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Irritable Bowel Syndrome
Published in Peter Sagar, Andrew G. Hill, Charles H. Knowles, Stefan Post, Willem A. Bemelman, Patricia L. Roberts, Susan Galandiuk, John R.T. Monson, Michael R.B. Keighley, Norman S. Williams, Keighley & Williams’ Surgery of the Anus, Rectum and Colon, 2019
In North-Western Europe, adult lactase persistence, caused by a mutation in the gene MCM6 (minichromosome maintenance 6) that controls down-regulation of lactase production in enterocytes, co-evolved with dairy-based farming, and today the vast majority of people in Ireland, the UK, the Netherlands, Germany and Scandinavia retain as adults the ability to digest lactose to glucose and galactose. Lactase activity can be directly measured in biopsies from small bowel mucosa, but for clinical purposes the most accurate indirect test for lactase activity is genotyping for LCT-13910 C/T. Only those with ‘wild-type’, i.e. CC, have lactose malabsorption. Several other mutations, like LCT-22019 G/A, have been found to cause lactase persistence in other parts of the world.
Establishment of the prediction model and biological mechanism exploration for secondary imatinib-resistant in gastrointestinal stromal tumor
Published in Scandinavian Journal of Gastroenterology, 2022
Chao Wang, Zhanlong Shen, Kewei Jiang, Zhidong Gao, Yingjiang Ye
We found most of the 44 DEGs biologically enriched in DNA replication, which is the frequent cellular process that can lead to genome instability [25]. The minichromosome maintenance protein complex is composed of six proteins (MCM2-7) and is a key player in the initiation of DNA replication [26]. Shim et al. evaluated MCM6 expression in 211 GIST samples and found high MCM6 expression was associated with tumor size, mitosis, tumor necrosis, presence of recurrence/metastasis, and poor overall survival [27]. AXL is involved in the cell cycle, which expression was strong in KIT-negative GIST samples, and knockdown of AXL inhibited viability in KIT-negative GIST cell lines [28]. Sugase et al. found inhibition of the FAK signaling showed an inhibitory effect on cell growth and suppressed the phosphorylation of AKT, indicating a cross-talk between the AKT and FAK pathways in the secondary imatinib-resistant GIST cells [29].
An overview of potential novel mechanisms of action underlying Tumor Treating Fields-induced cancer cell death and their clinical implications
Published in International Journal of Radiation Biology, 2021
Narasimha Kumar Karanam, Michael D. Story
Interestingly, TTFields exposure in and of itself was shown to produce γ-H2AX foci, which is a marker of DNA damage as well as a marker for stalled replication forks, suggesting that TTFields not only delay DNA damage repair, but also induces replication stress. TTFields treatment downregulates the expression of MCM6 and MCM10 genes, essential components of the DNA replication complex and members of the FA pathway genes, leading to an elevated number of chromatid type aberrations. Furthermore, as part of the induction of replication stress, there is a decrease in the length of newly synthesized DNA and an increase in R-loop formation (Karanam et al. 2018, 2019). Mitosis and DNA damage pathways are tightly regulated through feedback mechanisms. By monitoring temporal gene expression changes associated with regulators of mitosis and DNA damage pathways, Karanam et al. showed that mitotic aberrations and DNA damage events while certainly linked to one another likely also occur independent of each other. These results established the role of TTFields in DNA damage repair and replication stress pathways. Key events in mitosis and DNA damage and replication stress pathways that are affected by TTFields are shown schematically in Figure 2.
Long-term 1800MHz electromagnetic radiation did not induce Balb/c-3T3 cells malignant transformation
Published in Electromagnetic Biology and Medicine, 2021
Zhen Ding, Xiaoyong Xiang, Jintao Li, Shuicai Wu
The PPI network analysis inplied that there are a strong interaction protein network of ribosomal proteins (RPs) and minichromosome maintenance cmplex (Mcms). Ribosome biogenesis and protein translation are finely coordinated with and essential for cell growth, proliferation, differentiation, and animal development. Highly proliferating cancer cells demand a huge amount of proteins, which means that cancer cells need more highly efficient ribosome translational machineries than normal cells (Ruggero and Pandolfi 2003; Silvera et al. 2010). Many RPs have been found to be up-regulated at either mRNA or protein level in various human tumors (Shuda et al. 2000; Kondoh et al. 2001; Artero-Castro et al. 2011; Chen and Dittmer 2011; Dong et al. 2019). Besides, the minichromosome maintenance family (MCMs) plays a central role in the replication, as replicative DNA helicase, and forms a hexameric ring-shaped complex around DNA. Studies have indicated that MCM proteins are highly expressed in several types of cancers, such as lung, breast, colon, and other cancers (Giaginis et al. 2009; Liu et al. 2017; Shetty et al. 2005). ZK Liu et al (Liu et al. 2018) found that MCM6 was identified as a driver of S/G2 cell cycle progression and a potential diagnostic and prognostic marker in HCC.