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PURPOSE: To measure the micro-foci distance away from gross tumor and to provide reference to create the clinical target volume (CTV) margin for boost radiotherapy in rectal adenocarcinoma. METHODS: Twenty-eight rectal cancer surgical specimens of only total mesorectal excision were collected. The pathological specimens were retrospectively measured, and the nearest distance between the tumor micro-foci and gross tumor was microscopically measured. The "in vivo-in vitro" retraction factor was calculated as the ratio of the deepest thickness laterally and the vertical height superior/inferiorly of the rectal tumor measured in MRI and those measured in immediate pathological specimens. The retraction factor during pathological specimen processing was calculated as the distance ratio before and after dehydration in the lateral, superior, and inferior sides by the "knot marking method." The distances of tumor micro-foci were individually corrected with these two retraction factors. RESULTS: The mean "in vivo-in vitro" tumor retraction factors were 0.913 peripherally and 0.920 superior/inferiorly. The mean tumor specimen processing retraction factors were 0.804 peripherally, 0.815 inferiorly, and 0.789 superiorly. Of 28 patients, 14 cases (50.0%) had 24 lateral micro-foci, 8 cases (28.6%) had 13 inferior micro-foci, and 7 cases (25.0%) had 19 superior micro-foci. The 95th percentiles of the micro-foci distance for 28 patients were 6.44 mm (peripheral), 5.54 mm (inferior), and 5.42 mm (superior) after retraction correction. CONCLUSION: The micro-foci distances of 95% of rectal adenocarcinoma patients examined were within 6.44 mm peripherally, 5.54 mm inferiorly, and 5.42 mm superiorly. These findings provide reference to set the boost radiotherapy CTV margin for rectal cancer.
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BACKGROUND: Perineural invasion is a pathological feature that may affect cancer cell progression and thus can result in prognostic impacts, especially in oral squamous cell carcinoma (OSCC). However, factors regulating perineural invasion during OSCC remain obscure. METHODS: Expression of miR-21 and phosphatase and tensin homolog was checked in surgical specimens from cases of OSCC. The results were analyzed for histopathologic factors, including perineural invasion and clinical prognosis. RESULTS: One-hundred cases of OSCC patients were enrolled in this study. High expression of miR-21 was related to perineural invasion and worse prognosis in OSCC patients. CONCLUSION: miR-21 was an independent factor of disease survival of OSCC. miR-21/phosphatase and tensin homolog disregulation was related to perineural invasion.
Assuntos
Carcinoma de Células Escamosas/patologia , Neoplasias de Cabeça e Pescoço/patologia , MicroRNAs/fisiologia , Neoplasias Bucais/patologia , Adulto , Idoso , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/mortalidade , Feminino , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Masculino , MicroRNAs/análise , Pessoa de Meia-Idade , Neoplasias Bucais/genética , Neoplasias Bucais/mortalidade , Invasividade Neoplásica , PTEN Fosfo-Hidrolase/análise , Fosfatidilinositol 3-Quinases/fisiologia , Proteínas Proto-Oncogênicas c-akt/fisiologia , Carcinoma de Células Escamosas de Cabeça e PescoçoRESUMO
Oral squamous cell carcinoma (OSCC) is one of the most common cancers worldwide. Aberrations in miRNA regulation are known to play important roles in OSCC pathogenesis. miR-187 was shown to be up-regulated in head and neck malignancies in our previous screening. This study further investigated the oncogenic potential, clinical implications, and targets of miR-187 in OSCC. We observed that miR-187 increased oncogenicity, particularly migration, of OSCC cells. miR-187 expression increased the xenografic tumorigenicity and metastasis in mice. In addition, metastatic human OSCC had higher miR-187 expression than did non-metastatic tumors. Through vigorous screening, we confirmed BarH-like Homeobox 2 (BARX2) gene as an miR-187 target. BARX2 expression suppressed the migration, invasion, anchorage-independent colony formation, and orthotopic tumorigenesis of OSCC cells. The migratory phenotype and neck metastasis induced by miR-187 was rescued by BARX2 expression. BARX2 expression was down-regulated in the vast majority of OSCC, and this down-regulation was particularly conspicuous in tumors with advanced nodal metastasis. In addition, plasma miR-187 was significantly higher in OSCC patients than in normal individuals. This study highlights the roles of miR-187-BARX2 in driving the carcinogenesis of OSCC. The results suggest that miR-187 is a potential serological marker for OSCC and that targeting of miR-187 might prove effective in attenuating nodal metastasis.
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Carcinogênese/genética , Carcinoma de Células Escamosas/genética , Regulação Neoplásica da Expressão Gênica , Proteínas de Homeodomínio/genética , MicroRNAs/metabolismo , Neoplasias Bucais/genética , Animais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células , Regulação para Baixo , Técnicas de Silenciamento de Genes , Genes Supressores de Tumor , Proteínas de Homeodomínio/metabolismo , Humanos , Linfonodos/patologia , Metástase Linfática , Camundongos , Camundongos Nus , MicroRNAs/sangue , Neoplasias Bucais/sangue , Neoplasias Bucais/patologia , Pescoço , Oncogenes , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Língua/patologia , Regulação para Cima , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Squamous cell carcinoma (SCC) occurring in the head and neck region and the esophagus causes tremendous cancer mortality around the world. miR-31 is among the most eminently upregulated MicroRNAs in SCC, when it occurs in the head and neck region and the esophagus. We established miR-31 transgenic mouse lines, in which miR-31 is under the control of the K14 promoter. 4-nitroquinoline 1-oxide (4NQO) is a mutagen that causes double strand breaks. The transgenic mice exhibited a higher potential for tumor induction than wild-type (Wt) mice of the tongue and esophagus after 4NQO treatment. After 4NQO treatment or irradiation, p-γH2AX expression in squamous epithelium of transgenic mice was increased more than in Wt mice. Exogenous expression of miR-31 was also found to be associated with the higher p-γH2AX expression induced by 4NQO in human oral SCC (OSCC) cell lines. The repair genes PARP1 and Ku80 were validated as new targets of miR-31 in human OSCC cell lines, and were found to be downregulated in the squamous epithelium of the tongue in transgenic mice. However, only the downregulation of Ku80 was essential for maintaining the high level of p-γH2AX induced by 4NQO in OSCC cells. Inverse expression profiles for miR-31 and Ku80 were noted in human OSCC tissue. Our study identifies the high sensitivity of K14-EGFP-miR-31 transgenic mice to chemical carcinogen-induced squamous cell tumorigenesis and shows that this seems to be associated with the downregulation of Ku80 and an impairment of repair activity in squamous cells, which are mediated by miR-31.
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4-Nitroquinolina-1-Óxido/toxicidade , Antígenos Nucleares/fisiologia , Carcinoma de Células Escamosas/induzido quimicamente , Proteínas de Ligação a DNA/fisiologia , MicroRNAs/fisiologia , Neoplasias Bucais/induzido quimicamente , Animais , Linhagem Celular Tumoral , Dano ao DNA , Neoplasias Esofágicas/induzido quimicamente , Proteínas de Fluorescência Verde/metabolismo , Histonas/análise , Humanos , Autoantígeno Ku , Camundongos , Camundongos Transgênicos , Poli(ADP-Ribose) Polimerase-1 , Poli(ADP-Ribose) Polimerases/fisiologiaRESUMO
MicroRNAs (miRNAs) play important roles in modulating the neoplastic process of cancers including head and neck squamous cell carcinoma (HNSCC). A genetic polymorphism (rs2292832, C>T) has been recently identified in the precursor of miR-149; nevertheless its clinicopathological implications remain obscure. In this study, we showed that miR-149 is down-regulated in HNSCC compared to normal mucosa and this is associated with a poorer patient survival. In addition, HNSCC patients with the T/T genotype have more advanced tumors and a worse prognosis. Multivariate analysis indicated that patients carried the T/T genotype have a 2.81-fold (95% CI: 1.58-4.97) increased risk of nodal metastasis and 1.66-fold (95% CI: 1.05-2.60) increased risk of mortality compared to other groups. T/T genotype also predicted the worse prognosis of buccal mucosa carcinoma subset of HNSCC. In vitro analysis indicated that exogenous miR-149 expression reduces the migration of HNSCC cells. Moreover, HNSCC cell subclones carrying the pri-mir-149 sequence containing the T variant show a low processing efficacy when converting the pre-mir-149 to mature miR-149. These findings suggest that miR-149 suppresses tumor cell mobility, and that the pre-mir-149 polymorphism may affect the processing of miR-149, resulting in a change in the abundance of the mature form miRNA, which, in turn, modulates tumor progression and patient survival.
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Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/metabolismo , MicroRNAs/genética , Polimorfismo Genético , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/diagnóstico , Estudos de Casos e Controles , Movimento Celular , Progressão da Doença , Feminino , Genótipo , Neoplasias de Cabeça e Pescoço/diagnóstico , Humanos , Hibridização In Situ , Masculino , Pessoa de Meia-Idade , Plasmídeos/metabolismo , Reação em Cadeia da Polimerase/métodos , Prognóstico , Análise de Regressão , Risco , Resultado do TratamentoRESUMO
PIK3CA and PAK1 are critical genes in the PI3K/AKT/PAK pathway. Amplification and strong expression of PIK3CA and PAK1 were identified in around 50% and 88% oral carcinomas, respectively, while co-expression of PIK3CA and PAK1 together was found to be present in 80% of oral carcinomas. PIK3CA and PAK1 amplification was more obvious in recurrent tumors than their primary counterparts. Low grade amplification of PAK1 was prevalent in tumor risk individuals. Knockdown of expression of PIK3CA and PAK1 reduced the oncogenic potential of tumor cells. This study is the first to demonstrate the concordant PIK3CA and PAK1 alterations in oral carcinoma.
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Carcinoma de Células Escamosas/genética , Amplificação de Genes , Neoplasias Bucais/genética , Recidiva Local de Neoplasia/genética , Fosfatidilinositol 3-Quinases/genética , Quinases Ativadas por p21/genética , Carcinoma de Células Escamosas/metabolismo , Classe I de Fosfatidilinositol 3-Quinases , Humanos , Neoplasias Bucais/metabolismo , Recidiva Local de Neoplasia/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Quinases Ativadas por p21/metabolismoRESUMO
BACKGROUND: Validating markers for prediction of nodal metastasis could be beneficial in treatment of oral cavity cancer. Decoy receptor 3 (DcR3), locus on 20q13, functions as a death decoy inhibiting apoptosis mediated by the tumor necrosis factor receptor (TNFR) family. METHODS: This study analyzed the serum level of DcR3 in relationship to the clinical parameters of oral cavity cancer patients together with detection of DcR3 genomic copy number in primary and recurrent tumors. RESULTS: Elevated serum DcR3 was associated with nodal metastasis and worse prognosis. Gain of DcR3 copy number was detected in 17% of primary tumor tissue but not found in healthy areca chewers. Tissue from recurrent tumors showed more frequent DcR3 copy number alteration (48%) than the paired primary tumor tissue. CONCLUSIONS: Serum DcR3 level is a predictor for the nodal metastasis and survival among oral cavity cancer patients and the DcR3 copy number alteration could underlie oral carcinogenesis progression.
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Biomarcadores Tumorais/sangue , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/secundário , Neoplasias Bucais/sangue , Neoplasias Bucais/mortalidade , Membro 6b de Receptores do Fator de Necrose Tumoral/sangue , Adulto , Idoso , Biópsia por Agulha , Carcinoma de Células Escamosas/mortalidade , Estudos de Coortes , Intervalos de Confiança , Intervalo Livre de Doença , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Modelos Logísticos , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/patologia , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Razão de Chances , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Membro 6b de Receptores do Fator de Necrose Tumoral/genética , Medição de Risco , Análise de SobrevidaRESUMO
Oral squamous cell carcinoma (OSCC) in Asians is highly associated with the abuse of areca (betel) chewing. There are several hundred million Asians who chew areca and are therefore at high risk of OSCC. Aberrance in cyclin D1 (CCND1) and/or cortactin (CTTN), which are localized on 11q13, seems to be critical events for the development of oral carcinogenesis. This study identified amplifications of CCND1 and CTTN by quantitative (Q)-PCR analysis in 50% and 45% of OSCC samples, respectively. Co-amplification of both genes was identified in 20% of tumors. Higher CTTN expression was associated with nodal metastasis of the OSCC, while the amplification of CCND1 was identified in 28% of oral brushed samples from areca chewers, who form a high risk group for OSCC. This study confirms the importance of alterations in CCND1 and CTTN with respect to areca-associated OSCC, and demonstrates that there is an early occurrence of amplification of these genes in the risk population. The non-invasive brushing sampling method coupling with Q-PCR analysis needs to be validated for use as an early detection system for gene copy changes, which should aid oral cancer prevention.