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1.
Head Face Med ; 17(1): 7, 2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33637098

RESUMO

BACKGROUND: As a tumor-accelerating transcriptional factor, E2F transcription factor 7 (E2F7) was up-regulated in many forms of cancers. Nevertheless, little has been reported about the impacts of E2F7 on oral squamous cell carcinoma (OSCC). Here, we aimed to probe whether E2F7 had influences on OSCC and its potential mechanism. METHODS: The expression of E2F7 in OSCC tissues was analyzed using the data acquired from TCGA and ONCOMINE databases. E2F7 prognostic value in OSCC patients was analyzed utilizing TCGA database. The expression of E2F7 in OSCC cell lines was detected by qRT-PCR. Gain-and loss-function of E2F7 assays in TCA-83 and CAL27 cells were performed respectively to inquire the function of E2F7. Western blotting was applied to test the alternations of EMT-related markers. RESULTS: In OSCC tissues, E2F7 was highly expressed. Besides, high expression of E2F7 predicted worse prognosis in OSCC patients. Moreover, E2F7 was over-expressed in TCA-83, HSC-4 and CAL27 (all OSCC cell lines) cells relative to that in HNOK (a normal cell line) cells. Gain-and loss-function assays displayed that deficiency of E2F7 suppresses CAL27 cell growth, migration, invasion and E2F7 high-expression resulted in inverse outcomes in TCA-83 cells. Finally, we found that silencing of E2F7 facilitated E-cadherin protein expression level and reduced N-cadherin, Vimentin and Snail protein levels in CAL27 cells, whilst E2F7 high-expression exhibited the opposite effects in TCA-83 cells. CONCLUSIONS: These outcomes indicated that E2F7 performs a carcinogenic role in OSCC, which provides a theoretical basis for the therapeutic strategies of OSCC.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Carcinoma de Células Escamosas/genética , Linhagem Celular Tumoral , Proliferação de Células , Fatores de Transcrição E2F , Humanos , Neoplasias Bucais/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética
2.
Adv Clin Exp Med ; 30(1): 41-48, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33529506

RESUMO

BACKGROUND: Hypopharyngeal cancer is one of the most frequent head and neck cancers and is associated with a poor prognosis because of recurrence and metastases. Therefore, there is a need to improve the prognosis, which requires the identification of prognostic factors and elucidation of the mechanisms involved in tumor progression. Accumulated evidence has demonstrated that cluster of differentiation 147 (CD147) is strongly expressed in malignant tumors, including head and neck squamous cell carcinoma (HNSCC), and contributes to tumor progression. OBJECTIVES: To investigate CD147-induced signaling pathways in HNSCC cells to evaluate the mechanisms of tumor progression mediated by CD147, and the association between CD147 expression in tumors and the survival rate of hypopharyngeal cancer patients. MATERIAL AND METHODS: To determine the downstream signaling of CD147 in HNSCC, expression levels of phosphorylated AKT1, MEK1, p38 MAPK, STAT3, and NF-κB were evaluated using enzyme-linked immunosorbent assay (ELISA) in FaDu, a hypopharyngeal cell line, exposed to cyclophilin A, a CD147 ligand. RESULTS: We found that hypopharyngeal cancer patients expressing CD147 showed a poor five-year overall survival (OS) of 11.1% compared with those without CD147 expression (43.0%) (p = 0.02). We confirmed that the expression of phosphorylated MEK and matrix metalloproteinase-9 (MMP-9), as well as cell invasion ability, were enhanced in hypopharyngeal cancer cells. In addition, this increased cell infiltration and enhancement of MMP-9 expression induced by CD147 were abolished by a MEK inhibitor. CONCLUSIONS: These results suggest that CD147 can be a predictor of a poor prognosis, and that a CD147-induced MEK-mediated intracellular signaling pathway plays a crucial role in tumor progression in hypopharyngeal carcinoma.


Assuntos
Basigina/metabolismo , Neoplasias Faríngeas , Carcinoma de Células Escamosas de Cabeça e Pescoço , Diferenciação Celular , Linhagem Celular Tumoral , Humanos , Sistema de Sinalização das MAP Quinases , Metaloproteinase 9 da Matriz , Quinases de Proteína Quinase Ativadas por Mitógeno , Recidiva Local de Neoplasia , Prognóstico , Transdução de Sinais
3.
Int J Mol Med ; 47(4): 1, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33537835

RESUMO

Metastasis is the primary cause of the high mortality rates in head and neck squamous cell carcinoma (HNSCC). MicroRNA (miR)­411­5p has been discovered to serve an important role in cancer metastases. However, to the best of our knowledge, the association between miR­411­5p expression levels and HNSCC metastasis has not been thoroughly investigated. The present study aimed to research the function of miR­411­5p in HNSCC metastasis. The results of the present study revealed that miR­411­5p expression levels were upregulated in patients with HNSCC with lymph node metastasis and the upregulated expression levels of miR­411­5p were positively associated with the metastatic potential of HNSCC. Moreover, miR­411­5p promoted HNSCC cell migration, invasion and epithelial­mesenchymal transition (EMT). The results of the dual­luciferase reporter assays identified RING1 and YY1 binding protein (RYBP) as a functional downstream target gene for miR­411­5p. Therefore, whether miR­411­5p downregulated the expression levels of RYBP in HNSCC cells was subsequently investigated. Notably, the silencing of RYBP expression restored the stimulatory effects of miR­411­5p on HNSCC cell migration, invasion and EMT. In addition, the mRNA expression levels of miR­411­5p and RYBP were found to be inversely correlated in HNSCC samples. In conclusion, the results of the present study indicated that the miR­411­5p­mediated downregulation of RYBP expression levels may exert an important role in HNSCC metastasis and may provide a novel target for the treatment of HNSCC.


Assuntos
Metástase Linfática/genética , MicroRNAs/genética , Proteínas Repressoras/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Regulação para Cima/genética , Sequência de Bases , Linhagem Celular Tumoral , Movimento Celular/genética , Transição Epitelial-Mesenquimal/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Metástase Linfática/patologia , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Invasividade Neoplásica , Metástase Neoplásica , Prognóstico , Proteínas Repressoras/genética
4.
Laryngoscope ; 131(3): 529-534, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33593036

RESUMO

The rate of positive margins in head and neck cancers has remained stagnant over the past three decades and is consistently associated with poor overall survival. This suggests that significant improvements must be made intraoperatively to ensure negative margins. We discuss the important role of fluorescence imaging to guide surgical oncology in head and neck cancer. This review includes a general overview of the principles of fluorescence, available fluorophores used for fluorescence imaging, and specific clinical applications of fluorescence-guided surgery, as well as challenges and future directions in head and neck surgical oncology. Laryngoscope, 131:529-534, 2021.


Assuntos
Neoplasias de Cabeça e Pescoço/cirurgia , Imagem Óptica/métodos , Carcinoma de Células Escamosas de Cabeça e Pescoço/cirurgia , Cirurgia Assistida por Computador/métodos , Fluorescência , Humanos , Margens de Excisão
5.
Medicine (Baltimore) ; 100(4): e24184, 2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33530209

RESUMO

ABSTRACT: Head and neck squamous cell carcinoma (HNSCC) is the sixth common malignancy worldwide. The tumor microenvironment is highly related to tumor initiation, progression, and prognosis. This study aims to screen the tumor microenvironment related key genes of prognostic value for HNSCC.The gene expression and clinical data for HNSCC were downloaded from the cancer genome atlas (TCGA). The immune/stromal/ESTIMATE scores were downloaded from the website of the MD Anderson Cancer Center. Correlation of patient gender and tumor grade with immune/stromal/ESTIMATE score was tested. Patients were divided into low and high immune/stromal/ESTIMATE score subgroups. Survival analysis was performed to evaluate the prognostic value of the immune/stromal/ESTIMATE score. Tumor microenvironment related differentially expressed genes were determined and applied for functional enrichment analysis and protein-protein interaction network was predicted. The prediction value of the common differentially expressed genes on patient survival was tested.Four hundred eighty samples with complete clinical, expression data, and immune/stromal/ESTIMATE scores were enrolled for analysis. Immune/stromal/ESTIMATE score was higher in female patients than males. A total of 44 common differentially expressed genes were screened in high and low immune/stromal/ESTIMATE score subgroups. Of the 44 genes, 7 genes (ADGRG7, CSN3, CST8, KRT81, MUC7, MYH6, and SEZ6) were found to be closely related to patient survival. Enrichment analysis showed that the differentially expressed genes mainly enriched in the protein-coupled receptor signaling pathway, extracellular region, G-protein coupled receptor activity, salivary secretion, and regulation of lipolysis in adipocytes. Protein-protein interaction analysis revealed that POSTN and OGN were crucial microenvironments related genes.Tumor microenvironment related genes ADGRG7, CSN3, CST8, KRT81, MUC7, MYH6, and SEZ6 are valuable predictors for HNSCC patient survival. POSTN and OGN are crucial in modulating the microenvironment and tumor biology for HNSCC.


Assuntos
Neoplasias de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Microambiente Tumoral/genética , Idoso , Biomarcadores Tumorais , Bases de Dados Genéticas , Feminino , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Prognóstico , Mapas de Interação de Proteínas , Fatores Sexuais , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Análise de Sobrevida
6.
Medicine (Baltimore) ; 100(3): e24327, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33546063

RESUMO

OBJECTIVES: In this study, a meta-analysis was conducted to evaluate the occult lymph node metastasis rate in patients with early-stage (T1-T2) oral tongue squamous cell carcinoma. Also, the correlation between occult lymph node metastasis rate and T2 ratio among T1-T2 or the reported year of each study was analyzed to adjust other confound variables. STUDY DESIGN: Literature search. METHODS: A systematic computerized search of the electronic databases was carried out for articles published between January 1, 1980, and December 31, 2018, which reported occult nodal metastasis rate in T1 and T2 (separately) tongue cancer patients. Statistical analysis was performed using Comprehensive Meta Analysis version 3.3.070. Publication bias was assessed by the Egger test and Begg funnel plot method. The correlation between occult nodal metastasis rate and T2 ratio or reported year, respectively, was assessed by meta-regression analysis. RESULTS: From 19 studies, a total of 1567 cases were included in the meta-analysis. By random effects model, the mean occult cervical lymph node metastasis was 24.4% (95% confidence interval; 0.205-0.248). The meta-regression revealed that the T2 ratio and the reported year of the studies did not have a significant effect on the occult metastasis rate (correlation coefficient = 0.531 and 0.002, respectively, and P = .426 and 0.921, respectively). CONCLUSION: The meta-analysis revealed that the early-stage oral tongue squamous cell carcinoma had a rate of 24.4% for occult nodal metastasis. The occult nodal metastasis rate was not significantly affected by neither T2 ratio among T1-T2 nor reported year of the studies.


Assuntos
Protocolos Clínicos , Metástase Neoplásica/fisiopatologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/complicações , Carcinoma de Células Escamosas de Cabeça e Pescoço/fisiopatologia , Humanos , Metanálise como Assunto , Revisões Sistemáticas como Assunto
7.
Medicine (Baltimore) ; 100(4): e24339, 2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33530227

RESUMO

BACKGROUND: In recent years, a number of clinical trials for antibody drugs targeting programmed cell death protein 1 (PD1)/programmed cell death 1 ligand 1 (PD-L1) have been carried out on recurrent or metastatic head and neck squamous cell carcinoma (R/M SCCHN) and reported promising prospects. To further evaluate and understand the effects and risk of anti-PD1/PD-L1 monotherapy vs standard of care (SoC) in R/M SCCHN, we conducted this meta-analysis of published randomized controlled trials. METHOD: The potential eligible trials were searched from Cochrane library and Pubmed and Embase databases. Randomized controlled trials evaluating the effects and risk of anti-PD1/PD-L1 monotherapy vs SoC in platinum refractory R/M SCCHN were selected. The outcomes, including objective response rate, disease control rate, progression-free survival, overall survival, and treatment-related adverse events, were extracted and pooled. RESULTS: 1345 patients with R/M SCCHN from three randomized controlled trials were enrolled in this analysis. Compared with SoC, anti-PD1/PD-L1 monotherapy could provide statistically significant overall survival benefit, hazard ratio (95% confidence interval ) = 0.79 [0.70-0.90]. However, we observed no significant difference between 2 treatments in progression-free survival (hazard ratio [95% confidence interval] = 0.96 [0.85-1.09]). Furthermore, anti-PD1/PD-L1 monotherapy caused less treatment-related adverse events than standard of care. CONCLUSION: Anti-PD1/PD-L1 monotherapy could indeed reduce the risk of death in R/M SCCHN patients, and provide higher safety vs SoC. Expression level of PD-L1 may be a useful biomarker for selecting patients with better response to anti-PD1/PD-L1 monotherapy.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Padrão de Cuidado/estatística & dados numéricos , Adulto , Antígeno B7-H1/imunologia , Biomarcadores Tumorais/imunologia , Feminino , Neoplasias de Cabeça e Pescoço/imunologia , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/imunologia , Recidiva Local de Neoplasia/mortalidade , Seleção de Pacientes , Receptor de Morte Celular Programada 1/imunologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Carcinoma de Células Escamosas de Cabeça e Pescoço/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Resultado do Tratamento
9.
Zhonghua Kou Qiang Yi Xue Za Zhi ; 56(2): 221-225, 2021 Feb 09.
Artigo em Chinês | MEDLINE | ID: mdl-33557511

RESUMO

Oral squamous cell carcinoma (OSCC) is a common cancer that develops from oral epithelial cells, it has a high incidence, mortality and teratogenic rate, which poses a serious threat to people's life and health.The Hippo signaling pathway plays a key role in tumorigenesis, regulation of stem cell homeostasis, tissue regeneration, and organ size control. In OSCC, activation of Hippo signaling pathway can inhibit malignant biological behavior, epithelial mesenchymal transformation and distant metastasis of tumors, and improve the survival rate of patients. Considering the importance of the Hippo signaling pathway in the development of cancer, this paper summarized the composition and regulatory mechanism of Hippo pathway, elaborated the role of Hippo signaling pathway in the occurrence and development of OSCC.At the same time, make a simple generalization about the potential therapeutic approaches and strategies to reduce the risk of drug resistance for OSCC patients targeting this pathway.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Humanos , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais , Carcinoma de Células Escamosas de Cabeça e Pescoço
10.
Artigo em Chinês | MEDLINE | ID: mdl-33541006

RESUMO

Radiomics refers to extract advanced quantitative features in radiological images in a high-throughput way, to invert the features into extensible data with the help of mathematical algorithms, and to establish descriptive and predictive models of tumors. It has important value in the diagnosis, treatment and prognosis of tumors. As an entirely new field, radiomics becomes the research hotspot of clinical medicine and biomedical engineering because of its objective, holistic, non-invasive characteristics. Head and neck squamous cell cancer is one of the common malignant tumors. Radiomics is gradually applied to the study of head and neck squamous cell cancer. This article reviews the research progress of radiomics and its application in head and neck cancer.


Assuntos
Neoplasias de Cabeça e Pescoço , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Humanos , Prognóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico por imagem
11.
Nat Commun ; 12(1): 1047, 2021 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-33594075

RESUMO

Despite the success of checkpoint blockade in some cancer patients, there is an unmet need to improve outcomes. Targeting alternative pathways, such as costimulatory molecules (e.g. OX40, GITR, and 4-1BB), can enhance T cell immunity in tumor-bearing hosts. Here we describe the results from a phase Ib clinical trial (NCT02274155) in which 17 patients with locally advanced head and neck squamous cell carcinoma (HNSCC) received a murine anti-human OX40 agonist antibody (MEDI6469) prior to definitive surgical resection. The primary endpoint was to determine safety and feasibility of the anti-OX40 neoadjuvant treatment. The secondary objective was to assess the effect of anti-OX40 on lymphocyte subsets in the tumor and blood. Neoadjuvant anti-OX40 was well tolerated and did not delay surgery, thus meeting the primary endpoint. Peripheral blood phenotyping data show increases in CD4+ and CD8+ T cell proliferation two weeks after anti-OX40 administration. Comparison of tumor biopsies before and after treatment reveals an increase of activated, conventional CD4+ tumor-infiltrating lymphocytes (TIL) in most patients and higher clonality by TCRß sequencing. Analyses of CD8+ TIL show increases in tumor-antigen reactive, proliferating CD103+ CD39+ cells in 25% of patients with evaluable tumor tissue (N = 4/16), all of whom remain disease-free. These data provide evidence that anti-OX40 prior to surgery is safe and can increase activation and proliferation of CD4+ and CD8+ T cells in blood and tumor. Our work suggests that increases in the tumor-reactive CD103+ CD39+ CD8+ TIL could serve as a potential biomarker of anti-OX40 clinical activity.


Assuntos
Epitopos/imunologia , Terapia Neoadjuvante , Receptores OX40/antagonistas & inibidores , Carcinoma de Células Escamosas de Cabeça e Pescoço/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Biópsia , Linfócitos T CD8-Positivos/imunologia , Proliferação de Células , Células Clonais , Intervalo Livre de Doença , Papillomavirus Humano 16/fisiologia , Humanos , Estimativa de Kaplan-Meier , Ativação Linfocitária/imunologia , Subpopulações de Linfócitos/imunologia , Linfócitos do Interstício Tumoral/imunologia , Terapia Neoadjuvante/efeitos adversos , Receptores de Antígenos de Linfócitos T/metabolismo , Receptores OX40/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/sangue , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Células Estromais/metabolismo
12.
Medicine (Baltimore) ; 100(6): e24618, 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33578572

RESUMO

ABSTRACT: MicroRNAs (miRNAs) play critical roles in carcinogenesis and development of cancers. In this study, we analyzed the eccentrically expressed miRNAs in head and neck squamous cell carcinoma (HNSCC) tissues based on the miRNA-Seq data of HNSCC patients available in the Cancer Genome Atlas database. Aberrant expression of 2589 miRNAs was detected in HNSCC tissues (1128 downregulated and 1461 upregulated). The differential expression levels of the miRNAs were further validated by analysis of 25 HNSCC samples and paired control tissues and compared with the Gene Expression Omnibus database to determine the candidate miRNAs. Quantitative reverse transcription polymerase chain reaction was used to compare the expression of these candidate miRNAs between 22 fresh HNSCC tissue samples and 11 control samples. In addition, the relationship between the expression of these candidate miRNAs and Tumor, Node, Metastases staging of HNSCC was analyzed. Compared with the expression in control tissues, the levels of hsa-miR-410-3p, hsa-miR-411-5p, hsa-miR-125b-2-3p, and hsa-miR-99a-3p were significantly lower in HNSCC. According to the Cancer Genome Atlas dataset analyzed, all 4 miRNAs were shown to inhibit tumor progression (T stage), positive lymph node metastasis (N stage), and distant metastasis (M stage) in HNSCC. Kyoto Encyclopedia of Genes and Genomes analysis showed that genes regulated by these 4 miRNAs were enriched in certain pathways, including the transforming growth factor-ß signaling pathway and the Hippo pathway. Enriched gene ontology terms mainly included regulation of transcription, cell proliferation, and apoptosis, which are well-characterized functions of miRNAs. Moreover, all 4 miRNAs inhibited the progression of primary tumors (T stage) and metastasis of regional lymph nodes (N stage). The top 4 aberrantly expressed miRNAs identified in this study have great clinical value in developing strategies for early diagnosis and treatment of HNSCC. More intensive studies are required to elucidate the mechanism underlying the roles of these miRNAs in HNSCC.


Assuntos
Neoplasias de Cabeça e Pescoço/genética , MicroRNAs/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Idoso , Biomarcadores Tumorais/genética , Regulação para Baixo , Feminino , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma de Células Escamosas de Cabeça e Pescoço/sangue
13.
J Immunother Cancer ; 9(2)2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33574054

RESUMO

By the beginning of the global pandemic, SARS-CoV-2 infection has dramatically impacted on oncology daily practice. In the current oncological landscape, where immunotherapy has revolutionized the treatment of several malignancies, distinguishing between COVID-19 and immune-mediated pneumonitis can be hard because of shared clinical, radiological and pathological features. Indeed, their common mechanism of aberrant inflammation could lead to a mutual and amplifying interaction.We describe the case of a 65-year-old patient affected by metastatic squamous head and neck cancer and candidate to an experimental therapy including an anti-PD-L1 agent. COVID-19 ground-glass opacities under resolution were an incidental finding during screening procedures and worsened after starting immunotherapy. The diagnostic work-up was consistent with ICIs-related pneumonia and it is conceivable that lung injury by SARS-CoV-2 has acted as an inflammatory primer for the development of the immune-related adverse event.Patients recovered from COVID-19 starting ICIs could be at greater risk of recall immune-mediated pneumonitis. Nasopharyngeal swab and chest CT scan are recommended before starting immunotherapy. The awareness of the phenomenon could allow an easier interpretation of radiological changes under treatment and a faster diagnostic work-up to resume ICIs. In the presence of clinical benefit, for asymptomatic ICIs-related pneumonia a watchful-waiting approach and immunotherapy prosecution are suggested.


Assuntos
/diagnóstico , Neoplasias Pulmonares/diagnóstico , Pneumonia/diagnóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico , Idoso , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/imunologia , /imunologia , Diagnóstico Diferencial , Humanos , /efeitos adversos , Imunoterapia/efeitos adversos , Lesão Pulmonar/diagnóstico , Lesão Pulmonar/diagnóstico por imagem , Lesão Pulmonar/patologia , Lesão Pulmonar/virologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/virologia , Masculino , Nasofaringe/metabolismo , Nasofaringe/patologia , Metástase Neoplásica , Pandemias , Pneumonia/tratamento farmacológico , Pneumonia/imunologia , Pneumonia/virologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia
14.
Anticancer Res ; 41(2): 1089-1099, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33517320

RESUMO

BACKGROUND/AIM: Prognosis plays a vital role in head and neck squamous cell carcinoma (HNSCC) patient management and decision-making. This study aimed to identify the role of BP180 as a prognostic factor in HNSCC. PATIENTS AND METHODS: Protein expression of bullous pemphigoid antigen II (BP180) was verified by immunohistochemistry (IHC) in a tissue microarray study of 202 cases. RESULTS: IHC analysis revealed that protein expression of BP180 among HNSCC patients differed significantly in the presence and absence of neural invasion, and according to T status in laryngeal and pharyngeal cancer subgroups. Overall survival and multivariate analysis showed that positive BP180-IHC and advanced clinical stage were significant independent positive predictors of mortality in HNSCC patients. In addition, in the oral cancer subgroup, independent positive predictors were positive BP180-IHC, advanced N status and neural invasion. In laryngeal and pharyngeal cancer subgroups, predictors were positive BP180-IHC and advanced clinical stage. CONCLUSION: BP180 is a prognostic factor in head and neck squamous cell carcinoma.


Assuntos
Autoantígenos/metabolismo , Biomarcadores Tumorais/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Colágenos não Fibrilares/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Tomada de Decisão Clínica , Feminino , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Análise de Sobrevida , Análise Serial de Tecidos
15.
Braz J Med Biol Res ; 54(3): e10504, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33503201

RESUMO

Molecular changes that affect mitochondrial glycolysis have been associated with the maintenance of tumor cells. Some metabolic factors have already been described as predictors of disease severity and outcomes. This systematic review was conducted to answer the question: Is the glycolytic pathway correlated with the prognosis of oral squamous cell carcinoma (OSCC)? A search strategy was developed to retrieve studies in English from PubMed, Scopus, and ISI Web of Science using keywords related to squamous cell carcinoma, survival, and glycolytic pathway, with no restriction of publication date. The search retrieved 1273 publications. After the titles and abstracts were analyzed, 27 studies met inclusion criteria. Studies were divided into groups according to two subtopics, glycolytic pathways and diagnosis, which describe the glycolytic profile of OSCC tumors. Several components of tumor energy metabolism found in this review are important predictors of survival of patients with OSCC.


Assuntos
Glicólise , Neoplasias Bucais/diagnóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico , Humanos , Neoplasias Bucais/metabolismo , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo
16.
Anticancer Res ; 41(2): 885-893, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33517294

RESUMO

BACKGROUND/AIM: Circulating tumor cells (CTCs) may be affected by the environment encountered during blood circulation. We aimed to explore the association between the molecular phenotype of CTCs and systemic inflammatory markers. PATIENTS AND METHODS: CTCs isolated from patients with recurrent/metastatic head and neck squamous cell carcinoma by CD45-negative selection were analyzed for the expression of multiple genes. The correlations between gene expression levels in CTCs and systemic inflammation markers were examined. RESULTS: Thirty-five (83.3%) of the 42 patients were positive for CTCs. No significant differences in systemic inflammatory markers were observed between CTC-positive and CTC-negative patients. Notably, VIM or ZEB2 expression was strongly correlated with that of CD44 or ALDH1. PIK3CA, CD44, ALDH1A1, and PDCD1LG2 expression in CTCs was correlated with lymphocyte- and/or albumin-related systemic inflammatory markers. CONCLUSION: CTCs acquire a survival advantage through phenotypic alterations in the hostile blood environment, and evade circulatory immune surveillance.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias de Cabeça e Pescoço/metabolismo , Recidiva Local de Neoplasia/metabolismo , Células Neoplásicas Circulantes/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Idoso , Idoso de 80 Anos ou mais , Transição Epitelial-Mesenquimal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Prognóstico , Análise de Sobrevida , Evasão Tumoral , Microambiente Tumoral
17.
Anticancer Res ; 41(2): 687-697, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33517273

RESUMO

BACKGROUND/AIM: We investigated drugs that could sensitize P-glycoprotein (P-gp)-overexpressing drug-resistant cancer cells to vincristine (VIC) or eribulin treatment and assessed their associated mechanisms of action. MATERIALS AND METHODS: We investigated 15 bipolar drugs (quetiapine, risperidone, clozapine, asenapine, iloperidone, paliperidone, ziprasidone, trifluoperazine, loxapine succinate, pilocarpine, valproic acid, carbamazepine, levetiracetam, topiramate, and felbamate) to identify drugs with a sensitizing effect on VIC-resistant KBV20C cells at relatively low doses. Fluorescence-activated cell sorting (FACS), annexin V analyses, and rhodamine uptake tests were performed to further investigate the mechanism of action. RESULTS: We found that co-treatment with half the tested drugs (quetiapine, iloperidone, trifluoperazine, loxapine, risperidone, ziprasidone, or felbamate) at low doses could highly sensitize VIC-resistant KBV20C cells. With lower amounts of the bipolar drugs or VIC, we found that among the 15 bipolar drugs tested, 2 combinations (VIC-quetiapine and VIC-trifluoperazine) had much higher sensitization effects, suggesting that lower effective doses were sufficient for sensitizing P-gp-overexpressing resistant cells compared to those required with the other drugs. Furthermore, when we compared quetiapine and trifluoperazine to previously known bipolar drugs (fluphenazine, thioridazine, pimozide, or aripiprazole), we found that aripiprazole, administered at lower doses, had a much higher sensitization effect. We also demonstrated that co-treatment with another anti-mitotic drug (eribulin) increased the sensitization of KBV20C cells similar to VIC. We also found that aripiprazole had higher P-gp-inhibitory activity than the other bipolar drugs, indicating that this activity was involved in the higher level of VIC-aripiprazole sensitization. CONCLUSION: Co-treatment of anti-mitotic drug-resistant cancer cells with a low dose of aripiprazole had the strongest sensitization effect and is highly dependent on P-gp-inhibitory activity.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/antagonistas & inibidores , Antineoplásicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Antipsicóticos/farmacologia , Aripiprazol/farmacologia , Reposicionamento de Medicamentos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Furanos/farmacologia , Cetonas/farmacologia , Neoplasias Bucais/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Vincristina/farmacologia , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Humanos , Neoplasias Bucais/genética , Neoplasias Bucais/metabolismo , Neoplasias Bucais/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia
18.
Anticancer Res ; 41(1): 113-122, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33419804

RESUMO

BACKGROUND/AIM: The aim of the study was to investigate the effects of hypoxia on proliferation and the expression of HIF-1α (hypoxia-inducible factor 1 alpha) and JMJD1A (jumonji domain 1A) in head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: FaDu and HLaC78 cells were incubated for 1-24 h in hypoxia and normoxia. Cell proliferation, mRNA and protein levels of HIF-1α and JMJD1A were quantified by counting, PCR and western blot. RESULTS: Hypoxia led to a constant decrease in cell proliferation. Short hypoxia resulted in an increase in HIF-1α mRNA levels. This effect was reversed after longer incubation. The western blot for HIF-1α showed a maximum accumulation after 3-6 h of hypoxia. In FaDu cells, the concentration of JMJD1A reached a peak after 6 h and decreased thereafter, whereas in HLaC78 cells, it presented a second peak after 48 h. CONCLUSION: The transcription factors HIF-1α and JMJDA1 were confirmed as relevant hypoxia-dependent regulators of carcinogenesis in HNSCC.


Assuntos
Regulação Neoplásica da Expressão Gênica , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Hipóxia/genética , Hipóxia/metabolismo , Histona Desmetilases com o Domínio Jumonji/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Hipóxia Celular/genética , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular/genética , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Histona Desmetilases com o Domínio Jumonji/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia
19.
Anticancer Res ; 41(1): 269-277, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33419821

RESUMO

AIM: To investigate the level of agreement between three non-invasive methods for hrHPV diagnosis in oral and oropharyngeal squamous cell carcinoma (OSCC, OPSCC) and in oral mucosal lesions. MATERIALS AND METHODS: For hrHPV DNA FTA Elute card™ and Anyplex II HPV28™ were used and for hrHPV mRNA PreTect SEE™ in tumour patients (n=60), non-tumour lesions (n=51), immunosuppression or previous hrHPV-infection (n=32). RESULTS: The level of agreement between the DNA-methods was 82.2% (k=0.54, p=0.001). Pair-wise comparison for the FTA Elute card were close to the reference (AUC=0.83, 95% CI=0.73-0.90). hrHPV mRNA was diagnosed in 50% of the tumours, with an agreement level of 58.3%, compared to Anyplex II (k=0.17, p=0.04). The hrHPV positivity in oral lesions was 3.9% for immunosuppression and for previous HPV infection 9.4%. CONCLUSION: The FTA card is reliable for hrHPV DNA diagnosis while mRNA gives an insight into viral activity and correlates with severity of the lesion.


Assuntos
Papillomaviridae/genética , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/virologia , Estomatite/diagnóstico , Estomatite/virologia , Adulto , Idoso , Biópsia , DNA Viral , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Técnicas de Diagnóstico Molecular , Infecções por Papillomavirus/complicações , Reação em Cadeia da Polimerase , Prevalência , Curva ROC , Carcinoma de Células Escamosas de Cabeça e Pescoço/epidemiologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/etiologia , Estomatite/complicações , Suécia/epidemiologia
20.
Anticancer Res ; 41(1): 477-484, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33419846

RESUMO

BACKGROUND/AIM: Patients with unresectable head-and-neck cancer (SCCHN) unable to tolerate radiochemotherapy may receive unconventionally fractionated radiotherapy. This retrospective study compared both treatments. PATIENTS AND METHODS: Eight patients unsuitable for chemotherapy were assigned to accelerated fractionation with concomitant boost (AF-CB, 69.6 Gy/39 fractions) over 5.5 weeks (group A) and 72 patients to cisplatin-based radiochemotherapy (70 Gy/35 fractions) over 7 weeks (group B). Groups were matched (cancer site, gender, age, performance score, T-/N-stage, histologic grade) and compared for loco-regional control (LRC), metastases-free survival (MFS), overall survival (OS) and toxicities. RESULTS: LRC, MFS, OS and radiation-related toxicities were not significantly different between groups A and B. Improved outcomes were associated with favorable cancer site, better performance score and T3-stage. In group B, toxicity led to reduction/discontinuation of chemotherapy in 38.9% and interruptions of radiotherapy >7 days in 19.3% of patients. CONCLUSION: AF-CB appeared a reasonable alternative for patients who cannot safely receive radio-chemotherapy for unresectable SCCHN.


Assuntos
Quimiorradioterapia , Fracionamento da Dose de Radiação , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Idoso , Quimiorradioterapia/métodos , Terapia Combinada , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Dosagem Radioterapêutica , Resultado do Tratamento
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