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1.
Otolaryngol Head Neck Surg ; 171(1): 172-179, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38639320

RESUMEN

OBJECTIVES: To assess the value of carbon dioxide transoral laser microsurgery (CO2 TOLMS) for early-stage glottic cancer with special regard to involvement of the anterior commissure (AC). STUDY DESIGN: Single-center retrospective cohort study. SETTING: Grade-A tertiary hospital. METHODS: A retrospective analysis of patients with early-stage (Tis-T2) glottic cancer who underwent CO2 TOLMS. All patients had at least 2 years of follow-up. The univariate and multivariate survival analyses were used to identify the risk factors for recurrence and the Kaplan-Meier method was used to analyze OS and DSS rates. RESULTS: A total of 102 patients were included in the study. Eleven patients (10.78%) had recurrence. The univariate analysis showed that the recurrence was associated with the AC classification, T staging, tumor size, and tobacco use (P < .05). However, on multivariate analysis, the AC classification was the only independent risk factor for recurrence (P < .001, HR = 3.179). AC classification were distributed as follows: 59 (57.84%) AC0, 29 (28.43%) AC1, 8 (7.84%) AC2, and 6 (5.88%) AC3, 2-year/5-year OS and DSS rates were progressively reduced in the AC0, AC1, AC2, and AC3 groups (P < .001). At the same T staging, the OS rates incrementally decreased as the level of involvement of the AC became higher (P = .004). CONCLUSION: CO2 TOLMS is an effective treatment for early-stage glottic cancer. AC involvement is an independent risk factors for recurrence and poor prognosis. The AC classification system may be better at grading the prognosis of patients with early-stage glottic cancer and has prognostic value independent of T staging.


Asunto(s)
Glotis , Neoplasias Laríngeas , Terapia por Láser , Microcirugia , Estadificación de Neoplasias , Humanos , Neoplasias Laríngeas/cirugía , Neoplasias Laríngeas/patología , Neoplasias Laríngeas/mortalidad , Masculino , Glotis/cirugía , Glotis/patología , Estudios Retrospectivos , Femenino , Microcirugia/métodos , Persona de Mediana Edad , Terapia por Láser/métodos , Anciano , Resultado del Tratamiento , Recurrencia Local de Neoplasia , Adulto , Láseres de Gas/uso terapéutico , Anciano de 80 o más Años
3.
Technol Cancer Res Treat ; 19: 1533033820962114, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33267716

RESUMEN

OBJECTIVE: To explore the inhibitory and synergistic effects of 5-fluorouracil and curcumin on Hep-2 laryngeal cancer cells and clarify the effect of mesoporous silica nanoparticles as drug carriers. METHODS: The inhibitory effects of 5-fluorouracil and curcumin on Hep-2 cells were detected using the CCK-8 assay. CompuSyn was used to calculate the synergistic effect of the 2 drugs. Flow cytometry was used to detect apoptosis and cell cycle arrest induced by 5-fluorouracil and curcumin. The drugs were loaded into mesoporous nanoparticles. Western blotting was used to detect the expression of related proteins after treatment. The growth of subcutaneous tumors in BALB/c nude after the intraperitoneal injection with drug-loaded mesoporous silica nanoparticles was recorded. RESULTS: 5-Fluorouracil and curcumin synergistically induced apoptosis and cell cycle arrest in Hep-2 cells. Mesoporous silica nanoparticles as drug carriers enhanced the therapeutic effects of 5-fluorouracil and curcumin. CONCLUSIONS: Mesoporous silica nanoparticles are expected to be effective drug carriers that enhance the synergistic effects of 5-fluorouracil and curcumin on laryngeal cancer.


Asunto(s)
Curcumina/farmacología , Sistemas de Liberación de Medicamentos , Neoplasias Laríngeas/tratamiento farmacológico , Nanopartículas/química , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Curcumina/química , Portadores de Fármacos/química , Portadores de Fármacos/farmacología , Fluorouracilo/química , Fluorouracilo/farmacología , Humanos , Neoplasias Laríngeas/patología , Dióxido de Silicio/química
4.
Cell Commun Signal ; 17(1): 173, 2019 12 27.
Artículo en Inglés | MEDLINE | ID: mdl-31881947

RESUMEN

BACKGROUND: Accumulation of immunosuppressive protein programmed death-ligand 1 (PD-L1) has been documented in several cancers and contributes to the evasion of the host immune system. However, cancer cell-intrinsic signaling-dependent control of PD-L1 expression remains to be elucidated. Herein, we aimed to identify the let-7 family of microRNAs as candidates that up-regulate tumor cell PD-L1 expression and mediates immune evasion of head and neck squamous cell carcinoma (HNSCC). METHODS: The expression of let-7 family and PD-L1 was quantified in HNSCC tissues and adjacent normal tissues. PD-L1 degradation was evaluated in HNSCC cells in response to elevated expressions of let-7a or let-7b. The regulation of let-7 family on PD-L1 degradation through a mechanism involving T-cell factor-4 (TCF-4) control of ß-catenin/STT3 pathway was evaluated. Immune recognition of HNSCC in vivo was examined in subcutaneous tumor-bearing C3H mice in the presence of let-7a/b and/or CTLA-4 antibody. RESULTS: The let-7 family were significantly down-regulated in the context of HNSCC, sharing a negative correlation with PD-L1 expression. Glycosylated PD-L1 was detected in HNSCC cells, which was reduced by let-7a/b over-expression. TCF-4, the target of let-7a/b, activated the ß-catenin/STT3 pathway and promoted PD-L1 degradation. In vivo analysis demonstrated that let-7a/b over-expression potentiated anticancer immunotherapy by CTLA-4 blockade. CONCLUSIONS: Taken together, our findings highlight targeting let-7 family as a potential strategy to enhance immune checkpoint therapy for HNSCC.


Asunto(s)
Antígeno B7-H1/metabolismo , Neoplasias de Cabeza y Cuello/inmunología , MicroARNs/genética , Proteolisis , Carcinoma de Células Escamosas de Cabeza y Cuello/inmunología , Antígeno B7-H1/antagonistas & inhibidores , Células Cultivadas , Glicosilación , Células HEK293 , Neoplasias de Cabeza y Cuello/diagnóstico , Neoplasias de Cabeza y Cuello/terapia , Humanos , Transducción de Señal/efectos de los fármacos , Transducción de Señal/inmunología , Carcinoma de Células Escamosas de Cabeza y Cuello/diagnóstico , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia
5.
Pathol Oncol Res ; 25(4): 1437-1443, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-30361911

RESUMEN

To study the expression of programmed death-ligand 1 (PD-L1), and its effects on CD8+ tumor infiltrating lymphocytes (TILs) and tumor associated macrophages (TAMs) in human laryngeal squamous cell carcinoma. Sixty-nine patients with laryngeal carcinoma and 10 with vocal cord leukoplakia received tumor resection at Neck Surgery Department in the Second Affiliation Hospital of Jilin University (Changchun, Jilin) from Jan. 2010 to Dec. 2015. The expressions of PD-L1, CD8, CD16 and CD206 in laryngeal carcinoma, paracancerous and vocal cord leukoplakia tissues were detected with immunohistochemistry. The associations between PD-L1 expression and clinicopathologic features, expression of TAMs and CD8+ T cell infiltration were analyzed. Expression of PD-L1 is significantly higher in laryngeal carcinoma than in paracancerous or leukoplakia tissue. The expression of PD-L1 is closely associated with stage of laryngeal cancer, histological differentiation and neck lymphatic metastasis. PD-L1 expression is negatively correlated with the number of CD8+ TILs and CD16+ cells (M1 type TAMs), while is positively associated with CD206+ (M2 type TAMs). PD-L1 is highly expressed in the laryngeal cancer with the tumor microenvironment immunosuppression.


Asunto(s)
Antígeno B7-H1/metabolismo , Linfocitos T CD8-positivos/inmunología , Carcinoma de Células Escamosas/inmunología , Neoplasias Laríngeas/inmunología , Linfocitos Infiltrantes de Tumor/inmunología , Microambiente Tumoral/inmunología , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/secundario , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Laríngeas/metabolismo , Neoplasias Laríngeas/patología , Metástasis Linfática , Masculino , Persona de Mediana Edad
6.
J Mater Chem B ; 5(2): 307-317, 2017 Jan 14.
Artículo en Inglés | MEDLINE | ID: mdl-32263549

RESUMEN

Eukaryotic translation initiation factor (eIF) 4E is a valuable marker in cancer prognostics in many human cancers. Silencing eIF4E via delivery of siRNA may be able to overcome chemoresistance. Cisplatin, used as a first-line anti-cancer reagent, has been widely accepted for its great success in clinical applications but it is restricted due to severe side effects such as nephrotoxicity, peripheral neuropathy, and hearing loss. Moreover, platinum drug resistance is a major obstacle to its use. Platinum(iv) prodrugs (denoted as Pt(iv)) which could be reduced to Pt(ii) by various reductants, including mercaptan and glutathione, within cancer cells have very limited toxicity and might overcome platinum resistance because of their chemical inertness. Moreover, combinational therapies that could sensitize the cancer cells to Pt drugs have received great attention nowadays around the world. Here we report a simple and effective upconversion nanoparticle carrier system loaded with both eIF4E siRNA and Pt(iv). We find that this theranostic system could sensitize laryngeal cancer cells to cisplatin based chemotherapy and allow bioimaging both in vitro and in vivo.

7.
Int J Med Sci ; 13(12): 914-922, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27994496

RESUMEN

There is accumulating evidence indicating that long non-coding RNA H19 and its mature product miR-675 play essential roles for tumor growth and progression. However, their prognostic value in human head and neck squamous cell carcinoma (HNSCC), particular in laryngeal carcinoma, remains to be elucidated. In this study, we observed that both H19 and miR-675 were significantly overexpressed in a cohort of 65 primary tumor samples and two HNSCC cell lines. Importantly, when paired with patient follow-up data, higher expression of either H19 or miR-675 was significantly correlated with higher risk of patient relapse, and associated with worse overall survival and poor disease-free survival. Knockdown miR-675 caused significant reduction of cell viability, migratory and invasive capabilities. Taken together, these results suggest that the strong correlation of H19 overexpression together with higher miR-675 and lymph node metastases could be useful predictive markers, indicating a potentially therapeutic strategy for HNSCC patients.


Asunto(s)
Regulación Neoplásica de la Expresión Génica , Neoplasias de Cabeza y Cuello/genética , MicroARNs/genética , ARN Largo no Codificante/genética , Anciano , Carcinogénesis/genética , Línea Celular Tumoral , Proliferación Celular/genética , Proliferación Celular/fisiología , Femenino , Humanos , Técnicas In Vitro , Masculino , Persona de Mediana Edad , Reacción en Cadena en Tiempo Real de la Polimerasa
8.
Artículo en Chino | MEDLINE | ID: mdl-27373039

RESUMEN

OBJECTIVE: To assess the effect of CPAP therapy on sleep quality and quality of life in patients with moderate or severe OSAHS. METHOD: Seventy-two patients diagnosed as OSAHS by polysomnography (PSG) were assigned to receive CPAP therapy for 3 months. At baseline and three months after treatment patients underwent polysomnography (PSG). Analyze the results of PSG, sleep quality, excessive daytime sleepiness, quality of life and the general well-being. RESULT: The lowest average oxygen saturation and the average blood oxygen saturation improved significantly after CPAP therapy, and the longest sleep apnea time and AHI decreased obviously (P < 0.01). Except body pain, the other seven dimensions of SF-36 improved obviously (P < 0.01); ESS, PSQI and GWB also improved (P < 0.05). CONCLUSION: For patients with moderate or severe OSAHS, CPAP therapy can obviously improve the sleep quality, excessive daytime sleepiness, improve patients' life quality and the general well-being.


Asunto(s)
Presión de las Vías Aéreas Positiva Contínua , Calidad de Vida , Apnea Obstructiva del Sueño/terapia , Humanos , Oximetría , Polisomnografía
9.
Acta Otolaryngol ; 136(8): 764-7, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27056263

RESUMEN

CONCLUSION: BDET might be effective for the patients with OME, and proved to be an efficacious and mini-invasive treatment for OME. OBJECTIVES: To evaluate the therapeutic benefits of balloon dilation eustachian tuboplasty (BDET) in the treatment of adult patients with otitis media with effusion (OME) caused by eustachian tube dysfunction (ETD). METHODS: After informed consent, eight adult patients with OME were included in this study. After investigated patients' case history and oto-function, all patients underwent BDET treatment. Then four criteria including tympanic membrane, pure tone audiometry (PTA), tympanometry, and subjective symptoms were adopted to evaluate the therapeutic benefits of BDET. RESULTS: None of the involved patients complained of problems or complications during the post-operative period, or with absence of pain and bleeding after the operation. Prominent post-operative improvement was observed in tympanic membrane and otoscopic appearance. In addition, cure rates after 3 months and 6 months post-operatively were gradually increased.


Asunto(s)
Trompa Auditiva/cirugía , Otitis Media con Derrame/cirugía , Enfermedad Crónica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento
10.
Oncol Lett ; 10(2): 631-636, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-26622545

RESUMEN

According to the cancer stem cell theory, a small subpopulation of cancer cells, known as cancer stem cells (CSCs), exist that are self-renewing and are involved in tumor invasion, metastasis and recurrence. A number of studies have reported that certain cancer cells are able to efflux the Hoechst 33342 dye. These cells are termed side population (SP) cells and share characteristic features of CSCs. The results of the present study revealed that 2.7% of primary head and neck squamous cell carcinoma (HNSCC) cells were SP cells. This was reduced to 0.7% following treatment with verapamil. The immunofluorescence and reverse transcription polymerase chain reaction analysis revealed that SP cells have an enhanced expression of the ATP-binding cassette (ABC) transporter protein ABC subfamily G, member 2 (ABCG2), which has been identified to be actively involved in drug exclusion. Similarly, the mRNA level of the oncogene B lymphoma Mo-MLV insertion region-1 and the stem cell surface proteins nestin and octamer-binding transcription factor-4 were highly expressed in the SP cells compared with the non-SP cells. In addition, it was demonstrated that HNSCC SP cells exhibited increased proliferation and were highly resistant to multiple drugs. These findings suggest that the presence of CSCs, such as SP cells, may be responsible for chemotherapy failure and tumor relapse in patients with HNSCC. Therefore, the identification of a novel therapeutic drug that could effectively target CSCs may help to eradicate refractory tumors.

11.
Int J Clin Exp Pathol ; 8(9): 10995-1004, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26617817

RESUMEN

BACKGROUND: There is increasing evidence demonstrating the role of human trophoblast cell surface antigen 2 (TROP2) in cancer development and progression. However, their prognostic value in Epstein-Barr virus (EBV) associated nasopharyngeal carcinoma (NPC) remains to be elucidated. METHOD: The prognostic significances of TROP2 and Ki-67 were determined by immunohistochemistry in 58 NPC samples. TROP2 mRNA expression level and biological functions were evaluated. The presence of EBV was assessed using in situ hybridization. Analyses were conducted on the association between each of these variables as well as clinical outcome. RESULTS: TROP2 was exhibited over expression in 64% of NPC samples and significantly associated with highly proliferative tumor cells (P = 0.05) and lymph node metastases (P = 0.03). Overexpression of TROP2 significantly correlated with worse overall survival (P = 0.026) and poor disease-free survival (P = 0.021). By univariate analysis, high expression of TROP2 significantly correlated with patients with distant metastases, Ki-67 and EBV infection. Multivariate analysis further revealed that TROP2 along with Ki-67 and distant metastasis are independent prognostic predictors for NPC patients. CONCLUSION: Our findings have demonstrated that overexpression of TROP2 appears to be an independent predictor for poor clinical outcome in NPC. The strong correlation of overexpression of TROP2 with Ki-67 and distant metastases indicates a potentially therapeutic strategies targeting TROP2 for NPC patients.


Asunto(s)
Antígenos de Neoplasias/metabolismo , Biomarcadores de Tumor/análisis , Moléculas de Adhesión Celular/metabolismo , Neoplasias Nasofaríngeas/patología , Adulto , Anciano , Western Blotting , Carcinoma , Supervivencia sin Enfermedad , Infecciones por Virus de Epstein-Barr/complicaciones , Femenino , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Antígeno Ki-67/metabolismo , Masculino , Persona de Mediana Edad , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/mortalidad , Neoplasias Nasofaríngeas/virología , Pronóstico , Modelos de Riesgos Proporcionales , ARN Interferente Pequeño , Reacción en Cadena en Tiempo Real de la Polimerasa , Transfección , Adulto Joven
12.
Mol Med Rep ; 12(3): 4352-4357, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26081022

RESUMEN

The presence of cancer stem cells (CSCs) has major implications in the choice of cancer treatment strategy and is responsible for tumor relapse. CSCs have been isolated and characterized in several types of cancer; however, studies concerning the CSCs from nasopharyngeal carcinoma (NPC) are limited. Thus, the present study was designed to isolate and characterize the cancer stem-like side population (SP) cells from NPC samples. The fluorescence-activated cell sorting (FACS)-based Hoechst 33342 dye exclusion technique identified that 3.9% of cells from NPC samples were cancer stem-like SP cells. Upon treatment with verapamil (ABC transporter inhibitor), the percentage of SP cells was significantly reduced to 0.7%, which confirms that the ABC transporter protein exhibits a significant role in drug exclusion. Fluorescence microscopy analysis revealed that the FACS purified SP cells showed increased expression of ABCG2 (ATP transporter protein), Oct-4 and CD44 (stem cell surface protein). Furthermore, these SP cells exhibited increased mRNA expression of ABCG2 and anti-apoptotic factor Bmi-1, which contribute to multi-drug resistance and increased cell survival rate. Notably, the Wnt/ß-catenin signaling pathways are altered in SP cells. In addition, using reverse transcription­quantitative polymerase chain reaction analysis it was observed that the cells exhibited increased expression of DKK1 and AXIN2. In conclusion, data from the present study clearly demonstrated that the presence of cancer stem-like SP cells from NPC may be responsible for chemotherapeutic drug resistance, tumor recurrence and invasion.


Asunto(s)
Transportadoras de Casetes de Unión a ATP/metabolismo , Antineoplásicos/farmacología , Resistencia a Antineoplásicos , Neoplasias Nasofaríngeas/metabolismo , Proteínas de Neoplasias/metabolismo , Células Madre Neoplásicas/metabolismo , Células de Población Lateral/metabolismo , Vía de Señalización Wnt , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2 , Transportadoras de Casetes de Unión a ATP/genética , Carcinoma , Expresión Génica , Humanos , Carcinoma Nasofaríngeo , Proteínas de Neoplasias/genética , Células Madre Neoplásicas/efectos de los fármacos , Complejo Represivo Polycomb 1/genética , Complejo Represivo Polycomb 1/metabolismo , Células de Población Lateral/efectos de los fármacos , Células Tumorales Cultivadas
13.
Mol Med Rep ; 12(2): 2457-64, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-25936657

RESUMEN

The present study aimed to identify key genes and relevant microRNAs (miRNAs) involved in laryngeal squamous cell carcinoma (LSCC). The gene expression profiles of LSCC tissue samples were analyzed with various bioinformatics tools. A gene expression data set (GSE51985), including ten laryngeal squamous cell carcinoma (LSCC) tissue samples and ten adjacent non-neoplastic tissue samples, was downloaded from the Gene Expression Omnibus. Differential analysis was performed using software package limma of R. Functional enrichment analysis was applied to the differentially expressed genes (DEGs) using the Database for Annotation, Visualization and Integrated Discovery. Protein-protein interaction (PPI) networks were constructed for the protein products using information from the Search Tool for the Retrieval of Interacting Genes/Proteins. Module analysis was performed using ClusterONE (a software plugin from Cytoscape). MicroRNAs (miRNAs) regulating the DEGs were predicted using WebGestalt. A total of 461 DEGs were identified in LSCC, 297 of which were upregulated and 164 of which were downregulated. Cell cycle, proteasome and DNA replication were significantly over-represented in the upregulated genes, while the ribosome was significantly over-represented in the downregulated genes. Two PPI networks were constructed for the up- and downregulated genes. One module from the upregulated gene network was associated with protein kinase. Numerous miRNAs associated with LSCC were predicted, including miRNA (miR)-25, miR-32, miR-92 and miR-29. In conclusion, numerous key genes and pathways involved in LSCC were revealed, which may aid the advancement of current knowledge regarding the pathogenesis of LSCC. In addition, relevant miRNAs were also identified, which may represent potential biomarkers for use in the diagnosis or treatment of the disease.


Asunto(s)
Biomarcadores de Tumor/genética , Carcinoma de Células Escamosas/genética , Ciclo Celular/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias Laríngeas/genética , Programas Informáticos , Biomarcadores de Tumor/metabolismo , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Biología Computacional , Replicación del ADN , Bases de Datos Genéticas , Perfilación de la Expresión Génica , Redes Reguladoras de Genes , Humanos , Neoplasias Laríngeas/metabolismo , Neoplasias Laríngeas/patología , MicroARNs/genética , MicroARNs/metabolismo , Anotación de Secuencia Molecular , Complejo de la Endopetidasa Proteasomal/genética , Complejo de la Endopetidasa Proteasomal/metabolismo , Mapeo de Interacción de Proteínas , Proteínas Quinasas/genética , Proteínas Quinasas/metabolismo , Ribosomas/genética , Ribosomas/metabolismo
14.
Int J Clin Exp Pathol ; 7(9): 5683-91, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25337209

RESUMEN

Despite of the variety of combined modality treatments for laryngeal carcinoma have been introduced, the distance recurrence rate and 5-year overall survival rate over the past decades are still the major issues, underlining the importance to better understand the biological bases that contribute to disease progression. Here, we reported that miR-423-3p overexpressed in primary laryngeal carcinoma cell line where it plays a critical role in tumor progression. Suppression of miR-423-3p expression resulted in decreasing cell proliferation, clonogenicity, cell migration and invasion. By using in silico prediction algorithms for target identification, AdipoR2 (adiponectin receptor 2) and DUSP4 (MAP kinase phosphatase 2) were identified to be potential targets of miR-423-3p. Overexpression of miR-423-3p was associated with epigenetic silencing of AdipoR2 in human laryngeal carcinoma samples, which have been previously implicated in suppression of tumor proliferation and angiogenesis. Luciferase reporter assays and western blot further confirmed the direct interaction of miR-423-3p with AdipoR2. Our findings have demonstrated that miR-423-3p plays an important oncogenic role in laryngeal carcinoma progression, and further suggest that suppression of miR-423-3p expression might be useful for its clinical management.


Asunto(s)
Carcinoma/metabolismo , Neoplasias Laríngeas/metabolismo , MicroARNs/metabolismo , Receptores de Adiponectina/metabolismo , Regiones no Traducidas 3' , Algoritmos , Sitios de Unión , Carcinoma/genética , Carcinoma/patología , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Biología Computacional , Simulación por Computador , Bases de Datos Genéticas , Epigénesis Genética , Regulación Neoplásica de la Expresión Génica , Silenciador del Gen , Humanos , Neoplasias Laríngeas/genética , Neoplasias Laríngeas/patología , MicroARNs/genética , Invasividad Neoplásica , Receptores de Adiponectina/genética , Transducción de Señal , Transfección , Regulación hacia Arriba
15.
Ear Nose Throat J ; 93(8): E8-10, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-25181675

RESUMEN

B-cell lymphoma of the paranasal sinuses is rare. We present the case of a 42-year-old woman who presented with proptosis, diplopia, and vision disturbances in the right eye. She was diagnosed with diffuse large B-cell lymphoma of the ethmoid sinus. We describe the general clinical presentation, diagnosis, and differential diagnosis of this entity, and we review the pathology of diffuse large B-cell lymphoma.


Asunto(s)
Senos Etmoidales , Linfoma de Células B Grandes Difuso/diagnóstico , Neoplasias de los Senos Paranasales/diagnóstico , Adulto , Diplopía/etiología , Exoftalmia/etiología , Femenino , Humanos , Linfoma de Células B Grandes Difuso/patología , Neoplasias de los Senos Paranasales/patología
16.
Int J Clin Exp Med ; 7(2): 337-47, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24600487

RESUMEN

The mammalian target of rapamycin (mTOR) kinase forms two multiprotein complexes, mTORC1 and mTORC2, which regulate cell growth, survival, and autophagy. Allosteric inhibitors of mTORC1, such as rapamycin, have been extensively used to study tumor cell growth, proliferation, and autophagy but have shown only limited clinical utility. Here, we describe AZD8055, a novel ATP-competitive inhibitor of mTOR kinase activity, against all class I phosphatidylinositol3-kinase (PI3K) and other members of the PI3K-like kinase family. The study was to determine the effect of AZD8055 on proliferation and apoptosis on Hep-2, a human laryngeal cancer cell line and to investigate the underlying mechanism(s) of action. Hep-2 cells were treated with AZD8055 for 24, 48 or 72 h. MTT was used to determine cell proliferation. Rhodamine 123 and TUNEL staining were used to determine mitochondrial membrane potential and cell apoptosis analyzed by fluorescence-activated cell sorting (FACS). Protein expressions were examined by western blotting. Treatment with AZD8055 inhibited proliferation and induced apoptosis in Hep-2 cells in a dose- and time-dependent manner. During the prolonged treatment with AZD8055, AZD8055 inhibits the mammalian target of rapamycin mTOR. Further experiments showed which signaling cascade p-4EBP1 and substrate EIF4E as well as downstream proteins were down regulated. Furthermore, our study showed that the expression profiles of various BH3-only proteins including Bid, Bad, and Bim, apoptosis regulatory protein cleaved caspase3 was up regulated in a time-dependent manner in Hep-2 cells treated with AZD8055. Thus, in vitro, AZD8055 potently inhibits proliferation and induces apoptosis in head and neck squamous cell carcinoma.

17.
Exp Ther Med ; 6(5): 1317-1321, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-24223665

RESUMEN

Chemoresistance is one of the major barriers to chemotherapeutic treatment and it has been established that CD133+ cancer stem cells are responsible for drug resistance in laryngeal carcinoma. In the present study, curcumin and cisplatin were used as a combined treatment to induce the sensitivity of CD133+ cancer stem cells to chemotherapeutic agents and to enhance therapeutic effectiveness. The results revealed that in untreated and cisplatin-treated HEp-2 cell groups, the percentage of CD133+ cells was 4.50 and 6.89%, respectively. However, in the combined treatment group, the percentage of CD133+ cells was markedly reduced to 1.49%, indicating that curcumin may increase the sensitivity of CD133+ cells to cisplatin, leading to the suppression of chemoresistance in HEp-2 cells. Furthermore, the expression of ATP-binding cassette sub-family G member 2 (ABCG2), which is an important gene for chemoresistance, was demonstrated to be reduced in CD133+ cancer stem cells following combined treatment. These results suggest that the combined application of curcumin with chemotherapeutic drugs may be a reliable and effective approach for the treatment of laryngeal carcinoma.

18.
Int J Clin Exp Pathol ; 6(10): 2071-81, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-24133585

RESUMEN

OBJECTIVE: To investigate the inhibitory effect of plasmid-based survivin-specific short hairpin RNA and GRIM-19 on the growth of Hep-2 laryngeal cancer cells. METHODS: The plasmid expressing survivin-specific short hairpin RNA (shRNA) and GRIM-19 (p-siRNA survivin/GRIM-19) was prepared and transfected into Hep-2 cells with Lipofectamine 2000. The mRNA and protein expression of surviving and GRIM-19 were measured with RT-PCR and western blot assay, respectively. MTT assay was employed to detect the proliferation of Hep-2 cells, and flow cytometry and AO/EB assay were done to determine the apoptosis of Hep-2 cells. RESULTS: In the p-siRNA survivin/GRIM-19, the mRNA and protein expression of survivin was markedly reduced by 54.4% and 42.2%, and the reduction in protein expression of surviving was more obvious than that in the p-siRNA survivin group (37%) (P<0.05). The protein expression of GRIM-19 was markedly enhanced when compared with the control group (P<0.01). MTT assay revealed the proliferation of Hep-2 cells undergoing transfection with p-siRNA survivin/GRIM-19 was markedly inhibited, and the inhibition rate was as high as 79%, which was higher than that in the psi-survivin group (45%) and p-GRIM-19 group (35%). AO/EB assay and flow cytometry indicated that the apoptotic cells in the p-siRNA survivin/GRIM-19 group were dramatically increased as compared to the psi-survivin group and p-GRIM-19 group. CONCLUSION: The p-siRNA survivin/GRIM-19 has marked decrease in survivin expression and dramatic increase in GRIM-19 expression. Moreover, silencing of survivin and over-expression of GRIM-19 can significantly inhibit the growth and induce the apoptosis of Hep-2 in vitro and in vivo.


Asunto(s)
Proteínas Reguladoras de la Apoptosis/genética , Proliferación Celular , Proteínas Inhibidoras de la Apoptosis/genética , Neoplasias Laríngeas/genética , NADH NADPH Oxidorreductasas/genética , Animales , Apoptosis/genética , Proteínas Reguladoras de la Apoptosis/metabolismo , Línea Celular Tumoral , Modelos Animales de Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica , Silenciador del Gen , Terapia Genética , Humanos , Proteínas Inhibidoras de la Apoptosis/metabolismo , Neoplasias Laríngeas/metabolismo , Neoplasias Laríngeas/patología , Masculino , Ratones , Ratones Desnudos , NADH NADPH Oxidorreductasas/metabolismo , Interferencia de ARN , ARN Interferente Pequeño , Survivin
19.
Int J Med Sci ; 10(12): 1639-48, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-24155656

RESUMEN

An effective cancer therapeutic should target tumours specifically with limited systemic toxicity. Here, we transformed an attenuated Salmonella typhimurium (S. typhimurium) with an Apoptin expressing plasmid into a human laryngeal carcinoma cell line. The expression of the inserted gene was measured using fluorescence and immunoblotting assays. The attenuated S. typhimurium-mediated Apoptin significantly decreased cytotoxicity and strongly increased cell apoptosis through the activation of caspase-3. The process was mediated by Bax, cytochrome c and caspase-9. A syngeneic nude murine tumour model was used to determine the anti-tumour effects of the recombinant bacteria in vivo. Systemic injection of the recombinant bacteria with and without re-dosing caused significant tumour growth delay and reduced tumour microvessel density, thereby extending host survival. Our findings indicated that the use of recombinant Salmonella typhimurium as an Apoptin expression vector has potential cancer therapeutic benefits.


Asunto(s)
Proteínas de la Cápside/genética , Técnicas de Transferencia de Gen , Terapia Genética , Neoplasias Laríngeas/genética , Salmonella typhimurium/genética , Animales , Apoptosis/genética , Proteínas de la Cápside/administración & dosificación , Caspasa 3/biosíntesis , Caspasa 9/metabolismo , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Vectores Genéticos , Humanos , Neoplasias Laríngeas/tratamiento farmacológico , Neoplasias Laríngeas/patología , Ratones , Salmonella typhimurium/química
20.
Chin Med J (Engl) ; 124(7): 1055-60, 2011 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-21542968

RESUMEN

BACKGROUND: Mounting evidence suggests that tumors are histologically heterogeneous and are maintained by a small population of tumor cells termed cancer stem cells. CD133 has been identified as a candidate marker of cancer stem cells in laryngeal carcinoma. This study aimed to analyze the chemoresistance of CD133(+) cancer stem cells. METHODS: The response of Hep-2 cells to different chemotherapeutic agents was investigated and the expression of CD133 was studied. Fluorescence-activated cell sorting analysis was used to identify CD133, and the CD133(+) subset of cells was separated and analyzed in colony formation assays, cell invasion assays, chemotherapy resistance studies, and analyzed for the expression of the drug resistance gene ABCG2. RESULTS: About 1% - 2% of Hep-2 cells were CD133(+) cells, and the CD133(+) proportion was enriched by chemotherapy. CD133(+) cancer stem cells exhibited higher potential for clonogenicity and invasion, and were more resistant to chemotherapy. This resistance was correlated with higher expression of ABCG2. CONCLUSIONS: This study suggested that CD133(+) cancer stem cells are more resistant to chemotherapy. The expression of ABCG2 could be partially responsible for this. Targeting this small population of CD133(+) cancer stem cells could be a strategy to develop more effective treatments for laryngeal carcinoma.


Asunto(s)
Antígenos CD/metabolismo , Antineoplásicos/farmacología , Carcinoma/metabolismo , Glicoproteínas/metabolismo , Neoplasias Laríngeas/metabolismo , Células Madre Neoplásicas/citología , Células Madre Neoplásicas/efectos de los fármacos , Péptidos/metabolismo , Antígeno AC133 , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2 , Transportadoras de Casetes de Unión a ATP/genética , Transportadoras de Casetes de Unión a ATP/metabolismo , Antígenos CD/genética , Western Blotting , Carcinoma/genética , Línea Celular Tumoral , Cisplatino/farmacología , Citometría de Flujo , Fluorouracilo/farmacología , Glicoproteínas/genética , Humanos , Neoplasias Laríngeas/genética , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Células Madre Neoplásicas/metabolismo , Paclitaxel/farmacología , Péptidos/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
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