Clinical case report of patients with osteosarcoma and anticancer benefit of calycosin against human osteosarcoma cells.

Osteosarcoma (OS) is a malignant neoplasia in bone, characterized with main occurrence in teenagers. Calycosin (CC), a bioactive compound, is found to play potent pharmacological effects against cancer. Our previous study indicates CC-exerted benefits for anti-OS effect. However, further molecular mechanism behind this action needs to be investigated. In this study, human OS samples and clinical data were collected and used for further test and analysis. In addition, human osteosarcoma cell line (143B) and tumor-xenograft nude mice were used to evaluate antineoplastic activities of CC through a series of biochemical methods and immunoassays, respectively. Compared with non-OS controls, human OS samples showed increased levels of neoplastic microRNA-223 (miR-223), and elevated expressions of NF-κBp65, IκBα proteins in tumor cells. In cell culture study, CC-treated 143B cells showed reduced cell growth, increased lactic dehydrogenase (LD) content, and downregulated cellular miR-223 level. Immunolabeled cells of proliferating cell nuclear antigen, B-cell lymphoma 2 (Bcl-2), poly(ADP-ribose) polymerase (PARP) in CC treatments were decreased dose-dependently, while caspase-3 positive cells were elevated. Further, protein expressions of NF-κBp65, IκBα in CC-treated cells were downregulated. In addition, tumor-xenograft nude mice followed by CC treatments exhibited reductions of tumor mass, miR-223 levels, and Bcl-2, PARP-positive cells, as well as downregulations of NF-κBp65, IκBα protein expressions in OS samples. Taken together, these experimental findings reveal that CC exhibits potential pharmacological activities against OS through inducing apoptosis and inhibiting miR-223-IκBα signaling pathway in neoplastic cells.

The clinicopathologic impacts and prognostic significance of GLUT1 expression in patients with lung cancer: A meta-analysis.

BACKGROUND: Accumulating studies have reported that GLUT1 is aberrantly expressed in lung cancer; nevertheless, the clinicopathologic significance and the prognostic role of GLUT1 still remain controversial. The aim of this meta-analysis was to identify the clinicopathologic and prognostic implications of the GLUT1 expression in lung cancer patients. MATERIALS AND METHODS: Databases with literature published in English, including Cochrane Library, Embase, Web of Science, and PubMed, and the China National Knowledge Infrastructure (CNKI) and WanFang database in Chinese were searched comprehensively for relevant studies in August 2017. The pooled odds ratio (OR) or hazard ratio (HR) with 95% confidence intervals (CIs) were calculated to evaluate the clinicopathologic significance and prognostic value of GLUT1 in lung cancer. RESULTS: A total of 26 studies (2653 cases) were included in the current study. Totally, 1423 patients from nineteen studies were included to assess the relationships between GLUT1 and clinicopathological parameters, the pooled OR indicated that positive GLUT1 expression was significantly related with classification (adenocarcinomas vs. squamous carcinomas, OR = 0.276, 95% CIs: 0.117-0.651, P = 0.003), tumor differentiation (G3-4 vs. G2~1, OR = 1.944, 95% CIs: 1.384-2.730; P < 0.001), lymph node metastasis (positive vs. negative, OR = 3.65, 95% CIs: 1.82-7.32, P < 0.001),tumor size (large tumor size vs. small tumor size, OR = 2.03, 95% CI: 1.42-2.91, P < 0.001), and advanced tumor stages (OR = 2.527, 95% CIs: 1.325-4.820). Regarding the significance of GLUT1 in the overall survival (OS) of lung cancer, the pooled HRs with 1731 lung cancer patients was 1.41 (P = 0.002; 95% CIs: 1.13-1.76). Additionally, the overexpression of GLUT1 could significantly predict the shorter disease-free survival (HR = 1.68, 95% CIs: 1.01-2.79) and disease-specific survival (HR = 1.59, 95% CIs: 1.11-2.29). CONCLUSIONS: A positive expression of GLUT1 significantly predicts a poor prognosis in lung cancer patients. GLUT1 may server as a helpful biomarker and a potential target for the treatment strategies of lung cancer.

Synthesis and evaluation of hydroxychalcones as multifunctional non-purine xanthine oxidase inhibitors for the treatment of hyperuricemia.

A series of hydroxychalcone derivatives have been designed, synthesized and evaluated for human xanthine oxidase (XO) inhibitory activity. Most of the tested compounds acted moderate XO inhibition with IC50 values in the micromolar rang. Molecular docking and kinetic studies have been performed to explain the binding modes of XO with the selected compounds. In addition, in vitro antioxidant screening results indicated that some of the hydroxychalcones possessed good anti-free radical activities. Furthermore, the preferred compounds 16 and 18 were able to significantly inhibit hepatic xanthine oxidase activity and reduced serum uric acid level of hyperuricemic mice in vivo. In summary, compounds 16 and 18 with balanced activities of antioxidant, XO inhibition and serum uric acid reduction, which are promising candidates for the treatment of hyperuricemia and gout.