Establishment and characterization of a non-gestational choriocarcinoma patient-derived xenograft model.

BACKGROUND: Non-gestational choriocarcinoma (NGC) is a rare subtype of malignant germ cell tumour and there is no consensus on its treatment. The lack of suitable preclinical models for NGC is a challenge in drug discovery research. Patient-derived xenograft (PDX) models recapitulate the tumour microenvironment of the original cancer tissue. Therefore, they have received considerable attention for studies on rare cancer. Here, we aimed to establish a PDX model from a patient with recurrent NGC. METHODS: Fresh NGC tumour tissue was immediately transplanted into a severely immune-deficient mouse (NOD.Cg-Prkdcscid1l2rgtm1Wjl/SzJ) and maintained for more than three in vivo passages. Subsequently, we evaluated the molecular characteristics of the PDX model using immunohistochemistry, polymerase chain reaction, and RNA sequencing. Moreover, the PDX tumours were transplanted into BALB/c nude mice, and we evaluated their sensitivity for cisplatin and methotrexate. RESULTS: The PDX tumour maintained the morphological features of NGC. Moreover, Immunohistochemistry revealed that the human chorionic gonadotropin, cytokeratin 7, and EpCAM expression levels were similar to those in the primary tumour. Furthermore, serum human chorionic gonadotropin levels were elevated in both the primary tumour and the PDX models. Additionally, using PCR analysis with species-specific primers, we confirmed that the PDX tumour contained human genes and was derived from human tissue. Moreover, the gene expression profile of the NGC was compared with that of epithelial ovarian cancer samples and cell lines, and 568 dysregulated genes in the NGC were extracted. The expression of the dysregulated genes in PDX was significantly correlated with that in the primary tumour (R2 = 0.873, P < 0.001). Finally, we demonstrated that the PDX tumour was sensitive to cisplatin and methotrexate; therefore, its clinical response to the agents was similar to that of the primary tumour. CONCLUSIONS: We successfully established a PDX model of NGC, to the best of our knowledge, for the first time. The established PDX retained the molecular and transcriptome characteristics of the primary tumour and can be used to predict drug effects. It may facilitate further research and the development of novel therapeutic agents for NGC.

A case of complete remission of intractable gestational choriocarcinoma with subsequent chemotherapy after pembrolizumab.

OBJECTIVE: Gestational choriocarcinoma is a gestational trophoblastic neoplasia (GTN) that originates from abnormal trophoblast proliferation. Although chemotherapy is effective for choriocarcinoma, personalized treatment becomes essential when patients develop chemoresistance. Here, we present the clinical course of a case of intractable choriocarcinoma that achieved complete remission with pembrolizumab following cytotoxic chemotherapy. CASE REPORT: A 38-year-old woman was initially diagnosed with low-risk GTN and treated with single- and multi-agent chemotherapy. She underwent a hysterectomy and was diagnosed with pathological choriocarcinoma with high-risk GTN. She was treated with multiple courses of several chemotherapy regimens. However, she did not achieve remission. Her choriocarcinoma showed high microsatellite instability; therefore, she took ten courses of pembrolizumab, but her hCG value increased. Subsequently, she underwent eight courses of paclitaxel and carboplatin alternating with paclitaxel and etoposide and achieved remission. CONCLUSION: This case suggests that pembrolizumab may improve the efficacy of subsequent chemotherapy.

Dimensional changes of buccal bone in the edentulous maxilla with telescopic-retained implant-supported fixed dental prostheses.

STATEMENT OF PROBLEM: The buccal bone in an edentulous maxilla loses thickness over time because of physiological changes. However, the dimensional changes of the buccal bone in an edentulous maxilla with an implant-supported fixed dental prosthesis are unknown. PURPOSE: The purpose of this retrospective clinical study was to evaluate cone beam computed tomography (CBCT) images of the dimensional changes of the buccal bone in edentulous maxillae with complete arch telescopic-retained implant-supported fixed dental prostheses (CTI-FDPs) after 6 years by using a professional retrieval system. MATERIAL AND METHODS: This study included 17 participants with edentulous maxillae who had been provided with CTI-FDP with 121 taper joint implants. A three-dimensional radiographic analysis by using CBCT was performed at implant insertion (0 years) and after 6 years. Vertical and horizontal bone measurement values were evaluated. During horizontal bone thickness measurement, 4 different levels, 0, 2, 4, and 6 mm apical to the implant shoulder, were evaluated as bone value (BV)0mm, BV2mm, BV4mm, and BV6mm, respectively. The BVs were compared with the Wilcoxon signed-rank test and Kruskal-Wallis test (α=.05). In addition, the Spearman rank correlation coefficient was used to identify 0yBV factors that influence the 6yBVs. A nonlinear regression analysis was used to clarify the slopes of 0yBVs and 6yBV0mm. RESULTS: Significant decreases in vertical and horizontal BVs were found between 0 years and 6 years (P<.05). However, no significant difference was observed in bone loss at 6 years at any of the vertical and horizontal measurement points (P≥.05). When 0yBVs related to 6yBV0mm were analyzed, 0yBV0mm and 0yBV2mm showed strong correlations with 6yBV0mm (|r|≥.7). In the regression analysis, a 0yBV0mm of 0.58 mm and 0yBV2mm of 0.78 mm could be critical factors associated with a 6yBV0mm of 0 mm. A 6yBV0mm of 0yBV0mm more than 0.58 mm was significantly higher than a 6yBV0mm of 0yBV0mm less than 0.58 mm (P<.001). Moreover, a 6yBV0mm of 0yBV2mm more than 0.78 mm was significantly higher than a 6yBV0mm of 0yBV2mm less than 0.78 mm (P<.001). CONCLUSIONS: The buccal bone in an edentulous maxilla with fixed implant-supported prostheses lost significant vertical and horizontal bone thicknesses after 6 years. At implant insertion, both a 0.58-mm buccal bone on the platform and a 0.78-mm buccal bone at 2 mm apical to the implant shoulder are necessary for longer term maintenance of bone on the platform of implants specifically supporting CTI-FDPs.

Direct visualization of cooperative adsorption of a string-like molecule onto a solid.

Natural systems, composite materials, and thin-film devices adsorb macromolecules in different phases onto their surfaces. In general, polymer chains form interfacial layers where their aggregation states and thermal molecular motions differ from the bulk. Here, we visualize well-defined double-stranded DNAs (dsDNAs) using atomic force microscopy and molecular dynamics simulations to clarify the adsorption mechanism of polymer chains onto solid surfaces. Initially, short and long dsDNAs are individually and cooperatively adsorbed, respectively. Cooperative adsorption involves intertwining of multiple chains. The dependence of adsorption on the chain affects the formation of the interfacial layer, realizing different mechanical properties of DNA/filler bulk composites. These findings will contribute to the development of light and durable polymer composites and films for various industrial, biomedical, and environmental applications.

Implant Treatment in Patient with Periodontitis: A Case Report with 13-year Follow-up.

This report describes long-term implant treatment in a patient with chronic periodontitis. The patient was a 59-year-old man who attended our facility requesting a dental implant. An initial examination revealed generalized gingival inflammation and subgingival calculus. Clinical examination revealed 55.3% of sites with a probing depth (PD) of >4 mm and 41.3% of sites with bleeding on probing. Radiographic examination revealed vertical bone resorption in #23, #33, #33, #35, and #47. Initial periodontal therapy consisting of plaque control, scaling and root planing, and tooth extraction was subsequently performed based on a clinical diagnosis of severe chronic periodontitis. Open flap debridement was performed for teeth with a PD >5 mm (#21, #22, #23, 333, #34, #35 and #47). After confirming the stability of the periodontal tissue, 3 implants were first placed in the maxilla (#25, #26, and #27). Final prostheses comprising a screw retaining-type implant superstructure were then placed (#25, #26, and 327). Following reevaluation, the patient was placed on supportive periodontal therapy. At 15 years after the first visit, the periodontal and implant conditions have remained stable. These results indicate that periodontal treatment before implantation and subsequent maintenance yield a clinically favorable and long-lasting outcome.

Overcoming Complications with Implants in the Esthetic Zone: An Innovative Approach.

Owing to the satisfactory esthetic and functional outcomes of implant surgery for the anterior teeth, some dentists consider it the gold standard treatment. However, the risk of developing peri-implantitis is positively associated with the long-term use of the implant. This necessitates the development of an implant design that reduces the risk of peri-implantitis, especially considering the long-term use of implants in young patients. This case report describes a new approach for an implant surgery using a two-stage implant in a 28-year-old woman. Her clinical course was satisfactory during the 4-year postoperative follow-up period; no inflammation was noted in the surrounding tissues. The two-stage implants allow for the removal of an implant body from an infected area and its replacement with a new abutment if peri-implantitis develops in the future.

Cell surface membrane lysosome-associated membrane glycoprotein 2 promotes cell adhesion via abundant N-glycans in choriocarcinoma.

INTRODUCTION: Lysosome-associated membrane glycoprotein 2 (LAMP-2) is a target protein for glycosylation by N-acetylglucosaminyltransferase IV (GnT-IV), which catalyzes the formation of ß1,4GlcNAc branches on the mannose core of N-glycans in choriocarcinoma cells. However, the role of LAMP-2, especially when it is expressed in the cell surface membrane of choriocarcinoma cells, has not been well investigated in the progression of choriocarcinoma. This study aimed to elucidate the function of the cell surface membrane LAMP-2 in the malignancy of choriocarcinoma. METHODS: We evaluated the localization of LAMP-2 in some choriocarcinoma cell lines and clinical samples of choriocarcinoma, normal placenta, hydatidiform mole, and invasive mole by flow cytometry, immunocytochemistry, and immunohistochemistry. We performed functional experiments using the knockout or overexpression model of LAMP-2 in the presence or absence of galectins. RESULTS: LAMP-2 was observed in the cell surface membrane of some choriocarcinoma cell lines and tumor cells of choriocarcinoma tissue and trophoblasts of the placenta, hydatidiform mole, and invasive mole. Cell surface membrane LAMP-2 knockout decreased cell adhesion and invasion in choriocarcinoma cells. Conversely, cell surface membrane LAMP-2A overexpression increased cell adhesion and invasion. Experiments in the presence of galectins revealed that abundant N-glycans bound to the peptide core of the luminal side of the cell surface membrane LAMP-2 mediated cell adhesion of choriocarcinoma cells by interacting with galectins in the extracellular matrix (ECM). DISCUSSION: Cell surface membrane LAMP-2, which is glycosylated by GnT-IV, contributes to the malignancy of choriocarcinoma by promoting cell adhesion with the ECM via abundant N-glycans.

Clinical evaluation of periodontal pathogen levels by real-time polymerase chain reaction in peri-implantitis patients.

OBJECTIVE: The mechanisms underlying the onset and progression of peri-implantitis are similar to those of periodontitis, and the causative bacteria are believed to similar. Previous studies support an association between peri-implantitis and periodontal pathogen. Thus, we investigated the bacterial flora of peri-implantitis patients in comparison to those of healthy implant and periodontitis patients. MATERIALS AND METHODS: In total, 70 patients visiting Tokyo Dental College Chiba Hospital were divided into four groups: healthy, periodontitis, healthy implant, and peri-implantitis. For each group, the following five periodontal pathogens were detected using real-time polymerase chain reaction: Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Tannerella forsythia, Treponema denticola, and Prevotella intermedia. RESULTS: The average copy number of total bacteria was significantly higher in the periodontitis group than in the other groups. P. gingivalis was detected in the periodontitis and peri-implantitis groups at levels as high as 18.92% and 12.29%, respectively, and P. intermedia was found in the peri-implantitis group at a rate of 2.06%. Nevertheless, periodontal pathogens were generally detected at lower levels in the peri-implantitis group than in the periodontitis group. CONCLUSION: We found lower bacterial counts in the peri-implantitis group relative to the periodontitis group. Our results suggest that the peri-implant tissue is less resistant to bacteria, so even a small number of bacteria can be a risk factor for peri-implantitis and the causative agent of peri-implantitis can be bacteria other than periodontal pathogen.

Short tandem repeat analysis to identify the causative pregnancy of high-risk gestational trophoblastic neoplasia: Molar versus nonmolar pregnancy and its relation to the outcome.

INTRODUCTION: Gestational trophoblastic neoplasia (GTN) include a group of malignant neoplasms that originate from the trophoblasts of placental tissue in molar or nonmolar pregnancy. Currently, it is unclear whether the prognosis of high-risk GTN or gestational choriocarcinoma succeeding molar pregnancy or that following a nonmolar one is better. Comparison of the genetic short tandem repeat (STR) patterns of the DNA extracted from the tumor, patient, and her partner allows the genetic origins of the choriocarcinoma to be distinguished - whether it is gestational or non-gestational and whether it is derived from a molar or nonmolar pregnancy in the event it is gestational. This study aimed to investigate the causative pregnancy of patients with high-risk GTN, especially those with poor outcomes, and assess the impact of the causative pregnancy on patient outcome. METHODS: We evaluated 24 patients who were diagnosed with high-risk GTN between January 2000 and October 2019, including 15 cases of pathologically proven gestational choriocarcinomas and the causative pregnancy was investigated by STR analysis in which tumor DNA could be extracted. RESULTS: In high-risk GTN without history of anteceding molar pregnancies, nonmolar pregnancy was the causative pregnancy, which was confirmed in three cases. Molar pregnancy appeared be the causative pregnancy of high-risk GTN in patients with a history of antecedent molar pregnancies either with or without interruption by subsequent nonmolar pregnancies prior to developing high-risk GTN. High-risk GTN in most of the evaluated deceased cases (three of four) was due to nonmolar pregnancy, while all but one case with molar pregnancy as the causative pregnancy survived. DISCUSSION: STR analysis can distinguish the causative pregnancy of high-risk GTN, and nonmolar pregnancy as the causative pregnancy might have negative effects on the outcome of the disease.

Next-generation genome sequencing of a matched normal-tumor pair from a patient with intractable gestational choriocarcinoma: A case report.

Gestational choriocarcinoma is a gestational trophoblastic neoplasia (GTN) originating from trophoblastic cells with abnormal proliferation. Although chemotherapy is effective for treating this cancer, when patients develop chemoresistance, personalized treatment, such as the use of drugs matching their genomes, is required. The present report describes a case of intractable gestational choriocarcinoma identified using a next-generation sequencing (NGS)-based tumor panel. A 51-year-old woman was diagnosed with gestational choriocarcinoma via pathological and short tandem repeat analyses. The patient did not achieve remission despite many regimens of chemotherapy, including high-dose therapy with autologous peripheral blood stem cell transplantation. To identify drugs tailored to this particular choriocarcinoma, NGS was performed on the tumor of the patient, and the tumor genome was compared with that of the patient's blood sample using the NCC Oncopanel System. Consequently, 245 single nucleotide variants (SNVs) with a mean SNV allele frequency of 63.1% were identified. This high frequency was because the genome of the gestational choriocarcinoma contained part of the genome of the partner. Therefore, our experience of the present intractable case of choriocarcinoma suggested that matched normal-tumor pair analysis is not appropriate for treatment decisions in GTN cases. When using an NGS-based tumor panel to assess choriocarcinoma, researchers must consider whether the genomic DNA of the patient and their partner are involved in the GTN.

Marginal bone loss and the risk indicators of fixed screw-retained implant-supported prostheses and fixed telescopic-retained implant-supported prostheses in full arch: A retrospective case-control study.

OBJECTIVES: This study compared full-arch screw-retained implant-supported fixed dental prostheses (FSI-FDPs) and full-arch telescopic-retained implant-supported fixed dental prostheses with a professional retrieval system (FTI-FDPs) on marginal bone loss (MBL), the risk indicators and peri-implantitis rate after 7-13 years. MATERIAL AND METHODS: Sixty five edentulous patients were treated with 86 prostheses and 592 implants. The FSI-FDP group comprised 26 patients (32 prostheses, 202 implants), and the FTI-FDP group comprised 39 patients (54 prostheses, 390 implants). MBL and the risk indicators of MBL ≥1 mm were assessed. Peri-implantitis rates at 13 years were also calculated. RESULTS: Full-arch screw-retained implant-supported fixed dental prostheses and FTI-FDP implants exhibited comparable mean MBLs of 0.60 ± 0.51 and 0.41 ± 1.03 mm, respectively. MBL ≥1 mm was noted for 25% of FSI-FDP implants and 6.9% of FTI-FDP implants. Superstructure-abutment connection (screw retention:FSI-FDPs >telescopic retention:FTI-FDPs) and implant-abutment connection (External butt joint, Internal butt joint >Morse taper joint) were associated with MBL ≥1 mm. Peri-implantitis rates at the implant level were 3.99% (95%CI = 3.93-20.5) in FSI-FDP group and 3.85% (95%CI = 3.85-34.3) in FTI-FDP group with no significance. CONCLUSIONS: It was concluded that FSI-FDP and FTI-FDP implants exhibited comparable MBL; however, the risk of MBL ≥1 mm in FTI-FDPs was lower than in FSI-FDPs. Besides, implant-abutment connection was the risk indicator of MBL ≥1 mm. In peri-implantitis rate, FSI-FDPs and FTI-FDPs behave similarly.

Effects of 2% sodium fluoride solution on the prevention of streptococcal adhesion to titanium and zirconia surfaces.

Streptococci are associated with dental plaque formation as the early-colonizing bacteria that adhere to titanium (CpTi) and zirconia (TZP) implant abutment surfaces. Effective prevention of peri-implantitis may be possible by removing streptococci as target. This study aimed to evaluate the effects of 2% NaF on the prevention of streptococcal adhesion to CpTi and TZP. After immersion in 2% NaF for 90 min, surface characterization of mirror-polished CpTi and TZP disks were assesed using XPS, EPMA, and SEM. S. sanguinis, S. gordonii, and S. oralis were used as the streptococcal bacterial strains. After 24 h culture, bacterial adhesion was evaluated using an ATP-bioluminescent assay and SEM. In XPS, EPMA, and SEM analyses, fluoride was detected on the CpTi and TZP surfaces after 2% NaF immersion with no signs of localization, and no corrosion on the CpTi disks. Based on the adhesion assay, the adherences of S. sanguinis, S. gordonii, and S. oralis were significantly lower with NaF than without NaF in CpTi (p = 0.005, 0.001, and 0.001, respectively) and TZP (p = 0.003, 0.002, and 0.001). This was also confirmed by SEM. In conclusion, 2% NaF reduced the adhesion of streptococci to the CpTi and TZP surfaces.

Direct observation of morphological transition for an adsorbed single polymer chain.

A better understanding of the structure of polymers at solid interfaces is crucial for designing various polymer nano-composite materials from structural materials to nanomaterials for use in industry. To this end, the first step is to obtain information on how synthetic polymer chains adsorb onto a solid surface. We closely followed the trajectory of a single polymer chain on the surface as a function of temperature using atomic force microscopy. Combining the results with a full-atomistic molecular dynamics simulation revealed that the chain became more rigid on the way to reaching a pseudo-equilibrium state, accompanied by a change in its local conformation from mainly loops to trains. This information will be useful for regulating the physical properties of polymers at the interface.

Adhesion of streptococci to titanium and zirconia.

The purpose of this study was to evaluate the adherence of streptococci to disks of titanium (commercially pure titanium: CpTi) and zirconia (tetragonal zirconia polycrystals: TZP). CpTi and yttria-stabilized TZP disks with a mirror-polished surface were used as specimens. The arithmetic mean surface roughness (Ra and Sa) and the surface wettability of the experimental specimens were measured. For analyzing the outermost layer of the experimental specimens, X-ray photoelectron spectroscopy (XPS) analysis was performed. Streptococcus sanguinis, S. gordonii, S. oralis, and S. mutans were used as streptococcal bacterial strains. These bacterial cultures were grown for 24 h on CpTi and TZP. The number of bacterial adhesions was estimated using an ATP-bioluminescent assay, and scanning electron microscope (SEM) observation of the adhered bacterial specimens was performed. No significant differences in surface roughness or wettability were found between CpTi and TZP. In XPS analyses, outermost layer of CpTi included Ti0 and Ti4+, and outermost layer of TZP included Zr4+. In the cell adhesion assay, the adherences of S. sanguinis, S. gordonii, and S. oralis to TZP were significantly lower than those to CpTi (p < 0.05); however, significant difference was not observed for S. mutans among the specimens. The adherence to CpTi and TZP of S. mutans was significantly lower than that of S. sanguinis, S. gordonii, and S. oralis. These results were confirmed by SEM. S. sanguinis, S. gordonii, and S. oralis adhered less to TZP than to CpTi, but the adherence of S. mutans was similar to both surfaces. S. mutans was less adherent compare with the other streptococci tested in those specimens.

Evaluation of a routine second curettage for hydatidiform mole: a cohort study.

OBJECTIVE: The aim of this study was to evaluate routine second curettage for hydatidiform mole (HM) by comparing the characteristics and outcomes of developing gestational trophoblastic neoplasia (GTN). STUDY DESIGN: This was a cohort study including 173 patients diagnosed with HM between January 2002 and August 2019 who were followed up at Nagoya University Hospital, Japan. After an evacuation, 105 and 68 patients were managed with the routine method (routine group) and elective method (elective group) for a second curettage, respectively. The routine second curettage was performed around 7 days after the first evacuation. Patients in the elective group underwent a second curettage if there was ultrasonographic evidence of molar remnants in the uterine cavity. Socio-clinical factors were retrospectively compared between the routine and elective groups, and between patients showing regression and those who developed GTN. RESULTS: The incidence of GTN was 15.2% in the routine group and 20.6% in the elective group, and the difference was not significant (P = 0.364). The median GTN risk score was significantly higher in the routine group than in the elective group (P = 0.033). Presence of a complete HM, gestational age, and a pre-treatment human chorionic gonadotropin level of ≥ 200,000 mIU/mL were independent risk factors for GTN in molar patients. CONCLUSION: The incidence of GTN was unchanged but the risk score of GTN was higher in the routine group than in the elective group. Routine second curettage may not be necessary, but further study will be needed to confirm this.

Full-Arch Implant-Supported Fixed Dental Prosthesis Retained by a Combination of Galvano-Telescopic Copings and Screws: A Clinical Report.

Full-arch screw-retained implant-supported fixed dental prostheses have a high long-term success rate and are considered the gold standard by many clinicians. However, accurate fabrication of a passive fit long-span prosthesis can be challenging. A novel intraoral adhesion method using galvano-telescopic copings was proposed as a way of improving prosthetic fit for edentulous patients. This report describes the treatment of a 74-year-old female with a full-arch implant-supported dental prosthesis, supported by a combination of galvano-telescopic copings and screws to prevent retention loss. Four years have passed since this superstructure was placed, during this time she exhibited a good clinical course with no inflammation noted in surrounding tissues. Treatment with an implant-supported fixed dental prosthesis, retained by a combination of galvano-telescopic copings and screws, can be a useful alternative treatment for edentulous patients.

Bioinspired Approach to Silica Nanoparticle Synthesis Using Amine-Containing Block Copoly(vinyl ethers): Realizing Controlled Anisotropy.

Core-shell polymer-silica hybrid nanoparticles smaller than 50 nm in diameter were formed in the presence of micelles of poly(2-aminoethyl vinyl ether-block-isobutyl vinyl ether) (poly(AEVEm-b-IBVEn)) through the hydrolysis and polycondensation of alkoxysilane in aqueous solution at a mild pH and temperature. The size of the nanoparticles as well as the number and size of the core parts were effectively controlled by varying the molecular weight of the copolymers. The polymers could be removed by calcination to give hollow silica nanoparticles with Brunauer-Emmett-Teller surface areas of more than 500 m2 g-1. Among these, silica nanoparticles formed with poly(AEVE115-b-IBVE40) displayed an anisotropy of single openings in the shell. The use of an alternative copolymer, poly(AEVE-b-2-naphthoxyethyl vinyl ether) (poly(AEVE113-b-ßNpOVE40)), yielded core-shell nanoparticles with less pronounced anisotropy. These results showed that the degree of anisotropy could be controlled by the rigidity of micelles; the micelle of poly(AEVE115-b-IBVE40) was more deformable during silica deposition than that of poly(AEVE113-b-ßNpOVE40) in which aromatic interactions were possible. This bioinspired, environmentally friendly approach will enable large-scale production of anisotropic silica nanomaterials, opening up applications in the field of nanomedicine, optical materials, and self-assembly.

Clinical evaluation of full-arch screw-retained implant-supported fixed prostheses and full-arch telescopic-retained implant-supported fixed prostheses: A 5-12 year follow-up retrospective study.

OBJECTIVE: To assess the prostheses and implants survival rate and peri-implantitis rate in edentulous patients treated with full-arch screw-retained implant-supported fixed dental prostheses (FSIFDPs) and full-arch telescopic-retained implant-supported fixed dental prostheses (FTIFDPs) over an observation period of at least 5 years. MATERIALS AND METHODS: From 2004 to 2012, 696 implants were inserted into 78 patients with 102 prostheses. The FSIFDP group comprised 31 patients (37 prostheses, 232 implants), whereas the FTIFDP group comprised 47 patients (65 prostheses, 464 implants). Prosthesis and implant estimated cumulative survival rates (ECSR) and estimated cumulative peri-implantitis rates (ECPR) were assessed. The follow-up period was 5-12 years. Kaplan-Meier survival curves with the log-rank test were used to evaluate outcomes. RESULTS: The 12-year prosthesis ECSR was 96.8% (95% CI: 79.2-99.5, 36/37 prostheses) in the FSIFDP group and 96.4% (95% CI: 86.3-99.1, 63/65 prostheses) in the FTIFDP group, whereas the 12-year implant ECSR was 99.5% (95% CI: 96.4-99.9, 231/232 implants) in the FSIFDP group and 98.7% (95% CI: 96.9-99.5, 459/464 implants) in the FTIFDP group. The 12-year ECPR at the prosthesis level was 12.8% (95% CI: 12.7-47.6, 4/37 prostheses) in the FSIFDP group and 12.8% (95% CI: 11.4-24.1, 6/65 prostheses) in the FTIFDP group. The 12-year ECPR at the implant level was 4.4% (95% CI: 4.3-23.0, 6/232 implants) in the FSIFDP group and 2.2% (95% CI: 2.0-12.3, 7/464 implants) in the FTIFDP group. CONCLUSION: FTIFDPs have clinical results comparable to those of FSIFDPs. Therefore, FTIFDPs can be useful.

Bone marrow stromal cells from low-turnover osteoporotic mouse model are less sensitive to the osteogenic effects of fluvastatin.

This study aimed to investigate the effects of fluvastatin on the differentiation of bone marrow stromal cells (BMSCs) into osteoblasts in senescence-accelerated mouse prone 6 (SAMP6) compared with that in the normal senescence-accelerated-resistant mouse (SAMR1) model. SAMP strains arose spontaneously from the AKR/J background and display shortened life span and an array of signs of accelerated aging, compared with control SAMR strains. The dose effects of fluvastatin were also evaluated. BMSCs were cultured with/without fluvastatin (0 µM, 0.1 µM, 0.5 µM, and 1.0 µM). WST-1-based colorimetry was performed to evaluate cell proliferation. To evaluate cell differentiation, gene expression levels of bmp2 and runx2 were determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR), and protein expression levels were determined using enzyme-linked immunosorbent assay (BMP2) and immunofluorescence staining (BMP2 and Runx2). Alkaline phosphatase (ALP) activity assay and histochemical detection were determined; the effect of noggin, a BMP-specific antagonist, was examined using ALP histochemical detection. To assess for mature osteogenic marker, gene expression levels of bglap2 were determined by qRT-PCR and mineralization was determined by alizarin red staining. RhoA activity was also examined by Western blotting. In SAMP6, BMP2, Runx2 and Bglap2 mRNA and protein expressions were significantly increased by fluvastatin, and ALP activity was increased by BMP2 action. RhoA activity was also inhibited by fluvastatin. The concentration of fluvastatin sufficient to increase BMP2 and Runx2 expression and ALP activity was 0.5 µM in SAMP6 and 0.1 µM in SAMR1. In conclusion, the present study revealed that fluvastatin promoted BMSC differentiation into osteoblasts by RhoA-BMP2 pathway in SAMP6. BMSCs of SAMP6 are less sensitive to the osteogenic effects of fluvastatin than SAMR1.