Peri‐implant squamous cell carcinoma Ito, K; Takahashi, K; Eda, T ...
Australian dental journal,
June 2018, Letnik:
63, Številka:
2
Journal Article
Recenzirano
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Peri‐implant squamous cell carcinoma is an uncommon pathological manifestation, whereas peri‐implantitis is commonly found in association with dental implants. Both present similarly with loss of ...supporting soft and hard tissue around dental implants; therefore, a careful differential diagnosis is required. The present case concerns a 62‐year‐old Japanese man who had a dental implant which had been in the left maxillary incisor region for 4 years who apparently developed peri‐implantitis. This did not respond to localized therapy and antibiotics so was referred for specialist surgical management. A biopsy confirmed it to be a squamous cell carcinoma rather than an inflammatory lesion. A literature review shows that this is an unusual presentation without a previous history of malignancy, mucosal disease or risk factors for cancers. Although rare, the possibility of peri‐implant squamous cell carcinoma should be borne in mind by all practitioners who monitor implant patients.
ABSTRACT—Fractalkine (now also called CX3CL1) is a unique chemokine that functions not only as a chemoattractant but also as an adhesion molecule and is expressed on endothelial cells activated by ...proinflammatory cytokines, such as interferon-γ and tumor necrosis factor-α. The fractalkine receptor, CX3CR1, is expressed on cytotoxic effector lymphocytes, including natural killer (NK) cells and cytotoxic T lymphocytes, which contain high levels of intracellular perforin and granzyme B, and on macrophages. Soluble fractalkine causes migration of NK cells, cytotoxic T lymphocytes, and macrophages, whereas the membrane-bound form captures and enhances the subsequent migration of these cells in response to secondary stimulation with other chemokines. Furthermore, stimulation through membrane-bound fractalkine activates NK cells, leading to increased cytotoxicity and interferon-γ production. Recently, accumulating evidence has shown that fractalkine is involved in the pathogenesis of various clinical disease states or processes, such as atherosclerosis, glomerulonephritis, cardiac allograft rejection, and rheumatoid arthritis. In addition, polymorphisms in CX3CR1, which reduce its binding activity to fractalkine, have been reported to increase the risk of HIV disease and to reduce the risk of coronary artery disease. This review will examine new concepts underlying fractalkine-mediated leukocyte migration and tissue damage, focusing primarily on the pathophysiological roles of fractalkine in various clinical conditions, especially in atherosclerosis and vascular injury.
Engagement of the Fas receptor (CD95) initiates multiple signaling pathways that lead to apoptosis, such as the formation of death-inducing signaling complex (DISC), activation of caspase cascades, ...and the generation of the lipid messenger, ceramide. Sphingomyelin (SM) is a major component of lipid rafts, which are specialized structures that enhance the efficiency of membrane receptor signaling and are a main source of ceramide. However, the functions of SM in Fas-mediated apoptosis have yet to be clearly defined, as the responsible genes have not been identified. After cloning a gene responsible for SM synthesis, SMS1, we established SM synthase-defective WR19L cells transfected with the human Fas gene (WR/Fas-SM(-)), and cells that have been functionally restored by transfection with SMS1 (WR/Fas-SMS1). We show that expression of membrane SM enhances Fas-mediated apoptosis through increasing DISC formation, activation of caspases, efficient translocation of Fas into lipid rafts, and subsequent Fas clustering. Furthermore, WR/Fas-SMS1 cells, but not WR/Fas-SM(-) cells, showed a considerable increase in ceramide generation within lipid rafts upon Fas stimulation. These data suggest that a membrane SM is important for Fas clustering through aggregation of lipid rafts, leading to Fas-mediated apoptosis.
Purpose:
Lung adenocarcinoma is histologically diverse but has distinct histologic growth patterns. There is no consensus on the clinical benefit of this histologic model. We aimed to evaluate the ...differences in the distribution of the preoperative primary tumor positron emission tomography (PET)/computed tomography (CT) standardized uptake values (SUVs) and survival in the lung adenocarcinoma subtypes.
Methods:
We retrospectively evaluated the data of 107 patients with resected lung adenocarcinoma who had preoperative PET/CT between 2005 and 2017 in a single center. Patients had lepidic, acinar, papillary, micropapillary, and solid histologic subtypes. We compared fluorodeoxyglucose SUVs and survival data of histologic subtypes.
Results:
The median age of the patients was 62 years (40–75), 76.4% were male, the median SUVmax was 9.4 (1–36.7), and the median follow-up time was 29 months (3–135 months). The median overall survival (OS) was 71 months and the median progression-free survival (PFS) was 33 months. SUVmax was significantly different in histologic subtypes: values for papillary, micropapillary, solid, acinar, and lepidic subtypes were 9.7, 8, 12, 9.1, and 3.9, respectively (p = 0.000). Solid predominant adenocarcinoma had significantly higher SUVmax than the other subtypes (p = 0.001). Lepidic predominant adenocarcinoma had significantly lower SUVmax than the other subtypes (p = 0.000). There was no significant difference in OS between histologic subtypes (p = 0.66), but PFS was significantly different between the groups (p = 0.017), and the solid subtype had a shorter PFS than the other histologic subtypes.
Conclusion:
Lung adenocarcinoma consists of a diverse group of diseases. Different SUVmax values are seen in different histologic subtypes of nonmetastatic lung adenocarcinoma. Solid predominant types have high SUVmax values while lepidic predominant types have lower SUVmax values. The solid subtype had a shorter PFS than the other histologic subtypes.
Abstract The aim of this study was to investigate the capacity of human dental follicle cells (hDFCs) for bone formation in vivo. hDFCs were obtained from wisdom teeth extracted from patients aged 14 ...and 22 years. hDFCs from the 5th to 8th passages were grown in three-dimensional (3D) culture using gelatin sponges. Cells were transplanted onto the calvaria of F344/NJcl-rnu/rnu male rats (immunodeficient rats). Haematoxylin and eosin (HE) staining and immunohistochemistry were performed, and newly formed bone was evaluated by micro-computed tomography (micro-CT). HE staining showed newly formed bone in 3D culture. Immunohistochemistry showed bone morphogenetic protein 2 (BMP-2), runt-related transcription factor 2 (RUNX2), and osterix staining in areas with newly formed bone. Furthermore, micro-CT showed that, in comparison to controls, transplanted hDFCs promoted better bone quality and bone mineral density (BMD 582 ± 131.1 vs. 300.5 ± 77.7 mg/cm3 ; P = 0.039), bone mineral content (BMC 5.6 ± 1.1 vs. 2.1 ± 0.4 mg; P = 0.006), bone volume (BV 9.7 ± 0.5 × 10−3 vs. 7.0 ± 0.4 × 10−3 cm3 ; P = 0.002), BMC/total volume (TV) (399.9 ± 76.3 vs. 147.7 ± 30.8 mg/cm3 ; P = 0.006), and BV/TV (69.1 ± 3.6% vs. 49.6 ± 3.1%; P = 0.002). This suggests that human dental follicles are potentially useful for regenerative therapy.
During T cell activation, TCRs cluster at the center of the T cell–antigen-presenting cell interface forming the central supramolecular activation cluster. Although it has been suggested that ...sphingolipid- and cholesterol-rich microdomains, termed lipid rafts, form platforms for the regulation and transduction of TCR signals, an actual role for membrane sphingomyelin (SM), a key component of lipid rafts, has not been reported. After cloning a gene responsible for SM synthesis, sphingomyelin synthase (SMS) 1, we established a SM-knockdown cell line (Jurkat-SMS1/kd) by transfection of SMS1-short-interfering RNA into Jurkat T cells, which is deficient in membrane expression of SM. Upon CD3 stimulation, expression of CD69 (the earliest leukocyte activation antigen), activation-induced cell adhesion and proliferation as well as TCR clustering was severely impaired in Jurkat-SMS1/kd cells. CD3-induced tyrosine phosphorylation and association of linker for activation of T cell with ZAP-70 and Grb2 and phosphorylation of protein kinase C (PKC) θ were also severely impaired in Jurkat-SMS1/kd cells. Finally, translocation of TCR, ZAP-70 and PKCθ into lipid rafts was markedly decreased in Jurkat-SMS1/kd cells. These findings indicate that membrane SM is crucial for TCR signal transduction, leading to full T cell activation through lipid raft function.
BackgroundCarticel is an autologous cultured chondrocyte product that has been approved by the United States Food and Drug Administration for the repair of symptomatic cartilaginous defects of the ...femoral condyle that are caused by acute or repetitive trauma in patients who have been previously managed with arthroscopy or other surgical procedures. The present report describes the adverse events following Carticel implantation as reported to the Food and Drug Administration from 1996 to 2003.MethodsWe reviewed adverse event reports that had been submitted to the Food and Drug Administrationʼs MedWatch system for information on demographic characteristics, adverse events, and surgical revisions. Adverse events were categorized into sixteen non-mutually exclusive groups. Five categories were used to classify reoperations. Food and Drug Administration regulations require manufacturers to report adverse events; however, reporting by clinicians and others is voluntary. Therefore, adverse event reporting is likely to underestimate the number of event occurrences. Adverse events may be either causally or coincidentally related to the product.ResultsA total of 497 adverse events among 294 patients receiving Carticel were reported. The median interval from Carticel implantation to the diagnosis of an adverse event was 240 days (range, one to 2105 days). The median age of the patients was thirty-eight years, and 63% of the patients were male. Of the 270 events for which the anatomic site was noted, 258 (96%) involved the femoral condyles. More than one adverse event was reported for 135 patients (46%). The most commonly reported events were graft failure (seventy-three patients; 25%), delamination (sixty-five patients; 22%), and tissue hypertrophy (fifty-two patients; 18%). In addition, eighteen surgical site infections were reported, including eleven joint and seven soft-tissue infections. Surgical revision subsequent to Carticel implantation was mentioned in the records for 273 patients (93%). The reasons for the 389 revision procedures included graft-related problems (187 procedures; 48.1%), periarticular soft-tissue problems (ninety-seven procedures; 24.9%), and intra-articular problems (sixty-three procedures; 16.2%). Eight patients had a total knee replacement. Based on the manufacturerʼs reported distribution of 7500 Carticel lots between 1995 and 2002, 285 patients (3.8%) had an adverse event that was reported to the Food and Drug Administration.ConclusionsThe most common adverse events reported in association with the Carticel technique involved graft failure, delamination, and tissue hypertrophy.Level of EvidenceTherapeutic Level IV. See Instructions to Authors for a complete description of levels of evidence.
Leukocyte adhesion and trafficking at the endothelium requires both cellular adhesion molecules and chemotactic factors. A newly identified CX3C chemokine, fractalkine, expressed on activated ...endothelial cells, plays an important role in leukocyte adhesion and migration. We examined the functional effects of fractalkine on beta1 and beta2 integrin-mediated adhesion using a macrophage-like cell line, THP-1 cells. In this study, we report that THP-1 cells express mRNA encoding a receptor for fractalkine, CX3CR1, determined by Northern blotting. Scatchard analysis using fractalkine-SEAP (secreted form of placental alkaline phosphatase) chimeric proteins revealed that THP-1 cells express a single class of CX3CR1 with a dissociation constant of 30 pM and a mean expression of 440 sites per cell. THP-1 cells efficiently adhered, in a fractalkine-dependent manner, to full-length of fractalkine immobilized onto plastic and to the membrane-bound form of fractalkine expressed on ECV304 cells or TNF-alpha-activated HUVECs. Moreover, soluble-fractalkine enhanced adhesion of THP-1 cells to fibronectin and ICAM-1 in a dose-dependent manner. Pertussis toxin, an inhibitor of Gi, inhibited the fractalkine-mediated enhancement of THP-1 cell adhesion to fibronectin and ICAM-1. Finally, we found that soluble-fractalkine also enhanced adhesion of freshly separated monocytes to fibronectin and ICAM-1. These results indicate that fractalkine may induce firm adhesion between monocytes and endothelial cells not only through an intrinsic adhesion function itself, but also through activation of integrin avidity for their ligands.
Endothelial cells (ECs) are primary targets of immunological attack, and their injury can lead to vasculopathy and organ dysfunction in vascular leak syndrome and in rejection of allografts or ...xenografts. A newly identified CX3C-chemokine, fractalkine, expressed on activated ECs plays an important role in leukocyte adhesion and migration. In this study we examined the functional roles of fractalkine on NK cell activity and NK cell-mediated endothelial cell injury. Freshly separated NK cells expressed the fractalkine receptor (CX3CR1) determined by FACS analysis and efficiently adhered to immobilized full-length fractalkine, but not to the truncated forms of the chemokine domain or mucin domain, suggesting that fractalkine functions as an adhesion molecule on the interaction between NK cells and ECs. Soluble fractalkine enhanced NK cell cytolytic activity against K562 target cells in a dose- and time-dependent manner. This enhancement correlated well with increased granular exocytosis from NK cells, which was completely inhibited by the G protein inhibitor, pertussis toxin. Transfection of fractalkine cDNA into ECV304 cells or HUVECs resulted in increased adhesion of NK cells and susceptibility to NK cell-mediated cytolysis compared with control transfection. Moreover, both enhanced adhesion and susceptibility of fractalkine-transfected cells were markedly suppressed by soluble fractalkine or anti-CX3CR1 Ab. Our results suggest that fractalkine plays an important role not only in the binding of NK cells to endothelial cells, but also in NK cell-mediated endothelium damage, which may result in vascular injury.
NK cells, a component of the innate immune system, provide a first line of defense against viral infections and malignancies, interact with the adaptive immune system and have a role in rejection of ...allogeneic bone marrow transplants and solid allo- and xenotransplants. Immunoregulatory activity by the anti-hypercholesterolemia agents, 3-hydroxy-3-methyl-glutaryl Coenzyme A (HMG-CoA) reductase inhibitors, known as statins, has recently been reported. We analyzed the effects of three statins on human NK cell cytotoxicity. Two lipophilic statins (simvastatin and fluvastatin) suppressed the cytotoxic activity of fresh and IL-2-stimulated NK cells, while pravastatin, a hydrophilic statin, did not. Suppression was not associated with changes in intracellular perforin, granzyme A or granzyme B levels, or with changes in expression of leukocyte function-associated antigen-1, an integrin known to regulate NK activity and reported to be altered by statin treatment. Decreased cytotoxicity was associated with decreased CD107a surface expression, indicating that the exocytosis pathway was compromised by simvastatin and fluvastatin but not by pravastatin. Mevalonate, the immediate downstream product of HMG-CoA reductase, partially reversed the effect of lipophilic statins on cytotoxicity and CD107a expression. Lipophilic statins also suppressed the release of the granule component, granzyme B, by IL-2-activated NK cells following stimulation with K562. That lipophilic statins suppress NK cell activity through inhibition of the exocytosis pathway suggest an additional potential role for statins in inhibition of transplantation responses.
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