JKAP correlates with lower disease risk and inflammation, and its increment during etanercept treatment associates with commendable treatment efficiency in rheumatoid arthritis patients.

OBJECTIVE: This study aimed to investigate the correlation of Jun N-terminal kinase pathway associated phosphatase (JKAP) with disease risk and inflammation, also to explore the association of its longitudinal change with etanercept (ETN) treatment efficiency in rheumatoid arthritis (RA) patients. PATIENTS AND METHODS: A total of 107 active RA patients about to receive ETN treatment and 60 healthy controls (HCs) were enrolled in this study. Serum JKAP level was measured by enzyme-linked immunosorbent assay in RA patients (at week 0 (W0), W6, W12, and W24) and HCs (at recruitment). RA patients were categorized into W24 response patients and W24 non-response patients, or W24 remission patients and W24 non-remission patients, respectively, according to clinical response status or remission status at W24. RESULTS: JKAP level was reduced in RA patients compared with HCs. In RA patients, decreased baseline JKAP was correlated with elevated C-reaction protein level and anti-citrullinated protein antibodies positive status. Moreover, JKAP level was increased during ETN treatment. Subgroup analyses revealed that JKAP level during ETN therapy was increased in W24 response patients, while no difference was discovered in JKAP level among different time points in W24 non-response patients. Meanwhile, JKAP level during ETN treatment was elevated in both W24 remission patients and W24 non-remission patients, however, its increment was more evident in W24 remission patients. CONCLUSIONS: JKAP correlates with reduced disease risk and inflammation, and its increment during ETN treatment associates with commendable treatment efficiency in RA patients.

Prognostic impact of prognostic nutritional index in advanced (stage IIIB/IV) non-small cell lung cancer patients.

Prognostic nutritional index (PNI) is a parameter reflecting prognosis for various cancers, including resected lung cancer. However, there were few reports to study the relationship between the PNI and overall survival (OS) in patients with advanced (stage IIIB/IV) non-small lung cancer (NSCLC). In this study, we collected the clinical data of 315 patients with advanced (stage IIIB/IV) NSCLC who had received chemotherapy or epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) between January 2010 and June 2011. Survival curves were plotted using the Kaplan-Meier method. Multivariate analyses were used to evaluate prognostic significance of PNI in patients with advanced (stage IIIB/IV) NSCLC. In our analysis, we found that PNI (p=0.001) was significantly associated with OS in patients with advanced (stage IIIB/IV) NSCLC, so was smoking (p<0.001) and disease stage (p=0.005). We demonstrated that PNI could be utilized to predict survival outcomes in patients with advanced (stage IIIB/IV) NSCLC. Patients with a lower PNI may have worse prognosis.

Knockdown of human serine/threonine kinase 33 suppresses human small cell lung carcinoma by blocking RPS6/BAD signaling transduction.

Small cell lung cancer (SCLC) is characterized by rapid growth rate and a tendency to metastasize to distinct sites of patients' bodies. The human serine/threonine kinase 33 (STK33) gene has shown its potency as a therapeutic target for prevention of lung carcinomas including non-small cell lung cancer (NSCLC), but its function in the oncogenesis and development of SCLC remains unrevealed. In the current study, it was hypothesized that STK33 played a key role in the proliferation, survival, and invasion of SCLC cells. The expression of STK33 in human SCLC cell lines NCI-H466 and DMS153 was inhibited by specific shRNA. The cell proliferation, cell apoptosis, and cell invasion of the cells were assessed with a series of in vitro assays. To explore the mechanism through which STK33 gene exerted its function in the carcinogenesis of SCLC cells, the effect of STK33 knockdown on the activity of S6K1/RPS6/BAD signaling was detected. Then the results were further confirmed with STK33 inhibitor ML281 and in vivo assays. The results demonstrated that inhibition of STK33 in SCLC cells suppressed the cell proliferation and invasion while induced cell apoptosis. Associated with the change in the phenotypic features, knockdown of STK33 also decreased the phosphorylation of RPS6 and BAD while increased the expression of cleaved caspase 9, indicating that apoptosis induced by STK33 suppression was mediated via mitochondrial pathway. Similar to the results of STK33 knockdown, incubating NCI-H466 cells with STK33 inhibitor also reduced the cell viability by suppressing RPS6/BAD pathways. Additionally, STK33 knockdown also inhibited tumor growth and RPS6/BAD activity in mice models. Findings outlined in our study were different from that in NSCLC to some extent: knockdown of STK33 in SCLC cells induced the apoptosis through mitochondrial pathway but independent of S6K1 function, inferring that the function of STK33 might be cancer type specific.

Crown gall -- a plant tumour with biological activities.

Petroleum ether, acetone, 80% MeOH and water extracts of crown gall, a plant tumour, obtained from Eucalyptus globulus tree were screened for cytotoxic, antioxidant, antiinflammatory, embryotoxic, antitumour-promoting and antimicrobial activities. In terms of bioactivity the 80% MeOH extract was most effective followed by the acetone extract. The petroleum ether extract showed weak to moderate cytotoxic activity in dose-dependent manner against PC12 cells, mouse L fibroblasts and 1321N1 glia cells, whereas the hydroalcohol extract had no or a weak cytotoxic effect. The 80% MeOH extract exhibited strong antioxidant activity. Based on the in vitro HET-CAM assay all the extracts were effective against inflammation. The extracts did not show any embryotoxic effect at the concentrations tested. Antitumour-promoting activity (100% inhibition; 100 microg/mL) was observed in the 80% MeOH and acetone extracts. In the antimicrobial screening all extracts displayed predominantly antifungal activity against Candida sp. The extracts also showed various levels of antibacterial activity against E. faecalis, Ps. aeruginosa, Bac. subtilis and Staph. epidermidis. From the results of the investigations it can be concluded that crown gall is a valuable plant tumour tissue having interesting biological activities.

Cancer chemoprevention by ginseng in mouse liver and other organs.

Oral administration of red ginseng extracts (1% in diet for 40 weeks) resulted in the significant suppression of spontaneous liver tumor formation in C3H/He male mice. Average number of tumors per mouse in control group was 1.06, while that in red ginseng extracts-treated group was 0.33 (p<0.05). Incidence of liver tumor development was also lower in red ginseng extracts-treated group, although the difference from control group was not statistically significant. Anti-carcinogenic activity of white ginseng extracts, besides red ginseng extracts, was also investigated. In the present study, the administration of white ginseng extracts was proven to suppress tumor promoter-induced phenomena in vitro and in vivo. It is of interest that oral administration of the extracts of Ren-Shen-Yang- Rong-Tang, a white ginseng-containing Chinese medicinal prescription, resulted in the suppression of skin tumor promotion by 12-o-tetradecanoylphorbol-13-acetate in 7,12-dimethylbenz[a]anthracene-initiated CD-1 mice. These results suggest the usefulness of ginseng in the field of cancer prevention.

Inhibitory effects of 6-O-acylated L-ascorbic acids possessing a straight- or branched-acyl chain on Epstein-Barr virus activation.

6-O-Acylated L-ascorbic acids possessing a straight- or branched-acyl chain of varying length from C(4) to C(18) have been synthesized and evaluated their anti-tumor promoting effects on the activation of the Epstein-Barr virus early antigen. The derivatives having a straight- or branched-acyl chain of C(6) to C(11) carbon atoms exhibited marked effects.

Lignans as anti-tumor-promoter from the seeds of Hernandia ovigera.

Seven lignans (2-8) isolated from the seeds of Hernandia ovigera L. (Hernandiaceae) were tested for their inhibitory effects on Epstein-Barr virus early antigen activation induced by 12-O-tetradecanoylphorbol 13-acetate in Raji cells. Using a primary screening test, all the lignans showed inhibitory activity with IC50 470-590 mol ratio/32 pmol TPA. The data demonstrated that these lignans might be valuable anti-tumor-promoters.

Antitumor promoting activities of 3-O-acyl-(-)epigallocatechins.

As an exploratory investigation of antitumor promoting compounds, 3-O-acyl-(-)-epigallocatechins possessing a straight-, branched-, phenyl-inserted- or 1,4-phenylene-inserted-acyl chain of varying length from C4 to C18 were synthesized and evaluated their inhibitory effects against the activation of the Epstein-Barr virus early antigen (EBV-EA). It was indicated that the epigallocatechin derivatives having the straight- or branched-acyl chain of C8 to C11 carbon atoms achieve marked effects.

Conversion of quassinoids for enhancement of inhibitory effect against Epstein-Barr virus early antigen activation. Introduction of lipophilic side chain and esterification of diosphenol.

Introduction of a senecioyl group into shinjulactones B and C, and esterification of the diosphenol moiety in brusatol and brucein A enhanced inhibitory effect against Epstein-Barr virus early antigen activation.

Inhibitory effect of flavonoids from citrus plants on Epstein-Barr virus activation and two-stage carcinogenesis of skin tumors.

To search for possible anti-tumor promoters, thirteen flavones (1-13) obtained from the peel of Citrus plants were examined for their inhibitory effects on the Epstein-Barr virus early antigen (EBV-EA) activation by a short-term in vitro assay. Of these flavones, 3,5,6,7,8,3',4'-heptamethoxyflavone (HPT) (13) exhibited significant inhibitory effects on the EBV-EA activation induced by the tumor promoter, 12-O-tetradecanoylphorbol 13-acetate (TPA). Further, compound 13 exhibited remarkable inhibitory effects on mouse skin tumor promotion in an in vivo two-stage carcinogenesis test.