Dihydroartemisinin accentuates the anti-tumor effects of photodynamic therapy via inactivation of NF-κB in Eca109 and Ec9706 esophageal cancer cells.

BACKGROUND: Photodynamic therapy (PDT) is a new treatment for esophageal cancer which has been shown to be effective in the elimination of tumor. However, PDT could induce the activation of nuclear factor-kappa B (NF-κB) in many photosensitizers based PDT, which plays a negative role in PDT. In addition, our previous results have shown that dihydroartemisinin (DHA), which was the most potent one of artemisinin derivatives, has anticancer activity in esophageal cancer cells. METHODS: Cell viability was determined by MTT analysis, and apoptosis was evaluated by flow cytometry. Nuclear extract was obtained for determining NF-κB DNA-binding activity, while total protein extract obtained for downstream gene expression by western blot. RESULTS: We demonstrated DHA enhanced PDT-induced growth inhibition and apoptosis in both human esophageal cancer cell lines Eca109 and Ec9706 in vitro. The mechanism was at least partially due to DHA deactivated PDT-induced NF-κB activation, so as to decrease tremendously the expression of its target gene Bcl-2. CONCLUSION: Our results demonstrate that DHA augments PDT-induced growth inhibition and apoptosis in esophageal cancer cells, and that inactivation of NF-κB activity is a potential mechanism by which DHA sensitizes esophageal cancer cells to PDT-induced growth inhibition and apoptosis.

A nomogram model for early recurrence of HBV-related hepatocellular carcinomas after radical hepatectomy.

Background: To identify the risk factors and construct a predictive model for early recurrence of hepatitis B virus(HBV-)- related hepatocellular carcinomas(HCCs) after radical resection. Data and methods: A total of 465 HBV-related HCC patients underwent radical resections between January 1, 2012 and August 31, 2018.Their data were collected through the inpatient information management system of the First Affiliated Hospital of University of Science and Technology of China. Survival and subgroup analyses of early recurrence among male and female patients were performed using Kaplan-Meier curves. The independent risk factors associated with early postoperative tumor recurrence were analyzed using multivariate Cox proportional hazards regression model. Based on these independent risk factors, a risk function model for early recurrence was fitted, and a column chart for the prediction model was drawn for internal and external validation. Results: A total of 181 patients developed early recurrences, including 156 males and 25 females. There was no difference in the early recurrence rates between males and females. Tumor diameters>5cm, microvascular invasion and albumin level<35 g/L were independent risk factors for early recurrence. A nomogram for the early recurrence prediction model was drawn; the areas under the curve for the model and for external verification were 0.638 and 0.655, respectively. Conclusion: Tumor diameter>5 cm, microvascular invasion, and albumin level<35 g/L were independent risk factors for early recurrence. The prediction model based on three clinical indicators could predict early recurrence, with good discrimination, calibration, and extrapolation.

Interaction of XRCC1 Arg399Gln Polymorphism and Alcohol Consumption Influences Susceptibility of Esophageal Cancer.

Background. To explore the correlation between the Arg399Gln polymorphism and susceptibility to esophageal cancer in Korean and Han Chinese individuals in Harbin, China, and its potential interaction with alcohol consumption. Methods. This prospective study included 203 patients with esophageal squamous cell carcinoma; 88 were of Korean descent and 115 were of Han Chinese descent. A group of healthy controls included 105 participants of Korean descent and 105 of Han Chinese descent. Genotyping of the Arg399Gln locus of XRCC1 was performed by PCR-RFLP. Results. The allelic and genotypic frequencies were not significantly different between individuals with esophageal cancer and controls or between individuals of Korean and Han Chinese descent (P > 0.05). However, when individuals with the wild-type Arg/Arg genotype also consumed alcohol, the risk of esophageal cancer was lower (OR = 3.539; 95% CI = 2.039-6.142; P < 0.05). Conclusions. The XRCC1 Arg399Gln polymorphism does not appear to be associated with esophageal cancer in individuals of Korean or Han Chinese descent in Harbin, China. However, alcohol consumption may decrease the risk of esophageal cancer in persons with the wild-type genotype.

Imaging guided photothermal therapy using iron oxide loaded poly(lactic acid) microcapsules coated with graphene oxide.

A novel multifunctional theranostic agent has been successfully fabricated by loading iron oxide nanoparticles into poly(lactic acid) (PLA) microcapsules followed by surface functionalization with graphene oxide. Both in vitro and in vivo experiments proved that the resulting microcapsules could serve as contrast agents to simultaneously enhance ultrasound, magnetic resonance and photoacoustic imaging. The composite microcapsules show good biocompatibility and rapid response to magnetic fields. Due to the strong absorption of the near-infrared light, the composite microcapsules could efficiently kill cancer cells upon NIR laser irradiation. In addition, it was found that such a photothermal effect could be obviously enhanced by applying an external magnetic field. In a nutshell, this multifunctional microcapsule can be developed as a promising platform that integrates multimodality imaging and therapy capabilities for effective cancer theranostics.

Initiation of apoptosis, cell cycle arrest and autophagy of esophageal cancer cells by dihydroartemisinin.

Dihydroartemisinin (DHA) has recently been shown anti-tumor activity in various cancer cells. However, its effect on esophageal cancer remains unclear. In this study, for the first time, we demonstrated that DHA reduced viability of esophageal cancer cells in a dose-dependent manner. The mechanism was at least partially due to DHA induced apoptosis by upregulating the expression of Bax, downregulating Bcl-2, Bcl-xL and Procaspase-3, and increasing caspase-9 activation, induced cell cycle arrest by downregulating cyclin E, CDK2 and CDK4. Furthermore, we firstly found that DHA induced autophagy in cancer cells. We concluded DHA might be a novel agent against esophageal cancer.