Research progress on the development of hepatocyte growth factor/c-Met signaling pathway in gastric cancer: A review.

Hepatocyte growth factor (HGF) and its receptor, c-Met, play important roles in the occurrence, development, and treatment of gastric cancer (GC). This review explored the function of the HGF/c-Met signaling pathway in GC and its potential targeted therapeutic mechanisms. As one of the most common malignant tumors worldwide, GC has a complex pathogenesis and limited therapeutic options. Therefore, a thorough understanding of the molecular mechanism of GC is very important for the development of new therapeutic methods. The HGF/c-Met signaling pathway plays an important role in the proliferation, migration, and invasion of GC cells and has become a new therapeutic target. This review summarizes the current research progress on the role of HGF/c-Met in GC and discusses targeted therapeutic strategies targeting this signaling pathway, providing new ideas and directions for the treatment of GC.

[Effects of ursolic acid in ameliorating insulin resistance in liver of KKAy mice via peroxisome proliferator-activated receptors α and γ].

OBJECTIVE: To explore the effects and mechanism of ursolic acid in improving hepatic insulin resistance in KKAy mice with spontaneous type 2 diabetes. METHODS: Thirty-five KKAy mice were divided into five groups according to the randomized block design, namely, control, rosiglitazone, fenofibrate, and high- and low-dose ursolic acid groups with seven mice in each group. C57BL/6J mice were used as the normal control group. At the end of the 4th week, free fatty acid (FFA), tumor necrosis factor-α (TNF-α) and adiponectin contents in serum were detected by enzyme-linked immunosorbent assay; the protein expressions of phosphoenolpyruvate carboxykinase (PEPCK), insulin receptor substrate-2 (IRS-2) and glucose transport factor-2 (GLUT-2) were detected by Western blot method; the mRNA expressions of PEPCK, IRS-2 and GLUT-2 were detected by real-time polymerase chain reaction; the expressions of peroxisome proliferator-activated receptor α (PPARα) and peroxisome proliferator-activated receptor γ (PPARγ) in liver tissue were detected by immunohistochemical method. RESULTS: After four weeks of intervention, the contents of FFA, TNF-α and adiponectin in serum of the high-dose ursolic acid group had changed, showing statistically significant difference compared to those of the control group (P<0.01); high dose of ursolic acid had depressant effect on the expressions of PEPCK protein and PEPCK mRNA (P<0.01); low dose of ursolic acid depressed the expression of PEPCK mRNA and induced phosphorylation of IRS-2 in the liver (P<0.05); both high and low dose of ursolic acid improved the expression of PPARα in the liver (P<0.01). CONCLUSION: The effects of ursolic acid in improving hepatic insulin resistance in KKAy mice with spontaneous type 2 diabetes may be closely related to affecting the contents of FFA, TNF-α and adiponectin, improving the expression of PPARα protein, regulating transcription of PEPCK protein and inducing phosphorylation of IRS-2.

[Effects of ursolic acid on c-Cbl-associated protein expression in 3T3-L1 adipocytes with insulin resistance].

OBJECTIVE: To observe the effects of ursolic acid (UA) on insulin resistance and cell differentiation in 3T3-L1 adipocytes and to explore the mechanisms. METHODS: 3T3-L1 adipocytes were cultured in Dulbecco's modified Eagle's medium (DMEM) supplemented with glucose (25 mmol/L) and insulin (10(-6) mol/L) to induce insulin resistance. After culture, glucose consumption of the adipocytes was detected by glucose oxidase method and glucose uptake was detected by using tritium-marked glucose. Drug concentration for following test was determined through detecting the effects of different concentrations of UA on the activity of 3T3-L1 adipocytes with insulin resistance by methyl thiazolyl tetrazolium (MTT) staining. 3T3-L1 adipocytes with insulin resistance were cultured with DMEM, rosiglitazone, and low- and high-dose UA, and then, glucose uptake and differentiation of 3T3-L1 adipocytes were detected. Finally, real-time fluorescence quantitative polymerase chain reaction and Western blot methods were used to detect the effects of UA on expressions of adipocyte lipid binding protein (aP2), c-Cbl-associated protein (CAP) and matrix metalloproteinase-1 (MMP-1) in 3T3-L1 cells with insulin resistance. RESULTS: After dealing with high glucose/hyperinsulin for 24 h, insulin resistance was induced successfully in the 3T3-L1 adipocytes. The concentrations of UA were defined to be 4 to 20 µmol/L. Compared with the model group, the glucose uptake was significantly increased in the rosiglitazone group and groups treated with low- and high-dose UA (P<0.01). The differentiation levels of 3T3-L1 adipocytes in the UA groups were lower than those in the control group and the rosiglitazone group. Effects of UA on the expressions of aP2 and MMP-1 were not obvious, but UA could up-regulate expression of CAP both in mRNA and protein levels (P<0.01). CONCLUSION: Low- and high-dose UA can improve the glycometabolism and differentiation of 3T3-L1 adipocytes with insulin resistance by up-regulating the expression of CAP.

[Integrated traditional Chinese and Western medicine versus Western medicine in treatment of arteriosclerosis obliterans: a systematic review of randomized controlled trials].

BACKGROUND: The conventional therapy for arteriosclerosis obliterans (ASO) is Western medicine. However, it has some adverse effects and does not respond to some patients, and it is also very expensive. OBJECTIVE: To evaluate the efficacy of integrated traditional Chinese (TCM) and Western medicine (WM) in treatment of ASO. SEARCH STRATEGY: Electronic and manual searches were conducted and the searches ended on May 20, 2009. INCLUSION CRITERIA: We included randomized controlled trials (RCT) evaluating integrated TCM and WM (as treatment group) versus WM used alone (as control group), and no language limits were set. DATA EXTRACTION AND ANALYSIS: Selection of trials for inclusion, assessment for methodological quality, data extraction and data syntheses were conducted according to protocol of a Cochrane systematic review by the authors. RESULTS: Thirteen RCT were included, which encompassed a total of 968 patients. The results showed that all of the 13 included trials did not report mortality rate of ASO. The studies displayed that the amputation rate in the treatment group was lower than that in the control group, but there was no statistical significance. Ten studies adopted inefficiency analysis and 2 of them showed that the ineffective rate in the treatment group was lower than that in the control group, and the relative risk (RR) and 95% CI were 0.36 [0.13, 0.99]. We performed descriptive analysis on other 8 studies; analyses of secondary outcomes such as intermittent claudication, ankle brachial index, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) showed that integrated TCM and WM therapy was more effective than WM treatment alone; one study showed that WM was better than integrated TCM and WM therapy in decreasing the content of fibrinogen. All of the included trials did not report any critical adverse reactions occurred in the treatment group. CONCLUSION: The current evidence shows that integrated TCM and WM therapy is safe and effective in treating ASO, and tends to reduce amputation rate, improve intermittent claudication, decrease the levels of fibrinogen, HDL and LDL, and increase ankle brachial index, without obvious adverse reactions. Due to the low methodological quality of trials included, more prospective, multicenter, large-scale, high-quality RCTs are needed.

Treatment of cholecystitis with Chinese herbal medicines: a systematic review of the literature.

AIM: To analyze the literature on the use of Chinese herbal medicines for the treatment of cholecystitis. METHODS: The literature on treatment of cholecystitis with traditional Chinese medicines (TCM) was analyzed based on the principles and methods described by evidence-based medicine (EBM). Eight databases including MEDLINE, EMbase, Cochrane Central (CCTR), four Chinese databases (China Biological Medicine Database, Chinese National Knowledge Infrastructure Database, Database of Chinese Science and Technology Periodicals, Database of Chinese Ministry of Science and Technology) and Chinese Clinical Registry Center, were searched. Full text articles or abstracts concerning TCM treatment of cholecystitis were selected, categorized according to study design, the strength of evidence, the first author's hospital type, and analyzed statistically. RESULTS: A search of the literature published from 1977 through 2009 yielded 1468 articles in Chinese and 9 in other languages; and 93.92% of the articles focused on clinical studies. No article was of level I evidence, and 9.26% were of level II evidence. The literature cited by Science Citation Index (SCI), MEDLINE and core Chinese medical journals accounted for 0.41%, 0.68% and 7.29%, respectively. Typically, the articles featured in case reports of illness, examined from the perspective of EBM, were weak in both quality and evidence level, which inconsistently conflicted with the fact that most of the papers were by authors from Level-3 hospitals, the highest possible level evaluated based on their comprehensive quality and academic authenticity in China. CONCLUSION: The published literature on TCM treatment of cholecystitis is of low quality and based on low evidence, and cognitive medicine may functions as a useful supplementary framework for the evaluation.

[A rare vascular malformation of the lung: discussion of the CT findings and nomenclature].

OBJECTIVE: To investigate the characteristic findings of an anomalous systemic arterial supply to the lung without the pulmonary artery on spiral CT and discuss its nomenclature. METHODS: Four cases of anomalous systemic arterial supply to the left basal segment of the lung without the pulmonary artery were retrospectively reviewed with analysis of the characteristic CT findings. RESULTS: On spiral CT scans, the involved left lower lung including the entire left basal segments (n=2), the lateral and posterior basal segment (n=1), and the anterior, medial, and posterior basal segment (n=1) had mild volume loss and areas of ground-glass opacity but with normal bronchial trees. The absence of the entire or part of the basal segments of the normal left lower lobar pulmonary artery, anomalous systemic artery originating from the abdominal aorta, diffuse dilatation of the systemic arterial branches distributed in the basal segments of the left lower lobe, and left lower pulmonary venous drainage into left atrium were found in all these patients. CONCLUSION: This anomaly presents with characteristic findings on chest spiral CT, for which the nomenclature of local absent pulmonary artery better shows the characteristics of the disease.