RESUMO
INTRODUCTION: The aim of this study was to compare body weight loss between postoperative intermaxillary fixation with metal wire and elastic traction and to investigate factors related to body weight loss after orthognathic surgery. MATERIALS AND METHODS: Subjects were 59 patients with dentofacial deformity, comprising 31 patients treated with intermaxillary fixation (IMF) and 28 patients treated with elastic traction without IMF (ELT) just after surgery. Body weight loss was measured at 1 week (T1) and 2 weeks (T2) after surgery. Body weight loss was compared between IMF and ELT, and factors related to body weight loss were statistically analyzed. RESULTS: Body weight loss ratio was significantly increased in IMF (2.6%) rather than in ELT (1.4%) at T1, but only tended to be increased in both groups at T2, showing no statistical difference. Body weight loss ratio was significantly increased at T2 compared to T1 in both groups. Body weight loss was significantly greater at T2 than at T1. CONCLUSION: Both IMF and ELT cause body weight loss after orthognathic surgery, but IMF causes body weight loss earlier than ELT and increased early body weight loss increases continuous body weight loss after orthognathic surgery.
RESUMO
Objectives: We investigated whether the positivity of anti-citrullinated peptide antibody (ACPA) is associated with cigarette-smoking status and human T-cell leukaemia virus type 1 (HTLV-1) infection in a general population in Nagasaki, Japan, which is an ageing and HTLV-1-endemic area.Method: Baseline data from community-dwelling people in the Nagasaki Islands Study (NaIS) were included in this cross-sectional analysis. ACPA and HTLV-1 were measured in 3887 subjects without a history of treatment for rheumatoid arthritis. A logistic regression analysis was performed to assess the relationship between ACPA positivity and candidates of correlation with ACPA, i.e. the cigarette-smoking status quantified by Brinkman's index (BI) and HTLV-1 positivity.Results: Fifty-one subjects (1.3%) showed ACPA positivity, and 650 subjects (16.6%) were HTLV-1 carriers. In an age- and gender-adjusted logistic regression analysis, the BI [odds ratio (OR) 1.09, 95% confidence interval (CI)1.02-1.14, p = 0.0031] and a BI value > 500 (OR 3.92, 95% CI 1.72-9.22, p = 0.0014) were each significantly associated with ACPA positivity. HTLV-1 positivity did not show any association with ACPA positivity.Conclusion: A significant effect of cigarette-smoking status on ACPA production was revealed, whereas HTLV-1 positivity was not associated with ACPA production in this general population.
Assuntos
Anticorpos Antiproteína Citrulinada/sangue , Fumar Cigarros/imunologia , Infecções por HTLV-I/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Fumar Cigarros/sangue , Estudos Transversais , Feminino , Infecções por HTLV-I/sangue , Vírus Linfotrópico T Tipo 1 Humano , Humanos , Vida Independente , Japão , Masculino , Pessoa de Meia-IdadeRESUMO
In this study we investigated the relation between anterior disc displacement (ADD) and maxillomandibular morphology in skeletal anterior open bite with changes to the mandibular condyle. Thirty female patients (60 joints) with both conditions were evaluated. Magnetic resonance imaging of the temporomandibular joint (TMJ) was used to diagnose both ADD and changes to the mandibular condyle (erosion, osteophyte, and deformity). The relations among ADD, changes to the mandibular condyle, and maxillomandibular morphology were examined statistically. Changes to the mandibular condyle had a higher score than sym anterior open bite, the deviated side in asymmetric anterior open bite, and the non-deviated side. The score for disc displacement on the non-deviated side was lower than both the sym side and the deviated side. Unilateral changes to the mandibular condyle and unilateral disc displacement were not apparent in sym anterior open bite, but a unilateral non-displaced disc was seen only on the asymmetric side. Mandibular condylar changes were significantly more common on the deviated, than on the non-deviated, side. The SNB angle was significantly smaller, and the ANB, GZN, and SN-mandibular plane angles were significantly larger in sym anterior open bite. Overjet, ANB angle, GZN angle, and SN-MP angle were significantly larger, and the SNB angle was significantly smaller, in the presence of ADD without reduction and mandibular condylar deformity. We conclude that the prevalence of ADD without reduction and changes to the mandibular condyle were related to mandibular asymmetry and mandibular morphology in anterior open bite. This retrospective study suggests that ADD without reduction and mandibular condylar bone changes may be related to the progression of skeletal class II open bite and mandibular asymmetry in cases of skeletal open bite.
Assuntos
Luxações Articulares , Mordida Aberta , Feminino , Humanos , Luxações Articulares/diagnóstico por imagem , Imageamento por Ressonância Magnética , Côndilo Mandibular/diagnóstico por imagem , Mordida Aberta/diagnóstico por imagem , Estudos Retrospectivos , Articulação Temporomandibular , Disco da Articulação Temporomandibular/diagnóstico por imagemRESUMO
Objective: Successful rheumatoid arthritis (RA) outcome depends on treatment efficacy in the early stages of the disease and its sustainability. It is thus critical to identify factors predicting treatment persistence with biological agents, such as abatacept. We compared clinical profiles, including early changes in autoantibody titres at 3 months, between patients with RA demonstrating sustained persistence and those discontinuing abatacept treatment.Method: We prospectively enrolled 71 and 78 active RA patients treated with abatacept and tumour necrosis factor inhibitors (TNF-Is), respectively, who had previous disease-modifying anti-rheumatic drug) failure. Clinical characteristics were compared between non-continuation and continuation groups stratified according to abatacept or TNF-I persistence for at least 12 months from treatment initiation.Results: Significantly larger decreases in rheumatoid factor titre and anti-citrullinated protein autoantibody (ACPA) titre were observed in the continuation group of abatacept therapy at 3 months, and early reduction in ACPA titre remained a significant and independent predictor of sustained persistence with abatacept in multivariate analysis. In addition, we obtained the area under the receiver operator characteristics curve of 0.904 from a model including baseline ACPA titre and reduction of ACPA titre at 3 months. Sustained reduction of RA disease activity score at 12 months was significantly and independently associated with reduced ACPA titre at 3 months.Conclusions: Persistence with abatacept and sustained therapeutic response are associated with an early reduction in ACPA titre. Prediction of abatacept continuation and efficacy will facilitate the optimal design of therapy in the early stages of RA.
Assuntos
Abatacepte/administração & dosagem , Anticorpos Antiproteína Citrulinada/sangue , Artrite Reumatoide/imunologia , Idoso , Anticorpos Antiproteína Citrulinada/imunologia , Antirreumáticos/administração & dosagem , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/tratamento farmacológico , Biomarcadores/sangue , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Humanos , Infusões Intravenosas , Injeções Subcutâneas , Japão , Masculino , Estudos Prospectivos , Resultado do Tratamento , UltrassonografiaRESUMO
Ral small GTPases, consisting of RalA and RalB, are members of the Ras family. Their activity is upregulated by RalGEFs. Since several RalGEFs are downstream effectors of Ras, Ral is activated by the oncogenic mutant Ras. Ral is negatively regulated by RalGAP complexes that consist of a catalytic α1 or α2 subunit and its common partner ß subunit and similarly regulate the activity of RalA as well as RalB in vitro. Ral plays an important role in the formation and progression of pancreatic and lung cancers. However, the involvement of Ral in oral squamous cell carcinoma (OSCC) is unclear. In this study, we investigated OSCC by focusing on Ral. OSCC cell lines with high Ral activation exhibited higher motility. We showed that knockdown of RalGAPß increased the activation level of RalA and promoted the migration and invasion of HSC-2 OSCC cells in vitro. In contrast, overexpression of wild-type RalGAPα2 in TSU OSCC cells attenuated the activation level of RalA and inhibited cell migration and invasion. Real-time quantitative polymerase chain reaction analysis of samples from patients with OSCC showed that RalGAPα2 was downregulated in oral cancer tissues as compared with normal epithelia. Among patients with OSCC, those with a lower expression of RalGAPα2 showed a worse overall survival rate. A comparison of DNA methylation and histone modifications of the RalGAPα2 gene in OSCC cell lines suggested that crosstalk among DNA methylation, histone H4Ac, and H3K27me2 was involved in the downregulation of RalGAPα2. Thus, activation of Ral GTPase by downregulation of RalGAP expression via a potential epigenetic mechanism may enhance OSCC progression.
Assuntos
Carcinoma de Células Escamosas/genética , Proteínas Ativadoras de GTPase/genética , Neoplasias Bucais/genética , Proteínas ral de Ligação ao GTP/genética , Linhagem Celular Tumoral , Metilação de DNA , Progressão da Doença , Regulação para Baixo , Epigênese Genética , Técnicas de Silenciamento de Genes , Histonas , HumanosRESUMO
BACKGROUND: Lupus nephritis (LN) is a major determinant of mortality in systemic lupus erythematosus (SLE). Here we evaluated the association between complete renal response (CR) and mortality in LN. METHODS: We retrospectively analyzed the cases of 172 of 201 patients with LN for whom data on the therapeutic response at 6 and 12 months after induction therapy were available. The patients underwent a renal biopsy at Nagasaki University Hospital and community hospitals in Nagasaki between the years 1990 and 2016. We determined the CR rates at 6 and 12 months after induction therapy initiation and evaluated the predictive factors for CR and their relationship with mortality. We performed univariate and multivariable competing risks regression analyses to determine the factors predictive of CR. The patients' survival data were analyzed by the Kaplan-Meier method with a log-rank test. RESULTS: The median follow-up duration after renal biopsy was 120 months (interquartile range: 60.3-191.8 months). The 5-, 10-, 15- and 20-year survival rates of our cohort were 99.3, 94.6, 92.0 and 85.4%, respectively. During follow-up, nine patients (5.2%) died from cardiovascular events, infection, malignancy and other causes. The multivariate analysis revealed that the following factors were predictive of CR. At 6 months: male gender (odds ratio (OR) 0.23, 95% confidence interval (CI) 0.08-0.65, p = 0.0028), proteinuria (g/gCr) (OR 0.83, 95% CI 0.71-0.97, p = 0.0098) and index of activity (0-24) (OR 0.84, 95% CI 0.71-0.99, p = 0.0382). At 12 months: male gender (OR 0.25, 95% CI 0.09-0.67, p = 0.0043) and index of activity (0-24) (OR 0.82, 95% CI 0.69-0.98, p = 0.0236). The Kaplan-Meier analysis showed that compared to not achieving CR at 12 months, achieving CR at 12 months was significantly correlated with the survival rate (OR 0.18, 95% CI 0.04-0.92, p = 0.0339). CONCLUSIONS: Our results suggest that the survival rate of patients with LN is associated with the achievement of CR at 12 months after induction therapy, and that male gender and a higher index of activity (0-24) are the common predictive factors for failure to achieve CR at 6 and 12 months.
Assuntos
Glucocorticoides/uso terapêutico , Imunossupressores/uso terapêutico , Nefrite Lúpica/tratamento farmacológico , Nefrite Lúpica/mortalidade , Prednisolona/uso terapêutico , Adulto , Idade de Início , Estudos de Casos e Controles , Feminino , Humanos , Estimativa de Kaplan-Meier , Modelos Logísticos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Proteinúria , Indução de Remissão , Estudos Retrospectivos , Índice de Gravidade de Doença , Fatores SexuaisRESUMO
BACKGROUND: Lupus nephritis (LN) is a major risk factor for overall morbidity and mortality in systemic lupus erythematosus (SLE). METHODS: We retrospectively analyzed cases of proliferative and membranous LN patients who underwent a renal biopsy at our hospital in 1993-2016. We analyzed the association between complete renal response (CR) rates at 12 months after induction therapy and predictive factors for CR and their association with renal flares. RESULTS: Of the 95 cases analyzed, we were able to track the therapeutic responses of 81 patients at 12 months after their induction therapy. The median follow-up duration after renal biopsy was 51 months (interquartile range: 16.5-154.5 months). The Cox proportional hazards model showed that, compared to not attaining CR at 12 months, the attainment of CR at 12 months was correlated with being free from renal flares. The multivariate logistic analysis revealed that the predictive factors for CR at 12 months were the anti-La/SSB antibodies (U/ml) (odds ratio (OR) 1.22, 95% confidence interval (CI) 1.01-1.63, p = 0.0220), blood urea nitrogen (BUN) (OR 0.68, 95% CI 0.44-0.90, p = 0.00048) and serum ß2 microglobulin (MG) (OR 0.26, 95% CI 0.06-0.74, p = 0.00098) levels. CONCLUSIONS: Among LN patients, being free from renal flares was associated with attaining CR at 12 months after induction therapy. Anti-La/SSB antibodies were a positive predictive factor, and BUN and serum ß2MG levels were negative predictive factors of CR at 12 months.
Assuntos
Hospitais Universitários , Imunossupressores/uso terapêutico , Nefrite Lúpica/tratamento farmacológico , Nefrite Lúpica/etiologia , Adulto , Autoantígenos/sangue , Nitrogênio da Ureia Sanguínea , Feminino , Seguimentos , Humanos , Japão , Estimativa de Kaplan-Meier , Rim/patologia , Modelos Logísticos , Nefrite Lúpica/sangue , Nefrite Lúpica/mortalidade , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fragmentos de Peptídeos/sangue , Modelos de Riscos Proporcionais , Recidiva , Indução de Remissão , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Microglobulina beta-2/sangueRESUMO
The aim of this study was to investigate the incidence of anterior disc displacement without reduction (ADDwoR) of the temporomandibular joint (TMJ) in patients with dentofacial deformity. Eighty-eight female patients (176 joints) with skeletal class III malocclusion and 33 female patients (66 joints) with skeletal class II malocclusion, with or without anterior open bite and asymmetry, were evaluated. Magnetic resonance imaging (MRI) of the TMJ was used to diagnose ADDwoR. A statistical analysis was performed to examine the relationship between ADDwoR and skeletal structure. ADDwoR was present in 37 of the 66 joints (56.1%) in class II compared to 34 of the 176 joints (19.3%) in class III (P<0.05). In class III, ADDwoR was significantly more common in joints with mandibular asymmetry (24/74; 32.4%) than in joints with open bite (9/62; 14.5%) and joints with open bite and without mandibular asymmetry (1/38; 2.6%). In class II, ADDwoR was significantly less common in joints with mandibular asymmetry and without open bite (1/8; 12.5%). ADDwoR was only observed on the deviated side in both class III and class II with mandibular asymmetry. The prevalence of ADDwoR differed according to the dentofacial morphology.
Assuntos
Má Oclusão Classe III de Angle/complicações , Má Oclusão Classe II de Angle/complicações , Disco da Articulação Temporomandibular/patologia , Transtornos da Articulação Temporomandibular/epidemiologia , Transtornos da Articulação Temporomandibular/etiologia , Adolescente , Adulto , Feminino , Humanos , Incidência , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Prevalência , Disco da Articulação Temporomandibular/diagnóstico por imagem , Transtornos da Articulação Temporomandibular/diagnóstico por imagemAssuntos
Artrite Reumatoide/imunologia , Citocinas/imunologia , Febre Familiar do Mediterrâneo/imunologia , Adulto , Idoso , Sedimentação Sanguínea , Proteína C-Reativa/imunologia , Quimiocina CX3CL1/imunologia , Quimiocina CXCL10/imunologia , Feminino , Fator Estimulador de Colônias de Granulócitos/imunologia , Humanos , Inflamação , Interleucina-10/imunologia , Interleucina-17/imunologia , Interleucina-6/imunologia , Masculino , Pessoa de Meia-Idade , Fator de Necrose Tumoral alfa/imunologia , Fator A de Crescimento do Endotélio Vascular/imunologiaRESUMO
The expression of mucosa-associated lymphoid tissue 1 (MALT1) that activates nuclear factor (NF)-κB in lymphocyte lineages is rapidly inactivated in oral carcinoma cells at the invasive front and the patients with worst prognosis. However, its mechanism to accelerate carcinoma progression remains unknown, and this study was carried out to examine the role in invasion. HSC2 oral carcinoma cells stably expressing wild-type MALT1 (wtMALT1) reduced the invasion of basement membrane matrices and collagen gels, and the dominant-negative form (∆MALT1)-expressing cells aggressively invaded into collagen gels. MALT1 decelerated proliferation and migration of cells and downregulated expression of matrix metalloproteinase 2 and 9, which were confirmed by short interfering RNA transfections. Reporter assays and immunoblot analysis showed that MALT1 does not affect the NF-κB pathway but inhibits ERK/MAPK activation. This was confirmed by endogenous MALT1 expression in oral carcinoma cell lines. Orthotopic implantation of ∆MALT1-expressing HSC2 cells in mice grew rapid expansive and invasive tongue tumors in contrast to an absence of tumor formation by wtMALT1-expressing cells. These results demonstrate that MALT1 suppresses oral carcinoma invasion by inhibiting proliferation, migration, and extracellular matrix degradation and that the ERK/MAPK pathway is a target of MALT1 and further suggests a role as a suppressor of carcinoma progression.
Assuntos
Caspases/fisiologia , Sistema de Sinalização das MAP Quinases/fisiologia , Neoplasias Bucais/metabolismo , Neoplasias Bucais/patologia , Invasividade Neoplásica/patologia , Invasividade Neoplásica/prevenção & controle , Proteínas de Neoplasias/fisiologia , Animais , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Progressão da Doença , Ativação Enzimática , Regulação Neoplásica da Expressão Gênica , Immunoblotting , Camundongos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Neoplasias Bucais/genética , Proteína de Translocação 1 do Linfoma de Tecido Linfoide Associado à Mucosa , NF-kappa B/metabolismo , Interferência de RNA , RNA Interferente PequenoRESUMO
The purpose of this study was to compare retrospectively postoperative differences in maxillary stability after Le Fort I osteotomy and fixation with an unsintered hydroxyapatite (u-HA)/poly-l-lactic acid (PLLA) plate with or without self-setting α-tricalcium phosphate (Biopex(®)) as interpositional material. Subjects comprised 45 patients diagnosed with mandibular prognathism with maxillary retrognathism and mandibular prognathism with bimaxillary asymmetry. All patients underwent Le Fort I osteotomy and bilateral sagittal split ramus osteotomy with fixation by uHA/PLLA plates. Patients were divided into 4 groups consisting of 9 maxillary impaction cases with Biopex(®) (group 1) to fill the gap between the bone segments, 14 maxillary advancement cases with Biopex(®) (group 2), 8 maxillary impaction cases without Biopex(®) (group 3) and 14 maxillary advancement cases without Biopex(®) (group 4). Changes in cepahalometric parameters at time intervals (1, 3 and 12 months) between the groups were compared. Results showed that stability did not depend on the use or otherwise of Biopex(®).
Assuntos
Implantes Absorvíveis , Materiais Biocompatíveis/uso terapêutico , Cimentos Ósseos/uso terapêutico , Placas Ósseas , Fosfatos de Cálcio/uso terapêutico , Durapatita/química , Maxila/patologia , Osteotomia de Le Fort/métodos , Poliésteres/química , Adolescente , Adulto , Materiais Biocompatíveis/química , Cefalometria/métodos , Sulfatos de Condroitina/uso terapêutico , Assimetria Facial/cirurgia , Feminino , Seguimentos , Humanos , Hidroxiapatitas/uso terapêutico , Incisivo/patologia , Técnicas de Fixação da Arcada Osseodentária/instrumentação , Masculino , Mandíbula/cirurgia , Maxila/cirurgia , Pessoa de Meia-Idade , Osso Nasal/patologia , Osteotomia de Le Fort/instrumentação , Osteotomia Sagital do Ramo Mandibular/métodos , Prognatismo/cirurgia , Estudos Retrospectivos , Sela Túrcica/patologia , Succinatos/uso terapêutico , Adulto JovemRESUMO
OBJECTIVES: Bone oedema is a pathological change in rheumatoid arthritis (RA) that is detectable by magnetic resonance imaging (MRI). Recent histological analyses revealed that a prominent feature of bone oedema is the replacement of adipose tissue with inflammatory cells. Here, we demonstrate the possible roles of mesenchymal stromal cells (MSCs) in bone oedema formation and the pathogenic potential of the cells in RA. METHODS: Adipogenesis of bone marrow-derived human MSCs was induced by a standard adipogenic induction medium in the presence or absence of cytokines. The cytokine productions from MSCs were screened by an antibody array system and confirmed by ELISA. The migration assay was performed to determine the locomotive abilities of undifferentiated MSCs or MSCs after adipogenesis. The expression of α smooth muscle actin (SMA) and F-actin was examined by immunostaining and phalloidin staining, respectively. RESULTS: TNF-α, interleukin (IL)-1ß, IL-6, and TGF-ß clearly inhibited the adipogenesis of MSCs. Production of IL-6 was markedly reduced, and IL-8 secretion was augmented in MSCs after adipogenesis. The mobility of MSCs after adipogenesis was clearly reduced in migration assays compared to that of undifferentiated MSCs. Consistent with these findings, SMA and F-actin expressions were clearly suppressed in MSCs committed to adipogenesis. CONCLUSIONS: Our data suggest that the inflammatory milieu promotes bone oedema by blocking adipogenesis of MSCs. In bone oedema, the enhanced IL-6 production and the increased mobility of MSCs may contribute to the progression of RA. Therefore, bone oedema may be an important target lesion in the treatment of RA.
Assuntos
Adipócitos/citologia , Adipogenia/fisiologia , Artrite Reumatoide/patologia , Edema/patologia , Células-Tronco Mesenquimais/citologia , Adipogenia/efeitos dos fármacos , Artrite Reumatoide/metabolismo , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/fisiologia , Movimento Celular/efeitos dos fármacos , Movimento Celular/fisiologia , Células Cultivadas , Progressão da Doença , Humanos , Interleucina-1beta/farmacologia , Interleucina-6/metabolismo , Interleucina-6/farmacologia , Interleucina-8/metabolismo , Imageamento por Ressonância Magnética , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Fator de Crescimento Transformador beta/farmacologia , Fator de Necrose Tumoral alfa/farmacologiaRESUMO
OBJECTIVE: To determine the association of distinct clinical subsets with myositis-specific autoantibodies (MSAs) towards anti-155/140-kDa polypeptides [anti-155/140 antibodies (Abs)], anti-140-kDa polypeptides (anti-140 Abs), and anti-aminoacyl tRNA synthetases (ARS Abs) in Japanese patients with dermatomyositis (DM). METHODS: We compared the clinical features and short-term prognoses of 30 DM patients whose serological status included these MSAs. The MSAs were determined by immunoprecipitation. RESULTS: Anti-155/140 Abs (n = 5), anti-140 Abs (n = 8), and anti-ARS Abs (n = 7) did not overlap each other. All of the anti-155/140 Ab-positive patients (n = 5) were complicated by malignancies, as were all of the anti-140 Ab-positive patients (n = 8), who showed rapidly progressive interstitial lung disease (ILD). The survival rate at 6 months from the diagnosis of DM was significantly lower in the anti-140 Ab-positive patients than in the other patients. CONCLUSION: This is the first study to report, in a single cohort of DM patients, that distinct clinical subsets are distributed in an anti-155/140 Ab-positive group, an anti-140 Ab-positive group, or an anti-ARS Ab-positive group. Our data also confirm previous evidence that anti-155/140 Abs are involved in malignancies and that anti-140 Abs are involved in rapidly progressive ILD.
Assuntos
Aminoacil-tRNA Sintetases/imunologia , Autoanticorpos/imunologia , Dermatomiosite/diagnóstico , Dermatomiosite/imunologia , RNA de Transferência/imunologia , Adulto , Idoso , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Imunoprecipitação , Japão , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Peptídeos/imunologia , Probabilidade , Estatísticas não ParamétricasRESUMO
A 32-year-old female patient with systemic lupus erythematosus was admitted to our hospital with fever and cytopenia, and diagnosed as haemophagocytic syndrome (HPS) by bone marrow aspiration study showing haemophagocytosis. Since the serologic activity of lupus was not increased at that time and HPS was refractory to the conventional therapies, an additional aetiological factor was suspected. Real-time PCR analysis identified reactivation of Epstein-Barr virus (EBV). A combination therapy targetting EBV-associated HPS, consisting of intravenous administration of cyclosporine A as well as immunoglobulin with a high titre of anti-EBV antibody, significantly suppressed EBV viraemia and led to the remission of HPS until the time of writing.
Assuntos
Infecções por Vírus Epstein-Barr/etiologia , Glucocorticoides/efeitos adversos , Imunossupressores/efeitos adversos , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Linfo-Histiocitose Hemofagocítica/etiologia , Adulto , Anticorpos Antivirais/análise , Biópsia por Agulha , Medula Óssea/patologia , DNA Viral/análise , Diagnóstico Diferencial , Quimioterapia Combinada , Infecções por Vírus Epstein-Barr/patologia , Infecções por Vírus Epstein-Barr/virologia , Feminino , Seguimentos , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/imunologia , Humanos , Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/complicações , Linfo-Histiocitose Hemofagocítica/patologia , Linfo-Histiocitose Hemofagocítica/virologiaRESUMO
BACKGROUND: Using an orthotopic implantation model in which oral cancer invasion and metastasis can be reproduced, we investigated the inhibitory effects of anticancer agents on invasion and metastasis. METHODS: A highly invasive and metastatic human oral squamous cell carcinoma cell line, OSC-19, was implanted into the oral floor of nude mice, and cisplatin or peplomycin was administered to the mice 7 or 14 days after implantation. The effects of each anticancer drug and different administration timings on cancer invasion and metastasis were investigated. RESULTS: Tumor size and the ratio of proliferating cell nuclear antigen-positive cells was significantly reduced. In the control group, the tumors showed grade 4C mode of invasion, whereas in the groups treated with anticancer drugs, grade 3 was observed in 77.3% of the mice, with an inhibitory effect on tumor invasion being observed. The rate of metastasis in the cervical lymph node was significantly decreased in the groups treated with the cisplatin or peplomycin on day 7 after implantation. The tumor stage progression in the metastatic lymph nodes was also inhibited. CONCLUSIONS: Chemotherapy is effective not only for tumor diminution but also for inhibiting invasion and metastasis. In light of these effects, administration of anticancer drugs may be clinically useful in this regard.
Assuntos
Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias Bucais/tratamento farmacológico , Animais , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/uso terapêutico , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Linhagem Celular , Cisplatino/administração & dosagem , Cisplatino/uso terapêutico , Modelos Animais de Doenças , Esquema de Medicação , Metástase Linfática , Camundongos , Camundongos Nus , Invasividade Neoplásica , Metástase Neoplásica , Peplomicina/administração & dosagem , Peplomicina/uso terapêuticoRESUMO
The presence of occult metastasis is the most important factor that influences the prognosis in patients with head and neck cancer. To reproduce occult metastasis of oral cancer cells, we serially resected the primary focus in an orthotopic implantation model to examine when metastasis of cancer cells occurs. Human squamous cell carcinoma was implanted into the tongue of nude mice divided into two groups, non-surgery and surgery groups. Mice in the non-surgery group were sacrificed, and the tongue cancer and cervical lymph nodes were resected simultaneously. In the surgery-group, resection of the tongue cancer was performed, and the cervical lymph nodes were resected on day 28. For the non-surgery-group, the incidences of metastasis were 0%, 9%, 36%, 91% and 100% on days 3, 7, 14, 21 and 28, respectively. For the surgery-group, resection of the tongue cancer was performed on days 3, 7 and 14, and the incidence of metastasis on day 28 was 0%, 82% and 91%, respectively. The occult metastasis was reproduced using resected primary cancer on day 7. This time-based model may be useful to clarify the mechanism of metastasis and to develop new treatments.
Assuntos
Carcinoma de Células Escamosas/patologia , Neoplasias de Cabeça e Pescoço/patologia , Metástase Linfática , Animais , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos NusRESUMO
We have previously reported that immune anti-tumor effector cells, both cytotoxic T lymphocytes (CTLs) and IL-2-activated natural killer (A-NK) cells, are effective at eliminating human head-and-neck cancer (HNC) targets in vitro and in vivo in xenograft models. In this study, these 2 types of human effector cell were compared for the ability to prevent the development of lymph node metastases in a metastasis model of human squamous-cell carcinoma of the head and neck (SCCHN) established in nude mice. A tumor cell line, OSC-19, was injected into the floor of the mouth in nude mice, and the tumor grew progressively and metastasized to cervical lymph nodes by day 21. As effector cells, a human HLA-A2-restricted CTL line recognizing a shared antigen on OSC-19 and human non-MHC-restricted A-NK cells were used. Both types of effector cell mediated high levels of lysis against OSC-19 targets in 4-hr (51)Cr-release assays. Administration of human CTLs or A-NK cells and IL-2 to the site of tumor growth in mice with 7-day OSC-19 tumors resulted in significant reduction of the number of lymph node metastases relative to untreated or sham-operated controls or to mice treated with IL-2 without the effector cells. Our results suggest that in a xenograft model of human SCCHN implanted in the oral cavity of nude mice, the development of lymph node metastases can be successfully controlled by adoptive transfer of human SCCHN-specific CTLs or SCCHN-reactive A-NK cells plus IL-2.
Assuntos
Carcinoma de Células Escamosas/terapia , Neoplasias de Cabeça e Pescoço/terapia , Imunoterapia Adotiva/métodos , Células Matadoras Ativadas por Linfocina/transplante , Linfócitos T Citotóxicos/transplante , Animais , Peso Corporal , Carcinoma de Células Escamosas/secundário , Progressão da Doença , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Imunofenotipagem , Metástase Linfática , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias Bucais/patologia , Neoplasias Bucais/terapiaRESUMO
The binding of urokinase-type plasminogen activator (uPA) to its receptor (uPAR) has been implicated in cancer invasion and metastasis. This activity is known to be regulated by several inhibitors such as plasminogen activator inhibitors (PAIs). To elucidate the participation of the uPA system in the malignant behaviour of squamous cell carcinoma (SCC) in the oral cavity, uPA, uPAR, PAI-1 and -2 expression and localisation in 34 primary oral cancers were examined immunohistochemically. The results were then compared with clinicopathological findings. The positive rates of uPA, uPAR, PAI-1 and -2 expression were 23.5, 29.4, 29.4 and 11.8%, respectively. uPA expression correlated with mode of cancer invasion according to Yamamoto-Kohama's criteria (p < 0.01) and with secondary regional lymph node metastasis. uPAR expression also correlated with mode of invasion. In particular, the tumours of both uPA- and uPAR-positive [uPA(+)/uPAR(+)] cases were highly invasive. In the present study, neither PAI-1 nor PAI-2 expression correlated with clinicopathological parameters. However, PAI-2 negative cases of uPA(+)/uPAR(+) were significantly more invasive (p < 0.0001). Such uPA(+)/uPAR(+)/PAI-2(-) cases almost always showed secondary lymph node metastasis (p < 0.01). These results indicate that the uPA system plays a significant role in the invasive and metastatic processes of oral SCC, and that this system may be a powerful aid in evaluating the clinical course or prognosis of patients with oral cancer.
Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/enzimologia , Neoplasias Bucais/enzimologia , Ativador de Plasminogênio Tipo Uroquinase/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/secundário , Feminino , Humanos , Técnicas Imunoenzimáticas , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/patologia , Invasividade Neoplásica , Ativadores de Plasminogênio/metabolismo , Receptores de Superfície Celular/metabolismo , Receptores de Ativador de Plasminogênio Tipo UroquinaseRESUMO
To assess the clinical significance of angiogenesis in oral squamous cell carcinoma (SCC), we examined vessel density immunohistochemically in 44 primary oral SCCs using the JC-70A antibody which reacts specifically with vascular endothelial cells. In addition, the expression of vascular endothelial growth factor (VEGF) and its receptors, KDR, Flt-1 and Flt-4 in oral SCCs was examined in relation to the vessel density and lymph node metastasis. There was no association of vessel density with tumour site, T-category (tumour size), degree of differentiation or cervical lymph node metastasis, except that the vessel density of carcinomas with a well-defined tumour-stromal boundary was higher than that of diffusely invasive carcinomas. The intensity of VEGF expression correlated with lymph node metastasis (P < 0.01), but not with vessel density. The expression of KDR and Flt-1 did not correlate with vessel density and lymph node metastasis. However, the vessel density in Flt-4-positive carcinomas was higher than that in Flt-4-negative carcinomas (P < 0.05), and expression of Flt-4 most significantly correlated with lymph node metastasis (P < 0.001). These results suggest that the expression of VEGF or Flt-4 rather than vessel density may be a predictor of lymph node metastasis in oral SCC.
Assuntos
Carcinoma de Células Escamosas/irrigação sanguínea , Neoplasias Bucais/irrigação sanguínea , Neovascularização Patológica/metabolismo , Carcinoma de Células Escamosas/patologia , Fatores de Crescimento Endotelial/metabolismo , Humanos , Metástase Linfática , Linfocinas/metabolismo , Neoplasias Bucais/patologia , Invasividade Neoplásica , Neovascularização Patológica/patologia , Receptores Proteína Tirosina Quinases/metabolismo , Receptores de Fatores de Crescimento/metabolismo , Receptores de Fatores de Crescimento do Endotélio Vascular , Fator A de Crescimento do Endotélio Vascular , Fatores de Crescimento do Endotélio VascularRESUMO
Juvenile xanthogranuloma is commonly seen in the dermis, and only very rarely develops in the oral mucosa. Here were report a case that occurred in the anterior palate of a 9-year-old boy. The lesion appeared as a dark red and well-defined nodule measuring 12 x 14 mm. Histologically, it consisted of a proliferation of histiocytes and fibroblastic stroma intermingled with foamy cells. Many lipid droplets without limiting membrane were observed in the cytoplasm under electron microscopy, but no Langerhans' cell granules were observed. The proliferative histiocytes were positive for lysozyme and macrophage HAM56 under immunohistochemical observation, but not for S-100 protein. From these findings, the lesion was diagnosed as juvenile xanthogranuloma. The post-operative course, now amounting to 7 years, has been uneventful.