humanos , Isotiocianatos , Monócitos/fisiologia , Fator 2 Relacionado a NF-E2/fisiologia , NF-kappa B/metabolismo , Plasmídeos/genética , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Transdução de Sinais/efeitos dos fármacos , Sulfóxidos , Transfecção , Células U937
20.
Hepatol Res ; 39(2): 177-86, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19208038

RESUMO

AIM: To investigate the status of Phosphatidylinositol 3-kinase (PI3K)/PTEN/AKT/mammalian target of rapamycin (mTOR) pathway and its correlation with clinicopathological features and matrix metalloproteinase-2, -9 (MMP-2, 9) in human hepatocellular carcinoma (HCC). METHODS: PTEN, Phosphorylated AKT (p-AKT), Phosphorylated mTOR (p-mTOR), MMP-2, MMP-9 and Ki-67 expression levels were evaluated by immunohistochemistry on tissue microarrays containing 200 HCCs with paired adjacent non-cancerous liver tissues. PTEN, MMP-2 and MMP-9 mRNA levels were determined by real-time RT-PCR in 36 HCCs. The relationships between PI3K/PTEN/AKT/mTOR pathway and clinicopathological factors and MMP-2, 9 were analyzed in HCC. RESULTS: In HCC, PTEN loss and overexpression of p-AKT and p-mTOR were associated with tumor grade, intrahepatic metastasis, vascular invasion, TNM stage and high Ki-67 labeling index (P < 0.05). PTEN loss was correlated with p-AKT, p-mTOR and MMP-9 overexpression. Furthermore, PTEN and MMP-2, 9 mRNA levels were down-regulated and up-regulated in HCC compared with paired non-cancerous liver tissues, respectively (P < 0.01). PTEN, MMP-2 and MMP-9 mRNA levels were correlated with tumor stage and metastasis. There was an inverse correlation between PTEN and MMP-9 mRNA expression. However, PI3K/PTEN/AKT/mTOR pathway was not correlated with MMP-2. CONCLUSIONS: PI3K/PTEN/AKT/mTOR pathway, which is activated in HCC, is involved in invasion and metastasis through up-regulating MMP-9 in HCC.

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