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1.
Int J Health Sci (Qassim) ; 16(4): 22-29, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35949697

RESUMEN

Objective: Accessory nerve (AN) manipulation or resection during neck dissection (ND) generates accessory nerve shoulder dysfunction (ANSD). The aim of the present study was to assess adherence to a supervised physiotherapy protocol and subsequent changes in the functionality scores of patients with ASND with accessory nerve (AN) preservation. Methods: This study consisted of an uncontrolled clinical trial was carried out at the Department of Head and Neck Surgery and Otorhinolaryngology at the A.C. Camargo Cancer Center, comprising progressive isotonic and isometric strengthening of scapular stabilizer muscles. In patients with head-and-neck cancer underwent ND with AN preservation and patients with ANSD. Shoulder range of motion (ROM), middle trapezius, lower trapezius, rhomboid and anterior serratus muscle strength, pain, and quality of life (QoL) were measured in the pre-operative and 1st and 3rd post-operative months. There were included patients over 18 years old, with head-and-neck cancer who underwent ND with AN preservation and patients with ANSD. Results: A total of 55 patients were evaluated, with a mean age of 53 (±13.23). Significant improvement in the functionality scores of almost all variables between pre- and post- physiotherapy was observed. Most patients (70.9%) adhered and completed the protocol, obtaining significantly greater ROM abduction (P = 0.009) and lower trapezius strength (P = 0.011) than partially performing patients. Conclusion: When performed completely, the proposed physiotherapy protocol can minimize loss in muscle movements and strength, especially limited after ND. The results indicate that the proposed protocol is safe and has the potential to reduce ANSD.

2.
Oral Oncol ; 123: 105620, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34798575

RESUMEN

Human papilloma virus (HPV) is a well-established causative factor in a subset of squamous cell carcinomas of the head and neck (HNSCC). Although HPV can be detected in various anatomical subsites, HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) is the most common HPV-related malignancy of the head and neck, and its worldwide incidence is constantly rising. Patients with OPSCC are generally younger, have less co-morbidities and generally have better prognosis due to different biological mechanisms of carcinogenesis. These facts have generated hypotheses on potential treatment modifications, aiming to minimize treatment-related toxicities without compromising therapy efficacy. Numerous randomized clinical trials have been designed to verify this strategy and increasingly real-world evidence data from retrospective, observational studies is becoming available. Until now, the data do not support any modification in contemporary treatment protocols. In this narrative review, we outline recent data provided by both randomized controlled trials and real-world evidence of HPV-positive OPSCC in terms of clinical value. We critically analyze the potential value and drawbacks of the available data and highlight future research directions. This article was written by members and invitees of the International Head and Neck Scientific Group.(www.IHNSG.com).


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias Orofaríngeas , Infecciones por Papillomavirus , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/virología , Neoplasias de Cabeza y Cuello , Humanos , Neoplasias Orofaríngeas/diagnóstico , Neoplasias Orofaríngeas/virología , Papillomaviridae , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/diagnóstico , Estudios Retrospectivos
3.
Sci Adv ; 6(26): eaba3231, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32637605

RESUMEN

Cancer risk is highly variable in carriers of the common TP53-R337H founder allele, possibly due to the influence of modifier genes. Whole-genome sequencing identified a variant in the tumor suppressor XAF1 (E134*/Glu134Ter/rs146752602) in a subset of R337H carriers. Haplotype-defining variants were verified in 203 patients with cancer, 582 relatives, and 42,438 newborns. The compound mutant haplotype was enriched in patients with cancer, conferring risk for sarcoma (P = 0.003) and subsequent malignancies (P = 0.006). Functional analyses demonstrated that wild-type XAF1 enhances transactivation of wild-type and hypomorphic TP53 variants, whereas XAF1-E134* is markedly attenuated in this activity. We propose that cosegregation of XAF1-E134* and TP53-R337H mutations leads to a more aggressive cancer phenotype than TP53-R337H alone, with implications for genetic counseling and clinical management of hypomorphic TP53 mutant carriers.

4.
Eur Arch Otorhinolaryngol ; 276(7): 2047-2053, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31161362

RESUMEN

PURPOSE: Many authors have described clinicopathologic parameters as factors related to cervical lymph node metastasis development in CN0 stage lip cancer. However, predictive factors for occult lymph node metastasis and criteria for elective neck dissection, especially for early tumour, remain undefined. METHODS: A multi-institutional study with 193 consecutive patients with early lip SCC treated from January 1990 to March 2006 was carried out retrospectively to determine factors predicting occult metastasis. RESULTS: The overall late LNM rate was 13% (25/193). In the multivariate logistic regression study, tumour size and pattern of tumour invasion were factors related to the occurrence of late LNM with rates of sensitivity, specifity and accuracy for occult LNM prediction of 50%, 89.5% and 87%, respectively. CONCLUSION: Our results indicate that patients with stage I and II SCC of the lip with tumour size greater than 18 mm and more aggressive pattern of invasion must be considered a high-risk group for LNM and an END should be performed.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de los Labios , Disección del Cuello/métodos , Adulto , Anciano , Anciano de 80 o más Años , Brasil , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/patología , Procedimientos Quirúrgicos Electivos/métodos , Femenino , Humanos , Neoplasias de los Labios/diagnóstico , Neoplasias de los Labios/patología , Modelos Logísticos , Ganglios Linfáticos/patología , Ganglios Linfáticos/cirugía , Metástasis Linfática/patología , Masculino , Persona de Mediana Edad , Cuello , Invasividad Neoplásica , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Carga Tumoral
5.
Rev. bras. cir. plást ; 34(2): 237-242, apr.-jun. 2019. ilus
Artículo en Inglés, Portugués | LILACS | ID: biblio-1015976

RESUMEN

Atualmente, o Gothenburg Trismus Questionnaire (GTQ) é o único questionário de qualidade de vida específico sobre trismo. A afecção, definida como restrição à abertura da boca, gera prejuízo a atividades habituais como comer, engolir, falar e fazer a higiene oral, trazendo grande desconforto aos pacientes. A tradução de questionários de qualidade de vida desempenha um importante papel no conhecimento da saúde das populações nos diferentes países. O objetivo do presente estudo é apresentar a validação do GTQ para a língua portuguesa, a fim de permitir sua aplicação efetiva nas populações de idioma português. O GTQ foi validado com sucesso para a língua portuguesa conforme os seguintes passos: Tradução, Retradução (back translation), Adaptação cultural e Revalidação.


Currently, the Gothenburg Trismus Questionnaire (GTQ) is the only quality-of-life questionnaire specific for the assessment of trismus. The disease, characterized by limited mouth opening, impairs usual activities such as eating, swallowing, talking, and performing oral hygiene, causing great discomfort to patients. Translation of quality-of-life questionnaires plays an important role in promoting health awareness in the populations of different countries. This study aimed to validate the Portuguese version of the GTQ to allow its effective application in Portuguesespeaking populations. The Portuguese version of the GTQ was successfully validated through the following steps: translation, back translation, cultural adaptation, and revalidation.


Asunto(s)
Humanos , Calidad de Vida , Traducción , Trismo/cirugía , Trismo/complicaciones , Trismo/radioterapia , Estudio de Evaluación , Cuestionario de Salud del Paciente/normas , Cuestionario de Salud del Paciente/estadística & datos numéricos
6.
Eur Arch Otorhinolaryngol ; 275(11): 2615-2626, 2018 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-30267218

RESUMEN

PURPOSE: Management of the facial nerve is instrumental in the surgical treatment of parotid cancer. METHODS: A literature search was conducted using PubMed and ScienceDirect database. A total of 195 articles were finally included into the analysis, based on relevance, scientific evidence and actuality. RESULTS: In the majority of cases the facial nerve is not involved by tumor. In these cases, identification and preservation of the nerve, in addition to complete tumor removal, are essential for successful surgery. When the nerve is infiltrated by tumor, the affected portion of the nerve must be resected as part of radical parotidectomy. Primary nerve reconstruction or other reanimation techniques give the best long-term functional and cosmetic results. A comprehensive diagnostic evaluation with current imaging and electrophysiological studies will provide the surgeon with the best knowledge of the relationship of the facial nerve to the tumor. Several standardized methods are helpful in finding, dissecting and preserving the nerve during parotid cancer surgery. When radical parotidectomy is indicated, the initial diagnostic work-up can assist in defining the need for adjuvant postoperative therapy and facial reanimation. The aim of rehabilitation is to restore tone, symmetry, and movement to the paralyzed face. CONCLUSIONS: The surgical management of facial paralysis has undergone many improvements in recent years. This review gives an overview of recent advances in the diagnostic work-up, surgical techniques and any necessary rehabilitation of the facial nerve in parotid cancer surgery.


Asunto(s)
Traumatismos del Nervio Facial/prevención & control , Nervio Facial/cirugía , Neoplasias de la Parótida/cirugía , Estimulación Eléctrica , Electromiografía , Nervio Facial/diagnóstico por imagen , Nervio Facial/patología , Parálisis Facial/etiología , Parálisis Facial/terapia , Humanos , Monitorización Neurofisiológica Intraoperatoria , Invasividad Neoplásica , Complicaciones Posoperatorias
7.
Artículo en Inglés | MEDLINE | ID: mdl-27013077

RESUMEN

The total amount of scientific literature has grown rapidly in recent years. Specifically, there are several million citations in the field of cancer. This makes it difficult, if not impossible, to manually retrieve relevant information on the mechanisms that govern tumor behavior or the neoplastic process. Furthermore, cancer is a complex disease or, more accurately, a set of diseases. The heterogeneity that permeates many tumors is particularly evident in head and neck (HN) cancer, one of the most common types of cancer worldwide. In this study, we present HNdb, a free database that aims to provide a unified and comprehensive resource of information on genes and proteins involved in HN squamous cell carcinoma, covering data on genomics, transcriptomics, proteomics, literature citations and also cross-references of external databases. Different literature searches of MEDLINE abstracts were performed using specific Medical Subject Headings (MeSH terms) for oral, oropharyngeal, hypopharyngeal and laryngeal squamous cell carcinomas. A curated gene-to-publication assignment yielded a total of 1370 genes related to HN cancer. The diversity of results allowed identifying novel and mostly unexplored gene associations, revealing,for example, that processes linked to response to steroid hormone stimulus are significantly enriched in genes related to HN carcinomas. Thus, our database expands the possibilities for gene networks investigation, providing potential hypothesis to be tested. Database URL:http://www.gencapo.famerp.br/hndb.


Asunto(s)
Carcinoma de Células Escamosas/genética , Bases de Datos Genéticas , Bases de Datos de Proteínas , Genes Relacionados con las Neoplasias , Neoplasias de Cabeza y Cuello/genética , Bandeo Cromosómico , Redes Reguladoras de Genes , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello
8.
Thyroid ; 26(3): 373-80, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26914539

RESUMEN

BACKGROUND: Age is a critical factor in outcome for patients with well-differentiated thyroid cancer. Currently, age 45 years is used as a cutoff in staging, although there is increasing evidence to suggest this may be too low. The aim of this study was to assess the potential for changing the cut point for the American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) staging system from 45 years to 55 years based on a combined international patient cohort supplied by individual institutions. METHODS: A total of 9484 patients were included from 10 institutions. Tumor (T), nodes (N), and metastasis (M) data and age were provided for each patient. The group was stratified by AJCC/UICC stage using age 45 years and age 55 years as cutoffs. The Kaplan-Meier method was used to calculate outcomes for disease-specific survival (DSS). Concordance probability estimates (CPE) were calculated to compare the degree of concordance for each model. RESULTS: Using age 45 years as a cutoff, 10-year DSS rates for stage I-IV were 99.7%, 97.3%, 96.6%, and 76.3%, respectively. Using age 55 years as a cutoff, 10-year DSS rates for stage I-IV were 99.5%, 94.7%, 94.1%, and 67.6%, respectively. The change resulted in 12% of patients being downstaged, and the downstaged group had a 10-year DSS of 97.6%. The change resulted in an increase in CPE from 0.90 to 0.92. CONCLUSIONS: A change in the cutoff age in the current AJCC/UICC staging system from 45 years to 55 years would lead to a downstaging of 12% of patients, and would improve the statistical validity of the model. Such a change would be clinically relevant for thousands of patients worldwide by preventing overstaging of patients with low-risk disease while providing a more realistic estimate of prognosis for those who remain high risk.


Asunto(s)
Diferenciación Celular , Técnicas de Apoyo para la Decisión , Estadificación de Neoplasias/métodos , Neoplasias de la Tiroides/patología , Factores de Edad , Brasil , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Nueva Gales del Sur , América del Norte , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Neoplasias de la Tiroides/mortalidad , Neoplasias de la Tiroides/terapia , Resultado del Tratamiento
9.
PLoS One ; 10(11): e0140009, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26562784

RESUMEN

OBJECTIVE: To evaluate changes in apparent diffusion coefficients (ADC) as measured by magnetic resonance imaging (MRI) before and after the treatment of primary tumors and cervical metastases in patients with squamous-cell carcinoma (SCC) of the head and neck, and to compare these values to the results of widely used morphological criteria and [18F]-FDG PET/CT findings. MATERIAL AND METHOD: This was a longitudinal, prospective, single-center nonrandomized trial involving patients with head and neck SCC treated with chemotherapy alone or in combination with radiotherapy. Imaging examinations ([18F]-FDG PET/CT and diffusion-weighted MRI) were performed on the same day, up to one day prior to the beginning of the first treatment cycle, and on the 14th day of the first chemotherapy cycle. Treatment response was evaluated based on the Response Evaluation Criteria in Solid Tumors (RECIST) and World Health Organization (WHO) morphological criteria, as well as PET Response Criteria in Solid Tumors (PERCIST) metabolic criteria. RESULTS: Seventy-five lesions were examined in 23 patients. Pre- and post-treatment comparisons of data pertaining to all target lesions revealed reductions in tumor size and SUV, as well as increases in ADC values, all of which were statistically significant. The increase in ADC following treatment was significantly higher in patients classified as complete responders by both morphological criteria than that observed in any of the other patient groups of response. Patients with a complete metabolic response also showed greater increases in ADC values as compared to the remaining groups. CONCLUSION: The assessment of tumor response based on diffusion-weighted MRI showed an increase in the ADC of cervical lesions following treatment, which was corroborated by morphological and metabolic findings. Associations between changes in ADC values and treatment response categories using morphologic criteria and [18F]-FDG PET/CT were only identified in complete responders.


Asunto(s)
Carcinoma de Células Escamosas/terapia , Imagen de Difusión por Resonancia Magnética/métodos , Neoplasias de Cabeza y Cuello/terapia , Tomografía de Emisión de Positrones/métodos , Tomografía Computarizada por Rayos X/métodos , Anciano , Carcinoma de Células Escamosas/diagnóstico por imagen , Quimioradioterapia , Femenino , Fluorodesoxiglucosa F18 , Neoplasias de Cabeza y Cuello/diagnóstico por imagen , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Ensayos Clínicos Controlados no Aleatorios como Asunto , Evaluación de Resultado en la Atención de Salud/métodos , Estudios Prospectivos , Inducción de Remisión , Factores de Tiempo
10.
Eur J Cancer ; 51(17): 2596-603, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26318725

RESUMEN

BACKGROUND: Locoregionally advanced oral cavity cancers are aggressive tumours with high risk of relapse after definitive treatment. This study was performed to assess the effectiveness and safety of induction chemotherapy prior to surgery for untreated oral cavity cancer patients. MATERIAL AND METHODS: Only prospective phase III randomised studies comparing induction chemotherapy followed by surgery with or without postoperative radiotherapy (Chemo Group) compared with surgery with or without postoperative radiotherapy (Control Group) were eligible. Two of the authors independently selected and assessed the studies regarding eligibility criteria and risk of bias. RESULTS: Two studies were selected. A total of 451 patients were randomly assigned to Chemo Group (n=226) versus Control Group (n=225). Most patients had tumours at clinical stages III/IV (89.1%). Both trials were classified as having low risk of bias. No significant overall benefit in favour of induction chemotherapy was found regarding loco-regional recurrence, disease-free survival and overall survival. A subgroup analysis of individual data from cN2 patients showed statistically significant overall survival benefit in favour of induction chemotherapy. The included studies did not directly compare toxicity between the groups and no statistical analysis was performed regarding safety outcomes. CONCLUSIONS: Based on the available studies, induction chemotherapy when administered before surgery with curative intent did not improve clinical outcomes in locoregionally advanced oral cavity cancer patients. Clinically assessed N2 patients might benefit from induction chemotherapy.


Asunto(s)
Neoplasias de la Boca/tratamiento farmacológico , Neoplasias de la Boca/cirugía , Ensayos Clínicos Fase III como Asunto , Terapia Combinada , Humanos , Quimioterapia de Inducción/métodos , Neoplasias de la Boca/radioterapia , Periodo Posoperatorio , Periodo Preoperatorio , Ensayos Clínicos Controlados Aleatorios como Asunto , Análisis de Supervivencia , Resultado del Tratamiento
11.
Ann Surg Oncol ; 21(9): 3049-55, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24728823

RESUMEN

PURPOSE: There is evidence to suggest that a nodal yield <18 is an independent prognostic factor in patients with clinically node negative (cN0) oral squamous cell carcinoma (SCC) treated with elective neck dissection (END). We sought to evaluate this hypothesis with external validation and to investigate for heterogeneity between institutions. PATIENTS AND METHODS: We analyzed pooled individual data from 1,567 patients treated at nine comprehensive cancer centers worldwide between 1970 and 2011. Nodal yield was assessed with Cox proportional hazard models, stratified by study center, and adjusted for age, sex, pathological T and N stage, margin status, extracapsular nodal spread, time period of primary treatment, and adjuvant therapy. Two-stage random-effects meta-analyses were used to investigate for heterogeneity between institutions. RESULTS: In multivariable analyses of patients undergoing selective neck dissection, nodal yield <18 was associated with reduced overall survival [hazard ratio (HR) 1.69; 95 % confidence interval (CI) 1.22-2.34; p = 0.002] and disease-specific survival (HR 1.88; 95 % CI 1.21-2.91; p = 0.005), and increased risk of locoregional recurrence (HR 1.53; 95 % CI 1.04-2.26; p = 0.032). Despite significant differences between institutions in terms of patient clinicopathological factors, nodal yield, and outcomes, random-effects meta-analysis demonstrated no evidence of heterogeneity between centers in regards to the impact of nodal yield on disease-specific survival (p = 0.663; I (2) statistic = 0). CONCLUSION: Our data confirm that nodal yield is a robust independent prognostic factor in patients undergoing END for cN0 oral SCC, and may be applied irrespective of the underlying patient population and treating institution. A minimum adequate lymphadenectomy in this setting should include at least 18 nodes.


Asunto(s)
Carcinoma de Células Escamosas/cirugía , Escisión del Ganglio Linfático/normas , Neoplasias de la Boca/cirugía , Recurrencia Local de Neoplasia/cirugía , Nivel de Atención , Anciano , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/secundario , Femenino , Estudios de Seguimiento , Humanos , Agencias Internacionales , Metástasis Linfática , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/mortalidad , Neoplasias de la Boca/patología , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Pronóstico , Tasa de Supervivencia
12.
Histopathology ; 59(1): 81-9, 2011 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-21668474

RESUMEN

AIMS: This study aimed to evaluate the copy number alteration on 2q24, its association with ACVR1 transcript expression and the prognostic value of these data in head and neck squamous cell carcinomas. METHODS AND RESULTS: Twenty-eight samples of squamous cell carcinoma were evaluated by fluorescence in situ hybridization (FISH) using the probes RP11-546J1 (2q24) and RP11-21P18 (internal control). Significant gains at 2q24 were detected in most cases at frequencies varying from 3 to 35%. ACVR1 gains and amplifications were associated with longer overall survival (P = 0.022). ACVR1 mRNA expression analysis in 78 cases revealed overexpression in 44% (34 of 78) of these tumours, suggesting that gene copy number alterations could be involved in gene overexpression. In laryngeal carcinomas, overexpression of ACVR1 mRNA levels was associated with longer overall survival (P = 0.013). Multivariate analysis revealed that ACVR1 is an independent prognostic marker in laryngeal carcinomas (P = 0.012, hazard ratio = 0.165, 95% confidence interval =0.041-0.668). CONCLUSIONS: These findings suggest that copy number alterations at 2q24 can be involved in ACVR1 overexpression, which is associated with longer overall survival in laryngeal carcinomas. To our knowledge, this is the first report indicating the relevance of ACVR1 expression in head and neck cancers.


Asunto(s)
Receptores de Activinas Tipo I/genética , Carcinoma de Células Escamosas/genética , Dosificación de Gen , Neoplasias de Cabeza y Cuello/genética , Anciano , Secuencia de Bases , Carcinoma de Células Escamosas/patología , Cromosomas Humanos Par 2/genética , Femenino , Neoplasias de Cabeza y Cuello/patología , Humanos , Hibridación Fluorescente in Situ , Estimación de Kaplan-Meier , Neoplasias Laríngeas/genética , Neoplasias Laríngeas/patología , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/genética , Neoplasias de la Boca/patología , Neoplasias Faríngeas/genética , Neoplasias Faríngeas/patología , Pronóstico , ARN Mensajero/genética , ARN Mensajero/metabolismo , ARN Neoplásico/genética , ARN Neoplásico/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Regulación hacia Arriba
13.
Int J Oncol ; 36(1): 141-9, 2010 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-19956843

RESUMEN

A growing body of evidence has confirmed the involvement of dysregulated expression of HOX genes in cancer. HOX genes are a family of 39 transcription factors, divided in 4 clusters (HOXA to HOXD), that during normal development regulate cell proliferation and specific cell fate. In the present study it was investigated whether genes of the HOXB cluster play a role in oral cancer. We showed that most of the genes in the HOXB network are inactive in oral tissues, with exception of HOXB2, HOXB7 and HOXB13. Expression of HOXB7 was significantly higher in oral squamous cell carcinomas (OSCC) compared to normal oral mucosas. We further demonstrated that HOXB7 overexpression in HaCAT human epithelial cell line promoted proliferation, whereas downregulation of HOXB7 endogenous levels in human oral carcinoma cells (SCC9 cells) decreased proliferation. In OSCCs, expression of HOXB7 and Ki67, a marker of proliferation, correlate strongly with each other (rs=0.79, p<0.006). High immunohistochemical expression of HOXB7 was correlated with T stage (p=0.06), N stage (p=0.07), disease stage (p=0.09) and Ki67 expression (p=0.01), and patients with tumors showing high number of HOXB7-positive cells had shorter overall survival (p=0.08) and shorter disease-free survival after treatment (p=0.10) compared with patients with tumors exhibiting low amount of HOXB7-positive cells. Our data suggest that HOXB7 may contribute to oral carcinogenesis by increasing tumor cell proliferation, and imply that HOXB7 may be an important determinant of OSCC patient prognosis.


Asunto(s)
Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/metabolismo , Regulación Neoplásica de la Expresión Génica , Proteínas de Homeodominio/biosíntesis , Neoplasias de la Boca/diagnóstico , Neoplasias de la Boca/metabolismo , Anciano , Apoptosis , Proliferación Celular , Supervivencia sin Enfermedad , Femenino , Perfilación de la Expresión Génica , Humanos , Inmunohistoquímica/métodos , Antígeno Ki-67/biosíntesis , Masculino , Persona de Mediana Edad , Pronóstico , Resultado del Tratamiento
14.
Neoplasia ; 11(12): 1329-39, 2009 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-20019841

RESUMEN

Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease affecting the epithelium of the oral cavity, pharynx and larynx. Conditions of most patients are diagnosed at late stages of the disease, and no sensitive and specific predictors of aggressive behavior have been identified yet. Therefore, early detection and prognostic biomarkers are highly desirable for a more rational management of the disease. Hypermethylation of CpG islands is one of the most important epigenetic mechanisms that leads to gene silencing in tumors and has been extensively used for the identification of biomarkers. In this study, we combined rapid subtractive hybridization and microarray analysis in a hierarchical manner to select genes that are putatively reactivated by the demethylating agent 5-aza-2'-deoxycytidine (5Aza-dC) in HNSCC cell lines (FaDu, UM-SCC-14A, UM-SCC-17A, UM-SCC-38A). This combined analysis identified 78 genes, 35 of which were reactivated in at least 2 cell lines and harbored a CpG island at their 5' region. Reactivation of 3 of these 35 genes (CRABP2, MX1, and SLC15A3) was confirmed by quantitative real-time polymerase chain reaction (PCR; fold change, >or=3). Bisulfite sequencing of their CpG islands revealed that they are indeed differentially methylated in the HNSCC cell lines. Using methylation-specific PCR, we detected a higher frequency of CRABP2 (58.1% for region 1) and MX1 (46.3%) hypermethylation in primary HNSCC when compared with lymphocytes from healthy individuals. Finally, absence of the CRABP2 protein was associated with decreased disease-free survival rates, supporting a potential use of CRABP2 expression as a prognostic biomarker for HNSCC patients.


Asunto(s)
Carcinoma de Células Escamosas/genética , Metilación de ADN , Proteínas de Unión al GTP/genética , Neoplasias de Cabeza y Cuello/genética , Receptores de Ácido Retinoico/genética , Azacitidina/análogos & derivados , Azacitidina/farmacología , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Línea Celular Tumoral , Islas de CpG/genética , Decitabina , Epigénesis Genética , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Neoplasias de Cabeza y Cuello/metabolismo , Neoplasias de Cabeza y Cuello/patología , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Proteínas de Resistencia a Mixovirus , Análisis de Secuencia por Matrices de Oligonucleótidos , Pronóstico , Receptores de Ácido Retinoico/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Análisis de Matrices Tisulares
15.
Pathol Oncol Res ; 15(2): 231-40, 2009 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-19096916

RESUMEN

Myofibroblasts are frequent in the stroma of neoplasm and by the expression of proteinases they can influence tumor infiltration and progression. In the present study, presence of myofibroblasts and expression of matrix metalloproteinase-2 (MMP-2) and urokinase plasminogen activator (uPA) were examined in intra-osseous solid multicystic ameloblastomas to determine their roles in the clinicopathological features of the tumors. Fifty seven ameloblastomas were analyzed immunohistochemically with antibodies against the isoform alpha of the smooth muscle actin (alpha-SMA), a specific marker of myofibroblasts, MMP-2 and uPA. Myofibroblasts were found in the stroma, in close contact with neoplastic cell islands, of approximately 58% (n = 33) of the ameloblastomas. MMP-2 and uPA were found in the cytoplasm of both neoplastic and stromal cells. A significant correlation between presence of myofibroblasts and MMP-2 expression was observed. Abundant presence of myofibroblast in the stroma of the tumors and expression of MMP-2 in the neoplastic or stromal cells were significantly correlated with rupture of the osseous cortical, which has been considered an important prognostic marker of ameloblastoma aggressiveness. Ours results suggest that abundant presence of myofibroblasts and expression of MMP-2 in solid ameloblastomas may be associated with a more aggressive infiltrative behavior.


Asunto(s)
Ameloblastoma/enzimología , Neoplasias Óseas/enzimología , Fibroblastos/patología , Metaloproteinasa 2 de la Matriz/metabolismo , Adolescente , Adulto , Anciano , Ameloblastoma/patología , Biomarcadores de Tumor/metabolismo , Neoplasias Óseas/patología , Niño , Citoplasma/metabolismo , Progresión de la Enfermedad , Femenino , Fibroblastos/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Músculo Liso/enzimología , Pronóstico , Células del Estroma/enzimología , Activador de Plasminógeno de Tipo Uroquinasa/metabolismo , Adulto Joven
16.
Head Neck ; 30(10): 1352-60, 2008 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-18720518

RESUMEN

BACKGROUND: The application of appropriate adjuvant treatment after surgery for oral cavity squamous cell carcinoma (OCSCC) is predicated on accurate patient risk stratification. METHODS: A nomogram for estimating locoregional recurrence-free survival (LRFS) after treatment of OCSCC was constructed from a cohort of 590 patients with OCSCC who were treated at Memorial Sloan-Kettering Cancer Center (MSKCC). The nomogram was validated using a series of 417 patients with OCSCC who were treated at Hospital do Cancer AC Camargo (HACC) in São Paulo, Brazil. RESULTS: Despite significant differences between the MSKCC and HACC cohorts, the nomogram was able to predict LRFS from OCSCC with a concordance index of 0.693. Further statistical analysis showed that the nomogram was well calibrated. CONCLUSIONS: This preliminary nomogram is the first prognostic model developed and externally validated to predict the likelihood of LRFS after treatment for an individual patient with OCSCC and may have practical utility for deciding adjuvant treatment.


Asunto(s)
Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/cirugía , Neoplasias de la Boca/radioterapia , Neoplasias de la Boca/cirugía , Nomogramas , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/patología , Estudios de Cohortes , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/patología , Oregon , Cuidados Posoperatorios , Valor Predictivo de las Pruebas , Radioterapia Adyuvante/métodos , Riesgo , Medición de Riesgo
17.
Head Neck ; 30(1): 85-92, 2008 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-17685455

RESUMEN

BACKGROUND: This study aims to compare the alterations in the methylation profiles of E-cadherin in oral cancer, especially in tumors with lowest metatastic potential. METHODS: Nine oral verrucous carcinomas (VCs), 20 oral well-differentiated squamous cell carcinomas without lymph node involvement (SCC-pN0), and 17 with lymph node involvement (SCC-pN+) were analyzed using methylation-specific polymerase chain reaction and immunohistochemical expression of E-cadherin gene. RESULTS: The immunohistochemical expression of E-cadherin in VC was significantly higher (p = .016) when compared with SCC-pN0 and SCC-pN+ groups. The E-cadherin gene methylation was not correlated with its abnormal immunohistochemical expression in VC and SCC-pN0. All tumors of the SCC-pN+ group with unmethylated E-cadherin gene showed significant loss of E-cadherin immunoexpression (p = .044). CONCLUSIONS: The E-cadherin gene methylation presence in tumors with lowest invasive and metastatic potential, such as VC, suggests the early involvement of this epigenetic event in the multistep progression of the oral carcinogenesis.


Asunto(s)
Cadherinas/genética , Islas de CpG/genética , Metilación de ADN , Neoplasias de la Boca/genética , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/genética , Carcinoma Verrugoso/genética , Femenino , Humanos , Inmunohistoquímica , Metástasis Linfática , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa
18.
Oral Oncol ; 44(5): 509-17, 2008 May.
Artículo en Inglés | MEDLINE | ID: mdl-17826300

RESUMEN

Several lines of evidence demonstrated that the stroma surrounding the tumors plays an important role in the growth and progression of several neoplasms, including oral squamous cell carcinomas (OSCC). We evaluated the presence of myofibroblasts in OSCC and determined whether their presence is associated with clinicopathological features of the tumors. We also investigated the mutual paracrine effects of tumor cells and myofibroblasts on fibroblast-myofibroblast transdifferentiation and tumor cell proliferation. Immunohistochemical analysis showed the approximately 60% of the OSCCs contained myofibroblasts in the stroma of the tumor. Abundant presence of myofibroblasts significantly correlated with N stage, disease stage, regional recurrence, and proliferative potential of the tumor cells. Using OSCC cell lines and primary oral normal fibroblasts (ONF), we demonstrated that tumor cells induced transdifferentiation of ONFs to myofibroblasts via secretion of transforming growth factor-beta 1 (TGF-beta 1). In turn, myofibroblasts secreted factors that stimulated OSCC cell proliferation, as revealed by measuring BrdU incorporation and Ki67 expression. The results of the study suggest that during tumor invasion OSCC-derived TGF-beta 1 promote fibroblast-myofibroblast transdifferentiation, and that tumor cellular proliferation can be induced by factors released from myofibroblasts, which may favor tumor growth.


Asunto(s)
Carcinoma de Células Escamosas/patología , Transformación Celular Neoplásica/patología , Fibroblastos/citología , Neoplasias de la Boca/patología , Comunicación Paracrina/fisiología , Factor de Crecimiento Transformador beta/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/metabolismo , Proliferación Celular , Transdiferenciación Celular , Transformación Celular Neoplásica/química , Transformación Celular Neoplásica/metabolismo , Femenino , Fibroblastos/fisiología , Perfilación de la Expresión Génica , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/metabolismo , Fenotipo , Células del Estroma/patología , Células Tumorales Cultivadas/citología
19.
Cad Saude Publica ; 23(6): 1473-81, 2007 Jun.
Artículo en Portugués | MEDLINE | ID: mdl-17546338

RESUMEN

The most solidly established risk factors for laryngeal cancer are tobacco and alcohol. As for occupational factors, the only established carcinogen is exposure to strong inorganic acid mists. However, asbestos, pesticides, paints, gasoline, diesel engine emissions, dusts, and other factors have been reported in the literature as occupational agents that increase the risk of laryngeal cancer. A hospital-based case-control study was conducted to investigate occupational risk factors for laryngeal cancer. Detailed data on smoking, alcohol consumption, and occupational history were collected for 122 laryngeal cancers and 187 controls matched by frequency (according to sex and age). Laryngeal cancer was associated with exposure to respirable free crystalline silica (OR = 1.83; 95%CI: 1.00-3.36), soot (from coal, coke, fuel oil, or wood) (odds ratio - OR = 1.78; 95% confidence interval - 95%CI: 1.03-3.03), fumes (OR = 2.55; 95%CI: 1.14-5.67), and live animals (OR = 1.80; 95%CI: 1.02-3.19).


Asunto(s)
Consumo de Bebidas Alcohólicas/efectos adversos , Neoplasias Laríngeas/etiología , Exposición Profesional/efectos adversos , Fumar/efectos adversos , Adulto , Anciano , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Encuestas y Cuestionarios
20.
Cad. saúde pública ; 23(6): 1473-1481, jun. 2007. tab
Artículo en Portugués | LILACS | ID: lil-452250

RESUMEN

O tabagismo e o consumo de álcool são os fatores de risco mais bem estabelecidos para o câncer de laringe. Com relação aos fatores ocupacionais, o único carcinógeno estabelecido é a exposição a névoas de ácidos inorgânicos fortes. Entretanto, asbesto, pesticidas, tintas, gases de combustão de gasolina e diesel e poeiras, entre outros, aparecem na literatura como agentes ocupacionais que aumentam o risco de câncer de laringe. Um estudo caso-controle de base hospitalar foi conduzido para investigar fatores de risco ocupacionais para câncer de laringe. Foram coletadas informações detalhadas sobre tabagismo, consumo de álcool e história ocupacional de 122 casos de câncer de laringe e 187 controles pareados por freqüência (segundo sexo e idade). Encontrou-se risco aumentado de câncer de laringe nos indivíduos com exposição à sílica cristalina livre respirável (OR = 1,83; IC95 por cento: 1,00-3,36), à fuligem (de carvão mineral, coque, madeira, óleo combustível) (OR = 1,78; IC95 por cento: 1,03-3,03), a fumos em geral (OR = 2,55; IC95 por cento: 1,14-5,67) e a animais vivos (OR = 1,80; IC95 por cento: 1,02-3,19).


The most solidly established risk factors for laryngeal cancer are tobacco and alcohol. As for occupational factors, the only established carcinogen is exposure to strong inorganic acid mists. However, asbestos, pesticides, paints, gasoline, diesel engine emissions, dusts, and other factors have been reported in the literature as occupational agents that increase the risk of laryngeal cancer. A hospital-based case-control study was conducted to investigate occupational risk factors for laryngeal cancer. Detailed data on smoking, alcohol consumption, and occupational history were collected for 122 laryngeal cancers and 187 controls matched by frequency (according to sex and age). Laryngeal cancer was associated with exposure to respirable free crystalline silica (OR = 1.83; 95 percentCI: 1.00-3.36), soot (from coal, coke, fuel oil, or wood) (odds ratio - OR = 1.78; 95 percent confidence interval - 95 percentCI: 1.03-3.03), fumes (OR = 2.55; 95 percentCI: 1.14-5.67), and live animals (OR = 1.80; 95 percentCI: 1.02-3.19).


Asunto(s)
Humanos , Masculino , Femenino , Bebidas Alcohólicas , Neoplasias Laríngeas/mortalidad , Riesgos Laborales , Tabaquismo , Estudios de Casos y Controles , Oportunidad Relativa , Factores de Riesgo
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