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1.
Oxid Med Cell Longev ; 2022: 8200189, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35355866

RESUMEN

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease of unknown cause which leads to alveolar epithelial cell apoptosis followed by basement membrane disruption and accumulation of extracellular matrix, destroying the lung architecture. Oxidative stress is involved in the development of alveolar injury, inflammation, and fibrosis. Oxidative stress-mediated alveolar epithelial cell (AEC) apoptosis is suggested to be a key process in the pathogenesis of IPF. Therefore, the present study investigated whether grape seed proanthocyanidin extract (GSPE) could inhibit the development of pulmonary fibrosis via ameliorating epithelial apoptosis through the inhibition of oxidative stress. We found that GSPE significantly ameliorated the histological changes and the level of collagen deposition in bleomycin (BLM)-induced lungs. Moreover, GSPE attenuated lung inflammation by reducing the total number of cells in bronchoalveolar lavage (BAL) fluid and decreasing the expression of IL-6. We observed that the levels of H2O2 leading to oxidative stress were increased following BLM instillation, which significantly decreased with GSPE treatment both in vivo and in vitro. These findings showed that GSPE attenuated BLM-induced epithelial apoptosis in the mouse lung and A549 alveolar epithelial cell through the inhibition of oxidative stress. Furthermore, GSPE could attenuate mitochondrial-associated cell apoptosis via decreasing the Bax/Bcl-2 ratio. The present study demonstrates that GSPE could ameliorate bleomycin-induced pulmonary fibrosis in mice via inhibition of epithelial apoptosis through the inhibition of oxidative stress.


Asunto(s)
Bleomicina , Fibrosis Pulmonar Idiopática , Animales , Apoptosis , Bleomicina/toxicidad , Extracto de Semillas de Uva , Peróxido de Hidrógeno , Fibrosis Pulmonar Idiopática/inducido químicamente , Fibrosis Pulmonar Idiopática/patología , Ratones , Estrés Oxidativo , Proantocianidinas
2.
Abdom Radiol (NY) ; 46(8): 3729-3737, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-33141259

RESUMEN

PURPOSE: To evaluate associations between pathology and CT assessments made according to the mRECIST in HCC treated by conventional TACE (cTACE), and to identify predictors of complete tumor necrosis. METHODS: From March 2016 to July 2018, 83 patients with a total of 100 masses were retrospectively included. Patients underwent sequential cTACE and portal vein embolization, and later hepatic surgery. Evaluation of treatment response and measurement of baseline lipiodol accumulation as mean HU was performed on CT at the time point closest to the time of operation (mean, 54.5 days after cTACE). Significant predictors associated with complete necrosis were identified by multivariate analysis. The optimal cut-off HU value of lipiodol accumulation for prediction of complete necrosis was determined using a ROC analysis. RESULTS: According to mRECIST, complete response (CR, n = 70) and partial response (n = 30) were classified. 34.3% (24/70) masses classified as CR according to mRECIST were found to have viable lesions on pathology. On multivariate analysis, mean HU of lipiodol accumulation was the only significant predictor of complete necrosis (p = .003, odds ratio 1.746, 95% CI 1.201-2.539). On ROC analysis, 460 HU as a cut-off value was significantly associated with complete necrosis (67.4% sensitivity, 75.0% specificity). CONCLUSIONS: A threshold value for lipiodol accumulation > 460 HU was highly sensitive and specific for complete necrosis, even in complete response according to mRECIST. Therefore, if lipiodol accumulation is insufficient in post-TACE CT, recurrence should be monitored more sensitively.


Asunto(s)
Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/terapia , Aceite Etiodizado , Humanos , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/terapia , Necrosis , Recurrencia Local de Neoplasia , Estudios Retrospectivos , Tomografía Computarizada por Rayos X , Resultado del Tratamiento
3.
Korean J Radiol ; 20(3): 385-398, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30799569

RESUMEN

OBJECTIVE: To compare the safety and efficacy of radioembolization with that of sorafenib for the treatment of hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). MATERIALS AND METHODS: MEDLINE, EMBASE, and Cochrane databases were searched for studies reporting outcomes in patients with HCC and PVTT treated with radioembolization or sorafenib. Meta-analyses of cumulative overall survival (OS) and Kaplan-Meier survival rates according to the time to progression (TTP) and incidence of adverse events (AEs) were performed. Subgroup analyses were conducted on 1-year OS data. RESULTS: Seventeen studies were identified (four involving radioembolization, 10 involving sorafenib, and three comparing both). Pooled OS rates were higher in the radioembolization group, notably at 6 months {76% (95% confidence interval [CI], 64-85%) vs. 54% (95% CI, 45-62%)} and 1 year (47% [95% CI, 38-57%] vs. 24% [95% CI, 18-30%]); TTP was also longer with radioembolization. In patients undergoing radioembolization, the proportion of patients with Eastern Cooperative Oncology Group status 0 (p < 0.0001), Child-Pugh A (p < 0.0001), extrahepatic metastasis (p = 0.0012), and a history of cancer treatment (p = 0.0048) was identified as a significant source of heterogeneity for the 1-year OS. Radioembolization was associated with a lower incidence of grade 3/4 AEs than sorafenib (9% [95% CI, 3-27%] vs. 28% [95% CI, 17-43%]). CONCLUSION: Compared with sorafenib, radioembolization is a safer and more effective treatment for HCC with PVTT and is associated with prolonged survival, delayed tumor progression, and fewer grade 3/4 AEs.


Asunto(s)
Antineoplásicos/uso terapéutico , Carcinoma Hepatocelular/diagnóstico , Quimioembolización Terapéutica , Neoplasias Hepáticas/diagnóstico , Sorafenib/uso terapéutico , Trombosis de la Vena/diagnóstico , Antineoplásicos/efectos adversos , Carcinoma Hepatocelular/complicaciones , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica/efectos adversos , Diarrea/etiología , Humanos , Estimación de Kaplan-Meier , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/terapia , Índice de Severidad de la Enfermedad , Sorafenib/efectos adversos , Trombosis de la Vena/complicaciones
4.
Pharm Biol ; 56(1): 183-191, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-29521146

RESUMEN

CONTEXT: Salicornia europaea (Amaranthaceae) (SE) has been shown to reduce obesity, but it remains a problem as a food supplement because of its high salt content (25-35% NaCl). OBJECTIVES: This study investigated the anti-obesity effects and mechanism of action of desalted SE powder (DSP). MATERIALS AND METHODS: Sprague-Dawley rats (n = 50) were divided into a normal control group (NC), a high-fat diet (HFD)-induced obesity control group (HFD), and HFD groups co-administered DSP (250 and 500 mg/kg) or Garcinia cambogia (Clusiaceae) extract (GE, 200 mg/kg, standard control) orally each day for 12 weeks. RESULTS: The body weight was significantly reduced by co-administration of DSP (596.51 ± 19.84 kg, 4.60% and 562.08 ± 9.74 kg, 10.10%, respectively) and GE (576.00 ± 11.29 kg, 7.88%) relative to the HFD group (625.25 ± 14.02 kg) and was accompanied by reduced abdominal fat mass, and serum lipid levels, with no effects on feed intake. To find the underlying mechanism of the anti-obesity effects, trans-ferulic acid (TFA) was identified as the main ingredient and investigated with regard to whether it attenuated adipogenesity in 3T3L-1 cells. DSP-derived TFA suppressed adipocyte differentiation and accumulation of intracellular lipids. TFA also down-regulated the adipogenesis-related gene expression of sterol regulatory element-binding protein 1, peroxisome proliferator-activated receptor γ, CCAAT/enhancer binding protein-α and fatty acid synthase. CONCLUSIONS: These findings suggest that DSP may be considered for use as a food supplement intent of controlling obesity through its antiobesity and antiadipogenic properties.


Asunto(s)
Adipogénesis/efectos de los fármacos , Fármacos Antiobesidad/uso terapéutico , Chenopodiaceae , Ácidos Cumáricos/uso terapéutico , Obesidad/tratamiento farmacológico , Extractos Vegetales/uso terapéutico , Células 3T3-L1 , Adipogénesis/fisiología , Animales , Fármacos Antiobesidad/aislamiento & purificación , Fármacos Antiobesidad/farmacología , Peso Corporal/efectos de los fármacos , Peso Corporal/fisiología , Ácidos Cumáricos/aislamiento & purificación , Ácidos Cumáricos/farmacología , Relación Dosis-Respuesta a Droga , Masculino , Ratones , Obesidad/metabolismo , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacología , Ratas , Ratas Sprague-Dawley
6.
World J Gastroenterol ; 22(1): 407-16, 2016 Jan 07.
Artículo en Inglés | MEDLINE | ID: mdl-26755886

RESUMEN

The natural history of hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) is dismal (approximately 2-4 mo), and PVTT is reportedly found in 10%-40% of HCC patients at diagnosis. According to the Barcelona Clinic Liver Cancer (BCLC) Staging System (which is the most widely adopted HCC management guideline), sorafenib is the standard of care for advanced HCC (i.e., BCLC stage C) and the presence of PVTT is included in this category. However, sorafenib treatment only marginally prolongs patient survival and, notably, its therapeutic efficacy is reduced in patients with PVTT. In this context, there have been diverse efforts to develop alternatives to current standard systemic chemotherapies or combination treatment options. To date, many studies on transarterial chemoembolization, 3-dimensional conformal radiotherapy, hepatic arterial chemotherapy, and transarterial radioembolization report better overall survival than sorafenib therapy alone, but their outcomes need to be verified in future prospective, randomized controlled studies in order to be incorporated into current treatment guidelines. Additionally, combination strategies have been applied to treat HCC patients with PVTT, with the hope that the possible synergistic actions among different treatment modalities would provide promising results. This narrative review describes the current status of the management options for HCC with PVTT, with a focus on overall survival.


Asunto(s)
Carcinoma Hepatocelular/complicaciones , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/terapia , Vena Porta , Trombosis de la Vena/etiología , Trombosis de la Vena/terapia , Proteína ADAM17/administración & dosificación , Quimioembolización Terapéutica , Terapia Combinada , Embolización Terapéutica , Humanos , Niacinamida/administración & dosificación , Niacinamida/análogos & derivados , Niacinamida/uso terapéutico , Compuestos de Fenilurea/administración & dosificación , Compuestos de Fenilurea/uso terapéutico , Radioterapia Conformacional , Sorafenib
7.
Artículo en Inglés | MEDLINE | ID: mdl-25744061

RESUMEN

T-cell exhaustion has become an important issue in chronic infection because exhausted antigen-specific T cells show impaired abilities to eradicate persistently infected pathogens and produce effector cytokines, such as IFN-γ and TNF-α. Thus, strategies to either restore endogenous exhausted T cell responses or provide functional T cells are needed for therapeutics of chronic infection. Despite promising developments using antibodies and cell immunotherapy, there have been no reported attempts to restore exhausted T cells using treatment with materials derived from natural resources. Here, using a mouse model of chronic infection with lymphocytic choriomeningitis virus (LCMV), we found that vinegar-processed flowers (flos) of Daphne genkwa (vp-genkwa), which was composed mainly of four index components, restored exhausted CD4(+) and CD8(+) T cells significantly, as corroborated by evidence that vp-genkwa treatment enhanced functional LCMV-specific CD4(+) and CD8(+) T cells, both quantitatively and qualitatively. Furthermore, pretreatment with vp-genkwa prevented the generation of exhausted LCMV-specific CD8(+) T cells. Such restorations of exhausted LCMV-specific CD4(+) and CD8(+) T cells by vp-genkwa were closely associated with reduced viral burden in sera and tissues. More interestingly, vp-genkwa treatment induced down-regulation of negative molecules, such as PD-1 and Tim-3, in exhausted CD4(+) and CD8(+) T cells with more apparent down-regulation of Tim-3, suggesting that Tim-3 molecule may be a major target in restoring exhausted T cell responses. Collectively, these results provide valuable new insights into the use of vp-genkwa to develop a therapeutic strategy for chronic human diseases, such as hepatitis B and C virus, human immunodeficiency virus, and cancers.


Asunto(s)
Infecciones por Arenaviridae/inmunología , Infecciones por Arenaviridae/terapia , Linfocitos T CD4-Positivos/inmunología , Daphne , Fitoterapia , Preparaciones de Plantas/uso terapéutico , Carga Viral/efectos de los fármacos , Ácido Acético , Animales , Linfocitos T CD8-positivos/inmunología , Enfermedad Crónica/tratamiento farmacológico , Enfermedad Crónica/prevención & control , Modelos Animales de Enfermedad , Regulación hacia Abajo , Flores , Receptor 2 Celular del Virus de la Hepatitis A , Virus de la Coriomeningitis Linfocítica , Ratones , Ratones Endogámicos C57BL , Receptores Virales/metabolismo , Factor de Necrosis Tumoral alfa/inmunología
8.
Biomed Pharmacother ; 69: 367-73, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25661384

RESUMEN

Pathologic angiogenesis induced by hypoxia is a hallmark of ischemic retinopathy including diabetic retinopathy and retinopathy of prematurity. These 2 diseases affect substantial number of working population and preterm babies, respectively, resulting in visual deterioration. It is essential for novel therapeutics for ischemic retinopathy to demonstrate the potency in reducing pathologic angiogenesis and the safety without definite toxicity on the retina and the whole body. In this review, we suggest a novel platform of integrative studies from in vitro to in vivo experiments on angiogenesis and toxicity with the aim of accelerating and facilitating the development of novel therapeutic agents for ischemic retinopathy. Robust in vitro and in vivo studies with bridging microfluidic and ex vivo systems help researchers to evaluate the efficacy and anticipate the toxicity of candidate drugs. We hope that novel therapeutic approach based on this platform will be developed in near future and reduce the incidence of vision loss from ischemic retinopathy.


Asunto(s)
Descubrimiento de Drogas , Evaluación Preclínica de Medicamentos , Isquemia/tratamiento farmacológico , Enfermedades de la Retina/tratamiento farmacológico , Animales , Modelos Animales de Enfermedad , Humanos , Neovascularización Patológica/tratamiento farmacológico
9.
AJR Am J Roentgenol ; 203(5): 1127-31, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25341154

RESUMEN

OBJECTIVE: The objective of our study was to compare the effectiveness of radiofrequency ablation (RFA) for viable hepatocellular carcinoma (HCC) including areas of retained oil after transarterial chemoembolization (TACE) versus RFA treatment of viable HCC alone for ablation coverage. MATERIALS AND METHODS: Eighty-five patients with 88 viable HCCs underwent RFA of residual viable HCCs around retained iodized oil after TACE. RFA of both viable HCC and retained iodized oil was performed on 47 viable tumors (group A), and RFA of viable HCC only was used to treat the remaining 41 viable tumors (group B). RESULTS: After initial RFA, the endpoint of ablation was successfully achieved for 45 of 47 tumors in group A and for all 41 tumors in group B. Two residual viable tumors in group A were successfully treated by additional RFA. Major complications occurred after initial RFA treatment of one tumor each in group A (pleural effusion) and group B (collateral damage). During follow-up (mean, 37.1 months; range, 5-116.5 months), local tumor progression of treated lesions was found in 28% in group A and 59% in group B. The respective 1-, 3-, 5-, and 7-year local tumor progression rates were significantly lower in group A (15%, 32%, 32%, and 32%) than in group B (43%, 71%, 81%, and 81%) (p = 0.001). CONCLUSION: In treatment of viable tumors after TACE in patients with HCC, RFA of both viable tumor and retained iodized oil may reduce rates of local tumor progression compared with RFA of viable tumor only.


Asunto(s)
Carcinoma Hepatocelular/terapia , Ablación por Catéter/métodos , Quimioembolización Terapéutica/métodos , Aceite Yodado/uso terapéutico , Neoplasias Hepáticas/terapia , Antineoplásicos/uso terapéutico , Carcinoma Hepatocelular/diagnóstico por imagen , Terapia Combinada/métodos , Femenino , Hemostáticos/uso terapéutico , Humanos , Neoplasias Hepáticas/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Radiografía , Resultado del Tratamiento
10.
Am J Gastroenterol ; 109(8): 1234-40, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24935276

RESUMEN

OBJECTIVES: To compare the effectiveness of transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) for treating small (≤2 cm) hepatocellular carcinomas (HCCs). METHODS: This retrospective study consisted of 287 patients (mean age, 57.1 years; age range, 29-84 years; 221 men, 66 women; 73.5% with HBV; 100% with liver cirrhosis) with Barcelona Clinic Liver Cancer very early-stage HCC (≤2 cm single HCC) who were initially treated with TACE (n=122) or RFA (n=165). The primary study end point was overall patient survival. Secondary study end points were time to progression and tumor response. RESULTS: The RFA and TACE groups were well balanced in terms of baseline variables. The two groups did not differ significantly in overall survival (P=0.079) or major complication (P>0.999) rates. The respective cumulative survival rates at 1, 3, 5, and 8 years were 97.6, 86.7, 74.5, and 60.0% for RFA and 93.4, 75.4, 63.1, and 51.1% for TACE. Their objective tumor regression (complete or partial response) rates were 100% (165/165) and 95.9% (117/122), respectively (P=0.013). The median times to progression for RFA and TACE were 27.0±3.8 (95% confidence intervals (CIs): 19.6-34.4) and 18.0±2.9 (95% CIs: 12.2-23.8) months, respectively. RFA yielded a significantly longer time to progression (P=0.034). CONCLUSIONS: TACE may be a viable alternative treatment for ≤2 cm HCCs when RFA is not feasible.


Asunto(s)
Carcinoma Hepatocelular/terapia , Ablación por Catéter/métodos , Quimioembolización Terapéutica/métodos , Neoplasias Hepáticas/terapia , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/virología , Progresión de la Enfermedad , Aceite Etiodizado/uso terapéutico , Femenino , Esponja de Gelatina Absorbible/uso terapéutico , Hemostáticos/uso terapéutico , Hepatitis B Crónica/complicaciones , Humanos , Cirrosis Hepática/complicaciones , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/virología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del Tratamiento , Carga Tumoral
11.
Phytother Res ; 28(3): 387-94, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23640957

RESUMEN

Although beta-sitosterol has been well known to have anti-tumor activity in liver, lung, colon, stomach, breast and prostate cancers via cell cycle arrest and apoptosis induction, the underlying mechanism of anti-cancer effect of beta-sitosterol in multiple myeloma cells was never elucidated until now. Thus, in the present study, the role of reactive oxygen species (ROS) in association with AMP-activated protein kinase (AMPK) and c-Jun N-terminal kinase (JNK) pathways was demonstrated in beta-sitosterol-treated multiple myeloma U266 cells. Beta-sitosterol exerted cytotoxicity, increased sub-G1 apoptotic population and activated caspase-9 and -3, cleaved poly (ADP-ribose) polymerase (PARP) followed by decrease in mitochondrial potential in U266 cells. Beta-sitosterol promoted ROS production, activated AMPK, acetyl-CoA carboxylase (ACC) and JNK in U266 cells. Also, beta-sitosterol attenuated the phosphorylation of AKT, mammalian target of rapamycin and S6K, and the expression of cyclooxygenase-2 and VEGF in U266 cells. Conversely, AMPK inhibitor compound C and JNK inhibitor SP600125 suppressed apoptosis induced by beta-sitosterol in U266 cells. Furthermore, ROS scavenger N-acetyl L-cysteine attenuated beta-sitosterol-mediated sub-G1 accumulation, PARP cleavage, JNK and AMPK activation in U266 cells. Overall, these findings for the first time suggest that ROS-mediated activation of cancer metabolism-related genes such as AMPK and JNK plays an important role in beta-sitosterol-induced apoptosis in U266 multiple myeloma cells.


Asunto(s)
Proteínas Quinasas Activadas por AMP/metabolismo , Apoptosis/efectos de los fármacos , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Mieloma Múltiple/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Sitoesteroles/farmacología , Acetil-CoA Carboxilasa/metabolismo , Acetilcisteína/farmacología , Antracenos/farmacología , Caspasa 3/metabolismo , Caspasa 9/metabolismo , Puntos de Control del Ciclo Celular , Línea Celular Tumoral , Ciclooxigenasa 2/metabolismo , Humanos , Sistema de Señalización de MAP Quinasas , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Fosforilación , Poli(ADP-Ribosa) Polimerasas/metabolismo
12.
Artículo en Inglés | MEDLINE | ID: mdl-23818927

RESUMEN

Background. Combination cancer therapy is one of the attractive approaches to overcome drug resistance of cancer cells. In the present study, we investigated the synergistic effect of decursin from Angelica gigas and doxorubicin on the induction of apoptosis in three human multiple myeloma cells. Methodology/Principal Findings. Combined treatment of decursin and doxorubicin significantly exerted significant cytotoxicity compared to doxorubicin or decursin in U266, RPMI8226, and MM.1S cells. Furthermore, the combination treatment enhanced the activation of caspase-9 and -3, the cleavage of PARP, and the sub G1 population compared to either drug alone in three multiple myeloma cells. In addition, the combined treatment downregulated the phosphorylation of mTOR and its downstream S6K1 and activated the phosphorylation of ERK in three multiple myeloma cells. Furthermore, the combined treatment reduced mitochondrial membrane potential, suppressed the phosphorylation of JAK2, STAT3, and Src, activated SHP-2, and attenuated the expression of cyclind-D1 and survivin in U266 cells. Conversely, tyrosine phosphatase inhibitor pervanadate reversed STAT3 inactivation and also PARP cleavage and caspase-3 activation induced by combined treatment of doxorubicin and decursin in U266 cells. Conclusions/Significance. Overall, the combination treatment of decursin and doxorubicin can enhance apoptotic activity via mTOR and/or STAT3 signaling pathway in multiple myeloma cells.

13.
Artículo en Inglés | MEDLINE | ID: mdl-23243457

RESUMEN

Though melatonin was known to regulate gap junctional intercellular communication (GJIC) in chick astrocytes and mouse hepatocytes, the underlying mechanism by melatonin was not elucidated in hydrogen peroxide- (H(2)O(2)-) treated HaCaT keratinocyte cells until now. In the current study, though melatonin at 2 mM and hydrogen peroxide (H(2)O(2)) at 300 µM showed weak cytotoxicity in HaCaT keratinocyte cells, melatonin significantly suppressed the formation of reactive oxygen species (ROS) in H(2)O(2)-treated HaCaT cells compared to untreated controls. Also, the scrape-loading dye-transfer assay revealed that melatonin enhances the intercellular communication by introducing Lucifer Yellow into H(2)O(2)-treated cells. Furthermore, melatonin significantly enhanced the expression of connexin 26 (Cx26) and connexin 43 (Cx43) at mRNA and protein levels, but not that of connexin 30 (Cx30) in H(2)O(2)-treated HaCaT cells. Of note, melatonin attenuated the phosphorylation of extracellular signal-regulated protein kinases (ERKs) more than p38 MAPK or JNK in H(2)O(2)-treated HaCaT cells. Conversely, ERK inhibitor PD98059 promoted the intercellular communication in H(2)O(2)-treated HaCaT cells. Furthermore, combined treatment of melatonin (200 µM) and vitamin C (10 µg/mL) significantly reduced ROS production in H(2)O(2)-treated HaCaT cells. Overall, these findings support the scientific evidences that melatonin facilitates gap junctional intercellular communication in H(2)O(2)-treated HaCaT keratinocyte cells via inhibition of connexin 26/43 and ERK as a potent chemopreventive agent.

14.
Acta Radiol ; 53(5): 545-50, 2012 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-22547388

RESUMEN

BACKGROUND: The decreased portal blood flow and the potential decrease in arterial nutrient hepatic blood flow after creation of a transjugular intrahepatic portosystemic shunt (TIPS) makes the treatment of hepatocellular carcinoma (HCC) challenging. PURPOSE: To evaluate the safety and efficacy of transarterial chemoembolization (TACE) after TIPS in patients with HCC. MATERIAL AND METHODS: From 1998 to 2009, 20 patients underwent selective (segmental or subsegmental) TACE for HCC after TIPS. Among 20 patients, seven patients had undergone one to three sessions of TACE for HCC before TIPS creation. TACE was performed using a mixture of iodized oil and cisplatin, and absorbable gelatin sponge particles. Tumor response, complications, and patient survival were evaluated after TACE. RESULTS: After TACE, 14 of the 20 (70%) patients showed a tumor response, with only one (5%) experiencing a TACE-related major complication, spontaneous bacterial peritonitis. None of the patients who underwent TACE after TIPS died within 30 days. During the follow-up period (range 2.2-107 months; mean 32.6 months), 18 patients died and two remained alive. The median survival period after TACE was 23 months. Multivariate Cox regression analysis showed that tumor stage was the only independent prognostic factor for patient survival (P = 0.049). CONCLUSION: Selective TACE may be safe and effective for the palliative treatment of HCC in patients with TIPS. Late tumor stage ( ≥III) was poor prognostic factor for determining the patient survival period after post-TIPS TACE.


Asunto(s)
Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica/métodos , Neoplasias Hepáticas/terapia , Derivación Portosistémica Intrahepática Transyugular , Carcinoma Hepatocelular/patología , Cisplatino/administración & dosificación , Aceite Etiodizado/administración & dosificación , Femenino , Esponja de Gelatina Absorbible/administración & dosificación , Humanos , Pruebas de Función Hepática , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Modelos de Riesgos Proporcionales , Radiografía Intervencional , Stents , Tasa de Supervivencia , Tomografía Computarizada por Rayos X , Resultado del Tratamiento
15.
Fish Physiol Biochem ; 38(5): 1331-42, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22367486

RESUMEN

Metallothionein (MT) has been used extensively as a potential molecular biomarker to detect heavy metal pollution in aquatic organisms. In order to investigate the modulation effect of heavy metals and to establish suitable biomarkers for the monitoring of heavy metal pollution, Pelteobagrus fulvidraco metallothionein gene was characterized as the first report in the family Bagridae. Pf-MT transcript was detected at high levels in liver, gonad, kidney, and brain compared to other tissues. A time-course study in response to waterborne Cd (5 ppm) revealed that a significant increase in the Pf-MT transcript abundance was observed at 6 h in gill, kidney, and liver. These elevated levels were kept for 96 h, implying that Cd distributed fast into different organs and was involved in the tissue-specific induction pattern. We observed a significant Pf-MT transcript increase in liver tissues at 48 h, followed by gill at 12 h and intestine at 48 h after Cd exposure. This indicates hepatic MT expression as a potential biomarker of acute Cd exposure in this species. Cd-binding ability of recombinant Pf-MT protein provided evidence for sensitivity to Cd and other heavy metal exposure. In the case of Zn exposure (1 ppm), a significant increase in Pf-MT transcript abundance was observed at 12 h, and a peak induction level reaching sixfold at 24 h was kept until 48 h, showing similar transcript induction patterns with Cd. A high level of Pf-MT mRNA after exposure to Cu (1 ppm) was observed at 12 h that gradually increased until 96 h with a 12-fold induction, revealing a long-lasting induction and somewhat dissimilar pattern compared to other metals in liver. Our results demonstrate that Pf-MT can be induced by heavy metals in a tissue-specific and metal-specific manner and plays probably a conserved role in metal detoxification. This study provides new information on P. fulvidraco metallothionein gene for the use of biomarkers indicating metal pollution in fish.


Asunto(s)
Bagres/fisiología , Clonación Molecular , ADN Complementario/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Metalotioneína/metabolismo , Metales Pesados/toxicidad , Animales , Cadmio/toxicidad , Cobre/toxicidad , ADN Complementario/genética , Metalotioneína/genética , Contaminantes Químicos del Agua/toxicidad , Zinc/toxicidad
16.
Radiology ; 255(1): 270-7, 2010 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-20308463

RESUMEN

PURPOSE: To evaluate the clinical effectiveness of transcatheter arterial chemoembolization (TACE) performed in patients with nonresectable combined hepatocellular carcinoma (HCC) and cholangiocarcinoma and analyze the prognostic factors of patient survival after TACE. MATERIALS AND METHODS: Each patient provided informed consent for TACE. The institutional review board approved the current study and waived the requirement for patient consent for this retrospective review. From 1997 to 2009, 50 patients underwent TACE for nonresectable combined HCC-cholangiocarcinoma. Tumor response was evaluated on the basis of findings on computed tomographic (CT) scans obtained a mean of 30.7 days after TACE. The survival rate and the prognostic factors of patient survival were evaluated. RESULTS: After TACE, 35 (70%) of the 50 patients were classified as responders--having either a partial response or stable disease with successful (>50%) tumor necrosis--and 15 (30%) were classified as nonresponders. Tumor response was significantly related to tumor vascularity: One (10%) of the 10 patients with hypovascular tumors and 34 (85%) of the 40 patients with hypervascular tumors were responders (P < .001). The median patient survival period was 12.3 months. Results of multivariable Cox regression analyses confirmed that tumor size (hazard ratio [HR], 2.49; P = .028), tumor vascularity (HR, 4.19; P = .001), Child-Pugh class (HR, 4.3; P = .001), and portal vein invasion (HR, 6.45; P < .001) were the independent factors associated with patient survival duration after TACE. CONCLUSION: TACE is safe and may be effective for prolonging the survival of patients with nonresectable combined HCC-cholangiocarcinoma, as compared with the historically reported survivals of these patients. Tumor vascularity is highly associated with tumor response. The patient survival period after TACE for combined HCC-cholangiocarcinoma is significantly dependent on tumor size, tumor vascularity, Child-Pugh class, and presence or absence of portal vein invasion.


Asunto(s)
Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica/métodos , Colangiocarcinoma/terapia , Neoplasias Hepáticas/terapia , Adulto , Anciano , Carcinoma Hepatocelular/diagnóstico por imagen , Colangiocarcinoma/diagnóstico por imagen , Cisplatino/administración & dosificación , Medios de Contraste , Femenino , Esponja de Gelatina Absorbible/administración & dosificación , Humanos , Aceite Yodado/administración & dosificación , Yohexol/análogos & derivados , Neoplasias Hepáticas/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Tasa de Supervivencia , Tomografía Computarizada por Rayos X , Resultado del Tratamiento
17.
AJR Am J Roentgenol ; 193(5): W446-51, 2009 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-19843726

RESUMEN

OBJECTIVE: Portal vein embolization (PVE) has been widely used to facilitate major liver resection; however, curative surgery even after PVE may not be possible mainly because of inadequate hypertrophy of remnant liver or disease progression. For these patients, transcatheter arterial chemoembolization (TACE) is the next therapeutic option. We evaluated the safety and efficacy of TACE after PVE in 25 patients with hepatocellular carcinoma (HCC). CONCLUSION: TACE using a single chemotherapeutic agent can be performed safely and effectively in HCC patients who previously underwent PVE. TACE after PVE allowed two of the patients to be downstaged so they could undergo surgical resection.


Asunto(s)
Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica/métodos , Arteria Hepática , Neoplasias Hepáticas/terapia , Adulto , Anciano , Medios de Contraste , Femenino , Humanos , Aceite Yodado/administración & dosificación , Pruebas de Función Hepática , Masculino , Persona de Mediana Edad , Vena Porta , Radiografía Intervencional , Estudios Retrospectivos , Estadísticas no Paramétricas , Tasa de Supervivencia , Tomografía Computarizada por Rayos X , Resultado del Tratamiento
18.
J Vasc Interv Radiol ; 16(1): 75-80, 2005 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-15640413

RESUMEN

PURPOSE: To evaluate the therapeutic efficacy and complications of fluoroscopically guided double balloon dilation for treatment of colorectal anastomotic strictures. MATERIALS AND METHODS: Under fluoroscopic guidance, 17 patients with colorectal anastomotic strictures underwent transanal double balloon dilation. Thirteen of 17 strictures were the consequence of surgery for malignant disease and the other four were secondary to surgery for benign disease. Sixteen of 17 patients had difficult or frequent defecation caused by partial obstruction. In the remaining one asymptomatic patient, the stricture was detected by endoscopy and barium enema after total proctocolectomy and a temporary ileostomy for ulcerative colitis. The therapeutic efficacy and complications were evaluated during the follow-up. RESULTS: Seventeen patients underwent double balloon dilation in a single session. The diameter of the first balloon was 20 mm and the second balloon's diameter was 10, 15, or 20 mm. Technical success was achieved in all 17 patients. After balloon dilation, complete (n = 12, 71%) or incomplete (n = 5, 29%) improvement of symptoms was achieved in all patients. Major complications such as perforation or severe hemorrhage did not occur. During the mean follow-up period of 23 months (range, 1-62 months), one patient (6%) developed a recurrent stricture and required a second session of double balloon dilation 6 months after initial balloon dilation. CONCLUSION: Fluoroscopically guided double balloon dilation is an effective and safe method for the treatment of colorectal anastomotic strictures.


Asunto(s)
Anastomosis Quirúrgica/efectos adversos , Cateterismo/métodos , Obstrucción Intestinal/terapia , Adolescente , Adulto , Anciano , Enfermedades del Colon/cirugía , Femenino , Fluoroscopía , Humanos , Obstrucción Intestinal/etiología , Masculino , Persona de Mediana Edad , Enfermedades del Recto/cirugía , Estudios Retrospectivos , Resultado del Tratamiento
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