The immune system plays a key role in the protective response against oral cancer; however, the tumor microenvironment (TME) impairs this anti-cancer response by modulating T helper (Th) responses and promoting an anti-inflammatory environment. Regulatory T cells (Tregs) and Th2 effector cells (Teff) are associated with poor prognosis in oral squamous cell carcinoma (OSCC). However, the main immunomodulatory mechanisms associated with the enrichment of these subsets in OSCC remain unknown. We characterized Th-like lineages in Tregs and Teff and evaluated immunomodulatory changes induced by the TME in OSCC. Our phenotypic data revealed a higher distribution of tumour-infiltrating CCR8+ and Th2-like Treg in OSCC compared with non-malignant samples, whereas the percentages of Th1 cells were reduced in cancer. We then analyzed the direct effect of the TME by exposing T cell subsets to cancer secretomes and observed the OSCC secretome induced CCR8 expression and reduced cytokine production from both subsets. Transcriptomic analysis showed that the co-culture with OSCC secretome induced several gene changes associated with the vitamin D (VitD) signaling pathway in T cells. In addition, proteomic analysis identified the presence of several proteins associated with prostaglandin E2 (PGE2) production by rapid membrane VitD signaling and a reduced presence of the VitD binding protein. Thus, we analyzed the effect of VitD and PGE2 and observed that VitD promotes a regulatory Th2-like response with CCR8 expression whilst PGE2 also modulated CCR8 but inhibited cytokine production in combination with VitD. Finally, we evaluated the presence of CCR8 ligand in OSCC and observed increased chemokine CCL18, which was also able to upregulate CCR8 in activated Th cells. Overall, our data showed the immunomodulatory changes induced by the TME involving CCR8 expression and regulatory Th2 phenotypes, which are associated with PGE2 mediated VitD signaling pathway and CCL18 expression in OSCC.
Summary:Craniofacial microsomia is a broad term that covers a variety of craniofacial malformation conditions that are caused by alterations in the derivatives of the first and second pharyngeal arches. In general terms, diverse therapeutic alternatives are proposed according to the growth stage and the severity of the alteration. When craniofacial growth has concluded, conventional orthognathic surgery (Le Fort I osteotomy, bilateral sagittal split osteotomy, and genioplasty) provides good alternatives for MI and MIIA type cases. Reconstruction of the mandibular ramus and temporomandibular joint before orthognathic surgery is the indicated treatment for cases MIIB and MIII. The goal of this article is to establish a surgical treatment algorithm for orthognathic surgery on patients with craniofacial microsomia, analyzing the points that allow the ideal treatment for each patient to be chosen.
SANDOVAL, C.; NUÑEZ, M. & ROA, I.Dental pulp fibroblast and sex determination in controlled burial conditions. Int. J. Morphol., 32(2):537-541, 2014.
SUMMARY:The need to identify bodies that are found as a result of disappearances with a diversity of causes, illegal burials and massive disasters, represent a wide percentage of dentistry practice on forensic research. The following study determined the performance of Barr Body Test, in fibroblasts of healthy teeth, under different conditions of burial (in vitro) with variations in pH, humidity and salinity in terms of general accuracy and sensitivity for men and women. Analyzed sample considered 47 dental pulps, taken from teeth under burial conditions during a period of a month. From dental pulps samples, 265 histological cuts valid for this study, were obtained, which were observed with an optical microscope under conventional H/E staining. Results showed a 98.9% of well-diagnosed cases, which correspond to the overall accuracy of the method. Sensitivity for men was 97.5% and 100% for women, over the analyzed sample. In low humidity conditions, 3 samples of badly diagnosed cases in men were observed, with a group accuracy of a 90%, with a sensitivity of 25% for men and 100% for women. The present study establishes that based on these results, the performance of Barr Body Test in fibroblasts, proposed for healthy pulp teeth, is not affected by burial conditions in terms of pH (acid-alkaline), salinity (high-low) and high humidity.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.