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1.
Ann Surg Oncol ; 27(11): 4133-4140, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32767223

RESUMEN

BACKGROUND: Sentinel node biopsy (SNB) for melanoma patients has been questioned. We aimed to study high-risk stage II melanoma patients who underwent SNB to determine what the prognostic factors regarding recurrence and mortality were, and evaluate how relevant SNB status is in this scenario. METHODS: This was a retrospective analysis of clinical stage IIB/IIC melanoma patients who underwent SNB from 2000 to 2015 in a single institution. Prognostic factors related to distant recurrence-free survival (DRFS) and melanoma-specific survival (MSS) were assessed from multiple Cox regression. Relevant variables were used to create risk predictor nomograms for DRFS and MSS. RESULTS: From 1213 SNB, 259 were performed for clinical stage IIB/IIC melanoma patients. SNB status was the most important variable for both endpoints. Patients with positive SNB presented median DRFS of 35.73 months (95% CI 21.38-50.08, SE 7.32) and median MSS of 66.4 months (95% CI 29.76-103.03, SE 18.69), meanwhile both median DRFS and MSS were not achieved for those with negative SNB (logrank < 0.0001). Both nomograms have been internally validated and presented adequate calibration (C-index was 0.734 for DRFS and 0.718 for MSS). CONCLUSIONS: SNB status was the most important risk factor in our cohort of clinical stage IIB and IIC patients and, in conjunction with well-established primary tumor characteristics, should not be abandoned. Their use in prognosis for these patients remains extremely useful for daily practice.


Asunto(s)
Melanoma , Ganglio Linfático Centinela , Neoplasias Cutáneas , Humanos , Melanoma/cirugía , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Ganglio Linfático Centinela/cirugía , Biopsia del Ganglio Linfático Centinela , Neoplasias Cutáneas/cirugía
2.
Int J Mol Sci ; 21(4)2020 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-32075009

RESUMEN

Salivary gland aquaporins (AQPs) are essential for the control of saliva production and maintenance of glandular structure. However, little is known of their role in salivary gland neoplasia. Salivary gland tumors comprise a heterogeneous group of lesions, featuring variable histological characteristics and diverse clinical behaviors. Mucoepidermoid carcinoma (MEC) is the most common salivary gland malignancy. The aim of this study was to evaluate the expression of AQP1, AQP3, and AQP5 in 24 MEC samples by immunohistochemistry. AQP1 expression was observed in vascular endothelium throughout the tumor stroma. AQP3 was expressed in epidermoid and mucosal cells and AQP5 was expressed in mucosal cells of MEC. These proteins were expressed in the human MEC cell line UH-HMC-3A. Cellular ultrastructural aspects were analyzed by electron microscopy to certificate the tumor cell phenotype. In summary, our results show that, despite the fact that these molecules are important for salivary gland physiology, they may not play a distinct role in tumorigenesis in MEC. Additionally, the in vitro model may offer new possibilities to further investigate mechanisms of these molecules in tumor biology and their real significance in prognosis and possible target therapies.


Asunto(s)
Acuaporina 1/metabolismo , Acuaporina 3/metabolismo , Acuaporina 5/metabolismo , Carcinoma Mucoepidermoide/patología , Neoplasias de las Glándulas Salivales/patología , Adulto , Carcinoma Mucoepidermoide/metabolismo , Carcinoma Mucoepidermoide/mortalidad , Línea Celular Tumoral , Células Epiteliales/patología , Células Epiteliales/ultraestructura , Femenino , Humanos , Inmunohistoquímica , Masculino , Microscopía Electrónica , Persona de Mediana Edad , Fenotipo , Proyectos Piloto , Neoplasias de las Glándulas Salivales/metabolismo , Neoplasias de las Glándulas Salivales/mortalidad , Tasa de Supervivencia
3.
Ann Surg Oncol ; 26(2): 395-405, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30456681

RESUMEN

BACKGROUND: Non-sentinel node (NSN) positivity impacts the prognosis of melanoma patients; however, the benefits of completion lymph node dissection in patients with positive sentinel nodes (SNs) are limited. OBJECTIVE: We aimed to present a predictive nomogram for NSN positivity in melanoma patients with a positive SN biopsy. METHODS: This retrospective analysis from patients who underwent SN biopsy in a Brazilian institution from 2000 to 2015 was used for the construction and internal validation of the nomogram. This nomogram was then externally validated in a cohort of Dutch patients. RESULTS: The Brazilian cohort comprised 1213 patients, with a mean follow-up of 5.11 years. Breslow thickness (odds ratio [OR] 1.170, 95% confidence interval [CI] 1.043-1.314]; p = 0.008), number of positive SNs (OR 1.092, 95% CI 1.034-1.153; p = 0.001), and largest diameter of the metastatic deposit (OR 3.217, 95% CI 1.551-6.674; p = 0.002) were statistically significant for NSN positivity. Internal validation was performed using a bootstrapping technique. A good performance was observed (Brier score 0.097) and an excellent power of discrimination was achieved (area under the curve [AUC] 0.822). The nomogram was then applied to the Dutch cohort, and its overall performance (Brier score 0.085), calibration (Hosmer-Lemeshow goodness-of-fit test; p = 0.198), and discriminatory power (AUC 0.752, 95% CI 0.615-0.890) were all adequate. CONCLUSIONS: We presented a nomogram for assessing NSN probability that should not only be used for surgical considerations but also for risk stratification and clinical decisions. Internal validation has shown that this is an adequate model, while external validation increases the model's reliability and suggests that it can be globally incorporated.


Asunto(s)
Ganglios Linfáticos/patología , Melanoma/patología , Nomogramas , Biopsia del Ganglio Linfático Centinela , Neoplasias Cutáneas/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Brasil , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Ganglios Linfáticos/cirugía , Masculino , Melanoma/cirugía , Persona de Mediana Edad , Invasividad Neoplásica , Países Bajos , Valor Predictivo de las Pruebas , Curva ROC , Estudios Retrospectivos , Neoplasias Cutáneas/cirugía , Adulto Joven
4.
J Am Acad Dermatol ; 80(3): 722-726, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30395920

RESUMEN

BACKGROUND: Melanoma patients with negative nodes after sentinel lymph node biopsy are a heterogeneous group. Current guidelines fail to adequately stratify surveillance and treatment for this group. Also, there is scarce data on adjuvant treatments for these patients. OBJECTIVE: To create a nomogram including clinical and pathologic characteristics capable of evaluating the risk for recurrence of primary melanoma patients with negative sentinel lymph node biopsies (SLNBs). METHODS: We used a retrospective cohort of patients who underwent SLNB during 2000-2015 at a single institution. RESULTS: Our cohort comprised 1213 patients. Among these patients, 967 (79.7%) had a negative SLNB, and mean follow-up was 59.67 months. There were 133 recurrences (13.8%); 45 (33.8%) presented with nodal recurrence, and 35 (26.3%) recurred where a SLNB was performed. Breslow thickness, ulceration, and microsatellitosis were found to be predictive of risk for recurrence at 1, 2, 5, and 10 years. LIMITATION: Single center analysis. CONCLUSION: We created a predictive nomogram for melanoma patients with negative SLNBs. This nomogram is easy to use and identifies high-risk patients who should have more strict surveillance and be considered for adjuvant treatment.


Asunto(s)
Melanoma/secundario , Nomogramas , Neoplasias Cutáneas/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Metástasis Linfática , Masculino , Melanoma/complicaciones , Persona de Mediana Edad , Estudios Retrospectivos , Medición de Riesgo/métodos , Factores de Riesgo , Ganglio Linfático Centinela/patología , Biopsia del Ganglio Linfático Centinela , Neoplasias Cutáneas/complicaciones , Úlcera Cutánea/etiología , Carga Tumoral , Adulto Joven
6.
Hum Genomics ; 10(1): 36, 2016 11 18.
Artículo en Inglés | MEDLINE | ID: mdl-27863505

RESUMEN

BACKGROUND: Genome-wide profiling of rare tumors is crucial for improvement of diagnosis, treatment, and, consequently, achieving better outcomes. Desmoplastic small round cell tumor (DSRCT) is a rare type of sarcoma arising from mesenchymal cells of abdominal peritoneum that usually develops in male adolescents and young adults. A specific translocation, t(11;22)(p13;q12), resulting in EWS and WT1 gene fusion is the only recurrent molecular hallmark and no other genetic factor has been associated to this aggressive tumor. Here, we present a comprehensive genomic profiling of one DSRCT affecting a 26-year-old male, who achieved an excellent outcome. METHODS: We investigated somatic and germline variants through whole-exome sequencing using a family based approach and, by array CGH, we explored the occurrence of genomic imbalances. Additionally, we performed mate-paired whole-genome sequencing for defining the specific breakpoint of the EWS-WT1 translocation, allowing us to develop a personalized tumor marker for monitoring the patient by liquid biopsy. RESULTS: We identified genetic variants leading to protein alterations including 12 somatic and 14 germline events (11 germline compound heterozygous mutations and 3 rare homozygous polymorphisms) affecting genes predominantly involved in mesenchymal cell differentiation pathways. Regarding copy number alterations (CNA) few events were detected, mainly restricted to gains in chromosomes 5 and 18 and losses at 11p, 13q, and 22q. The deletions at 11p and 22q indicated the presence of the classic translocation, t(11;22)(p13;q12). In addition, the mapping of the specific genomic breakpoint of the EWS-WT1 gene fusion allowed the design of a personalized biomarker for assessing circulating tumor DNA (ctDNA) in plasma during patient follow-up. This biomarker has been used in four post-treatment blood samples, 3 years after surgery, and no trace of EWS-WT1 gene fusion was detected, in accordance with imaging tests showing no evidence of disease and with the good general health status of the patient. CONCLUSIONS: Overall, our findings revealed genes with potential to be associated with risk assessment and tumorigenesis of this rare type of sarcoma. Additionally, we established a liquid biopsy approach for monitoring patient follow-up based on genomic information that can be similarly adopted for patients diagnosed with a rare tumor.


Asunto(s)
Neoplasias Abdominales/diagnóstico por imagen , Tumor Desmoplásico de Células Pequeñas Redondas/diagnóstico por imagen , Neoplasias Abdominales/genética , Neoplasias Abdominales/terapia , Adulto , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/genética , Cromosomas Humanos Par 11/genética , ADN de Neoplasias/sangre , ADN de Neoplasias/genética , Tumor Desmoplásico de Células Pequeñas Redondas/genética , Tumor Desmoplásico de Células Pequeñas Redondas/terapia , Humanos , Masculino , Técnicas de Diagnóstico Molecular , Polimorfismo Genético , Translocación Genética
7.
Clin Oral Investig ; 21(5): 1647-1657, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-27628318

RESUMEN

INTRODUCTION: Podoplanin and ezrin connection through Rho-A phosphorylation have been suggested as part of the activation pathway, in the process of tumor invasion and cell movement in oral squamous cell carcinomas. OBJECTIVE: The aim of this study was to evaluate the correlation among podoplanin, ezrin, and Rho-A immunoexpressions in 91 squamous cells carcinomas of the lower lip and their influence in patient's prognosis. MATERIAL AND METHODS: The immunoexpressions of podoplanin, ezrin, and Rho-A were evaluated through a semi-quantitative score method, based on the capture of 10 microscopic fields at the front of tumor invasion. The association and correlation of these proteins with the clinicopathological features were verified by Fischer's exact test and Spearman's test. The prognostic values were analyzed by Kaplan-Meier method and log-rank test. RESULTS: A statistically significant association between strong cytoplasmic podoplanin expression and alcohol (p = 0.024), loco-regional recurrences (p = 0.028), and lymph node metastasis (pN+) (p = 0.010) was found. The membranous (p = 0.000 and r = 0.384) and cytoplasmic (p = 0.000 and r = 0.344) podoplanin expression was statistically correlated with ezrin expression. Also, membranous podoplanin was significantly correlated with Rho-A expression (p = 0.006 and r = 0.282). The expressions of podoplanin, ezrin, and Rho-A were not significant prognostic factors for patients with squamous cell carcinomas of the lower lip. CONCLUSIONS: Therefore, our results confirm a correlation among podoplanin, ezrin, and Rho-A expressions in squamous cell carcinoma of the lip suggesting a cooperative participation of these proteins in cell movement and invasion. CLINICAL RELEVANCE: Furthermore, strong cytoplasmic podoplanin expression could be helpful to identify patients with squamous cell carcinoma of the lip and lower risk of loco-regional recurrences.


Asunto(s)
Carcinoma de Células Escamosas/patología , Proteínas del Citoesqueleto/metabolismo , Neoplasias de los Labios/patología , Glicoproteínas de Membrana/metabolismo , Invasividad Neoplásica/patología , Proteína de Unión al GTP rhoA/metabolismo , Anciano , Biomarcadores de Tumor/metabolismo , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Fosforilación , Pronóstico , Factores de Riesgo
8.
Pak J Pharm Sci ; 30(5): 1545-1550, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-29084671

RESUMEN

Glutamate decarboxylase or glutamic acid decarboxylase (GAD) is a protein associated with autoimmune diseases, including type-1 diabetes. This disease is primarily associated with the occurrence of a specific isoform: GAD65. Conversely, some specific peptides of this protein may block autoimmunity in diabetes. In this respect, understanding the relationship between GAD and the development of diabetes is important, and it is necessary to understand the role of each GAD peptide to design effective autoimmune diabetes treatments. The purpose of the present study was to analyze the effects of treatment with GAD-derived peptides p217 and p290 on INS receptors in the salivary epithelium of nonobese diabetic (NOD) animals. Three groups of 7 mice each were studied: I, BALB/c mice (control); II, NOD mice; and III, NOD mice treated with peptides p290 and p217. Groups I and II only received buffered saline solution. Glucose levels were measured daily during the 21 days of the experiment. After the study, the animals were euthanized and the parotid and submandibular glands were removed for the analysis of INS-R by fluorescence microscopy. Therapy with two peptides together was associated with reduced glucose levels in NOD mice and intense INS-R expression in both salivary organs. Our approach of combining GAD p217 and p290 peptides contributed to hormonal balance and promoted the repair of INS-R.


Asunto(s)
Diabetes Mellitus Tipo 1/tratamiento farmacológico , Células Epiteliales/efectos de los fármacos , Glutamato Descarboxilasa/metabolismo , Hipoglucemiantes/farmacología , Glándula Parótida/efectos de los fármacos , Fragmentos de Péptidos/farmacología , Receptor de Insulina/metabolismo , Glándula Submandibular/efectos de los fármacos , Animales , Biomarcadores/sangre , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/enzimología , Diabetes Mellitus Tipo 1/patología , Modelos Animales de Enfermedad , Células Epiteliales/enzimología , Células Epiteliales/patología , Femenino , Ratones Endogámicos BALB C , Ratones Endogámicos NOD , Glándula Parótida/enzimología , Glándula Parótida/patología , Glándula Submandibular/enzimología , Glándula Submandibular/patología
9.
J Surg Oncol ; 112(2): 179-82, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-26227662

RESUMEN

BACKGROUND: Sentinel lymph nodes (SLN) in popliteal basins are rare, and there is controversy in literature regarding their origin, management, and outcomes. OBJECTIVES: To correlate clinical and pathological features of popliteal basin drainage and analyze the impact of popliteal lymph node drainage on survival. MATERIALS AND METHODS: Retrospective analysis of SLN biopsies performed at a single institution between 2000 and 2010. RESULTS: SLN biopsies were performed in 254 patients with melanoma in lower limbs, 247 of which were evaluated. In this group, there were 59 patients (24%) with a positive SLN. Twenty-seven cases (11%) presented with popliteal drainage, one of which lacked concurrent groin drainage. Among these 27 patients, three (11%) had popliteal metastasis, one of which had exclusive involvement of this basin. Popliteal drainage was associated with worse 5-year disease-free survival (DFS) (P = 0.028) but not 5-year overall survival (OS) (P = 0.219) in univariate analysis. In multivariate analysis, Breslow thickness, mitotic index, and positive SLN were prognostic factors for DFS. Only mitotic index correlated significantly with OS (P = 0.044). CONCLUSIONS: Popliteal drainage seems to be associated with worse prognostic features of the primary tumor.


Asunto(s)
Extremidad Inferior , Ganglios Linfáticos/patología , Melanoma/patología , Melanoma/cirugía , Biopsia del Ganglio Linfático Centinela , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/cirugía , Adulto , Anciano , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Escisión del Ganglio Linfático , Ganglios Linfáticos/cirugía , Metástasis Linfática/diagnóstico , Masculino , Persona de Mediana Edad , Vena Poplítea , Estudios Retrospectivos
10.
Dermatol Ther ; 28(5): 296-9, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26032175

RESUMEN

The purpose of our study was to verify the results of the association of Q-switched Nd: YAG non-ablative fractionated with intense pulsed light, in order to treat patients with refractory melasma. The combination of these two devices seems to be the best treatment to combat hyperpigmentation produced by melasma, with low occurrence of side effects, which may be justified by the selective photothermolysis at subcellular level.


Asunto(s)
Láseres de Estado Sólido/uso terapéutico , Terapia por Luz de Baja Intensidad/métodos , Melanosis/radioterapia , Adulto , Estudios de Seguimiento , Humanos , Melanosis/patología , Resultado del Tratamiento
12.
Arch Oral Biol ; 162: 105943, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38479278

RESUMEN

OBJECTIVE: Pleomorphic adenoma (PA), mucoepidermoid carcinoma (MEC), and adenoid cystic carcinoma (ACC) are the most prevalent salivary gland tumors. Their pathogenesis has been recently associated with complex molecular cascades, including the TGFß signaling pathway. The aim of this study was to evaluate the expression of genes associated with the TGFß signaling pathway (TGFB1, ITGB6, SMAD2, SMAD4, FBN1, LTBP1, and c-MYC) to map possible downstream alterations in the TGFß cascade. DESIGN: Thirteen PA, 17 MEC, 13 ACC, and 10 non-neoplastic salivary gland samples were analyzed by real-time RT-PCR. RESULTS: Cases of PA presented increased TGFB1, LTPB1, c-MYC, and FBN1 expressions, whereas SMAD2 expression was decreased when compared to non-neoplastic tissue. MEC patients displayed increased expressions of TGFB1, ITGB6, FBN1, and c-MYC and decreased expressions of SMAD2 and SMAD4. ACC cases exhibited elevated expressions of the investigated genes except TGFB1. The present results suggest that decreased expression of SMAD2 and SMAD4 does not impede the transcriptional regulation of c-MYC, especially in PA and MEC. Increased expressions of ITGB6, TGFB1, LTBP1, and FBN1 appear to be related to the regulation of the TGFß signaling pathway in these tumors. Additionally, we observed a higher expression of SMAD4 in ACC and a raised expression of ITGB6 and lowered expression of SMAD2 in MEC. CONCLUSIONS: Our study demonstrated the differential expression of TGFß cascade members in salivary gland tumors such as SMAD2/SMAD4 and c-MYC as well as the participation of ITGB6, TGFB1, LTBP1, and FBN1, contributing to the understanding of the mechanisms involved in tumor progression.


Asunto(s)
Adenoma Pleomórfico , Carcinoma Adenoide Quístico , Carcinoma Mucoepidermoide , Neoplasias de las Glándulas Salivales , Factor de Crecimiento Transformador beta , Humanos , Adenoma Pleomórfico/genética , Adenoma Pleomórfico/metabolismo , Adenoma Pleomórfico/patología , Biomarcadores de Tumor/metabolismo , Carcinoma Adenoide Quístico/genética , Carcinoma Adenoide Quístico/metabolismo , Carcinoma Mucoepidermoide/metabolismo , Neoplasias de las Glándulas Salivales/genética , Neoplasias de las Glándulas Salivales/metabolismo , Transducción de Señal , Factor de Crecimiento Transformador beta/metabolismo
13.
J Bras Pneumol ; 50(2): e20230343, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38747814

RESUMEN

OBJECTIVE: To review the pathological diagnosis of possible cases and/or hidden cases of malignant mesothelioma (MM) between 2000 and 2012 using the Hospital-Based Cancer Registry database in the state of São Paulo, Brazil. METHODS: Possible cases were retrieved by assessing the database. Inclusion criteria were being older than 30 years of age and having ICD-O-3 topography and morphology codes related to MM. A board of expert pathologists reviewed the pathology reports and requested paraffin blocks in cases that demanded revision. After staining with calretinin, D2-40, WT-1 (as positive MM markers) and Ber-EP4 and MOC31 (as negative MM markers), cases were divided and studied independently by a pair of pathologists to confirm or discard the diagnosis of MM. RESULTS: Our sample comprised 482 cases from 25 hospitals, and 130 needed further histological revision. We received 73 paraffin blocks with adequate material. After board analysis, there were 9 cases with a definitive diagnosis of MM, improving the diagnostic rate in 12%. Two cases of previously diagnosed MM were discarded by review. CONCLUSIONS: Our results confirm that part of MM underdiagnosis and underreporting in Brazil is due to incomplete or mistaken pathological diagnosis.


Asunto(s)
Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Sistema de Registros , Humanos , Brasil/epidemiología , Mesotelioma/patología , Mesotelioma/epidemiología , Mesotelioma/diagnóstico , Mesotelioma Maligno/patología , Masculino , Femenino , Persona de Mediana Edad , Anciano , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/epidemiología , Adulto , Anciano de 80 o más Años , Biomarcadores de Tumor/análisis , Neoplasias Pleurales/patología , Neoplasias Pleurales/epidemiología , Neoplasias Pleurales/diagnóstico
14.
Oral Oncol ; 143: 106462, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37331036

RESUMEN

Clear cell odontogenic carcinoma (CCOC) is a rare malignant odontogenic tumour (MOT) that mainly affects the mandible, with a slight female predominance in adult patients. In this study, we described an exuberant CCOC in mandible of a 22-year-female patient. On radiographic examination, a radiolucent lesion in the region of tooth 36 to 44 with tooth displacement and alveolar cortical resorption was observed. Histopathological study revealed a malignant neoplasm of the odontogenic epithelium, composed of PAS-positive clear cells and immunoreactivity for CK5, CK7, CK19, p63. The Ki-67 index was low (<10 %). Fluorescent in situ hybridization revealed EWSR1 gene rearrangement. The diagnosis of CCOC was established and the patient was referred for surgical treatment.


Asunto(s)
Carcinoma , Neoplasias de la Boca , Tumores Odontogénicos , Femenino , Humanos , Hibridación Fluorescente in Situ , Mandíbula/patología , Tumores Odontogénicos/diagnóstico , Tumores Odontogénicos/genética , Tumores Odontogénicos/patología , Proteína EWS de Unión a ARN/genética , Adulto Joven
15.
Biomed Pharmacother ; 167: 115559, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37742611

RESUMEN

Oral cavity squamous cell carcinoma (OSCC) is a complex and dynamic disease characterized by clinicopathological and molecular heterogeneity. Spatial and temporal heterogeneity of cell subpopulations has been associated with cancer progression and implicated in the prognosis and therapy response. Emerging evidence indicates that aberrant epigenetic profiles in OSCC may foster an immunosuppressive tumor microenvironment by modulating the expression of immune-related long non-coding RNAs (lncRNAs). DNA methylation analysis was performed in 46 matched OSCC and normal adjacent tissue samples using a genome-wide platform (Infinium HumanMethylation450 BeadChip). Reference-based computational deconvolution (MethylCIBERSORT) was applied to infer the immune cell composition of the bulk samples. The expression levels of genes encoding immune markers and differentially methylated lncRNAs were investigated using The Cancer Genome Atlas dataset. OSCC specimens presented distinct immune cell composition, including the enrichment of monocyte lineage cells, natural killer cells, cytotoxic T-lymphocytes, regulatory T-lymphocytes, and neutrophils. In contrast, B-lymphocytes, effector T-lymphocytes, and fibroblasts were diminished in tumor samples. The hypomethylation of three immune-associated lncRNAs (MEG3, MIR155HG, and WFDC21P) at individual CpG sites was confirmed by bisulfite-pyrosequencing. Also, the upregulation of a set of immune markers (FOXP3, GZMB, IL10, IL2RA, TGFB, IFNG, TDO2, IDO1, and HIF1A) was detected. The immune cell composition, immune markers alteration, and dysregulation of immune-associated lncRNAs reinforce the impact of the immune microenvironment in OSCC. These concurrent factors contribute to tumor heterogeneity, suggesting that epi-immunotherapy could be an efficient alternative to treat OSCC.

16.
Sci Rep ; 13(1): 28, 2023 01 02.
Artículo en Inglés | MEDLINE | ID: mdl-36593236

RESUMEN

Lesions with bone loss may require autologous grafts, which are considered the gold standard; however, natural or synthetic biomaterials are alternatives that can be used in clinical situations that require support for bone neoformation. Collagen and hydroxyapatite have been used for bone repair based on the concept of biomimetics, which can be combined with chitosan, forming a scaffold for cell adhesion and growth. However, osteoporosis caused by gonadal hormone deficiency can thus compromise the expected results of the osseointegration of scaffolds. The aim of this study was to investigate the osteoregenerative capacity of collagen (Co)/chitosan (Ch)/hydroxyapatite (Ha) scaffolds in rats with hormone deficiency caused by experimental bilateral ovariectomy. Forty-two rats were divided into non-ovariectomized (NO) and ovariectomized (O) groups, divided into three subgroups: control (empty defect) and two subgroups receiving collagen/chitosan/hydroxyapatite scaffolds prepared using different methods of hydroxyapatite incorporation, in situ (CoChHa1) and ex situ (CoChHa2). The defect areas were submitted to macroscopic, radiological, and histomorphometric analysis. No inflammatory processes were found in the tibial defect area that would indicate immune rejection of the scaffolds, thus confirming the biocompatibility of the biomaterials. Bone formation starting from the margins of the bone defect were observed in all rats, with a greater volume in the NO groups, particularly the group receiving CoChHa2. Less bone formation was found in the O subgroups when compared to the NO. In conclusion, collagen/chitosan/hydroxyapatite scaffolds stimulate bone growth in vivo but abnormal conditions of bone fragility caused by gonadal hormone deficiency may have delayed the bone repair process.


Asunto(s)
Quitosano , Durapatita , Femenino , Ratas , Animales , Regeneración Ósea , Materiales Biocompatibles , Colágeno , Andamios del Tejido
17.
Head Neck ; 44(3): 691-697, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-34904762

RESUMEN

BACKGROUND: To evaluate margins for oral carcinoma according to types of invasion front. METHODS: Retrospective cohort of 772 patients with worst pattern of invasion (WPOI) graded 1-5. Local recurrence was the outcome of interest. RESULTS: Local recurrences occurred in 164 patients (21.2%) and was affected by WPOI type 4/5, margin distance, perineural invasion, and adjuvant radiotherapy. In patients with WPOI types 1/2/3, a cutoff of 1.7 mm was considered ideal margin extent and in patients with WPOI types 4/5, the cutoff was 7.8 mm. Patients below these thresholds had a significantly higher incidence of local recurrence. CONCLUSIONS: Different WPOI determine the ideal extent of surgical margins as 1.7 mm for patients with types 1-3, and 7.8 mm in patients with types 4/5.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/cirugía , Neoplasias de Cabeza y Cuello/patología , Humanos , Márgenes de Escisión , Neoplasias de la Boca/patología , Neoplasias de la Boca/cirugía , Invasividad Neoplásica/patología , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Carcinoma de Células Escamosas de Cabeza y Cuello/patología
18.
Arch Dermatol Res ; 314(6): 563-571, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34152481

RESUMEN

Facial melanoma presents itself as a brownish macula, being difficult to differentiate it from benign pigmented lesions of the face on clinical examination. Reflectance confocal microscopy (RCM) assists in diagnosing facial lesions in which dermoscopy has limitations, allowing to increase the diagnostic accuracy. The study aimed to analyze the RCM features of pigmented isolated lesions of the face for diagnosing melanoma. Also, we sought to establish the chance of a pigmented lesion on the face being a melanoma using RCM criteria. In this retrospective and prospective study, 105 clinical pigmented lesions on the face underwent RCM, and cytoarchitectural features in the epidermis, the dermo-epidermal junction (DEJ), and dermis were described. For statistical analysis, the exact chi-square test was applied to the RCM criteria. The odds ratio was estimated using univariate logistic regression. Finally, we used the multiple logistic regression method for creating a nomogram to predict the chance of a lesion being a melanoma. After univariate and multivariate logistic regression, atypical round nucleated cells within the epidermis, pagetoid spread, and follicular dendritic cells presented as statistically significant features. Then, a complex nomogram was created to give the chance of a pigmented lesion on the face being a melanoma. The presence of these three features resulted in a 98% probability for melanoma. This study allowed to estimate the diagnosis of melanoma on the face, using RCM, practicable and feasible in the daily routine, through the presence of some RCM nomogram criteria.


Asunto(s)
Melanoma , Neoplasias Cutáneas , Dermoscopía/métodos , Diagnóstico Diferencial , Humanos , Melanoma/diagnóstico por imagen , Melanoma/patología , Microscopía Confocal/métodos , Probabilidad , Estudios Prospectivos , Estudios Retrospectivos , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/patología
19.
An Bras Dermatol ; 97(5): 583-591, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35803765

RESUMEN

BACKGROUND: Basal cell and squamous cell carcinomas (BCC and SCC) are the most common types of cancer worldwide. Intraoperative assessment of surgical margins by frozen section has been widely used to ensure disease-free margins. The intraoperative "en face" freezing technique evaluates all peripheral and deep margins. OBJECTIVE: To report the results of the "en face" freezing technique in relation to tumor recurrence and agreement with paraffin-embedded tissue examination. METHODS: Retrospective analysis of patients undergoing surgical excision of BCC and SCC at the A. C. Camargo Cancer Center, Brazil. RESULTS: This study included 542 skin carcinomas, which were excised from 397 patients. A total of 201 male patients (50.6%), and 196 female patients (49.4%) were assessed, whose mean age was 64 years. The tumors were mostly located on the head and neck region (87.8%). BCC corresponded to 79.7% of the cases. The mean follow-up was 38 months. Tumor relapse occurred in 0.86% of the primary tumors and 3.7% of recurrent tumors. The result of the intraoperative "en face" frozen section evaluation was in agreement with the final result of the anatomopathological examination (paraffin test) in 98% of the lesions. STUDY LIMITATIONS: Not having a minimum follow-up time of 5 years for all patients. CONCLUSION: The "en face" freezing technique shows low tumor relapse, being reliable and safe to guarantee negative surgical margins of the tumor.


Asunto(s)
Carcinoma Basocelular , Neoplasias Cutáneas , Femenino , Secciones por Congelación , Humanos , Masculino , Márgenes de Escisión , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Estudios Retrospectivos
20.
Braz J Otorhinolaryngol ; 88(4): 523-528, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-32972866

RESUMEN

INTRODUCTION: Papillary thyroid carcinoma is the most frequent endocrine neoplasia and its incidence has tripled over the past 35 years. Although papillary thyroid carcinoma carries a good prognosis, 10%-30% of patients still develop recurrence and metastasis. Some clinical and genetic features are associated with worse prognosis. The most frequent mutation is the BRAF p.V600E, which has been associated with many clinical features of poor prognosis. However, many studies have produced controversial results without any association between BRAF mutation and clinicopathological features of poor prognosis. OBJECTIVE: Since the prognostic value of BRAF mutations remains controversial, this study aims to investigate the importance of this mutation in therapeutic decisions for papillary thyroid carcinoma. METHODS: Therefore, we evaluated whether the presence of BRAF mutation is associated with features of poor prognosis in 85 patients with papillary thyroid carcinoma older than 45 years treated at A.C. Camargo Cancer Center, from 1980 to 2007. BRAF mutation was evaluated by pyrosequencing. Statistical analysis was performed using SPSS. RESULTS: The mean age of patients was 54 years (range: 45 - 77 years), 73 were women (85.8%) and 12 were men (14.2%). Among them, 39 cases (45.9%) presented extrathyroidal extension and 11 cases had recurrent disease. BRAF mutation was detected in 57 (67%) patients. No significant association was observed between BRAF mutation and gender (p  = 0.743), age (p  = 0.236), N-stage (p  = 0.423), vascular and perineural infiltration (p  = 0.085 or multifocality (p  = 1.0). Although not statistically significant, the majority of patients with recurrent disease were BRAF positive (9 out of 11) (p  = 0.325). Patients affected by BRAF mutation are associated with tumors larger than 1 cm (p  = 0.034) and with extrathyroidal extension (p  = 0.033). CONCLUSION: Although BRAF testing is widely available, there are no consistent data to support improvement in outcomes from incorporating it into therapeutic decision for thyroid cancer.


Asunto(s)
Proteínas Proto-Oncogénicas B-raf , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mutación , Pronóstico , Proteínas Proto-Oncogénicas B-raf/genética , Cáncer Papilar Tiroideo/genética , Cáncer Papilar Tiroideo/patología , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/patología
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