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Anatomy and Embryology of the External and Middle Ear
Published in John C Watkinson, Raymond W Clarke, Christopher P Aldren, Doris-Eva Bamiou, Raymond W Clarke, Richard M Irving, Haytham Kubba, Shakeel R Saeed, Paediatrics, The Ear, Skull Base, 2018
The sebaceous glands produce an oily material (sebum) from the breakdown of their fat-containing cells which is usually excreted into the root canals of the hair follicles. The mixture of desquamated cells, cerumen and sebum forms wax. Human earwax is a Mendelian trait consisting of wet and dry forms. Dry wax, lacking cerumen, is yellowish or grey and brittle, while wet wax is brownish and sticky. The wet phenotype is dominant over the dry type, and is frequently seen in populations of European and African origins. East Asians show the dry phenotype and there are intermediate frequencies among the Native American and Inuit of Asian ancestry. A single-nucleotide polymorphism in the ABCC11 gene is responsible for the determination of earwax type, with the AA genotype corresponding to dry wax and GA and GG to wet wax.10 There is dispute with regard to the specific antibacterial activity of cerumen in in vitro studies.11,12 However, the areas of skin that take part in cerumen production have all the components of an active local immune system and probably protect the canal by an antibody-mediated local immune response.13
A novel tumor-homing TRAIL variant eradicates tumor xenografts of refractory colorectal cancer cells in combination with tumor cell-targeted photodynamic therapy
Published in Drug Delivery, 2022
Zhao Li, Tianshan She, Hao Yang, Tao Su, Qiuxiao Shi, Ze Tao, Yanru Feng, Fen Yang, Jingqiu Cheng, Xiaofeng Lu
The chemotherapeutic MDR of cancer cells is predominantly attributed to overexpressed chemical efflux pumps, such as ABC transporters. To investigate the expression of ABC transporters in tumor tissues derived from CRC patients, public RNA-seq data obtained from TCGA and GTEx were analyzed by GEPIA. As shown in Figure 1(A) and Supplementary Figure S1, bioinformatics analysis demonstrated that the tumor tissue levels of ABC transporters, including ABCB1, ABCB7, ABCC1, ABCC2, ABCC3, ABCC4, ABCC6, ABCC10, ABCC11, and ABCG1, were significantly higher than those in normal tissues, suggesting the MDR of CRC cells. In fact, cytotoxicity assays revealed that CRC cells, such as COLO205, HCT116, LS174T, and HT29, showed resistance (IC50 > 1000 nM) to all tested chemical drugs, including cisplatin, vincristine, doxorubicin, and bortezomib (Figure 1(B)). Interestingly, bioinformatics analysis also demonstrated that death receptors, including DR4 and DR5, were overexpressed in CRC tumor tissues (Figure 1(A)), suggesting the potential of TRAIL as an anticancer agent for CRC. In fact, TRAIL showed robustly (ICs50 < 10 nM) cytotoxicity in CRC cells, including COLO205, HCT116, and LS174T cells overexpressing DR5 and/or DR4 (Figure 1(C, D)), indicating that TRAIL might overcome the chemotherapeutic MDR of CRC cells. Nevertheless, due to the low expression of death receptors, some CRC cells, such as HT29, showed moderate resistance (IC50s > 50 nM) to TRAIL (Figure 1(C, D)), suggesting the need to improve the cytotoxicity of TRAIL in these cells.