Dynamic tracing for epidermal growth factor receptor mutations in urinary circulating DNA in gastric cancer patients.

The mutations of epidermal growth factor receptor are detected in gastric cancer, indicating its suitability as a target for receptor tyrosine kinase inhibitors, as well as a marker for clinical outcome of chemotherapeutic treatments. However, extraction of quality tumor tissue for molecular processes remains challenging. Here, we aimed to examine the clinical relevance of urinary cell-free DNA as an alternative tumor material source used specifically for monitoring epidermal growth factor receptor mutations. Therefore, 120 gastric cancer patients with epidermal growth factor receptor mutations and 100 healthy controls were recruited for the study. The gastric patients also received epidermal growth factor receptor inhibitor treatment for a serial monitoring study. Paired primary tumor specimens were obtained with blood and urine samples, which were taken at a 1-month interval for a duration of 12 months. We found that urinary cell-free DNA yielded a close agreement of 92% on epidermal growth factor receptor mutation status when compared to primary tissue at baseline, and of 99% epidermal growth factor receptor mutation status when compared to plasma samples at different time points. Thus, our data suggest that urinary cell-free DNA may be a reliable source for screening and monitoring epidermal growth factor receptor mutations in the primary gastric cancer.

Emodin Attenuates Cigarette Smoke Induced Lung Injury in a Mouse Model via Suppression of Reactive Oxygen Species Production.

Emodin has antioxidative activities. Here, we investigated the effects of emodin on cigarette smoke (CS)-induced acute lung inflammation. Mice (C57BL/6) were exposed to CS. Emodin was administrated with intraperitoneal bolus injection of emodin (20 or 40 mg/kg) daily 1 h before CS exposure. Emodin inhibited CS-induced inflammatory cells infiltration in mouse lungs, especially at 40 mg/kg. Moreover, emodin resulted in significant reductions in total bronchoalveolar lavage fluid (BALF) cells, as compared with air exposure control, coupled with decreases in BALF cytokines. The activities of superoxide dismutase, catalase, and glutathione peroxidase were remarkably enhanced by emodin in CS-exposed mice. Emodin enhanced CS-induced expression of heme oxygenase-1 and nuclear factor-erythroid 2-related factor-2 (both are antioxidative genes) at both mRNA and protein levels, and profoundly promoted their activities in CS-treated mice. Collectively, our results suggested that emodin protects mouse lung from CS-induced lung inflammation and oxidative damage, most likely through its antioxidant activity.

Involvement of Akt in synergistic effects of thermo-chemotherapy on human small cell lung cancer H446 cell apoptosis.

BACKGROUND AND OBJECTIVE: Akt pathway plays an important role in cell growth and apoptosis. This study was to characterize the role of Akt in the synergistic effects of thermo-chemotherapy on lung cancer cell growth and its underlying mechanisms. METHODS: H446 cells were subjected to different thermo-chemotherapy schemes: 43centigrade + paclitaxel (120 microg/L) (thermo-chemotherapy group), 43centigrade + paclitaxel (120 microg/L) + Wortmannin (1 micromol/L, PI3K/Akt pathway inhibitor) (Wortmannin group), 43centigrade + paclitaxel (120 microg/L) + N-acety-L-cysteine (NAC) (30 micromol/L, reactive oxygen species, ROS inhibitor) (NAC group), and paclitaxel (120 microg/L) group. The cells without any treatment were used as the control. MTT assay was conducted to measure the cell proliferation rate. Cell apoptosis was analyzed by flow cytometry (FCM). ROS was detected with fluorescence. Phosphorylation of Akt and the expressions of Caspase-3 were determined by Western blot. RESULTS: The cell proliferation rate was significantly lower in the thermo-chemotherapy group than in the control and the chemotherapy groups ((59.83 +/- 3.36)% vs. (100.00 +/- 0.00)% and (69.16 +/- 2.95)%, P < 0.05). The rate of cell apoptosis was the highest in the thermo-chemotherapy group (27.59 +/- 5.47)% (P < 0.05). The ROS expression level was higher in the cells of thermo-chemotherapy group (102.14 +/- 18.34) than in the other groups (P < 0.05), which could be inhibited by NAC(28.01 +/- 1.19), but not by the PI3K inhibitor Wortmannin (99.87 +/- 8.35). Phosphorylation of Akt significantly decreased in the thermo-chemotherapy group (0.69+/-0.03) (P < 0.05), which could be blocked by Wortmannin (0.00 +/- 0.00), but increased by NAC (1.05 +/- 0.29) (P < 0.05). The expression level of Caspase-3 was higher in the thermo-chemotherapy group (1.07 +/- 0.08) than in other groups (P < 0.05). CONCLUSION: Thermo-chemotherapy has a stronger inhibitory effect than chemotherapy alone in lung tumor cell growth, probably through induction of ROS production and subsequent inhibition of Akt pathway activation and Caspase pathway-induced cancer cell apoptosis.

Study on effect of Traditional Chinese Medicine Jianpi Chushi decoction and ointment on chronic eczema.

OBJECTIVE: To study the effects of Traditional Chinese Medicine Jianpi Chushi decoction and ointment on chronic eczema. METHODS: DNCB acetone solution was used to sensitize the skin of back and ears of 36 rats in order to establish chronic eczema model. A total of 36 rats were divided into four groups of 9 randomly including oral medicine group, external inunctum group, combination therapy group, and model control group respectively. Besides, the blank group of 4 healthy rats were set. The oral medicine group was given Traditional Chinese Medicine Jianpi Chushi decoction [(Poria cocos, Chinese yam, Cortex dictamni, Zaocys dhumnade, Rhizoma atractylodis, Pericarpium citri reticulatae, Scutellaria baicalensis, Radix Sophorae Flavescentis, Raw Radix Paeoniae Alba, Licorice roots (Northwest Origin)] by gastric infusion (1.6 g/mL·5 mL/d); the external inunctum group was given Qingpeng ointment on the skin, the combination therapy group was given Jianpi Chushi decoction by gastric infusion and Qingpeng ointment combination therapy. The model control group was given normal saline (NS) of the same volume by gastric infusion and vaseline on skin. Continuous administration 15 d and stopped for 3 d. The thickness difference and weight difference of left and right ear of every group were measured and the degree of ear swelling were evaluated. The CD4+ and CD8+ content and the IL-2, IL-4 level of serum were detected, and the inflammatory cells counts of back skin were recorded. RESULTS: After treatment, the degree of ear swelling of oral medicine group, external inunctum group and combination therapy group significant decreased compared with model control group (P < 0.05). The CD4+, CD8+ cell content and IL-2 level of oral medicine group, external inunctum group, combination therapy group and model control group significant decreased compared with blank group, and IL-2 level and the inflammatory cells count increased. After 15 d of treatment, the CD4+, CD8+ cell content and IL-2 level of serum of oral medicine group, external inunctum group and combination therapy group raised and the IL-4 level and the inflammatory cells count had significant decreased compared with model control group, and the effect of combination therapy group was more obvious (P < 0.05). CONCLUSIONS: Qral Jianpi Chushi decoction could treat chronic eczema effectively, and oral Chinese medicine combined with ointment could enhance and speed up the efficacy.

Induction of microRNA-9 mediates cytotoxicity of curcumin against SKOV3 ovarian cancer cells.

BACKGROUND: Curcumin, a phenolic compound extracted from the rhizomes of Curcuma longa, has shown cytotoxic effects against a variety of cancers. The aim of this study was to identify potential microRNA (miRNA) mediators of the anticancer effects of curcumin in ovarian cancer cells. MATERIALS AND METHODS: SKOV3 ovarian cancer cells were treated with curcumin (10-60 µM) and miR-9 expression, cell proliferation, and apoptosis were assessed. The effects of miR-9 depletion on curcumin-mediated growth suppression were also examined. Phosphorylation of Akt and forkhead box protein O1 (FOXO1) was measured in cells with miR-9 overexpression or curcumin treatment. RESULTS: Curcumin caused a significant and dose-dependent increase of miR-9 expression in SKOV3 cells, while significantly impeding cell proliferation and stimulating apoptosis. Depletion of miR-9 significantly (p<0.05) attenuated the growth-suppressive effects of curcumin on SKOV3 cells, coupled with reduced percentages of apoptotic cells. In contrast, overexpression of miR-9 significantly enhanced the cleavage of caspase-3 and poly(ADP-ribose) polymerase and promoted apoptotic death in SKOV3 cells. Western blot analysis showed that both miR-9 overexpression and curcumin similarly caused a significant (p<0.05) decline in the phosphorylation of Akt and FOXO1, compared to untreated cells. CONCLUSIONS: The present study provided evidence that curcumin exerts its cytotoxic effects against SKOV3 ovarian cancer cells largely through upregulation of miR-9 and subsequent modulation of Akt/FOXO1 axis. Further studies are needed to identify direct targets of miR-9 that mediate the anticancer effects of curcumin in ovarian cancer cells.