Inhibition of the migration of human oral squamous cell carcinoma by lysyl oxidase pro-peptide

PLEASE NOTE: This work is protected by copyright. Downloading is restricted to the BU community: please click Download and log in with a valid BU account to access. If you are the author of this work and would like to make it publicly available, please contact [email protected] (MSD) --Boston University, Henry M. Goldman School of Dental Medicine, 2013 (Department of Periodontology and Oral Biology).Includes bibliographic references: leaves 66-77.Squamous cell carcinoma of the oral cavity (SCC) is the sixth most common cancer worldwide and is associated with high morbidity and mortality [1-3]. Invasion and metastasis are perhaps the most challenging and important aspects of cancer progression, and metastasis is the most prevalent cause of death of patients with oral SCC [4]. Invasion occurs through the degradation of the basement membrane and the interstitial extracellular matrix (ECM) and is followed by migration of tumor cells into the adjacent tissue. Thus, cell migration is considered one of the earliest stages of metastasis; a better understanding of these early interactions between carcinoma, stromal cells and the ECM could lead to enhanced diagnostic and treatment protocols. Lysyl oxidase (LOX) enzyme catalyzes the final enzymatic step required for collagen and elastin cross-linking [5, 6]. LOX is synthesized as a 50 kDa secreted precursor, Pro-LOX, that is processed to the 32 kDa active enzyme (LOX) and to a 18 kDa propeptide (LOX-PP) [6, 7]. Expression of the LOX gene was found to inhibit the transforming activity of the ras oncogene and was hence named the “ras recession gene” (rrg) [8, 9]. Recently, it has been reported that LOX-PP but not LOX enzyme contains tumor suppressor activity [10, 11]. Expression of LOX-PP was found to inhibit growth and migration of breast [12, 13] and prostate cancer cells [14]. Similarly, LOX-PP was found to inhibit the invasive phenotype of lung and pancreatic cancer cells [15]. The MEK/ERK pathway, as well as the integrin signaling pathway, which leads to phosphorylation of the focal adhesion kinase (FAK) [13] have been identified as downstream targets of LOX-PP. [TRUNCATED

Risk factors, diagnosis, and treatment of peri-implantitis: A cross-cultural comparison of U.S. and European periodontists’ considerations

BackgroundPeri-implantitis (PI) is a growing concern in the dental community worldwide. The study aimed to compare U.S. versus European periodontists’ considerations of risk factors, diagnostic criteria, and management of PI.MethodsA total of 393 periodontists from the United States and 100 periodontists from Europe (Germany, Greece, Netherlands) responded to anonymous surveys electronically or by mail.ResultsCompared to U.S. periodontists, European respondents were younger, more likely to be female and placed fewer implants per month (9.12 vs 13.90; P = 0.003). Poor oral hygiene, history of periodontitis, and smoking were considered as very important risk factors by both groups (rated > 4 on 5-point scale). European periodontists rated poor oral hygiene (4.64 vs 4.45; P = 0.005) and history of periodontitis (4.36 vs 4.10; P = 0.006) as more important and implant surface (2.91 vs 3.18; P = 0.023), occlusion (2.80 vs 3.75; P < 0.001) and presence of keratinized tissue (3.27 vs 3.77; P < 0.001) as less important than did U.S. periodontists. Both groups rated clinical probing, radiographic bone loss, and presence of bleeding and suppuration as rather important diagnostic criteria. They rated implant exposure/mucosal recession as relatively less important with U.S. periodontists giving higher importance ratings than European periodontists (3.99 vs 3.54; P = 0.001). Both groups nearly always used patient education, plaque control and mechanical debridement when treating PI. U.S. periodontists were more likely to use antibiotics (3.88 vs 3.07; P < 0.001), lasers (2.11 vs 1.68; P = 0.005), allograft (3.39 vs 2.14; P < 0.001) and regenerative approaches (3.57 vs 2.56; P < 0.001), but less likely to use resective surgery (3.09 vs 3.53; P < 0.001) than European periodontists.ConclusionsU.S. and European periodontists’ considerations concerning risk factors, diagnosis and management of PI were evidence-based. Identified differences between the two groups can inform future educational efforts.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/172247/1/jper10847.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/172247/2/jper10847_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/172247/3/jper10847-sup-0001-SuppMat.pd

The effect of blue light on periodontal biofilm growth in vitro

We have previously shown that blue light eliminates the black-pigmented oral bacteria Porphyromonas gingivalis, Prevotella intermedia, Prevotella nigrescens, and Prevotella melaninogenica. In the present study, the in vitro photosensitivity of the above black-pigmented microorganisms and four Fusobacteria species (Fusobacterium nucleatum ss. nucleatum, F. nucleatum ss. vincentii, F. nucleatum ss. polymorphum, Fusobacterium periodonticum) was investigated in pure cultures and human dental plaque suspensions. We also tested the hypothesis that phototargeting the above eight key periodontopathogens in plaque-derived biofilms in vitro would control growth within the dental biofilm environment. Cultures of the eight bacteria were exposed to blue light at 455 nm with power density of 80 mW/cm(2) and energy fluence of 4.8 J/cm(2). High-performance liquid chromatography (HPLC) analysis of bacteria was performed to demonstrate the presence and amounts of porphyrin molecules within microorganisms. Suspensions of human dental plaque bacteria were also exposed once to blue light at 455 nm with power density of 50 mW/cm(2) and energy fluence of 12 J/cm(2). Microbial biofilms developed from the same plaque were exposed to 455 nm blue light at 50 mW/cm(2) once daily for 4 min (12 J/cm(2)) over a period of 3 days (4 exposures) in order to investigate the cumulative action of phototherapy on the eight photosensitive pathogens as well as on biofilm growth. Bacterial growth was evaluated using the colony-forming unit (CFU) assay. The selective phototargeting of pathogens was studied using whole genomic probes in the checkerboard DNA-DNA format. In cultures, all eight species showed significant growth reduction (p < 0.05). HPLC demonstrated various porphyrin patterns and amounts of porphyrins in bacteria. Following phototherapy, the mean survival fractions were reduced by 28.5 and 48.2 % in plaque suspensions and biofilms, respectively, (p < 0.05). DNA probe analysis showed significant reduction in relative abundances of the eight bacteria as a group in plaque suspensions and biofilms. The cumulative blue light treatment suppressed biofilm growth in vitro. This may introduce a new avenue of prophylactic treatment for periodontal diseases

Non-surgical peri-implantitis treatment with or without systemic antibiotics:a randomized controlled clinical trial

OBJECTIVES: To assess the adjunctive effect of systemic amoxicillin (AMX) and metronidazole (MTZ) in patients receiving non‐surgical treatment (NST) for peri‐implantitis (PI). MATERIALS AND METHODS: Thirty‐seven patients were randomized into an experimental group treated with NST plus AMX + MTZ (N = 18) and a control group treated with NST alone (N = 19). Clinical parameters were evaluated at 12 weeks post‐treatment. The primary outcome was the change in peri‐implant pocket depth (PIPD) from baseline to 12 weeks, while secondary outcomes included bleeding on probing (BoP), suppuration on probing (SoP), and plaque. Data analysis was performed at patient level (one target site per patient). RESULTS: All 37 patients completed the study. Both groups showed a significant PIPD reduction after NST. The antibiotics group showed a higher mean reduction in PIPD at 12 weeks, compared with the control group (2.28 ± 1.49 mm vs. 1.47 ± 1.95 mm), however, this difference did not reach statistical significance. There was no significant effect of various potential confounders on PIPD reduction. Neither treatment resulted in significant improvements in BoP at follow‐up; 30 of 37 (81%) target sites still had BoP after treatment. Only two implants, one in each group, exhibited a successful outcome defined as PIPD < 5 mm, and absence of BoP and SoP. CONCLUSIONS: Non‐surgical treatment was able to reduce PIPD at implants with PI. The adjunctive use of systemic AMX and MTZ did not show statistically significant better results compared to NST alone. NST with or without antibiotics was ineffective to completely resolve inflammation around dental implants

Non-surgical peri-implantitis treatment with or without systemic antibiotics: a randomized controlled clinical trial

Objectives: To assess the adjunctive effect of systemic amoxicillin (AMX) and metronidazole (MTZ) in patients receiving non-surgical treatment (NST) for peri-implantitis (PI). Materials and methods: Thirty-seven patients were randomized into an experimental group treated with NST plus AMX + MTZ (N = 18) and a control group treated with NST alone (N = 19). Clinical parameters were evaluated at 12 weeks post-treatment. The primary outcome was the change in peri-implant pocket depth (PIPD) from baseline to 12 weeks, while secondary outcomes included bleeding on probing (BoP), suppuration on probing (SoP), and plaque. Data analysis was performed at patient level (one target site per patient). Results: All 37 patients completed the study. Both groups showed a significant PIPD reduction after NST. The antibiotics group showed a higher mean reduction in PIPD at 12 weeks, compared with the control group (2.28 ± 1.49 mm vs. 1.47 ± 1.95 mm), however, this difference did not reach statistical significance. There was no significant effect of various potential confounders on PIPD reduction. Neither treatment resulted in significant improvements in BoP at follow-up; 30 of 37 (81%) target sites still had BoP after treatment. Only two implants, one in each group, exhibited a successful outcome defined as PIPD < 5 mm, and absence of BoP and SoP. Conclusions: Non-surgical treatment was able to reduce PIPD at implants with PI. The adjunctive use of systemic AMX and MTZ did not show statistically significant better results compared to NST alone. NST with or without antibiotics was ineffective to completely resolve inflammation around dental implants

Submucosal microbiome of peri‐implant sites: a cross‐sectional study

AIM: To study the peri‐implant submucosal microbiome in relation to implant disease status, dentition status, smoking habit, gender, implant location, implant system, time of functional loading, probing pocket depth (PPD), and presence of bleeding on probing. MATERIALS AND METHODS: Biofilm samples were collected from the deepest peri‐implant site of 41 patients with paper points, and analysed using 16S rRNA gene pyrosequencing. RESULTS: We observed differences in microbial profiles by PPD, implant disease status, and dentition status. Microbiota in deep pockets included higher proportions of the genera Fusobacterium, Prevotella, and Anaeroglobus compared with shallow pockets that harboured more Rothia, Neisseria, Haemophilus, and Streptococcus. Peri‐implantitis (PI) sites were dominated by Fusobacterium and Treponema compared with healthy implants and peri‐implant mucositis, which were mostly colonized by Rothia and Streptococcus. Partially edentulous (PE) individuals presented more Fusobacterium, Prevotella, and Rothia, whereas fully edentulous individuals presented more Veillonella and Streptococcus. CONCLUSIONS: PPD, implant disease status, and dentition status may affect the submucosal ecology leading to variation in composition of the microbiome. Deep pockets, PI, and PE individuals were dominated by Gram‐negative anaerobic taxa

Submucosal microbiome of peri-implant sites: A cross-sectional study

Aim: To study the peri-implant submucosal microbiome in relation to implant disease status, dentition status, smoking habit, gender, implant location, implant system, time of functional loading, probing pocket depth (PPD), and presence of bleeding on probing. Materials and Methods: Biofilm samples were collected from the deepest peri-implant site of 41 patients with paper points, and analysed using 16S rRNA gene pyrosequencing. Results: We observed differences in microbial profiles by PPD, implant disease status, and dentition status. Microbiota in deep pockets included higher proportions of the genera Fusobacterium, Prevotella, and Anaeroglobus compared with shallow pockets that harboured more Rothia, Neisseria, Haemophilus, and Streptococcus. Peri-implantitis (PI) sites were dominated by Fusobacterium and Treponema compared with healthy implants and peri-implant mucositis, which were mostly colonized by Rothia and Streptococcus. Partially edentulous (PE) individuals presented more Fusobacterium, Prevotella, and Rothia, whereas fully edentulous individuals presented more Veillonella and Streptococcus. Conclusions: PPD, implant disease status, and dentition status may affect the submucosal ecology leading to variation in composition of the microbiome. Deep pockets, PI, and PE individuals were dominated by Gram-negative anaerobic taxa

Surgical treatment of peri‐implantitis defects with two different xenograft granules: A randomized clinical pilot study

Objectives: To investigate whether xenograft EB (EndoBon) is non-inferior to xenograft BO (Bio-Oss) when used in reconstructive surgery of peri-implant osseous defects. Materials and methods: Dental patients with one implant each demonstrating peri-implantitis were randomized to receive surgical debridement and defect fill with either BO or EB. Changes in bone level (BL) and intrabony defect depth (IDD) evaluated radiographically were the primary outcomes. The secondary outcomes included changes in probing pocket depth (PPD), bleeding on probing (BoP), and suppuration on probing (SoP). All outcomes were recorded before treatment and at 6 and 12 months post-treatment. Results: Twenty-four patients (n = 11 BO, n = 13 EB) completed the study. Both groups demonstrated significant within-group improvements in all clinical and radiographic parameters at 6 and 12 months (p ≤.001). At 12 months, both groups presented with IDD reductions of 2.5–3.0 mm on average. The inter-group differences were not statistically significant at all time points and for all the examined parameters (p >.05). While the radiographic defect fill in both groups exceeded > 1 mm and can be considered treatment success, successful treatment outcomes as defined by Consensus Reporting (no further bone loss, PPD ≤ 5 mm, no BOP, and no SoP) were identified in 2/11 (18%) BO and 0/13 (0%) EB individuals (Fisher's exact test, p =.199). Conclusions: Within the limitations of this pilot study, the application of xenograft EB showed to be non-inferior to xenograft BO when used in reconstructive surgery of peri-implant osseous defects