Background and purpose:Fumagillin is an inhibitor of type 2 methionine aminopeptidase that can block blood vessel formation. However, its molecular mechanism and therapeutic value in colon cancer still remain to be elucidated.In this study, the effect of Fumagillin on the growth of colon cancer was examined. Methods:Twenty mice were divided into 4 groups and injected subcutaneously with 5?105/L WiDr or HT-29 cells in 200 ?L phosphate-buffered saline (PBS) respectively. After 4 weeks, intraperitoneal injections of Fumagillin (0.1 mg/kg), Cyclo (1 mg/kg), or both were given every 2 days for 4 weeks. The tumor weight and microvessel density (MVD) were examined. Geneexpression profiles were examined by microarray analysis of human umbilical endothelial cells (HUVECs). Results: The Fumagillin-treated mice showed smaller tumor mass and lower MVD-CD105 levels than control ones. In vitro proliferation and tube formation of HUVEC was also significantly decreased by Fumagillin. Microarray analysis of Fumagillin-treated HUVECs showed up-regulation of 71 genes and down-regulation of 143 genes. Expression changes were involved in cell proliferation, migration, adhesion and gene transcription. Quantitative real time-polymerase chain reaction and Western blot revealed decreased expression of cyclin E2, activated leukocyte cell adhesion molecule (ALCAM), and intercellular adhesion molecule-1 (ICAM-1) genes in the presence of Fumagillin. Conclusion: Fumagillin was found to suppress colorectal cancer growth by suppressing angiogenesis. The down-regulation of cyclin E2, ALCAM and ICAM-1 by fumagillin may be involved in the anti-angiogenesis.

Background and purpose: Fumagillin is an inhibitor of type 2 methionine aminopeptidase that can block blood vessel formation. However, its molecular mechanism and therapeutic value in colon cancer still remain to be elucidated.ln this study, the effect of Fumagillin on the growth of colon cancer was examined. Methods: Twenty mice were divided into 4 groups and injected subcutaneously with 5×10~5/L WiDr or HT-29 cells in 200 μL phosphate-buffered saline (PBS) respectively. After 4 weeks, intraperitoneal injections of Fumagillin (0.1 mg/kg), Cyclo (1 mg/kg), or both were given every 2 days for 4 weeks. The tumor weight and microvessel density (MVD) were examined. Gene-expression profiles were examined by microarray analysis of human umbilical endothelial cells (HUVECs). Results: The Fumagillin-treated mice showed smaller tumor mass and lower MVD-CD105 levels than control ones. In vitro proliferation and tube formation of HUVEC was also significantly decreased by Fumagillin. Microarray analysis of Fumagillin-treated HUVECs showed up-regulation of 71 genes and down-regulation of 143 genes. Expression changes were involved in cell proliferation, migration, adhesion and gene transcription. Quantitative real time-polymerase chain reaction and Westem blot revealed decreased expression of cyclin E2, activated leukocyte cell adhesion molecule (ALCAM), and intercellular adhesion molecule-1 (ICAM-1) genes in the presence of Fumagillin. Conclusion: Fumagillin was found to suppress colorectal cancer growth by suppressing angiogenesis. The down-regulation of cyclin E2, ALCAM and ICAM-1 by fumagillin may be involved in the anti-angiogenesis.

Objective To establish a TLC identification method for Erhuang Capsule and to provide basis for the establishment of its quality standard.Methods TLC method was adopted.Results Nine kinds of medicinal materials such as Radix Rehmanniae,Radix Polygoni Multiflori,Rhizoma Gastrodiae had discriminating characteristics and distinctive spots.Conclusion TLC is a simple,reliable and specific method with good reproducibility,and can be used for the quality control of Erhuang Capsule.

Background::Epigenetics, and especially DNA methylation, contributes to the pathogenesis of sporadic amyotrophic lateral sclerosis (SALS). This study aimed to investigate the role of DNA methylation in SALS using whole blood of SALS patients.Methods::In total, 32 SALS patients and 32 healthy controls were enrolled in this study. DNA was isolated from whole blood collected from the participants. DNA methylation profiles were generated using Infinium MethylationEPIC BeadChip.Results::We identified 34 significant differentially methylated positions (DMPs) in whole blood from SALS patients, compared with the healthy controls. Of these DMPs, five were hypermethylated and 29 were hypomethylated; they corresponded to 13 genes. For the DMPs, ATAD3B and BLK were hypermethylated, whereas DDO, IQCE, ABCB1, DNAH9, FIGN, NRP1, TMEM87B, CCSAP, ST6GALNAC5, MYOM2, and RUSC1-AS1 were hypomethylated. We also identified 12 differentially methylated regions (DMRs), related to 12 genes (NWD1, LDHD, CIS, IQCE, TNF, PDE1C, LGALS1, CSNK1E, LRRC23, ENO2, ELOVL2, and ELOVL2-AS1). According to data from the Kyoto Encyclopedia of Genes and Genomes database, DNAH9 and TNF are involved in the amyotrophic lateral sclerosis (ALS) pathway. Correlation analysis between clinical features and DNA methylation profiling indicated that the methylation level of ELOVL2 and ARID1B was positively associated with the age of onset ( r = 0.86, adjust P = 0.001) and disease duration ( r = 0.83, adjust P = 0.01), respectively. Conclusions::We found aberrant methylation in DMP- and DMR-related genes, implying that many epigenetic alterations, such as the hypomethylation of DNAH9 and TNF, play important roles in ALS etiology. These findings can be helpful for developing new therapeutic interventions.

Although DNA 5-hydroxymethylcytosine (5hmC) is recognized as an important epige-netic mark in cancer, its precise role in lymph node metastasis remains elusive. In this study, we investigated how 5hmC associates with lymph node metastasis in breast cancer. Accompanying with high expression of TET1 and TET2 proteins, large numbers of genes in the metastasis-positive pri-mary tumors exhibit higher 5hmC levels than those in the metastasis-negative primary tumors. In contrast, the TET protein expression and DNA 5hmC decrease significantly within the metastatic lesions in the lymph nodes compared to those in their matched primary tumors. Through genome-wide analysis of 8 sets of primary tumors, we identified 100 high-confidence metastasis-associated 5hmC signatures, and it is found that increased levels of DNA 5hmC and gene expression of MAP7D1 associate with high risk of lymph node metastasis. Furthermore, we demonstrate that MAP7D1, regulated by TET1, promotes tumor growth and metastasis. In conclusion, the dynamic 5hmC profiles during lymph node metastasis suggest a link between DNA 5hmC and lymph node metastasis. Meanwhile, the role of MAP7D1 in breast cancer progression suggests that the metastasis-associated 5hmC signatures are potential biomarkers to predict the risk for lymph node metastasis, which may serve as diagnostic and therapeutic targets for metastatic breast cancer.