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Precision medicine in acute myeloid leukemia
Published in Debmalya Barh, Precision Medicine in Cancers and Non-Communicable Diseases, 2018
CD33 antibody-drug conjugates such as gemtuzumab ozogamicin and vadastuximab talirine (SGN-CD33A) (Burnett et al., 2012; Daver et al., 2016; Minagawa et al., 2016; Table 10.9); Hedgehog inhibitors like sonidebig (erismodegib, LDE255), glasdegib (PF-04449913), and vismodegib; neddylation and subsequent ubiquitination inhibitors (pevonedistat); and Wnt signaling pathway inhibitors (Fukushima et al., 2016; Hanna and Shevde, 2016; Ma et al., 2015; Medler et al., 2015; Swords et al., 2017) together with standard chemotherapy are in ongoing trials. Further therapeutic approaches including NF-κB signaling pathway inhibition (Bosman et al., 2016; Fuchs 2010; Siveen et al., 2017; Zhou et al., 2015), PI3 K/AKT/mTOR signaling pathway inhibition, (Brenner et al., 2016; Fuchs 2011; Hauge et al., 2016) and targeting the S100A8/S100A9-TLR4-ERK/JNK/p38 pathway (Laouedj et al., 2017; Tamburini, 2017) were studied. Cell division cycle 25 (CDC25) protein phosphatases inhibition had antiproliferative effects on primary human AML cells for a subset of patients identified by gene expression profiling (Brenner et al., 2017).
The S100A7/8/9 Proteins: Novel Biomarker and Therapeutic Targets for Solid Tumor Stroma
Published in Surinder K. Batra, Moorthy P. Ponnusamy, Gene Regulation and Therapeutics for Cancer, 2021
Sanjay Mishra, Dinesh Ahirwar, Mohd W. Nasser, Ramesh K. Ganju
The association between carcinogenesis and inflammation has long been recognized and chronic inflammation is considered as one of the hallmarks of cancer [1]. The very initial stage of cancer development is abrupt, persistent and chronic inflammation. Chronic inflammatory diseases often increase the risk of cancer development [2–4]. In addition, non-steroid anti-inflammatory drugs (NSAIDs), especially aspirin, have been shown to benefit different types of cancer patients [1, 5–8]. Chronic inflammation causes release of reactive oxygen species (ROS), which can induce DNA damage and initiate malignant transformation [2]. The proteins of S100 family are known to be expressed at the site of inflammation and abundantly present in various inflammatory diseases including cancer. Based on their inflammatory nature, S100 proteins have been analyzed for their ability to serve as biomarkers in cancers. Various comparative and functional genomics studies have reported that S100 genes are differentially expressed in cancer cells [9, 10]. Among various S100 family genes, S100A7, S100A8 and S100A9 (S100A8/A9) have emerged as critical genes involved in inflammatory processes. S100A8/A9 proteins are often produced together [11]. An elevated level of S100A7 and S100A8/A9 is often found in inflammatory diseases such as psoriasis, arthritis, diabetes, and inflammatory bowel disease [12–14]. In fact, strong up-regulation of these proteins has also been observed in many tumors, including gastric, esophageal, colon, pancreatic, bladder, ovarian, thyroid, breast and skin cancers [15, 16]. In this chapter, we will describe the altered expression, biological functions and therapeutic targeting of S100A7/8/9 in different types of human cancers.
Salmonella pathogenicity island 1 knockdown confers protection against myocardial fibrosis and inflammation in uremic cardiomyopathy via down-regulation of S100 Calcium Binding Protein A8/A9 transcription
Published in Renal Failure, 2022
Xinyong Cai, Lang Hong, Yuanyuan Liu, Xiao Huang, Hengli Lai, Liang Shao
S100 calcium binding protein A8 (S100A8) and S100A9, Ca2+-binding proteins belonging to the S100 family, have been documented to play a decisive role in the development of inflammation-related disorders [7]. As a heterodimer, S100A8/S100A9 is implicated in the process of neutrophil-related inflammation [8]. S100A8/A9 also irreversibly damages tubular epithelial cell contacts to orchestrate kidney fibrosis [9]. S100A8/A9 acts as a pro-inflammatory cytokine in acute hypertension and promotes the production of some cytokines in myocardial fibrosis [10]. Besides, S100A8/A9 plays a negative role in the early period of myocardial infarction [11]. Salmonella pathogenicity island 1 (SPI1, also called PU.1) pivotally orchestrates signaling in the immune system and plays an important part in the growth of lymphocytes and myeloid cells [12]. The inhibition of SPI1 may be a new and effective treatment approach for various fibrotic diseases [13]. The knockdown of SPI1 reduces the expression of pro-inflammatory genes to restrict microglial inflammation [14]. A previous study suggested that SPI1 repression ameliorates angiotensin-II-induced atrial fibrosis [15]. Of note, SPI1 is a transcription factor of the E26 transformation specific family, a large family of transcription factors that contains 28 family members and takes part in various cell processes, which was reported to be associated with the co-expression of S100A9 [16,17].
Identified potential biomarkers may predict primary nonresponse to infliximab in patients with ulcerative colitis
Published in Autoimmunity, 2022
Jixiang Zhang, Xiaohan Wu, Shuchun Wei, Chuan Liu, Xiaoli Wang, Weiguo Dong
Calprotectin comprises two monomers in mammals, S100A8 and S100A9, and belongs to the calcium-binding S100 leukocyte protein family [23, 24]. An increasing number of studies have confirmed that calprotectin, especially faecal calprotectin, is closely associated with the occurrence and development of UC. The S100A8/S100A9 complex not only stimulates and enhances the activation of immune cells but also orchestrates an inflammatory response [25, 26]. TNFα has been shown to work synergistically with S100A8/A9 in inflammatory responses by up-regulating the expression of S100A8/A9 and S100A8/A9, which in turn up-regulates TNFα expression in a functional feedback loop that represents a self-sustaining inflammatory loop. In our study, we found that in the colon tissues of UC patients with primary nonresponse to infliximab, the expressions of S100A8 and S100A9 were up-regulated. Based on previous reports and our findings, we speculate that while TNFα and S100A8/A9 as the pro-inflammatory factors were remarkably upregulated, the antagonistic effect of infliximab on TNFα was offset by the induction effect of S100A8/A9 leading to primary nonresponse to infliximab.
Identification of differentially expressed proteins associated with recurrence in ovarian endometriotic cysts
Published in Systems Biology in Reproductive Medicine, 2020
Genhai Zhu, Jiao Kong, Xinhui Fu, Fujin Liu, Haiyan Huang, Lan Hong, Kang Wang
S100 calcium-binding protein A8 (S100A8) and S100 calcium-binding protein A9 (S100A9) are both important members of the calcium-binding protein S100 family, and often bind to form heterodimers needed for various functions (Argyris et al. 2018). S100A8 and S100A9 function in regulating cell migration, promoting the production of proinflammatory factors, and as adhesion molecules (Cluzeau et al. 2017). They also mediate inflammatory reactions and modulate the amount and extent of a certain immune response. S100A8 is often included in tumor-related studies (Austermann et al. 2017; Wu et al. 2018). S100A8 and S100A9 are thought to play similar roles in the pathogenesis of endometriosis, despite the fact that no reports concerning their roles in endometriosis have been published. Adhesion, epithelial metaplasia, and immune factors exert critical function in the pathogenesis of endometriosis, and it can be speculated that S100A8 and S100A9 proteins may affect these factors to regulate the occurrence and recurrence of endometriosis (Moris et al. 2016). In addition, our results showed that the S100A8 and S100A9 proteins were expressed at different levels in normal ovarian tissues when compared to ovarian endometriotic cyst tissues, and were obviously up-regulated in ovarian endometriotic cysts. Consequently, S100A8 and S100A9 may be involved in the recurrence mechanism of ovarian endometriotic cysts, and represent new markers for the evaluation of disease severity, the effect of treatment, and disease recurrence.