Association of Stromal Factors With the Histologic Risk Assessment Model in Oral Squamous Cell Carcinoma.

The aim of the present study was to evaluate angiogenesis, lymphangiogenesis, and mast cell density in association with the histologic risk assessment (HRA) model in oral squamous cell carcinoma. One hundred oral squamous cell carcinomas were graded according to the HRA system and immunostained with antibodies against D2-40, CD34, and CD105 to determine lymphvessel density (LVD) and microvessel density (MVD). Mast cells were detected by toluidine blue and counted in all samples. Assessments were made between the evaluated factors and the histologic variables of HRA. Kruskal-Wallis and Mann-Whitney U test were used for statistical analysis and P<0.05 was considered significant. There were 32, 26, and 42 cases of low, intermediate, and high-grade neoplasms, respectively. Only LVD (P=0.05) and CD34MVD (P=0.03) showed significant associations with lymphocytic infiltration and were both higher in score 0 cases compared with score 3 tumors (P=0.05 and <0.001, respectively). None of the other variables showed significant relationships with the HRA risk scores or subcategories (P>0.05). According to our findings, it appears that the role of lymphangiogenesis and angiogenesis is limited in the HRA system. The significant relationship of lymphocytic infiltration with LVD and CD34MVD, but not CD105MVD, might indicate that "inflammatory lymphangiogenesis/angiogenesis" may differ from that induced by noninflamed neoplastic tissues. It also seems that the vasculature in inflamed tumor tissues is not entirely newly formed.

Correlation between invasion mode and the histologic risk assessment model in oral squamous cell carcinoma.

PURPOSE: The histologic risk assessment (HRA) model was proposed to assess clinical outcome of oral squamous cell carcinomas (SCCs), and its prognostic value has been confirmed in several studies, but its underlying molecular mechanisms has not been fully investigated. The objective of this study was to evaluate the association between immunohistochemical invasion mode of head and neck SCC and the HRA grading system. METHODS: The HRA model consisting of risk scores (RSs), based on perineural invasion (PI), lymphocytic infiltration (LI), and worst pattern of invasion (WPOI), was used for grading 80 samples of head and neck SCC, followed by immunohistochemical staining with antibodies against E-cadherin, N-cadherin, and podoplanin. The two major invasion modes were considered as epithelial-mesenchymal-transition (EMT) and collective cell invasion (CCI) with profiles of E-cadherin-/N-cadherin+/podoplanin- and E-cadherin+/N-cadherin-/podoplanin+, respectively. All other immunohistochemical profiles were classified as partial/incomplete EMT. Statistical analysis was performed by Kruskal-Wallis and Mann-Whitney U tests (P < 0.05). RESULTS: Invasion pattern was significantly different among the three RSs (P = 0.01) and across the different scores of LI (P = 0.03) but not perineural invasion (PNI) (P = 0.07) and WPOI (P = 0.70). CONCLUSIONS: Based on our results, it seems that there is a difference in EMT, CCI, and partial/incomplete EMT among the variables of the HRA model which might help clarify its functioning system.

Assessment of the Role of NO-cGMP Pathway in Orthodontic Tooth Movement Using PDE5 Inhibitors: An Animal Study.

OBJECTIVES: Nitric oxide (NO) is a signaling molecule that mediates mechanical bone loading. Cyclic guanosine 3', 5' monophosphate (cGMP) is a NO-induced effector molecule. The aim of this study was to assess the effect of NO-cGMP pathway on orthodontic tooth movement (OTM) in rats by use of two phosphodiesterase 5 (PDE5) inhibitors namely sildenafil and tadalafil as chemical tools. MATERIALS AND METHODS: Forty-five male Wistar rats were divided into three equal groups (n=15) based on the substance they received. The first group received daily injections of tadalafil; the second group received daily injections of sildenafil and the third group received daily injections of normal saline. The orthodontic appliances consisted of nickel-titanium closed-coil spring ligated between the maxillary right incisor and the first molar of the animals for 21 days. The amount of tooth movement was measured in all three groups at the end of this period. Histological analysis was performed to assess root resorption lacunae, osteoclast number and periodontal ligament (PDL) thickness. RESULTS: All appliance-treated molars in the experimental and control groups showed evidence of tooth movement. The mean OTM was calculated to be 0.39±0.16, 0.32±0.16 and 0.26±0.16mm in tadalafil, sildenafil and control groups, respectively and there were no significant differences in OTM among the study groups (P>0.05). In the tadalafil group, significantly greater root resorption on the tension side was seen when compared with controls (P≤0.05). CONCLUSIONS: Tadalafil and sildenafil PDE-5 inhibitors affecting the NO-cGMP pathway did not affect OTM in rats.

Isolation and Assessment of Mesenchymal Stem Cells Derived From Bone Marrow: Histologic and Histomorphometric Study in a Canine Periodontal Defect.

The aim of the present study was to investigate an isolation procedure to culture mesenchymal stem cells derived from bone marrow and evaluate their potential in periodontal regeneration. Potential stem cells from bone marrow, aspirated from the iliac crest of nine mongrel canines 1 to 2 years of age, were cultivated. After the examination of surface epitopes of the isolated cells, the total RNA from osteogenic, adipogenic, and chondrogenic cell cultures were analyzed by reverse transcription polymerase chain reaction (RT-PCR) to confirm stem cell gene expressions. 2 × 10(7) mL of the stem cells were loaded on 0.2 mL of anorganic bovine bone mineral (ABBM) granules. In each animal, bilateral acute/chronic intrabony periodontal defects were created surgically and by placement of ligatures around the cervical aspect of the teeth. At week 5, after flap debridement, the bilateral defects were randomly assigned to 2 treatment groups: the control group received ABBM, and the test group received BMSCs-loaded ABBM. Eight weeks after transplantation, regenerative parameters were analyzed histologically and histometrically. The RNA expressions confirmed the cultivation of mesenchymal stem cell. More new cementum and periodontal ligament (PDL) were measured in the test group (cementum: 3.33 ± 0.94 vs 2.03 ± 1.30, P = 0.027; PDL: 2.69 ± 0.73 vs 1.53 ± 1.21, P = 0.026). New bone formation was similar in both groups (2.70 ± 0.86 vs 1.99 ± 1.31; P = 0.193). Mesenchymal stem cells derived from bone marrow should be considered a promising technique for use in patients with periodontal attachment loss and merits further investigations.