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1.
Sci Rep ; 14(1): 10583, 2024 05 08.
Artículo en Inglés | MEDLINE | ID: mdl-38719848

RESUMEN

Identifying marker combinations for robust prognostic validation in primary tumour compartments remains challenging. We aimed to assess the prognostic significance of CSC markers (ALDH1, CD44, p75NTR, BMI-1) and E-cadherin biomarkers in OSCC. We analysed 94 primary OSCC and 67 metastatic lymph node samples, including central and invasive tumour fronts (ITF), along with clinicopathological data. We observed an increase in ALDH1+/CD44+/BMI-1- tumour cells in metastatic lesions compared to primary tumours. Multivariate analysis highlighted that elevated p75NTR levels (at ITF) and reduced E-cadherin expression (at the tumour centre) independently predicted metastasis, whilst ALDH1high exhibited independent predictive lower survival at the ITF, surpassing the efficacy of traditional tumour staging. Then, specifically at the ITF, profiles characterized by CSChighE-cadherinlow (ALDH1highp75NTRhighE-cadherinlow) and CSCintermediateE-cadherinlow (ALDH1 or p75NTRhighE-cadherinlow) were significantly associated with worsened overall survival and increased likelihood of metastasis in OSCC patients. In summary, our study revealed diverse tumour cell profiles in OSCC tissues, with varying CSC and E-cadherin marker patterns across primary tumours and metastatic sites. Given the pivotal role of reduced survival rates as an indicator of unfavourable prognosis, the immunohistochemistry profile identified as CSChighE-cadherinlow at the ITF of primary tumours, emerges as a preferred prognostic marker closely linked to adverse outcomes in OSCC.


Asunto(s)
Familia de Aldehído Deshidrogenasa 1 , Biomarcadores de Tumor , Cadherinas , Carcinoma de Células Escamosas , Neoplasias de la Boca , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Familia de Aldehído Deshidrogenasa 1/metabolismo , Biomarcadores de Tumor/metabolismo , Cadherinas/metabolismo , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/mortalidad , Receptores de Hialuranos/metabolismo , Inmunohistoquímica , Metástasis Linfática , Neoplasias de la Boca/patología , Neoplasias de la Boca/metabolismo , Neoplasias de la Boca/mortalidad , Neoplasias de la Boca/diagnóstico , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Proteínas del Tejido Nervioso/metabolismo , Complejo Represivo Polycomb 1/metabolismo , Complejo Represivo Polycomb 1/genética , Pronóstico , Receptores de Factor de Crecimiento Nervioso/metabolismo , Retinal-Deshidrogenasa/metabolismo
3.
Ultraschall Med ; 44(3): e148-e156, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35472773

RESUMEN

PURPOSE: To describe a new B-mode ultrasound examination technique to assess cheek tumors. MATERIALS AND METHODS: 30 cheek oral cavity lesions of different histological types (11 benign and 19 malignant) from 23 patients (11 women and 12 men, 7-82 years old, mean age of 49.5 years) were analyzed. Transcutaneous oral B-mode ultrasound (5-12 MHz transducer) was carried out in two stages. Initially it was performed conventionally with an empty mouth. Next, the patient was asked to keep their oral cavity filled with water (like when using a mouthwash) during imaging for the new test examination technique. The anatomical layers of this region and the characteristics of the tumors were evaluated. Lesions were classified as ill defined, partially defined, or defined. Conventional findings were compared to those of the new technique using the Wilcoxon signed-rank test. Ultrasound results were compared to histological findings analyzed by an independent team. RESULTS: The conventional empty mouth technique was able to confidently define lesion extension in only 6 of the 30 lesions, while the water-filled mouth technique was able to confidently define lesion extension in 29 of the 30 lesions (p<0.00001). CONCLUSION: We present a novel technique that dramatically improves ultrasound staging of cheek oral cavity tumors. In addition to the increase in ultrasound accuracy, this technique does not require any special equipment or extra cost, is very well tolerated by patients, and thus should be considered in the evaluation of every patient undergoing transcutaneous cheek ultrasound for oral cavity lesion characterization.


Asunto(s)
Neoplasias de la Boca , Masculino , Humanos , Femenino , Persona de Mediana Edad , Niño , Adolescente , Adulto Joven , Adulto , Anciano , Anciano de 80 o más Años , Mejilla/diagnóstico por imagen , Mejilla/patología , Neoplasias de la Boca/diagnóstico por imagen , Neoplasias de la Boca/patología , Ultrasonografía
4.
Arch. Head Neck Surg ; 51: e20220005, Jan-Dec. 2022.
Artículo en Inglés | LILACS-Express | LILACS | ID: biblio-1401157

RESUMEN

Introduction: Human anatomy is essential for both clinical and surgical practice. Although the anterior jugular veins (AJVs) are of great importance in many surgeries, there are few studies addressing the anatomic variations of these vessels. This study highlights the venous drainage of the head and neck and the importance of anatomical variations in the AJVs. Objective: To observe and describe the anatomy of the jugular veins and evaluate whether there are patterns influenced by anthropometric factors or comorbidities. Methods: Neck dissections were performed on 30 cadavers. The anatomical characteristics of the AJVs were described considering diameter, midline distance, anastomosis, and presence of the jugular venous arch. Results: Cadavers of 14 women and 16 men were dissected. Ninety percent (90%) of the jugular veins had a rectilinear path and 37% presented anastomosis: H-shaped (63.7%),N-shaped (27.3% ), and Y-shaped (9%). In relation to the number of veins, 20% of the cadavers had only one AJV, 63.3% had two, 10% had three, and 6.7% presented a total of four. Mean distance between jugular veins was 12 mm, and most veins (60%) had a diameter <5 mm. There was no statistically significant correlation between anatomical variations and anthropometric factors. Conclusion: AJVs were always present in the dissected cadavers, and the configuration most commonly found was two veins, each <5 mm in diameter. They were less than 10 mm away from the cervical midline and, when they presented anastomosis, it was H-shaped in most cases.

5.
Sci Rep ; 11(1): 18534, 2021 09 17.
Artículo en Inglés | MEDLINE | ID: mdl-34535708

RESUMEN

Extracellular vesicles (EVs) are mediators of the immune system response. Encapsulated in EVs, microRNAs can be transferred between cancer and immune cells. To define the potential effects of EVs originated from squamous cell carcinoma cells on immune system response, we performed microRNA profiling of EVs released from two distinct cell lines and treated dendritic cells derived from circulating monocytes (mono-DCs) with these EVs. We confirmed the internalization of EVs by mono-DCs and the down-regulation of microRNA mRNA targets in treated mono-DCs. Differences in surface markers of dendritic cells cultivated in the presence of EVs indicated that their content disrupts the maturation process. Additionally, microRNAs known to interfere with dendritic cell function, and detected in EVs, matched microRNAs from squamous cell carcinoma patients' plasma: miR-17-5p in oropharyngeal squamous cell carcinoma, miR-21 in oral squamous cell carcinoma, miR-16, miR-24, and miR-181a circulating in both oral and oropharyngeal squamous cell carcinoma, and miR-23b, which has not been previously described in plasma of head and neck squamous cell carcinoma, was found in plasma from patients with these cancer subtypes. This study contributes with insights on EVs in signaling between cancer and immune cells in squamous cell carcinoma of the head and neck.


Asunto(s)
Células Dendríticas/metabolismo , Vesículas Extracelulares/genética , Neoplasias de Cabeza y Cuello/genética , MicroARNs/genética , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Neoplasias de Cabeza y Cuello/sangre , Humanos , MicroARNs/sangre , Transcriptoma
6.
Ann Med Surg (Lond) ; 65: 102303, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-34094525

RESUMEN

INTRODUCTION: Immune cells contribute with mediators in the protein expression profile of the tumor microenvironment. Levels of plasminogen activator inhibitor-1 (PAI-1) are elevated in non-malignant inflammatory conditions; however, the association between PAI-1 expression and inflammation remains uncertain in oral squamous cell carcinoma (OSCC). This study aimed to investigate PAI-1 expression in mononuclear inflammatory cell infiltrate in OSCC and its role as a prognostic marker. METHODS: Samples were collected from patients with OSCC, treated surgically, and followed for 24 months after the procedure. Thirty-nine tumoral tissue were analyzed using immunohistochemistry. Correlation between protein expression, clinicopathological parameters, and the prognosis was investigated. RESULTS: Positive PAI-1 expression in mononuclear inflammatory cell infiltrate was significantly associated with lymph node status (p = 0.009) and with the cytoplasmic expression of vascular endothelial growth factor A (VEGFA) (p = 0.028). Multivariate analysis revealed weak PAI-1 expression as an independent marker for lymph node metastases, with approximately 8-fold increased risk compared to strong expression (OR = 8.60; CI = 1.54-48.08; p = 0.014). CONCLUSION: Our results suggest that the strong PAI-1 expression in intratumoral inflammatory infiltrate is an indicator of a better prognosis for patients diagnosed with oral squamous cell carcinoma.

7.
Laryngoscope ; 131(11): E2770-E2776, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-33949686

RESUMEN

OBJECTIVE: To determine the implication of the new AJCC staging system for pT classification in a cohort of patients with SCC of the lip mucosa and compare it to other oral cavity sites. METHODS: Retrospective cohort of 744 patients treated between 2002 and 2017, by the Head and Neck Surgery Department of the University of Sao Paulo. RESULTS: Of 95 lip patients, 42 had pT upstage (58.1% of pT1 to pT2-3 and 50% of pT2 to pT3). Similar DFS/OS observed for those pT1 maintained or upstaged to pT2-3, pT2 patients upstaged to pT3 presented worse OS (49.4% versus 92.3%, P = .032). The comparison between lip and other mouth topographies, denoted better prognosis for pT1-2, but not for pT3-4a. Lip tumors had lower DOI, rates of perineural/angiolymphatic invasion, nodal metastasis, recurrence, and death. CONCLUSION: The inclusion of DOI to the new pT classification better stratifies patients with SCC of the lip mucosa upstaged to pT3 by assessing inferior OS. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:E2770-E2776, 2021.


Asunto(s)
Carcinoma de Células Escamosas/diagnóstico , Neoplasias de los Labios/patología , Mucosa Bucal/patología , Neoplasias de la Boca/patología , Estadificación de Neoplasias/métodos , Anciano , Brasil/epidemiología , Carcinoma de Células Escamosas/clasificación , Carcinoma de Células Escamosas/mortalidad , Estudios de Cohortes , Supervivencia sin Enfermedad , Femenino , Humanos , Metástasis Linfática/patología , Masculino , Persona de Mediana Edad , Invasividad Neoplásica/patología , Recurrencia Local de Neoplasia/patología , Pronóstico , Estudios Retrospectivos
8.
Head Neck ; 43(8): 2364-2376, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-33834567

RESUMEN

BACKGROUND: We evaluated microRNAs and extracellular matrix component profiles in squamous cell carcinoma of the oral cavity (OSCC) in comparison to healthy mucosa. METHODS: Retrospective study investigating 64 microRNAs related to oncogenic process and to constituents of the extracellular matrix. We also performed immunohistochemical assays for molecules involved in the same biological processes. RESULTS: High expression of miR-21-5p (p < 0.001) and miR-106-5p (p < 0.001) and low expression of miR-320a (p = 0.001) and miR-222-3p (p = 0.001) were predictors of malignancy. Individually, miR-21-5p exhibited the best statistical performance (area under the curve = 0.972; 95% confidence interval: 0.911-1.000) in the differentiation between tumor tissue and healthy mucosa. Moreover, tumor sample showed increased expression of MMP-2, MMP-9, α-laminin, and ß-laminin in tumor-related fibroblasts and lower continuity of type IV collagen in the basement membrane. CONCLUSION: The present study demonstrates the biological effects of microRNAs on the carcinogenesis of OSCC as well as the intense modification of the tumor microenvironment.


Asunto(s)
Carcinoma de Células Escamosas , MicroARNs , Neoplasias de la Boca , Carcinoma de Células Escamosas/genética , Línea Celular Tumoral , Proliferación Celular , Matriz Extracelular/genética , Regulación Neoplásica de la Expresión Génica , Humanos , MicroARNs/genética , Neoplasias de la Boca/genética , Estudios Retrospectivos , Microambiente Tumoral/genética
9.
Oral Oncol ; 110: 104909, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32702628

RESUMEN

The objective of the present study was to evaluate the role of microRNA-mediated remodeling of the extracellular matrix in the process of tumor invasion of oral squamous cell carcinoma and to evaluate its relationship with the prognosis of these patients. This was a retrospective study on material from the paraffin blocks of patients operated on for oral squamous cell carcinoma, in addition to a group of healthy oral mucosa samples of paired patients. miR-1-3p, miR-133-3p, and miR-21-5p were differentially expressed between the superficial and deep tumor groups. miR-21-5p was the one with the greatest accuracy in the differentiation between superficial and deep tumors. By immunohistochemistry, the group of deep tumors showed greater immunoreactivity to matrix metalloproteinases 2 and 9 and laminin α in tumor-associated fibroblasts, with consequent degradation of the basal membrane, measured by greater loss of continuity of type IV collagen. This process was also associated with lower and higher expression of miR-1-3p and miR-21-5p, respectively. There was also a trend toward better overall and disease-free survival rates in patients with higher miR-133a-3p. The present study showed the interaction between microRNAs and extracellular matrix remodeling in oral squamous cell carcinoma.


Asunto(s)
Fibroblastos Asociados al Cáncer/metabolismo , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Regulación Neoplásica de la Expresión Génica , MicroARNs/genética , Neoplasias de la Boca/genética , Neoplasias de la Boca/metabolismo , Adulto , Anciano , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/terapia , Terapia Combinada , Femenino , Perfilación de la Expresión Génica , Humanos , Inmunohistoquímica , Masculino , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Persona de Mediana Edad , Neoplasias de la Boca/diagnóstico , Neoplasias de la Boca/terapia , Clasificación del Tumor , Invasividad Neoplásica , Estadificación de Neoplasias , Interferencia de ARN , Curva ROC
10.
Clinics (Sao Paulo) ; 75: e1623, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32667491

RESUMEN

OBJECTIVES: To verify the pyramidalis muscle's frequency (bilaterality, unilaterality, or absence) and morphometry (length of the medial border and width of its origin/base) in a sample of the Brazilian population and the anthropometric influence. METHODS: Dissection of 30 cadavers, up to 24h post-mortem. RESULTS: The pyramidalis muscle was present bilaterally and unilaterally in 83.33% and 3.33% of the cadavers, respectively, and absent in 13.33%. The muscles on the right and left sides were symmetrical in length but not in width; the pyramidalis muscles of men were longer, while those of the women were wider. We also found that there was greater variation in the dimensions (length and width) of the men's muscles. Finally, in this sample of the Brazilian population, the pyramidalis muscle's unilaterality was more prevalent than in other populations, and its complete absence was less prevalent. CONCLUSIONS: There were no cases of muscle duplication in one or both sides, as described in some studies. Despite all of its morphometric variation, the pyramidalis muscle maintained its triangular shape with longitudinal fibers in every case. Furthermore, no statistically significant correlation was noted between the muscles' dimensions and person's age, height, weight, or gender.


Asunto(s)
Músculos Abdominales , Adulto , Brasil , Cadáver , Femenino , Humanos , Masculino
11.
Clinics ; 75: e1623, 2020. tab, graf
Artículo en Inglés | LILACS | ID: biblio-1133402

RESUMEN

OBJECTIVES: To verify the pyramidalis muscle's frequency (bilaterality, unilaterality, or absence) and morphometry (length of the medial border and width of its origin/base) in a sample of the Brazilian population and the anthropometric influence. METHODS: Dissection of 30 cadavers, up to 24h post-mortem. RESULTS: The pyramidalis muscle was present bilaterally and unilaterally in 83.33% and 3.33% of the cadavers, respectively, and absent in 13.33%. The muscles on the right and left sides were symmetrical in length but not in width; the pyramidalis muscles of men were longer, while those of the women were wider. We also found that there was greater variation in the dimensions (length and width) of the men's muscles. Finally, in this sample of the Brazilian population, the pyramidalis muscle's unilaterality was more prevalent than in other populations, and its complete absence was less prevalent. CONCLUSIONS: There were no cases of muscle duplication in one or both sides, as described in some studies. Despite all of its morphometric variation, the pyramidalis muscle maintained its triangular shape with longitudinal fibers in every case. Furthermore, no statistically significant correlation was noted between the muscles' dimensions and person's age, height, weight, or gender.


Asunto(s)
Humanos , Masculino , Femenino , Adulto , Músculos Abdominales , Brasil , Cadáver
12.
Int J Oncol ; 53(6): 2458-2472, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30272273

RESUMEN

Oral squamous cell carcinoma (OSCC) is an extremely aggressive disease associated with a poor prognosis. Previous studies have established that cancer stem cells (CSCs) actively participate in OSCC development, progression and resistance to conventional treatments. Furthermore, CSCs frequently exhibit a deregulated expression of normal stem cell signalling pathways, thereby acquiring their distinctive abilities, of which self-renewal is an example. In this study, we examined the effects of GLI3 knockdown in OSCC, as well as the differentially expressed genes in CSC-like cells (CSCLCs) expressing high (CD44high) or low (CD44low) levels of CD44. The prognostic value of GLI3 in OSCC was also evaluated. The OSCC cell lines were sorted based on CD44 expression; gene expression was evaluated using a PCR array. Following this, we examined the effects of GLI3 knockdown on CD44 and ESA expression, colony and sphere formation capability, stem-related gene expression, proliferation and invasion. The overexpression of genes related to the Notch, transforming growth factor (TGF)ß, FGF, Hedgehog, Wnt and pluripotency maintenance pathways was observed in the CD44high cells. GLI3 knockdown was associated with a significant decrease in different CSCLC fractions, spheres and colonies in addition to the downregulation of the CD44, Octamer-binding transcription factor 4 (OCT4; also known as POU5F1) and BMI1 genes. This downregulation was accompanied by an increase in the expression of the Involucrin (IVL) and S100A9 genes. Cellular proliferation and invasion were inhibited following GLI3 knockdown. In OSCC samples, a high GLI3 expression was associated with tumour size but not with prognosis. On the whole, the findings of this study demonstrate for the first time, at least to the best of our knowledge, that GLI3 contributes to OSCC stemness and malignant behaviour. These findings suggest the potential for the development of novel therapies, either in isolation or in combination with other drugs, based on CSCs in OSCC.


Asunto(s)
Carcinoma de Células Escamosas/metabolismo , Neoplasias de la Boca/metabolismo , Células Madre Neoplásicas/metabolismo , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Proteína Gli3 con Dedos de Zinc/genética , Proteína Gli3 con Dedos de Zinc/metabolismo , Adulto , Anciano , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Transición Epitelial-Mesenquimal , Regulación Neoplásica de la Expresión Génica , Técnicas de Silenciamiento del Gen , Humanos , Receptores de Hialuranos/metabolismo , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/genética , Neoplasias de la Boca/patología , Invasividad Neoplásica , Células Madre Neoplásicas/patología , Pronóstico , Transducción de Señal , Análisis de Supervivencia , Carga Tumoral
13.
J Clin Endocrinol Metab ; 103(9): 3250-3259, 2018 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-29846642

RESUMEN

Context: Persistent disease after surgery is common in medullary thyroid cancer (MTC), requiring lifelong radiological surveillance. Staging workup includes imaging of neck, chest, abdomen, and bones. A study integrating all sites would be ideal. Despite the established use of gallium-68 (68Ga) positron emission tomography (PET)/CT with somatostatin analogues in most neuroendocrine tumors, its efficacy is controversial in MTC. Objective: Evaluate the efficacy of 68Ga PET/CT in detecting MTC lesions and evaluate tumor expression of somatostatin receptors (SSTRs) associated with 68Ga PET/CT findings. Methods: Prospective study evaluating 30 patients with MTC [group 1 (n = 16), biochemical disease; group 2 (n = 14), metastatic disease]. Patients underwent 68Ga PET/CT, bone scan, CT and ultrasound of the neck, CT of the chest, CT/MRI of the abdomen, and MRI of the spine. 68Ga PET/CT findings were analyzed by disease site as positive or negative and as concordant or discordant with conventional studies. Sensitivity and specificity were calculated using pathological or cytological analysis or unequivocal identification by standard imaging studies. Immunohistochemical analysis of SSTRs was compared with 68Ga PET/CT findings. Results: In both groups, 68Ga PET/CT was inferior to currently used imaging studies except for bone scan. In group 2, 68Ga PET/CT sensitivities were 56%, 57%, and 9% for detecting neck lymph nodes, lung metastases, and liver metastases, respectively, and 100% for bone metastases, superior to the bone scan (44%). Expression of SSTRs, observed in 44% of tumors, was not associated with 68Ga-DOTATATE uptake. Conclusions: 68Ga PET/CT does not provide optimal whole-body imaging as a single procedure in patients with MTC. However, it is highly sensitive in detecting bone lesions and could be a substitute for a bone scan and MRI.


Asunto(s)
Neoplasias Óseas/diagnóstico por imagen , Neoplasias Óseas/secundario , Carcinoma Neuroendocrino/diagnóstico por imagen , Carcinoma Neuroendocrino/secundario , Neoplasias de la Tiroides/diagnóstico por imagen , Neoplasias de la Tiroides/secundario , Adulto , Anciano , Femenino , Radioisótopos de Galio , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Compuestos Organometálicos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Estudios Prospectivos , Sensibilidad y Especificidad , Ultrasonografía , Adulto Joven
14.
Head Neck ; 40(8): 1759-1773, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-29607565

RESUMEN

BACKGROUND: Tongue squamous cell carcinoma (SCC) contains a cell subpopulation referred to as cancer stem cells (CSCs), which are responsible for tumor growth, metastasis, and resistance to chemotherapy and radiotherapy. The CSC markers have been used to isolate these cells and as biomarkers to predict overall survival. METHODS: The CSC markers CD44, NANOG, OCT4, and BMI1 were investigated using reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry and correlated with clinicopathological parameters. RESULTS: The CD44 overexpression was associated with disease-related death (P = 0.02) and worst prognosis. NANOG was upregulated in nontumoral margins and associated with T1/T2 classification, lymph node metastasis, and worst prognosis. OCT4 was associated with lymph node metastasis and worst overall survival. BMI1 and CD44v3 were overexpressed in tongue SCC. Coexpression of CD44++ /NANOG++ was associated with worst overall survival when compared with patients with CD44-/+ /NANOG-/+ . CONCLUSION: The CSC markers might play an important role not only in CSC trait acquisition but also in tongue SCC development and progression.


Asunto(s)
Carcinoma de Células Escamosas/mortalidad , Receptores de Hialuranos/metabolismo , Proteína Homeótica Nanog/metabolismo , Factor 3 de Transcripción de Unión a Octámeros/metabolismo , Complejo Represivo Polycomb 1/metabolismo , Neoplasias de la Lengua/mortalidad , Adulto , Biomarcadores de Tumor/metabolismo , Carcinoma de Células Escamosas/metabolismo , Células Epiteliales/metabolismo , Femenino , Humanos , Receptores de Hialuranos/genética , Inmunohistoquímica , Queratinocitos/metabolismo , Metástasis Linfática , Masculino , Proteína Homeótica Nanog/genética , Factor 3 de Transcripción de Unión a Octámeros/genética , Complejo Represivo Polycomb 1/genética , Pronóstico , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Neoplasias de la Lengua/metabolismo , Regulación hacia Arriba
15.
J Oral Pathol Med ; 47(6): 566-574, 2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-29693741

RESUMEN

BACKGROUND: In oral squamous cell carcinoma (OSCC), the HIF-1 complex promotes the expression of genes involved in specific mechanisms of cell survival under hypoxic conditions, such as plasminogen activator inhibitor-1 (PAI-1), carbonic anhydrase 9 (CAIX), and vascular endothelial growth factor A (VEGFA). The study aimed to investigate the presence and prognostic value of PAI-1, CAIX, and VEGFA in OSCC. MATERIALS AND METHODS: Immunohistochemistry was used to analyze the expressions of these proteins in 52 tumoral tissue samples of patients with OSCC, surgically treated and followed by a minimum of 24 months after surgery. The correlations between protein expressions and clinicopathological parameters and prognosis were analyzed. RESULTS: Positive PAI-1 membrane expression was significantly associated with local disease relapse (P = .027). Multivariate analysis revealed that the positive PAI-1 membrane expression is an independent marker for local disease relapse, with approximately 14-fold increased risk when compared to negative expression (OR = 14.49; CI = 1.40-150.01, P = .025). Strong PAI-1 cytoplasmic expression was significantly associated with the less differentiation grade (P = .027). Strong CAIX membrane expression was significantly associated with local disease-free survival (P = .038). Positive CAIX cytoplasmic expression was significantly associated with lymph node affected (P = .025) and with disease-specific survival (P = .022). Multivariate analysis revealed that the positive CAIX cytoplasmic expression is an independent risk factor for disease-related death, increasing their risk approximately 3-fold when compared to negative expression (HR = 2.84; CI = 1.02-7.87, P = .045). Positive VEGFA cytoplasmic expression was significantly associated with less differentiation grade (P = .035). CONCLUSION: Our results suggest a potential role for these expressions profiles as tumor prognostic markers in OSCC patients.


Asunto(s)
Antígenos de Neoplasias/biosíntesis , Biomarcadores de Tumor/biosíntesis , Anhidrasa Carbónica IX/biosíntesis , Neoplasias de la Boca/metabolismo , Inhibidor 1 de Activador Plasminogénico/biosíntesis , Carcinoma de Células Escamosas de Cabeza y Cuello/metabolismo , Factor A de Crecimiento Endotelial Vascular/biosíntesis , Anciano , Antígenos de Neoplasias/metabolismo , Biomarcadores de Tumor/metabolismo , Anhidrasa Carbónica IX/metabolismo , Supervivencia sin Enfermedad , Femenino , Humanos , Inmunohistoquímica , Ganglios Linfáticos/patología , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/patología , Análisis Multivariante , Recurrencia Local de Neoplasia/metabolismo , Recurrencia Local de Neoplasia/patología , Inhibidor 1 de Activador Plasminogénico/metabolismo , Pronóstico , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Análisis de Supervivencia , Factor A de Crecimiento Endotelial Vascular/metabolismo
16.
Head Neck ; 39(5): 960-964, 2017 05.
Artículo en Inglés | MEDLINE | ID: mdl-28276113

RESUMEN

BACKGROUND: The purpose of the present study was to investigate the role of tumor volume in the prognosis of patients with oral cavity squamous cell carcinoma (SCC). METHODS: One hundred twenty-three patients with T4a oral cavity SCCs underwent surgical treatment. The volumes of the primary cancer were calculated by the multiplication of 3 macroscopic dimensions of the surgical specimen and related to recurrence and death. RESULTS: There were 54 recurrences (43.9%) and 75 deaths (60.9%). The mean tumor volume among the patients living without disease during the follow-up period was 28.2 cc, compared to 88.2 cc for patients living with disease, and to 78.9 cc for patients who died of the disease (p < .001). Multivariate analyses showed that volume and perineural invasion were independent factors for recurrence, whereas volume and lymph node metastasis were independent factors for death. CONCLUSION: Among patients who already have advanced cancers, tumor volume can significantly impact their prognoses. © 2017 Wiley Periodicals, Inc. Head Neck 39: 960-964, 2017.


Asunto(s)
Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Neoplasias de la Boca/mortalidad , Neoplasias de la Boca/patología , Recurrencia Local de Neoplasia/epidemiología , Anciano , Carcinoma de Células Escamosas/terapia , Estudios Transversales , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/terapia , Invasividad Neoplásica , Factores de Riesgo , Tasa de Supervivencia , Carga Tumoral
17.
Oral Oncol ; 61: 47-54, 2016 10.
Artículo en Inglés | MEDLINE | ID: mdl-27688104

RESUMEN

INTRODUCTION: Diabetes mellitus (DM (Diabetes Mellitus)) is directly associated with some cancers. However, studies on the association between diabetes mellitus and head and neck cancer (HNC (Head and Neck Cancer)) have rendered controversial results. The objective of this study was to evaluate the association between DM and HNC, as well as the impact of metformin use on the risk of HNC. MATERIAL AND METHODS: This case-control study was conducted within the framework of the Brazilian Head and Neck Genome Project in 2011-2014. The study included 1021 HNC cases with histologically confirmed squamous cell carcinoma of the head and neck admitted to five large hospitals in São Paulo state. A total of 1063 controls were selected in the same hospitals. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using unconditional logistic regression. RESULTS: Diabetic participants had a decreased risk of HNC (OR=0.68; 95% CI: 0.49-0.95) than non-diabetic participants, and this risk was further decreased among diabetic metformin users (OR=0.54; 95% CI: 0.29-0.99). Diabetic metformin users that were current smokers (OR=0.13; 95% CI: 0.04-0.44) or had an alcohol consumption of >40g/day (OR=0.31; 95% CI: 0.11-0.88) had lower risk of HNC than equivalent non-diabetic participants. CONCLUSION: The risk of HNC was decreased among diabetic participants; metformin use may at least partially explain this inverse association.


Asunto(s)
Diabetes Mellitus/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/complicaciones , Hipoglucemiantes/uso terapéutico , Metformina/uso terapéutico , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad
18.
Eur J Endocrinol ; 173(4): 525-40, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26338373

RESUMEN

BACKGROUND: Thyroid cancer incidence has dramatically increased worldwide over the last two decades. The rise is mostly due to an increased detection of small papillary thyroid carcinomas (PTCs) (≤20  mm), predominantly microPTC (≤10  mm). Although small tumors generally have an excellent outcome, a considerable percentage may have a more aggressive disease and worse prognosis. The clinical challenge is to preoperatively identify those tumors that are more likely to recur. AIM: To improve risk stratification and patient management, we sought to determine the prognostic value of BRAF V600E, NRAS or RET/PTC mutations in patients with PTC measuring <20  mm, mainly microPTC. METHODS: The prevalence of RET/PTC fusion genes was examined by quantitative RT-PCR. BRAF V600E and NRAS Q61 mutations were determined by PCR sequencing. To further elucidate why some small PTC are less responsive to radioactive iodine treatment therapy, we explored if these genetic alterations may modulate the expression of iodine metabolism genes (NIS, TPO, TG, TSHR and PDS) and correlated with clinico-pathological findings that are predictors of recurrence. RESULTS: This study shows that tumors measuring ≤20  mm exhibited higher prevalence of BRAF V600E mutation, which correlated with aggressive histopathological parameters, higher risk of recurrence, and lower expression of NIS and TPO. Although this correlation was not found when microPTC were evaluated, we show that tumors measuring 7-10  mm, which were positive for BRAF mutation, presented more aggressive features and lower expression of NIS and TPO. CONCLUSION: We believe that our findings will help to decide the realistic usefulness of BRAF V600E mutation as a preoperative marker of poor prognosis in small PTC, primarily in microPTC.


Asunto(s)
Carcinoma Papilar/genética , GTP Fosfohidrolasas/genética , Proteínas de la Membrana/genética , Recurrencia Local de Neoplasia/genética , Proteínas de Fusión Oncogénica/genética , Proteínas Tirosina Quinasas/genética , Proteínas Proto-Oncogénicas B-raf/genética , Neoplasias de la Tiroides/genética , Adulto , Anciano , Autoantígenos/genética , Carcinoma Papilar/patología , Femenino , Humanos , Yoduro Peroxidasa/genética , Yodo/metabolismo , Proteínas de Unión a Hierro/genética , Masculino , Proteínas de Transporte de Membrana/genética , Persona de Mediana Edad , Mutación , Invasividad Neoplásica , Metástasis de la Neoplasia , Estadificación de Neoplasias , Pronóstico , Receptores de Tirotropina/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transportadores de Sulfato , Simportadores/genética , Tiroglobulina/genética , Neoplasias de la Tiroides/patología , Carga Tumoral , Adulto Joven
19.
Int J Epidemiol ; 44(1): 169-85, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25613428

RESUMEN

BACKGROUND: Increasing incidence of head and neck cancer (HNC) in young adults has been reported. We aimed to compare the role of major risk factors and family history of cancer in HNC in young adults and older patients. METHODS: We pooled data from 25 case-control studies and conducted separate analyses for adults ≤ 45 years old ('young adults', 2010 cases and 4042 controls) and >45 years old ('older adults', 17700 cases and 22 704 controls). Using logistic regression with studies treated as random effects, we estimated adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: The young group of cases had a higher proportion of oral tongue cancer (16.0% in women; 11.0% in men) and unspecified oral cavity / oropharynx cancer (16.2%; 11.1%) and a lower proportion of larynx cancer (12.1%; 16.6%) than older adult cases. The proportions of never smokers or never drinkers among female cases were higher than among male cases in both age groups. Positive associations with HNC and duration or pack-years of smoking and drinking were similar across age groups. However, the attributable fractions (AFs) for smoking and drinking were lower in young when compared with older adults (AFs for smoking in young women, older women, young men and older men, respectively, = 19.9% (95% CI=9.8%, 27.9%), 48.9% (46.6%, 50.8%), 46.2% (38.5%, 52.5%), 64.3% (62.2%, 66.4%); AFs for drinking=5.3% (-11.2%, 18.0%), 20.0% (14.5%, 25.0%), 21.5% (5.0%, 34.9%) and 50.4% (46.1%, 54.3%). A family history of early-onset cancer was associated with HNC risk in the young [OR=2.27 (95% CI=1.26, 4.10)], but not in the older adults [OR=1.10 (0.91, 1.31)]. The attributable fraction for family history of early-onset cancer was 23.2% (8.60% to 31.4%) in young compared with 2.20% (-2.41%, 5.80%) in older adults. CONCLUSIONS: Differences in HNC aetiology according to age group may exist. The lower AF of cigarette smoking and alcohol drinking in young adults may be due to the reduced length of exposure due to the lower age. Other characteristics, such as those that are inherited, may play a more important role in HNC in young adults compared with older adults.


Asunto(s)
Consumo de Bebidas Alcohólicas/epidemiología , Neoplasias de Cabeza y Cuello/epidemiología , Fumar/epidemiología , Adulto , Factores de Edad , Estudios de Casos y Controles , Femenino , Predisposición Genética a la Enfermedad , Neoplasias de Cabeza y Cuello/genética , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Sistema de Registros , Factores de Riesgo , Factores Sexuales
20.
Clinics (Sao Paulo) ; 68(6): 738-44, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23778492

RESUMEN

OBJECTIVE: As a lifestyle-related disease, social and cultural disparities may influence the features of squamous cell carcinoma of the head and neck in different geographic regions. We describe demographic, clinical, and pathological aspects of squamous cell carcinoma of the head and neck according to the smoking and alcohol consumption habits of patients in a Brazilian cohort. METHODS: We prospectively analyzed the smoking and alcohol consumption habits of 1,633 patients enrolled in five São Paulo hospitals that participated in the Brazilian Head and Neck Genome Project - Gencapo. RESULTS: The patients who smoked and drank were younger, and those who smoked were leaner than the other patients, regardless of alcohol consumption. The non-smokers/non-drinkers were typically elderly white females who had more differentiated oral cavity cancers and fewer first-degree relatives who smoked. The patients who drank presented significantly more frequent nodal metastasis, and those who smoked presented less-differentiated tumors. CONCLUSIONS: The patients with squamous cell carcinoma of the head and neck demonstrated demographic, clinical, and pathological features that were markedly different according to their smoking and drinking habits. A subset of elderly females who had oral cavity cancer and had never smoked or consumed alcohol was notable. Alcohol consumption seemed to be related to nodal metastasis, whereas smoking correlated with the degree of differentiation.


Asunto(s)
Consumo de Bebidas Alcohólicas/epidemiología , Carcinoma de Células Escamosas/patología , Neoplasias de Cabeza y Cuello/patología , Fumar/epidemiología , Distribución por Edad , Anciano , Consumo de Bebidas Alcohólicas/efectos adversos , Brasil , Carcinoma de Células Escamosas/epidemiología , Carcinoma de Células Escamosas/secundario , Estudios Transversales , Femenino , Neoplasias de Cabeza y Cuello/epidemiología , Humanos , Estilo de Vida , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Metástasis de la Neoplasia , Factores de Riesgo , Distribución por Sexo , Fumar/efectos adversos , Factores Socioeconómicos
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