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SUMMARY: Esophageal cancer is one of the most aggressive gastrointestinal cancers. Invasion and metastasis are the main causes of poor prognosis of esophageal cancer. SPRY2 has been reported to exert promoting effects in human cancers, which controls signal pathways including PI3K/AKT and MAPKs. However, the expression of SPRY2 in esophageal squamous cell carcinoma (ESCC) and its underlying mechanism remain unclear. In the present study, we aimed to investigate the detailed role of SPRY2 in the regulation of cell proliferation, invasion and ERK/AKT signaling pathway in ESCC. It was identified that the expression level of SPRY2 in ESCC was remarkably decreased compared with normal tissues, and it was related to clinicopathologic features and prognosis ESCC patients. The upregulation of SPRY2 expression notably inhibited the proliferation, migration and invasion of Eca-109 cells. In addition, the activity of ERK /AKT signaling was also suppressed by the SPRY2 upregulation in Eca-109 cells. Our study suggests that overexpression of SPRY2 suppress cancer cell proliferation and invasion of by through suppression of the ERK/AKT signaling pathways in ESCC. Therefore, SPRY2 may be a promising prognostic marker and therapeutic target for ESCC.
El cáncer de esófago es uno de los cánceres gastrointestinales más agresivos. La invasión y la metástasis son las principales causas de mal pronóstico del cáncer de esófago. Se ha informado que SPRY2 ejerce efectos promotores en los cánceres humanos, que controla las vías de señales, incluidas PI3K/AKT y MAPK. Sin embargo, la expresión de SPRY2 en el carcinoma de células escamosas de esófago (ESCC) y su mecanismo subyacente aún no están claros. En el presente estudio, nuestro objetivo fue investigar el papel detallado de SPRY2 en la regulación de la proliferación celular, la invasión y la vía de señalización ERK/AKT en ESCC. Se identificó que el nivel de expresión de SPRY2 en ESCC estaba notablemente disminuido en comparación con los tejidos normales, y estaba relacionado con las características clínico-patológicas y el pronóstico de los pacientes con ESCC. La regulación positiva de la expresión de SPRY2 inhibió notablemente la proliferación, migración e invasión de células Eca-109. Además, la actividad de la señalización de ERK/AKT también fue suprimida por la regulación positiva de SPRY2 en las células Eca-109. Nuestro estudio sugiere que la sobreexpresión de SPRY2 suprime la proliferación y la invasión de células cancerosas mediante la supresión de las vías de señalización ERK/AKT en ESCC. Por lo tanto, SPRY2 puede ser un marcador de pronóstico prometedor y un objetivo terapéutico para la ESCC.
Subject(s)
Humans , Esophageal Neoplasms/metabolism , Intracellular Signaling Peptides and Proteins/metabolism , Esophageal Squamous Cell Carcinoma/metabolism , Membrane Proteins/metabolism , Immunohistochemistry , Biomarkers, Tumor , Blotting, Western , Extracellular Signal-Regulated MAP Kinases , Cell Proliferation , Proto-Oncogene Proteins c-aktABSTRACT
Abstract Objective Cutaneous Squamous Cell Carcinoma (cSCC), a tumor with a significantly increasing incidence, is mostly diagnosed in the head region, where tumors have a worse prognosis and a higher risk of metastases. The presence of metastases reduces specific five-year survival from 99% to 50%. As the risk of occult metastases does not exceed 10%, elective dissection of the tributary parotid and neck lymph nodes is not recommended. Methods We retrospectively analyzed a group of 12 patients with cSCC of the head after elective dissections of regional (parotid and cervical) nodes by means of superficial parotidectomy and selective neck dissection. Results We diagnosed occult metastases neither in the cervical nor parotid nodes in any patient. None were diagnosed as a regional recurrence during the follow-up period. Conclucion Our negative opinion on elective parotidectomy and neck dissection in cSCC of the head is in agreement with the majority of published studies. These elective procedures are not indicated even for tumors showing the presence of known (clinical and histological) risk factors for lymphogenic spread, as their positive predictive value is too low. Elective parotidectomy is individually considered as safe deep surgical margin. If elective parotidectomy is planned it should include only the superficial lobe. Completion parotidectomy and elective neck dissection are done in rare cases of histologically confirmed parotid metastasis in the parotid specimen. Preoperatively diagnosed parotid metastases without neck involvement are sent for total parotidectomy and elective selective neck dissection. Cases of clinically evident neck metastasis with no parotid involvement, are referred for comprehensive neck dissection and elective superficial parotidectomy. The treatment of concurrent parotid and cervical metastases includes total conservative parotidectomy and comprehensive neck dissection. Level of evidence How common is the problem? Step 4 (Case-series) Is this diagnostic or monitoring test accurate? (Diagnosis) Step 4 (poor or non-independent reference standard) What will happen if we do not add a therapy? (Prognosis) Step 4 (Case-series) Does this intervention help? (Treatment Benefits) Step 4 (Case-series) What are the COMMON harms? (Treatment Harms) Step 4 (Case-series) What are the RARE harms? (Treatment Harms) Step 4 (Case-series) Is this (early detection) test worthwhile? (Screening) Step 4 (Case-series)
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ABSTRACT BACKGROUND: The prevalence of chronic kidney disease (CKD) has increased in the recent decades, along with the number of patients in the terminal stages of this disease, requiring transplantation. Some skin disorders are more frequent in patients with CKD and in renal transplant recipients (RTR). OBJECTIVES: To evaluate the frequency of skin diseases in RTR and patients with CKD receiving conservative treatment. DESIGN AND SETTING: This observational cross-sectional study recruited consecutive patients with CKD and RTR from a nephrology clinic at a teaching hospital in Brazil between 2015 and 2020. METHODS: Quantitative, descriptive, and analytical approaches were used. The sample was selected based on convenience sampling. Data were collected from dermatological visits and participants' medical records. RESULTS: Overall, 308 participants were included: 206 RTR (66.9%, median age: 48 years, interquartile range [IQR] 38.0-56.0, 63.6% men) and 102 patients with CKD (33.1%, median age: 61.0 years, IQR 50.0-71.2, 48% men). The frequency of infectious skin diseases (39.3% vs. 21.6% P = 0.002) were higher in RTR than in patients with CKD. Neoplastic skin lesions were present in nine (4.4%) RTR and in only one (1.0%) patient with CKD. Among the RTR, the ratio of basal cell carcinoma to squamous cell carcinoma was 2:1. CONCLUSIONS: This study revealed that an increased frequency of infectious skin diseases may be expected in patients who have undergone kidney transplantation. Among skin cancers, BCC is more frequently observed in RTR, especially in those using azathioprine.
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Background: The tongue is susceptible to a multitude of conditions that can be of developmental, neoplastic, or inflammatory nature, whose occurrence varies globally by age, sex, and ethnicity. The objective of the present study was to determine the incidence of tongue lesions among cases managed in a tertiary hospital in Tanzania. Methods: This study analyzed histological results of patients with tongue lesions diagnosed between 2016 and 2021. Data on the age and sex of the patients and histological diagnosis were collected. Data analysis was done using Statistical Package for the Social Sciences version 27. Results: A total of 190 samples of tongue lesions were studied and 18 different histological diagnoses were observed. Generally, a majority (84.2%) of the biopsied tongue lesions were malignant. The most common (74.7%) lesions diagnosed were squamous cell carcinoma followed by hemangioma (5.3%). A significant association was noted between the nature of the lesions and the age group and sex of the patients. Conclusion: This analysis depicts that tongue lesions are frequently encountered in patients managed in tertiary health facilities in Tanzania. A majority of these lesions are malignant tumors. The sex and age of the patients are determining factors for the occurrence of tongue lesions
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Humans , Male , Female , Tongue , Health FacilitiesABSTRACT
Objective@#To explore the molecular mechanism of resveratrol (RES) in the treatment of oral squamous cell carcinoma (OSCC) through the use of biological information methods such as network pharmacology and molecular docking and to provide a theoretical reference for the clinical application of RES in the treatment of OSCC.@*Methods@#The Swiss Target Prediction(http://www.swisstargetprediction.ch), SEA (http://sea.bkslab.org)database, and Pharm mapper database(http://lilab-ecust.cn) were used to retrieve RES-related targets, and the DISGENET (www.disgenet.org), OMIM (https://omim.org) and GeneCards (https://www.genecards.org) databases were used to screen OSCC disease targets. The intersection of drugs and disease targets was determined, and Cytoscape 3.7.2 software was used to construct a "drug-diseasetarget pathway" network. The Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database was used to construct a target protein interaction network, and the DAVID database was used for enrichment analysis of key proteins. Finally, molecular docking validation of key proteins was performed using AutoDock and PyMOL. The enrichment analysis and molecular docking results were integrated to predict the possible molecular mechanisms of RES treatment in OSCC; western blot was used to determine the effect of resveratrol at different concentrations (50, 100) μmol/L on the expression of Src tyrosine kinase (SRC), epidermal growth factor receptor (EGFR), estrogen receptor gene 1 (ESR1), and phosphatidylinositol 3 kinase/protein kinase B (PI3K/AKT) signaling pathway proteins in OSCC HSC-3 cells.@*Results@#A total of 243 targets of RES drugs and 6 094 targets of OSCC were identified. A total of 116 potential common targets were obtained by intersecting drugs with disease targets. These potential targets mainly participate in biological processes such as in vivo protein self-phosphorylation, peptide tyrosine phosphorylation, transmembrane receptor protein tyrosine kinase signaling pathway, and positive regulation of RNA polymerase Ⅱ promoter transcription, and they interfere with the PI3K/AKT signaling pathway to exert anti-OSCC effects. The docking results of resveratrol with OSCC molecules indicated that key targets, such as EGFR, ESR1, and SRC, have good binding activity. The results of cell-based experiments showed that resveratrol inhibited the protein expression of SRC, EGFR, ESR1, p-PI3K, and p-AKT in HSC-3 cells in a dose-dependent manner.@*Conclusion@#RES can inhibit the expression of its targets EGFR, ESR1, SRC, p-PI3K, and p-AKT in OSCC cells.
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Objective@#To explore the photodynamic treatment method and therapeutic effect of oral verrucous carcinoma and to provide a reference for the clinic.@*Methods@#This study follows the requirements of medical ethics. This paper summarized the photodynamic treatment of an oral verrucous carcinoma with a diameter of approximately 2.5 cm in the right buccal mucosa and retrospectively analyzed the characteristics and treatment of oral verrucous carcinoma and the photodynamic treatment of potential malignant lesions of the oral mucosa through a review of the literature.@*Results@#After four rounds of photodynamic therapy, the size of the right buccal lesion was significantly reduced. After 6 months of follow-up, the white verrucous hyperplasia of the right buccal mucosa had completely subsided, and there was no obvious scar formation. Three years after treatment, there was no recurrence of the lesion in the right buccal mucosa and no obvious scar formation in the treated area. The degree of mouth opening was 3 fingers, and there was no lymph node enlargement in the bilateral submandibular, submental or neck. The literature review shows that oral verrucous carcinoma is a rare subtype of squamous cell carcinoma with the characteristics and biological behaviors of slow growth, low malignancy, and rare metastasis. Surgery is the preferred treatment, but there are some limitations. Photodynamic therapy is a minimally invasive, repeatable treatment with mild adverse reactions. In recent years, photodynamic therapy has been gradually applied for the treatment of potential malignant disorders of the oral mucosa and early oral squamous cell carcinoma and has achieved positive results, but it has not been reported for the treatment of oral verrucous cancer@*Conclusion@#Photodynamic therapy is a new option for nonsurgical resection of oral verrucous carcinoma.
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@#Objective To investigate the effects of targeted silencing of CXCL5 on the related biological functions of laryngeal squamous cell carcinoma(LSCC)cell line AMC-HN-8,and analyze the regulation through TCGA database.Methods RNA-seq data related to LSCC were obtained from TCGA database,and the expression differences of CXCL5 gene in LSCC and the adjacent tissues were analyzed. Total 60 samples of LSCC and the adjacent tissues from January 2019 to December 2020 were selected from the First Hospital of Shanxi Medical University,and the expression of CXCL5 protein in LSCC tissues was detected by immunohistochemical staining. Human LSCC cell line AMC-HN-8 was cultured and the mRNA transcription level of CXCL5 in AMC-HN-8 cells was detected by qPCR. Two groups of SiRNA with high knock-down efficiency were screened,CCK8 assay was used to detect the cell proliferation,Transwell test was used to measure the cell invasion and migration,and flow cytometry was used to detect the cell cycle and apoptosis. The correlation between CXCL5and tumor immune invasion level of LSCC was analyzed by ssGSEA,and CXCL5 co-expression gene network was constructed and analyzed for GO and KEGG enrichment.Results Compared with the adjacent tissues and the cells in control group,the expression of CXCL5 in LSCC tissues and cells increased,which was consistent with the analysis of TCGA database;Inhibition of CXCL5 expression in AMC-HN-8 cells inhibited the proliferation,invasion and migration of tumor cells,and promoted the apoptosis through inhibiting the cell cycle in G1 phase;The immune cell scores in DC,neutrophils,NK and TH17 cells were different.Conclusion CXCL5gene is highly expressed in LSCC tissues,which might be one of the targets of LSCC targeted therapy.
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Introducción: El cáncer escamocelular de cavidad oral es una patología con bajas tasas de sobrevivencia. Cuando no es tratado adecuadamente es un tumor de alta recurrencia y resistente al tratamiento. Nuevas hipótesis plantean que las células tumorales progenitoras por sus propiedades de auto renovación, iniciación tumoral, migración y metástasis pueden ser responsables de la manutención y renovación de este tumor. Sin embargo, aún no existe un consenso sobre la verdadera participación de ellas, debido a que su identificación y caracterización es aún un reto experimental. Objetivo: En este trabajo se busca detectar células con expresión de marcadores de células tumorales Progenitoras en muestras cáncer escamocelular de cavidad oral y relacionarlo con los estadios de diferenciación del tumor. Metodología: En esta investigación se tomaron 32 muestras de pacientes con carcinoma escamocelular de cavidad oral. Se logró detectar in situ, mediante la técnica de inmunofluorescencia, cuatro reconocidos marcadores de células tumorales progenitoras. Resultados: Se identificaron los marcadores OCT4, SSEA4, NANOG y TRA-1-60 en los diferentes estadios de diferenciación tumoral, lo que sugiere la participación de las células progenitoras tumorales en la evolución de esta patología. Conclusiones: El establecimiento y correcta identificación de las células tumorales progenitoras abre nuevas vías terapéuticas para el abordaje de este tumor, en busca de mejorar el pronóstico, tasa de sobrevivencia y calidad de vida del paciente.
Introduction: Squamous cell carcinoma of the oral cavity is a pathology with poor survival rates. When it is not adequately treated, it is a tumor with high recurrence and resistance to treatment. According to new hypotheses, progenitor tumor cells, due to their properties of self-renewal, tumor initiation, migration, and metastasis, could be responsible for the maintenance and renewal of this tumor. However, there is still no consensus on their true participation, subsequent to difficult in their identification and characterization. Materials and methods: In this research, 32 samples provided from patients diagnosis with squamous cell carcinoma of the oral cavity were used. To detect specific markers progenitor tumor cells were used immunofluorescence microscopy. Results: The cells markers OCT4, SSEA4, NANOG and TRA-1-60 were identified in the different stages of the tumor samples, all these findings suggest the role of tumor progenitor cells in the evolution of this pathology. Conclusions: The establishment and correct identification of the progenitor tumor cells provide new therapeutic options for the approach of this tumor seeking to improve the prognosis, survival rate and quality of life of the patient.
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SUMMARY: This study is to investigate the effect of survivin down-regulation by Egr1-survivin shRNA combined with radiotherapy on the apoptosis and radiosensitivity of esophageal squamous cell carcinoma ECA109 and KYSE150 cells. ECA109 and KYSE150 cells were transfected with Egr1-survivin shRNA, and then treated with radiotherapy. After 24 h, the mRNA and protein levels of Egr1-survivin were detected by qPCR and Western-Blot. Cell cycle and apoptosis were detected by flow cytometry. Western blot also detected levels of cleavaged Caspase 3 and Caspase 9. YM155 was used as a positive control to inhibit survivin expression. The levels of survivin mRNA and protein in ECA109 and KYSE150 cells treated with Egr1-survivin shRNA combined with radiotherapy were significantly lower than those of the blank control group, the empty vector control group, and, the YM155 + radiotherapy group (P<0.05). Meanwhile, after survivin down-regulation, the ratio of G2 to S phase of ECA109 and KYSE150 cells increased significantly, leading to significant G2 and S phase arrest. Additionally, apoptosis of ECA109 and KYSE150 cells increased significantly (P <0.01). Further, protein levels of cleavaged Caspase 3 and Caspase 9 significantly increased in Egr1-survivin shRNA combined with radiotherapy group. Egr1-survivin shRNA combined with radiotherapy can down-regulate survivin expression, which further increases the apoptosis, and enhances the radiosensitivity of ECA109 and KYSE150 cells.
Este estudio tuvo como objetivo investigar el efecto de la regulación negativa de survivina por el shRNA de Egr1-survivina combinado con radioterapia sobre la apoptosis y la radiosensibilidad del carcinoma de células escamosas de esófago Células ECA109 y KYSE150. Las células ECA109 y KYSE150 se transfectaron con shRNA de survivina Egr1 y luego se trataron con radioterapia. Después de 24 h, los niveles de ARNm y proteína de Egr1-survivina se detectaron mediante qPCR y Western-Blot. El ciclo celular y la apoptosis se detectaron mediante citometría de flujo. La transferencia Western también detectó niveles de Caspasa 3 y Caspasa 9 escindidas. Se usó YM155 como control positivo para inhibir la expresión de survivina. Los niveles de ARNm y proteína de survivina en células ECA109 y KYSE150 tratadas con shRNA de survivina Egr1 combinado con radioterapia fueron significativamente más bajos que los del grupo control en blanco, el grupo control de vector vacío y el grupo de radioterapia YM155 + (P <0,05). Mientras tanto, después de la regulación negativa de survivina, la proporción entre las fases G2 y S de las células ECA109 y KYSE150 aumentó significativamente, lo que llevó a una detención significativa de las fases G2 y S. Además, la apoptosis de las células ECA109 y KYSE150 aumentó significativamente (P <0,01). Además, los niveles de proteína de Caspasa 3 y Caspasa 9 escindidas aumentaron significativamente en el shRNA de Egr1- survivina combinado con el grupo de radioterapia. El shRNA de survivina de Egr1 combinado con radioterapia puede regular negativamente la expresión de survivina, lo que aumenta aún más la apoptosis y mejora la radiosensibilidad de las células ECA109 y KYSE150.
Subject(s)
Humans , Esophageal Neoplasms/therapy , Survivin , Esophageal Squamous Cell Carcinoma/therapy , Radiation-Sensitizing Agents , Radiation Tolerance , RNA, Messenger , Esophageal Neoplasms/genetics , Esophageal Neoplasms/radiotherapy , Transfection , Down-Regulation , Blotting, Western , Apoptosis , Combined Modality Therapy , RNA, Small Interfering , Cell Line, Tumor/radiation effects , Early Growth Response Protein 1 , Caspase 3 , Caspase 9 , Real-Time Polymerase Chain Reaction , Flow Cytometry , Esophageal Squamous Cell Carcinoma/genetics , Esophageal Squamous Cell Carcinoma/radiotherapyABSTRACT
ABSTRACT Introduction: Previous research demonstrated benefits of late conversion to mTOR inhibitors against cutaneous squamous cell carcinomas (cSCC) in kidney transplant recipients (KTR), despite of poor tolerability. This study investigated whether stepwise conversion to sirolimus monotherapy without an attack dose modified the course of disease with improved tolerability. Methods: This prospective exploratory study included non-sensitized KTR with more than 12-months post-transplant, on continuous use of calcineurin inhibitors (CNI)-based therapy, and with poor-prognosis cSCC lesions. Incidence densities of high-risk cSCC over 3-years after conversion to sirolimus-monotherapy were compared to a non-randomized group with high-risk cSCC but unsuitable/not willing for conversion. Results: Forty-four patients were included (83% male, mean age 60 ± 9.7years, 62% with skin type II, mean time after transplantation 9 ± 5.7years). There were 25 patients converted to SRL and 19 individuals kept on CNI. There was a tendency of decreasing density of incidence of all cSCC in the SRL group and increasing in the CNI group (1.49 to 1.00 lesions/patient-year and 1.74 to 2.08 lesions/patient-year, p = 0.141). The density incidence of moderately differentiated decreased significantly in the SRL group while increasing significantly in the CNI group (0.31 to 0.11 lesions/patient-year and 0.25 to 0.62 lesions/patient-year, p = 0.001). In the SRL group, there were no sirolimus discontinuations, no acute rejection episodes, and no de novo DSA formation. Renal function remained stable. Conclusions: This study suggests that sirolimus monotherapy may be useful as adjuvant therapy of high-risk cSCC in kidney transplant recipients. The conversion strategy used was well tolerated and safe regarding key mid-term transplant outcomes.
RESUMO Introdução: Pesquisas anteriores demonstraram benefícios da conversão tardia para inibidores de mTOR contra carcinomas espinocelulares cutâneos (CECs) em receptores de transplante renal (RTR), apesar da baixa tolerabilidade. Este estudo investigou se a conversão gradual para monoterapia com sirolimo sem dose de ataque modificou o curso da doença com melhor tolerabilidade. Métodos: Esse estudo prospectivo exploratório incluiu RTR não sensibilizados com mais de 12 meses pós-transplante, uso contínuo de terapia imunossupressora baseado em inibidor de calcineurina (CNI) associado a micofenolato de sódio ou azatioprina, com lesões de CECs de mau prognóstico. Comparou-se densidades de incidência de CECs de alto risco durante 3 anos após conversão para monoterapia com sirolimo à um grupo não randomizado com CECs classificados conforme os mesmos critérios de gravidade do grupo sirolimo, mas inadequado/não disposto à conversão. Resultados: Foram incluídos 44 pacientes (83% homens, idade média 60 ± 9,7 anos, 62% com fototipo de pele II, tempo médio pós-transplante 9 ± 5,7 anos). 25 pacientes foram convertidos para SRL e 19 indivíduos mantidos em CNI. Foi observado tendência de diminuição da densidade de incidência de todos CECs no grupo SRL e de aumento no grupo CNI (1,49 a 1,00 lesões/paciente-ano; 1,74 a 2,08 lesões/paciente-ano; p = 0,141). A densidade de incidência de lesões moderadamente diferenciadas diminuiu significativamente no grupo SRL enquanto aumentou significativamente no grupo CNI (0,31 a 0,11 lesões/paciente-ano; 0,25 a 0,62 lesões/paciente-ano; p = 0,001). No grupo SRL não houve descontinuação do sirolimo, nenhum episódio de rejeição aguda e nenhuma formação de DSA de novo. Função renal permaneceu estável. Conclusões: Esse estudo sugere que a monoterapia com sirolimo pode ser útil como terapia adjuvante de CECs de alto risco em RTR. A estratégia de conversão usada foi bem tolerada e segura em relação aos principais desfechos do transplante a médio prazo.
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Introducción: El cáncer de pulmón es un problema de salud pública a escala mundial y Cuba no está exenta de este. Objetivo: Caracterizar a los pacientes diagnosticados con cáncer de pulmón según variables clínicas, epidemiológicas y morfológicas. Métodos: Se realizó un estudio transversal, descriptivo y retrospectivo de los 145 adultos diagnosticados con cáncer de pulmón en el Servicio de Neumología del Hospital General Docente Dr. Juan Bruno Zayas Alfonso de Santiago de Cuba, desde enero del 2018 hasta diciembre del 2019. A tal efecto, en el procesamiento estadístico se emplearon como medidas de resumen el porcentaje y la media para variables cualitativas y cuantitativas, respectivamente; asimismo, se aplicaron el coeficiente kappa para establecer el grado de concordancia entre datos y la prueba de independencia de la Χ2 para identificar asociación significativa entre los criterios de interés seleccionados (con p<0,05). Resultados: Se obtuvo un predominio del sexo masculino (62,1 %) y el grupo etario de 65-75 años (37,9 %). Respecto a la variedad histológica, resultó más frecuente el carcinoma epidermoide (42,7 %). El pulmón derecho fue el más afectado, específicamente su lóbulo superior (33,8 %); del mismo modo, existieron alteraciones morfológicas, como la infiltración bronquial (100,0 %), la irregularidad y el edema de la mucosa (con 98,5 % en cada caso) y la inflamación con engrosamiento de la pared bronquial (90,3 %). Conclusiones: La determinación de las características clínicas, epidemiológicas y morfológicas relacionadas con el cáncer de pulmón permite efectuar el correcto seguimiento de los pacientes y aplicar un adecuado protocolo terapéutico.
Introduction: Lung cancer is a public health problem worldwide and Cuba is not exempt from it. Objective: Characterize patients diagnosed with lung cancer according to clinical, epidemiological and morphological variables. Methods: A cross-sectional, descriptive and retrospective study was carried out on 145 adults diagnosed with lung cancer in the Pneumology Service of Dr. Juan Bruno Zayas Alfonso Teaching General Hospital in Santiago de Cuba, from January, 2018 to December, 2019. For this purpose, in the statistical processing, the percentage and mean were used as summary measures for qualitative and quantitative variables, respectively; Likewise, there were applied the kappa coefficient to establish the degree of agreement between data and the Χ2 independence test to identify a significant association between the selected criteria of interest (with p<0.05). Results: There was a predominance of the male sex (62.1%) and the age group of 65-75 years (37.9%). Regarding the histological type, squamous cell carcinoma was more common (42.7%). The right lung was the most affected, specifically its upper lobe (33.8%); also, there were morphological alterations, such as bronchial infiltration (100.0%), mucosal irregularity and edema (with 98.5% in each case), and inflammation with bronchial wall thickening (90.3%). Conclusions: The determination of the clinical, epidemiological and morphological characteristics related to lung cancer makes it possible to carry out the correct follow-up of the patients and apply an appropriate therapeutic protocol.
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Resumen Objetivo Describir el desarrollo de un carcinoma oral de células escamosas, en el que la irritación mecánica crónica aparenta tomar un rol protagonista en la carcinogénesis. Caso clínico Un paciente de 41 años de edad, argentino, con antecedentes de fisura labio alvéolo palatina, diabetes mellitus, convulsiones, consumo de cocaína y marihuana, enolismo crónico y tabaquismo, acude al Servicio de Odontología del Hospital Central de Mendoza para la evaluación de una úlcera dolorosa en el dorso de su lengua, de varias semanas de evolución, en íntima relación con un primer premolar superior derecho y una pieza supernumeraria. Se realizó una biopsia y de la anatomía patológica resultó el diagnóstico de carcinoma oral de células escamosas. Se ofreció al paciente posibles tratamientos que rechazó, por lo que se inició terapia paliativa y sintomática. Al avanzar su mal estado general, falleció por complicaciones relacionadas a la deglución. Si bien no está definido el rol de la irritación mecánica crónica en la etiología de la carcinogénesis, ejerce un efecto promotor del daño causado por el tabaco y el alcohol. Si bien el paciente era fumador y bebía alcohol, se puede observar que desarrolló un carcinoma de células escamosas en evidente relación a un trauma crónico, ya que la lesión en la cara dorsal de lengua está en íntimo contacto con el factor irritante. Aun así, la evidencia actual disponible es limitada y discute el protagonismo del trauma crónico por lo que se necesitan más estudios para evaluar y definir la posible relación causal de la irritación mecánica crónica en la carcinogénesis.
Abstract Aim To describe the development of an oral squamous cell carcinoma, in which chronic mechanical irritation appears to play a significant role in carcinogenesis. Clinical case A 41-year-old patient, from Argentina, with a history of cleft lip and palate, diabetes mellitus, seizures, cocaine and cannabis use, chronic alcoholism and smoking, comes to the Dentistry Service of the Central Hospital for the evaluation of a painful ulcer on the dorsum of the tongue, which had been developing for several weeks, in close relation to an upper right first premolar and a supernumerary tooth. A biopsy was performed, and the pathological anatomy resulted in the diagnosis of oral squamous cell carcinoma. Possible treatments were offered to the patient, which he rejected, so palliative and symptomatic therapy was initiated instead. As his poor general condition progressed, he died due to complications related to swallowing. Although the role of chronic mechanical irritation in the development of carcinogenesis is not yet fully defined, it has been shown to have a promoting effect on the damage caused by tobacco and alcohol. Although the patient was a smoker and drank alcohol, it can be observed that he developed a squamous cell carcinoma in obvious relation to a chronic trauma, since the lesion develops on the dorsal face of the tongue in close contact with the irritant factor. Still, the current evidence available is limited and discusses the role of chronic trauma, so more studies are needed to evaluate and define the possible causal relationship of chronic mechanical irritation in the development of carcinogenesis.
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Abstract Objective: With the increasing incidence and mortality of laryngeal squamous cell carcinoma worldwide, researchers continue to search for novel prognostic factors and treatment methods for preventing early laryngeal squamous cell carcinoma from becoming advanced laryngeal squamous cell carcinoma. This study aims to determine if tumor budding is an independent risk factor associated with the survival of patients with laryngeal squamous cell carcinoma. Methods: 268 cases of laryngeal squamous cell carcinoma were studied, and tumor budding was analyzed for associations with clinicopathological features and clinical outcomes. Results: Tumor budding was divided into low-grade tumor budding (0-6/0.785mm2) and high-grade tumor budding (≥7/0.785 mm2) based on the results of the receiver operating characteristics curve analysis. Logistic regression analysis showed that smaller tumor cell nests, the low levels of tumor-infiltrating lymphocytes, and higher pathological T staging were the risk factors for high-grade tumor budding (p < 0.05). In the low-grade tumor budding group, there was no statistic difference in survival between patients without tumor budding and those with 1 -6/0.785 mm2 tumor budding. Multivariate survival analysis showed high-grade tumor budding (p < 0.001) was independent prognostic factors for disease-free survival and overall survival in laryngeal squamous cell carcinoma. High-grade tumor budding was also an independent prognostic factor for disease-free survival (p = 0.037) and overall survival (p = 0.009) in T1-2N0 laryngeal squamous cell carcinoma. Conclusions: Smaller tumor cell nests, the low levels of tumor-infiltrating lymphocytes, and higher pathological T staging were closely associated with high-grade tumor budding in laryngeal squamous cell carcinoma. High-grade tumor budding may be an adverse risk factor that affects not only the disease-free survival and overall survival of laryngeal squamous cell carcinoma patients but also the survival of T1-2N0 laryngeal squamous cell carcinoma patients. Level of Evidence: Level 4.
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A Queilite Actínica (QA), também conhecida como "lábios de marinheiro", é uma patologia com potencial de malignização e, ainda que seja de fácil diagnóstico e prevenção, casos diagnosticados tardiamente podem evoluir para carcinoma de lábios. Seu principal fator etiológico é a exposição aos raios ultravioletas, e por este motivo, indivíduos que se expõem muito ao sol, incluindo militares, podem ser considerados grupo de risco para a doença. O objetivo principal deste trabalho foi descrever os principais fatores de risco e prognósticos da QA e apresentar uma revisão para o cirurgião-dentista, facilitando a identificação e conduta. Para tal, foi realizada busca de artigos pertinentes ao tema nas bases de dados Medline, Lilacs, SciELO e PubMed, de 1987 a 2022. O seguinte perfil do paciente com QA foi identificado: homem, na quinta década de vida, pele clara, com lesões no lábio inferior e com histórico de longo tempo de atividades ocupacionais ao ar livre/intensa exposição solar. O cirurgião-dentista possui papel fundamental na identificação dos grupos de risco, no reconhecimento precoce da doença e, em casos mais avançados, realizar o diagnóstico e o correto encaminhamento para atendimento especializado.
Actinic Cheilitis (AC), also known as "sailor's lips", is a premalignant pathology, and although it is easy to diagnose and prevent, late diagnosed cases may progress to lip carcinoma. Since its main etiological factor is exposure to ultraviolet rays, individuals often exposed to the sun, including military personnel, can be considered a risk group for the disease. The aim of this study was to describe the main risk and prognostic factors of AC and to create a clinical protocol for dental surgeons, making easier to identify and conduct each case. For this purpose, a search for articles relevant to the topic was carried out in Medline, Lilacs, SciELO and PubMed databases, from 1987 to 2022. The following AC patient profile was identified: male, in the fifth decade of life, fair skinned, with lesions on the lower lip and with a long history of outdoor occupational activities/intense sun exposure. The dentist has a fundamental role in identifying risk groups, early recognition of the disease and in more advanced cases, making the correct diagnosis and recommendation to specialized care.
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Abstract New methods of early detection and risk assessment have been studied aiming to predict the prognosis of patients and directing a specialized treatment of the oral tongue squamous cell carcinoma (OTSCC). In this context, several molecular biomarkers have been investigated for this purpose, and, among them, the heat shock protein 27 (HSP27) can be named. The study aimed to analyze whether heat shock protein 27 (HSP27) exerts any influence on OTSCC, correlating its immunoexpression with clinicopathological parameters, and patient survival. The sample comprised 55 OTSCC cases and 20 normal oral mucosa specimens. The malignancy grading systems proposed by the WHO in 2005, Brandwein-Gensler et al., and Almangush et al. were applied in a histomorphological study. HSP27 expressions were evaluated through the Immunoreactivity Score System (IRS). Significant values were considered at p <0.05 for all statistical tests. Higher IRS results were observed for normal oral mucosa specimens when compared to OTSCC cases (p <0.001). No significant associations between HSP27 immunostaining, the analyzed clinicopathological parameters and patient survival were observed. The results of the present study indicate lower HSP27 expression in OTSCC cases compared to normal oral mucosa specimens. Thus, HSP27 expression does not seem to influence patient prognosis.
Resumo Novos métodos de detecção precoce e avaliação de risco estão sendo estudados com o intuito de predizer o prognóstico dos pacientes e direcionar um tratamento diferenciado. Neste contexto, vários biomarcadores moleculares têm sido investigados com esta finalidade, dentre eles a heat shock protein 27 (HSP27). Esta pesquisa objetivou analisar se a HSP27 exerce alguma influência nos carcinomas de células escamosas de língua oral (CCELO), correlacionando a sua imunoexpressão com parâmetros clinicopatológicos e com a sobrevida dos pacientes. A amostra foi constituída por 55 casos de CCELO e 20 espécimes de mucosa oral normal. Os sistemas de gradação de malignidade propostos pela OMS em 2005, Brandwein-Gensler et al. e Almangush et al. foram aplicados em um estudo histomorfológico. A expressão da HSP27 foi avaliada através do Sistema de Escore de Imunorreatividade (IRS). Para todos os testes estatísticos foram considerados valores significativos com p<0,05. Foi observado um maior IRS para a mucosa oral normal quando comparado aos casos de CCELO (p<0,001). Não foram encontradas associações significativas entre a imunomarcação da HSP27 com os parâmetros clinicopatológicos analisados e com a sobrevida dos pacientes. Os resultados do presente estudo indicam uma menor expressão da HSP27 nos casos de CCELO quando comparados aos espécimes de mucosa oral normal. Assim, a expressão da HSP27 parece não influenciar o prognóstico dos pacientes.
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Abstract Studies have reported changes in the epidemiological profile of patients with oral cancer in recent decades, especially regarding gender and age. This study aimed to evaluate a historical series of oral malignant lesions prevalence over six decades and define characteristics associated with the occurrence, mainly, of oral squamous cell carcinoma (OSCC). A retrospective review of histopathological records from 1953 to 2019 was conducted in three oral pathology laboratories in South Brazil about age, sex, anatomical site, clinical aspect, and histopathological diagnosis. Descriptive and analytical analyses were performed comparing the histopathological diagnoses with other variables. Multivariable logistic regression was applied to determine the associated predictors of OSCC. Of the 53,065 records available in the institutions, 986 were oral malignant tumors (including all malignant neoplasms), representing 1.86% of all diagnoses. The occurrence of OSCC in the 1960's was 80.0%, decreasing over time reaching the lowest percentage of cases in the 1990's (75.8%) and significantly increasing to 88.7% in the 2010s. Females had a lower chance than males of having OSCC independently of the decade (odds ratio=0.30, p<0.001). This was the same for older individuals compared to those younger than 40 years. No interactions between sex, age, and decade were observed. The number of diagnoses of oral malignant lesions increased over time, and the occurrence of OSCC varied. Older individuals and males had higher chances of having OSCC independently of the decade. Therefore, in this study sample, no changes were observed in the epidemiological profile over the years concerning these predictors.
Resumo Alguns estudos relataram mudanças no perfil epidemiológico dos pacientes com câncer bucal nas últimas décadas, principalmente quanto ao gênero e a idade. Este estudo teve como objetivo avaliar, em uma série histórica, a prevalência de todas as lesões malignas bucais ao longo de seis décadas e definir características associadas na ocorrência, principalmente, de carcinoma espinocelular (CEC). Um levantamento retrospectivo dos registros histopatológicos de 1953 a 2019 foi realizado em três laboratórios de Patologia Bucal no Sul do Brasil em relação à idade, gênero, sítio anatômico, aspecto clínico e diagnóstico histopatológico. Análises descritivas e analíticas foram realizadas comparando-se os diagnósticos histopatológicos com as outras variáveis. A regressão logística multivariada foi aplicada para determinar os possíveis preditores associados ao CEC. Dos 53.065 prontuários disponíveis nas instituições, 986 eram tumores malignos bucais (incluindo todas as neoplasias malignas), representando 1,86% de todos os diagnósticos. A ocorrência de CEC na década de 1960 foi de 80,0%, diminuindo ao longo do tempo, atingindo o menor percentual de casos na década de 1990 (75,8%) e aumentando significativamente para 88,7% na década de 2010. As mulheres tiveram menor risco de desenvolver CEC do que os homens, independentemente da década (OR=0,30, p<0,001). Este foi o mesmo para indivíduos com idade mais avançada em comparação com aqueles com menos de 40 anos de idade. Não foram observadas interações entre gênero, idade e década. O número de diagnósticos de lesões malignas bucais aumentou ao longo das décadas e a ocorrência de CEC variou. Indivíduos com mais de 40 anos e do sexo masculino tiveram maiores chances de ter CEC, independentemente da década analisada. Portanto, nessa amostra estudada, não foram observadas mudanças no perfil epidemiológico ao longo dos anos com relação a esses preditores.
ABSTRACT
Context: Oral squamous cell carcinoma (OSCC) comprises more than 90% of oral cancers and is the most common carcinoma affecting the oral cavity. Early stage T1/T2 OSCC have a heterogeneous prognosis and a significant number of patients develop loco regional recurrence (LRR) and have reduced disease free survival (DFS) with increased disease related mortality. Aims and Objectives: To assess the impact of the three parameters used in Brandwein-Gensler risk model along with lympho-vascular invasion (LVI), depth of invasion (DOI) and lymph node metastases in predicting LRR in early stage OSCC. Materials and Methods: This was a retrospective study on early stage T1/2 OSCC patients over a period of 2 years who received treatment by surgical resection and had follow-up data. LRR was assessed based on recurrence of OSCC at the initial site or in regional lymph nodes. Results: Out of 1135 OSCC cases during our study period a total of 207 cases befitted our inclusion criteria. Recurrence was noted in 113 (54.6%) cases. Univariate analysis identified LVI (P < 0.00001), DOI (P < 0.00001), nodal involvement (P < 0.00001), worst pattern of invasion (WPOI) (P < 0.00001), lymphocytic host response (LHR) (P = 0.004), perineural invasion (PNI) (P = 0.012) as strong statistically significant risk factors for LRR. Conclusion: Adequate assessment of simple parameters on routine H and E by incorporating Brandwein-Gensler histological risk scoring model at the initial presentation can help prognosticate and predict LRR and select patients for post-surgical adjuvant therapy.
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Diversos autores desenvolveram estudos acerca da potencial associação entre a etiocarcinogênese do carcinoma espinocelular não melanocítico (CECNM) labial e o uso crônico da hidroclorotiazida (HCTZ). Objetivo: A atual revisão objetivou investigar a relação do diurético HCTZ e o risco de CECNM labial. Métodos: Realizou-se uma revisão de literatura nas bases de dados LILACS, PUBMED/MEDLINE e Periódico CAPES, em que foram incluídos artigos em inglês, português e francês, publicados no período de 2017 a 2022. Foram propostos 60 documentos e, dentre esses, 30 foram selecionados para compor a amostra no estudo. Resultados: Foi evidenciada uma relação entre o uso da HCTZ e a ocorrência de CENM com relação dose cumulativa devido às alterações provocadas pelo fármaco, no entanto, em virtude da heterogeneidade de desenhos metodológicos e concentração dos estudos em populações semelhantes, existem limitações quanto à confiabilidade dessas informações. Conclusão: Identificou-se uma desproporção entre a ocorrência e relevância do CENM e a produção científica vigente, demonstrando a necessidade de estudos com metodologias padronizadas que abranjam diferentes especificidades socioeconômicas e demográficas.(AU)
Several authors have developed studies about a potential association between the etiocarcinogenesis of non-melanocytic lip squamous cell carcinoma (NMSCC) and the chronic use of hydrochlorothiazide (HCTZ). Objective: The current study aimed to investigate the relation between the diuretic HCTZ and the risk of lip NMSCC. Methods: A literature review was carried out in the LILACS, PUBMED/MEDLINE and CAPES Periodical databases, which included articles in English, Portuguese and French, published between 2017 and 2022. Sixty documents were collected and, among these, 30 were selected to compose the sample in the study. Results: There was evidence of a relationship between the use of HCTZ and the occurrence of MSCC with a cumulative dose relationship due to changes caused by the drug, however, because of the heterogeneity of methodological designs and concentration of studies in similar populations, there are limitations regarding the reliability of this information. Conclusion: A disproportion between the occurrence and relevance of the NMSCC and the current scientific production was identified, demonstrating the need for studies with standardized methodologies that cover different demographic socioeconomic specificities.(AU)
Subject(s)
Humans , Lip Neoplasms/chemically induced , Carcinoma, Squamous Cell/chemically induced , Diuretics/adverse effects , Hydrochlorothiazide/adverse effects , Photosensitivity Disorders/chemically induced , Risk Factors , Carcinogenesis/chemically inducedABSTRACT
Current research highlighted the importance to recognize feasible biomarkers for early diagnoses and treatment in oral cancer. Our study analyzed the expression and spatial distribution of ALDH1A1, FGFR2, caspase-3, and CD44 in Oral Squamous Cell Carcinoma (OSCC) and leukoplakia with and without oral mucosal dysplasia. Paraffin-embedded samples of OSCC (n=5), leukoplakia with (n=5) and without (n=5) dysplasia obtained by incisional biopsies were processed using conventional histochemical techniques. Immunohistochemistry was performed using antibodies against ALDH1A1, FGFR2, caspase-3, and CD44. Images of the immunohistochemically stained tissue sections were analyzed according to the intensity of the immunostaining of each marker and classified in Scores. The Kruskal- Wallis test was performed (p≤0.05). Our results demonstrated a statically difference in the expression of all immunomarkers between OSCC and leukoplakia without dysplasia, being more significant in FGFR2 and ALDH1A1. Within the limitations of this study, our data showed that all biomarkers were overexpressed in OSCC and leukoplakia with oral mucosa dysplasia, suggesting that the presence of dysplasia is a significant clinic-pathologic predictor for malignant transformation.
La actual evidencia científica enfatiza la importancia de reconocer biomarcadores viables para el diagnóstico y tratamiento temprano del cáncer oral. Nuestro estudio piloto analizó la expresión y distribución espacial de ALDH1A1, FGFR2, caspasa-3 y CD44 en carcinoma oral de células escamosas (COCE) y en leucoplasia con o sin displasia de la mucosa oral. Las muestras incluidas en parafina de COCE (n=5), con (n=5) y sin (n=5) displasia fueron obtenidas mediante biopsias incisionales, las cuales se procesaron utilizando técnicas histoquímicas convencionales. El análisis inmunohistoquímico se realizó utilizando anticuerpos contra ALDH1A1, FGFR2, caspasa-3 y CD44. Las imágenes de las secciones de cada muestra fueron analizadas según la intensidad de inmunoexpresión de cada marcador y se clasificaron en diferentes escalas (scores). Se realizó la prueba de Kruskal-Wallis (valores de p<0,05). Nuestros resultados demostraron una diferencia estadística en la expresión de todos los inmunomarcadores entre COCE y las muestras con leucoplasia sin displasia, siendo más significativa en FGFR2 y ALDH1A1. Considerando las limitaciones de este estudio, los datos sugieren que la presencia de displasia en la mucosa oral es un importante predictor clínico-patológico de transformación maligna.
ABSTRACT
Epidermolysis bullosa dystrophica (EBD) is an inherited disease of the structural proteins in the upper dermis, characterized by blister formation at the site of trauma followed by scarring. Skin fragility and blistering are the hallmarks of this disease. Cutaneous squamous cell carcinoma (cSCC) is a dreadful complication in the epidermolysis bullosa (EB) patients and common cause of death. The recent advances in distinct tumor microenvironment explain the aggressive nature of SCC in recessive Recessive Dystrophic Epidermolysis Bullosa (RDEB) patients and the use of collagen VII re-expression as a possible therapeutic measure. Regular follow-up is a must in preventing complications.