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1.
Medicine (Baltimore) ; 98(45): e17883, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31702662

RESUMO

RATIONALE: Of all the parts of the larynx, the glottis has the highest frequency of cancer. With disease progression, the vocal cord movement is affected and for advanced stages its anatomical and functional preservation is rarely achievable, if at all. PATIENT CONCERNS: Here we describe a 72-year-old patient who presented with hoarseness for a year and was only able to whisper. DIAGNOSIS: A computed tomography (CT) scan of the vocal cords (without contrast) showed higher density tissue. Histological examination disclosed a well-differentiated verrucous squamous cell carcinoma of the glottis. INTERVENTIONS: The patient was treated with the oncolytic ECHO-7 virus Rigvir without any of the standard treatments. OUTCOMES: As shown by CT scans, the patient has been stabilized, and the laryngeal functions are preserved with the virotherapy still ongoing. The patient was diagnosed over 4.2 years ago. LESSONS: Considering the present patient being treated with Rigvir without any standard treatment, the results suggest that Rigvir therapy could be a possible treatment for glottic cancer.


Assuntos
Neoplasias Laríngeas/terapia , Terapia Viral Oncolítica/métodos , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Idoso , Glote/diagnóstico por imagem , Glote/patologia , Humanos , Neoplasias Laríngeas/diagnóstico por imagem , Neoplasias Laríngeas/patologia , Masculino , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico por imagem , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Tomografia Computadorizada por Raios X , Resultado do Tratamento
2.
Anticancer Res ; 39(11): 6041-6047, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31704830

RESUMO

BACKGROUND/AIM: We have previously reported that alternate-day S-1 had comparable effects and milder adverse events than the respective consecutive-day regimen in head and neck cancer (HNC) patients. The aim of this study was to investigate the anticancer effects of both regimens and underlying mechanisms in vitro. MATERIALS AND METHODS: Two head and neck squamous cell carcinoma (HNSCC) cell lines were treated with 5-FU given on an alternate-day or consecutive-day schedule. The relative inhibition (RI) of tumor growth was calculated. Cell cycle distributions and cyclin expression following 5-FU treatment were analyzed. RESULTS: The RI of both regimens was almost identical. The percentage of cells in S phase was significantly increased in the alternate-day group compared to the consecutive-day group (p<0.001). CONCLUSION: The cytotoxic effect of alternate-day was equivalent to that of consecutive-day. S-phase arrest was more prominently observed with the alternate-day regimen, which may help maintain 5-FU sensitivity in head and neck cancer cells.


Assuntos
Antimetabólitos Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Fluoruracila/farmacologia , Neoplasias de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Esquema de Medicação , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Humanos , Técnicas In Vitro , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Células Tumorais Cultivadas
3.
Int J Nanomedicine ; 14: 7549-7560, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31571863

RESUMO

Background: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignant tumor in the world. Studies in recent years have demonstrated that cancer stem cells (CSCs) are present in many tumor tissues, including HNSCC, and CSCs are the root cause of tumor recurrence and metastasis. Thus, taking new treatment measures to target the killing of CSCs that are resistant to chemotherapy and radiotherapy is key to the success of cancer treatment. Methods: We explored a method for preparing anti-CD44 antibody-modified superparamagnetic iron oxide nanoparticles (SPIONPs). Biocompatibility was evaluated by a CCK-8 assay. The CSCs were obtained by a 3D cell culture technique from Cal-27 (human oral squamous cell carcinoma) cells, and then the CSCs were identified by quantitative real-time polymerase chain reaction (qRT-PCR). The targeting efficiency of the CD44-SPIONPs to CSCs was confirmed by Prussian blue staining and visualized by laser scanning confocal microscopy (LSCM). Flow cytometry was used to detect the apoptosis of CSCs after alternating magnetic field (AMF) treatment. The efficacy of tumor growth inhibition by CD44-SPIONP-mediated magnetic hyperthermia therapy was evaluated with tumor xenografts in nude mice. Results: The CD44-SPIONPs exhibited no negative effect on CSCs, indicating good biocompatibility. After SPIONPs were cocultured with stem cells, the majority of CD44-SPIONPs labeled with FITC penetrated the cell membrane into the cytoplasm. After AMF treatment, CD44-SPIONPs induced CSCs to undergo programmed death. The inhibitory ratio of the treated group was 33.43%, and necrotic areas in the tumor tissue were mainly distributed around the magnetic fluid. Conclusion: These results demonstrate that it is possible to kill CSCs using targeted magnetic nanoparticles and an AMF and that magnetic fluid hyperthermia significantly inhibited the growth of grafted Cal-27 tumors in mice.


Assuntos
Apoptose , Receptores de Hialuronatos/metabolismo , Campos Magnéticos , Nanopartículas de Magnetita/uso terapêutico , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Animais , Linhagem Celular Tumoral , Proliferação de Células , Endocitose , Regulação Neoplásica da Expressão Gênica , Humanos , Nanopartículas de Magnetita/ultraestrutura , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Células-Tronco Neoplásicas/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia
4.
Med Oncol ; 36(11): 93, 2019 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-31595355

RESUMO

In patients with locally advanced human papillomavirus (HPV)-unrelated head and neck squamous-cell carcinoma (HNSCC), cisplatin and radiation therapy (CisRT) resulted in a local-regional recurrence (LRR) rate of 35%, progression-free survival (PFS) of 49%, and overall survival (OS) of 60%. We, and others, showed that nab-paclitaxel is an active agent in metastatic and locally advanced HNSCC. The aim of this report was to assess the efficacy of nab-paclitaxel-based induction chemotherapy and CisRT in HPV-unrelated HNSCC. We performed a retrospective single-institution analysis of patients treated with nab-paclitaxel-based chemotherapy and CisRT. Key inclusion criteria included stage III-IV HPV-unrelated HNSCC. Induction chemotherapy included nab-paclitaxel and cisplatin (AP), AP + 5-fluorouracil (APF), or APF + Cetuximab (APF-C). Endpoints included LRR, overall relapse, PFS, and OS. Thirty-eight patients were the subject of this analysis. Patient characteristics included median age 59 years (IQR: 54-64) and smoking history in 36 patients (95%). Primary tumor sites included larynx/hypopharynx (27), p16 negative oropharynx (10), and oral cavity (1). Most patients had bulky disease: 82% T3-4 (n = 31) and 74% N2b-3 (n = 28). Median follow-up was 44 months (IQR: 23-59). The three-year LRR rate was 16% (95% confidence interval [CI] 7-34) and the overall relapse rate was 22% (95% CI 11-41). The three-year PFS was 64% (95% CI 46-77) and OS was 72% (95% CI 54-84). Among patients with HPV-unrelated HNSCC, nab-paclitaxel-based induction chemotherapy and CisRT resulted in a lower-than-expected rate of LRR and more favorable PFS and OS compared to historical results with CisRT.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cisplatino/uso terapêutico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Adulto , Idoso , Albuminas/administração & dosagem , Quimiorradioterapia , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/virologia , Humanos , Quimioterapia de Indução , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Paclitaxel/administração & dosagem , Infecções por Papillomavirus/patologia , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia
5.
Anticancer Res ; 39(10): 5623-5630, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570459

RESUMO

BACKGROUND: This study aimed to investigate p16 and COX2 expression in oropharyngeal squamous cell carcinoma (OPSCC), and evaluate the prognostic role of COX2 expression under the new TNM classification. MATERIALS AND METHODS: Biopsy specimens obtained from 75 patients with OPSCC were stained for p16 and COX2 expression immunohistochemically. The results and clinical records were analyzed retrospectively. RESULTS: Fifty-nine patients (79%) were positive for p16. COX2 expression was correlated with poor relapse-free survival in patients overall, and in p16-positive patients. Smoking was positively associated with COX2 expression. Moreover, both positive COX2 expression and anterior wall tumor subsite were independently correlated with lymph node metastasis, which was the only independent prognostic factor in p16-positive OPSCC. CONCLUSION: The p16-positive rate in this study was comparable with that in the USA and Europe, and higher than that in other Asian countries. COX2 expression might affect the prognosis of p16-positive OPSCC through promoting lymph node metastasis.


Assuntos
Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Metástase Linfática/genética , Metástase Linfática/patologia , Neoplasias Orofaríngeas/genética , Neoplasias Orofaríngeas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Inibidor p16 de Quinase Dependente de Ciclina/genética , Ciclo-Oxigenase 2/genética , Intervalo Livre de Doença , Feminino , Humanos , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias/métodos , Prognóstico , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia
6.
J Cancer Res Clin Oncol ; 145(10): 2433-2444, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31485767

RESUMO

PURPOSE: The clinical importance of cancer stem cells (CSCs) in head and neck squamous cell carcinoma (HNSCC) is well recognized. However, a reliable method for the detection of functioning CSC has not yet been established. We hypothesized that YAP1, a transcriptional coactivator, and SOX2, a master transcription factor of SCC, may cooperatively induce stemness through transcriptional reprogramming. METHODS: We immunohistochemically examined the expression of SOX2 and YAP1 in the CD44 variant 9 (CD44v9)-positive invasion front. A CSC-inducible module was identified through a combination of siRNAs and sphere formation assays. YAP1 and SOX2 interactions were analyzed in vitro. RESULTS: The triple overexpression of SOX2, YAP1, and CD44v9 was significantly associated with poor prognosis. TCGA data revealed that the CSC-inducible module, which was related to EMT and angiogenesis, was significantly correlated with poor prognosis. The KLF7 expression, representatively chosen from the module, also correlated with poor prognosis and was essential for sphere formation and CSC propagation. Sphere stress-activated YAP1 enhanced SOX2 activity. CONCLUSIONS: The stress-triggered activation of YAP1/SOX2 transcriptionally reprograms HNSCC for the acquisition of stemness. Triple SOX2, YAP1, and CD44v9 immunostaining assays may be useful for the selection of high-risk patients with functioning CSCs, and YAP1 targeting may lead to the development of a CSC-targeting therapy.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Células-Tronco Neoplásicas/metabolismo , Fosfoproteínas/metabolismo , Fatores de Transcrição SOXB1/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Estresse Fisiológico , Ativação Transcricional , Biomarcadores , Linhagem Celular Tumoral , Perfilação da Expressão Gênica , Humanos , Imuno-Histoquímica , Células-Tronco Neoplásicas/patologia , RNA Interferente Pequeno/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Estresse Fisiológico/genética
7.
Braz Oral Res ; 33: e085, 2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31483051

RESUMO

The aim of this study was to evaluate the immunoexpression of human leukocyte antigen-DR (HLA-DR) in actinic cheilitis (AC) and lower lip squamous cell carcinoma (LLSCC), and to correlate the findings with clinical (tumor size/extent, regional lymph node metastasis, and clinical stage) and histopathological (grade of epithelial dysplasia and inflammatory infiltrate for AC and histopathological grade of malignancy for LLSCC) parameters. Twenty-four AC and 48 LLSCC cases (24 with regional nodal metastasis and 24 without regional nodal metastasis) were selected. The scores of immunopositive cells for HLA-DR in the epithelial component of the lesions were assessed and the results were analyzed statistically using the nonparametric Mann-Whitney test. Epithelial expression of HLA-DR was observed in only five (20.8%) cases of AC (two low-grade and three high-grade lesions), with a very low median score of immunopositivity. By contrast, expression of HLA-DR was found in most LLSCC (97.9%), with a relatively high median score of positive cells. The score of HLA-DR-positive cells tended to be higher in tumors with regional lymph node metastasis, tumors in advanced clinical stages, and low-grade tumors, but the difference was not statistically significant (p > 0.05). In addition, there was a tendency towards higher expression of HLA-DR in highly/moderately keratinized tumors, and tumors with little/moderate nuclear pleomorphism (p > 0.05). The results suggest a potential role of HLA-DR in lip carcinogenesis, particularly in the development and progression of LLSCC. The expression of this protein can be related to the degree of cell differentiation in these tumors.


Assuntos
Queilite/imunologia , Antígenos HLA-DR/imunologia , Neoplasias Labiais/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinogênese/imunologia , Queilite/patologia , Feminino , Humanos , Inflamação/patologia , Neoplasias Labiais/patologia , Neoplasias Labiais/secundário , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/secundário
8.
Zhonghua Zhong Liu Za Zhi ; 41(9): 641-647, 2019 Sep 23.
Artigo em Chinês | MEDLINE | ID: mdl-31550852

RESUMO

Over the past decades, although the clinical efficacy of advanced head and neck squamous cell carcinoma (HNSCC) has been moderately improved by the combination of cetuximab and chemotherapy, no remarkable treatment has emerged. The prognosis of HNSCC is still unsatisfied. With the deeper exploration of tumor immunological therapy, immunocheckpoint inhibitors such as monoclonal antibodies targeting on programmed cell death protein 1 (PD-1)/ cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) have shown appreciable anti-tumor effect on cancers such as melanoma and non-small cell lung cancer. Some successful clinical studies on HNSCC have also been reported, which provide a new opportunity for the improvement of HNSCC prognosis.Here we systemically review the progress of checkpoint inhibitors and its combination therapy in HNSCC, some immunotherapy efficacy-related biomarkers are also discussed.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Neoplasias de Cabeça e Pescoço/terapia , Imunoterapia/métodos , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Antígeno CTLA-4/antagonistas & inibidores , Neoplasias de Cabeça e Pescoço/imunologia , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Receptor de Morte Celular Programada 1/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia
9.
Anticancer Res ; 39(8): 4073-4077, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366490

RESUMO

BACKGROUND/AIM: ANRIL is a long noncoding RNA located on INK4 locus, which encodes p15 and p16 that cause G1 phase arrest in the cell cycle. ANRIL positively regulates proliferation of several kinds of cancer cells such as lung and gastric cancers. This study, examined the effect of ANRIL in head and neck squamous cell carcinoma cells. MATERIALS AND METHODS: Cells were transfected with siRNA oligonucleotides targeting ANRIL. Transfected cells were subjected to cell-cycle and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis. RESULTS: Depletion of ANRIL increased p15 mRNA in FaDu cells, and p15 and p16 mRNA in CAL27 cells and inhibited proliferation of these cells. Cell cycle analysis showed that depletion of ANRIL caused arrest at the G1 phase of the cell cycle. CONCLUSION: ANRIL promotes G1 phase progression by repressing p15 and p16, and thus promotes FaDu and CAL27 cell proliferation.


Assuntos
Inibidor de Quinase Dependente de Ciclina p15/genética , Inibidor p16 de Quinase Dependente de Ciclina/genética , RNA Longo não Codificante/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Pontos de Checagem da Fase G1 do Ciclo Celular/genética , Regulação Neoplásica da Expressão Gênica/genética , Humanos , RNA Mensageiro/genética , RNA Interferente Pequeno/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia
10.
Virchows Arch ; 475(4): 489-497, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31422502

RESUMO

Estimation of risk of recurrence in early-stage oral tongue squamous cell carcinoma (OTSCC) remains a challenge in the field of head and neck oncology. We examined the use of artificial neural networks (ANNs) to predict recurrences in early-stage OTSCC. A Web-based tool available for public use was also developed. A feedforward neural network was trained for prediction of locoregional recurrences in early OTSCC. The trained network was used to evaluate several prognostic parameters (age, gender, T stage, WHO histologic grade, depth of invasion, tumor budding, worst pattern of invasion, perineural invasion, and lymphocytic host response). Our neural network model identified tumor budding and depth of invasion as the most important prognosticators to predict locoregional recurrence. The accuracy of the neural network was 92.7%, which was higher than that of the logistic regression model (86.5%). Our online tool provided 88.2% accuracy, 71.2% sensitivity, and 98.9% specificity. In conclusion, ANN seems to offer a unique decision-making support predicting recurrences and thus adding value for the management of early OTSCC. To the best of our knowledge, this is the first study that applied ANN for prediction of recurrence in early OTSCC and provided a Web-based tool.


Assuntos
Aprendizado de Máquina , Recidiva Local de Neoplasia , Redes Neurais (Computação) , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Neoplasias da Língua/patologia , Adulto , Idoso , Feminino , Humanos , Internet , Masculino , Pessoa de Meia-Idade , Prognóstico , Sensibilidade e Especificidade
11.
Cancer Sci ; 110(11): 3453-3463, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31444923

RESUMO

Targeting the function of membrane transporters in cancer stemlike cells is a potential new therapeutic approach. Cystine-glutamate antiporter xCT expressed in CD44 variant (CD44v)-expressing cancer cells contributes to the resistance to oxidative stress as well as cancer therapy through promoting glutathione (GSH)-mediated antioxidant defense. Amino acid transport by xCT might, thus, be a promising target for cancer treatment, whereas the determination factors for cancer cell sensitivity to xCT-targeted therapy remain unclear. Here, we demonstrate that high expression of xCT and glutamine transporter ASCT2 is correlated with undifferentiated status and diminished along with cell differentiation in head and neck squamous cell carcinoma (HNSCC). The cytotoxicity of the xCT inhibitor sulfasalazine relies on ASCT2-dependent glutamine uptake and glutamate dehydrogenase (GLUD)-mediated α-ketoglutarate (α-KG) production. Metabolome analysis revealed that sulfasalazine treatment triggers the increase of glutamate-derived tricarboxylic acid cycle intermediate α-KG, in addition to the decrease of cysteine and GSH content. Furthermore, ablation of GLUD markedly reduced the sulfasalazine cytotoxicity in CD44v-expressing stemlike HNSCC cells. Thus, xCT inhibition by sulfasalazine leads to the impairment of GSH synthesis and enhancement of mitochondrial metabolism, leading to reactive oxygen species (ROS) generation and, thereby, triggers oxidative damage. Our findings establish a rationale for the use of glutamine metabolism (glutaminolysis)-related genes, including ASCT2 and GLUD, as biomarkers to predict the efficacy of xCT-targeted therapy for heterogeneous HNSCC tumors.


Assuntos
Sistema y+ de Transporte de Aminoácidos/metabolismo , Glutationa/metabolismo , Neoplasias de Cabeça e Pescoço/metabolismo , Terapia de Alvo Molecular/métodos , Células-Tronco Neoplásicas/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Sistema ASC de Transporte de Aminoácidos/genética , Sistema y+ de Transporte de Aminoácidos/antagonistas & inibidores , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Antineoplásicos/farmacologia , Adesão Celular , Diferenciação Celular , Linhagem Celular Tumoral , Cisplatino/farmacologia , Glutamato Desidrogenase/metabolismo , Glutamina/metabolismo , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Receptores de Hialuronatos/análise , Receptores de Hialuronatos/metabolismo , Ácidos Cetoglutáricos/metabolismo , Metaboloma , Camundongos , Camundongos Nus , Antígenos de Histocompatibilidade Menor/genética , Mitocôndrias/metabolismo , Oxirredução , Estresse Oxidativo , RNA Mensageiro/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Sulfassalazina/farmacologia
12.
Cancer Radiother ; 23(6-7): 559-564, 2019 Oct.
Artigo em Francês | MEDLINE | ID: mdl-31451359

RESUMO

Despite progress in the management of head and neck squamous cell carcinoma (HNSCC), a significant proportion of patients previously irradiated for head-and-neck cancer will develop locoregional recurrence or a second primary. Because of the heterogeneity of this population with respect to disease-related factors (localization, volume, recurrence or second primary, time interval from previous irradiation…) and patient-related factors (comorbidities, sequelae of previous irradiation…), the optimal reirradiation treatment remains to be defined. Salvage therapy using reirradiation, despite some encouraging results, has historically been avoided because of concerns regarding toxicity. The results of more recent studies using contemporary treatment techniques and conformal delivery methods such as intensity modulated radiation therapy (IMRT) or stereotactic radiotherapy (SBRT) have been somewhat more promising. The aim of this review is to discuss the reirradiation of HNSCC in terms of patient selection and modern radiotherapy techniques.


Assuntos
Recidiva Local de Neoplasia/radioterapia , Segunda Neoplasia Primária/radioterapia , Seleção de Pacientes , Radiocirurgia , Radioterapia de Intensidade Modulada , Reirradiação/métodos , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Braquiterapia , Humanos , Cuidados Pós-Operatórios , Terapia com Prótons , Lesões por Radiação/patologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Medição de Risco , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Fatores de Tempo
13.
Oncol Rep ; 42(4): 1319-1328, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31364748

RESUMO

Oral squamous cell carcinoma (OSCC), with high potential for metastasis, is the most common malignant tumor of the head and neck. Cancer­associated fibroblasts (CAFs) are the main stromal cells in the microenvironment and aggravate tumor progression. However, whether CAFs are associated with the progression of OSCC remains unknown and the underlying mechanism remains unclear. In the present study, the role of CAFs in mediating OSCC cell migration and invasion was investigated, and the participation of exosomal miR­382­5p in this process was elucidated. In this study, according to the α­SMA staining with immunohistochemistry, 47 OSCC patients were divided into CAFs­rich and CAFs poor groups, and association of CAF density and clinicopathologic features of the OSCC patients were analyzed with Pearson χ2 test. Transwell assay was used for evaluating cell migration and invasion ability of OSCC cells after being co­cultured with NFs or CAFs, or after added exosomes. qPCR was used to detect the expression of miR­382­5p. Western blot analysis was used to measure the expression of migration and invasion­associated proteins. In the present study, the CAF density in tumor tissues was found to be relevant to OSCC lymph node metastasis and TNM stage. Furthermore, we revealed that miR­382­5p was overexpressed in CAFs compared with that in fibroblasts of adjacent normal tissue and miR­382­5p overexpression was responsible for OSCC cell migration and invasion. Finally, we demonstrated that CAF­derived exosomes transported miR­382­5p to OSCC cells. The present study confirmed a new mechanism of CAF­facilitated OSCC progression and may be beneficial for identifying new cancer therapeutic targets.


Assuntos
Fibroblastos Associados a Câncer/patologia , Exossomos/genética , MicroRNAs/biossíntese , Neoplasias Bucais/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Actinas/biossíntese , Adulto , Idoso , Fibroblastos Associados a Câncer/metabolismo , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Exossomos/metabolismo , Exossomos/patologia , Feminino , Humanos , Imuno-Histoquímica , Masculino , MicroRNAs/genética , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Neoplasias Bucais/genética , Neoplasias Bucais/metabolismo , Metástase Neoplásica , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo
14.
Cancer Invest ; 37(8): 327-338, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31423851

RESUMO

Little is known about the endocannabinoid (eCB) system in squamous cell carcinoma of the oral tongue (SCCOT). Here we have investigated, at the mRNA level, expression of genes coding for the components of the eCB system in tumour and non-malignant samples from SCCOT patients. Expression of NAPEPLD and PLA2G4E, coding for eCB anabolic enzymes, was higher in the tumour tissue than in non-malignant tissue. Among genes coding for eCB catabolic enzymes, expression of MGLL was lower in tumour tissue while PTGS2 was increased. It is concluded that the eCB system may be dysfunctional in SCCOT.


Assuntos
Biomarcadores Tumorais/genética , Endocanabinoides/genética , RNA Mensageiro/genética , Transdução de Sinais/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Neoplasias da Língua/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Ciclo-Oxigenase 2/genética , Feminino , Perfilação da Expressão Gênica/métodos , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Fosfolipases A2 do Grupo IV/genética , Humanos , Masculino , Pessoa de Meia-Idade , Monoacilglicerol Lipases/genética , Análise de Sequência com Séries de Oligonucleotídeos , Fosfolipase D/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Neoplasias da Língua/patologia , Adulto Jovem
15.
Cell Prolif ; 52(5): e12651, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31297902

RESUMO

OBJECTIVE: It is essential to characterize underlying molecular mechanism associated with head and neck squamous cell carcinoma (HNSCC) and identify promising therapeutic targets. Herein, we explored role of homeobox transcript antisense RNA (HOTAIR) in HNSCC to regulate stanniocalcin-2 (STC2) by sponging microRNA-206 (miR-206). METHODS: HNSCC-related differentially expressed genes and regulation network amongst HOTAIR, miR-206 and STC2 were identified. Next, effect of HOTAIR on cell biological functions of HNSCC was identified after transfection of cells with HOTAIR overexpressed plasmids or siRNA against HOTAIR. PI3K/AKT signalling pathway-related gene expression was measured after miR-206 and STC2 were suppressed. Cell invasion, migration and proliferation were assessed. Finally, tumour growth was assessed to determine the effects of HOTAIR/miR-206/STC2 axis in vivo. RESULTS: HOTAIR specifically bound to miR-206 and miR-206 targeted STC2. Downregulated HOTAIR or upregulated miR-206 suppressed HNSCC cell proliferation, invasion and migration. miR-206 inhibited PI3K/AKT signalling pathway by down-regulating STC2. Besides, silenced HOTAIR or overexpressed miR-206 repressed the tumour growth of nude mice with HNSCC. CONCLUSION: HOTAIR regulated HNSCC cell biological functions by binding to miR-206 through STC2.


Assuntos
Glicoproteínas/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Animais , Apoptose , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Glicoproteínas/antagonistas & inibidores , Glicoproteínas/genética , Neoplasias de Cabeça e Pescoço/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Camundongos , Camundongos Nus , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Interferência de RNA , RNA Longo não Codificante/antagonistas & inibidores , RNA Longo não Codificante/genética , RNA Interferente Pequeno/metabolismo , Transdução de Sinais , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo
16.
Cancer Sci ; 110(9): 2783-2793, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31325403

RESUMO

Oral cancer, a subtype of head and neck cancer, is characterized by increased infiltrating regulatory T cells (Treg); however, the pathological significance of the increase in Tregs in disease prognosis and progression and their underlying mechanism remain unestablished. C-C motif chemokine ligand 22 (CCL22) has been implicated in the recruitment of Tregs. We used RT-qPCR to determine CCL22 mRNA expression in clinical specimens and cultured cells. Loss-of-function and gain-of-function studies were carried out to analyze the effects of CCL22 modulations on cell proliferation, migration, invasion, and tumorigenesis and the mechanism involved in the deregulation of CCL22. In oral cancer specimens, CCL22 mRNA was upregulated. The increase was not only associated with reduced disease-free survival but also strongly correlated with an increase in FOXP3 mRNA, a master regulator of Treg development and functions. Silencing CCL22 expression reduced cell proliferation, migration, and invasion, whereas ectopic overexpression showed opposite effects. Manipulation of CCL22 expression in cancer cells altered tumorigenesis in both immune-compromised and -competent mice, supporting both autonomous and non-autonomous actions of CCL22. Release of interleukin 1ß (IL-1ß) from cancer-associated fibroblasts (CAF) induces CCL22 mRNA expression in oral cancer cells by activating transcription factor nuclear factor kappa B (NF-κB). Our data support a model in which CAF-derived IL-1ß, CCL22, and its receptor CCR4 foster a protumor environment by promoting cell transformation and Treg infiltration. Intervention of the IL-1ß-CCL22-CCR4 signaling axis may offer a novel therapeutic strategy for oral cancer treatment.


Assuntos
Fibroblastos Associados a Câncer/metabolismo , Quimiocina CCL22/metabolismo , Interleucina-1beta/metabolismo , Neoplasias Bucais/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Animais , Fibroblastos Associados a Câncer/imunologia , Linhagem Celular Tumoral , Movimento Celular/imunologia , Transformação Celular Neoplásica/imunologia , Transformação Celular Neoplásica/patologia , Quimiocina CCL22/genética , Intervalo Livre de Doença , Feminino , Seguimentos , Fatores de Transcrição Forkhead/metabolismo , Técnicas de Silenciamento de Genes , Humanos , Interleucina-1beta/genética , Masculino , Camundongos , Pessoa de Meia-Idade , Mucosa Bucal/patologia , Mucosa Bucal/cirurgia , Neoplasias Bucais/imunologia , Neoplasias Bucais/mortalidade , Neoplasias Bucais/cirurgia , Invasividade Neoplásica/imunologia , Invasividade Neoplásica/patologia , Prognóstico , RNA Interferente Pequeno/metabolismo , Receptores CCR4/metabolismo , Transdução de Sinais/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/cirurgia , Análise de Sobrevida , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Regulação para Cima , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Eur J Radiol ; 117: 193-198, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31307647

RESUMO

PURPOSE: To develop magnetic resonance imaging (MRI)-based radiomic signature and nomogram for preoperatively predicting prognosis in head and neck squamous cell carcinoma (HNSCC) patients. METHOD: This retrospective study consisted of a training cohort (n = 85) and a validation cohort (n = 85) of patients with HNSCC. LASSO Cox regression model was used to select the most useful prognostic features with their coefficients, upon which a radiomic signature was generated. The receiver operator characteristics (ROC) analysis and association of the radiomic signature with overall survival (OS) of patients was assessed in both cohorts. A nomogram incorporating the radiomic signature and independent clinical predictors was then constructed. The incremental prognostic value of the radiomic signature was evaluated. RESULTS: The radiomic signature, consisted of 7 selected features from MR images, was significantly associated with OS of patients with HNSCC (P < 0.0001 for training cohort, P = 0.0013 for validation cohort). The radiomic signature and TNM stage were proved to be independently associated with OS of HNSCC patients, which therefore were incorporated to generate the radiomic nomogram. In the training cohort, the nomogram showed a better prognostic capability than TNM stage only (P =  0.005), which was confirmed in the validation cohort (P =  0.01). Furthermore, the calibration curves of the nomogram demonstrated good agreement with actual observation. CONCLUSIONS: MRI-based radiomic signature is an independent prognostic factor for HNSCC patients. Nomogram based on radiomic signature and TNM stage shows promising in non-invasively and preoperatively predicting prognosis of HNSCC patient in clinical practice.


Assuntos
Imagem por Ressonância Magnética , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico por imagem , Idoso , Biomarcadores Tumorais/sangue , Feminino , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/sangue , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia
18.
Toxicol Lett ; 314: 142-152, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31319114

RESUMO

Cadmium (Cd), an established carcinogen, is a risk factor for oral squamous cell carcinoma (OSCC). Macroautophagy/autophagy is proposed to play a pivotal role in Cd-mediated carcinogenic activity. However, the mechanisms underlying Cd-induced autophagy are poorly understood. In the present study, a CAL27 OSCC cell line exposed to 10-6 M Cd for 8 weeks was used as a model system. Repeated Cd exposure induced significant migration and invasion of CAL27 cells. Furthermore, we showed that Cd increased the autophagic flux in CAL27 cells, as evidenced by the upregulation of LC3-II and the downregulation of P62/SQSTM1. The genetic blocking of autophagy inhibited Cd-induced migration and invasion, indicating a carcinogenic role of autophagy in Cd-treated CAL27 cells. Cd-induced NUPR1 expression, which contributes to lysosomal biogenesis and expression of autophagy-related gene, was found to mechanistically initiate autophagy in CAL27 cells. Of note, NUPR1 shRNA abolished Cd-induced autophagy both in vitro and in vivo. We also found that Cd triggered the generation of MDA in a xenograft tumour model and that N-acetyl-l-cysteine, a reactive oxygen species (ROS) scavenger, abrogated the effects of Cd on NUPR1-dependent autophagy in vivo. Taken together, these results demonstrate that ROS-dependent NUPR1-mediated autophagy plays an important role in repeated Cd exposure -induced cell growth, migration and invasion in OSCC cells.


Assuntos
Acetilcisteína/farmacologia , Antioxidantes/farmacologia , Autofagia/efeitos dos fármacos , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Cloreto de Cádmio/toxicidade , Movimento Celular/efeitos dos fármacos , Neoplasias Bucais/tratamento farmacológico , Proteínas de Neoplasias/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Animais , Proteína 5 Relacionada à Autofagia/genética , Proteína 5 Relacionada à Autofagia/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Masculino , Camundongos Nus , Proteínas Associadas aos Microtúbulos/metabolismo , Neoplasias Bucais/genética , Neoplasias Bucais/metabolismo , Neoplasias Bucais/patologia , Invasividade Neoplásica , Proteínas de Neoplasias/genética , Proteína Sequestossoma-1/metabolismo , Transdução de Sinais , 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 , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Int J Mol Sci ; 20(11)2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31151182

RESUMO

Head and neck cancer encompass different malignancies that develop in and around the throat, larynx, nose, sinuses and mouth. Most head and neck cancers are squamous cell carcinomas (HNSCC) that arise in the flat squamous cells that makeup the thin layer of tissue on the surface of anatomical structures in the head and neck. Each year, HNSCC is diagnosed in more than 600,000 people worldwide, with about 50,000 new cases. HNSCC is considered extremely curable if detected early. But the problem remains in treatment of inoperable cases, residues or late stages. Circadian rhythm regulation has a big role in developing various carcinomas, and head and neck tumors are no exception. A number of studies have reported that alteration in clock gene expression is associated with several cancers, including HNSCC. Analyses on circadian clock genes and their association with HNSCC have shown that expression of PER1, PER2, PER3, CRY1, CRY2, CKIε, TIM, and BMAL1 are deregulated in HNSCC tissues. This review paper comprehensively presents data on deregulation of circadian genes in HNSCC and critically evaluates their potential diagnostics and prognostics role in this type of pathology.


Assuntos
Relógios Circadianos/genética , Ritmo Circadiano , Carcinoma de Células Escamosas de Cabeça e Pescoço/etiologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Animais , Relógios Biológicos/genética , Biomarcadores , Suscetibilidade a Doenças , Regulação Neoplásica da Expressão Gênica , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia
20.
J Cancer Res Clin Oncol ; 145(7): 1761-1772, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31115672

RESUMO

PURPOSE: This study investigated the characteristics of tumor-associated immune cells (TAICs) in laryngeal squamous cell carcinoma (LSCC) and their correlation with clinicopathological variables. METHODS: The immune cell infiltrates of 71 specimens of stages I-IV LSCC were examined. The density of TAICs expressing CD3, CD4, CD8, CD68, and CD163 was assessed using immunohistochemical staining and image analysis in peritumoral and intratumoral regions. RESULTS: Higher densities of CD3+ and CD8+ cell and lower densities of CD68+ and CD163+ cell infiltrations were found in early tumor stages than in late tumor stages. A higher percentage of patients with strong CD3+ and CD8+ immune cell infiltration and weak CD68+ cell infiltration in both tumor regions presented with T1 stage tumors compared with T4 stage tumors. Further, strong CD68+ cells infiltration in both regions was observed in a greater number of patients who had a relapse, while a weak CD3+ cells infiltration in both regions was found in a greater number of patients with nodal lymphatic metastasis. The univariate analysis showed that a high density of peritumoral CD3+ and CD8+ immune cells in both regions was significantly associated with a favorable overall survival (OS) (P = 0.004; P = 0.006; P = 0.042). In contrast, a high density of intratumoral CD68+ cells and peritumoral CD163+ cells was significantly associated with poor OS durations (P = 0.026; P = 0.030). The multivariate analysis demonstrated that a high density of peritumoral CD163+ cells correlated with poor OS after adjusting for tumor stage, recurrence, and nodal lymphatic metastasis (P = 0.034). This study found different patterns of TAIC infiltration in LSCC. The density and location of TAICs infiltration correlated with the clinicopathological characteristics of LSCC. CONCLUSION: A combined analysis of the density of TAICs and their location may help predict patient survival and response to checkpoint inhibitors.


Assuntos
Neoplasias Laríngeas/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD/imunologia , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Laríngeas/patologia , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia
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