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PURPOSE: The current supraomohyoid neck dissection (SOHND) is performed above the omohyoid muscle to dissect levels I, II, and III in the levels of cervical lymph nodes. However, the anatomical boundary between levels III and IV is the inferior border of the cricoid cartilage. We investigated the anatomical relationship between the omohyoid muscle and cricoid cartilage using contrast-enhanced CT (CE-CT) images to assess the validity of the current SOHND. METHODS: CE-CT images of the head and neck regions in patients were reviewed. The patients were divided into two groups: "malignant tumors" and "others". The vertebral levels corresponding to the positions of anatomical structures such as the intersection of the omohyoid muscle and internal jugular vein (OM-IJ), and the inferior border of the cricoid cartilage (CC), were recorded. RESULTS: The OM-IJ was located around the seventh cervical to the first thoracic vertebra. There was a significant difference between the malignant tumor and others groups in females (p = 0.036). The CC was located around the sixth to seventh cervical vertebrae. There was a significant sex difference in each group (malignant tumor: p < 0.0001; others: p = 0.008). Both sexes tended to have lower OM-IJ than CC, and females had significantly lower OM-IJ than males. CONCLUSION: This study provides clear anatomical evidence showing the difference between the SOHND dissection area and levels I, II, and III. It could be considered that in most cases SOHND invades level IV, not just levels I, II, and III, especially in female patients.
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Meios de Contraste , Neoplasias de Cabeça e Pescoço , Esvaziamento Cervical , Tomografia Computadorizada por Raios X , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Esvaziamento Cervical/métodos , Idoso , Adulto , Neoplasias de Cabeça e Pescoço/cirurgia , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Cartilagem Cricoide/anatomia & histologia , Cartilagem Cricoide/diagnóstico por imagem , Cartilagem Cricoide/cirurgia , Idoso de 80 Anos ou mais , Estudos Retrospectivos , Veias Jugulares/anatomia & histologia , Veias Jugulares/diagnóstico por imagem , Músculos do Pescoço/diagnóstico por imagem , Músculos do Pescoço/anatomia & histologiaRESUMO
OBJECTIVES: Immunotherapy with nivolumab for patients with recurrent/metastatic oral squamous cell carcinoma has not been evaluated. Here, we aimed to examine the efficacy, safety, and prognostic factors of nivolumab in these patients. MATERIALS AND METHODS: This multicenter retrospective observational study involved patients who received nivolumab between April 2017 and June 2019. The patient characteristics were evaluated for association with progression-free and overall survival. Progression-free and overall survival rates were calculated; parameters that were significant in the univariate analysis were used as explanatory variables. Independent factors for progression-free and overall survival were identified using multivariate analysis. RESULTS: Totally, 143 patients were included. The overall response and disease control rates were 27.3% and 46.2%, respectively. The median, 1- and 2-year progression-free survival rates were 2.7 months, 25.4%, and 19.2%, respectively; those for overall survival were 11.2 months, 47.3%, and 33.6%, respectively. The independent factors affecting progression-free survival were performance status and immune-related adverse event occurrence, whereas those affecting overall survival were performance status, target disease, and number of previous lines of systemic cancer therapy. Eight patients reported grade ≥3 immune-related adverse events. CONCLUSION: Nivolumab was effective for recurrent/metastatic oral squamous cell carcinoma treatment and was well tolerated by patients.
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It is widely accepted that cellular processes are controlled by protein phosphorylation and has become increasingly clear that protein degradation, localization and conformation as well as protein-protein interaction are the examples of subsequent cellular events modulated by protein phosphorylation. Enamel matrix proteins belong to members of the secretory calcium binding phosphoprotein (SCPP) family clustered on chromosome 4q21, and most of the SCPP phosphoproteins have at least one S-X-E motifs (S; serine, X; any amino acid, E; glutamic acid). It has been reported that mutations in C4orf26 gene, located on chromosome 4q21, are associated with autosomal recessive type of Amelogenesis Imperfecta (AI), a hereditary condition that affects enamel formation/mineralization. The enamel phenotype observed in patients with C4orf26 mutations is hypomineralized and partially hypoplastic, indicating that C4orf26 protein may function at both secretory and maturation stages of amelogenesis. The previous in vitro study showed that the synthetic phosphorylated peptide based on C4orf26 protein sequence accelerates hydroxyapatite nucleation. Here we show the molecular cloning of Gm1045, mouse homologue of C4orf26, which has 2 splicing isoforms. Immunohistochemical analysis demonstrated that the immunolocalization of Gm1045 is mainly observed in enamel matrix in vivo. Our report is the first to show that FAM20C, the Golgi casein kinase, phosphorylates C4orf26 and Gm1045 in cell cultures. The extracellular localization of C4orf26/Gm1045 was regulated by FAM20C kinase activity. Thus, our data point out the biological importance of enamel matrix-kinase control of SCPP phosphoproteins and may have a broad impact on the regulation of amelogenesis and AI.
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Amelogênese Imperfeita , Amelogênese , Sequência de Aminoácidos , Animais , Proteínas de Ligação ao Cálcio/metabolismo , Caseína Quinase I , Clonagem Molecular , Proteínas da Matriz Extracelular/metabolismo , Humanos , Camundongos , FosforilaçãoRESUMO
BACKGROUND: The prognosis of advanced oral cancer remains dismal. While multimodal therapy is beneficial, maintaining the quality of life of long-term survivors is important. Therefore, risk-adapted treatment regimens need to be designed. We herein investigated whether pathological responses in oral cancer patients treated with preoperative chemoradiotherapy predict locoregional recurrence. METHODS: We retrospectively reviewed the data of 51 oral cancer patients who received preoperative radiotherapy and concurrent pepleomycin, followed by curative surgery at our institution between January 2009 and June 2018. Each patient received preoperative external beam irradiation to the primary tumor and lymphatics (2 Gy per day for approximately 3 weeks) concurrent with pepleomycin (2.5 mg/day). Surgery was performed approximately 3-4 weeks after the completion of preoperative chemoradiotherapy. Pathological responses were defined based on the grading system of Oboshi and Shimosato. RESULTS: Eight, 22, 16, and 5 patients had Oboshi and Shimosato grades 2a, 2b, 3, and 4, respectively. Favorable pathological responses (grades 3 and 4) were observed in 41.2% of patients (21 out of 51 patients). The pathological response and number of pathological lymph node metastases were identified as significant prognostic factors for locoregional control in the univariate analysis. Three-year locoregional control rates were 100 and 56.6% in patients with favorable and unfavorable pathological responses, respectively. CONCLUSIONS: The present study demonstrated that pathological tumor responses to preoperative chemoradiotherapy are a useful predictive factor for locoregional control.
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Carcinoma de Células Escamosas/terapia , Quimiorradioterapia , Neoplasias Bucais/terapia , Terapia Neoadjuvante , Peplomicina/uso terapêutico , Radioterapia Conformacional , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/cirurgia , Quimiorradioterapia/efeitos adversos , Feminino , Seguimentos , Doenças Hematológicas/induzido quimicamente , Humanos , Estimativa de Kaplan-Meier , Irradiação Linfática , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/cirurgia , Esvaziamento Cervical , Terapia Neoadjuvante/efeitos adversos , Peplomicina/efeitos adversos , Pneumonia Aspirativa/induzido quimicamente , Dosagem Radioterapêutica , Radioterapia Conformacional/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento , Xerostomia/induzido quimicamenteRESUMO
BACKGROUND: Down syndrome is characterized by a variety of dysmorphic features and congenital malformations, such as congenital heart disease, gastrointestinal disease, and other conditions like leukemia and autoimmune disorders. Patients with Down syndrome are highly prone to respiratory tract infections, which might be fatal to them. However, there are only few available data on patients diagnosed with Down syndrome and agammaglobulinemia. In this report, we describe a case of successful prevention of post-dental treatment complications (e.g., pneumonia and other bacterial infections) in a patient with Down syndrome and agammaglobulinemia. CASE PRESENTATION: A 43-year-old man with Down syndrome, untreated agammaglobulinemia, and a history of recurrent pneumonia, was referred to our clinic for tooth mobility. To reduce the risk of post-operative infections, gammaglobulin treatment and prophylactic administration of antibiotics was scheduled before the dental procedure. Furthermore, the dental treatment, which included a filling and extractions, was conducted under general anesthesia and with the supervision of a hematologist. The dental procedures were successfully performed without any post-operative infection, and the patient is undergoing follow-up care. CONCLUSIONS: The purpose of this case report was to recommend a close liaison between physicians and dentists who may encounter a similar case, and to emphasize the importance of improving oral health of immunodeficient patients to prevent infections caused by oral microbial flora.
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Agamaglobulinemia/complicações , Antibacterianos/uso terapêutico , Antibioticoprofilaxia , Síndrome de Down/complicações , Imunoglobulinas Intravenosas/administração & dosagem , Pneumonia/complicações , Extração Dentária/efeitos adversos , gama-Globulinas/administração & dosagem , Administração Oral , Adulto , Humanos , Leucócitos Mononucleares , Masculino , Resultado do TratamentoRESUMO
By a bioinformatics approach, we have identified a novel cysteine knot protein member, VWC2 (von Willebrand factor C domain containing 2) previously known as Brorin. Since Brorin has been proposed to function as a bone morphogenetic protein (BMP) antagonist, we investigated the binding of Brorin/VWC2 to several BMPs; however, none of the BMPs tested were bound to VWC2. Instead, the ßA subunit of activin was found as a binding partner among transforming growth factor (TGF)-ß superfamily members. Here, we show that Vwc2 gene expression is temporally upregulated early in osteoblast differentiation, VWC2 protein is present in bone matrix, and localized at osteoblasts/osteocytes. Activin A-induced Smad2 phosphorylation was inhibited in the presence of exogenous VWC2 in MC3T3-E1 osteoblast cell line and primary osteoblasts. The effect of VWC2 on ex vivo cranial bone organ cultures treated with activin A was investigated, and bone morphometric parameters decreased by activin A were restored with VWC2. When we further investigated the biological mechanism how VWC2 inhibited the effects of activin A on bone formation, we found that the effects of activin A on osteoblast cell growth, differentiation, and mineralization were reversed by VWC2. Taken together, a novel secretory protein, VWC2 promotes bone formation by inhibiting Activin-Smad2 signaling pathway.
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Proteínas da Matriz Extracelular/metabolismo , Subunidades beta de Inibinas/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Osteogênese/fisiologia , Animais , Diferenciação Celular/fisiologia , Células HEK293 , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Osteoblastos/metabolismo , Transdução de Sinais/fisiologiaRESUMO
This clinico-statistical study includes 597 cases of oral squamous cell carcinoma treated at the Maxillofacial Surgery Section of Tokyo Medical and Dental University between January 2002 and December 2011. There were 373 male and 224 female patients (male to female ratio, 1.7 : 1), and the median age was 67 years. The tongue (53.3%) was the most commonly affected site. The 5-year disease-specific survival rate was 84.8%. Survival rates by clinical stage were as follows : Stage 1, 92.1% (n=195).; Stage , 86.0% (n = 221) ; Stage III, 77.7% (n=65) ; and Stage IV, 73.8% (n =116). Survival rates by primary site were as follows: tongue, 85.4% (n=318) ; lower gingiva, 82.8% (n =114) upper gingiva, 83.7% (n=59) ; buccal mucosa, 89.1% (n 54) ; oral floor, 81.4% (n=49) ; and hard palate, 100% (n=3). According to clinical growth patterns of Stage I / I tongue cancer cases, the 5-year disease-specific survival rate was significantly higher for patients with the exophytic/superficial type (97.3%, n =173) than for those with the endophytic type (77.5%, n=145). Among Stage I/II tongue cancer cases, the corresponding survival rate was significantly higher for patients who had not previously undergone invasive treatments (n=201), such as tooth extraction, compared to those who had previously done so (n=54) (92.7% and 79.7%, respectively). In addition, the incidence of secondary cervical lymph node metastasis was significantly higher in patients who had previously undergone invasive treatments.
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Carcinoma de Células Escamosas , Neoplasias Bucais , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/diagnóstico , Neoplasias Bucais/patologia , Neoplasias Bucais/terapia , Estadiamento de Neoplasias , Neoplasias da Língua/diagnóstico , Neoplasias da Língua/patologia , Neoplasias da Língua/terapia , Adulto JovemRESUMO
PURPOSE: Recently, it has been reported that sarcopenia and nutritional evaluation are associated with the prognosis of patients with cancer; however, there are only a few detailed reports on oral cancer. This single-center retrospective study aimed to analyze the relationship between computed tomography (CT)-assessed sarcopenia (CT-SP), immunocompetence, nutritional status, and the prognosis of patients with oral squamous cell carcinoma (OSCC). METHODS: This retrospective study included patients who underwent radical therapy with surgery for OSCC between January 2014 and January 2021. Skeletal muscle in the third cervical vertebra (C3) was measured using preoperative cervical CT, and the skeletal muscle index (SMI) was calculated. Nutritional status were investigated using blood tests. The correlation between each parameter and prognosis was analyzed. The primary predictor variables were SMI, ECOG performance status, BMI, and nutritional status. The primary outcome variable was the 5-year overall survival rate (OS) and the secondary outcome variable was 5-year disease-specific survival rate (DSS). RESULTS: One hundred sixty-three patients were registered retrospectively. The number of patients with CT-SP was 76 (52%). In the univariate analysis, CT-SP, prognostic nutritional index (PNI), and lymphocyte-monocyte ratio (LMR) were associated with poor prognosis, with statistically significant differences in OS and DSS. In the multivariate analysis, only CT-SP was identified as an independent prognostic factor for DSS. CT-SP was significantly correlated with the PNI. CONCLUSION: CT-SP was associated with a significant decrease in survival rate in patients with OSCC. Furthermore, CT-SP was correlated with the PNI.
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In search of new cysteine knot protein (CKP) family members, we found a novel gene called von Willebrand factor C domain-containing protein 2-like (Vwc2l, also known as Brorin-like) and its transcript variants (Vwc2l-1, Vwc2l-2 and Vwc2l-3). Based on the deduced amino acid sequence, Vwc2l-1 has a signal peptide and 2 cysteine-rich (CR) domains, while Vwc2l-2 lacks a part of 2nd CR domain and Vwc2l-3 both CR domains. Although it has been reported that the expression of Brorin-like was predominantly observed in brain, we found that Vwc2l transcript variants were detected in more ubiquitous tissues. In osteoblasts, the induction of Vwc2l expression was observed at matrix mineralization stage. When Vwc2l was stably transfected into osteoblasts, the matrix mineralization was markedly accelerated in Vwc2l-expressing clones compared to that in the control, indicating the modulatory effect of Vwc2l protein on osteoblastic cell function. The mechanistic insight of Vwc2l-modulation was further investigated and we found that the expression of Osterix, one of the key osteogenic markers, was significantly increased by addition of all Vwc2l isoform proteins. Taken together, Vwc2l is a novel secreted protein that promotes matrix mineralization by modulating Osterix expression likely through TGF-ß superfamily growth factor signaling pathway. Our data may provide mechanistic insights into the biological functions of this novel CKP member in bone and further suggest a novel approach to enhance osteoblast function, which enables to accerelate bone formation, regeneration and healing.
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Matriz Óssea/fisiologia , Calcificação Fisiológica , Proteínas do Tecido Nervoso/metabolismo , Células 3T3-L1 , Processamento Alternativo , Sequência de Aminoácidos , Animais , Matriz Óssea/metabolismo , Diferenciação Celular , Células HEK293 , Humanos , Masculino , Camundongos , Dados de Sequência Molecular , Proteínas do Tecido Nervoso/genética , Osteoblastos/metabolismo , Osteoblastos/fisiologia , Osteogênese , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Fator de Transcrição Sp7 , Fatores de Transcrição/metabolismo , Transcrição Gênica , Fator de Crescimento Transformador beta/metabolismoRESUMO
Endoscopic sinus surgery is commonly performed to treat odontogenic maxillary sinusitis. However, recurrence and natural ostium reclosure often occur due to the inadequate patency of the excretory route. Furthermore, classical maxillary sinus radical surgery is still performed for odontogenic maxillary sinusitis even though it can cause postoperative maxillary sinus deformation, loss of function, and a postoperative maxillary cyst. A management that addresses these issues has not yet been identified. This study reported a conservative maxillary sinus management, wherein a nasoantral window is prepared and the thickened maxillary sinus mucosa is preserved, using the Caldwell-Luc approach. This study presents a case of severe odontogenic maxillary sinusitis that spread to the frontal sinus. This novel management facilitated complete recovery from severe odontogenic maxillary sinusitis in this case.
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Amelogenesis Imperfecta (AI) represents a group of hereditary conditions that manifest tooth enamel defects. Several causative mutations in the WDR72 gene have been identified and patients with WDR72 mutations have brown (or orange-brown) discolored enamel, rough enamel surface, early loss of enamel after tooth eruption, and severe attrition. Although the molecular function of WDR72 is not yet fully understood, a recent study suggested that WDR72 could be a facilitator of endocytic vesicle trafficking, which appears inconsistent with the previously reported cytoplasmic localization of WDR72. Therefore, the aims of our study were to investigate the tissues and cell lines in which WDR72 was expressed and to further determine the sub-cellular localization of WDR72. The expression of Wdr72 gene was investigated in mouse tissues and cell lines. Endogenous WDR72 protein was detected in the membranous fraction of ameloblast cell lines in addition to the cytosolic fraction. Sub-cellular localization studies supported our fractionation data, showing WDR72 at the Golgi apparatus, and to a lesser extent, in the cytoplasmic area. In contrast, a WDR72 AI mutant form that lacks its C-terminal region was exclusively detected in the cytoplasm. In addition, our studies identified a putative prenylation/CAAX motif within the last four amino acids of human WDR72 and generated a WDR72 variant, called CS mutant, in which the putative motif was ablated by a point mutation. Interestingly, mutation of the putative CAAX motif impaired WDR72 recruitment to the Golgi. Cell fractionation assays confirmed subcellular distribution of wild-type WDR72 in both cytosolic and membranous fractions, while the WDR72 AI mutant and CS mutant forms were predominantly detected in the cytosolic fraction. Our studies provide new insights into the subcellular localization of WDR72 and demonstrate a critical role for the C-terminal CAAX motif in regulating WDR72 recruitment to the Golgi. In accordance with structural modelling studies that classified WDR72 as a potential vesicle transport protein, our findings suggest a role for WDR72 in vesicular Golgi transport that may be key to understanding the underlying cause of AI.
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Amelogênese Imperfeita , Ameloblastos/metabolismo , Amelogênese Imperfeita/genética , Amelogênese Imperfeita/metabolismo , Animais , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Camundongos , Mutação , Mutação Puntual , Proteínas/genética , Proteínas/metabolismoRESUMO
BACKGROUND: Previous studies suggest that the nerve to the mylohyoid muscle could have a cutaneous branch. However, its clinical relevance has rarely been discussed because there is insufficient evidence for it. Our aim in this study was to investigate the anatomy of the cutaneous branch of the nerve to the mylohyoid muscle and extend the discussion to surgical management. METHODS: Twenty sides from ten embalmed cadaveric heads were dissected to identify the cutaneous branch of the nerve to the mylohyoid muscle. The cutaneous branch was traced up to its termination. RESULTS: The cutaneous branch was observed in 90% and classified into types I and II. In type I, the terminal trunk reached the anterior belly of the digastric muscle. In type II there were two types of terminal trunks, superior and inferior branches, which were identified on all sides. The number of the terminal trunk was one in 23.1% (type I; 6/26) and two in 76.9% (type II; 20/26). The terminal points of the cutaneous branch were all located within a 3 cm × 2 cm rectangular segment in the center of the submental area. CONCLUSIONS: We propose a new dermatome including the nerve to the mylohyoid muscle in the center. Understanding the cutaneous branch of the nerve could help surgeons to prevent iatrogenic sensory loss of the submental area.
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Músculos do Pescoço , Cadáver , HumanosRESUMO
Maxillary gingival squamous cell carcinoma (MGSCC) occurs rather infrequently, compared to tongue and mandibular gingival carcinomas, among the cancers of the oral cavity. Therefore, significant numbers of MGSCC cases have not been statistically analysed. The aim of this study is to clarify the prognostic factors for MGSCC. We performed the statistical analysis of 90 MGSCC cases primarily treated in our department from 1999 to 2014. The patients (male: 36, female: 54) were aged between 38 and 93 years, and the mean age was 68.7 years. The number of patients in each tumour stage according to the TNM classification was as follows: T1: 15 cases, T2: 32 cases, T3: 13 cases, and T4: 30 cases. Forty-two patients were treated only by surgery, 5 only by radiotherapy, 3 by preoperative radiotherapy and surgery, and 40 patients were treated by combination therapy with preoperative chemoradiotherapy and surgery. Neck dissections were performed in 40 cases including 29 cases (11 primary and 18 secondary cases) of histopathologically diagnosed lymph node metastases. Extranodal extension was found in 74.3% cases with metastatic lymph nodes. The 5-year overall survival rate was 81.9%. In univariate analysis, the site of occurrence, stage of tumour, lymph node metastasis, and treatment contributed to the 5-year survival rate. Multivariate analysis demonstrated that the site of occurrence (posterior region) was an independent prognostic factor. Seventeen deaths occurred due to the primary disease, while three deaths were caused by other diseases. The posterior region cancers, according to the classification based on site of occurrence, were independent predictors of poor 5-year overall survival rate.
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Mitogen-activated protein kinases (MAPKs) regulate proliferation and differentiation in osteoblasts. The vertebral homologue of nemo, nemo-like kinase (NLK), is an atypical MAPK that targets several signaling components, including the T-cell factor/lymphoid enhancer factor (TCF/Lef1) transcription factor. Recent studies have shown that NLK forms a complex with the histone H3-K9 methyltransferase SETDB1 and suppresses peroxisome proliferator-activated receptor (PPAR)-gamma:: action in the mesenchymal cell line ST2. Here we investigated whether NLK regulates osteoblastic differentiation. We showed that NLK mRNA is expressed in vivo in osteoblasts at embryonic day 18.5 (E18.5) mouse calvariae. By using retrovirus vectors, we performed forced expression of NLK in primary calvarial osteoblasts (pOB cells) and the mesenchymal cell line ST2. Wild-type NLK (NLK-WT) suppressed alkaline phosphatase activity and expression of bone marker genes such as alkaline phosphatase, type I procollagen, runx2, osterix, steopontin and osteocalcin in these cells. NLK-WT also decreased type I collagen protein expression in pOB and ST2 cells. Furthermore, mineralized nodule formation was reduced in pOB cells overexpressing NLK-WT. In contrast, kinase-negative form of NLK (NLK-KN) did not suppress or partially suppress ALP activity and bone marker gene expression in pOB and ST2 cells. NLK-KN did not suppress nodule formation in pOB cells. In addition to forced expression, suppression of endogenous NLK expression by siRNA increased bone marker gene expression in pOB and ST2 cells. Finally, transcriptional activity analysis of gene promoters revealed that NLK-WT suppressed Wnt1 activation of TOP flash promoter and Runx2 activation of the osteocalcin promoter. Taken together, these results suggest that NLK negatively regulates osteoblastic differentiation.
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Diferenciação Celular/genética , Proteínas Quinases Ativadas por Mitógeno/genética , Osteoblastos/metabolismo , Osteoblastos/fisiologia , Animais , Desenvolvimento Ósseo/genética , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Regulação para Baixo/genética , Regulação para Baixo/fisiologia , Embrião de Mamíferos , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos ICR , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases Ativadas por Mitógeno/metabolismo , PPAR gama/genética , PPAR gama/metabolismo , Regiões Promotoras Genéticas/efeitos dos fármacos , Regiões Promotoras Genéticas/fisiologia , Proteínas Serina-Treonina Quinases , Estabilidade Proteica/efeitos dos fármacos , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/farmacologia , TransfecçãoRESUMO
BACKGROUND: Although chromosomal instability (CIN) has been detected in many kinds of human malignancies by means of various methods, there is no practical assessment for small clinical specimens. In this study, we evaluated CIN in fine-needle aspiration (FNA) biopsied oral squamous cell carcinomas (SCCs) using fluorescence in situ hybridization (FISH) analysis, and investigated its prognostic significance. METHODS: To evaluate CIN status of tumors, FISH with genomic probes for the centromeres of chromosomes 7, 9, and 11 was performed on specimens obtained by FNA from 77 patients with primary oral SCCs. RESULTS: High-grade CIN (CIN3) was observed in 11.7% (9/77) of patients with oral SCCs and was associated significantly with reduced disease-free survival (p = .008) and overall survival (p = .003). Multivariate Cox proportional hazards analysis showed that CIN status was significantly correlated with disease-free survival (p = .035) and overall survival (p = .041). CONCLUSION: Analysis of CIN status using FISH on FNA biopsy specimens may be useful in predicting of recurrence and poor prognosis in patients with oral SCCs.
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Biópsia por Agulha Fina , Carcinoma de Células Escamosas/genética , Instabilidade Cromossômica , Hibridização in Situ Fluorescente , Neoplasias Bucais/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/secundário , Carcinoma de Células Escamosas/terapia , Cromossomos Humanos Par 11 , Cromossomos Humanos Par 7 , Cromossomos Humanos Par 9 , Intervalo Livre de Doença , Feminino , Predisposição Genética para Doença , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/mortalidade , Neoplasias Bucais/patologia , Neoplasias Bucais/terapia , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
It is widely accepted that FAM20C functions as a Golgi casein kinase and has large numbers of kinase substrates within the secretory pathway. It has been previously reported that FAM20C is required for maintenance of healthy periodontal tissues. However, there has been no report that any extracellular matrix molecules expressed in periodontal tissues are indeed substrates of FAM20C. In this study, we sought to identify the binding partner(s) of FAM20C. FAM20C wild-type (WT) and its kinase inactive form D478A proteins were generated. These proteins were electrophoresed and the Coomassie Brilliant Blue (CBB)-positive bands were analyzed to identify FAM20C-binding protein(s) by Mass Spectrometry (MS) analysis. Periostin was found by the analysis and the binding between FAM20C and Periostin was investigated in cell cultures and in vitro. We further determined the binding region(s) within Periostin responsible for FAM20C-binding. Immunolocalization of FAM20C and Periostin was examined using mouse periodontium tissues by immunohistochemical analysis. In vitro kinase assay was performed using Periostin and FAM20C proteins to see whether FAM20C phosphorylates Periostin in vitro. We identified Periostin as one of FAM20C-binding proteins by MS analysis. Periostin interacted with FAM20C in a kinase-activity independent manner and the binding was direct in vitro. We further identified the binding domain of FAM20C in Periostin, which was mapped within Fasciclin (Fas) I domain 1-4 of Periostin. Immunolocalization of FAM20C was observed in periodontal ligament (PDL) extracellular matrix where that of Periostin was also immunostained in murine periodontal tissues. FAM20C WT, but not D478A, phosphorylated Periostin in vitro. Consistent with the overlapped expression pattern of FAM20C and Periostin, our data demonstrate for the first time that Periostin is a direct FAM20C-binding partner and that FAM20C phosphorylates Periostin in vitro.
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Caseína Quinase I/metabolismo , Moléculas de Adesão Celular/metabolismo , Proteínas da Matriz Extracelular/metabolismo , Fosforilação/fisiologia , Sequência de Aminoácidos , Animais , Linhagem Celular , Células HEK293 , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Ligamento Periodontal/metabolismo , Proteínas Quinases/metabolismo , Via Secretória/fisiologiaRESUMO
To determine whether staining with iodine solution provides an efficient criterion for determining the area of resection for the lesions surrounding squamous cell carcinoma (SCC) and leukoplakia of the tongue, we determined the optimum density of iodine solution and staining procedure and analyzed the color of lightly stained lesions (LSLs) in relation to the histopathologic findings. Sixty-five patients with SCC or leukoplakia of the tongue were divided into two groups: lesions stained with 3% Lugol solution and restained with either 5% Lugol solution (n=38) or 10% iodine glycerin (n=27). Among the lesions stained with 5% Lugol solution, significant differences were found in all color values. Color difference values (DeltaE*ab) using 3% and 5% Lugol solutions were significantly different between epithelial hyperplasia/mild epithelial dysplasia and moderate to severe dysplasia (P < 0.05). According to the evaluations of five clinicians in 46 LSLs, a distinctive boundary was most often obtained using 5% Lugol solution. These results suggest that the most effective method for obtaining a clear boundary and distinguishing moderate to severe dysplasia from mild or no epithelial dysplasia according to the measured color value was to stain with 3% followed by 5% Lugol solution.
Assuntos
Carcinoma de Células Escamosas/diagnóstico , Colorimetria/métodos , Corantes , Iodetos , Leucoplasia Oral/diagnóstico , Neoplasias da Língua/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/patologia , Corantes/administração & dosagem , Epitélio/patologia , Feminino , Violeta Genciana , Humanos , Hiperplasia , Iodetos/administração & dosagem , Leucoplasia Oral/patologia , Masculino , Pessoa de Meia-Idade , Lesões Pré-Cancerosas/diagnóstico , Lesões Pré-Cancerosas/patologia , Coloração e Rotulagem/métodos , Neoplasias da Língua/patologiaRESUMO
Dentigerous cysts are one of the most prevalent types of odontogenic cysts and are associated with the crown of an unerupted tooth, especially of the mandibular third molar. In this study, the characteristics of a dentigerous cyst developed around a mandibular third molar on panoramic radiographs were investigated. The panoramic images of 257 consecutive dentigerous cyst cases associated with a mandibular third molar were analyzed. The mean age of the patients was 45.9 ± 13.3 years. The size of the cyst did not significantly correlate to the age of the patient. The unilocular type (89.1%) and the crown side type (68.5%) were significant. The associated mandibular third molars had a high frequency of class III (64.6%) and position B (48.3%) in Pell and Gregory classification and of horizontal position (36.3%) in angulation. Dentigerous cysts were thought to originate and grow commonly around deeply impacted third molars. The associated third molar with dentigerous cyst tends to have a mesial inclination. Dentigerous cysts do not appear to develop gradually after the crown formation has finished, but arise at various periods randomly.
RESUMO
The lingual position of the mandibular second molar and narrow tongue space are associated with oral tongue squamous cell carcinoma (OTSCC) development in young mature patients. The present study aimed to assess the role of the mandibular second molar position and tongue space in young mature patients with OTSCC. The medical records of 21 patients with OTSCC aged <50 years, who had an intact mandibular second molar and had undergone computed tomography (CT) imaging between April 2009 and December 2015 at the Section of Maxillofacial Surgery in Tokyo Medical and Dental University, were retrospectively examined. As controls, 21 sex-matched patients of a similar age to the patients in the OTSCC group, and with a height and weight within 5% of those of the OTSCC group, were collected. The location of the mandibular second molar on the affected side and area of the tongue space were determined using coronal and axial CT images. Mann-Whitney U test analysis revealed that the location of the mandibular second molar and the area of the tongue space differed significantly between young mature patients with OTSCC and the controls. The present study thus revealed that the lingual position of the mandibular second molar and the narrow tongue space may be potential factors influencing OTSCC development in young maturity.