ABSTRACT
The RAS association domain family protein 1A (RASSF1A) is a tumor suppressor in colorectal cancer (CRC), and is often inactived by hypermethylation. Therefore, we evaluated the association between RASSF1A hypermethylation and the risk and prognosis in CRC. We identified literature through searching PubMed and China National Knowledge Infrastructure databases, and then validated and supplemented the meta-analysis with TCGA analysis. Twenty-three studies involving 2886 subjects of CRC were examined. The meta-analysis showed that RASSF1A promoter methylation inferred high CRC risk (odds ratio, 6.53, 95% confidence interval 3.88-11.01, P < .001) and poor overall survival (hazard ratio 2.85, 95% CI 1.88-4.31, P < .001). The TCGA analysis suggested that effect of RASSF1A promotor methylation was affected by tumor localization (colon vs. rectum). RASSF1A promoter methylation was a predictor of high risk (OR 2.38, 95%CI 1.02-5.6, P = .046) and poor disease free survival(HR 2.25, 95%CI 1.27-3.99, P = .006)in colon adenocarcinoma, but the association was statistically insignificant in rectum adenocarcinoma(HR 1.58, 95% CI 0.69-3.59, P = .28). These results suggested RASSF1A hypermethylation is a risk and a potential prognostic biomarker in CRC.
Subject(s)
Adenocarcinoma/genetics , Biomarkers, Tumor/genetics , Colorectal Neoplasms/genetics , Tumor Suppressor Proteins/genetics , DNA Methylation/genetics , Humans , Prognosis , Promoter Regions, Genetic/geneticsABSTRACT
Brevibacillus brevis GZDF3 is a gram-positive, plant growth-promoting rhizosphere bacterium (PGPR) isolated from the rhizosphere soil of Pinellia ternata (an important herb in traditional Chinese medicine). The GZDF3 strain produces certain active compounds, such as siderophores, which are the final metabolite products of non-ribosomal peptide synthetase (NRPS) and independent non-ribosomal peptide synthetase (NIS) activity. With the present study, we attempted to investigate the siderophore production characteristics and conditions of Bacillus sp. GZDF3. The antibacterial activity of the siderophores on pathogenic fungi was also investigated. Optimal conditions for the synthesis of siderophores were determined by single factor method, using sucrose 15 g/l, asparagine 2 g/l, 32°C, and 48 h. The optimized sucrose asparagine medium significantly increased the production of siderophores, from 27.09% to 54.99%. Moreover, the effects of different kinds of metal ions on siderophore production were explored here. We found that Fe3+ and Cu2+ significantly inhibited the synthesis of siderophores. The preliminary separation and purification of siderophores by immobilized-metal affinity chromatography (IMAC) provides strong antibacterial activity against Candida albicans. The synergistic effect of siderophores and amphotericin B was also demonstrated. Our results have shown that the GZDF3 strain could produce a large amount of siderophores with strong antagonistic activity, which is helpful in the development of new biological control agents.
Subject(s)
Antifungal Agents , Brevibacillus/metabolism , Candida albicans/drug effects , Pinellia/microbiology , Siderophores , Antifungal Agents/metabolism , Antifungal Agents/pharmacology , Brevibacillus/isolation & purification , Culture Media , Rhizosphere , Siderophores/metabolism , Siderophores/pharmacologyABSTRACT
Cucurbitacin B (CuB), the active component of a traditional Chinese herbal medicine, Pedicellus Melo, has been shown to exhibit antitumor and anti-inflammation effects, but its role in tumor angiogenesis, the key step involved in tumor growth and metastasis, and the involved molecular mechanism are unknown. Tumor angiogenesis is one of the hallmarks of the development in malignant neoplasias and metastasis. Effective targeting of tumor angiogenesis is a key area of interest for cancer therapy. Here, we demonstrated that CuB significantly inhibited human umbilical vascular endothelial cell (HUVEC) proliferation, migration, tubulogenesis in vitro, and blocked angiogenesis in chick embryo chorioallantoic membrane (CAM) assay in vivo. Furthermore, CuB induced HUVEC apoptosis and may induce apoptosis by triggering the mitochondrial apoptotic pathway. Finally, we found that CuB inhibiting angiogenesis was associated with inhibition of the activity of vascular endothelial growth factor receptor 2 (VEGFR2). Our investigations suggested that CuB was a potential drug candidate for angiogenesis related diseases.
