Investigation of Roles of SLC38A1 in Proliferation and Differentiation of Mouse Tongue Epithelium and Expression in Human Oral Tongue Squamous Cell Carcinoma.

The aerobic glycolytic pathway, boosting lactate formation, and glutamine addiction are two hallmarks of cancer pathophysiology. Consistent with this, several cell membrane glutamine transporters, belonging to different solute carrier (SLC) families, have been shown to be upregulated in a cell-specific manner to furnish the cells with glutamine and glutamine-derived metabolic intermediates. Among them, the system A transporter Slc38a1 has a higher affinity for glutamine compared to other SLC transporters, and it undergoes highly multifaceted regulation at gene and protein levels. The current study aimed to investigate the functional role of Slc38a1 in the proliferation and maturation of the mouse tongue epithelium. Secondly, we aimed to examine the expression of SLC38A1 and its regulation in human tongue oral squamous cell carcinoma (OTSCC). Employing Slc38a1 wild-type and knockout mice, we showed that Slc38a1 was not directly linked to the regulation of the proliferation and differentiation of the mouse tongue epithelium. External transcriptomic datasets and Western blot analyses showed upregulation of SLC38A1 mRNA/protein in human OTSCC and oral cancer cell lines as compared to the corresponding controls. Further, an investigation of external datasets indicated that mechanisms other than the amplification of the SLC38A1 chromosomal locus or hypomethylation of the SLC38A1 promoter region might be important for the upregulation of SLC38A1 in OTSCC.

In vivo behavior of a collagen-coated nano-hydroxyapatite enriched polycaprolactone membrane in rat mandibular defects.

BACKGROUND: This research investigated the ability of fabricated collagen (COL) coated nano-hydroxyapatite (nHA) enriched polycaprolactone (PCL) membrane to facilitate new bone formation (NBF) and its biocompatibility. METHODS: Unilateral mandibular angulus defects of 28 female 12-week-old long Evans rats were created with a trephine bur with 5 mm in diameter and divided into two groups. While the test group was treated with the membrane (M-1, M-2), the control was left as self-healing (C-1, C-2) and sacrificed at 2nd (M-1, C-1) and 8th week (M-2, C-2) postoperatively. The mandibular bone of the rats was evaluated histopathologically. Density of the regenerated bone was evaluated with PET/CT. RESULTS: Histopathologically, NBF which started from the periphery of the defect had rich cellular character in M-1. Significantly higher NBF was found in M-2 when compared to M-1 (P=0.003). Furthermore, significantly lesser degree of inflammation was found in M-2 when compared to M-1 (P<0.05). CONCLUSION: This study suggests that the novel COL-coated nHA-enriched PCL membrane can serve a promising design for tissue engineering as guided bone regeneration in alveolar defects.

Expression of p53, p63, podoplanin and Ki-67 in recurring versus non-recurring oral leukoplakia.

Oral leukoplakia (OL), a potentially malignant disorder, recurs in 40% of cases after surgical removal. Recurrence is a risk factor for malignant transformation. We aimed to examine the prognostic significance of four biomarkers related to cell proliferation: p53, p63, podoplanin (PDPN) and Ki-67 in predicting recurrence. Formalin-fixed-paraffin-embedded specimens from excised OL (n = 73, 33 recurrent; 40 non-recurrent) were collected in a prospective study. Immunohistochemistry was used to visualise expression of p53, p63, PDPN and Ki-67. Image analysis software was used for quantification of p53-, p63- and Ki-67-expressing cells, while PDPN was analysed visually. The expression of all four proteins were higher in recurrent compared with non-recurrent OL, only expression of p53 was statistically significant. In uni- and multivariable Cox regression analyses of individual markers, expression of p63 was significantly associated with higher recurrence risk (p = 0.047). OL with a combined high expression of both p53 and p63 had a significantly higher risk to recur [Log Rank, p = 0.036; multivariate Cox, HR: 2.48 (1.13-5.44; p = 0.024)]. Combination of p53 and p63 expression may be used as a prognostic biomarker for recurrence of OL.