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Microorganisms are one of the important factors which maintain the homeostasis of human health. Despite recent advances, the relationship between microorganisms and head and neck squamous cell carcinoma （HNSCC） is still unclear, and the impact of microorganisms on the incidence and prognosis of HNSCC cannot be neglected. Therefore, this article provides a systematic and comprehensive review summarizing the epidemiological evidence of microbial dysbiosis related to HNSCC and discusses the associations between them.
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Humans , Carcinoma, Squamous Cell/pathology , Epithelial Cells , Head and Neck Neoplasms , Microbiota , Prognosis , Squamous Cell Carcinoma of Head and NeckABSTRACT
With the aging of population, the elderly (≥65 years old) cancer patients have become one of the main populations for cancer care. For inoperable locally advanced head and neck squamous carcinomas, cisplatin-based concurrent chemoradiotherapy is the first-line choice. Several large clinical studies have shown that patients under 70 years of age can still benefit from concurrent chemoradiotherapy, while it should be cautious to apply chemotherapy to patients aged 70-80 years. For elderly patients who are intolerant to cisplatin, carboplatin or other regimens with less gastrointestinal and renal toxicity should be considered. Although anti-epidermal growth factor receptor (EGFR) monoclonal antibodies combined with radiotherapy has been proved to be more effective than radiotherapy alone in total patient population, age-subgroup analysis showed limited benefit in elderly patients. The safety of immune checkpoint inhibitors in elderly patients has been validated and those with high programmed death ligand-1 (PD-L1) expression may benefit from concurrent or neoadjuvant immunotherapy, however, high-level evidence is still lacking. For patients older than 80 years, radiotherapy alone may be superior to concurrent chemoradiotherapy, and hypofractionated radiotherapy for palliative purposes can be safely used in this population.
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Abstract Objective: The aim of this study is to find out if a single imaging test is enough to follow-up on an oncological post-treatment patient. In such a case, we would know which was more valuable after comparing the two, by CT or PET-CT. Methods: Between January 2012 and July 2018, we collected data from all patients with previous medical history who were treated with a head and neck squamous cell carcinoma in our hospital, through surgery or by using an organ preservation protocol which we had done. Patients were required to have a CT and a PET-CT performed in a maximum period of 30 days between techniques. We compared the post post-treatment stage given to each case by using only the physical examination (only the CT and the PET-CT), with the ones given by the Tumor Board. After treatment, we analysed the similarity through Cramer's V statistic test. Results: We performed a comparative analysis, obtaining a correlation of 0.426 between the stages given by the Tumor Board and the one assigned based on physical examination, without imaging techniques. By only using the computed tomography as an imaging method the correlation was 0.565, whereas with only the use of positron emission computed technology, it was estimated at 0.858. When we compared the statistical association between stages using exclusively one of the two imaging techniques, the correlation was 0.451. Conclusion: Independent of the modality, we have demonstrated that in patients who have received previous treatment, there was a higher correlation in the stages with respect to the diagnostic method conducted by the Tumor Board using PET-CT as the sole image. Level of evidence: Level 1.
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Abstract Objective: The prognostic importance of Tumor-Infiltrating Lymphocytes (TILs) in the tumor microenvironment of various cancers is increasingly recognized. In the present study, we aimed to investigate the prognostic value of CD3+, CD4+, CD8+, and CD45RO + TILs and their relation to histopathological features in larynx squamous cell carcinoma. Methods: Formalin-Fixed and Paraffin-Embedded (FFPE) samples from 63 primary larynx squamous cell carcinoma patients were immunostained for CD3, CD4, CD8, and CD45RO expression. Positive cells in micrographs from Invasive Margin (IM) and Tumor Center (CT) of tissue specimens counted by ImageJ software and their correlation with disease outcome were analyzed. Results: The expression level of TILs subpopulations was associated with clinicopathological markers as well as Overall Survival (OS) and Disease-Free Survival (DFS). In multivariate analysis, high frequency of CD45RO + cells in IM were confirmed as an independent prognostic marker for DFS (p = 0.007, HR = 4.968) and OS (p = 0.007, HR = 4.957). Similar findings were observed in the multivariate analysis of the combined frequency of CD45RO+cells in IM and CT. Conclusion: TILs are associated with patients clinicopathological features. Also, our findings indicate that CD45RO + TILs are a valuable marker for risk prediction in larynx SCC and could predict patients' outcomes.
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Abstract Introduction Extraparotid Warthin tumor (WT) is a very rare entity, especially when synchronous with oral cancer (OC). Objective The present study presents a case series of extraparotid WTs detected in the surgical specimen of patients treated for OC. Methods From 2007 to 2016, 336 patients were operated for OC in our institution. Neck dissection was performed in 306 patients. Results In the 306 patients operated for OC whose necks were dissected, unexpected WTs were observed in 4 surgical neck specimens. In 3 cases, extraparotid WTs were responsible for tumor, node, metastasis (TNM) overstaging before surgery. Conclusion Extraparotid WTs may be discovered during neck dissection in ∼ 1% of OC patients, and they may mimic neck metastasis, especially in positron-emission tomography/computed tomography (PET/CT) imaging.
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Background: Advanced head and neck squamous cell carcinoma (HNSCC) has limited treatment options. Programmed death-ligand1 (PD-L1) expressed by tumor cells interacts with PD-1 receptor on T lymphocytes leading to immune evasive response and survival advantage. Therapy with immune check-point inhibitors target PD-1/PD-L1 blockade inducing tumor regression. Immunohistochemistry (IHC) for PD-L1 expression enables patient selection for immunotherapy and may be considered a potential predictor of clinical response. Methods: A retrospective analysis of IHC for PD-L1 expression using manual laboratory developed technique (LDT) with antibody clone 22C3 (Dako) in 93 cases of HNSCC. PD-L1 expression was correlated with age, gender, tumor site, grade and stage. Results: PD-L1 IHC was performed in 93 cases and immunopositivity was noted in 59 (63.4%) cases. High expression with combined proportion score (CPS) ?50 was seen in 15 (16.1%) cases and low expression with CPS ?1 expression was seen in 44 (47.3%) cases. An almost-perfect interobserver agreement was noted by two pathologists for PD-L1 IHC expression (Cohen’s kappa coefficient = 0.910). No statistically significant correlation was noted between PD-L1 score and patient demographics, tumor site, grade or stage. Conclusion: Detection of PD-L1 status by IHC enables identification of HNSCC patients eligible for future targeted immunotherapy.
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Head and neck squamous cell carcinoma of the head and neck is a very aggressive cancer with a poor prognosis in the late stages. Studies have revealed that head and neck squamous cell carcinoma is highly heterogeneous and immunosuppressive. The tumor microenvironment plays a key role in the development of head and neck squamous cell carcinoma, facilitating its evolution and resistance to treatment, thus adversely affecting patient prognosis. A comprehensive understanding of the tumor microenvironment could lead to new therapeutic interventions for head and neck squamous cell carcinoma. In this review, recent research findings on the tumor microenvironment and therapeutic strategies targeting the tumor microenvironment were reviewed, leading to the development of novel combination therapies to address head and neck squamous cell carcinoma and the tumor microenvironment, with the aim of gaining a deeper understanding of the disease and developing more accurate treatment plans for head and neck squamous cell carcinoma.
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Introdução:O carcinoma de células escamosas de cavidade oral e orofaringe é uma neoplasia epitelial maligna comum, respondendo pela maioria dos casos de tumores de cabeça e pescoço. Ele está relacionado a hábitos comportamentais, como tabagismo e etilismo de longa duração, e à infecção pelo Papilomavírus humano. Objetivos:Esse estudo objetivou descrever o perfil epidemiológico dos pacientes diagnosticados com essa neoplasia na Liga Mossoroense de Estudos e Combate ao Câncer. Metodologia: Foi realizado um estudo observacional com delineamento transversal a partir de dados presentes nos prontuários clínicos e laudos anatomopatológicos e no Sistema de Informações sobre Mortalidade no período entre 2006 a 2018. Os dados foram analisados a partir do Software R, utilizandoo teste de Wilcoxon-Mann-Whitney para as análises inferenciais e o método de Kaplan-Meier para análise da sobrevida. Resultados:225 prontuários foram analisados, sendo 70,22% de homens, 65,33% na faixa etária entre 46-70 anos e cor branca (51,57%). Destes, 25,78% eram tabagistas e 39,11% tabagistas e etilistas. O principal tratamento identificado foi a associação de cirurgia, quimioterapia e radioterapia. Observou-se que 49,10% dos óbitos foram em decorrência dessa neoplasia. O principal estádio patológico encontrado foi o quatro A (34,22%). Foi identificada maior sobrevida nos pacientes acima de 70 anos, cujo tratamento foi exclusivamente cirúrgico. Menor sobrevida foi identificada em indivíduos que tinham associação de hábitos (etilismo e tabagismo). Conclusões:Nossos resultados sugerem que a evolução à óbito foi o principal desfecho clínico e, isso pode estar relacionado aos hábitos comportamentais que influenciam diretamente o curso e prognóstico da doença. Ademais, destaca-se a importância do diagnóstico precoce a fim de reduzir óbitos e melhorar a qualidade de vida dos indivíduos, assim como a necessidade de implementar políticas educativas sobre os principais fatores de risco associados ao desenvolvimento dessa neoplasia (AU).
Introduction: Squamous cell carcinoma of the oral cavity and oropharynx is a common malignant epithelial neoplasm, accounting for most cases of head and neck tumors. It is related to behavioral habits, such as long-standing smoking and alcoholism, as well as to the human Papillomavirus infection. Objectives: This study aimed at describing the epidemiological profile of the patients diagnosed with this neoplasm in the Mossoró League for Studying and Combating Cancer. Methodology:An observational study with a cross-sectional design was carried out based on data present in the medical records and anatomopathological reports and in the Mortality Information System during the 2006-2018 period. The data were analyzed using the R Software, resorting to the Wilcoxon-Mann-Whitneytest for the inferential analyses and to the Kaplan-Meier method for survival analysis. Results: 225 medical records were analyzed: 70.22% belonging to men, 65.33% aged between 46 and 70 years old and white-skinned (51.57%). Of these, 25.78% were smokers and 39.11% were smokers and alcoholics. The main treatment identified was the association of surgery, chemotherapy and radiotherapy. It was observed that 49.10% of the deaths were due to this neoplasm. The main pathological stage found wasfour A(34.22%).Longer survival was identified in patients over 70 years of age, whose treatment was exclusively surgical. Shorter survival was identified in individuals who had associated habits (alcoholism and smoking). Conclusions:Our results suggest that evolution to death was the main clinical outcome; this can be related to the behavioral habits that exert a direct influence on the course and prognosis of the disease. Furthermore, the importance of early diagnosis is highlighted in order to reduce the number of deaths and improve the individuals' quality of life, as well as the need to implement educational policies on the main risk factors associated with the development of this neoplasm (AU).
Introducción: El carcinoma de células escamosas de la cavidad oral y la orofaringe es una neoplasia epitelial maligna común, que representa la mayoría de los casos de tumores de cabeza y cuello. Se relaciona con hábitos de comportamiento, como el tabaquismo y el alcoholismo, y la infección por el virus papiloma humano. Objetivos:Este estudio tuvo como objetivo describir el perfil epidemiológico de los pacientes diagnosticados con esta neoplasiaen la Liga Mossoroense de Estudios y Combate al Cáncer. Metodología: Se realizó un estudio observacional, transversal a partir de los datos presentes en las historias clínicas e informes patológicos y en el Sistema de Información de Mortalidad en el período 2006-2018. Los datos se analizaron mediante el Software R, con utilización de la Prueba de Wilcoxon-Mann-Whitney para análisis inferencial y el método de Kaplan-Meier para análisis de supervivencia. Resultados:Se analizaron 225 historias clínicas, 70,22% en hombres, 65,33% con edades entre 46-70 años y blancos (51,57%). De estos, 25,78% eran fumadores y 39,11% eran fumadores y alcohólicos. El principal tratamiento identificado fue la asociación de cirugía, quimioterapia y radioterapia. 49,10% de las muertes se debieron a esta neoplasia. El principal estadio patológico encontrado fue cuatro A (34,22%). Se identificó mayor sobrevida en pacientes mayores de 70 años, cuyo tratamiento fue exclusivamente quirúrgico. Se identificó una menor sobrevida en personas que tenían hábitos asociados. Conclusiones:Nuestros resultados sugieren que la evolución hacia la muerte fue el principal resultado clínico y esto puede estar relacionado con hábitos de comportamiento que influyen directamente en el curso y pronóstico de la enfermedad. Además, se destaca la importancia del diagnóstico precoz para reducir las muertes y mejorar la calidad de vida, así como la necesidad de implementar políticas educativas sobre los principales factores de riesgo asociados al desarrollo de esta neoplasia (AU).
Subject(s)
Humans , Health Profile , Brazil/epidemiology , Mouth Neoplasms/pathology , Carcinoma, Squamous Cell/pathology , Oropharyngeal Neoplasms/pathology , Head and Neck Neoplasms/pathology , Tobacco Use Disorder , Survival Analysis , Epidemiology , Cross-Sectional Studies , Statistics, Nonparametric , Papillomavirus Infections , Research Report , SmokersABSTRACT
Objective@#To investigate the role of long non-coding RNA double homeobox A pseudogene 9 (DUXAP9) in head and neck squamous cell carcinoma (HNSCC) and to evaluate the expression level, molecular function and mechanism of DUXAP9 in HNSCC cells.@*Methods@#Differential expression of lncRNAs between normal and tumor tissues in HNSCC tissues were screened using lncRNA microarray, the expression level of DUXAP9 in HNSCC tissues and its relationship with prognosis were analyzed in the TCGA database. The expression levels of DUXAP9 in HNSCC tissues and cell lines were detected using qRT-PCR. The function in HNSCC cells after DUXAP9 silencing was evaluated using the CCK-8 assay, wound healing assay, Transwell migration assay and subcutaneous xenograft assay in nude mice. Changes in the transcription and translation of epithelial-mesenchymal transition (EMT)-related proteins in head and neck squamous cell carcinoma cells after DUXAP9 silencing were detected using qRT-PCR and Western blot.@*Results@#lncRNA microarray results showed that, compared to adjacent normal tissues, DUXAP9 was abnormally upregulated in HNSCC tissues. Analysis from TCGA database showed that, compared to HNSCC patients with low DUXAP9 expression, HNSCC patients with high DUXAP9 expression had poorer survival. The relative expression of DUXAP9 in HNSCC tissues and 4 HNSCC cell lines increased compared to paired adjacent normal tissues as detected using qRT-PCR. Silencing DUXAP9 significantly inhibited the proliferation, migration and expression of EMT-related genes in HNSCC cells. The silencing of DUXAP9 significantly inhibited subcutaneous tumorigenesis of the HNSCC cell line CAL27 in nude mice.@* Conclusion@#Silencing DUXAP9 significantly inhibited the proliferation of HNSCC cells and subcutaneous xenografts in nude mice. DUXAP9 may mediate the migration of head and neck squamous cell carcinoma cells via the EMT pathway.
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Head and neck squamous cell carcinoma (HNSCC), as the most common type (>90%) of head and neck cancer, includes various epithelial malignancies that arise in the nasal cavity, oral cavity, pharynx, and larynx. In 2020, approximately 878 000 new cases and 444 000 deaths linked to HNSCC occurred worldwide (Sung et al., 2021). Due to the associated frequent recurrence and metastasis, HNSCC patients have poor prognosis with a five-year survival rate of 40%-50% (Jou and Hess, 2017). Therefore, novel prognostic biomarkers need to be developed to identify high-risk HNSCC patients and improve their disease outcomes.
Subject(s)
Humans , Biomarkers, Tumor/genetics , Head and Neck Neoplasms/genetics , Kaplan-Meier Estimate , RNA , Squamous Cell Carcinoma of Head and Neck , Survival Analysis , Survival RateABSTRACT
Objective:To explore the clinical significance and prognostic value of fibrinogen (FIB) in the treatment of locally advanced head and neck squamous cell carcinoma with induction chemotherapy combined with radiotherapy.Methods:A retrospective analysis was conducted for the clinical data of 114 patients with locally advanced head and neck squamous cell carcinoma receiving non-surgical treatment in the Department of Head and Neck Oncology, the Affiliated Cancer Hospital of Guizhou Medical University from May 2011 to May 2021. The FIB critical value was determined based on the median FIB level before induction chemotherapy, by which patients were divided into high-FIB and low-FIB groups. The ROC curves were used to determine the optimal cut-off value for other hematologic-related parameters such as neutrophils, lymphocytes, and platelets. Statistical methods were used to analyze the results. The enumeration data were analyzed by Chi-square test or Fisher exact probability method. Survival curves for OS and PFS were plotted by Kalplan-Meier method and tested by Log-rank method. Prognostic factors were evaluated by Cox proportional hazard regression model.Results:There were 59 cases in the high-FIB group (FIB > 3.6 g/L) and 55 cases in the low-FIB group (FIB ≤ 3.6 g/L). The high FIB group had higher neutrophils, platelets, NLR, and PLR ( χ2= 7.84, 12.80, 15.04, 9.14; P<0.05) than the low FIB group. The 3- and 5-year overall survival (OS) rates were significantly longer in the low FIB group than those in the high-FIB group (62.9% vs. 39.6%; 46.9% vs. 25.8%), and progression-free survival (PFS) rates of the low FIB group significantly longer than those of the high-FIB group (63.3% vs. 40.3%; 48.1% vs. 26.2%). The univariate analysis showed that the OS and PFS in patients with locally advanced head and neck squamous cell carcinoma were related to FIB, the application of concurrent chemoradiotherapy, and the efficacy of radiotherapy for lymph nodes. The multivariate analysis showed that FIB, the application of concurrent chemoradiotherapy, and the efficacy of radiotherapy for lymph nodes were independent prognostic factors of the OS [ HR (95% CI): 1.89 (1.08-3.31), 3.76 (1.12-12.65), 2.14 (1.09-4.21), P < 0.05]and PFS HR (95% CI): 1.92 (1.90-3.36), 3.93 (1.01-11.34), 2.15 (1.09-4.22), P < 0.05]of patients with locally advanced head and neck squamous cell carcinoma. Conclusions:Patients with low FIB receive high OS and PFS rates after induction chemotherapy combined with radiotherapy. Therefore, FIB can be used as a prognostic factor in the evaluation of non-surgical treatment of patients with locally advanced head and neck squamous cell carcinoma.
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Head and neck squamous cell carcinoma is the sixth most common malignant carcinoma worldwide, about 60% of patients are in advanced stage at the time of visit, the incidence rate is increasing gradually while the 3-year-survival rate has not been improved .Since most patients have reached advanced stage at the time of diagnosis, it brings great difficulties to treatment and leads to poor prognosis. In recent years, many articles have found out that Tertiary lymphoid structures are in and around samples of HNSCC patients and are positively related to disease progession and outcome of patients. In-depth analysis of TLS in the formation of HNSCC and the function in tumor micro environment can help estimate the prognosis of patients and provide guidance for future treatment In this article, the compositions, functions, current research of TLS with its prognostic factors and its influence on future treatment in HNSCC will be reviewed.
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Abstract Introduction: Head and neck squamous cell carcinoma is the seventh most common malignant tumor. The advances in treatment have improved the global survival rates in the past years, although the prognosis is still grave. Objective: The aim of the present study is to evaluate the correlation between positron emission computed tomography and computed tomography at the time of staging a previously untreated head and neck squamous cell carcinoma, and to determine which of the two imaging techniques gives us more information at the time of initial diagnosis. Methods: Data from all patients diagnosed in our hospital of head and neck squamous cell carcinoma by a biopsy of any location or unknown primary tumor was collected, between January 2012 and July 2017. In all cases, computed tomography and positron emission computed tomography were performed with a maximum of 30 days difference between them and patients had not received any prior treatment to staging. The stage given to each case was compared based solely on the physical examination, only on the computed tomography/positron emission computed tomography, with respect to the stage given by the tumor board, observing the concordance obtained through Cramer's V statistical test. Results: We performed a comparative analysis obtaining a correlation of 0.729 between the stage given by the tumor board and the one assigned based on the physical examination without imaging techniques. When only using computed tomography as an imaging method, the correlation was 0.848, whereas with only the use of positron emission computed tomography it was estimated at 0.957. When comparing the statistical association between staging using exclusively one of the two imaging techniques, correlation was 0.855. Conclusion: Positron emission computed tomography is useful for the diagnosis of head and neck squamous cell carcinoma, improving the patient's staging especially when detecting cervical and distant metastases. Therefore, we consider that the use of positron emission computed tomography for the staging of patients with head and neck squamous cell carcinoma is a diagnostic test to be considered.
Resumo Introdução: O carcinoma espinocelular de cabeça e pescoço é o sétimo tumor maligno mais comum. Os avanços no tratamento melhoraram as taxas de sobrevida global nos últimos anos, embora o prognóstico ainda seja grave. Objetivo: Avaliar a correlação entre a tomografia computadorizada por emissão de pósitrons e a tomografia computadorizada no estadiamento de carcinomas espinocelulares da cabeça e pescoço não tratados previamente e verificar qual das duas técnicas de imagem nos fornece mais informações no momento do diagnóstico inicial. Método: Os dados de todos os pacientes diagnosticados em nosso hospital com carcinoma espinocelular de cabeça e pescoço por biópsia de qualquer região ou adenopatias de origem desconhecida foram colhidos no período entre janeiro de 2012 e julho de 2017. Em todos os casos, uma tomografia computadorizada e uma tomografia computadorizada por emissão de pósitrons foram realizadas com um máximo de 30 dias de diferença entre elas. Nenhum paciente deveria ter recebido tratamento antes do estadiamento. O estadiamento atribuído a cada caso foi comparado com base apenas no exame físico, pela tomografia computadorizada ou apenas pela tomografia computadorizada por emissão de pósitrons, com relação ao estadiamento concedido pela margem tumoral, observou-se a concordância obtida pelo teste estatístico de V de Cramer. Resultado: Realizamos a análise comparativa obtendo uma correlação de 0,729 entre o estadio concedido pela margem tumoral e aquele atribuído com base no exame físico sem técnicas de imagem. Usando apenas a tomografia computadorizada como método de imagem, a correlação foi de 0,848, enquanto que a correlação com a tomografia computadorizada por emissão de pósitrons foi estimada em 0,957. Ao comparar a associação estatística entre o estadiamento usando exclusivamente uma das duas técnicas de imagem, foi de 0,855. Conclusão: Tomografia computadorizada por emissão de pósitrons é útil para o diagnóstico de carcinoma espinocelular de cabeça e pescoço, melhora o estadiamento, especialmente na detecção de metástases cervicais e à distância. Portanto, concluimos que seu uso para o estadiamento de pacientes com carcinoma espinocelular de cabeça e pescoço é um exame diagnóstico a ser considerado.
Subject(s)
Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/therapy , Carcinoma, Squamous Cell/diagnostic imaging , Head and Neck Neoplasms/therapy , Head and Neck Neoplasms/diagnostic imaging , Tomography, X-Ray Computed , Sensitivity and Specificity , Radiopharmaceuticals , Fluorodeoxyglucose F18 , Positron Emission Tomography Computed Tomography , Squamous Cell Carcinoma of Head and Neck/diagnostic imaging , Neoplasm StagingABSTRACT
Objective To observe the efficacy and safety of nimotuzumab combined with docetaxel and cisplatin in the first-line treatment of recurrent or metastatic head and neck squamous cell carcinoma patients. Methods We retrospectively analyzed the clinical data of recurrent or metastatic head and neck squamous cell carcinoma patients treated with nimotuzumab combined with docetaxel+cisplatin (observation group, n=28) and docetaxel+cisplatin (control group, n=30). We compared the ORR, DCR, PFS and OS between two regimens, and evaluated the safety. Results The ORR of observation and control groups were 42.9% and 16.7%, the DCR were 78.6% and 53.3%, and the median PFS were 6.2 and 4.3 months, respectively (all P < 0.05), and the median OS were 12.2 and 8.5 months (P > 0.05). There was no significant difference in adverse reactions between two groups (P > 0.05). Conclusion Compared with simple chemotherapy, nimotuzumab combined with docetaxel and cisplatin in the first-line treatment could improve the short-term clinical efficacy and prolong the progression-free survival of the patients with recurrent or metastatic head and neck squamous cell carcinoma, and caused no additional adverse reactions.
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Objective:To explore the role of casein kinase 1 gamma 2 (CSNK1G2) in the development and progression of head and neck squamous cell carcinoma (HNSC).Methods:Based on the Cancer Genome Atlas (TCGA), LinkedOmics and UALCAN were used to analyze the relationship among the mRNA expression of CSNK1G2, methylation, copy number variation and clinical indicators in HNSC, as well as to analysis CSNK1G2 related co-expression genes and proteins. The expression of CSNK1G2 in HNSC was verified by RT-qPCR experiments of clinical samples. Protein interaction network analysis on CSNK1G2 expression-related proteins was performed using STRING database.Results:UALCAN analysis showed that the expression of CSNK1G2 mRNA in HNSC was higher than that in normal tissues ( P<0.001), and the expression of CSNK1G2 mRNA was up-regulated in lower differentiation and Human Papilloma Virus (HPV)-positive HNSC (all P<0.05). But in HNSC with different pathological stages, different age stages and different lymph node metastasis stages (N stage), there was no difference in the amount of CSNK1G2 mRNA expression (all P>0.05). The RT-qPCR experiment confirmed the increased expression of CSNK1G2 mRNA in HNSC. LinkedOmincs analysis results showed that CSNK1G2 mRNA expression was positively correlated with CSNK1G2 copy number variation ( P<0.001) and negatively correlated with methylation ( P<0.001). Survival analysis results showed that high CSNK1G2 mRNA expression and copy number mutations predicted better survival ( P=0.033, P=0.015), while methylation levels were not associated with survival ( P=0.458). Gene set enrichment analysis results showed that CSNK1G2-related co-expression genes were mainly in DNA replication. The STRING's protein interaction network analysis results showed that TP53, CHEK1, and CHEK2 may be key proteins. These proteins are significantly associated with high expression levels of CSNK1G2. Conclusions:CSNK1G2 may cooperate with TP53, CHEK1 and CHEK2 related proteins to promote the development of HNSC and tumor proliferation, but does not affect the metastasis and spread of HNSC. An increase in the expression of CSNK1G2 in HNSC may indicate a better survival prognosis.
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@#Head and neck squamous cell carcinoma (HNSCC) is a common malignant tumor that seriously threatens human health and life. With increasing studies on the mechanism of tumor immune escape, programmed death receptor 1 (PD-1) and programmed death ligand receptor 1 (PD-L1) have been proven to be involved in tumor immune escape. The primary mechanism is that PD-1 recruits protein tyrosine phosphatase (SHP-2) to dephosphorylate downstream tyrosine kinase (SyK) and phosphatidylinositol 3-kinase (PI3K), thereby inhibiting downstream protein kinase B (AKT), extracellular regulated protein kinases (ERK) and other important signaling pathways, ultimately inhibiting T cell activation. In recent years, PD-1/PD-L1 inhibitors have become popular immunotherapies. Pembrolizumab and nivolumab have been approved for HNSCC patients by the U.S. Food and Drug Administration. Both durvalumab and atezolizumab are still in clinical trials, and published data show that both have certain safety and efficacy but still need much clinical data to support them. Meanwhile, the combination of PD-1/PD-L1 inhibitors with radiotherapy, chemotherapy and immunotherapy is still controversial in terms of clinical efficacy and adverse events, and further research is needed. However, serious immune-related adverse reactions limit the clinical application of PD-1/PD-L1 inhibitors, despite promising curative effects. Therefore, developing novel inhibitors and investigating stable and effective biomarkers and upstream and downstream signaling mechanisms are urgent issues.
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Background: Head-and-neck squamous cell carcinoma (HNSCC) is one of the most common cancers that contribute to 20%–40% of all cancer incidences in India. Indian patients with HNSCC are mostly associated with tobacco usage and may have different genetic alterations compared with Western patients who are mostly associated with human papillomavirus infection. Polymorphisms in DNA repair genes are correlated to individuals' susceptibility and progression of cancer. XRCC1 is a DNA repair enzyme. Materials and Methods: In the present prospective study, Indian population of HNSCC patients (n = 45) were screened for Arg399Gln variant of XRCC1 using polymerase chain reaction-restriction fragment length polymorphism technique, prospective evaluation of the patients was done after treatment, and the single-nucleotide polymorphism results were correlated to survival functions. Results: Out of 45 patients, 28 patients were Arg/Arg, 12 patients were Arg/Gln, and 5 patients were Gln/Gln. Overall survival for the entire cohort and Arg/Arg, Arg/Gln, and Gln/Gln cohort was 36.3 (95% confidence interval [CI]: 33–39.5), 38.6 (95% CI: 35.3–41.9), 35.8 (95% CI: 28.6–42.9), and 26.4 (95% CI: 13.7–39.1) months (P = 0.097), respectively. Progression-free survival (PFS) of the entire patient cohort and Arg/Arg, Arg/Gln, and Gln/Gln cohort was 35.2 (95% CI: 31.4–39.1), 38.2 (95% CI: 34.3–42.1), 32.7 (95% CI: 26.2–39.1), and 22.3 (95% CI: 9.4–35.3) (P = 0.061), respectively. Conclusions: This study suggests that HNSCC patients with Gln substitution in place of Arg at position 399 (both homozygous and heterozygous) in XRCC1 protein have significantly inferior survival functions, higher recurrence rate, and events after radical treatment
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Objective: The aim of this study was to review the published literature and investigate whether sex determining region Y-box 2 (SOX2) is a prognostic factor in head and neck squamous cell carcinoma (HNSCC) by conduct a meta-analysis. Materials and Methods: Trials were identified from the major electronic databases (MEDLINE, EMBASE, and Cochrane Library) using the key words “HNSCC” and “SOX2.” The overall survival (OS), disease-specific survival (DPS), and disease-free survival (DFS) were the primary outcome measures. Results: We identified 371 articles, 9 articles 11 studies with a total number of 1334 cases were eligible for inclusion of this meta-analysis. The results showed that OS (DPS) in low-expression group was higher than that in high-expression group. However, the difference between the two groups was not significant (hazard ratio [HR] = 1.30, 95% confidence interval [95% CI] = [0.88, 1.91]; P = 0.18), and there was great statistical heterogeneity (I2 = 66%, P = 0.002). After subgroup analysis, the HR for OS of the patients with reduced expression of SOX2 was 1.34 (95% CI = [1.04, 1.74], P = 0.03), and the heterogeneity became acceptable (I2 = 32%, P = 0.16). The HR for DFS of the patients with reduced expression of SOX2 was 1.39 (95% CI = [1.00, 1.93]; P = 0.05). Conclusion: The findings of this meta-analysis are indicative of that high SOX2 expression is a negative prognostic factor of HNSCC and exhibit both worse OS and DFS. However, the small sample size available for this systematic review limited the power of this quantitative meta-analysis. It may therefore be too early to place complete confidence in these results
ABSTRACT
Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignant tumors. Ethanol extract of Antrodia cinnamomea (EEA) has been widely studied for its health benefits including anticancer effects. The purpose of this study was to assess the effects of EEA on HNSCC. Cell proliferation, transwell, and wound healing assays were performed. The impact of EEA on tumor growth was investigated using a xenograft model. Expressions of migration-related proteins (MMP-2, MMP-9, TIMP-1, and TIMP-2) and apoptosis-related proteins (cleaved caspase-9 and cleaved PARP) were determined using western blot analysis. The results indicated that EEA significantly inhibited the capacities of proliferation, invasion, and migration of HNSCC cells in a dose-dependent manner. Cleaved caspase-9 and cleaved PARP expressions were increased in cells treated with an increasing concentration of EEA, which suggested that EEA induced apoptosis of HNSCC. MMP-2 and MMP-9 were downregulated when cells were administered EEA, while TIMP-1 and TIMP-2 were not affected, which uncovered the mechanisms mediating the EEA-induced inhibition on cell invasion and migration. The animal experiment also suggested that EEA inhibited tumor growth. Our study confirmed the inhibitive effects of EEA on cell proliferation, invasion, and migration of HNSCC in vitro and in vivo, providing the basis for further study of the application of EEA as an effective candidate for cancer treatment.
Subject(s)
Humans , Animals , Female , Rabbits , Biological Products/pharmacology , Ethanol/pharmacology , Antrodia/chemistry , Squamous Cell Carcinoma of Head and Neck/pathology , Lung Neoplasms/pathology , Time Factors , Blotting, Western , Apoptosis/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Ethanol/isolation & purification , Squamous Cell Carcinoma of Head and Neck/drug therapy , Lung Neoplasms/drug therapy , Mice, Inbred BALB CABSTRACT
Resumen: El Carcinoma oral de células escamosas es la patología oral maligna más frecuente, asociada principalmente al tabaco, alcohol y virus del papiloma humano. El objetivo del estudio fue determinar el perfil de dicha patología, en el Laboratorio de Anatomía Patológica de la Facultad de Odontología de la Universidad de la República entre 1982-2015. Se realizó un estudio retrospectivo, transversal, analítico. Análisis estadístico usando el modelo de Cox, el test exacto de Fisher y el método de Kaplan Meier. Con 207 casos el 59,9% fueron hombres y el 98.5% mayores de 40 años. Localizándose preferentemente en la lengua, con predominio de los carcinomas histopatologicamente bien y moderadamente diferenciados. Se encontró asociación entre el grado histopatológico, género y edad; con un tiempo medio de sobrevida de 2.36 años y una tasa de sobrevida del 43% a los 5 años. El estudio permitió conocer dicha patología en un servicio de referencia y generar una base de datos para posteriores estudios.
Sumário: O carcinoma epidermóide de boca é a patologia maligna mais frequente, principalmente associada ao tabaco, álcool e papiloma vírus humano. O objetivo do estudo foi determinar o perfil dessa patologia, no Laboratório de Anatomia Patológica da Faculdade de Odontologia da Universidade da República entre 1982-2015. Foi realizado um estudo analítico retrospectivo, transversal. Análise estatística pelo modelo de Cox, teste exato de Fisher e método de Kaplan Meier. Em 207 casos, 59,9% eram homens e 98,5% tinham mais de 40 anos. De preferência localizado na língua, com predominância de carcinomas histopatologicamente bem e moderadamente diferenciados. Foi encontrada associação entre grau histopatológico, sexo e idade; com tempo médio de sobrevivência de 2,36 anos e taxa de sobrevivência de 43% aos 5 anos. O estudo permitiu conhecer essa patologia em um serviço de referência e gerar um banco de dados para estudos subsequentes.
Abstract Oral squamous cell carcinoma is the most frequent malignant oral pathology, mainly associated with tobacco, alcohol, and human papillomavirus. This study aimed to determine the profile of this pathology at the Laboratory of Anatomic Pathology of the School of Dentistry of Universidad de la República between 1982 and 2015. A retrospective, cross-sectional, analytical study was conducted. Statistical analysis performed using the Cox model, Fisher's exact test, and the Kaplan-Meier method. Of 207 cases, 59.9% were men and 98.5% older than 40. It is usually located on the tongue, with a predominance of histopathologically well and moderately differentiated carcinomas. There was an association between histopathological grade, gender, and age, with an average survival time of 2.36 years and a 43% five-year survival rate. The study allowed us to determine the situation of this pathology in a reference health service and create a database for subsequent studies.