HOXA1 is overexpressed in oral squamous cell carcinomas and its expression is correlated with poor prognosis

<p>Abstract</p> <p>Background</p> <p>HOX genes encode homeodomain-containing transcription factors involved in the regulation of cellular proliferation and differentiation during embryogenesis. However, members of this family demonstrated oncogenic properties in some malignancies. The present study investigated whether genes of the HOXA cluster play a role in oral cancer.</p> <p>Methods</p> <p>In order to identify differentially expressed HOXA genes, duplex RT-PCR in oral samples from healthy mucosa and squamous cell carcinoma was used. The effects of HOXA1 on proliferation, apoptosis, adhesion, invasion, epithelial-mesenchymal transition (EMT) and anchorage-independent growth were assessed in cells with up- and down-regulation of HOXA1. Immunohistochemical analysis using a tissue microarray (TMA) containing 127 oral squamous cell carcinomas (OSCC) was performed to determine the prognostic role of HOXA1 expression.</p> <p>Results</p> <p>We showed that transcripts of HOXA genes are more abundant in OSCC than in healthy oral mucosa. In particular, HOXA1, which has been described as one of the HOX members that plays an important role in tumorigenesis, was significantly more expressed in OSCCs compared to healthy oral mucosas. Further analysis demonstrated that overexpression of HOXA1 in HaCAT human epithelial cells promotes proliferation, whereas downregulation of HOXA1 in human OSCC cells (SCC9 cells) decreases it. Enforced HOXA1 expression in HaCAT cells was not capable of modulating other events related to tumorigenesis, including apoptosis, adhesion, invasion, EMT and anchorage-independent growth. A high number of HOXA1-positive cells was significantly associated with T stage, N stage, tumor differentiation and proliferative potential of the tumors, and was predictive of poor survival. In multivariate analysis, HOXA1 was an independent prognostic factor for OSCC patients (HR: 2.68; 95% CI: 1.59-2.97; p = 0.026).</p> <p>Conclusion</p> <p>Our findings indicate that HOXA1 may contribute to oral carcinogenesis by increasing tumor cell proliferation, and suggest that HOXA1 expression might be helpful as a prognostic marker for patients with OSCC.</p

Homogenous demineralized dentin matrix for application in cranioplasty of rabbits with alloxan-induced diabetes: Histomorphometric analysis

Purpose: The aim of this work was to evaluate the bone-repair process after implantation of homogenous demineralized dentin matrix (HDDM) slices in surgical defects created in the parietal bones of rabbits with alloxan-induced diabetes. Materials and Methods: Forty-eight rabbits were selected and divided into 4 groups of 12 rabbits: the control group, diabetic rabbits (D), diabetic rabbits with a PTFE barrier (D-PTFE), and diabetic rabbits with a PTFE barrier and with slices of homogenous demineralized dentin matrix (D-PTFE+HDDM). The diabetic animals received a single dose of alloxan monohydrate (90 mg/kg) intravenously on the marginal ear vein, and their blood glucose was verified daily. The rabbits were sacrificed after 15, 30, 60, and 90 days. The histologic findings show both better bone structure and significantly greater bone density, as determined by histomorphometric analysis, for the D-PTFE + HDDM group than for the other 3 groups (P <.01). It was also observed that the mean bone density increased gradually from 15 to 90 days (except in the D-PTFE group). Conclusion: It was concluded that the HDDM was biocompatible with the bone repair of diabetic rabbits and that HDDM slices stimulated bone tissue formation. Facilitation of bone repair with HDDM could be useful in diabetic patients.22693994