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1.
World J Gastroenterol ; 19(36): 5981-7, 2013 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-24106398

RESUMO

The liver has particular tolerogenic properties that allow its spontaneous acceptance in some animal species. Liver structure is considered to favor a tolerogenic environment. The peripheral tolerance mechanisms also play a role in spontaneous tolerance to liver graft. In a clinical setting, the main challenge nowadays facing liver transplantation is minimization of immunosuppression with the goal of donor-specific tolerance. Mechanisms involved in tolerance to transplanted organs are complex and partly unknown. A significant mechanism in tolerance induction is chimerism. Chimerism can be induced through transplantation of allogeneic donor bone marrow/stem cells under appropriate host conditioning. This review focuses on the tolerance mechanisms in liver transplantation and highlights the role of chimerism and allogeneic bone marrow/stem cell transplantation in tolerance development.


Assuntos
Células da Medula Óssea/imunologia , Transplante de Medula Óssea , Transplante de Fígado , Fígado/imunologia , Transplante de Células-Tronco , Células-Tronco/imunologia , Quimeras de Transplante/imunologia , Tolerância ao Transplante , Animais , Transplante de Medula Óssea/efeitos adversos , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto , Humanos , Transplante de Fígado/efeitos adversos , Transplante de Células-Tronco/efeitos adversos , Transplante Homólogo , Resultado do Tratamento
2.
J Clin Nurs ; 22(9-10): 1262-9, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23279292

RESUMO

AIMS AND OBJECTIVES: This study explores how sleep and energy levels were affected in Chinese women diagnosed with HIV in China employing the Actiwatch actigraphy system to collect data on the women's sleep characteristics. BACKGROUND: The worldwide AIDS pandemic, a major impetus behind the recent focus on global aspects of health, is one area in which the behavioural and biomedical expertise of nursing science is sorely needed. In particular, few studies of HIV+ women have examined the association of HIV-related stress with sleep disturbance and fatigue. Especially, fatigue and sleep disturbances are a common complaint among people with HIV. DESIGN: A qualitative study with actigraphy device used. METHODS: In-depth interviews were conducted with 19 HIV+ women in Shanghai, China, from December 2009-March 2010 and within this group, nine of the women agreed to wear an Actiwatch actigraphy device for 72 hours. RESULTS: Two major themes emerged from the in-depth interviews are as follows: sleep disturbance and fatigue. Participants presented varying amounts of sleeplessness, and fatigue resulting from nightmares, worrying about whether to disclose their diagnosis, and whether they might transmit the disease to their partners or children. Among the nine Actiwatch study participants, data shown that those who experienced fragmented sleep also slept more during the daytime. CONCLUSIONS: In this study, Chinese HIV+ women described how stress had caused them to become sleepless. The objective data collected via Actiwatch showed that these women required longer nap times, which indicates they did not have refreshing nocturnal sleep. Designing a culturally acceptable stress management intervention for these women is urgently needed. RELEVANCE TO CLINICAL PRACTICE: Sleep and fatigue level should be evaluated in each visit with HIV care. Nurses need to be trained in evaluating the HIV+ patients' sleep and fatigue status and refer them to psychologist and/or relaxation technique accordingly. Self-management intervention for HIV+ individuals should also include the sleep hygiene into consideration.


Assuntos
Fadiga/complicações , Infecções por HIV/complicações , Transtornos do Sono-Vigília/complicações , Actigrafia , Adulto , Fármacos Anti-HIV/uso terapêutico , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/fisiopatologia , Humanos , Pessoa de Meia-Idade , Pesquisa Qualitativa
3.
Hepatogastroenterology ; 58(110-111): 1742-6, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21940333

RESUMO

BACKGROUND/AIMS: The aim of this study was to investigate the effects of antisense oligodeoxynucleotides transfection of angiopioetin-like protein 3 (ANGPTL3) on the proliferation and invasion capacities of human hepatocellular carcinoma SMMC-7721 cells in vitro. METHODOLOGY: ANGPTL3 antisense oligodeoxynucleotides was transfected into SMMC-7721 cells with Lipofectamine 2000. We used MTT assay to evaluate cell growth. ANGPTL3, p38 mitogen-activated protein kinases (MAPKs) and Matrix metalloproteinase-9 (MMP-9) mRNA expression levels were evaluated by RT-PCR. The invasive potency of SMMC-7721 cells was measured by the transwell cell invasion assay. RESULTS: ANGPTL3 antisense oligodeoxynucleotides were successfully transfected into SMMC-7721 cells, resulting in the significant inhibition of ANGPTL3, p38MAPK and MMP-9 mRNA expression. Downregulation of ANGPTL3 inhibited cell proliferation and decreased invasion of SMMC-7721 cells. CONCLUSIONS: ANGPTL3 may be functionally involved in hepatocellular carcinoma cell proliferation and invasion and is a potential target for hepatocellular carcinoma therapy.


Assuntos
Angiopoietinas/metabolismo , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Oligodesoxirribonucleotídeos/farmacologia , Análise de Variância , Proteína 3 Semelhante a Angiopoietina , Proteínas Semelhantes a Angiopoietina , Proliferação de Células/efeitos dos fármacos , Regulação para Baixo , Humanos , Técnicas In Vitro , Metaloproteinase 9 da Matriz/metabolismo , Invasividade Neoplásica , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transfecção , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
4.
Hepatogastroenterology ; 57(102-103): 1241-6, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-21410066

RESUMO

BACKGROUND/AIMS: Resveratrol, a polyphenolic phytochemical present in berries, grapes, and wine, has emerged as a promising chemopreventive candidate. The aim of the present study was to determine the inhibitory effect of resveratrol on vascular endothelial growth factor (VEGF) expression and angiogenesis in hepatocellular carcinoma (HCC) and to explore its mechanism. METHODOLOGY: VEGF protein was detected by western blot, whereas VEGF mRNA expression was investigated by RT-PCR. Nuclear factor-kappa B (NF-kappa B) was measured by electrophoretic mobility shift assay (EMSA). Xenograft sections were stained for CD34 to study microvessels in vivo. RESULTS: We found that VEGF protein and mRNA expressions in the cells treated with resveratrol were significantly decreased. The activation of NF-kappa B was also intensely inhibited by resveratrol. Growth of tumours in nude mice was inhibited by resveratrol. Microvessel density was decreased with resveratrol treatment. CONCLUSIONS: The inhibitory effect of resveratrol on VEGF activity may occur partly through suppression of the activation of NF-kappa B in HepG2 cells. Resveratrol also significantly inhibited tumour growth and angiogenesis.


Assuntos
Inibidores da Angiogênese/farmacologia , Anticarcinógenos/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , NF-kappa B/antagonistas & inibidores , Estilbenos/farmacologia , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Células Hep G2 , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , NF-kappa B/fisiologia , RNA Mensageiro/análise , Resveratrol , Fator A de Crescimento do Endotélio Vascular/genética
5.
Oncol Rep ; 23(1): 255-61, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19956890

RESUMO

Hypoxia was shown to increase tumor cell invasion into the extracellular matrix in vitro. This result suggests that heparanase (Hpa), one of the key enzymes involved in tumor invasion and metastasis, may be regulated by hypoxia. RT-PCR, Western blot and Matrigel invasive assays were used to study the regulation of Hpa under hypoxia in human pancreatic MIA PaCa-2 cancer cells. Compared with those in normoxia (20% O2), Hpa mRNA, protein and enzymatic activity levels, were up-regulated by a reduction in the oxygen level (1% O2). Invasion by tumor cells into the extracellular matrix was found to be significantly enhanced. A reduction in Hpa protein levels was observed when nuclear factor kappaB (NF-kappaB) activation was blocked by pyrrolidine dithiocarbamate. The levels of Hpa were also reduced when Hpa was inhibited by an Hpa-specific antisense oligonucleotide. The MMP-9 mRNA, protein and gelatinase B activity levels in supernatants decreased significantly when Hpa was inhibited. We conclude that up-regulation of Hpa by hypoxia is NF-kappaB-dependent in MIA PaCa-2 cells and inhibition of Hpa reduces MMP-9 activity. This reduction in MMP-9 activity may be an important mechanism in tumor metastasis.


Assuntos
Glucuronidase/metabolismo , Hipóxia , NF-kappa B/metabolismo , Antioxidantes/farmacologia , Progressão da Doença , Ativação Enzimática , Matriz Extracelular , Metaloproteinase 9 da Matriz/metabolismo , Invasividade Neoplásica , Oligonucleotídeos Antissenso/química , Oxigênio/química , Prolina/análogos & derivados , Prolina/farmacologia , RNA Mensageiro/metabolismo , Tiocarbamatos/farmacologia , Fatores de Tempo
6.
Zhong Xi Yi Jie He Xue Bao ; 7(10): 952-7, 2009 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-19828106

RESUMO

OBJECTIVE: To explore the sensitization effects of resveratrol on CNE2 nasopharyngeal carcinoma cell line with hypoxia-induced chemotherapy resistance and the potential mechanism. METHODS: Human CNE2 nasopharyngeal carcinoma cell line was cultured under hypoxic conditions (37 degrees centigrade, 5% CO(2), 2% O(2)) in vitro. The cultured cells were treated with different concentrations of resveratrol for 48 h. Reversal fold (RF) of reseratrol to chemotherapeutic drugs in CNE2 cells was measured by methyl thiazolyl tetrazolium (MTT) assay. Apoptotic rate of CNE2 cells was observed by flow cytometry. Reverse transcription-polymerase chain reaction (RT-PCR) method and Western blotting were used to investigate the expressions of multidrug resistance gene 1 (mdr1), multidrug resistance-associated protein 1 (MRP1) and hypoxia inducible factor 1alpha (HIF-1alpha) in CNE2 cells. RESULTS: Resveratrol combined with chemotherapeutics produced a synergistic effect. The RF of 200 micromol/L resveratrol to paclitaxel was 2.58. Combined with paclitaxel, 25, 50, 100 and 200 micromol/L of resveratrol increased the apoptotic rate of CNE2 cells from (22.14+/-1.09)% to (23.24+/-1.37)%, (27.57+/-2.01)%, and (30.36+/-2.31)%, respectively. Resveratrol could down-regulate the expressions of HIF-1alpha, mdr1 and MRP1 significantly. After being treated with resveratrol at different concentrations separately, the expressions of HIF-1alpha, mdr1 and MRP1 in CNE2 cells decreased significantly as compared with paclitaxel alone or paclitaxel plus verapamil (P<0.01). CONCLUSION: Resveratrol can enhance the sensitivity of CNE2 cells to chemotherapeutic drugs under hypoxia. The potential mechanism is partly attributed to inhibiting the gene expressions of HIF-1alpha, mdr1 and MRP1.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Carcinoma/patologia , Neoplasias Nasofaríngeas/patologia , Estilbenos/farmacologia , Hipóxia Celular , Linhagem Celular Tumoral , Regulação para Baixo/efeitos dos fármacos , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/efeitos dos fármacos , Proteínas Associadas à Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Paclitaxel/farmacologia , Resveratrol
7.
Artigo em Chinês | MEDLINE | ID: mdl-19484992

RESUMO

OBJECTIVE: To explore the reversal effect and potential mechanism of resveratrol on multidrug resistance of human oral epidermoid carcinoma KBv200 cells. METHODS: MTT assay was used to investigate reversal index of resveratrol to vincristine, adriamycin and paclitaxel. Cell apoptosis were measured by flow cytometry. RT-PCR and Western blot were used to detect mRNA and protein expression of multidrug resistant 1 (MDR1) and B cell lymphoma leukemia-2 (Bcl-2). RESULTS: Resveratrol produced a synergistic effect with chemotherapeutics and obviously reversed the multidrug resistant phenotype of KBv200 cells. The reversal fold (RF) of 200 micromol/L resveratrol to vincristine, paclitaxel and adriamycin were 77.1, 61.3 and 5.9, respectively. The gene array results showed that resveratrol greatly downregulated expression levels of Bcl-2 and MDR1. After treated with 100 micromol/L, 200 micromol/L resveratrol, the expression level of Bcl-2 and MDR1 in KBv200 cells were markedly decreased in comparison with those untreated (t were 2.98, 3.51 and 3.12, 4.56, P < 0.05). CONCLUSIONS: Resveratrol can efficiently reverse multidrug resistance in KBv200 cells. The potential mechanism may be via inhibiting the multidrug resistant gene expressions and/or promoting cell apoptosis.


Assuntos
Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Estilbenos/farmacologia , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Sinergismo Farmacológico , Humanos , Paclitaxel/farmacologia , Resveratrol , Vincristina/farmacologia
8.
Nan Fang Yi Ke Da Xue Xue Bao ; 29(1): 44-6, 2009 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-19218109

RESUMO

OBJECTIVE: To investigate the expression of heparin-binding epidermal growth factor-like growth factor (HB-EGF) in patients with gastric carcinoma in different stages. METHODS: The expressions of HB-EGF protein and mRNA in normal gastric tissues, metaplasic intestinal mucosa, early-stage gastric cancer and advanced-stage gastric cancer tissues were detected by immunohistochemistry and in situ hybridization. RESULTS: HB-EGF expression was only detected in the parietal cells of the gastric fundic glands and in gastrin cells of the pyloric glands in normal gastric tissues. Weak HB-EGF expression was detected in the epithelial cells of the gastric mucosa in intestinal metaplasic mucosa, and the expression increased in all layers of the gastric mucosa in early-stage gastric cancer. Intense HB-EGF expression was observed in advanced gastric cancer. CONCLUSION: Increased HB-EGF expression may be implicated in the pathogenesis and development of gastric carcinoma.


Assuntos
Adenocarcinoma/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Neoplasias Gástricas/metabolismo , Adenocarcinoma/patologia , Adulto , Idoso , Feminino , Mucosa Gástrica/metabolismo , Fator de Crescimento Semelhante a EGF de Ligação à Heparina , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Neoplasias Gástricas/patologia , Células Tumorais Cultivadas
9.
Biomed Pharmacother ; 63(6): 404-8, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18849136

RESUMO

This study explores the novel H22 whole-cell vaccine of active specific immunotherapy in the treatment of hepatocellular carcinoma. H22 hepatoma tumor vaccine modified by human interleukin-2 (hIL-2) and mouse granulocyte-monocyte colony-stimulating factor (mGM-CSF) fusion gene was prepared to study its specific anti-tumor immunity. Mice were inoculated by these vaccines. Then tumor cells were injected into mouse models. The (51)Cr release assay was used to examine the cytotoxicities of the splenocytes to H22 hepatoma cells in immunized mice, tumor-bearing mice and control mice. The blood was needed to test the level of IL-10 and interferon (IFN)-gamma in serum. Survival time of mice was calculated. Specific cytotoxicity rate of splenocytes from the immunized mice to H22 cancer cell was 38%, significantly higher than 13.6% in the tumor-bearing group, 7.5% in the control group, and 9.1% in S180 cells (p<0.05). Serum IFN-gamma in the immunized group was significantly increased compared with other groups (p<0.01), and serum IL-10 in the immunized group was significantly decreased compared with other groups (p<0.01). The survival time of the transgenic vaccinated group was significantly longer.


Assuntos
Vacinas Anticâncer/imunologia , Carcinoma Hepatocelular/imunologia , Imunoterapia Ativa/métodos , Neoplasias Hepáticas Experimentais/imunologia , Animais , Carcinoma Hepatocelular/mortalidade , Radioisótopos de Cromo/metabolismo , Fator Estimulador de Colônias de Granulócitos e Macrófagos/genética , Humanos , Interferon gama/imunologia , Interleucina-10/imunologia , Interleucina-2/imunologia , Neoplasias Hepáticas Experimentais/mortalidade , Camundongos , Camundongos Endogâmicos BALB C , Ratos , Baço/citologia , Baço/imunologia , Taxa de Sobrevida , Transfecção
10.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 24(12): 1143-6, 2008 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-19068195

RESUMO

AIM: To construct a recombinant adeno-associated virus vector harboring fusion gene NT4-Ant-Shepherdin[79-87] and investigate Survivin as a anticancer therapeutic target by use of Shepherdin[79-87]. METHODS: The gene of Ant-Shepherdin[79-87] was obtained by PCR and T-vector method. After inserted in PBV220-NT4 vector and digested with restricted enzyme, The fusion gene of NT4-Ant-Shepherdin[79-87] was sub-cloned into the shuttle plasmid of adeno-associated virus; the products were co-transferred into HEK-293 cell line with helper plasmid pAAV-Ad and adeno-plasmid pFG140. The recombinant adeno-associated virus was produced by homologous recombination of above 3 plasmids in HEK-293 cells and its titer was measured by Dot-blot hybridization. The effect of rAAV-NT4-Ant-Shepherdin[79-87] on A549 cell line was measured by a colorimetric 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide (MTT) assay. RESULTS: DNA sequencing results verified that the sequence of Ant-Shepherdin[79-87] was consistent with that we had designed. After transformed E.coli DH5alpha, a fragment of 321 bp was confirmed. High titer of recombinant adeno-associated virus was obtained by homologous recombination in HEK-293 cell lines (3.4x10(13)pfu/L). rAAV-NT4-Ant-Shepherdin[79-87] had strong induce apoptosis effect on A549 cells. CONCLUSION: The recombinant adeno-associated virus vector encoding fusion gene NT4-Ant-Shepherdin[79-87] is successfully constructed in this experiment by molecular cloning and in vitro recombination techniques, which provided the basis of further research of Survivin for cancer gene therapy.


Assuntos
Dependovirus/genética , Vetores Genéticos/genética , Fragmentos de Peptídeos/fisiologia , Proteínas Recombinantes de Fusão/fisiologia , Apoptose/genética , Apoptose/fisiologia , Linhagem Celular , Linhagem Celular Tumoral , Humanos , Immunoblotting , Fragmentos de Peptídeos/genética , Reação em Cadeia da Polimerase , Proteínas Recombinantes de Fusão/genética
11.
Biomed Pharmacother ; 62(9): 622-9, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18804944

RESUMO

A multidrug-resistant clone of human oral epidermoid carcinoma KB cells was isolated by stepwise selection on exposure to increasing doses of vincristine. The final clone, KBv200, obtained after ethylmethane sulfonate mutagenesis showed 156-fold higher resistance to vincristine than KB cells. The cells were also cross-resistant to paclitaxel and adriamycin. The aim of this study was to explore the reversal effect and potential mechanism of resveratrol on KBv200 cells. MTT assay was used to investigate the reversal index of resveratrol to vincristine, adriamycin and paclitaxel. Cell apoptosis was measured by flow cytometry. RT-PCR and western blot were used to detect mRNA and protein expression of multidrug-resistant gene MDR1 and apoptosis-suppressing gene Bcl-2. Resveratrol produced a synergistic effect combined with the chemotherapeutic agents and reversed the multidrug-resistant phenotype of KBv200 cells. Flow cytometry confirmed that the percentage of apoptotic cell increased when KBv200 cells were exposed to resveratrol. The results of gene detection showed that the expression levels of MDR1 and Bcl-2 were decreased upon resveratrol treatment. Resveratrol can efficiently reverse multidrug resistance in KBv200 cells. The potential mechanism may be via inhibiting the multidrug-resistant gene expressions and/or promoting cell apoptosis.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Estilbenos/farmacologia , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/biossíntese , Apoptose , Linhagem Celular Tumoral , Humanos , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Resveratrol , Vincristina/farmacologia
12.
ANZ J Surg ; 78(6): 501-3, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18522574

RESUMO

BACKGROUND: Management of patients with spontaneous rupture of hepatocellular carcinoma in a single centre is reported and the diagnosis and treatment are discussed. METHODS: The clinical presentations, diagnosis and treatment of 28 cases of spontaneous rupture of hepatocellular carcinoma were reviewed. RESULTS: Twenty-six patients had sudden right upper-quadrant abdominal pain and 53.5% patients were in hypovolaemic shock on admission. The median survival of the patients who received one-stage, two-stage tumour resection and only transarterial embolization was 370, 483.5 and 60 days, respectively. The prognosis of the patients who underwent only conservative treatment or surgical haemostasis was poor. CONCLUSION: Transarterial embolization is the treatment of choice for those who are haemodynamically unstable on admission. Careful evaluations, including functional liver reserve, coagulopathy, tumour size and location should be made before tumour resection.


Assuntos
Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Embolização Terapêutica , Feminino , Hepatectomia , Humanos , Masculino , Pessoa de Meia-Idade , Ruptura Espontânea
13.
Zhong Xi Yi Jie He Xue Bao ; 6(3): 270-3, 2008 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-18334147

RESUMO

OBJECTIVE: To observe the effects of resveratrol on proliferation of human hepatocellular carcinoma cell line SMMC-7721 cells and expression of matrix metalloproteinase-9 (MMP-9) in vitro. METHODS: SMMC-7721 cells were treated with different concentrations of resveratrol for 24, 48 and 72 h, respectively. The effect of resveratrol on proliferation of SMMC-7721 cells was assessed with methyl thiazolyl tetrazolium (MTT). The expression of MMP-9 mRNA was determined by reverse transcription polymerase chain reaction (RT-PCR). MMP-9 protein was identified by Western blot analysis. RESULTS: Resveratrol could inhibit the proliferation of SMMC-7721 cells with dose- and time-dependent effects. Moreover, both MMP-9 mRNA expression and MMP-9 protein production were markedly reduced after resveratrol treatment. CONCLUSION: Resveratrol can inhibit the proliferation of SMMC-7721 cells and down-regulate MMP-9 expression. It is presumed that resveratrol may suppress the invasion and metastasis of hepatocellular carcinoma.


Assuntos
Carcinoma Hepatocelular/enzimologia , Neoplasias Hepáticas/enzimologia , Metaloproteinase 9 da Matriz/metabolismo , Estilbenos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Carcinoma Hepatocelular/patologia , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Regulação para Baixo/efeitos dos fármacos , Humanos , Neoplasias Hepáticas/patologia , Metaloproteinase 9 da Matriz/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Resveratrol , Células Tumorais Cultivadas
14.
Biomed Pharmacother ; 62(6): 366-72, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-17988825

RESUMO

Resveratrol is an active polyphenol found in red wine that has anti-cancer effects, but the molecular mechanisms of resveratrol on tumor invasion inhibition have not been well documented. The aim of this study was to elucidate the effects of resveratrol on invasion ability of human hepatocellular carcinoma cells and TNF-alpha-mediated MMP-9 expression. The expression activity of MMP-9 was measured by zymography, RT-PCR and western blot analysis. The expression of NF-kappa B was measured by EMSA and western blot analysis. TNF-alpha induced the MMP-9 expression in HepG2 cells. Resveratrol significantly inhibited TNF-alpha-mediated MMP-9 expression in HepG2 cells. NF-kappa B inhibitor induced a marked reduction in MMP-9 expression, and it suggested that NF-kappa B could play an important role in TNF-alpha-mediated MMP-9 expression. Furthermore, resveratrol significantly suppressed TNF-alpha-mediated NF-kappa B expression and invasion of HepG2 cells. Our results showed that resveratrol inhibited TNF-alpha-mediated MMP-9 expression and invasion of human hepatocellular carcinoma cells. The inhibitory effects are partly associated with the downregulation of the NF-kappa B signaling pathway.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Metaloproteinase 9 da Matriz/metabolismo , Estilbenos/farmacologia , Fator de Necrose Tumoral alfa/metabolismo , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Metaloproteinase 9 da Matriz/efeitos dos fármacos , NF-kappa B/efeitos dos fármacos , NF-kappa B/metabolismo , Invasividade Neoplásica , Resveratrol , Transdução de Sinais/efeitos dos fármacos
15.
J Gastroenterol Hepatol ; 23(3): 491-7, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17524042

RESUMO

BACKGROUND AND AIM: Heparanase is an endo-beta-glucuronidase that cleaves heparan sulfate and has been implicated in tumor angiogenesis and metastasis. The present study was to analyze the expression of and explore the prognostic value of heparanase and two important transcriptional factors, namely hypoxia-inducible factor-1alpha (HIF-1alpha) and nuclear transcriptional factor kappa B p65 (NF-kappaB p65) in gallbladder cancer. METHODS: Heparanase, HIF-1alpha and NF-kappaB p65 protein levels in 38 patients with gallbladder carcinoma were detected by immunohistochemistry and analyzed for clinicopathological significance. RESULTS: The heparanase, HIF-1alpha and NF-kappaB p65 proteins were found in 24 (63.2%), 13 (34.2%) and 22 (57.9%) specimens, respectively. High heparanase expression was closely related to advanced TNM stage (P = 0.007), depth of tumor invasion (P = 0.016), lymph node metastasis (P = 0.040) and decreased postoperative survival at 3 years (50.0% vs 20.8%, P = 0.001). Both HIF-1alpha and NF-kappaB p65 proteins were correlated with tumor size (P = 0.039 and P = 0.027, respectively) and patients positive for HIF-1alpha expression had a decreased survival rate compared with those negative for HIF-1alpha expression (40.0% vs 15.4%, P = 0.035). In addition, heparanase-positive cases had high expression of NF-kappaB p65 compared with the heparanase-negative cases (P = 0.047). CONCLUSION: Heparanase and HIF-1alpha are frequently expressed in gallbladder carcinoma and are associated with decreased survival. High expression of heparanase, combined with NF-kappaB p65, may contribute to the highly invasive and metastatic behavior of gallbladder carcinoma.


Assuntos
Adenocarcinoma/enzimologia , Carcinoma Adenoescamoso/enzimologia , Neoplasias da Vesícula Biliar/enzimologia , Glucuronidase/análise , Adenocarcinoma/química , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Adenoescamoso/química , Carcinoma Adenoescamoso/mortalidade , Carcinoma Adenoescamoso/patologia , Carcinoma Adenoescamoso/cirurgia , Colecistectomia , Feminino , Neoplasias da Vesícula Biliar/química , Neoplasias da Vesícula Biliar/mortalidade , Neoplasias da Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/cirurgia , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/análise , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Fator de Transcrição RelA/análise , Resultado do Tratamento , Regulação para Cima
16.
Nan Fang Yi Ke Da Xue Xue Bao ; 27(8): 1267-70, 2007 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-17715045

RESUMO

OBJECTIVE: To detect the expressions of heparanase and nuclear factor kappa B p65 (NF-kappaB p65) in pancreatic adenocarcinomas and analyze their relation to patients' prognosis and the regulatory mechanism of NF-kappaB on heparanase expression. METHODS: Heparanase and NF-kappaB p65 proteins in the tumor and adjacent tissues were detected by immunohistochemistry in 48 patients with pancreatic adenocarcinoma and analyzed for their clinicopathological significance. RESULTS: Heparanase and NF-kappaB p65 proteins were found in 30 (62.5%) and 22 (45.9%) tumor specimens, respectively, a rate significantly higher than that in the adjacent tissues. High heparanase expression was closely related to advanced TNM stage (P=0.031), lymph node metastasis (P=0.003) and decreased 3-year postoperative survival (20.0% vs 0%, P=0.001). NF-kappaB p65 expression was associated with lymph node metastasis (P=0.017) and distant metastasis (P=0.031), but had a higher positive rate in heparanase-positive cases than in heparanase-negative cases (P=0.018). Multivariate analysis showed that neither heparanase nor NF-kappaB p65 was the independent prognostic factors. CONCLUSION: Heparanase is overexpressed in pancreatic adenocarcinomas in association with decreased postoperative survival. NF-kappaB may up-regulate heparanase expression and promote heparanase-dependent tumor invasion and metastasis.


Assuntos
Adenocarcinoma/genética , Regulação Neoplásica da Expressão Gênica , Glucuronidase/metabolismo , Neoplasias Pancreáticas/genética , Fator de Transcrição RelA/metabolismo , Adenocarcinoma/diagnóstico , Adulto , Idoso , Animais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Neoplasias Pancreáticas/diagnóstico , Prognóstico , Fatores de Risco
17.
Hepatobiliary Pancreat Dis Int ; 6(3): 326-9, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17548261

RESUMO

BACKGROUND: Cholecystectomy is the most commonly performed procedure in general surgery. However, bile duct injury is a rare but still one of the most common complications. These injuries sometimes present variably after primary surgery. Timely detection and appropriate management decrease the morbidity and mortality of the operation. METHODS: Five cases of iatrogenic bile duct injury (IBDI) were managed at the Department of Surgery, First Affiliated Hospital, Xi'an Jiaotong University. All the cases who underwent both open and laparoscopic cholecystectomy had persistent injury to the biliary tract and were treated accordingly. RESULTS: Recovery of the patients was uneventful. All patients were followed-up at the surgical outpatient department for six months to three years. So far the patients have shown good recovery. CONCLUSIONS: In cases of IBDI it is necessary to perform the operation under the supervision of an experienced surgeon who is specialized in the repair of bile duct injuries, and it is also necessary to detect and treat the injury as soon as possible to obtain a satisfactory outcome.


Assuntos
Ductos Biliares/lesões , Procedimentos Cirúrgicos do Sistema Biliar/efeitos adversos , Adulto , Colecistectomia Laparoscópica/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
18.
Zhong Xi Yi Jie He Xue Bao ; 4(6): 611-4, 2006 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-17090378

RESUMO

OBJECTIVE: To investigate the curative effect and mechanism of beta-elemene interventional treatment on VX2 carcinoma transplanted on kidney in rabbits. METHODS: The rabbits were all transplanted with VX2 carcinoma on kidney. Fifty-five rabbits were randomly divided into 11 groups. Rabbits in these groups were administered interventional treatment of normal saline, iodinated oil, mitomycin, 5-fluorouracil, beta-elemene, cisplatin, carboplatin, adriamycin, thiotepa, cyclophopsphamide, and vincristine, respectively. After corresponding intervention, the tumor volume in each group was measured by ultrasonography and spiral computed tomography, and the tumor growth rate (TGR) was calculated. Nenal and hepatic functions of the rabbits in each group were compared 1 day, 7 and 14 days after the interventional treatment. Morphologic change of the tumor was observed by a light microscopy and a transmission electron microscopy 14 days after interventional treatment. The expressions of Bax and Bcl-2 were measured by immunohistochemical straining. RESULTS: There was statistical significance in the effects of different medicines intervened on VX2 kidney transplanted carcinoma. The VX2 carcinoma of rabbits had high-sensitivity to iodized oil embolism, mitomycin, cisplatin and carboplatin, which showed serious damage to the kidney function, medium-sensitivity to beta-elemene, adriamycin and 5-fluorouracil, in which beta-elemene showed slight damage to the kidney function, and resistance to thiotepa, cyclohosphamide and vincristine. Most tumor cells displayed apoptosis in the beta-elemene interventional treatment group under light microscopy and transmission electron microscopy, and only few tumor cells displayed necrosis. The Bax expression was up-regulated (P<0.05) and the Bcl-2 expression had no significant difference (P>0.05) in the beta-elemene interventional treatment group. CONCLUSION: Intervention treatment of beta-elemene has significant effect on VX2 kidney transplanted carcinoma and little side effect on the kidney function. Its mechanism is related to enhancing the apoptosis of tumor cells, and Bax gene participates in this action.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioembolização Terapêutica , Neoplasias Renais/terapia , Sesquiterpenos/administração & dosagem , Animais , Antineoplásicos Fitogênicos/administração & dosagem , Feminino , Imuno-Histoquímica , Injeções Intra-Arteriais , Rim/metabolismo , Rim/patologia , Rim/ultraestrutura , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Masculino , Microscopia Eletrônica , Transplante de Neoplasias , Fitoterapia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Coelhos , Distribuição Aleatória , Proteína X Associada a bcl-2/metabolismo
19.
Zhong Xi Yi Jie He Xue Bao ; 4(4): 392-6, 2006 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-16834978

RESUMO

OBJECTIVE: To investigate the radiosensitization of beta-elemene on VX2 carcinoma transplanted on kidney in rabbits in vivo. METHODS: The rabbits were all transplanted with VX2 carcinoma on kidney. The appropriate dose of beta-elemene infusion via renal artery for further study on radiosensitization was determined. Then fifty-five rabbits were divided into three groups: untreated group, radiation group and radiation plus beta-elemene-treated group. After corresponding intervention for each group, the tumor volume was measured by ultrasonography and spiral computed tomography. The sensitization enhancement ratio (SER) of beta-elemene was calculated. The pathological change of tumor tissue in kidney was observed by light microscopy and electron transmission microscopy. The apoptotic index was also examined by TdT-mediated dUTP-biotin nick end labeling method. RESULTS: The most significant radiosensitivity was observed in the radiation plus beta-elemene-treated group with 6 Mev X-ray radiation dose of 3 Gy.Fx(-1).d(-1) x 5 d and beta-elemene dose of 10 mg.kg(-1).d(-1). The average time delayed for tumor growth was obviously longer in the radiation plus beta-elemene-treated group than those in the untreated group and radiation group. The SER of beta-elemene was 1.89. The apoptotic index of tumor cells in the radiation plus beta-elemene-treated group was also significantly higher than those in the untreated group and radiation group. CONCLUSION: The beta-elemene can enhance the effects of irradiation on VX2 carcinoma transplanted to kidney in rabbits in vivo by inducing apoptosis of tumor cells.


Assuntos
Carcinoma/tratamento farmacológico , Extratos Vegetais/farmacologia , Sesquiterpenos/farmacologia , Animais , Apoptose/efeitos dos fármacos , Rim , Coelhos
20.
Pharmacol Res ; 54(1): 19-23, 2006 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16517175

RESUMO

AIM: To study the effect of resveratrol (RES) on the apoptosis of lymphocytes in allograft in a rat liver transplantation model. METHODS: Male Sprague-Dawley (SD) rats were selected as donors and male Wistar rats as recipients for a rejection model. The recipients were divided into four groups after orthotopic liver transplantation (OLTx). In the RES A, B, and C groups, RES was given intraperitoneally once a day (25, 50, and 100 mgkg(-1), respectively) after OLTx, whereas in the control group vehicle buffer was given intraperitoneally once a day. The survival period, lymphocytes apoptosis, expressions of Bcl-2/Bax proteins in lymphocytes, and histopathological findings were then compared among these groups. RESULTS: The mean survival period after OLTx in RES C group was significantly longer than that in control group (P < 0.05). On the seventh post-transplant day, the apoptosis index (AI) of lymphocytes in portal area and the positive rate of Bax protein in lymphocytes in RES C group were significantly increased in comparison with those in control group (both P < 0.05), whereas there is no obvious difference in the expression of Bcl-2 protein in lymphocytes between the control group and various drug groups (all P < 0.05), and a histological examination revealed apparent difference in the severity of rejection between the RES C group and control group (P < 0.05). CONCLUSION: RES has an immunosuppressive effect on lymphocytes under allograft rejection in rat. Inducing apoptosis of lymphocytes and upregulating the ratio of Bax/bcl-2 proteins in lymphocytes in allograft liver may be part of the mechanisms.


Assuntos
Apoptose/efeitos dos fármacos , Transplante de Fígado/imunologia , Estilbenos/farmacologia , Linfócitos T/efeitos dos fármacos , Animais , Rejeição de Enxerto , Imunossupressores/farmacologia , Transplante de Fígado/patologia , Masculino , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Resveratrol , Linfócitos T/imunologia , Linfócitos T/metabolismo , Transplante Homólogo , Proteína X Associada a bcl-2/biossíntese
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