Tumor-initiating cells (T-ICs) discovered in various tumors have been widely reported. However, T-IC populations in salivary gland tumors have yet to be elucidated. Using the established Pleomorphic Adenoma Gene-1 (Plag1) transgenic mouse model of a salivary gland tumor, we identified CD44high (CD44hi) tumor cells, characterized by high levels of CD44 cell surface expression, as the T-ICs for pleomorphic adenomas. These CD44hi tumor cells incorporated 5-bromo-2-deoxyuridine (BrdU), at a lower rate than their CD44negative (CD44neg) counterparts, and also retained BrdU for a long period of time. Cell surface maker analysis revealed that 25% of the CD44hi tumor cells co-express other cancer stem cell markers such as CD133 and CD117. As few as 500 CD44hi tumor cells were sufficient to initiate pleomorphic adenomas in one third of the wildtype mice, whereas more than 1×104 CD44neg cells were needed for the same purpose. In NIH 3T3 cells, Plag1 was capable of activating the gene transcription of Egr1, a known upregulator for CD44. Furthermore, deletion of sequence 81–96 in the Egr1 promoter region abolished the effect of Plag1 on Egr1 upregulation. Our results establish the existence of T-ICs in murine salivary gland tumors, and suggest a potential molecular mechanism for CD44 upregulation.
Over-expression of the proto-oncogene pleomorphic adenoma gene 1 (PLAG1) plays a crucial role in the formation of pleomorphic adenoma, which is the most common type of salivary gland tumor. To understand the molecular mechanisms governing PLAG1-mediated tumorigenesis, we used a microarray-based approach to identify PLAG1 target genes. We validated the expression of several genes, including Bax, Fas, p53, p21, p16, Cyclin D1, Egfr, Trail-R/DR5, c-Fos, c-myc and Igf2, by real-time RT-PCR or western blotting. Using luciferase reporter gene assays, we determined that the promoters of Bax, Fas, p53, TRAIL-R/DR5, and c-Fos were transactivated by PLAG1. PLAG1 not only activates genes that promote cell proliferation and tumor formation but also genes that inhibit these cellular processes. Therefore, we conclude that PLAG1 may play a dual role in tumor formation.
Multiple intraglandular sialolithiasis for stones deep in the glandular parenchyma may require submandibulectomies, especially if sialendoscopic facilities are unavailable. We describe a gland-sparing intraoral sialolithotomy approach for both hilar and intraparenchymal multiple sialoliths. Nine patients with obstructive sialadenitis resulting from multiple sialoliths in both the deep hilar region and the submandibular gland parenchyma were selected for this study. Ultrasonography and computer tomography (CT) scans were performed to determine the location, number and sizes of the calculi and the distance between hilar and intraparenchymal sialoliths. All sialoliths were removed via gland-sparing, intraoral sialolithotomy. In all, 27 stones were found in the 9 patients. The hilar and deeper sialoliths were 4.5–11 and 0.8–4.5 mm, respectively, in diameter. The largest distance between the hilar and intraparenchymal sialoliths was 28.3 mm. Sialoliths in the hilar region were excised through an intraoral incision before deeper intraparenchymal stones were eased out of the same incision site. Postoperative follow-up imaging verified complete sialolith removal. Therefore, submandibular gland multiple sialoliths in the hilum and parenchyma can be successfully removed via an intraoral sialolithotomy under general anesthesia, thereby preserving the gland and restoring its secretory function.
Immediate mandibular reconstruction is always necessary for the patients receiving segmental mandibulectomy to recover the facial contour and function of occlusion. When 3D modeling is unavailable, temporary external fixator is necessary to maintain the occlusion relationship and facial contour. In this study, we introduce the clinical application of temporary external fixator for immediate mandibular reconstruction in patients receiving segmental mandibulectomy, which consists of 2 anchor claws, 2 all-round retentive arms, and 1 central locking structure. From August 2016 to September 2017, temporary external fixator was applied in 13 patients. Clinical data of gender, age, surgical procedure, duration of operation, and clinical outcomes were recorded and analyzed. Among the 13 patients, there were 4 men and nine women whose ages ranged from 21 to 64 (mean 47.7) years old. There were 9 benign and 4 malignant lesions. All lesions expended at the buccal side of mandible. 12 fibular flaps and 1 vascularized iliac bone graft were used. The mandibular defect ranged from 6 to 14 (mean 10) cm. The operation duration of surgery ranged from 5 to 10 (mean 7) hours. All flaps survived with primary healing. The occlusion and facial contour were good, without significant changes of the length of mandibular body and width of mandible before and after surgery. No functional sequelae were noted at the donor sites. From these results, the temporary external fixator is easy to operate; the surgical procedure is simple and time-saving for surgeon when 3D modeling is unavailable. The indication for temporary external fixator usage is the mandibular lesion growing outward to cheek soft tissue.
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.