Predicating Candidate Cancer-Associated Genes in the Human Signaling Network Using Centrality
CURRENT BIOINFORMATICS
Authors: Liu, Xueming; Pan, Linqiang
Abstract
The development of cancer evolves gene mutations according to the somatic mutation theory. The identification and prediction of the cancer-associated genes is one of the most important aims in cancer research. We apply four centrality metrics (degree, betweenness, closeness and PageRank) to prioritize and predict the candidate cancer-associated genes in the human signaling network. We find that the genes with higher centrality scores are more likely to be cancer-associated. Taking the top 47 genes for each centrality measure, we get 89 central genes. Among these 89 central genes, 58 genes are known to be cancer-associated, 4 genes encode non-protein and 27 genes are inferred genes. For the 27 inferred genes, by literature mining we find that 21 genes have been confirmed to be cancer-associated and the other 6 genes (CAMP, GSK3A, MTG1, GNGT1, ISGF3G and DYT10) are strong candidates for cancer research. These results show that the four centrality metrics are effective in predicting candidate cancer-associated genes for further experimental analysis.
Phytosomal curcumin inhibits tumor growth in colitis-associated colorectal cancer
JOURNAL OF CELLULAR PHYSIOLOGY
Authors: Marjaneh, Reyhaneh Moradi; Rahmani, Farzad; Hassanian, Seyed Mahdi; Rezaei, Nastaran; Hashemzehi, Milad; Bahrami, Afsane; Ariakia, Fatemeh; Fiuji, Hamid; Sahebkar, Amirhosein; Avan, Amir; Khazaei, Majid
Abstract
Colorectal-cancer (CRC) is the third leading cause of death due to cancer, supporting the need for identification of novel anticancer drug to improve the efficacy of current-therapy. There is growing bodies of data showing the antitumor-activity of curcumin, although it is associated with low absorption. The aim of current study was explored the therapeutic-potential of novel phytosomal curcumin as well as its application in combination with 5-Flurouracil (5-FU) in a mouse-model of colitis-associated colon-cancer. The anti-proliferative-activity of phytosomal curcumin was assessed in 2- and 3-dimensional cell-culture-models as well as in a mouse-model of colitis-associated colon-cancer. The expression-levels of CyclinD1, beclin, E-cadherin, and p-GSK3a/b were investigated by qRT-PCR and/or Western-blotting. We evaluated the anti-inflammatory of this agent by pathological-evaluation and disease-activity-index (DAI). Moreover, oxidant/antioxidant activity was examined by malondialdehyde (MDA), total-thiols (T-SH), superoxide-dismutase (SOD), and catalase (CAT) activity parameters. Our data showed that phytosomal curcumin and its combination with 5-FU inhibited cell growth and invasive behavior of CRC cells through modulation of Wnt-pathway and E-cadherin. Combination of curcumin with 5-FU dramatically reduced the tumor-number and tumor-size in both distal and middle parts of colon in colitis-associated colon cancer followed by reduction in DAI. Also, curcumin suppressed the colonic inflammation and notably recovered the increased levels of MDA, decreased thiol level and reduced activity of CAT. We demonstrated the antitumor-activity of novel form of curcumin in CRC, supporting further investigations on the therapeutic-potential of this approach in colorectal-cancer.