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1.
Cell Physiol Biochem ; 50(6): 2017-2028, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30415246

RESUMEN

BACKGROUND/AIMS: Canopy homolog 2 (CNPY2) is a signature gene highly associated with tumor progression, including hepatocellular carcinoma (HCC). The presence of tumor hemorrhage (TH) implies a fast-growing and worse tumor microenvironment. We examined a possible association between CNPY2 levels and TH and evaluated their prognostic values in patients with HCC. METHODS: CNPY2 mRNA and protein levels were respectively determined in two independent cohorts of HCC specimens using quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry of tissue microarrays. Kaplan-Meier survival and Cox regression analyses were executed to evaluate the prognosis of HCC. CNPY2 knockout HCC cell lines were established by the CRISPR/Cas9 gene editing system, and the functional role of CNPY2 in HCC cell proliferation and growth was examined in vitro and in vivo. RESULTS: qRT-PCR showed that CNPY2 expression was significantly higher in HCC tumor tissue than in adjacent non-tumor tissue. Immunohistochemistry of HCC tissue microarrays demonstrated that CNPY2 expression was significantly correlated with TH and clinicopathological features indicating worse HCC progression. The prognostic value of CNPY2 expression and TH was validated by Cox proportional hazards analyses. Furthermore, CNPY2 knockout resulted in the significant suppression of MHCC97H cell proliferation, tumor growth, and hemorrhage. Bioinformatics analysis revealed that CNPY2 was closely associated with the expression levels of 6 positive impact genes in HCC, namely, ROMO1, BOLA2, HSF1, ATG4B, ATF4, and DENR, which are implicated in the regulation of the tumor microenvironment. CONCLUSION: CNPY2 is an oncogene that plays a critical role in the progression of HCC with TH. CNPY2 could be exploited as a novel prognostic marker and potential target for therapeutic intervention in HCC.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/metabolismo , Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico , Proteínas Adaptadoras Transductoras de Señales/deficiencia , Proteínas Adaptadoras Transductoras de Señales/genética , Adolescente , Adulto , Animales , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Proliferación Celular , Progresión de la Enfermedad , Femenino , Hemorragia/complicaciones , Humanos , Estimación de Kaplan-Meier , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Masculino , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Ratones , Persona de Mediana Edad , Proteínas Mitocondriales/genética , Proteínas Mitocondriales/metabolismo , Pronóstico , Modelos de Riesgos Proporcionales , Microambiente Tumoral , Adulto Joven
2.
Hepatology ; 57(6): 2326-37, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23325674

RESUMEN

UNLABELLED: Epithelial-mesenchymal transition (EMT) is a critical step in the metastasis of hepatocellular carcinoma (HCC). BTB/POZ domain-containing protein 7 (BTBD7) regulates EMT-associated proteins implicated in HCC progression. However, the role(s) of BTBD7 in HCC have not been identified. Using highly metastatic HCC HCCLM3 cells, immortalized L02 hepatocytes, metastatic HCC animal models, and three independent cohorts of HCC patient specimens, we aimed to determine the involvement of BTBD7 in HCC metastasis. We show that BTBD7 messenger RNA and protein was highly expressed in HCC cells and tumor tissues, with such expression being associated with: enhanced cell motility, venous invasion, and poor prognosis. BTBD7 promoted HCC angiogenesis and metastasis in vitro and in vivo, but did not influence cell proliferation or colony formation. BTBD7 enhancement of HCC invasion and EMT phenotype occurred through activation of a RhoC-Rock2-FAK-signaling pathway, resulting in matrix metalloproteinase-2/9 production and microvessel formation. Applying a predictive risk score model, Cox regression analysis revealed that high BTBD7 expression integrated with high microvessel density was a powerful independent predictive factor of HCC clinical outcome. CONCLUSION: The present study identifies BTBD7 as a novel candidate prognostic factor and a potential therapeutic target of HCC. (HEPATOLOGY 2013; 57:2326-2337).


Asunto(s)
Biomarcadores de Tumor/metabolismo , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Proteínas de Neoplasias/metabolismo , Recurrencia Local de Neoplasia/metabolismo , Proteínas Adaptadoras Transductoras de Señales , Animales , Carcinoma Hepatocelular/diagnóstico , Transición Epitelial-Mesenquimal , Células Hep G2 , Humanos , Neoplasias Hepáticas/diagnóstico , Masculino , Metaloproteinasas de la Matriz/metabolismo , Ratones , Ratones Endogámicos BALB C , Metástasis de la Neoplasia , Neovascularización Patológica , Pronóstico , Modelos de Riesgos Proporcionales , Transducción de Señal , Proteínas de Unión al GTP rho/metabolismo , Proteína rhoC de Unión a GTP
3.
Sci Total Environ ; 946: 173935, 2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38880145

RESUMEN

BACKGROUND: Air pollutants are important exogenous stimulants to eye diseases, but knowledge of associations between long-term exposure to air pollutants and the risk of primary open-angle glaucoma (POAG) is limited. This study aimed to determine whether long-term exposure to air pollutants, genetic susceptibility, and their joint effects lead to an elevated risk of incident POAG. METHODS: This is a population-based prospective cohort study from UK Biobank participants with complete measures of air pollution exposure and polygenetic risk scores. Cox proportional hazard models were fitted to assess the individual and joint effects of long-term exposure to air pollutants and genetics on the risk of POAG. In addition, the effect modification of genetic susceptibility was examined on an additive or multiplicative scale. RESULTS: Among 434,290 participants with a mean (SD) age of 56.5 (8.1) years, 6651 (1.53 %) were diagnosed with POAG during a median follow-up of 13.7 years. Long-term exposure to air pollutants was associated with an increased risk of POAG. The hazard ratios associated with per interquartile range increase in PM2.5, PM2.5 absorbance, PM10, NO2, and NOX individually ranged from 1.027 (95 % CI: 1.001-1.054) to 1.067 (95 % CI: 1.035-1.099). Compared with individuals residing in low-pollution areas and having low polygenic risk scores, the risk of incident POAG increased by 105.5 % (95 % CI: 78.3 %-136.9 %), 79.7 % (95 % CI: 56.5 %-106.5 %), 103.2 % (95 % CI: 76.9 %-133.4 %), 89.4 % (95 % CI: 63.9 %-118.9 %), and 90.2 % (95 % CI: 64.8 %-119.5 %) among those simultaneously exposed to high air pollutants levels and high genetic risk, respectively. Genetic susceptibility interacted with PM2.5 absorbance and NO2 in an additive manner, while no evidence of multiplicative interaction was found in this study. Stratification analyses revealed stronger effects in Black people and the elderly. CONCLUSION: Long-term air pollutant exposure was associated with an increased risk of POAG incidence, particularly in the population with high genetic predisposition.

4.
Photodiagnosis Photodyn Ther ; 38: 102784, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35219895

RESUMEN

Inflammatory myofibroblastic tumor (IMT) is a rare intermediate tumor that exhibits both benign and malignant behaviors. Whether IMT is an inflammatory or a neoplastic disease remains controversial, and there is currently no standard treatment for this disease. The treatment strategies include surgical tumor removal and drug therapy; however, several patients experience tumor recurrence post-treatment. Herein, we report the endoscopic manifestations and treatment process in a case of IMT. We performed photodynamic therapy (PDT) after endoscopic tumor resection, and no recurrence was found in the patient's re-examination a year later. This indicates that PDT can improve IMT prognosis and reduce its local recurrence, signifying the therapy's potential application value for IMT.


Asunto(s)
Granuloma de Células Plasmáticas , Fotoquimioterapia , Granuloma de Células Plasmáticas/diagnóstico , Granuloma de Células Plasmáticas/patología , Granuloma de Células Plasmáticas/cirugía , Humanos , Fotoquimioterapia/métodos , Pronóstico
5.
Fish Shellfish Immunol ; 29(1): 75-81, 2010 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-20202477

RESUMEN

GH18 chitinase is a multi-gene family. The family plays important physiological roles in Crustacea, e.g. ecdysis and defense against pathogen. However, data about GH18 family are rather limited in Crustacea. In the study, different cloning strategies were adopted to clone chitinase genes of Litopenaeus vannamei, which is the most widely cultured shrimp. Seven chitinase family members were identified. Analysis of domain architectures showed the repeated CBM18 modules and catalytic domain of enzymatically inactive chitolectin in Crustacea for the first time. Comparing to the three known groups of crustacean chitinase, four of the seven members are located on new evolutionary clades thus enriched the chitinase family of Crustacea. Tissue expression profiles were investigated in eight tissues. Expression of CHT5 and CHID1 were both detected in the hemocyte by which the innate immunity activity was carried out. The domain architectures, evolutionary relationships and tissue expression patterns all provide reasonable explanation for the existence of multiple genes in crustacean chitinase family.


Asunto(s)
Quitinasas/inmunología , Inmunidad Innata/inmunología , Penaeidae/inmunología , Filogenia , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Quitinasas/genética , Etiquetas de Secuencia Expresada , Hemolinfa/enzimología , Hemolinfa/inmunología , Inmunidad Innata/genética , Datos de Secuencia Molecular , Penaeidae/enzimología , Penaeidae/genética , ARN/química , ARN/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Alineación de Secuencia , Análisis de Secuencia de ADN
6.
Pharmacol Rep ; 72(5): 1383-1396, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32207090

RESUMEN

BACKGROUND: Telomerase plays an essential role in cancer cell proliferation. In this study, we investigated inhibition mechanism of aloe emodin (AE) on three different types of breast cancer cell lines, MDA-MB-453, MDA-MB-231 and MCF-7. METHODS: The cells were treated with different concentrations of AE. Relative length of telomere and human telomerase reverse-transcriptase (hTERT) mRNA level was analyzed by quantitative PCR (qPCR). Protein level was assayed by Western blot. Sodium bisulfite methylation sequencing was performed to assess the methylation status of gene promoter. Enzymology kinetics was applied to reveal the interaction between AE and telomerase. Ultraviolet-visible titration and fluorescence resonance energy transfer (FRET) melting experiment were carried out to study the interaction between AE and telomeric DNA. RESULTS: Continuous AE exposure of these cells for 48 h results in shortening of telomeres and inhibition of telomerase. The transcription of hTERT was repressed by activation of E2F1 and inactivation of c-myc proteins. Significant demethylation of CpG islands in hTERT gene promoter was observed in MDA-MB-453 and MCF-7 cells. AE competed with dNTP for occupation of the enzyme active site. AE was a telomeric G-quadruplex structure stabilizer as indicated by titration test and FRET experiments. CONCLUSIONS: AE was a competitive inhibitor of telomerase and a G-quadruplex structure stabilizer. AE decreased the transcription of hTERT gene in the three breast cancer cell lines via up-regulation E2F1 and down-regulation c-myc expressions. The suppressed transcription was also related to the demethylation of the gene promoter.


Asunto(s)
Antraquinonas/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Telomerasa/metabolismo , Transcripción Genética/efectos de los fármacos , Neoplasias de la Mama/metabolismo , Línea Celular Tumoral , Islas de CpG/efectos de los fármacos , Regulación hacia Abajo/efectos de los fármacos , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Células MCF-7 , Regiones Promotoras Genéticas/efectos de los fármacos , Proteínas Proto-Oncogénicas c-myc/metabolismo , ARN Mensajero/metabolismo , Activación Transcripcional/efectos de los fármacos
7.
Cancer Epidemiol Biomarkers Prev ; 18(2): 409-16, 2009 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-19208663

RESUMEN

OBJECTIVE: Inhibitor of growth 4 (ING4) is a candidate tumor suppressor that plays an important role in tumor growth and angiogenesis. Here, we examined the expression of ING4 in hepatocellular carcinoma (HCC) tissues and analyzed its correlation with the progression of HCC. METHODS: Specimens from 136 HCC patients were determined immunohistochemically for ING4 expression. The correlation of ING4 levels with clinicopathologic variables, prognosis, and metastatic potential was analyzed. Among the 136 cases, 36 paired HCC and paracarcinomatous liver tissue specimens were analyzed for ING4 expression levels by real-time quantitative reverse transcription-PCR and Western blotting. MVD was determined by CD34 immunostaining to test whether it correlated with ING4 protein expression level. RESULTS: The ING4 mRNA and protein levels were significantly lower in HCC than paracarcinomatous liver tissue from both real-time quantitative reverse transcription-PCR and Western blotting (P = 0.039 and 0.012, respectively). Importantly, the ING4 protein level correlated with the Edmondson-Steiner grade (P = 0.035), vein invasion (P = 0.015), and microvessel density (P = 0.005). Survival and metastasis analysis indicated that HCC patients with lower ING4 expression had poorer overall survival and disease-free survival than those with high expression (P = 0.0001 and 0.0065; respectively). Multivariable Cox regression analysis revealed that the ING4 expression level was an independent factor for prognosis (hazard risk, 9.63; P = 0.001). CONCLUSIONS: ING4 expression is down-regulated in HCC tissues. ING4 expression level correlates with prognosis and metastatic potential, which suggests that ING4 is a candidate prognostic marker of HCC.


Asunto(s)
Carcinoma Hepatocelular/metabolismo , Proteínas de Ciclo Celular/metabolismo , Proteínas de Homeodominio/metabolismo , Neoplasias Hepáticas/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Adolescente , Adulto , Anciano , Western Blotting , Carcinoma Hepatocelular/cirugía , Regulación hacia Abajo , Femenino , Hepatectomía , Humanos , Técnicas para Inmunoenzimas , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Estadísticas no Paramétricas , Análisis de Supervivencia
8.
Dig Dis Sci ; 54(2): 389-94, 2009 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-18592377

RESUMEN

Hepatocellular carcinoma (HCC) is the second leading cause of cancer death in China. We aimed to first present the expression of endocan in HCC tissue and its correlation with the clinicopathological features and overall survival of patients with HCC after curative hepatectomy. Immunohistochemical detection of endocan, CD34, and vascular endothelial growth factor (VEGF) were performed on samples from 100 patients with HCC. Endocan protein was expressed in endothelium of HCC tissue in all specimens, but was not expressed in endothelium of pericarcinomatous liver tissue and normal liver tissue. Microvessel density (MVD) denoted by endocan (endocan-MVD) in HCC was correlated with microscopic venous invasion and VEGF expression (P < 0.05). Survival analysis showed that overall survival of patients was inversely associated with endocan-MVD (P < 0.01). Multivariate analysis showed that endocan-MVD was an independent prognostic marker for overall survival of HCC (P < 0.01). In conclusion, endocan-MVD was a significant factor to predict the prognosis of HCC patients after curative hepatectomy.


Asunto(s)
Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Hígado/patología , Microvasos/patología , Proteínas de Neoplasias/metabolismo , Proteoglicanos/metabolismo , Adulto , Anciano , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/cirugía , China/epidemiología , Femenino , Hepatectomía , Humanos , Estimación de Kaplan-Meier , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Modelos de Riesgos Proporcionales , Factor A de Crecimiento Endotelial Vascular/metabolismo , Adulto Joven
9.
Zhonghua Wai Ke Za Zhi ; 47(20): 1569-73, 2009 Oct 15.
Artículo en Zh | MEDLINE | ID: mdl-20092749

RESUMEN

OBJECTIVE: To investigate the relationship between UNC5b gene expression and angiogenesis of hepatocellular carcinoma (HCC). METHODS: In situ hybridization was performed to detect the expression of UNC5b mRNA in HCC samples, paracarcinomatous liver tissues samples and normal liver samples. The relationship between UNC5b mRNA expression and the HCC clinicopathological features were also analyzed. Human umbilical artery endothelial cells were isolated and stimulated with HCC tissues homogenate, vascular endothelial growth factor and basic fibroblast growth factor. Then RT-PCR was employed to detect the expression of UNC5b mRNA in normal HUAEC as well as activated HUAEC. RESULTS: In situ hybridization results showed that UNC5b mRNA expression was detected majorly in endothelial cells of all normal liver tissues, and partial PCLTs but was weak or even undetectable in endothelial cells of the corresponding HCC tissues. The expression levels of UNC5b gene in PCLTs were significantly correlated with capsular formation of HCC. Furthermore, RT-PCR results showed that the expression levels of UNC5b mRNA in activated HUAEC were significantly higher than those in normal HUAEC. CONCLUSIONS: Down-regulation of UNC5b gene expression is related to angiogenesis of HCC, which may be associated with the progression of HCC.


Asunto(s)
Carcinoma Hepatocelular/irrigación sanguínea , Neoplasias Hepáticas/irrigación sanguínea , Neovascularización Patológica/genética , Receptores de Superficie Celular/genética , Carcinoma Hepatocelular/genética , Regulación hacia Abajo , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Hepáticas/genética , Receptores de Netrina , ARN Mensajero/genética
10.
Zhonghua Wai Ke Za Zhi ; 47(22): 1732-5, 2009 Nov 15.
Artículo en Zh | MEDLINE | ID: mdl-20137729

RESUMEN

OBJECTIVE: To investigate the expression of Abi1 in hepatocellular carcinoma (HCC) and the correlation between its expression level and clinical pathological characteristics as well as prognosis of HCC. METHODS: Abi1 expression was determined at both mRNA and protein levels in 40 HCC tissues and their corresponding para carcinomatous liver tissues by RT-PCR and immunohistochemistry. The correlations between Abi1 expression levels and pathological characteristics as well as prognosis were also analyzed. RESULTS: The expression level of Abi1 mRNA in HCC tissues were significantly higher than those in corresponding para carcinomatous liver tissue (P < 0.05), and the expression level of Abi1 mRNA in nodular HCC tissues were also significantly higher than those in solitary large HCC tissues. Immunohistochemistry results showed that Abi1 protein located in cytoplasm of HCC cells and the expression level of Abi1 protein were significant positive correlated with the number of HCC, capsular formation, venous invasion and Edmondson-Steiner grade (P < 0.05). Combined with follow-up data, the results also showed that HCC patients with high Abi1 protein expression had a higher risk of invasion/metastasis and a shorter survival than those with low Abi1 protein expression (P < 0.05). CONCLUSIONS: Expression level of Abi1 is up-regulated in HCC tissues compared with corresponding para carcinomatous liver tissue and the expression level of Abi1 is significantly correlated with the number of tumor, capsular formation, venous invasion, Edmondson-Steiner grade and prognosis of HCC.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/metabolismo , Carcinoma Hepatocelular/metabolismo , Proteínas del Citoesqueleto/metabolismo , Neoplasias Hepáticas/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Adulto , Anciano , Carcinoma Hepatocelular/patología , Proteínas del Citoesqueleto/genética , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Metástasis de la Neoplasia , Pronóstico , ARN Mensajero/genética
11.
Zhongguo Zhen Jiu ; 39(3): 281-6, 2019 Mar 12.
Artículo en Zh | MEDLINE | ID: mdl-30942016

RESUMEN

OBJECTIVE: To observe the effects of acupuncture at "Baihui" (GV 20) and "Shenshu" (BL 23) on the ultrastructure of hippocampal dentate gyrus in rats with Alzheimer's disease. METHODS: Forty SPF Wistar male rats were randomly divided into a normal group, a sham operation group, a model group and an acupuncture group, 10 rats in each one. The rats in the model group and the acupuncture group were treated with injection of 5 µL Aß1-42 at bilateral hippocampus, while the rats in the sham operation group were treated with injection of 5 µL 0.9% NaCl. Three days after modeling, the rats in the acupuncture group were treated with acupuncture at "Baihui" (GV 20) and "Shenshu" (BL 23) for 20 min, once a day, six treatments constituted a course, and totally two courses were given with an interval of 1 day between courses. The rats in the other groups received normal diet and no treatment was given. Before modeling, four days after modeling and after treatment, water maze test was performed to observe the escape latency and the number of crossing platforms. The hippocampal dentate gyrus was collected and transmission electron microscope was applied to observe the ultrastructure changes of neurons and astrocytes. RESULTS: ①Four days after modeling, compared with the normal group and the sham operation group, the escape latency was significantly prolonged and the number of crossing platforms was reduced in the model group (all P<0.01); after treatment, compared with the model group, the escape latency was significantly reduced and the number of crossing platforms was increased in the acupuncture group (both P<0.01). ②In the normal group and the sham operation group, the morphology of neurons and astrocytes was intact, the nuclear and membrane structure were clear, and the morphology of organelles such as mitochondria, endoplasmic reticulum and lysosomes was normal. In the model group, the morphology of neurons was irregular, the nucleus was severely constricted with edema in the cytoplasm, the color of heterochromatin was deepened, the endoplasmic reticulum was expanded, the granulation was removed and the number of mitochondria was decreased, even with malformed-like change in mitochondrial cristae; there was severe edema around astrocytes, few organelles in the cytoplasm, severe swelling of mitochondria and mild expansion of the endoplasmic reticulum. In the acupuncture group, the edema of the neuron and astrocytes was still evident, and the mitochondrial was mildly swollen but relieved compared with that in the model group, and there were no obvious abnormalities in neuronal endoplasmic reticulum and ribosomes. CONCLUSION: Acupuncture could improve the ultrastructure of neurons and astrocytes in the hippocampal dentate gyrus in rats with Alzheimer's disease induced by Aß1-42.


Asunto(s)
Terapia por Acupuntura , Enfermedad de Alzheimer , Péptidos beta-Amiloides , Animales , Astrocitos , Giro Dentado , Hipocampo , Masculino , Neuronas , Fragmentos de Péptidos , Ratas , Ratas Sprague-Dawley , Ratas Wistar
12.
Int J Biol Macromol ; 114: 898-905, 2018 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-29626603

RESUMEN

Peroxidase (POD) from jackfruit bulb was purified using ammonium sulfate precipitation, hydrophobic interaction and gel filtration columns. The POD was a dimer with a molecular weight of 104kDa. The Km and Vmax values for guaiacol, gallic acid and o­phenylenediamine (OPD) were estimated. OPD was the most suitable substrate. The enzyme showed its maximum activity at pH5.5 and 55-60°C. The activation energy (Ea) of heat inactivation was estimated to be 206.40kJ/mol. The enthalpy, free energy and entropy values for the thermal inactivation were also determined. The POD activity was enhanced by K+, Zn2+, Ba2+, citric acid, malic acid, benzoic acid and EDTA·Na2, but inhibited by Cu2+, Ca2+, glutathione, cysteine and ascorbic acid. Chemical modification indicated a histidine residue was located in the enzyme active site. The POD activity in fruit extracts significantly decreased when heated at 80°C and 90°C. The ferric-reducing antioxidant power, ABTS radical scavenging activity and total phenolics decreased with increasing heating temperature and time.


Asunto(s)
Artocarpus/enzimología , Peroxidasas/aislamiento & purificación , Proteínas de Plantas/aislamiento & purificación , Antioxidantes/aislamiento & purificación , Antioxidantes/farmacología , Catecol Oxidasa/antagonistas & inhibidores , Catecol Oxidasa/aislamiento & purificación , Catecol Oxidasa/farmacología , Cationes/farmacología , Inhibidores Enzimáticos/farmacología , Aditivos Alimentarios/farmacología , Depuradores de Radicales Libres/aislamiento & purificación , Depuradores de Radicales Libres/farmacología , Calor , Concentración de Iones de Hidrógeno , Cinética , Peso Molecular , Oxidación-Reducción , Peroxidasas/antagonistas & inhibidores , Peroxidasas/farmacología , Fenoles/análisis , Proteínas de Plantas/agonistas , Proteínas de Plantas/antagonistas & inhibidores , Proteínas de Plantas/farmacología , Raíces de Plantas/enzimología , Estabilidad Proteica , Especificidad por Sustrato
13.
Transl Oncol ; 11(2): 552-558, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-29525632

RESUMEN

Spontaneous tumor hemorrhage (TH) is frequently observed in solid tumors including human hepatocellular carcinoma (HCC). TH implies fast-growing and worse tumor immunological microenvironment; however, the underlying mechanism remains largely unknown. CLEC1B is a signature gene highly associated with tumor progression. PD-L1 expression is a key biomarker predictive of immune checkpoint therapies, which showed astonishing effect on various types of tumor. We assume that, in HCC, TH may closely associate with the expression of these two molecules. In this study, 136 patients with HCC were enrolled. qRT-PCR showed that CLEC1B expression is significantly lower in HCC tumor tissue. Immunohistochemistry of HCC tissue microarrays demonstrated that PD-L1high and CLEC1Blow expressions were significantly correlated with TH and clinicopathological features indicating worse HCC progression. According to univariate/multivariate analysis, a combination of PD-L1high and CLEC1Blow expression was an independent prognostic factor indicating the poor outcome. The prognostic value of PD-L1high and CLEC1Blow was validated by Cox proportional-hazard analyses. Collectively, tumor with TH is closely associated with CLEC1Blow & PD-L1high expression, which may imply high response of PD-L1/PD-1 immune checkpoint therapies. CLEC1B may be a potential therapeutic target for PD-L1/PD-1 immunotherapy. PD-L1high and CLEC1Blow can be a valuable prognosis factor implying worse clinical outcomes.

14.
Clin Cancer Res ; 12(19): 5673-9, 2006 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-17020969

RESUMEN

PURPOSE: Because of its role in cell migration, the Wiskott-Aldrich syndrome protein family verprolin-homologous protein (WAVE) 2 has been implicated in cancer metastasis. Evidence to support such a role of WAVE2 in human cancer, however, is lacking. We thus examined the expression of WAVE2 in hepatocellular carcinoma (HCC) tissues to test whether the levels of WAVE2 expression correlated to the progression of HCC. EXPERIMENTAL DESIGN: Samples of 112 HCC patients were determined immunohistochemically for WAVE2 expression and the correlation of WAVE2 levels with prognosis was analyzed. Among the 112 cases, 31 paired HCC and paracarcinomatous liver tissue specimens were analyzed for WAVE2 levels by reverse transcription-PCR and Western blotting, respectively. RESULTS: Among 112 cases of HCCs, the immunohistochemistry data indicated significant increase of WAVE2 expression levels in 71 cases. Importantly, the increased WAVE2 expression correlated with the multiple tumor nodules (P = 0.008), the absence of capsular formation (P = 0.035), Edmondson-Steiner grade (P = 0.009), vein invasion (P = 0.023), and a shortened median survival time (326 versus 512 days; P = 0.003). Multivariable Cox regression analysis revealed the WAVE2 expression level was an independent factor for prognosis. The immunohistochemistry data were further confirmed by results of reverse transcription-PCR and Western analysis of 31 HCC cases, in which the WAVE2 mRNA and protein in HCC tissues were significantly elevated when compared with paracarcinomatous liver tissue (P < 0.001). CONCLUSIONS: WAVE2 expression is elevated in HCC tissues, which correlates with a poor prognosis, suggesting WAVE2 as a candidate prognostic marker of HCC.


Asunto(s)
Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Familia de Proteínas del Síndrome de Wiskott-Aldrich/metabolismo , Adolescente , Adulto , Anciano , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Western Blotting , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Femenino , Humanos , Técnicas para Inmunoenzimas , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Masculino , Persona de Mediana Edad , Invasividad Neoplásica/genética , Invasividad Neoplásica/patología , Pronóstico , ARN Mensajero/genética , ARN Mensajero/metabolismo , ARN Neoplásico/genética , ARN Neoplásico/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Tasa de Supervivencia , Familia de Proteínas del Síndrome de Wiskott-Aldrich/genética
15.
Artículo en Inglés | MEDLINE | ID: mdl-17675753

RESUMEN

Jerusalem artichoke (Helianthus tuberosus L.) seedlings cultured in sandy media were treated with Hoagland nutrition solution with different concentrations of Cd(NO(3))(2) from 0 to 400 micromol/L. After 50 days' treatment, Cd accumulation, activities of peroxidase (POD, EC 1.11.1.7), superoxide dismutase (SOD, EC 1.15.1.1), catalase (CAT, EC 1.11.1.6) were measured and electrophoretograms of POD isoenzymes were analyzed. The accumulation of Cd in seedlings increased from Cd 50-100 micromol/L, after which further increases in Cd concentration resulted in only small increases in accumulation of Cd in seedlings. MDA content was markedly higher than control values indicating the enhanced membrane lipid peroxidation in roots and leaves. POD activities in leaf and root extracts increased with an increase of Cd concentration from 0 to 50 and 100 micromol/L and then decreased with further increases to 200 and 400 micromol/L. Under moderate Cd level of 50-200 micromol/L, SOD activities in leaf and root extracts increased whereas with a higher Cd level of 400 micromol/L marked inhibitions in enzyme activities were observed. With increase in Cd concentration marked elevations in CAT activities in leaves and roots were observed. Results of electrophoresis show that the alteration of POD isoenzyme was noticeable to Cd and an additional POD isoenzyme LP10 appeared. It is suggested that POD isoenzyme of Jerusalem artichoke seedlings could be used as bioindicator for soil contamination by Cd.


Asunto(s)
Cadmio/farmacología , Helianthus/efectos de los fármacos , Peroxidación de Lípido/efectos de los fármacos , Peroxidasa/metabolismo , Plantones/efectos de los fármacos , Catalasa/metabolismo , Helianthus/enzimología , Isoenzimas/metabolismo , Lípidos de la Membrana/metabolismo , Plantones/enzimología , Superóxido Dismutasa/metabolismo
18.
World J Gastroenterol ; 11(14): 2061-6, 2005 Apr 14.
Artículo en Inglés | MEDLINE | ID: mdl-15810069

RESUMEN

AIM: To comprehend the risk factors of recurrence of hepatocellular carcinoma (HCC) and its relationship with the infection patterns of hepatitis B virus (HBV). METHODS: All materials of 270 cases of postoperative HCC were statistically analyzed by SPSS software. Recurrence and metastasis were classified into early (< or =2 years) and late phase (>2 years). Risk factors for recurrence and metastasis after surgery in each group were analyzed. RESULTS: Out of 270 cases of HCC, 162 cases were followed up in which recurrence and metastasis occurred in 136 cases. There were a lot of risk factors related to recurrence and metastasis of HCC; risk factors contributing to early phase recurrence were serum AFP level, vascular invasion, incisal margin and operative transfusion, gross tumor classification and number of intrahepatic node to late phase recurrence. The HBV infective rate of recurrent HCC was 94.1%, in which "HBsAg, HBeAb, HbcAb" positive pattern reached 45.6%. The proportion of HBV infection in solitary large hepatocellular carcinoma (SLHCC) evidently decreased compared to nodular hepatocellular carcinoma (NHCC) (P<0.05). CONCLUSION: The early and late recurrence and metastasis after hepatectomy of HCC were associated with different risk factors. The early recurrence may be mediated by vascular invasion and remnant lesion, the late recurrence by tumor's clinical pathology propert, as multicentric carcinogenesis or intrahepatic carcinoma de novo. HBV replication takes a great role in this process. From this study, we found that SLHCC has more satisfactory neoplasm biological behavior than NHCC.


Asunto(s)
Carcinoma Hepatocelular/epidemiología , Hepatitis B Crónica/epidemiología , Neoplasias Hepáticas/epidemiología , Recurrencia Local de Neoplasia/epidemiología , Adulto , Carcinoma Hepatocelular/secundario , Femenino , Humanos , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Factores de Riesgo
19.
World J Gastroenterol ; 11(17): 2656-61, 2005 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-15849829

RESUMEN

AIM: To identify the role of alpha-fetoprotein (AFP) mRNA expression in peripheral blood one week after surgery as a predictor for recurrence of hepatocellular carcinoma (HCC). METHODS: Published studies fulfilling the selection criteria were identified by searching several databases online. After a methodology assessment using a quality scale designed by European Lung Cancer Working Party, data in each research were aggregated by means of meta-analysis. RESULTS: Altogether 368 cases were included in the 9 selected studies, which fulfilled the selection criteria. The quality scores ranged from 35% to 84% with a median score of 55%. The 'design' subscore had the lowest median value (38%). By aggregating the data, a high chi2 value (77.576) was presented. The fail-safe number was 136 and 64 for P = 0.05 and 0.01, respectively. CONCLUSION: AFP mRNA expression in peripheral blood 1 wk after surgery correlated with the recurrence of HCC and was a good predictor for tumor recurrence.


Asunto(s)
Carcinoma Hepatocelular/fisiopatología , Neoplasias Hepáticas/fisiopatología , Recurrencia Local de Neoplasia/fisiopatología , alfa-Fetoproteínas/genética , Biomarcadores de Tumor , Carcinoma Hepatocelular/cirugía , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Hepáticas/cirugía , Recurrencia Local de Neoplasia/diagnóstico , Valor Predictivo de las Pruebas , ARN Mensajero
20.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 30(5): 540-3, 2005 Oct.
Artículo en Zh | MEDLINE | ID: mdl-16320584

RESUMEN

OBJECTIVE: To analyze the risk factors for metastasis and recurrence of hepatocellular carcinoma (HCC) postoperatively. METHODS: Data of 270 cases of postoperative HCC were analyzed by SPSS software retrospectively. RESULTS: Out of the 270 cases, 162 got follow-up study and 136 showed metastasis and recurrence. Lots of risk factors induced the recurrence of HCC, such as AFP, tumor form, venous blood invasion, HBV infection, resection dimension and perioperative transfusion. There were different risk factors at different stages. CONCLUSION: The early recurrence of HCC may be mediated by macro- or micro-vessel blood invasion and metastasis, the late recurrence by multicentric carcinogenesis or introhepatic cacinoma de novo.


Asunto(s)
Carcinoma Hepatocelular/cirugía , Neoplasias Hepáticas/cirugía , Recurrencia Local de Neoplasia/epidemiología , Adulto , China/epidemiología , Femenino , Estudios de Seguimiento , Hepatectomía , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Periodo Posoperatorio , Estudios Retrospectivos , Factores de Riesgo
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