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1.
Clin Otolaryngol ; 2024 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-39358666

RESUMO

OBJECTIVE: To assess the prevalence of depression, anxiety, insomnia and somatic symptom disorder (SSD) in chronic rhinosinusitis (CRS) patients who were waiting for surgery and to predict these psychiatric disorders using the 22-item Sinonasal Outcome Test (SNOT-22). DESIGN: A prospective cross-sectional study. SETTING: The rhinology ward at our institution, a tertiary hospital. PARTICIPANTS: Adult patients (> 18 years) diagnosed with CRS who were admitted to the rhinology ward for endoscopic sinus surgery and were able to understand and complete the study questionnaires. MAIN OUTCOME MEASURES: Patient Health Questionnaire-9 (PHQ-9), Generalised Anxiety Disorder-7 (GAD-7), Insomnia Severity Index (ISI), Patient Health Questionnaire-15 (PHQ-15) and SNOT-22. RESULTS: Of the 159 participants recruited, 58 were at risk of depression (defined by PHQ-9 > 4, while 25 with PHQ-9 > 9), 49 were at risk of anxiety (defined by GAD-7 > 4, while 25 with GAD-7 > 9), 81 were at risk of insomnia (defined by ISI > 7, while 51 with ISI > 14) and 69 were at risk of SSD (defined by PHQ-15 > 4, while 24 with PHQ-15 > 9). The SNOT-22 score was closely correlated with the scores of psychometric tests and was an independent predictor of these psychiatric disorders. Patients with a high SNOT-22 score (> 30) are likely to be affected by comorbid psychiatric disorders and should be further evaluated by otolaryngologists. CONCLUSION: Depression, anxiety, insomnia and SSD are prevalent in CRS patients. Otolaryngologists should have a low threshold to ask the patient about psychiatric symptoms, especially for patients with an SNOT-22 score > 30.

2.
Lancet Oncol ; 22(3): 381-390, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33600761

RESUMO

BACKGROUND: The role of surgery compared with reirradiation in the primary treatment of patients with resectable, locally recurrent nasopharyngeal carcinoma (NPC) who have previously received radiotherapy is a matter of debate. In this trial, we compared the efficacy and safety outcomes of salvage endoscopic surgery versus intensity-modulated radiotherapy (IMRT) in patients with resectable locally recurrent NPC. METHODS: This multicentre, open-label, randomised, controlled, phase 3 trial was done in three hospitals in southern China. We included patients aged 18-70 years with a Karnofsky Performance Status score of at least 70 who were histopathologically diagnosed with undifferentiated or differentiated, non-keratinising, locally recurrent NPC with tumours confined to the nasopharyngeal cavity, the post-naris or nasal septum, the superficial parapharyngeal space, or the base wall of the sphenoid sinus. Eligible patients were randomly assigned (1:1) to receive either endoscopic nasopharyngectomy (ENPG group) or IMRT (IMRT group). Randomisation was done manually using a computer-generated random number code and patients were stratified by treatment centre. Treatment group assignment was not masked. The primary endpoint was overall survival, compared between the groups at 3 years. Efficacy analyses were done by intention to treat. Safety analysis was done in patients who received treatment according to the treatment they actually received. This trial was prospectively registered at the Chinese Clinical Trial Registry, ChiCTR-TRC-11001573, and is currently in follow-up. FINDINGS: Between Sept 30, 2011, and Jan 16, 2017, 200 eligible patients were randomly assigned to receive either ENPG (n=100) or IMRT (n=100). At a median follow-up of 56·0 months (IQR 42·0-69·0), 74 patients had died (29 [29%] of 100 patients in the ENPG group and 45 [45%] of 100 patients in the IMRT group). The 3-year overall survival was 85·8% (95% CI 78·9-92·7) in the ENPG group and 68·0% (58·6-77·4) in the IMRT group (hazard ratio 0·47, 95% CI 0·29-0·76; p=0·0015). The most common grade 3 or worse radiation-related late adverse event was pharyngeal mucositis (in five [5%] of 99 patients who underwent ENPG and 26 [26%] of 101 patients who underwent IMRT). Five [5%] of the 99 patients who underwent ENPG and 20 [20%] of the 101 patients who underwent IMRT died due to late toxic effects specific to radiotherapy; attribution to previous radiotherapy or trial radiotherapy is unclear due to the long-term nature of radiation-related toxicity. INTERPRETATION: Endoscopic surgery significantly improved overall survival compared with IMRT in patients with resectable locally recurrent NPC. These results suggest that ENPG could be considered as the standard treatment option for this patient population, although long-term follow-up is needed to further determine the efficacy and toxicity of this strategy. FUNDING: Sun Yat-sen University Clinical Research 5010 Program.


Assuntos
Carcinoma Nasofaríngeo/mortalidade , Neoplasias Nasofaríngeas/mortalidade , Cirurgia Endoscópica por Orifício Natural/mortalidade , Recidiva Local de Neoplasia/mortalidade , Radioterapia de Intensidade Modulada/mortalidade , Adulto , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/patologia , Carcinoma Nasofaríngeo/radioterapia , Carcinoma Nasofaríngeo/cirurgia , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/radioterapia , Neoplasias Nasofaríngeas/cirurgia , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/radioterapia , Recidiva Local de Neoplasia/cirurgia , Prognóstico , Taxa de Sobrevida
3.
Cancer Immunol Immunother ; 68(2): 221-232, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30357458

RESUMO

Regulatory T cells (Tregs) mediate immunosuppressive signals that can contribute to the progression of head and neck squamous cell carcinoma (HNSCC). Interleukin-33 (IL-33) is defined as an 'alarmin', an endogenous factor that is expressed during tissue and cell damage, which has been shown to promote Treg proliferation in non-lymphoid organs. However, the interaction between IL-33 and Tregs in the HNSCC tumor microenvironment remains uncertain. In this study, we examined IL-33+ and Foxp3+ cells by immunohistochemistry in 68 laryngeal squamous cell cancer patients, followed by functional analysis of IL-33 in Tregs. In addition, the suppressive function of Tregs was assessed by cell proliferation assays. The level of stromal IL-33 was significantly upregulated in advanced versus early stage HNSCC patients and positively correlated with Foxp3+ Treg infiltration as well as a poor prognosis. ST2 is regarded as the only receptor of IL-33. Infiltrated ST2-expressing Tregs were responsive to IL-33, and the percentage of Tregs was increased upon IL-33 stimulation. Functional investigation demonstrated that IL-33 increased the proportion of Foxp3+GATA3+ Tregs and improved the suppressive functions of Tregs by inducing IL-10 and TGF-ß1 as well as decreasing the proliferation of responder T cells. Blockade of ST2 abrogated the immunosuppression caused by IL-33. Our data demonstrate that stromal IL-33 both expands the Treg population and enhances their functions in the tumor microenvironment. Furthermore, stromal IL-33 has prognostic value for tumor progression. Thus, stromal IL-33 is a potential target for future HNSCC immunotherapy.


Assuntos
Carcinoma de Células Escamosas/imunologia , Neoplasias de Cabeça e Pescoço/imunologia , Tolerância Imunológica/imunologia , Interleucina-33/imunologia , Linfócitos T Reguladores/imunologia , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Células Cultivadas , Feminino , Fatores de Transcrição Forkhead/imunologia , Fatores de Transcrição Forkhead/metabolismo , Fator de Transcrição GATA3/imunologia , Fator de Transcrição GATA3/metabolismo , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Interleucina-10/imunologia , Interleucina-10/metabolismo , Interleucina-33/metabolismo , Masculino , Pessoa de Meia-Idade , Prognóstico , Linfócitos T Reguladores/metabolismo , Fator de Crescimento Transformador beta1/imunologia , Fator de Crescimento Transformador beta1/metabolismo
4.
Br J Cancer ; 117(11): 1631-1643, 2017 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-28949956

RESUMO

BACKGROUND: Foxp3+ regulatory T (Treg) cells and M2 macrophages are associated with increased tumour progression. However, the interaction between Treg cells and M2 macrophages remains unclear. METHODS: The expression of FoxP3 and CD163 was detected by immunohistochemistry in 65 cases of laryngeal squamous cell carcinoma (LSCC). In vitro, the generation of activated Treg (aTreg) cells and M2 macrophages by interactions with their precursor cells were analysed by flow cytometry and ELISA. In vivo, the antitumour effects were assessed by combined targeting aTreg cells and M2 macrophages, and intratumoural immunocytes were analysed by flow cytometry. RESULTS: In LSCC tissue, accumulation of aTreg cells and M2 macrophages predicted a poor prognosis and were positively associated with each other. In vitro, aTreg cells were induced from CD4+CD25- T cells by cancer cell-activated M2-like macrophages. Consequently, these aTreg cells skewed the differentiation of monocytes towards an M2-like phenotype, thereby forming a positive-feedback loop. Combined targeting aTreg cells and M2 macrophages led to potent antitumour immunity in vivo. CONCLUSIONS: The positive-feedback loop between aTreg cells and M2 macrophages is essential to maintain or promote immunosuppression in the tumour microenvironment and may be a potential therapeutic target to inhibit tumour progression.


Assuntos
Carcinoma de Células Escamosas/imunologia , Neoplasias de Cabeça e Pescoço/imunologia , Neoplasias Laríngeas/imunologia , Linfócitos do Interstício Tumoral/imunologia , Macrófagos/fisiologia , Linfócitos T Reguladores/imunologia , Animais , Diferenciação Celular , Linhagem Celular Tumoral , Progressão da Doença , Retroalimentação Fisiológica , Humanos , Tolerância Imunológica , Masculino , Camundongos , Camundongos Endogâmicos C3H , Carcinoma de Células Escamosas de Cabeça e Pescoço
6.
Front Immunol ; 13: 952059, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36045683

RESUMO

Background: PD-1/PD-L1 blockade is a promising immunotherapeutic strategy with the potential to improve the outcomes of various cancers. However, there is a critically unmet need for effective biomarkers of response to PD-1/PD-L1 blockade. Materials and methods: Potential biomarkers of response to PD-1/PD-L1 blockade were obtained from the Cancer Treatment Response gene signature Database (CTR-DB). A comprehensive pan-cancer analysis was done on The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) datasets. Correlations between gene expression and infiltration by immune cells were assessed using TIMER, EPIC, MCPcounter, xCell, CIBERSORT, and quanTIseq. Immunophenoscore (IPS) was used to assess the potential application of the biomarkers to all TCGA tumors. Results: Analysis of CTR-DB data identified CD69 and SBK1 as potential biomarkers of response to PD-1/PD-L1 blockade. Correlation analysis revealed that in various TCGA cancer datasets, CD69 expression level correlated positively with most immune checkpoints and tumor-infiltrating immune cells, while SBK1 expression level correlated negatively with infiltrating immune cells. IPS analysis demonstrated the ability of CD69 and SBK1 to predict PD-1/PD-L1 blockade responses in various cancers. Conclusion: CD69 and SBK1 are potential predictors of response to cancer immunotherapy using PD-1/PD-L1 blockade. These biomarkers may guide treatment decisions, leading to precise treatment and minimizing the waste of medical resources.


Assuntos
Neoplasias Pulmonares , Melanoma , Antígeno B7-H1/genética , Humanos , Inibidores de Checkpoint Imunológico , Imunoterapia , Neoplasias Pulmonares/patologia , Melanoma/tratamento farmacológico , Receptor de Morte Celular Programada 1
7.
Front Oncol ; 12: 958142, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36132140

RESUMO

Purpose: The aim of this study was to retrospectively evaluate the oncologic outcomes of sinonasal malignancies (SNMs) of various histologic subtypes and investigate the impact of multimodality treatment on prognosis of SNM. Methods: SNM patients treated with curative-intent surgery from 2000 to 2018 were included. The primary outcomes were overall survival (OS). Survival was then assessed through Cox proportional hazards models. Results: Three hundred and three patients were eligible for the analysis. The 5-year OS and event-free survival (EFS) were 61.0% (95% CI: 55.4%-67.1%) and 46.2% (95% CI: 40.4%-52.7%). The 5-year OS was the worst for malignant melanoma and the best for adenocarcinoma. Patients who received surgery had better OS than those who only received radiotherapy and/or chemotherapy. Endoscopic surgery had better OS than the open approach (p < 0.05). Microscopically margin-negative resection (R0 resection) significantly benefited OS and EFS (p < 0.001). No significant difference in OS was observed between patients who received macroscopic complete resection (R1 resection) followed by adjuvant therapy and patients who received R0 resection. Older age (HR = 1.02, p = 0.02), R1 resection (HR = 1.99, p = 0.02), sinonasal surgical history of more than 3 months before diagnosis (HR = 2.77, p = 0.007), and radiotherapy history (HR = 3, p = 0.006) are risk factors for worse EFS. Conclusions: Curative-intent surgery is irreplaceable in the treatment of SNM. The endoscopic approach is an effective alternative to the open approach. EFS is worse among patients with older age, R1 resection, sinonasal surgical history of more than 3 months before diagnosis, and radiotherapy history.

8.
Aging (Albany NY) ; 13(8): 11491-11506, 2021 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-33864445

RESUMO

Ferritin is the most important iron storage form and is known to influence tumor immunity. We previously showed that expression of ferritin light chain (FTL) and ferritin heavy chain (FTH1) subunits is increased in head and neck squamous cell carcinoma (HNSC). Here, we analyzed solid tumor datasets from The Cancer Genome Atlas and Genotype-Tissue Expression databases to investigate correlations between FTL and FTH1 expressions and (i) patient survival, using univariate, multivariate, Kaplan-Meier and Receiver Operator Characteristic analysis; and (ii) tumor-infiltrating immune cell subsets, using the bioinformatics tools Estimation of Stomal and Immune cells in Malignant Tumor tissues, Microenvironment Cell Population-counter, Tumor Immune Estimation Resource, and Tumor Immunology Miner. We found that FTL and FTH1 are upregulated and downregulated, respectively, in most of the human cancers analyzed. Tumor FTL levels were associated with prognosis in patients with lower grade glioma (LGG), whereas FTH1 levels were associated with prognosis in patients with liver hepatocellular carcinoma, HNSC, LGG, and kidney renal papillary cell carcinoma. In many cancers, FTL and FTH1 levels was significantly positively correlated with tumor infiltration by tumor-associated macrophages and T regulatory cells. These results suggest an important role for FTL and FTH1 in regulating tumor immunity to solid cancers.


Assuntos
Apoferritinas/genética , Biomarcadores Tumorais/genética , Ferritinas/genética , Regulação Neoplásica da Expressão Gênica/imunologia , Neoplasias/imunologia , Oxirredutases/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Conjuntos de Dados como Assunto , Feminino , Perfilação da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Linfócitos do Interstício Tumoral/imunologia , Masculino , Pessoa de Meia-Idade , Neoplasias/mortalidade , Neoplasias/patologia , Prognóstico , Linfócitos T Reguladores/imunologia , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia , Macrófagos Associados a Tumor/imunologia , Adulto Jovem
9.
Front Cell Dev Biol ; 9: 727762, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34527677

RESUMO

OBJECTIVE: To investigate the role of ferroptosis, an iron-dependent form of non-apoptotic cell death, in the head and neck squamous cell carcinoma (HNSCC) immune microenvironment. MATERIALS AND METHODS: A list of ferroptosis-related genes was obtained from the FerrDb database. Gene expression data were acquired from the cancer genome atlas (TCGA) and analyzed using the R language. Protein-protein interaction analysis was conducted using STRING and GeneMANIA. The correlations between gene expression levels and a patient's survival were analyzed using GEPIA, the Kaplan-Meier estimate, and a multivariate Cox proportional hazards model. The expression results were verified using Oncomine and Human Protein Atlas data. We used the TIMER, GEPIA2, GEPIA2021, and TIMER2 databases to investigate the relationships between gene expression and infiltrating immune cells. RESULTS: Analysis of differentially expressed genes (DEGs) identified nine each ferroptosis drivers and ferroptosis suppressors, among which four genes correlated with survival as follows: two drivers (SOCS1, CDKN2A) associated with better survival and two suppressors (FTH1, CAV1) associated with poorer survival. Multivariate Cox survival analysis identified SOCS1 and FTH1 as independent prognostic factors for HNSCC, and their higher expression levels were verified using Oncomine and HPA data. The results acquired using TIMER, GEPIA2, GEPIA2021, and TIMER2 data revealed that the driver SOCS1 and the suppressor FTH1 independently correlated with M1 and M2 macrophage infiltration. CONCLUSIONS: The ferroptosis driver SOCS1 and suppressor FTH1 are independent prognostic factors and that correlate with M1 and M2 macrophage infiltration in HNSCC. Targeting ferroptosis-immunomodulation may serve as a strategy to enhance the activity of immunotherapy.

10.
Head Neck ; 41(7): 2380-2388, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30737970

RESUMO

BACKGROUND: There are currently no data predicting chemosensitivity of induction chemotherapy (ICT) for hypopharyngeal squamous cell carcinomas (SCC). METHODS: Associations between immune cells and overall response (OR) to ICT and changes in immune cells during ICT were observed in 40 patients with hypopharyngeal SCC undergoing ICT. RESULTS: CD4+ and CD8+ T-cell and regulatory T-cell (Treg) frequencies reached diagnostic accuracy for OR to ICT. OR rate was significantly higher in CD4+ -high T cell, CD8+ -high T cell, and low Treg groups. A transient reduction in Tregs and increases in Tregs in the non-OR and OR groups were observed during the course of ICT. Conversely, increases in CD8+ T cells and reductions in CD8+ T cells in the non-OR and OR groups were observed. CONCLUSION: High CD4+ T-cell, high CD8+ T-cell, and low Treg frequencies can be predictors for high efficacy of ICT in patients with hypopharyngeal SCC.


Assuntos
Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Carcinoma de Células Escamosas/imunologia , Neoplasias Hipofaríngeas/imunologia , Quimioterapia de Indução , Linfócitos T Reguladores/metabolismo , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Cisplatino/administração & dosagem , Docetaxel/administração & dosagem , Feminino , Citometria de Fluxo , Fluoruracila/administração & dosagem , Humanos , Neoplasias Hipofaríngeas/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
11.
Chin Med J (Engl) ; 130(15): 1816-1823, 2017 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-28748855

RESUMO

BACKGROUND: Foreign bodies within the sinuses, orbit, and skull base (FBSOS) are rare; hence, diagnosis and management guidelines are lacking. Endoscopic sinus surgery (ESS) removal is preferred because of the less invasiveness and minimal morbidity. This study was designed to summarize clinical experience with ESS management of FBSOS. METHODS: We retrospectively reviewed clinical manifestations, imaging findings, treatment, and outcomes in consecutive patients with ESS removal of FBSOS between 2004 and 2015 at a tertiary academic medical center. The Chi-square test was performed to compare the infection rate between wooden and nonwooden FBSOS. RESULTS: There were 23 male and five female patients, with median age of 11 years. FBSOS were located within the sinuses (86%), orbit (75%), and skull base/intracranial region (46%). Wooden FBSOS had a significantly higher risk of infection (78%) compared with nonwooden FBSOS (5%, P < 0.05). Contrast-enhanced computed tomography (CT) plus three-dimensional reconstruction was sensitive in all cases. Twenty-seven (96%) FBSOS were removed by ESS alone, while 1 (4%) FBSOS was removed using the combined ESS and lateral cervical approach. Four of the nine intracranial penetrating FBSOS patients had intraoperative cerebrospinal fluid (CSF) leak and received endoscopic CSF leak repair. Twelve (43%) patients suffered complications (meningitis, diplopia, and vision loss). CONCLUSIONS: ESS is a minimally invasive, safe, and promising surgical approach for FBSOS removal. Contrast-enhanced CT is effective in preoperative diagnosis and intraoperative guidance. Wooden FBSOS had higher risk of infection, thus antibiotics are recommended.


Assuntos
Corpos Estranhos/cirurgia , Órbita/cirurgia , Base do Crânio/cirurgia , Adolescente , Adulto , Pré-Escolar , Endoscópios , Feminino , Humanos , Masculino , Estudos Retrospectivos
12.
J Exp Clin Cancer Res ; 35: 18, 2016 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-26795730

RESUMO

BACKGROUND: Dendritic cells (DCs) have been used successfully in clinical pilot studies. However, tumor-specific immunity and clinical responses were only induced in certain cancer patients. It has been well documented that immunotherapy efficacy can be optimized for responses using antigen pulsing. METHODS: The human laryngeal squamous cell cancer (LSCC) cell line SNU899 was used to evaluate the in vitro anti-tumor efficacy of three different preparations of dendritic cell (DC) vaccines consisting of either whole tumor cells or their derivatives including: i) DCs pulsed with a tumor cell supernatant (DC-TCS), ii) DCs pulsed with whole-cell tumor stressed lysate (DC-TSL), and iii) DCs pulsed with irradiated tumor cells (DC-ITC). RESULTS: Our results showed that DC-TSL is an effective source of tumor-associated antigens (TAAs) for pulsing DCs. DC-TSL induced the highest expansion of TAA-specific T cells, the strongest Th1 cytokine response, and the most potent cytotoxic T lymphocyte (CTL) activity. DC-TCS and DC-ITC inhibited T cell activation but induced a certain extent of CTL activity. CONCLUSIONS: These data suggest that DC-TSL is a more potent inducer of antitumor immunity against laryngeal cancer than other antigen-loading strategies using whole tumor cell materials. This strategy provides an alternative approach for DC-based immunotherapy for laryngeal cancer.


Assuntos
Antígenos de Neoplasias/imunologia , Carcinoma de Células Escamosas/imunologia , Células Dendríticas/imunologia , Neoplasias Laríngeas/imunologia , Linfócitos T Citotóxicos/imunologia , Apresentação de Antígeno , Vacinas Anticâncer/imunologia , Carcinoma de Células Escamosas/terapia , Técnicas de Cultura de Células , Extratos Celulares/imunologia , Linhagem Celular Tumoral , Células Dendríticas/citologia , Humanos , Imunoterapia/métodos , Neoplasias Laríngeas/terapia
13.
Mol Med Rep ; 12(2): 2367-73, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25891118

RESUMO

MicroRNA (miR)-9 has been demonstrated to regulate the radiosensitivity of tumor cells. In the present study, the mechanism by which miR-9 modulates the sensitivity of nasopharyngeal carcinoma (NPC) cells to ultraviolet (UV) radiation was investigated. The results demonstrated that exposure of NPC cells to UV light resulted in a significant increase in the expression of miR-9, and that CNE2 cells overexpressing miR-9 exhibited reduced levels of DNA damage and increased levels of total glutathione upon UV exposure. Accordingly, the inhibition of the expression of miR-9 promoted UV-induced DNA damage and apoptosis. Although miR-9 inhibited the expression of E-cadherin in the CNE2 cells and increased their resistance to UV radiation, the use of small interfering RNA to inhibit the expression of E-cadherin was not sufficient to decrease the radiosensitivity of the NPC cells. These data demonstrated that miR-9 did not modulate the sensitivity of the CNE2 cells to UV radiation through E-cadherin, but suggested that miR-9 regulated radiosensitivity through its effects on glutathione. These findings suggest that miR-9 may be a potential target for modulating the radiosensitivity of NPC cells.


Assuntos
Células Epiteliais/efeitos da radiação , Regulação Neoplásica da Expressão Gênica , Glutationa/metabolismo , MicroRNAs/genética , Tolerância a Radiação/genética , Apoptose , Caderinas/genética , Caderinas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos da radiação , Dano ao DNA , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Glutationa/agonistas , Glutationa/antagonistas & inibidores , Humanos , MicroRNAs/antagonistas & inibidores , MicroRNAs/metabolismo , Nasofaringe/metabolismo , Nasofaringe/patologia , Nasofaringe/efeitos da radiação , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Raios Ultravioleta
14.
Oncol Rep ; 33(1): 354-62, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25333227

RESUMO

CD4+ regulatory T cells (Tregs) mediate immune tolerance in laryngeal squamous cell carcinoma (LSCC). However, Tregs are functionally heterogeneous. Recently, we reported that three distinct Treg subsets (resting Tregs, activated Tregs and cytokine-secreting CD45RA-Foxp3lowCD4+ T cells) vary in the peripheral circulation of patients with head and neck squamous cell carcinoma (HNSCC); however, the potential implication of these Treg subsets in LSCC immunity is unclear. Here, we report that activated Tregs and cytokine­secreting CD45RA-Foxp3lowCD4+ T cells were increased in LSCC patients compared with healthy donors (HD) (p<0.001, p<0.001), whereas resting Tregs were decreased (p<0.001). Activated Tregs inhibited the proliferation of CD4+CD25- T cells (p<0.001) and secreted lower levels of interleukin-2 (p<0.001), interferon-γ (p<0.001) and tumor necrosis factor-α (p<0.001) compared with the cytokine-secreting CD45RA-Foxp3lowCD4+ T cells. Importantly, activated Treg prevalence was correlated with tumor stage (p=0.001) and nodal status (p=0.007). The prevalence of naïve CD4+ (p<0.001), naïve CD8+ (p=0.002), and Th1 T-cell subsets (p<0.001, p<0.001) was decreased in the LSCC patients. In conclusion, our findings showed that activated Tregs with suppressive activity are a distinct subset of Tregs in LSCC, and correlate with disease progression. Several immune system abnormalities in LSCC patients are represented by expansion of functionally activated Tregs, both in the circulation and tumor microenvironment along with decreased frequencies of naïve T-cell populations and Th1-cell populations.


Assuntos
Neoplasias Laríngeas/imunologia , Neoplasias de Células Escamosas/imunologia , Linfócitos T Reguladores/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Estudos de Casos e Controles , Progressão da Doença , Feminino , Fatores de Transcrição Forkhead/metabolismo , Humanos , Subunidade alfa de Receptor de Interleucina-2/metabolismo , Neoplasias Laríngeas/patologia , Antígenos Comuns de Leucócito/metabolismo , Subpopulações de Linfócitos/imunologia , Masculino , Pessoa de Meia-Idade , Neoplasias de Células Escamosas/patologia , Valores de Referência , Linfócitos T Reguladores/metabolismo , Células Th1/imunologia
15.
Artigo em Zh | MEDLINE | ID: mdl-24195825

RESUMO

OBJECTIVE: To investigate the effects of down-regulated miR-9 expression on ultraviolet rays (UV)-induced reactive oxygen species (ROS) damage in nasopharyngeal carcinoma (NPC) cells. METHODS: The NPC cells were transfected with inhibitors of miR-9 by lipofectamine to decrease the expression of miR-9, and the cells transfected with inhibitor control as the control. ROS levels following UV exposure were examined with DCF-DA method and the concentration of glutathione was analyzed via the benzoic acid method; DNA damage and apoptosis also were evaluated. RESULTS: There was significant difference in ROS levels between miR-9 expression-inhibited cells and control cells (26 895 ± 218 vs 15 765 ± 927, t = 39.754, P < 0.001), and also there were significant differences in DNA damage rates (28.0% ± 10.0% vs 23.6% ± 9.2%) and in apoptosis rates (8.0% ± 0.9% vs 4.5% ± 0.8%) following UV exposure between two groups of cells. The miR-9 expression-inhibited cells showed lower level (1.87 ± 0.15) µmol/L of glutathione compared with the control cells (9.85 ± 0.15) µmol/L (t = -48.832, P < 0.001). CONCLUSION: Inhibition of miR-9 expression promoted UV-induced ROS damage in nasopharyngeal carcinoma cells.


Assuntos
MicroRNAs/metabolismo , Neoplasias Nasofaríngeas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Apoptose , Carcinoma , Linhagem Celular Tumoral , Dano ao DNA , Humanos , Carcinoma Nasofaríngeo , Transfecção
16.
Head Neck ; 35(3): 311-5, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22367764

RESUMO

BACKGROUND: The clinical efficiency and functional outcomes of supracricoid partial laryngectomy (SCPL) with cricothyroidopexy (CTP) were compared with those of the traditional SCPL with cricohyoidoepiglottopexy (CHEP) in treating laryngeal squamous carcinoma involving anterior vocal commissure (AVC). METHODS: From January 2000 to June 2009, 50 patients diagnosed with early- or intermediate-stage (T1b-T3 classification) glottic cancer involving AVC were treated with SCPL-CHEP or SCPL-CTP. Postoperative complications, local recurrence, survival rate, and speech performance were compared between these 2 surgical procedures. RESULTS: Patients undergoing SCPL-CHEP or SCPL-CTP manifested similar levels of postoperative complications, tumor recurrence, and survival rates. However, the SCPL-CTP group showed significantly lower Voice Handicap Index (VHI) scores, higher maximum phonation time, and improved glottic reconstruction and closure than the SCPL-CHEP group. CONCLUSION: The SCPL-CTP procedure better preserves postoperative speech performance than the SCPL-CHEP procedure, underscoring the moderate effectiveness of SCPL-CTP as a treatment for laryngeal squamous carcinoma involving AVC.


Assuntos
Carcinoma de Células Escamosas/cirurgia , Cartilagem Cricoide/patologia , Neoplasias de Cabeça e Pescoço/cirurgia , Neoplasias Laríngeas/cirurgia , Laringectomia/métodos , Procedimentos de Cirurgia Plástica/métodos , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/mortalidade , Cartilagem Cricoide/cirurgia , Feminino , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Neoplasias Laríngeas/mortalidade , Neoplasias Laríngeas/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Complicações Pós-Operatórias , Carcinoma de Células Escamosas de Cabeça e Pescoço , Taxa de Sobrevida , Resultado do Tratamento , Qualidade da Voz
17.
PLoS One ; 8(1): e52723, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23326350

RESUMO

OBJECTIVE: The therapeutic effect of middle frontal horizontal partial laryngectomy (MFHPL) in treating stage T1b squamous cell carcinoma of the glottic larynx involving anterior vocal commissure (AVC) was compared with that of the anterior frontolateral vertical partial laryngectomy (AFVPL). The feasibility and practical significance of MFHPL in clinical application was discussed in the present study. METHODS: From January 1996 to January 2010, a total of 65 patients diagnosed with stage T1bN0M0 glottic laryngeal cancer were treated with MFHPL or AFVPL. The postoperative complications, glottic reconstruction, recurrence rate, voice quality and survival rates were evaluated and compared between two treatments. RESULTS: AFVPL and MFHPL were performed in 34 and 31 patients, respectively. Flexible fiberoptic laryngoscopy revealed that in the MFHPL-treated patients the reconstructed glottis was spacious and symmetric. In contrast, AFVPL treatment resulted in irregular glottic area with poor symmetry and tubular glottis. The incidence of postoperative laryngeal stenosis significantly differed between the MFHPL- and AFVPL-treated groups (P = 0.025). No significant difference was detected in the 3- and 5-year overall- or tumor-free survival rates between two treatments. The Voice Handicap Index (VHI) and maximum phonation time (MPT) after surgery were 51.0±12.99 and 12.42±3.44 sec in the AFVPL-treated group; while in the MFHPL-treated patients they were 31.81±7.48 and 7.65±1.98 sec, respectively. Both differences in VHI (P = 0.012) and MPT (P = 0.024) were significant between two treatments. CONCLUSIONS: MFHPL was comparable to AFVPL with respect to postoperative complications, recurrence rate and survival rates, but possessed advantages over AFVPL in terms of the incidence of laryngeal stenosis and voice quality. Our study indicated that MFHPL has a potential value in clinical practice of treating stage T1b squamous cell carcinoma of the glottic larynx involving AVC.


Assuntos
Carcinoma de Células Escamosas/cirurgia , Neoplasias Laríngeas/cirurgia , Laringectomia/métodos , Laringe/cirurgia , Prega Vocal/cirurgia , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Feminino , Glote/patologia , Glote/cirurgia , Humanos , Estimativa de Kaplan-Meier , Neoplasias Laríngeas/mortalidade , Neoplasias Laríngeas/patologia , Laringectomia/mortalidade , Laringoscopia , Laringoestenose/etiologia , Laringe/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Complicações Pós-Operatórias/etiologia , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Prega Vocal/patologia , Qualidade da Voz
18.
J Exp Clin Cancer Res ; 31: 94, 2012 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-23151319

RESUMO

BACKGROUND: DJ-1 can induce the tumor cell proliferation and invasion via down-regulating PTEN in many malignant tumors, and correlated to prognostic significance. However, the tumorigenesis role and clinical significance of DJ-1 in supraglottic squamous cell carcinoma (SSCC) is unclear. We aimed to evaluate the DJ-1 the relationship between DJ-1 and clinicopathological data including patient survival. METHODS: The expression of DJ-1 and PTEN in SSCCs (52) and adjacent non-cancerous tissues (42) was assessed by immunohistochemistry (IHC), and the relationship between DJ-1 and clinicopathological data was analyzed. RESULTS: DJ-1 was detected mainly in SSCCs (88.5%) and less frequently in adjacent non-cancerous tissues (21.0%). PTEN expression was detected in 46.2% of SSCCs and in 90.5% of adjacent non-cancerous tissues. DJ-1 expression was linked to nodal status (P = 0.009), a highly significant association of DJ-1 expression with shortened patient overall survival (5-year survival rate 88.0% versus 53.9%; P = 0.007; log rank test) was demonstrated. CONCLUSIONS: Our data suggested that DJ-1 over-expression was linked to nodal status, and might be an independent prognostic marker for patients with SSCC.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Peptídeos e Proteínas de Sinalização Intracelular , Neoplasias Laríngeas , Proteínas Oncogênicas , PTEN Fosfo-Hidrolase , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Transformação Celular Neoplásica , Feminino , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Neoplasias Laríngeas/genética , Neoplasias Laríngeas/metabolismo , Neoplasias Laríngeas/patologia , Masculino , Pessoa de Meia-Idade , Proteínas Oncogênicas/genética , Proteínas Oncogênicas/metabolismo , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , Prognóstico , Proteína Desglicase DJ-1 , Carcinoma de Células Escamosas de Cabeça e Pescoço , Taxa de Sobrevida
19.
Arch Otolaryngol Head Neck Surg ; 138(2): 183-8, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22351866

RESUMO

OBJECTIVE: To compare the real-time diagnostic accuracy of conventional white-light imaging (WLI) endoscopy with that of narrow-band imaging (NBI) endoscopy in patients at high risk for nasopharyngeal carcinoma (NPC). DESIGN: Prospective study. SETTING: A university tertiary care center. PATIENTS: From July 28 through October 27, 2009, a total of 211 consecutive patients at high risk for NPC were enrolled. A high-performance endoscopic system equipped with WLI and NBI modes was used for a detailed examination of the nasopharynx during the same endoscopy. MAIN OUTCOME MEASURES: Diagnostic efficacies of WLI and NBI were compared with pathologic findings. Lesions were classified according to the detailed morphologic epithelial microvessel observations during NBI. RESULTS: A total of 285 lesions were detected, including 66 cancerous lesions. The sensitivity and negative predictive values of NBI in NPC screening were significantly higher than those of WLI (93.9% vs 71.2%, P = .001; and 98.1% vs 91.7%, P = .003; respectively); specificity and positive predictive value were not significantly different. During NBI, the presence of superficial, distorted, irregularly shaped microvessels indicated malignant lesions; 53 of 55 lesions (96.4%) with type IV intrapapillary capillary loops were confirmed on histologic testing as malignant. The false-negative and false-positive rates for NBI were 4.5% and 3.6%, respectively. CONCLUSIONS: Narrow-band imaging endoscopy is a promising tool to differentiate nonmalignant from malignant nasopharyngeal lesions on the basis of the morphologic findings of mucosal capillary vessels in vivo. In addition, NBI may increase the diagnostic value of endoscopy in populations at high risk for NPC.


Assuntos
Carcinoma de Células Escamosas/diagnóstico , Endoscopia/métodos , Neoplasias Nasofaríngeas/diagnóstico , Adulto , Carcinoma , Carcinoma de Células Escamosas/patologia , Distribuição de Qui-Quadrado , Diagnóstico Precoce , Feminino , Humanos , Masculino , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/patologia , Valor Preditivo dos Testes , Estudos Prospectivos , Sensibilidade e Especificidade
20.
Laryngoscope ; 122(11): 2367-72, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22865513

RESUMO

OBJECTIVES/HYPOTHESIS: The aim of this article was to describe our surgical technique for the treatment of nasal septal perforations with diameters of 1 to 2 cm. STUDY DESIGN: Retrospective clinical research. METHODS: We reviewed 13 patients with moderate nasal septal perforations (1-2 cm diameter) treated with a sandwich technique (bone or cartilage and quadriceps fascia graft as an interposition graft) by an endoscope-assisted intranasal approach from January 2008 to June 2011. Follow-up periods were 3 months. RESULTS: Thirteen patients were treated with the sandwich technique. Twelve cases (92.3%) were completely healed. One case received incomplete closures without any postoperative symptoms. All patients were found not to have any complications after surgery. CONCLUSIONS: The transnasal endoscopic sandwich technique for repairing moderate nasal septal perforation (1-2 cm) has a high success rate and is easy to perform.


Assuntos
Endoscopia/métodos , Perfuração do Septo Nasal/cirurgia , Rinoplastia/métodos , Adolescente , Adulto , Criança , Fáscia/transplante , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Retalhos Cirúrgicos , Resultado do Tratamento
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