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BACKGROUND/AIMS: Postoperative abdominal fluid collection (PAFC) is a frequent complication of pancreatobiliary cancer surgery. The effects of the existence and duration of PAFC are not well known. This study aimed to assess the effects of PAFC on patient prognosis after surgery for pancreatobiliary adenocarcinoma and the association of longstanding PAFC with the recurrence of pancreatic cancer. METHODS: We retrospectively analyzed the data of 194 consecutive patients with pancreatobiliary adenocarcinoma who underwent curative operations from August 2005 to December 2019. The presence of PAFC was assessed using computed tomography within a week of surgery; PAFC lasting > 4 weeks was defined as longstanding PAFC. RESULTS: Among 194 patients, PAFC occurred in 165 (85.1%), and 74 of these had longstanding PAFC. The recurrence rate of pancreatobiliary adenocarcinoma was significantly higher in patients with longstanding PAFC than in patients with non-longstanding PAFC (p = 0.025). Recurrence was also significantly associated with high T stage (T3, T4; p = 0.040), lymph node involvement (p < 0.001), perineural invasion (p < 0.006), and non-receipt of adjuvant chemotherapy (p = 0.025). Longstanding PAFC was significantly associated with the recurrence of pancreatic adenocarcinoma (p = 0.016). However, cancer-specific survival was related to neither the presence nor the duration of PAFC. CONCLUSION: The presence of longstanding PAFC was associated with the recurrence of pancreatic adenocarcinoma. However, a larger prospective study is necessary to confirm the findings.
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Adenocarcinoma , Neoplasias Pancreáticas , Adenocarcinoma/cirurgia , Humanos , Recidiva Local de Neoplasia , Neoplasias Pancreáticas/cirurgia , Estudos Prospectivos , Estudos RetrospectivosRESUMO
BACKGROUND: Antiviral therapy with or without hepatitis B immune globulin (HBIG) is a common strategy for the prevention of hepatitis B virus (HBV) reinfection. But there is no consensus on management protocols, and long-term data are relatively rare on recurrence of HBV infection after liver transplantation using a nucleoside analogue and HBIG prophylaxis. METHODS: We performed 56 liver transplants since June 2006. Among them, 32 liver recipients had liver cirrhosis associated with HBV, 9 with hepatocellular carcinoma (HCC), and 23 without HCC. Three operative mortalities, 3 deaths within 1 year related to infection, and 1 follow-up loss less than 1 year were excluded from analysis. We analyzed 25 liver transplants retrospectively. We prevented HBV reinfection with entecavir or tenofovir lifelong with 7 days of daily intravenous HBIG, 10,000 units, including operative day, and then once a week for the next 3 weeks, and then once a month for 1 year. Afterward, 4000 or 6000 units every 2 or 3 months were given to maintain patients' serum hepatitis B antibody titer >200 mIU/mL. RESULTS: Mean follow-up period for HBV reinfection was 120.3 months. No patients have had reinfection. CONCLUSIONS: Lifelong HBIG and nucleoside is an excellent prevention strategy for HBV reinfection after liver transplant.
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Hepatite B/patologia , Transplante de Fígado , Adulto , Antivirais/uso terapêutico , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/cirurgia , Esquema de Medicação , Feminino , Guanina/análogos & derivados , Guanina/uso terapêutico , Hepatite B/complicações , Hepatite B/tratamento farmacológico , Hepatite B/prevenção & controle , Anticorpos Anti-Hepatite B/sangue , Vírus da Hepatite B/fisiologia , Humanos , Imunoglobulinas/uso terapêutico , Cirrose Hepática/complicações , Cirrose Hepática/cirurgia , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Tenofovir/uso terapêuticoRESUMO
We previously demonstrated that anthocyanins from the fruits of Vitis coignetiae Pulliat (AIMs) induced the apoptosis of hepatocellular carcinoma cells. However, many researchers argued that the concentrations of AIMs were too high for in vivo experiments. Therefore, we performed in vitro at lower concentrations and in vivo experiments for the anti-cancer effects of AIMs. AIMs inhibited the cell proliferation of Hep3B cells in a dose-dependent manner with a maximum concentration of 100 µg/mL. AIMs also inhibited the invasion and migration at 100 µg/mL concentration with or without the presence of TNF-α. To establish the relevance between the in vitro and in vivo results, we validated their effects in a Xenograft model of Hep3B human hepatocellular carcinoma cells. In the in vivo test, AIMs inhibited the tumorigenicity of Hep3B cells in the xenograft mouse model without showing any clinical signs of toxicity or any changes in the body weight of mice. AIMs inhibited the activation NF-κB and suppressed the NF-κB-regulated proteins, intra-tumoral microvessel density (IMVD) and the Ki67 activity of Hep3B xenograft tumors in athymic nude mice. In conclusion, this study indicates that AIMs have anti-cancer effects (inhibition of proliferation, invasion, and angiogenesis) on human hepatocellular carcinoma xenograft through the inhibition of NF-κB and its target protein.
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Antocianinas/farmacologia , Antineoplásicos Fitogênicos/farmacologia , NF-kappa B/metabolismo , Extratos Vegetais/farmacologia , Transdução de Sinais/efeitos dos fármacos , Vitis/química , Animais , Antocianinas/química , Antineoplásicos Fitogênicos/química , Biomarcadores , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Camundongos Nus , Extratos Vegetais/química , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Anthocyanins isolated from Vitis coignetiae Pulliat (Meoru in Korea) (AIMs) have various anti-cancer properties by inhibiting Akt and NF-κB which are involved in drug resistance. Cisplatin (CDDP) is one of the popular anti-cancer agents. Studies reported that MCF-7 human breast cancer cells have high resistance to CDDP compared to other breast cancer cell lines. In this study, we confirmed CDDP resistance of MCF-7 cells and tested whether AIMs can overcome CDDP resistance of MCF-7 cells. Cell viability assay revealed that MCF-7 cells were more resistant to CDDP treatment than MDA-MB-231 breast cancer cells exhibiting aggressive and high cancer stem cell phenotype. AIMs significantly augmented the efficacy of CDDP with synergistic effects on MCF-7 cells. Molecularly, Western blot analysis revealed that CDDP strongly increased Akt and moderately reduced p-NF-κB and p-IκB and that AIMs inhibited CDDP-induced Akt activation, and augmented CDDP-induced reduction of p-NF-κB and p-IκB in MCF-7 cells. In addition, AIMs significantly downregulated an anti-apoptotic protein, XIAP, and augmented PARP-1 cleavage in CDDP-treated MCF-7 cells. Moreover, under TNF-α treatment, AIMs augmented CDDP efficacy with inhibition of NF-κB activation on MCF-7 cells. In conclusion, AIMs enhanced CDDP sensitivity by inhibiting Akt and NF-κB activity of MCF-7 cells that show relative intrinsic CDDP resistance.
Assuntos
Antocianinas/farmacologia , Neoplasias da Mama/tratamento farmacológico , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos , NF-kappa B/metabolismo , Extratos Vegetais/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Vitis/química , Antineoplásicos/farmacologia , Apoptose , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Ciclo Celular , Movimento Celular , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , NF-kappa B/genética , Proteínas Proto-Oncogênicas c-akt/genética , Células Tumorais CultivadasRESUMO
PURPOSE: Many studies have concluded that cancer patients may have better outcomes when their surgery is performed in high-volume centers, especially when the procedure is pancreaticoduodenectomy (PD). However, some studies concluded that experienced surgeons or incorporation of expertise from high-volume centers may achieve satisfactory outcomes after PD in low-volume centers. METHODS: I retrospectively collected and analyzed the outcomes of PD for periampullary cancers treated with curative intent in my center. RESULTS: From August 2, 2005 to December 10, 2018, 160 pancreatic resections were done with curative intent in my center. The number of operations per year was 1 in 2005 and gradually increased to 21 in 2018. Thirty-day mortality was 0, and 90-day mortality was 1 (0.6%). Morbidity was found in 65 cases (40.6%). The median follow-up period was 23.2 months and 5-year survival rates were 28.5% for pancreas head cancer, 48.2% for distal CBD cancer, and 72.6% for AOV cancer. I divided patients into 2 groups by the number of annual operations, which is more than 21 per 2 years. The 2 groups showed no differences in terms of morbidity and mortality. CONCLUSION: A well-trained low-volume surgeon may perform PD safely at a well-equipped low-volume center.
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Evidence suggests that auranofin (AF) exhibits anticancer activity by inhibiting thioredoxin reductase (TrxR). Here, in this study, we have investigated the synergistic effects of AF and morin and their mechanism for the anticancer effects focusing on apoptosis in Hep3B human hepatocellular carcinoma cells. We assessed the anticancer activities by annexin V/PI double staining, caspase, and TrxR activity assay. Morin enhances the inhibitory effects on TrxR activity of AF as well as reducing cell viability. Annexin V/PI double staining revealed that morin/AF cotreatment induced apoptotic cell death. Morin enhances AF-induced mitochondrial membrane potential (ΔΨm) loss and cytochrome c release. Further, morin/AF cotreatment upregulated death receptor DR4/DR5, modulated Bcl-2 family members (upregulation of Bax and downregulation of Bcl-2), and activated caspase-3, -8, and -9. Morin also enhances AF-induced reactive oxygen species (ROS) generation. The anticancer effects results from caspase-dependent apoptosis, which was triggered via extrinsic pathway by upregulating TRAIL receptors (DR4/DR5) and enhanced via intrinsic pathway by modulating Bcl-2 and inhibitor of apoptosis protein family members. These are related to ROS generation. In conclusion, this study provides evidence that morin can enhance the anticancer activity of AF in Hep3B human hepatocellular carcinoma cells, indicating that its combination could be an alternative treatment strategy for the hepatocellular carcinoma.
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Auranofina/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Flavonoides/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/patologia , Caspases/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Citocromos c/metabolismo , Regulação para Baixo/efeitos dos fármacos , Humanos , Proteínas Inibidoras de Apoptose/metabolismo , Neoplasias Hepáticas/patologia , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Transdução de Sinais/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacosRESUMO
Tetraarsenic hexoxide (As4O6) has been used in Korean folk medicines for the treatment of cancer, however its anti-cancer mechanisms remain obscured. Here, this study investigated the anti-cancer effect of As4O6 on SW620 human colon cancer cells. As4O6 has showed a dose-dependent inhibition of SW620 cells proliferation. As4O6 significantly increased the sub-G1 and G2/M phase population, and Annexin V-positive cells in a dose-dependent manner. G2/M arrest was concomitant with augment of p21 and reduction in cyclin B1, cell division cycle 2 (cdc 2) expressions. Nuclear condensation, cleaved nuclei and poly (adenosine diphosphateribose) polymerase (PARP) activation were also observed in As4O6-treated SW620 cells. As4O6 induced depolarization of mitochondrial membrane potential (MMP, ΔΨm) but not reactive oxygen species (ROS) generation. Further, As4O6 increased death receptor 5 (DR5), not DR4 and suppressed the Bcell lymphoma2 (Bcl-2) and X-linked inhibitor of apoptosis protein (XIAP) family proteins. As4O6 increased the formation of AVOs (lysosomes and autophagolysosomes) and promoted the conversion of microtubule-associated protein 1A/1B-light chain 3 (LC3)-I to LC3-II in a dose- and time- dependent manner. Interestingly, a specific phosphoinositide 3-kinase (PI3K)/Akt inhibitor (LY294002) augmented the As4O6 induced cell death; whereas p38 mitogen-activated protein kinases (p38 MAPK) inhibitor (SB203580) abrogated the cell death. Thus, the present study provides the first evidence that As4O6 induced G2/M arrest, apoptosis and autophagic cell death through PI3K/Akt and p38 MAPK pathways alteration in SW620 cells.
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Apoptose/efeitos dos fármacos , Arsenicais/farmacologia , Autofagia/efeitos dos fármacos , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Óxidos/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Antineoplásicos/farmacologia , Trióxido de Arsênio , Western Blotting , Proteína Quinase CDC2 , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Ciclina D1/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Quinases Ciclina-Dependentes/metabolismo , Relação Dose-Resposta a Droga , Ativação Enzimática/efeitos dos fármacos , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Fatores de TempoRESUMO
PURPOSE: This study evaluated the benefits of adjuvant chemotherapy on elderly patients with advanced gastric cancer (AGC) using meta-analysis of well-designed randomized controlled clinical studies. MATERIALS AND METHODS: PubMed, Embase, and Cochrane were searched to retrieve clinical studies evaluating the benefits of adjuvant chemotherapy in the elderly with AGC. Hazards ratios (HRs) with 95% confidence intervals (CIs) were pooled across studies using a fixed-effects model. RESULTS: Two studies were included in this meta-analysis to estimate HR for the overall survival (OS), and relapse-free survival (RFS) between adjuvant chemotherapy and surgery in elderly and non-elderly patients. HR for OS in the elderly and non-elderly was 0.745 (95% CI, 0.552 to 1.006, p=0.055) and 0.636 (95% CI, 0.522 to 0.776; p < 0.001), respectively, which showed no heterogeneity regarding HR between the two groups (pinteraction=0.389). HR for RFS in the elderly and non-elderly was 0.613 (95% CI, 0.466 to 0.806; p < 0.001) and 0.633 (95% CI, 0.533 to 0.753; p < 0.001), respectively (pinteraction=0.846). CONCLUSION: Meta-analysis suggests that the benefit of adjuvant chemotherapy to the elderly is not big enough to reach statistical significance while the HR for OS is less than 1 (0.745) and no heterogeneity are observed regarding the HR between the elderly and non-elderly patients.
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Neoplasias Gástricas/tratamento farmacológico , Fatores Etários , Quimioterapia Adjuvante/efeitos adversos , Quimioterapia Adjuvante/métodos , Humanos , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Ensaios Clínicos Controlados Aleatórios como Assunto , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Resultado do TratamentoRESUMO
Genetic alterations of TERT and CTNNB1 have been documented in hepatocellular carcinoma. TERT promoter mutations are the earliest genetic events in the multistep process of hepatocarcinogenesis related to cirrhosis. However, analyses of TERT promoter and CTNNB1 mutations in hepatocellular carcinoma tumor samples have not been performed in the Korean population, where hepatitis B virus-related hepatocellular carcinoma is prevalent. In order to identify the role of TERT promoter and CTNNB1 mutations in the hepatocarcinogenesis and pathogenesis of recurrent hepatocellular carcinoma, we performed the sequence analyses in 140 hepatocellular nodules (including 107 hepatocellular carcinomas), and 8 pairs of matched primary and relapsed hepatocellular carcinomas. TERT promoter and CTNNB1 mutations were only observed in hepatocellular carcinomas but not in precursor lesions. Of 109 patients with hepatocellular carcinoma, 41 (39.0%) and 15 (14.6%) harbored TERT and CTNNB1 mutations, respectively. TERT promotermutations were significantly more frequent in hepatocellular carcinomas related to hepatitis C virus infection (5/6; 83.3%) compared to tumors of other etiologies (P = 0.001). In two cases, discordance in TERT promoter mutation status was observed between the primary and the corresponding recurrent hepatocellular carcinoma. The two patients with discordant cases had early relapses. In conclusion, we identified TERT promoter and CTNNB1 mutations as the most frequent somatic genetic alterations observed in hepatocellular carcinoma, indicating its pivotal role in hepatocarcinogenesis. Furthermore, we suggest the possibility of intratumoral genetic heterogeneity of TERT promoter mutations in hepatocellular carcinoma as indicated by the discordance in TERT promoter mutations between primary and corresponding recurrent hepatocellular carcinoma.
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Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Mutação , Regiões Promotoras Genéticas/genética , Telomerase/genética , beta Catenina/genética , Adulto , Idoso , Povo Asiático/genética , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/etnologia , Análise Mutacional de DNA/métodos , Feminino , Hepatite C/complicações , Humanos , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/etnologia , Masculino , Pessoa de Meia-Idade , República da CoreiaRESUMO
De novo hepatitis B infection in patients receiving liver transplants from hepatitis B core antibody-positive donors is well known, but the effective prevention strategy has not been well established. In our hospital, recipients receive hepatitis B immunoglobulin monotherapy if they are hepatitis B surface antigen negative at the time of transplant and are receiving a liver from a hepatitis B core antibody-positive donor. Since August 2006, we have had 4 patients who were naïve to hepatitis B virus and received a hepatitis B core antibody-positive graft. Two patients died of other causes, and 2 patients, who had liver transplant in October 2006 and October 2009, developed de novo hepatitis B. Both patients were tested annually for serum hepatitis B surface antigen as part of routine visit. Tests were negative; however, both patients recently became hepatitis B surface antigen positive. Other laboratory results, including liver function test, were unremarkable, except HBsAb titer was undetectable even though hepatitis B immunoglobulin monotherapy had been administrated 2 months previously in both patients. The patients had hepatitis B virus DNA levels of 3.07E+08 copies/mL and 1.51E+08 copies/mL. We suggest that additional prophylactic therapies above hepatitis B immunoglobulin monotherapy are needed for these recipients.
Assuntos
Carcinoma Hepatocelular/cirurgia , Anticorpos Anti-Hepatite B/sangue , Vírus da Hepatite B/imunologia , Hepatite B/transmissão , Imunoglobulinas/administração & dosagem , Neoplasias Hepáticas/cirurgia , Transplante de Fígado/efeitos adversos , Doadores de Tecidos , Biomarcadores/sangue , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/etiologia , DNA Viral/genética , Hepatite B/diagnóstico , Hepatite B/tratamento farmacológico , Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B/genética , Humanos , Cirrose Hepática Alcoólica/complicações , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/etiologia , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Resultado do Tratamento , Carga ViralRESUMO
AIM: We investigated the prognostic value of clinicopathological factors in patients with a distal bile duct adenocarcinoma after curative resection. PATIENTS AND METHODS: This retrospective study included 25 patients who underwent (18)F-fluorodeoxyglucose positron-emission tomography/computed tomography (FDG-PET/CT) before surgery. The maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured using FDG-PET/CT. FDG-PET/CT parameters and other clinicopathological factors were assessed to evaluate survival. RESULTS: Univariate survival analysis showed that high TLG, high MTV, and high SUVmax were significant prognostic predictors for poor overall survival. For progression-free survival, high TLG and large tumor size were significant predictors for a poor prognosis. After multivariate survival analysis, only high TLG was an independent prognostic predictor for poor overall survival (p=0.025). CONCLUSION: Preoperative assessment of TLG by FDG-PET/CT might be a useful prognostic predictor in patients with a distal bile duct adenocarcinoma after curative resection.
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Neoplasias dos Ductos Biliares/diagnóstico , Colangiocarcinoma/diagnóstico , Idoso , Neoplasias dos Ductos Biliares/metabolismo , Neoplasias dos Ductos Biliares/cirurgia , Colangiocarcinoma/metabolismo , Colangiocarcinoma/cirurgia , Feminino , Fluordesoxiglucose F18 , Glicólise , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Prognóstico , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Análise de Sobrevida , Tomografia Computadorizada por Raios X , Carga TumoralRESUMO
BACKGROUND: Cisplatin (cis-diaminedichloroplatinum, CDDP) is a widely used chemotherapeutic agent for the treatment of many cancers. However, initial resistance to CDDP is a serious problem in treating these cancers. Vitis coignetiae Pulliat (Meoru in Korea) have shown anti-nuclear factor kappa B and anti-epidermal growth factor receptor activities in cancer cells. METHODS: In this study, in order to seeking an approach to increase the anti-cancer effects of CDDP with natural products. Here, we investigated anthocyanins isolated from Vitis coignetiae Pulliat (anthocyanidins isolated from meoru, AIMs) can enhance anti-cancer effects of cisplatin (CDDP) in stomach cancer cells. The cell viability of SNU-1 and SNU-16 cells after treated with AIMs and CDDP were analyzed by MTT assay. The expressions of Akt and X-linked inhibitor of apoptosis protein (XIAP) proteins were examined by western blot in AIMs- and CDDP-treated cells. RESULTS: We found that AIMs enhanced anticancer effects of CDDP, which activity was additive but not synergistic. AIMs suppressed Akt activity of the cancer cells activated by CDDP. AIMs also suppressed in XIAP an anti-apoptotic protein. CONCLUSIONS: This study suggests that the anthocyanins isolated from fruits of Vitis coignetiae Pulliat enhanced anti-cancer effects of CDDP by inhibiting Akt activity activated by CDDP.
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Tetraarsenic hexoxide (As4O6) has been used in Korean traditional medicine for the treatment of cancer since the late 1980's, and arsenic trioxide (As2O3) is currently used as a chemotherapeutic agent. Previous studies suggest that the As4O6-induced cell death pathway is different from that of As2O3 and its mechanism of anticancer activity remains unclear. Nuclear factor (NF)-κB is a well-known transcription factor involved in cell proliferation, invasion and metastasis. Hence, in the present study, we investigated the effects of As4O6 on NF-κB activity and NF-κB-regulated gene expression in vitro and in vivo. The cytotoxicity assay revealed that As4O6 inhibited the growth of SW620 cells in a dose-dependent manner, and the half maximal inhibitory concentration (IC50) was ~1 µM after a 48 h treatment. As4O6 suppressed NF-κB activation and suppressed inhibitory κBα (IκBα) phosphorylation stimulated by tumor necrosis factor (TNF). As4O6 also suppressed downstream NF-κB-regulated proteins involved in cancer anti-apoptosis, proliferation, invasion and metastasis. In addition, As4O6 marginally suppressed tumor growth and the anti-NF-κB activity was confirmed using an in vivo xenograft mouse model in which animals were injected with SW620 cells. The present study provides evidence that As4O6 has anticancer properties through suppression of NF-κB activity and NF-κB-mediated cellular responses.
Assuntos
Antineoplásicos/administração & dosagem , Arsenicais/administração & dosagem , Neoplasias do Colo/tratamento farmacológico , NF-kappa B/biossíntese , Óxidos/administração & dosagem , Animais , Apoptose/efeitos dos fármacos , Trióxido de Arsênio , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Regulação Neoplásica da Expressão Gênica , Humanos , Quinase I-kappa B/biossíntese , Camundongos , NF-kappa B/antagonistas & inibidores , NF-kappa B/genética , Fosforilação , Fator de Necrose Tumoral alfa/biossínteseRESUMO
BACKGROUND: The extract of Allium cepa Linn is commonly used as adjuvant food for cancer therapy. We assumed that it includes a potential source of anti-cancer properties. METHODS: We investigated anti-cancer effects of polyphenols extracted from lyophilized A. cepa Linn (PEAL) in AGS human cancer cells. RESULTS: PEAL inhibited cell growth in a dose-dependent manner. It was related to caspase-dependent apoptosis. We confirmed this finding with annexin V staining. PEAL up-regulated p53 expression, and subsequent Bax induction, down regulated Bcl-2 protein, anti-apoptotic protein. In addition, PEAL suppressed Akt activity and PEAL-induced apoptosis were significantly accentuated with Akt inhibitor (LY294002). CONCLUSIONS: Our data suggested that PEAL induce caspase-dependent apoptosis through mitochondrial pathway by up-regulating p53 protein, and subsequent Bax protein as well as by modulating Bcl-2 protein, and that PEAL induces caspase-dependent apoptosis at least in part through the inhibition of phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. This study provides evidence that PEAL might be useful for the treatment of cancer.
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Intraperitoneal bleeding after radiofrequency ablation (RFA) is the most common major vascular complication due to direct needle injury to a vessel or liver capsule. However, intraperitoneal bleeding as a result of a delayed hepatic rupture after RFA for liver tumors is an extremely rare complication. The present report describes a case of intraperitoneal hemorrhage caused by delayed hepatic rupture resulting from arterioportal fistula after RFA for hepatic metastasis from colorectal cancer and successful management using transcatheter embolization.
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Arsenic hexoxide (As4O6) has been used in Korean folk remedy for the treatment of cancer since the late 1980s. Evidence suggests that the anticancer effects of As4O6 are different from those of As2O3. Tumor necrosis factor-α (TNF-α) is generally increased in advanced cancer and is closely related to cancer progression, although it has cancer-killing effects. The reason is that TNF-α activates nuclear factor-κB (NF-κB) that is involved in cell proliferation, invasion, drug resistance and metastasis. In the present study, we investigated the effects of As4O6 on NF-κB activity, NF-κB-mediated cellular responses, and NF-κB-regulated gene expressions involved in metastasis at the concentrations of As4O6 where no cytotoxicity was observed. As4O6 suppressed NF-κB activation in both TNF-α-treated and control cells, and also suppressed IκB phosphorylation in a time-dependent manner, suggesting the suppression of NF-κB results, in part, from the inhibition of IκB degradation. We also confirmed the anti-NF-κB activity of As4O6 with synergism with TNF-α by augmenting caspase-8 activation. As4O6 also suppressed NF-κB activation induced by TNF-α, and some of the downstream NF-κB-regulated proteins involved in cancer proliferation, anti-apoptosis and metastasis. In conclusion, the present study demonstrated that As4O6 has anticancer properties by inhibiting NF-κB activation and NF-κB-regulated proteins at least in part through the inhibition of IκB phosphorylation, especially in the conditions of advanced cancer where TNF-α is highly secreted.
Assuntos
Arsenicais/farmacologia , Neoplasias da Mama/tratamento farmacológico , Óxidos/farmacologia , Fator de Transcrição RelA/antagonistas & inibidores , Fator de Necrose Tumoral alfa/metabolismo , Apoptose/efeitos dos fármacos , Arsênio/farmacologia , Caspase 8/biossíntese , Linhagem Celular Tumoral , Proliferação de Células , Resistencia a Medicamentos Antineoplásicos , Ativação Enzimática/efeitos dos fármacos , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Quinase I-kappa B/metabolismo , Células MCF-7 , Invasividade Neoplásica , Metástase Neoplásica , Fosforilação/efeitos dos fármacosRESUMO
BACKGROUND: Percutaneous ablation of incompetent perforators has been introduced as a safe and efficacious alternative. OBJECTIVE: To compare two methods of treating incompetent thigh perforator and great saphenous veins (GSV). MATERIALS AND METHODS: Patients with varicose veins of CEAP C2 and C3 with incompetent perforating veins (IPVs) in the thigh without evidence of saphenofemoral reflux and with obvious venous reflux from IPVs into the GSV distal to IPVs were included. Endovenous laser ablation was done using two methods (IPV ablation (IPVA) versus GSV ablation: GSVA). Their technical success rate, clinical success rate, and complications were compared at 1 week, and 1, 3, 6, and 12 months. RESULTS: Sixty-nine consecutive patients were randomized to IPVA (n = 34) or GSVA (n = 35). Technical success was significantly lower with IPVA than GSVA (p = .002). Clinical success, defined as continued closure of treated veins, was similar with IPVA and GSVA (96.1% vs 100% at 1 week, 100% vs 97.1% at 1 month, and 100% for both at 3, 6, and 12 months, respectively). CONCLUSION: IPVA has clinical results and complications similar to those of GSVA in individuals with C2 and C3 chronic venous disease with IPVs in the thigh combined with incompetent GSV, but its higher technical failure rate makes it difficult to choose it as the primary treatment method.
Assuntos
Procedimentos Endovasculares/métodos , Terapia a Laser , Veia Safena/cirurgia , Coxa da Perna/irrigação sanguínea , Varizes/cirurgia , Idoso , Estudos de Viabilidade , Veia Femoral , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
OBJECTIVE: We wanted to evaluate the effectiveness of endovenous ablation of the incompetent vein of Giacomini using a 980-nm diode laser. MATERIALS AND METHODS: A total of 18 patients (18 limbs, 4%) had the incompetent vein of Giacomini. Retrograde reflux originating from the great saphenous vein was noted in sixteen limbs and paradoxical diastolic anterograde reflux from the saphenopopliteal junction was observed in two limbs. After tumescent anesthesia, laser ablation using a 980-nm wavelength laser fiber was performed under ultrasound and/or fluoroscopic guidance. Patients were evaluated clinically and with duplex ultrasound at one week and at one, three, six and twelve months after laser ablation for the technical and clinical success. RESULTS: In the 18 limbs, the technical success rate was 100%. Continued closure of the vein of Giacomini was seen in 18 of 18 limbs after one month, in 12 of 12 limbs after three and six months and in six of six limbs after twelve months. No recanalization of the vein and no major complications occurred. CONCLUSION: Endovenous laser ablation with a 980-nm wavelength is an effective and safe procedure for treating an incompetent vein of Giacomini.
Assuntos
Terapia a Laser/métodos , Perna (Membro)/irrigação sanguínea , Veia Safena/cirurgia , Insuficiência Venosa/cirurgia , Adulto , Feminino , Fluoroscopia , Humanos , Lasers Semicondutores , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
BACKGROUND: Many risk factors affect survival after liver resection for hepatocellular carcinoma (HCC), but these lack specificity for the prognosis. Studies of gene expression profiles successfully predicted the survival of HCC. To date, few studies have focused on HBV-associated HCC. Therefore, we investigated the genes involved in tumor prognosis in patients with HBV-associated HCC. MATERIALS AND METHODS: We analyzed clinical data and microarray test results in 51 patients who underwent liver resection for HBV-associated HCC between August 1998 and December 2002. We used Kaplan-Meier plots to analyze survival rates and some well-known clinical staging systems. In addition, we performed microarray survival analysis using Cox univariate regression. Then, we devised a scoring system that adds the survival-associated gene expression signature to one or two independent clinical risk factors for survival. RESULTS: The mean follow-up period was 61.4 mo. Thirty-six patients had recurrence during this period, and 22 died. The 5-y survival rate was 58.0%. Multivariate analysis showed that tumor size was an independent risk factor for survival. We identified 194 spots on the microarray in survival analysis. These genes were clustered into two groups and showed a statistically significant difference in the survival rates. In the clinical analysis, the CLIP and Okuda staging systems showed statistically significant relationships. When we added the survival-associated gene expression signature to tumor size, our new method showed a more statistically significant relationship between stage and survival. CONCLUSIONS: We propose that adding the results of microarray survival analysis to the staging system predicts survival more precisely.
Assuntos
Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/mortalidade , Perfilação da Expressão Gênica , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/mortalidade , Análise de Sequência com Séries de Oligonucleotídeos , Adulto , Idoso , Carcinoma Hepatocelular/cirurgia , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Fatores de RiscoRESUMO
A 53-year-old woman with liver cirrhosis and hepatocellular carcinoma underwent living donor liver transplantation. After transplantation, her hemoglobin and hematocrit levels decreased to 6.3 g/dl and 18.5%, respectively, during the course of 3 days. A contrast-enhanced abdominal computed axial tomography (CAT) scan showed a hemoperitoneum in the right perihepatic space with no evidence of abdominal wall hematoma or pseudoaneurysm formation. An angiogram of the deep circumflex iliac artery (DCIA) showed extravasation of contrast media along the surgical drain, which had been inserted during the transplantation procedure. Transcatheter embolization of the branches of the DCIA was successfully performed using N-butyl cyanoacrylate.