The gastrointestinal system
C. Simon Herrington in Muir's Textbook of Pathology, 2020
The most common malignant salivary neoplasm is mucoepidermoid carcinoma (MEC) which may affect children as well as adults. Histologically it shows a variable mixture of squamoid, mucous, and intermediate cell types. The behaviour of mucoepidermoid carcinoma is variable with prognosis reflecting tumour grade. A t(11;19)(q21;p13) translocation and CRTC1-MAML2 gene fusion is found in most MECs. Adenoid cystic carcinoma tends to occur in older individuals and often shows a distinctive cribriform or ‘lace-like’ growth pattern (Figure 10.16). It has a particular tendency for perineural spread, thus making it very difficult to eradicate surgically. The majority of tumours have a t(6;9) translocation and MYB-NFIB gene fusion.
Experience and activity-dependent control of glucocorticoid receptors during the stress response in large-scale brain networks
Published in Stress, 2021
Damien Huzard, Virginie Rappeneau, Onno C. Meijer, Chadi Touma, Margarita Arango-Lievano, Michael J. Garabedian, Freddy Jeanneteau
Intracellular calcium (Ca2+) is a central mediator of transcriptional regulation and is controlled by neuronal activity that could gate GR and MR responsiveness either through the direct or indirect mode of transcriptional regulation (Zhang et al., 2009). Several phosphatases, proteases, and cargo transporters operating as Ca2+-sensors are involved in the response to glucocorticoids in multiple cellular compartments. Actions on synaptic neurotransmission and on nuclear gene transcription, which are mediated by GR and MR, require coincident Ca2+ mobilization from the mitochondria and the endoplasmic reticulum (Chameau et al., 2007; Harris et al., 2019; Mayanagi et al., 2008; Simard et al., 1999). Mobilization of Ca2+ and cAMP are both required for the nuclear import of the CREB-regulated transcription coactivators (CRTC1/2/3), a family of cofactors for CREB and GR (Altarejos & Montminy, 2011; Hill et al., 2016). In particular, CRTC2 can integrate BDNF and glucocorticoid signals in the hypothalamus to control the direction and magnitude of transcription at the corticotropin-releasing hormone (Crh) promoter and the response of the hypothalamic-pituitary-adrenocortical (HPA) axis to stressors (Jeanneteau et al., 2012). This molecular pathway also regulates glucose metabolism and the energetic adaptation to stress by controlling the expression of the rate-limiting enzymes glucose-6-phosphatase and phosphoenolpyruvate carboxykinase in the liver (Hill et al., 2016).
Adenosquamous carcinoma of the digestive system: a literature review
Published in Scandinavian Journal of Gastroenterology, 2020
Hong-Shuai Li, Tao He, Li-Li Yang
MEC is like ASC in that it has both SCC and AC components, but the squamous component often lacks the typical keratinized bead structure and the AC component has a distinct mucin secretion profile. ASC usually has a clear boundary between the glandular and squamous components or contains a transition zone, whereas MEC is a homologous mixture of the two components [9]. In addition, MEC usually characteristically expresses the CRTC1-MAML2 fusion gene [30], which is important for its identification. Kiyoshi et al. [31] suggested that pancreatic MECs and ASC-Ps have similar clinicopathological and molecular characteristics, speculating that the former may be a morphological variant of the latter, and suggesting that the term ‘pancreatic MEC’ should be renamed ‘ASC-P with MEC-like features.’ AA is an AC-containing squamous chemotaxis, which contains both the AC and chemotaxis components. The SCC component is benign and often involves a discontinuous focal distribution [29], which is easier to distinguish.
Genomics in non-adenoid cystic group of salivary gland cancers: one or more druggable entities?
Published in Expert Opinion on Investigational Drugs, 2019
Stefano Cavalieri, Francesca Platini, Cristiana Bergamini, Carlo Resteghini, Donata Galbiati, Paolo Bossi, Federica Perrone, Elena Tamborini, Pasquale Quattrone, Lisa Licitra, Laura Deborah Locati, Salvatore Alfieri
In addition to the aforementioned genomic alterations, salivary gland malignancies can be driven by recurrent gene fusions as well. Even though many of them are not druggable, the presence of a specific translocation could be pathognomonic for a particular subtypes [81,82]. Other recurrent genetic fusions are CRTC1-MAML2 in mucoepidermoid carcinoma, especially in low/intermediate grade types [83], and MECT1-MAML2 translocation, which can be found in up to 88% cases of mucoepidermoid carcinoma [84]. EWRS1-ATF1 was reported in cases of hyalinizing clear cell salivary gland carcinoma [85]. Acinic cell carcinoma might bear HTN3-MSANTD3 translocation, leading to up-regulation of genes involved in regulation of translation [86].
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