RESUMEN
Long non-coding RNAs (lncRNAs) are reported to play a significant role in various malignant tumors, yet their potential functions in gastric cancer are not clear. In this study, we found a novel lncRNA, named TONSL-AS1, was downregulated in gastric cancer tissues and cell lines compared with the normal. TONSL-AS1 inhibited cell migration, invasion and proliferation in SGC-7901, MGC-803â¯cells. Furthermore, TONSL-AS1 could suppress cell tumorigenesis in vivo. Mechanistically, TONSL-AS1's genomic neighboring gene TONSL, which was reported as a tumor suppress gene, was upregulated by TONSL. Additionally, the TONSL-AS1 was positively associated with TONSL in cancer tissues. Our study revealed that the tumor-inhibiting effect of TONSL-AS1 in gastric cancer cells was associated with TONSL. In general, our results indicated that TONSL-AS1 works as a tumor suppressor lncRNA, which may be a new therapeutic target for gastric cancer.
Asunto(s)
Regulación Neoplásica de la Expresión Génica/genética , Genes Supresores de Tumor , FN-kappa B/fisiología , Proteínas de Neoplasias/fisiología , ARN Neoplásico/fisiología , Neoplasias Gástricas/genética , Adulto , Anciano , Animales , Carcinogénesis , Adhesión Celular , División Celular , Línea Celular Tumoral , Movimiento Celular , Progresión de la Enfermedad , Regulación hacia Abajo , Femenino , Genes Reporteros , Humanos , Masculino , Ratones Endogámicos BALB C , Ratones Desnudos , Persona de Mediana Edad , FN-kappa B/genética , Proteínas de Neoplasias/genética , Interferencia de ARN , ARN Neoplásico/genética , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/farmacología , Organismos Libres de Patógenos EspecíficosRESUMEN
BACKGROUND: To induce and collect tumor-derived autophagosomes (DRibbles) from tumor cells as an antitumor vaccine by inhibiting the functions of proteasomes and lysosomes. METHODS: Dendritic cells (DCs) generated from peripheral blood mononuclear cell (PBMC) of hepatocellular carcinoma (HCC) patients were cocultured with DRibbles, and then surface molecules of DCs, as well as surface molecules on DCs, were determined by flow cytometry. Meanwhile, immune responses of the DCs-DRibbles were examined by mixed lymphocyte reactions. RESULTS: DRibbles significantly induced the expression of CD80, CD83, CD86 and HLA-DR on DCs. The enzyme-linked immunosorbnent assay (ELISA) showed that IFN-γ levels after vaccination increased than before in most patients, but CD8+ proportion of PBMC increased only in nine patients. Higher levels of IFN-γ were detected in the CD8+ cells than CD4+ T cells. These results suggested that DCs-DRibbles vaccine could induce antigen-specific cellular immune response on HCC and could prime strong CD8+ T cell responses, supporting it as a tumor vaccine candidate. CONCLUSIONS: Our results demonstrate that HCC/DRibbles-pulsed DCs immunotherapy might be deployed as an effective antitumor vaccine for HCC immunotherapy in clinical trials.
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OBJECTIVE: To investigate the preoperative risk factors of portal venous thrombosis (PVT) after splenectomy and gastric pericardial devascularization in patients with liver cirrhosis and portal hypertension. METHODS: Clinical data was collected for 127 patients who underwent splenectomy and gastric pericardial devascularization for portal hypertension at our hospital between January 2010 and December 2012.The patient data were analyzed retrospectively according to patient status of presence or absence of PVT postoperatively.The preoperative risk factors of PVT were statistically analyzed. RESULTS: There were no significant differences between the postoperative PVT-positive and-negative groups in regards to sex, age, receipt of emergency surgery, presence of ascites, admission to hospital for upper gastrointestinal bleeding, grade of esophageal-gastric varices, Child-Pugh classification, spleen vein diameter, liver function (as determined by levels of alanine aminotransferase, total bilirubin, direct bilirubin, albumin, globulin, cholinesterase, and gamma-glutamyltransferase), renal function (as determined by creatinine level), and coagulation function (as determined by prothrombin time, prothrombin activity degree, activated partial thromboplastin time, international normalized ratio, fibrinogen, thrombin time, and antithrombin III).However, there were significant differences between the groups for the parameters of postoperative PVT presence, upper gastric bleeding history, aspartate aminotransferase level, and blood urea nitrogen level (all P less than 0.05).Portal vein diameter and history of upper gastric bleeding were both identified as independent risk factors for PVT (P less than 0.05).Incidence of postoperative PVT was higher in patients who had portal vein diameter > 13.15 mm (cutoff value of 13.75 mm) and in patients who had a history of upper gastric bleeding. CONCLUSION: Portal vein diameter and history of upper gastric bleeding were independent risk factors for PVT occurrence after splenectomy and gastric pericardial devascularization in patients with liver cirrhosis and portal hypertension.
Asunto(s)
Hipertensión Portal/cirugía , Vena Porta , Estómago/irrigación sanguínea , Trombosis de la Vena/etiología , Antitrombina III , Várices Esofágicas y Gástricas , Hemorragia Gastrointestinal , Humanos , Incidencia , Cirrosis Hepática , Estudios Retrospectivos , Factores de Riesgo , Esplenectomía , Estómago/cirugía , Trombosis de la Vena/epidemiología , gamma-GlutamiltransferasaRESUMEN
OBJECTIVE: To compare radiofrequency ablation (RFA) or microwave ablation (MWA) and transcatheter arterial chemoembolization (TACE) with RFA or MWA monotherapy in hepatocellular carcinoma (HCC). METHODS: A prospective, randomized, controlled trial was conducted on 94 patients with HCC ≤7 cm at a single tertiary referral center from June 2008 to June 2010 at the Department of Hepatobiliary Surgery, the Second Affiliated Hospital of Southeast University. The patients were randomly assigned into the TACE-RFA or TACE-MWA (combined treatment group) and the RFA-alone or MWA-alone groups (control group). The primary end point was overall survival. The secondary end point was recurrence-free survival, and the tertiary end point was adverse effects. RESULTS: Until the time of censor, 17 patients in the TACE-RFA or TACE-MWA group had died. The median follow-up time of the patients who were still alive for the TACE-RFA or TACE-MWA group was 47.5±11.3 months (range, 29 to 62 months). The 1-, 3- and 5-year overall survival for the TACE-RFA or TACE-MWA group was 93.6%, 68.1% and 61.7%, respectively. Twenty-five patients in the RFA or MWA group had died. The median follow-up time of the patients who were still alive for the RFA or MWA group was 47.0±12.9 months (range, 28 to 62 months). The 1-, 3- and 5-year overall survival for the RFA or MWA group was 85.1%, 59.6% and 44.7%, respectively. The patients in the TACE-RFA or TACE-MWA group had better overall survival than the RFA or MWA group [hazard ratio (HR), 0.526; 95% confidence interval (95% CI), 0.334-0.823; P=0.002], and showed better recurrence-free survival than the RFA or MWA group (HR, 0.582; 95% CI, 0.368-0.895; P=0.008). CONCLUSIONS: RFA or MWA combined with TACE in the treatment of HCC ≤7 cm was superior to RFA or MWA alone in improving survival by reducing arterial and portal blood flow due to TACE with iodized oil before RFA.
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The present retrospective study aimed to investigate the mid-term safety and efficacy of hepatectomy combined with microwave ablation of the partial spleen for treatment of liver cancer complicated with hypersplenism. A retrospective analysis was performed on 23 patients who underwent hepatectomy combined with microwave ablation of the partial spleen for liver cancer, complicated with hypersplenism that was secondary to cirrhosis. The splenic and ablated volumes were calculated according to a contrast-enhanced computed tomography scan prior to and 2 weeks after the operation. Complete blood count and liver function tests were examined prior to and following the surgery, and complications and changes in the blood tests were monitored for 6 months. Over this period of investigation, the splenic volume was reduced by a mean value of 34.0%. The levels of serum alanine aminotransferase and aspartate aminotransferase were increased on the first day after the operation (P<0.05), although they recovered to the normal level within 1 week (P<0.05). The total level of bilirubin increased slightly, along with moderately decreased levels of albumin and cholinesterase on the first day, although these changes were not significant compared with the baseline (P>0.05). The white blood cell count was persistently significantly higher compared with the baseline over the course of the 6 months (P>0.05). The platelet count did not increase significantly for the first week after the operation (P>0.05); however, it was revealed to be significantly increased 1 month after the surgery (P<0.05). No significant complications were occurred during the follow-up period. In conclusion, hepatectomy combined with microwave ablation of the spleen was demonstrated to be a safe and effective procedure for patients with liver cancer and hypersplenism in the mid-term.
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BACKGROUND: This analysis was conducted to evaluate the efficacy and safety of Trans-arterial Chemo- Embolization (TACE) in treating Elderly patients with Hepatocellular Carcinoma (EHPC). METHODS: Clinical studies evaluating the efficacy and safety of TACE on response and safety for patients with EHPC were identified by using a predefined search strategy. Pooled response rate of treatment were calculated. RESULTS: In TACE based regimen, clinical studies which including patients with EHPC were considered eligible for the evaluation of response. And, in these TACE based treatments, pooled analysis suggested that, in all 288 patients whose response could be assessed, the pooled reponse rate was 29.5%(85/288) in TACE based treatment. The most commonly encountered TACE-related morbidity was liver function impairment. No grade III or IV renal or liver toxicity were observed. No treatment related death occurred in EHPC patients with TACE based treatments. CONCLUSION: This evidence based analysis suggests that TACE based treatments are associated with mild response rate and accepted toxicities for treating patients with EHPC.