Browsing by Author "Chen, JZ"

Now showing 1 - 3 of 3
  • No Thumbnail Available
    Item
    Activation of signal pathways and the resistance to anti-EGFR treatment in colorectal cancer
    (Wiley-Blackwell, 2010-12-01) Chen, JZ; Huang, XF; Katsifis, A
    Colorectal cancer is the third most common cancer with a 5-year survival rate of less than 10%. It is caused by alterations of multiple signal pathways which are affected by both genetic and environmental factors. In some cases, EGFR is important in the carcinogenesis of colorectal cancer suggesting anti-EGFR therapy may be a potential treatment option. However, in other cases it is not effective, which may be related to its down-stream targeted gene mutations. KRAS is highly emphasized in the literature but other mutations like Src, PIK3CA, and BRAF may also be important. Furthermore, obesity may decrease the effectiveness of anti-EGFR treatment as it increases the risk factors for colorectal cancer. Using next-generation sequencing technology, it may be possible to identify all gene mutations in an individual with colorectal cancer. Therefore, gene mutations affecting anti-EGFR therapy in colorectal cancer patients can be identified. © 2010, Wiley-Blackwell. The definitive version is available at www3.interscience.wiley.com
  • Thumbnail Image
    Item
    Binding and dynamics demonstrate the destabilization of ligand binding for the S688Y mutation in the NMDA receptor GluN1 subunit
    (MDPI, 2023-05-15) Chen, JZ; Church, WB; Bastard, K; Duff, AP; Balle, T
    Encephalopathies are brain dysfunctions that lead to cognitive, sensory, and motor development impairments. Recently, the identification of several mutations within the N-methyl-D-aspartate receptor (NMDAR) have been identified as significant in the etiology of this group of conditions. However, a complete understanding of the underlying molecular mechanism and changes to the receptor due to these mutations has been elusive. We studied the molecular mechanisms by which one of the first mutations within the NMDAR GluN1 ligand binding domain, Ser688Tyr, causes encephalopathies. We performed molecular docking, randomly seeded molecular dynamics simulations, and binding free energy calculations to determine the behavior of the two major co-agonists: glycine and D-serine, in both the wild-type and S688Y receptors. We observed that the Ser688Tyr mutation leads to the instability of both ligands within the ligand binding site due to structural changes associated with the mutation. The binding free energy for both ligands was significantly more unfavorable in the mutated receptor. These results explain previously observed in vitro electrophysiological data and provide detailed aspects of ligand association and its effects on receptor activity. Our study provides valuable insight into the consequences of mutations within the NMDAR GluN1 ligand binding domain. © 2023 by the authors. Licensee MDPI, Basel, Switzerland. Open access CC BY.
  • No Thumbnail Available
    Item
    Insulin decreases therapeutic efficacy in colon cancer cell line HT29 via the activation of the PI3K/Akt pathway
    (Bentham Science Publishers Ltd, 2011-06-01) Chen, JZ; Katsifis, A; Hu, CH; Huang, XF
    Obesity has been associated with both the carcinogenesis and poor prognosis of colon cancer, one of the leading causes of cancer-related death. Increased blood levels of insulin in obese subjects have been demonstrated to play a key role in carcinogenesis. It is also possible that insulin affects treatment efficacy, leading to poor prognosis. In this study, we demonstrated that insulin can increase HT29 colon cancer cell line resistance to cycloheximide and 5- fluorouracil induced cytotoxicity. This effect can be inhibited by the PI3K/Akt inhibitor Ly294002, indicating the important role of this pathway in the insulin-induced inefficacy of chemotherapy. The insulin-induced resistance to cycloheximide and 5-fluorouracil can be used in drug screening to overcome the inefficacy of chemotherapy in obesity-associated colon cancer. © 2011 Bentham Science Publishers