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1.
Int J Hyperthermia ; 41(1): 2338542, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38684224

RESUMEN

OBJECTIVE: To investigate the changes in liver and kidney function, red blood cell (RBC) count and hemoglobin (HGB) levels in patients undergoing ultrasound-guided percutaneous microwave ablation (UPMWA) for uterine fibroids on postoperative day 1. METHODS: The changes in liver and kidney function, RBC count and HGB levels in 181 patients who underwent selective UPMWA in the Second Affiliated Hospital of Shantou University Medical College, China, between August 2017 and January 2023 were retrospectively analyzed. RESULTS: All patients underwent UPMWA for uterine fibroids; 179 patients had multiple uterine fibroids and 2 patients had single uterine fibroids. The maximum fibroid diameter ranged from 18 to 140 mm, with an average of 68.3 mm. Ultrasound imaging was used to confirm that the blood flow signal within the mass had disappeared in all patients, indicating that the ablation was effective. Within 24 h, compared with before UPMWA, levels of total bilirubin, direct bilirubin, indirect bilirubin and aspartate aminotransferase had significantly increased (p < 0.01), whereas levels of total protein, albumin, globulin, alanine aminotransferase, creatinine and urea had significantly decreased (p < 0.01). Acute kidney injury (AKI) occurred in 1 of the 181 patients. The RBC count and HGB levels decreased significantly after UPMWA (p < 0.01). CONCLUSION: Ultrasound-guided percutaneous microwave ablation for uterine fibroids can impose a higher detoxification load on the liver and cause thermal damage to and the destruction of RBCs within local circulation, potentially leading to AKI. Protein levels significantly decreased after UPMWA. Therefore, perioperative organ function protection measures and treatment should be actively integrated into clinical practice to improve prognosis and enhance recovery.


Asunto(s)
Hemoglobinas , Leiomioma , Humanos , Femenino , Leiomioma/cirugía , Leiomioma/sangre , Leiomioma/diagnóstico por imagen , Adulto , Persona de Mediana Edad , Hemoglobinas/metabolismo , Hemoglobinas/análisis , Recuento de Eritrocitos , Riñón/diagnóstico por imagen , Riñón/cirugía , Hígado/diagnóstico por imagen , Hígado/metabolismo , Hígado/cirugía , Estudios Retrospectivos , Microondas/uso terapéutico
2.
Cell Commun Signal ; 20(1): 35, 2022 03 19.
Artículo en Inglés | MEDLINE | ID: mdl-35305679

RESUMEN

BACKGROUND: As a class of the opioid receptors, the kappa opioid receptor (KOR) has been verified to be a potential biomarker and therapeutic target for human malignant tumors. However, a thorough understanding of whether KOR affects progression of esophageal squamous cell carcinoma (ESCC) is still lacking. This study focused on exploring the effect of knocking down KOR in ESCC and its underlying mechanism. METHODS: Bioinformatics analysis was used to compare the different expression level of OPRK1 (KOR gene) in tumor and adjacent normal tissues, and predict the relationship between KOR expression and overall survival. RNA-sequence analysis was performed to detect the altered functions and mechanisms after down regulating KOR. The in vitro and in vivo assays were used to detect the effects of down-regulated KOR on cell proliferation, migration and invasion. Substrate gel zymography and 3D cell culture assays were used to find the effect of KOR knockdown on the degradation of extracellular matrix (ECM), and immunefluorescence was performed to detect the altered cytoskeleton. Western blotting and immunohistochemistry were used to explore the underlying mechanism pathway. RESULTS: Bioinformatics analysis revealed that the expression of OPRK1 was lower in tumor tissue than that in adjacent normal tissues, and lowered expression of KOR was associated with poorer overall survival. The in vitro assays demonstrated that down-regulation of KOR enhanced ESCC proliferation, metastasis and invasion. Western blotting revealed that down-regulation of KOR could activate PDK1-AKT signaling pathway, which actively regulated the cancer progression. Down-regulation of KOR enhanced the formation of invadopodia, secretion of matrix metalloproteinase-2 (MMP2) and rearrangement of cytoskeleton, which were positively related with the invasion of ESCC. KOR knockdown enhanced the tumor invasion and elevated the AKT phosphorylation in nude mice. The AKT kinase inhibition could reverse the effect of down-regulation of KOR. CONCLUSION: KOR might act as a tumor suppressor in ESCC and down-regulation of KOR could enhance the ESCC tumor phenotype. Video Abstract.


Asunto(s)
Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Animales , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular/genética , Regulación hacia Abajo , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago/genética , Regulación Neoplásica de la Expresión Génica , Metaloproteinasa 2 de la Matriz/metabolismo , Ratones , Ratones Desnudos , Invasividad Neoplásica/patología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Receptores Opioides kappa/genética , Receptores Opioides kappa/metabolismo , Transducción de Señal/genética
3.
Cell Mol Biol Lett ; 27(1): 28, 2022 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-35305553

RESUMEN

BACKGROUND: Parecoxib plays an important role in inhibition of human cancer. However, the effect of parecoxib on esophageal squamous cell carcinoma (ESCC) is still not well known. The purpose of this study was to investigate the effect of parecoxib on ESCC and its underlying mechanism. METHODS: RNA-sequence analysis was performed to identify functional alterations and mechanisms. Cell cycle, proliferation, invasion, and migration were assessed using flow cytometry, CCK-8 assay, colony formation, transwell, and wound healing assays. Extracellular matrix (ECM) degradation was detected by substrate gel zymography and 3D cell culture assay. Western blotting was used to detect parecoxib-dependent mechanisms involving cell cycle, proliferation, invasion, and migration. Tumor formation in vivo was detected by mouse assay. RESULTS: Functional experiments indicated that parecoxib induced ESCC cell cycle arrest in G2 phase, and inhibited cell proliferation, invasion, and migration in vitro. Western blotting revealed that parecoxib downregulated the phosphorylation levels of AKT and PDK1, as well as the expression of the mutant p53, cyclin B1, and CDK1, while upregulating p21waf1. Parecoxib inhibited matrix metalloproteinase-2 (MMP2) secretion and invadopodia formation, which were related to ECM degradation. Furthermore, we found that parecoxib suppressed ESCC growth in heterotopic tumor models. CONCLUSION: Parecoxib inhibits ESCC progression, including cell cycle, proliferation, invasion, and migration, via the PDK1-AKT signaling pathway.


Asunto(s)
Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Animales , Línea Celular Tumoral , Movimiento Celular , Neoplasias Esofágicas/metabolismo , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Carcinoma de Células Escamosas de Esófago/metabolismo , Isoxazoles , Metaloproteinasa 2 de la Matriz , Ratones , Proteínas Proto-Oncogénicas c-akt/metabolismo
4.
Liver Int ; 41(2): 378-387, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-32562336

RESUMEN

BACKGROUND & AIMS: The lymphocyte-C-reactive protein ratio (LCR) is a novel inflammatory-based score, based solely on the lymphocyte and C-reactive protein. We aimed to clarify the prognostic value of the LCR score in intrahepatic cholangiocarcinoma (ICC) patients after resection. METHODS: We compared the prognostic accuracy of the LCR score with other inflammatory-based scores in this large, multicentre cohort study. The independent variables associated with overall survival (OS) were explored in both the primary (n = 228) and validation cohorts (n = 135). Harrell's concordance index (C-index) was used to compare the predictive ability of all the assessed inflammatory-based scores. RESULTS: The LCR score was differentiated two groups of ICC patients with distinct prognoses (1-, 3-, and 5-year OS rates: 94.4%, 66.3%, and 59.3%; and 66.6%, 45.6%, and 32.7%, respectively) (P < .001). Multivariate analysis showed that the LCR score, as well as the TNM stage and preoperative CA19-9 level, were independently associated with OS. The predictive accuracy of the LCR score (c score: 0.634) was superior to that of the other inflammatory-based scores (c scores: 0.508-0.615). These findings were supported by the external validation cohort. CONCLUSION: The LCR score is stable and consistently the best prognostic score and may offer as a simple, objective and discriminatory method in facilitating the risk stratification of ICC patients.


Asunto(s)
Neoplasias de los Conductos Biliares , Colangiocarcinoma , Neoplasias de los Conductos Biliares/cirugía , Proteína C-Reactiva , Colangiocarcinoma/cirugía , Estudios de Cohortes , Hepatectomía , Humanos , Linfocitos , Pronóstico
5.
Toxicol Ind Health ; 36(12): 1031-1038, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33215568

RESUMEN

To explore the protective mechanism of L-arginine against T-2 toxin-induced apoptosis in mouse Leydig cells, we investigated whether L-arginine can prevent T-2 toxin-induced apoptosis in mouse Leydig cells and explored the underlying mechanisms. Leydig cells were isolated and cultured with control, T-2 toxin (10 nM), L-arginine (0.25, 0.5, and 1.0 mM), and T-2 toxin (10 nM T-2 toxin) + L-arginine (0.25, 0.5, or 1.0 mM) for 24 h. Cells and supernatants were harvested to examine proliferation of the cells, the apoptosis rate, activity of caspase-3 and mitochondria, and the gene expression levels of Bcl-2, Bax, PARP, and caspase-3. Results showed that proliferation and mitochondrial activity of Leydig cells were inhibited by administration of T-2 toxin. Bcl-2 gene expression levels was decreased, while the gene expression levels of Bax and PARP were increased, which could trigger mitochondria-mediated apoptosis, activate downstream caspase-3, and then increased caspase-3 at both activity and gene expression levels. The expression of the Bcl-2 gene was upregulated and the expression of Bax, caspase-3, and PARP gene were downregulated when L-arginine was added to the cultured cells. The results of this study showed that L-arginine could block T-2 toxin-induced apoptosis in mouse Leydig cells by regulating specific intracellular death-related pathways.


Asunto(s)
Apoptosis/efectos de los fármacos , Arginina/farmacología , Células Intersticiales del Testículo/efectos de los fármacos , Sustancias Protectoras/farmacología , Toxina T-2/farmacología , Animales , Caspasa 3/biosíntesis , Proliferación Celular , Células Cultivadas , Relación Dosis-Respuesta a Droga , Masculino , Ratones , Mitocondrias/efectos de los fármacos , Proteínas de Neoplasias , Poli(ADP-Ribosa) Polimerasa-1/biosíntesis , Proteínas Proto-Oncogénicas c-bcl-2/biosíntesis , Proteína X Asociada a bcl-2/biosíntesis
6.
Zhongguo Dang Dai Er Ke Za Zhi ; 22(11): 1221-1225, 2020 Nov.
Artículo en Zh | MEDLINE | ID: mdl-33172559

RESUMEN

OBJECTIVE: To study the association between maternal Th1/Th2 immune level at different pregnancy stages and cow's milk protein allergy (CMPA) in infants. METHODS: The healthy women with a singleton pregnancy, as well as their offspring, who attended Yidu Central Hospital of Weifang and Qingzhou Traditional Chinese Medicine Hospital from July 2016 to December 2018 were enrolled. The maternal levels of interleukin-2 (IL-2), interferon gamma (IFN-γ), interleukin-4 (IL-4), and interleukin-10 (IL-10) at the second and third trimesters of pregnancy were measured. A CMPA questionnaire survey was conducted within one year after birth. Food avoidance and cow's milk oral challenge tests were performed in infants suspected of CMPA. The 48 infants who met the diagnostic criteria for CMPA were included in the observation group, and the remaining 977 normal infants were included in the control group. A univariate analysis was performed on the infants with CMPA. A Poisson regression analysis was used to determine the association between maternal Th1/Th2 immune factors at different pregnancy stages and CMPA. RESULTS: The detection rate of CMPA was 4.68%. The clinical manifestations included the symptoms of the digestive system, skin, and respiratory system and other symptoms. The univariate analysis showed that compared with the control group, the observation group had significantly higher incidence rates of maternal food allergy and maternal history of allergic diseases (P<0.05) and a significantly lower breastfeeding rate (P<0.05). The observation group had significantly lower maternal levels of IL-2 (second and third trimesters) and IFN-γ (third trimester) than the control group (P<0.05). Maternal low IFN-γ at the third trimester and maternal low IL-2 at the second and third trimesters were significantly associated with CMPA in infants (P<0.05). After correction of the factors of breastfeeding, maternal food allergy, and maternal history of allergic diseases, it was found that maternal low IL-2 and IFN-γ at the third trimester were still significantly associated with CMPA in infants (P<0.05). CONCLUSIONS: The maternal decrease in Th1 level at the third trimester of pregnancy may lead to the change in fetal immunity and thus increase the risk of CMPA in offspring.


Asunto(s)
Hipersensibilidad a la Leche , Alérgenos , Animales , Lactancia Materna , Bovinos , Femenino , Humanos , Lactante , Proteínas de la Leche/inmunología , Embarazo
7.
Toxicol Ind Health ; 35(3): 256-263, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30862294

RESUMEN

T-2 toxin is a type-A trichothecene produced by Fusarium found in several food commodities worldwide. T-2 toxin causes reproductive disorders, genotoxicity, and testicular toxicity in animals. Our previous research has reported that T-2 toxin can induce apoptosis via the Bax-dependent caspase-3 activation in mouse primary Leydig cells. However, little is known about the functions of autophagy and the cross talk between autophagy and apoptosis after exposure to T-2 toxin in Leydig cells. This study investigated these problems in mouse primary Leydig cells. Results showed that T-2 toxin treatment upregulated LC3-II and Beclin-1 expression, suggesting that T-2 toxin induced a high level of autophagy. Pretreatment with chloroquine (an autophagy inhibitor) and rapamycin (an autophagy inducer) increased and decreased the rate of apoptosis, respectively, in contrast to T-2 toxin-treated group. Autophagy delayed apoptosis in the T-2 toxin-treated Leydig cells. Therefore, autophagy may prevent cells from undergoing apoptosis by reducing T-2 toxin-induced cytotoxicity.


Asunto(s)
Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Células Intersticiales del Testículo/efectos de los fármacos , Toxina T-2/toxicidad , Animales , Cloroquina/farmacología , Masculino , Ratones , Sirolimus/farmacología
8.
BMC Cancer ; 18(1): 643, 2018 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-29879928

RESUMEN

BACKGROUND: The optimal therapeutic strategy in UICC stage T3 hepatocellular carcinoma (HCC) patients that maximizes both safety and long-term outcome has not yet been determined. Our aim was to compare clinical outcomes following hepatic resection (HR) versus transarterial chemoembolization (TACE) for stage T3 HCC. METHODS: From 2005 to 2013, 1179 patients with T3 HCC who underwent HR or TACE were divided into two groups, HR group (n = 280) or TACE group (n = 899). The clinical outcomes were compared before and after propensity score matching. RESULTS: The propensity model matched 244 patients in each group for further analyses. After matching, medium overall survival (OS), 1, 3, and 5-year OS rates in TACE group were 11.8 (95%CI, 9.9-13.7) months, 49.6, 16.5, and 8.4%, respectively; which in HR group were 17.8 (95% CI, 14.8-20.8) months, 63.1, 33.3, and 26.4%, respectively; (log rank = 19.908, P < 0.01). Patients in HR group were more likely to develop pleural effusion, compared with those in TACE group (0.4% vs. 5.3%, P = 0.01). However, no significant differences in other adverse events (AEs) were found between two groups. Similar results were also demonstrated prior to the matched analysis. Multivariate analysis indicated that prothrombin time (PT), tumor size, tumor numbers, UICC staging status, and initial treatment were independent prognostic factors. CONCLUSIONS: Our study revealed that TACE was an option for UICC T3 HCC patients. However, HR seemed to be safe and yield a survival benefit compared with TACE, especially for patients with a good underlying liver function.


Asunto(s)
Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica/métodos , Hepatectomía/métodos , Neoplasias Hepáticas/terapia , Adulto , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Quimioembolización Terapéutica/efectos adversos , Femenino , Hepatectomía/efectos adversos , Humanos , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Puntaje de Propensión , Análisis de Supervivencia , Resultado del Tratamiento
10.
J Vasc Interv Radiol ; 29(8): 1068-1077.e2, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-30042075

RESUMEN

PURPOSE: To compare the stability of stable and unstable water-in-oil emulsions and the efficacy and safety of these emulsions in a single-center, prospective double-blind trial of transarterial chemoembolization for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: A total of 812 patients with inoperable HCC were randomized (stable emulsion, n = 402; unstable emulsion, n = 410). The 2 emulsions were prepared by using the same protocol except that different solvents were used for chemotherapy agents, including epirubicin, lobaplatin, and mitomycin C. The solvent in the stable emulsion arm was contrast medium and distilled water, and the solvent in the unstable emulsion arm was distilled water. The primary endpoint was overall survival (OS), and secondary endpoints were time to progression (TTP), tumor response, adverse events (AEs), and plasma epirubicin concentrations. RESULTS: In vitro, stable emulsions did not occur until 1 day, and unstable emulsions, with a lower peak plasma concentration (P = .001) in vivo, exhibited rapid separation of the oil and aqueous phases after 10 minutes. Median OS times in the stable and unstable emulsion arms were 17.7 and 19.2 months, respectively (P = .81). No differences were found in TTP, tumor response, and AEs except for myelosuppression (anemia, 3.5% vs 7.6%; thrombocytopenia, 11.5% vs 17.7%), which was significantly more severe and frequent in the unstable emulsion arm (P = .013). CONCLUSIONS: Chemoembolization is equally effective with the use of stable and unstable emulsions, but the use of a stable emulsion has the advantage of less myelosuppression and a favorable pharmacokinetic profile.


Asunto(s)
Antineoplásicos/administración & dosificación , Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica/métodos , Aceite Etiodizado/administración & dosificación , Neoplasias Hepáticas/terapia , Antineoplásicos/efectos adversos , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Quimioembolización Terapéutica/efectos adversos , Quimioembolización Terapéutica/mortalidad , China , Método Doble Ciego , Estabilidad de Medicamentos , Emulsiones , Aceite Etiodizado/efectos adversos , Aceite Etiodizado/farmacocinética , Femenino , Humanos , Estimación de Kaplan-Meier , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento
11.
J Biochem Mol Toxicol ; 32(10): e22209, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-30091165

RESUMEN

To explore the protective mechanism of l-arginine against T-2 toxin-induced oxidative damage in mouse Leydig cells, Leydig cells were isolated and cultured with control, T-2 toxin (10 nM), l-arginine (0.25, 0.5, and 1.0 mM), and T-2 toxin (10 nM T-2 toxin) with l-arginine (0.25, 0.5, or 1.0 mM) for 24 hours. Cells and supernatants were harvested to examine cell viability, activities, and messenger RNA (mRNA) expression of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and catalase (CAT), malondialdehyde (MDA) content, and DNA damage. Results showed that T-2 toxin significantly reduced cell viability, improved MDA content and DNA damage, and decreased activities and mRNA expression of GSH-Px, SOD, and CAT. However, l-arginine reduced T-2 toxin-induced oxidative damage and tended to maintain normal levels. Furthermore, l-arginine upregulated mRNA expressions of GSH-Px, SOD, and CAT. Collectively, l-arginine, due to its antioxidative ability, could ameliorate T-2 toxin-induced cytotoxicities in mouse Leydig cells by regulating oxidative stress.


Asunto(s)
Arginina/farmacología , Células Intersticiales del Testículo/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Toxina T-2/toxicidad , Animales , Catalasa/genética , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Daño del ADN , Glutatión Peroxidasa/genética , Células Intersticiales del Testículo/enzimología , Células Intersticiales del Testículo/metabolismo , Masculino , Malondialdehído/metabolismo , Ratones , ARN Mensajero/genética , Superóxido Dismutasa/genética
12.
Toxicol Mech Methods ; 28(1): 23-28, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-28697680

RESUMEN

To explore the toxic effect of T-2 toxin on mouse Leydig cells and its underlying molecular mechanisms, we isolated Leydig cells from mature mice, set-up Leydig cells culture, treated cells with T-2 toxin, evaluated cell proliferation, detected the caspase-3 activity, mitochondrial activity and apoptosis rate, and measured the mRNA levels of Bcl-2, Bax, PARP and caspase-3. T-2 toxin inhibited cell proliferation at concentrations higher than 10-9 M or time more than 12 h, T-2 toxin also decreased Bcl-2 expression at the mRNA levels and mitochondrial activity at concentrations higher than 10-9 M. While, T-2 toxin increased the mRNA expressions of Bax and PARP at concentrations higher than 10-8 M and 10-9 M, respectively, triggered mitochondria-mediated apoptosis, activated downstream caspase-3, and then increased caspase-3 at the activity and mRNA levels at concentrations higher than 10-9 M. These data showed that T-2 toxin appears to activate specific intracellular death-related pathways leading to Bax-dependent caspase-3 activation and the induction of apoptosis in Leydig cells.


Asunto(s)
Apoptosis/efectos de los fármacos , Caspasa 3/metabolismo , Células Intersticiales del Testículo/efectos de los fármacos , Toxina T-2/toxicidad , Proteína X Asociada a bcl-2/metabolismo , Animales , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Relación Dosis-Respuesta a Droga , Activación Enzimática , Células Intersticiales del Testículo/enzimología , Células Intersticiales del Testículo/patología , Masculino , Ratones , Mitocondrias/efectos de los fármacos , Mitocondrias/enzimología , Mitocondrias/patología , Cultivo Primario de Células , Transducción de Señal/efectos de los fármacos , Factores de Tiempo
13.
Hepatology ; 63(4): 1227-39, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26660154

RESUMEN

UNLABELLED: Although many staging classifications have been proposed for hepatocellular carcinoma (HCC), determining a patient's prognosis in clinical practice is a challenge due to the molecular diversity of HCC. We investigated the relationship between MEP1A, a candidate oncogene, and clinical outcomes of HCC patients; furthermore, we explored the role of MEP1A in HCC. In this report, it was demonstrated by quantitative real-time polymerase chain reaction that MEP1A messenger RNA levels were significantly elevated in HCC tumor tissues compared with matched adjacent nonneoplastic tissues and nonmalignant liver disease tissues. Immunohistochemical analyses of tissue samples from two independent groups of 394 HCC patients showed that positive expression of MEP1A in tumor cells was an independent and significant risk factor affecting survival after curative resection in both cohort 1 (hazard ratio = 2.05, 95% confidence interval 1.427-2.946; P < 0.001) and cohort 2 (hazard ratio = 1.89, 95% confidence interval 1.260-2.833; P = 0.002). Analysis of Barcelona Clinic Liver Cancer stage 0-A subgroup further showed that patients with positive MEP1A expression in tumor cells had poorer surgical prognoses than those with negative MEP1A expression in tumor cells (cohort 1 P = 0.001, cohort 2 P < 0.001). Both in vitro and in vivo assays showed that MEP1A promoted HCC cell proliferation, migration, and invasion. Further analyses found that MEP1A played an important role in regulating cytoskeletal events and induced epithelial-mesenchymal transition in HCC cells. CONCLUSION: MEP1A is a novel prognostic predictor in HCC and plays an important role in the development and progression of HCC.


Asunto(s)
Biomarcadores de Tumor/sangre , Carcinoma Hepatocelular/sangre , Carcinoma Hepatocelular/mortalidad , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/mortalidad , Metaloendopeptidasas/metabolismo , Adulto , Anciano , Análisis de Varianza , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/cirugía , Estudios de Cohortes , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Hepatectomía/métodos , Humanos , Estimación de Kaplan-Meier , Neoplasias Hepáticas/parasitología , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Análisis Multivariante , Invasividad Neoplásica/patología , Estadificación de Neoplasias , Pronóstico , Modelos de Riesgos Proporcionales , ARN Mensajero/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Estudios Retrospectivos , Medición de Riesgo , Estadísticas no Paramétricas , Análisis de Supervivencia , Resultado del Tratamiento
15.
Toxicol Mech Methods ; 27(2): 100-106, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-27842451

RESUMEN

To explore the toxic mechanism of T-2 toxin on Leydig cells of mice, we would investigate the toxicity and oxidative stress induced by T-2 toxin in the cells. Leydig cells were isolated and cultured with control or T-2 toxin (10-7 M, 10-8 M, or 10-9 M) for 24 h, then cells and supernatants were harvested to examine cell viability, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) activities, expression of messenger RNA (mRNA) related to oxidative stress, malondialdehyde (MDA) content and DNA damage. The cell viability was evaluated in mouse Leydig cells by MTT assay, MDA content and SOD, GSH-Px and CAT activities were measured by routine kits, expression of mRNA related to oxidative stress were examined by quantitative real-time polymerase chain reaction (PCR), and DNA damage was investigated by comet assay. Leydig cells treated with T-2 toxin showed significant reductions in cell viability, SOD, GSH-Px and CAT activities, and expression of mRNA related to oxidative stress, and remarkable increases in MDA content and levels of DNA damage. This study proves that T-2 toxin is toxic to Leydig cells of mice. Furthermore, oxidative stress plays an important role in the above-mentioned negative effects of T-2 toxin.


Asunto(s)
Células Intersticiales del Testículo/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Toxina T-2/toxicidad , Animales , Catalasa/metabolismo , Técnicas de Cultivo de Célula , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Glutatión Peroxidasa/metabolismo , Células Intersticiales del Testículo/metabolismo , Masculino , Ratones , Superóxido Dismutasa/metabolismo
16.
Br J Cancer ; 115(9): 1039-1047, 2016 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-27701389

RESUMEN

BACKGROUND: The subgroups of patients with intermediate-stage (BCLC-B) hepatocellular carcinoma (HCC) who would truly benefit from hepatic resection (HR) are unknown. An objective point score was established to guide the selection of these patients for HR. METHODS: In all, 255 consecutive patients with intermediate-stage HCC treated with HR were evaluated retrospectively and included in this study (the training cohort). The variables on overall survival (OS, log-rank test) were investigated and a point score (the NSP score) was developed by using a Cox-regression model and validated in an independent external cohort from another institution (n=169). RESULTS: The NSP score differentiated two groups of patients (⩽1, >1 point) with distinct prognoses (median OS, 61.3 vs 19.3 months; P<0.001). A high NSP score was associated with increased major adverse events after HR (5.6 vs 13.8%, P=0.027). Its predictive accuracy as determined by the area under the receiver operating characteristic curve (AUC) at 1, 3, and 5 years (AUCs 0.688, 0.739, and 0.732) was greater than the other six staging systems for HCC (0.513-0.677). The findings were supported by the validation cohort. CONCLUSIONS: The NSP scoring system is more accurate in selecting patients with intermediate-stage HCC for HR.


Asunto(s)
Carcinoma Hepatocelular/cirugía , Toma de Decisiones , Hepatectomía/estadística & datos numéricos , Neoplasias Hepáticas/cirugía , Selección de Paciente , Adulto , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Femenino , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Reproducibilidad de los Resultados , Proyectos de Investigación , Estudios Retrospectivos , Análisis de Supervivencia
17.
Liver Int ; 36(10): 1516-24, 2016 10.
Artículo en Inglés | MEDLINE | ID: mdl-27105296

RESUMEN

BACKGROUND & AIMS: The discontinuation rules of transarterial chemoembolization (TACE) for patients who were assessed as progressive disease (PD) but stage progression-free (SP-free: still belongs to Barcelona Clinic Liver Cancer B) after TACE are unclear. We aimed to evaluate the impact of the PD-pattern on the survival of these patients retreated with TACE. METHODS: In total, 115 consecutive patients who were assessed as PD but SP-free after TACE and then underwent at least one subsequent TACE session were included. Sixty patients were assessed as PD with target lesion progression (TP), and 55 patients were assessed as PD with target lesion non-progression (TNP). Survival and treatment-related adverse events were compared between the two groups. Additional external validation was performed using a data set (n = 103) from another institution. RESULTS: Patients with TNP had significantly longer median post-progression survival (PPS) than those with TP (21.0 vs. 11.9 months, P = 0.004). After TACE retreatment, the incidence of liver dysfunction was significantly higher for patients with TP than for patients with TNP (45% vs. 20%, P = 0.031). In the multivariate analysis, the target lesion response was one of the most significant prognostic factors for PPS (HR = 2.01; 95% confidence interval: 1.23-3.27; P = 0.005). The findings were supported by an independent external cohort. CONCLUSIONS: Compared to patients with TNP, patients with TP might exhibit no improvement in survival and even present damaged liver function after retreatment with TACE. Target lesion response is useful as a clinical decision for repeated TACE in these patients.


Asunto(s)
Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/terapia , Adulto , Anciano , China/epidemiología , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estadificación de Neoplasias , Modelos de Riesgos Proporcionales , Tasa de Supervivencia , Resultado del Tratamiento
18.
Eur Radiol ; 26(7): 2078-88, 2016 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-26396105

RESUMEN

OBJECTIVES: To evaluate the outcomes of preoperative transarterial chemoembolization (TACE) for resectable hepatocellular carcinoma (HCC) with portal vein invasion. METHODS: From February 2006 to July 2011, 320 patients initially diagnosed with resectable HCC and portal vein invasion were prospectively non-randomized into two arms. In the immediate resection arm (Arm 1, n = 205) patients received immediate surgical resection. 115 patients were included in the preoperative TACE arm (Arm 2), and eventually 85 patients underwent TACE followed by surgical resection. RESULTS: The 1-, 3- and 5-year overall survival rates were 48.3 %, 18.7 % and 13.9 % for Arm 1 and 61.2 %, 31.7 % and 25.3 % for Arm 2 (P = 0.001), respectively. In the subgroup analysis of types I and II portal vein tumour thrombus (PVTT), the preoperative TACE arm demonstrated significantly better survival rates than the immediate resection arm (P I = 0.001, P II = 0.036). However, no significant difference was found for patients with type III PVTT (P III = 0.684). No significant difference was found between the two arms in terms of complications and mortality. CONCLUSIONS: Preoperative TACE seems to confer a survival benefit for resectable HCC with PVTT, especially for types I and II PVTT, and preoperative TACE should therefore be recommended as a routine procedure. KEY POINTS: • Preoperative TACE improves the clinical outcomes for patients with PVTT • Preoperative TACE could significantly improve the rate of en bloc thrombectomy • Preoperative TACE does not increase the related adverse events.


Asunto(s)
Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica/métodos , Neoplasias Hepáticas/terapia , Vena Porta/patología , Cuidados Preoperatorios/métodos , Neoplasias Vasculares/secundario , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/cirugía , Femenino , Humanos , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Vena Porta/cirugía , Estudios Prospectivos , Resultado del Tratamiento , Neoplasias Vasculares/cirugía
19.
Toxicol Ind Health ; 32(10): 1801-7, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26085520

RESUMEN

T-2 toxin is one of the mycotoxins, a group of type A trichothecenes produced by several fungal genera including Fusarium species, which may lead to the decrease of testosterone secretion in primary Leydig cells derived from mouse testis. The previous study demonstrated T-2 toxin decrease the testosterone biosynthesis in the primary Leydig cells derived from the mouse testis directly. In this study, we further examined the direct biological effects of T-2 toxin on the process of steroidogenesis, primarily in Leydig cells of mice. Leydig cells of mature mouse were purified by Percoll gradient centrifugation and the cell purity was determined by 3ß-hydroxysteroid dehydrogenase (3ß-HSD) staining. To examine the decrease in T-2 toxin-induced testosterone secretion, we measured the transcription level of three key steroidogenic enzymes including 3ß-HSD-1, cytochrome P450 side-chain cleavage (P450scc) enzyme, and steroidogenic acute regulatory (StAR) protein in T-2 toxin/human chorionic gonadotropin (hCG) co-treated cells. Our previous study showed that T-2 toxin (10(-7), 10(-8), and 10(-9) M) significantly suppressed hCG (10 ng/ml)-induced testosterone secretion. The studies demonstrated that the suppressive effect is correlated with a decrease in the level of transcription of 3ß-HSD-1, P450scc, and StAR (p < 0.05).


Asunto(s)
17-Hidroxiesteroide Deshidrogenasas/metabolismo , Células Intersticiales del Testículo/efectos de los fármacos , Células Intersticiales del Testículo/metabolismo , Toxina T-2/toxicidad , 17-Hidroxiesteroide Deshidrogenasas/análisis , 17-Hidroxiesteroide Deshidrogenasas/genética , Animales , Células Cultivadas , Centrifugación , Células Intersticiales del Testículo/enzimología , Masculino , Ratones , Fosfoproteínas/análisis , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , ARN Mensajero/análisis , ARN Mensajero/genética , ARN Mensajero/metabolismo
20.
Jpn J Clin Oncol ; 45(9): 837-43, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26079139

RESUMEN

OBJECTIVE: To compare the outcomes of hepatic resection and transcatheter arterial chemoembolization for resectable hepatocellular carcinoma with hepatic vein tumor thrombus. METHODS: From January 2006 to November 2013, 28 patients initially diagnosed with resectable hepatocellular carcinoma combined with hepatic vein tumor thrombus received hepatic resection. These patients were compared with 56 case-matched controls (1:2 ratio) selected from a pool of 91 patients who received transcatheter arterial chemoembolization as an initial treatment during the same period. Clinical characteristics, adverse events, overall survival and survival-related factors were analyzed. RESULTS: The 1-, 2- and 3-year overall survival rates were 66.5, 37.4 and 28.5% for the hepatic resection group and 32.3, 18.7 and 15.6% for the transcatheter arterial chemoembolization group (P = 0.015), respectively. No significant difference was found between the two groups in terms of complications and mortality. Multivariate analyses revealed combined portal vein tumor thrombosis (HR = 2.116; 95% CI: 1.26-3.57; P = 0.005) and treatment allocation (hepatic resection = 2.289; 95% CI, 1.30-4.02; P = 0.004) as risk factors for overall survival. CONCLUSIONS: Hepatic resection provides a good prognosis for hepatocellular carcinoma patients with hepatic vein tumor thrombus compared with patients undergoing transcatheter arterial chemoembolization, and the most important factor related to survival was co-existence with portal vein invasion.


Asunto(s)
Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica , Neoplasias Hepáticas/terapia , Trombosis de la Vena/complicaciones , Adulto , Anciano , Carcinoma Hepatocelular/complicaciones , Carcinoma Hepatocelular/mortalidad , Estudios de Casos y Controles , Femenino , Estudios de Seguimiento , Hepatectomía , Venas Hepáticas , Humanos , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/mortalidad , Masculino , Persona de Mediana Edad , Análisis Multivariante , Recurrencia Local de Neoplasia , Vena Porta , Factores de Riesgo , Tasa de Supervivencia
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