Faculty Bibliography

Tumor cell survival consists of an intricate balance between cell growth and cell death pathways involving receptor tyrosine kinases [RTK; i.e., HER1-4, insulin-like growth factor-1 receptor (IGF-1R), etc.], MDM2, and the tumor suppressor proteins phosphatase and tensin homolog deleted on chromosome ten (PTEN) and p53. We recently demonstrated that shedded E-cadherin extracellular domain fragment (sEcad) is a valid oncogenic target that is significantly increased in human clinical skin squamous cell cancers (SCC) samples, UV-induced mouse tumors, and cells and promotes tumor cell proliferation, migration, and invasion by interacting and activating with the HER-phosphatidylinositol 3-kinase (PI3K)-Akt-mammalian target of rapamycin (mTOR) and mitogen-activated protein kinase (MAPK) axis. In resected human SCC tumors, we reported enhanced sEcad-HER1, sEcad-HER2, and sEcad-IGF-1R, but not FL-Ecad-RTK interactions. Here, we demonstrate that a sEcad antibody against the ectodomain of E-cadherin suppressed SCC growth and increased tumor differentiation in orthotopic cutaneous SCC xenografts by inhibiting proliferation and inducing apoptosis. A similar anti-sEcad antibody-induced inhibition of proliferation and induction of cell death was evident in PAM212 cells in vitro. Mechanistically, anti-sEcad administration upregulated an array of cell death pathways (i.e., Bad, active caspase-3, and cleaved PARP) and inhibited inhibitors of apoptosis (IAP; survivin, livin, etc.), RTKs (HER1, HER2, p95HER2, and IGF-1R), MAPK and PI3K/mTOR prosurvival signaling. Interestingly, in anti-sEcad mAb-treated tumors and PAM212 cells, this effect was associated with a profound increase in membrane, cytosolic, and nuclear levels of PTEN; enhanced cytosolic p53; and a decrease in MDM2 levels. Overall, our studies suggest that an antibody-based therapy against sEcad may be a novel therapeutic platform for cutaneous SCCs by hampering key proto-oncogenes (RTKs, IAPs, and MDM2) and activating potent tumor suppressor proteins (PTEN and p53) intricately linked to tumor growth and survival.

UNLABELLED: Identification of unknown individuals using dental comparison is well established in the forensic setting. The identification technique can be time and resource consuming if many individuals need to be identified at once. Medical CT (MDCT) for dental profiling has had limited success, mostly due to artifact from metal-containing dental restorations and implants. DESCRIPTION: The authors describe a CBCT reformatting technique that creates images, which closely approximate conventional dental images. METHOD: Using a i-CAT Platinum CBCT unit and standard issue i-CAT Vision software, a protocol is developed to reproducibly and reliably reformat CBCT volumes. The reformatted images are presented with conventional digital images from the same anatomic area for comparison. CONCLUSION: The authors conclude that images derived from CBCT volumes following this protocol are similar enough to conventional dental radiographs to allow for dental forensic comparison/identification and that CBCT offers a superior option over MDCT for this purpose.

BACKGROUND: Staphylococcus aureus is an important health care-associated pathogen that often is resistant to antibiotics. The authors conducted a pilot study to determine if abiotic surfaces in a dental clinic were contaminated frequently. METHODS: The authors sampled surfaces with swabs that they then used to inoculate selective and differential media. CHRO-Magar Staph aureus (DRG International, Mountainside, N.J.) was the most effective. They used phenotypic and genotypic tests to identify presumptive S. aureus colonies. They determined the sensitivity of S. aureus isolates to five antibiotics, including oxacillin, according to the Kirby-Bauer method. RESULTS: The authors recovered S. aureus from 20 of 429 surfaces (4.7 percent). Most isolates were resistant to penicillin but none were resistant to the other antibiotics. No isolate carried the mecA gene encoding resistance to methicillin. The authors considered one site to be highly contaminated (> 200 colony-forming units [CFUs]), but all other sites that tested positive yielded fewer than 5 CFUs. CONCLUSIONS: Abiotic surfaces in the authors' dental clinic were not a reservoir for methicillin-resistant S. aureus. The authors identified and eliminated one nonclinical site of potential methicillin-sensitive S. aureus cross-contamination. CLINICAL IMPLICATIONS: Periodic sampling of surfaces for S. aureus may be a useful adjunct to standard infection control practices in dental health care settings.

A benign mesenchymoma is an unencapsulated soft tissue neoplasm composed of 2 or more mature mesenchymal tissues not normally associated with each other, excluding fibrous connective tissue. No single mesenchymal tissue should predominate with respect to the other mesenchymal elements. Ten well-documented examples of intraoral benign mesenchymoma have been reported in the English language literature. The purpose of this report is to document 10 additional cases and to review the clinicopathologic characteristics of this uncommon tumor