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Lipopolysaccharide-Binding Protein
Published in Helmut Brade, Steven M. Opal, Stefanie N. Vogel, David C. Morrison, Endotoxin in Health and Disease, 2020
In a review that will hopefully be read by persons outside the field, it will be puzzling if no mention of the term “Septin” is made, since it is common enough in the literature cited. Previous studies have suggested that a substance referred to as Septin was actually accomplishing the functions ascribed to LBP (24). This reviewer’s comments on septin have been recorded elsewhere (25,26), and the originator of the term has declared it “unnecessary” (27).
Screening for Colorectal Adenoma and Adenocarcinoma
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
At the present time, testing for faecal haemoglobin and endoscopy of the lower gastrointestinal endoscopy are the only recognised strategies for population screening for colorectal cancer screening, but, in addition to the faecal tests mentioned above, there are a number of novel approaches under development that might change this in the near future. Peripheral blood has been used to search for markers that might act as effective screening tests, especially as there is some evidence that people generally (although by no means universally) prefer blood tests to faecal tests. One particularly interesting approach is to look for increased levels of free-circulating methylated DNA in the plasma, and it has been shown that the SEPT9 DNA methylation-based biomarker can discriminate between samples from colorectal cancer patients and normal controls. This marker is derived from the Septin 9 gene, which belongs to a class of GTPases that play a role in multiple cellular processes, and methylation of this gene is associated with cancer. Initial work found SEPT9 to have a sensitivity for colorectal cancer of 70% whilst maintaining a specificity of 90%,43 and although this does not indicate superior performance to FIT, it has been argued that it represents a viable, if expensive, alternative for those who find faecal testing unacceptable. In any event, it is now commercially available, although it has not been incorporated into any population screening programme. Tumour associated proteins identified by mass spectrometry and microRNAs have also been studied, but no convincing candidates have yet emerged.
Botulinum toxins: Pharmacology, immunology, and current developments
Published in Anthony V. Benedetto, Botulinum Toxins in Clinical Aesthetic Practice, 2017
BoNT types A and E cleave SNAP-25 at different sites, and the effects of type E are much shorter. Evidence indicates that the type A light chain and its cleavage product (SNAP-25197) localize to the plasma membrane, whereas the type E light chain is distributed throughout the cell cytoplasm.44 The localization of type A light chain to the plasma membrane is decreased following mutation of the dileucine motif. Mutation of the dileucine motif of type A also leads to rapid recovery of neuromuscular function in rats.45 More recently, mutation of the two leucines has been found to prevent interactions between the light chain and septins—intracellular structural proteins found clustered with the light chain at the plasma membrane (Figure 2.5).46 The dileucine mutation also increases degradation of the type A light chain, as does interference with light chain-septin clustering. In contrast, the type E light chain does not interact with septins. These data indicate that the clustering of the type A light chain with septins at the plasma membrane via interactions with the dileucine motif is critical for its stability; these characteristics importantly contribute to the duration of action of BoNTA in clinical use.44,46 Type A is the only botulinum neurotoxin serotype that contains a dileucine motif at the C terminus of the light chain.44
Liquid biopsies in gastrointestinal malignancies: when is the big day?
Published in Expert Review of Anticancer Therapy, 2018
Anthony Lopez, Kazuto Harada, Dilsa Mizrak Kaya, Xiaochuan Dong, Shumei Song, Jaffer A. Ajani
Circulating DNA methylation analysis was widely evaluated [33–37]. Septins are a group of GTP-binding and filament-forming proteins, known to have diverse cellular roles including polarity determination, cytoskeletal reorganization, membrane dynamics, vesicle trafficking, and exocytosis. Downregulation of the expression of some transcripts of SEPT9 by methylation was suggested in ovarian tumorigenesis [38]. Plasma methylated SEPT9 (mSEPT9) was the most studied biomarker for CRC diagnosis, with sensitivity ranged from 48.2% to 79.3% [33,35,37]. In the PRESEPT trial, the accuracy of mSEPT9 was prospectively assessed for detecting CRC in a screening population [33]. Among 7941 asymptomatic individuals, ≥50 years old scheduled for screening colonoscopy at 32 US and German clinics, 53 CRC cases were diagnosed. mSEPT9 test showed a low sensitivity for CRC detection (48.2%), contrasting with a high specificity of 91.5%. These results are similar to those obtained with first-generation FOBT. As a consequence, a CRC screening exclusively based on circulating mSEPT9 does not seem relevant.
Septin9 DNA methylation as a promising biomarker for cervical cancer
Published in Journal of Obstetrics and Gynaecology, 2023
Qiaowen Bu, Xiping Luo, Lulu He, Jian Ma, Shaoyi He, Wen Lei, Weiping Zhou, Hua Deng, Yu Lin, Liang Zhang, Xiaoshan Hong
Septin9 is a novel tumour biomarker and a member of the Septin gene family involved in cell division, migration, apoptosis and DNA repair (Connolly et al. 2011). A recent study found that Septin9 was hypermethylated in cervical cancer tissues compared to the normal controls, with satisfactory sensitivity and specificity (Jiao et al. 2019). However, the feasibility of detecting Septin9 methylation in cervical scrapings has not yet been carried out. Our team previously established a high-quality qMS-PCR methylation method for non-invasive screening of colorectal cancer. In our pilot study, we also found Septin9 transcript isoform v2 was highly methylated in cervical cancer tissues. We further confirmed that in cervical scrapings, increases in Septin9 methylation were significantly correlated with greater severity of cervical lesions, which was consistent with Jiao’s recent report (Jiao et al. 2019).This study revealed a slightly poor sensitivity of methylated Septin9 in identifying ≥ HSIL than cytologic testing (70.42% vs 90.14%), while displayed a superior specificity (80.19% vs 51.89%), with a correspondingly equivalent AUC (0.80 vs 0.71). These data were similar with our previous work that methylated FAM19A4 had a lower sensitivity but higher specificity than cytologic testing in detecting ≥ HSIL (Bu et al. 2018). In brief, although Septin9 methylation showed a slightly poorer sensitivity in detecting ≥ HSIL, it still played an indispensable role in detecting cervical cancer. Septin9 methylation testing can reduce the rates of excessive colposcopy referral and over-diagnosis in clinical application; and improve the accuracy of detection rates of cervical lesions for its high specificity.
The involvement of liquid crystals in multichannel implanted neurostimulators, hearing and ENT infections, and cancer
Published in Acta Oto-Laryngologica, 2019
Chouard Claude-Henri, Christiane Binot, Jean-François Sadoc
Septins are a GTP-binding protein family [45]. They contribute to lateral compartmentalization of membranes (forming, we think, a lipid raft), to cortical rigidity, and to membrane traffic regulation by association with actin-based membrane lipids and microtubules, and regulate actomyosin contractibility [46]. Septins 4, 5, 7 are localized in inner and outer pillar cells and in Deiters cells; septins 5 and 7 are co-localized with presynaptic vesicles efferent nerve endings. The cell plasma membrane has been shown to contract equatorially (incurvature), and septins are essential agents in the contractile ring.