China
Africa
Explore chapters and articles related to this topic
Aberrant Methylation of UC Promoters in Human Pancreatic Ductal Carcinomas
Published in Surinder K. Batra, Moorthy P. Ponnusamy, Gene Regulation and Therapeutics for Cancer, 2021
Michiyo Higashi, Seiya Yokoyama
In PDAC, each MUC1 glycoform has a high expression level. Expression of MUC1 occurs in cell apical areas along the luminal side as well as in the luminal secretion of tubular structures, and at the basolateral membrane and in the cytoplasm, particularly in poorly differentiated areas. This expression pattern in PDACs differs from the pattern in the normal pancreas [8, 15, 16]. MUC1/DF3 high expression (more than 50% of cancer cells positive) was found to be significantly more frequent in pTNM stage IV than in stage III, and was associated with unfavorable overall survival in stage IV cases [17]. These data suggest that expression of MUC1/DF3 is associated with progression of PDAC. MUC2 is not expressed except mucinous (colloid) carcinoma or large extracellular stromal mucin pools containing suspended neoplastic cells [18]. MUC4 was highly expressed mainly in the cytoplasm [14]. The high MUC4 expression was an independent factor for a poor prognosis in PDAC [14]. MUC5AC also showed high expression [14, 19].
Host Defense II: Acquired Immunity
Published in Constantin A. Bona, Francisco A. Bonilla, Textbook of Immunology, 2019
Constantin A. Bona, Francisco A. Bonilla
Recently, a number of target antigens for immune rejection have been described in various human tumors. The gene MUC-1 encodes a mucin which is abnormally glycosylated in pancreatic and breast carcinomas; the abnormal mucin is is recognized by tumor-specific CTLs. An entire family of melanoma antigen encoding genes (MAGE) is located on the X chromosome. Melanoma-specific CTLs may recognize several of these antigens. At least one of this group of molecules is expressed in normal testis tissue; the functions of these proteins are not known.
Tumor immunology
Published in Gabriel Virella, Medical Immunology, 2019
Initiation of the process requires the release of tumor antigens into the tumor microenvironment. In general, there are two types of tumor antigens: (1) tumor-associated antigens (TAAs) and (2) tumor-specific antigens (TSAs). TAAs are derived from proteins that are expressed not only by tumors but also by other normal tissues. The difference is that in tumors these proteins are either overexpressed or have undergone some kind of posttranslational modification. For example, a common TAA is derived from the protein mucin-1 (MUC1). MUC1 is a heavily glycosylated transmembrane protein that is expressed on the apical surface of glandular epithelial cells. In tumor cells, MUC1 is overexpressed, underglycosylated, and its expression is no longer limited to the apical surface of cells. These changes in the expression pattern lead to generation of tumor-associated MUC1 antigens that are immunogenic. The immune system can mount a response against these antigens, but there is risk of cross-reactivity with normal tissues. TSAs (also known as neoantigens) are derived from “neoproteins” that are only expressed by the tumor itself. These proteins are different from normal proteins as a result of tumor-specific mutations. Neoantigens derived from these proteins are tumor specific, and immune responses to these types of antigens target only the tumor while sparing normal tissues. Clinical responses mediated by T lymphocytes targeting neoantigens have been identified in different types of cancers.
Chitosan-coated bovine serum albumin nanoparticles for topical tetrandrine delivery in glaucoma: in vitro and in vivo assessment
Published in Drug Delivery, 2022
Salma El-Sayed Radwan, Riham M. El-Moslemany, Radwa A. Mehanna, Eman H. Thabet, Elsayeda-Zeinab A. Abdelfattah, Amal El-Kamel
Chitosan-coated albumin NPs were first formulated by Karimi et al. (Karimi et al., 2013) using the phase separation method and ionic interaction to prepare albumin–CS core–shell NPs for DNA delivery. In preceding research, they were functionalized by MUC-1 to target cancers that overexpress MUC-1. The system was able to encapsulate the hydrophobic drug, paclitaxel, in the albumin inner core, enhancing its permeation to the cells which was attributed to CS positive charge and the active targeting moiety (Esfandyari-Manesh et al., 2016). Albumin NPs were designed as a growth factor carrier by desolvation method and were further stabilized by CS coating by Li et al. (2018). The CS-coated albumin NPs presented favorable stability and sustained release kinetics of the osteogenic protein NELL-1. Moreover, Piazzini et al. (2019) reported the study of CS coated albumin NPs as a promising strategy for the nose to brain drug delivery. However, to our knowledge, this is the first time that CS-coated albumin NPs are studied as an ocular drug delivery platform for topical delivery.
MUC1-C integrates type II interferon and chromatin remodeling pathways in immunosuppression of prostate cancer
Published in OncoImmunology, 2022
Masayuki Hagiwara, Atsushi Fushimi, Atrayee Bhattacharya, Nami Yamashita, Yoshihiro Morimoto, Mototsugu Oya, Henry G. Withers, Qiang Hu, Tao Liu, Song Liu, Kwok K. Wong, Mark D. Long, Donald Kufe
In support of MUC1-C involvement in promoting suppression of the PC TME, analysis of the TCGA-PRAD dataset demonstrated that MUC1 associates with enrichment of REACTOME INTERLEUKIN 10 SIGNALING and GO RESPONSE TO TRANSFORMING GROWTH FACTOR BETA pathways (Figure 7a). GSEA confirmed that MUC1-high tumors significantly associate with activation the IL-10 (Supplemental Fig. S8a) and TGFB1 (Supplemental Fig. S8b) gene signatures, which function as negative regulators of the immune TME.9,61 We also found that MUC1-high tumors associate with expression of CCL5 (Supplemental Fig. S8c), an inflammatory chemokine that recruits TAMs, MDSCs and T-regs into the TME and inhibits CTL activity.62 Consistent with these findings, MUC1 was significantly associated with negative regulation of (i) T cell and NK cell mediated immunity, (ii) T cell proliferation, and (iii) B cell activation (Figure 7b). In extending these analyses to the Beltran cohort (67 CRPC/NEPC samples),63 tumors were stratified by MUC1-high and MUC1-low expression. Hierarchical clustering based on cell type estimation (xCell)34 demonstrated that MUC1-high clusters associate with decreased estimates of immune cell infiltration (Figure 7c). Further analysis by immune cell type demonstrated that MUC1-high tumors significantly associate with decreases in CD4+ memory T cells, Th2 cells, B cells and M2 macrophages, among others, as well as the ImmuneScore (Figure 7d; Supplemental Fig. S8d).
Mucin receptors in chronic rhinosinusitis with nasal polyps
Published in Acta Oto-Laryngologica, 2022
Ahmet Bedir, Abdulkadir Özgür, Mustafa Bakırtaş, Doğukan Özdemir, Dursun Mehmet Mehel, Gökhan Akgül, Mehmet Çelebi
Different roles have been defined for MUCs depending on whether they are secreted or membrane-bound. MUC1, a membrane-bound MUC, acts as a sensor receptor and contributes to cell signal transmission [11]. MUC1 has recently emerged as an anti-inflammatory molecule that prevents bacteria and virus-induced inflammation in the airways [12–14]. A study by Milara et al. showed that MUC1 expression was low in CRS patients with oral steroid-resistant NPs [15]. In another study conducted by Milara et al., 22 patients with CRS and NPs were found to have high secretion of MUC4, and this high level of secretion may have been related to the steroid therapy resistance [16]. MUC2 and MUC6 receptor positivity was not detected in the NP tissues in our study group. No significant relationship was detected between MUC1 receptor positivity and clinical findings. MUC5A positivity was associated with a decreasing in the response to steroid treatment and the quality of the surgical site. Therefore, in patients with MUC5A receptor positivity in their preoperative biopsies, if surgical treatment is planned, the planning of these patients should be done more carefully. Considering that the surgical site quality may be worse in these patients, it may be recommended that these patients be operated by more experienced surgeons.