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1.
J Vestib Res ; 33(2): 137-142, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36847039

RESUMO

BACKGROUND: Diagnostic criteria of vestibular migraine (VM) by the Bárány classification consists of complex combinations of characteristics of dizziness: episodes, intensity, duration, migraine according to International Classification of Headache Disorders (ICHD), and migraine features accompanying vertigo. The prevalence according to strictly applied Bárány criteria may be much lower than preliminary clincal diagnosis. OBJECTIVE: The purpose of this study is to investigate the prevalence of VM according to strictly applied Bárány criteria among dizzy patients who visited the otolaryngology department. METHODS: The medical records of patients with dizziness from December 2018 to November 2020 were retrospectively searched using a clinical big data system. The patients completed a questionnaire designed to identify VM according to Bárány classification. Microsoft Excel function formulas were used to identify cases that met the criteria. RESULTS: During the study period, 955 new patients visited the otolaryngology department complaining of dizziness, of which 11.6% were assessed as preliminary clinical diagnosis of VM in outpatient clinic. However, VM according to strictly applied Bárány criteria accounted for only 2.9% of dizzy patients. CONCLUSION: The prevalence of VM according to strictly applied Bárány criteria could be significantly lower than that of preliminary clinical diagnosis in outpatient clinic.


Assuntos
Transtornos de Enxaqueca , Otolaringologia , Doenças Vestibulares , Humanos , Tontura/diagnóstico , Tontura/epidemiologia , Tontura/complicações , Estudos Retrospectivos , Prevalência , Vertigem/diagnóstico , Vertigem/epidemiologia , Vertigem/complicações , Transtornos de Enxaqueca/diagnóstico , Transtornos de Enxaqueca/epidemiologia , Doenças Vestibulares/diagnóstico , Doenças Vestibulares/epidemiologia
2.
Ann Occup Environ Med ; 33: e11, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34754472

RESUMO

BACKGROUND: Pure-tone audiometry is used as a gold standard for hearing measurement. However, since communication in the work environment occurs in noise, it might be difficult to evaluate the actual communication ability accurately based on pure-tone audiometry only. Therefore, the purpose of this study is to evaluate speech intelligibility in noisy environments by using Speech-in-Noise Tests and to check its relationship with pure-tone audiometry. METHODS: From January 2017 to September 2018, for 362 workers who visited a university hospital for the purpose of compensating for noise-induced hearing loss, several tests were conducted: pure-tone audiometry, speech reception threshold, speech discrimination score, and Speech-in-Noise Tests (Words-in-Noise Test [WIN] and quick-Hearing-in-Noise Test [quick-HINT]). The subjects were classified into serviceable hearing group and non-serviceable hearing group based on 40 dB hearing level (HL) pure-tone average. In both groups, we conducted age-adjusted partial correlation analysis in order to find out the relationship between pure-tone threshold, speech reception threshold, speech discrimination score and WIN and quick-HINT respectively. RESULTS: In non-serviceable hearing group, all results of partial correlation analysis were statistically significant. However, in serviceable hearing group, there were many results which showed little or no significant relationship between pure-tone threshold and Speech-in-Noise Tests (WIN and quick-HINT). CONCLUSIONS: The relationship between Speech-in-Noise Tests and the pure-tone thresholds were different by the hearing impairment levels; in mild to moderate hearing loss workers, there was little or no relationship; in severe cases, the relationship was significant. It is not enough to predict the speech intelligibility of hearing-impaired persons, especially in mild to moderate level, with pure-tone audiometry only. Therefore, it would be recommended to conduct Speech-in-Noise Test.

3.
Auris Nasus Larynx ; 47(6): 982-989, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32650961

RESUMO

OBJECTIVE: To compare the effect of injection time intervals of intratympanic (IT) dexamethasone (DEX) in patients with idiopathic sudden sensorineural hearing loss (ISSNHL). METHODS: Seventy-five adults with ISSNHL were grouped into four groups according to the IT DEX interval. In addition to concurrent oral steroid medication for two weeks, patients received IT DEX injections every 1, 2, 3, and four days, respectively. (Group 1, Group 2, Group 3, and Group 4). We evaluated the treatment outcomes according to modified criteria from "Clinical Practice Guideline: Sudden Hearing Loss" of the American Academy of Otolaryngology-Head and Neck Surgery (AAOHNS) to justify treatment success. RESULTS: There were no significant differences in demographic and baseline audiometric data. The mean of pure tone audiometry (PTA) and speech discrimination score (SDSs) were significantly improved after oral steroid and IT DEX treatment in all four groups. Group 1 showed significantly higher improvement than Group 4 in PTA after treatment. There was a significantly higher complete recovery (CR) rate in Group 1 than Group 4. CONCLUSION: We found a statistically significant difference in the complete hearing recovery rate and audiometric results (PTA) between the group with a daily interval of injections and the group with a four-day time interval. Therefore, daily time intervals in intratympanic steroid injection may be considered as an option for better improvement of hearing in patients with ISSNHL.


Assuntos
Dexametasona/administração & dosagem , Glucocorticoides/administração & dosagem , Perda Auditiva Súbita/tratamento farmacológico , Adulto , Análise de Variância , Audiometria de Tons Puros , Esquema de Medicação , Feminino , Audição/efeitos dos fármacos , Perda Auditiva Neurossensorial/tratamento farmacológico , Humanos , Injeção Intratimpânica , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
4.
Auris Nasus Larynx ; 47(1): 65-70, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31307674

RESUMO

OBJECTIVE: The posterior auricular muscle (PAM) functions in ear projection in normal position and is severed during the retroauricular approach, and some patients complain of a protruding ear postoperatively. This study was designed to determine whether suturing of the severed PAM reduces pinna projection after the retroauricular approach. METHODS: In a prospective controlled study, we enrolled 91 patients with chronic otitis media, all of who underwent canal wall up mastoidectomy with tympanoplasty via retroauricular approach. They were randomly assigned to the PAM-sutured (n=45) or PAM-non-sutured (n=46) group. Helical-mastoid distance and concho-mastoid angle were measured serially. RESULTS: In both groups, helical-mastoid distance was significantly longer than preoperatively until 1 month postoperatively but was similar to preoperatively by 6 months. Concho-mastoid angle increased significantly until 1 month after surgery in the PAM-non-sutured group but returned to the preoperative value at 6 months postoperatively. In the PAM-sutured group, concho-mastoid angle increased significantly at 3 days postoperatively, was similar to preoperatively at 1 month after surgery, and became narrower than preoperatively at 6 months postoperatively. In both groups, there were significant effects of time on the changes in helical-mastoid distance or concho-mastoid angle. Group assignment did not significantly affect these time-related changes. CONCLUSION: PAM suturing did not affect helical-mastoid distance by 6 months postoperatively, but it did reduce the concho-mastoid angle to below the preoperative value at 6 months. We recommend that PAM be left severed to maintain concho-mastoid angle in the long term when using the retroauricular approach.


Assuntos
Pavilhão Auricular , Músculos Faciais/cirurgia , Mastoidectomia/métodos , Aparência Física , Complicações Pós-Operatórias/prevenção & controle , Técnicas de Sutura , Timpanoplastia/métodos , Adulto , Doença Crônica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Otite Média , Procedimentos Cirúrgicos Otológicos/métodos
5.
Theranostics ; 8(15): 4226-4237, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30128049

RESUMO

A fundamental goal of many surgeries is nerve preservation, as inadvertent injury can lead to patient morbidity including numbness, pain, localized paralysis and incontinence. Nerve identification during surgery relies on multiple parameters including anatomy, texture, color and relationship to surrounding structures using white light illumination. We propose that fluorescent labeling of nerves can enhance the contrast between nerves and adjacent tissue during surgery which may lead to improved outcomes. Methods: Nerve binding peptide sequences including HNP401 were identified by phage display using selective binding to dissected nerve tissue. Peptide dye conjugates including FAM-HNP401 and structural variants were synthesized and screened for nerve binding after topical application on fresh rodent and human tissue and in-vivo after systemic IV administration into both mice and rats. Nerve to muscle contrast was quantified by measuring fluorescent intensity after topical or systemic administration of peptide dye conjugate. Results: Peptide dye conjugate FAM-HNP401 showed selective binding to human sural nerve with 10.9x fluorescence signal intensity (1374.44 ± 425.96) compared to a previously identified peptide FAM-NP41 (126.17 ± 61.03). FAM-HNP401 showed nerve-to-muscle contrast of 3.03 ± 0.57. FAM-HNP401 binds and highlight multiple human peripheral nerves including lower leg sural, upper arm medial antebrachial as well as autonomic nerves isolated from human prostate. Conclusion: Phage display has identified a novel peptide that selectively binds to ex-vivo human nerves and in-vivo using rodent models. FAM-HNP401 or an optimized variant could be translated for use in a clinical setting for intraoperative identification of human nerves to improve visualization and potentially decrease the incidence of intra-surgical nerve injury.


Assuntos
Imagem Molecular/métodos , Neuroimagem/métodos , Imagem Óptica/métodos , Coloração e Rotulagem/métodos , Cirurgia Assistida por Computador/métodos , Administração Intravenosa , Animais , Corantes Fluorescentes/administração & dosagem , Corantes Fluorescentes/metabolismo , Humanos , Camundongos , Peptídeos/administração & dosagem , Peptídeos/metabolismo , Ligação Proteica , Ratos
6.
Ann Occup Environ Med ; 28: 51, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27688888

RESUMO

BACKGROUND: The purpose of this study was to investigate hearing threshold changes of workers with unilateral conductive hearing loss who were exposed to workplace noise for 8-years. METHODS: Among 1819 workers at a shipyard in Ulsan, 78 subjects with an air-bone gap ≥10 dBHL in unilateral ears were selected. Factors that could affect hearing were acquired from questionnaires, physical examinations, and biochemistry examinations. Paired t-test was conducted to compare the hearing threshold changes over time between conductive hearing loss (CHL) ear and sensorineural hearing loss (SNHL) ear. RESULTS: The study included male subjects aged 48.7 ± 2.9, having worked for 29.8 ± 2.7 years. Hearing thresholds increased significantly in CHL ears and SNHL ears at all frequencies (0.5-6 kHz) during follow-up period (p < 0.05). The threshold change at 4 kHz was 3.2 dBHL higher in SNHL ears which was statistically significant (p < 0.05). When workers were exposed to noise levels of 85 dBA and above, threshold change at 4 kHz was 5.6 dBHL higher in SNHL ears which was statistically significant (p < 0.05). Among workers aged below 50, the threshold change values were lower in low-frequency (0.5-2 kHz) in SNHL ears, with a small range of changes, whereas in high-frequency (3-6 kHz), the range of changes was greater SNHL ears (p < 0.05). Among workers aged 50 and above, SNHL ears showed a wider range of changes in both high- and low-frequency areas (p < 0.05). CONCLUSIONS: At high-frequencies, particularly at 4 kHz, the range of hearing threshold changes was lower in ears with conductive hearing loss than in contralateral ears. This is suggested as a protective effect against noise exposure.

7.
Laryngoscope ; 126(5): 1241-5, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26928519

RESUMO

OBJECTIVES/HYPOTHESIS: To investigate the relationship between sleep-disordered breathing (SDB) and nocturnal enuresis (NE) in children and to prospectively evaluate the effectiveness of adenotonsillectomy on resolving enuresis in indicated SDB patients with NE. METHODS: We prospectively collected data from 183 children (121 males, mean age 8.17 ± 2.84 years) who underwent adenotonsillectomy to treat SDB between July 2011 and July 2013, and analyzed the prevalence of NE. Before and 3 months after surgery, all parents were requested to answer a self-reported SDB scale questionnaire (22 questions, 0-22 points) and a NE questionnaire (episodes of enuresis per month). Paired t test, Student t test, and Chi-square test were used to analyze the data. RESULTS: Overall prevalence of NE was 9.3% (17 patients) preoperatively and 1.5% postoperatively (four patients). After adenotonsillectomy, prevalence of NE and the mean SDB scale were significantly decreased (both P values < 0.001). After adenotonsillectomy, 13 of the 17 NE patients (76.5%) showed complete resolution. There was significantly higher prevalence of NE in patients with obstructive sleep apnea (OSA) than those without OSA (13.1%, 14 of 107 vs. 3.9%, 3 of 76; P = 0.036). CONCLUSION: There is strong association between NE and SDB, and adenotonsillectomy can markedly improve enuresis in the majority of children with NE and SDB. LEVELS OF EVIDENCE: 4. Laryngoscope, 126:1241-1245, 2016.


Assuntos
Adenoidectomia , Enurese Noturna/cirurgia , Síndromes da Apneia do Sono/cirurgia , Tonsilectomia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Enurese Noturna/complicações , Estudos Prospectivos , Síndromes da Apneia do Sono/complicações , Inquéritos e Questionários
9.
Audiol Neurootol ; 21(6): 399-405, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28384627

RESUMO

OBJECTIVES: Severe-to-profound sudden sensorineural hearing loss (SSNHL) has a poor prognosis. We aimed to compare the efficacy of simultaneous and sequential oral and intratympanic steroids for this condition. METHODS: Fifty patients with severe-to-profound SSNHL (>70 dB HL) were included from 7 centers. The simultaneous group (27 patients) received oral and intratympanic steroid injections for 2 weeks. The sequential group (23 patients) was treated with oral steroids for 2 weeks and intratympanic steroids for the subsequent 2 weeks. Pure-tone averages (PTA) and word discrimination scores (WDS) were compared before treatment and 2 weeks and 1 and 2 months after treatment. Treatment outcomes according to the modified American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) criteria were also analyzed. RESULTS: The improvement in PTA and WDS at the 2-week follow-up was 23 ± 21 dB HL and 20 ± 39% in the simultaneous group and 31 ± 29 dB HL and 37 ± 42% in the sequential group; this was not statistically significant. Complete or partial recovery at the 2-week follow-up was observed in 26% of the simultaneous group and 30% of the sequential group; this was also not significant. The improvement in PTA and WDS at the 2-month follow-up was 40 ± 20 dB HL and 37 ± 35% in the simultaneous group and 41 ± 25 dB HL and 48 ± 41% in the sequential group; this was not statistically significant. Complete or partial recovery at the 2-month follow-up was observed in 33% of the simultaneous group and 35% of the sequential group; this was also not significant. Seven patients in the sequential group did not need intratympanic steroid injections for sufficient improvement after oral steroids alone. CONCLUSIONS: Simultaneous oral/intratympanic steroid treatment yielded a recovery similar to that produced by sequential treatment. Because the addition of intratympanic steroids can be decided upon based on the improvement after an oral steroid, the sequential regimen can be recommended to avoid unnecessary intratympanic injections.


Assuntos
Dexametasona/administração & dosagem , Glucocorticoides/administração & dosagem , Perda Auditiva Neurossensorial/tratamento farmacológico , Perda Auditiva Súbita/tratamento farmacológico , Metilprednisolona/administração & dosagem , Administração Oral , Adulto , Idoso , Audiometria de Tons Puros , Feminino , Humanos , Injeção Intratimpânica , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Resultado do Tratamento
10.
Am J Forensic Med Pathol ; 34(3): 205-6, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23629395

RESUMO

Hanging is a common method of suicide. We present a case of vallecular rupture and cervical spine fracture without an external wound after a failed hanging suicide attempt. Surgical treatment involved posterior fusion of C2 to 3, followed by repair of the vallecular rupture via an external approach. The patient recovered with no residual physical or mental sequelae.


Assuntos
Vértebras Cervicais/lesões , Lesões do Pescoço/complicações , Fraturas da Coluna Vertebral/etiologia , Tentativa de Suicídio , Língua/lesões , Adulto , Vértebras Cervicais/cirurgia , Fraturas Ósseas/etiologia , Fraturas Ósseas/cirurgia , Humanos , Osso Hioide/lesões , Osso Hioide/cirurgia , Imageamento Tridimensional , Masculino , Ruptura , Fraturas da Coluna Vertebral/cirurgia , Fusão Vertebral , Enfisema Subcutâneo/etiologia , Tomografia Computadorizada por Raios X , Língua/cirurgia
11.
Otol Neurotol ; 33(4): 586-90, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22429943

RESUMO

OBJECTIVE: To assess anatomical and hearing results after different reconstruction methods of tympanic membrane in cases of severe middle ear granulation. STUDY DESIGN: Retrospective review. SETTING: Secondary care medical center. PATIENTS: Forty patients with severe middle ear granulation were included. INTERVENTIONS: Canal wall-up mastoidectomy with Type I tympanoplasty. Temporalis fascia was used in 22 patients, cartilage island flap was used in 10 patients, and cartilage palisade was used in 8 patients. MAIN OUTCOME MEASURES: Graft take, air-bone gap, and air-bone gap closure ratio of 50% or more. RESULTS: In the fascia group, the graft take rate was 91%, whereas the graft take rate for the cartilage island group and the cartilage palisades group was 100% (p = 0.617). Mean ± SD preoperative air-bone gaps for the fascia, island flap, and cartilage palisades were 30 ± 9.4, 26 ± 11.7, and 25 ± 10.8 dB, respectively. Postoperative air-bone gaps were 17 ± 10.2, 14 ± 8.4, and 19 ± 7.5 dB, respectively, in the same order. The cartilage palisades group failed to show statistically significant difference between preoperative and postoperative air-bone gaps (p = 0.195). Air-bone gap closure ratio of 50% or more was found in 11 cases (50%) of the fascia group, in 5 cases (50%) of the island flap group, and in 1 case (13%) of the cartilage palisades group. CONCLUSION: Cartilage palisades showed reliable graft take but slightly poor hearing results. Thus, fascia or cartilage island grafting might be better for tympanoplasty in cases of severe middle ear granulation tissue.


Assuntos
Orelha Média/cirurgia , Tecido de Granulação/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Membrana Timpânica/cirurgia , Timpanoplastia/métodos , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
13.
Auris Nasus Larynx ; 39(2): 204-7, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21903350

RESUMO

OBJECTIVES: To validate the Friedman stage and define the proper timing for airway intervention in adult cases of acute supraglottitis, we evaluated the clinical courses and management of adult patients. METHODS: 202 adult patients with acute supraglottitis were included in this study. The diagnosis of supraglottitis was established by flexible nasolaryngoscopic examination. Friedman stages were classified in each patient. In this study, the first three days of serial nasolaryngoscopic findings for each patient were evaluated. RESULTS: All patients were treated successfully with only conservative methods. There were no significant differences between patients with Friedman stages I or II/III. Among the patients that had serial nasolaryngoscopic findings, only one patient presented with progressive swelling of the epiglottis, and there were no cases of persistent swelling. CONCLUSION: The airway intervention threshold should be raised from Friedman stages II-III. And, airway intervention should not be needed if patients are tolerant of their respiratory discomfort.


Assuntos
Obstrução das Vias Respiratórias/terapia , Laringoscopia , Supraglotite/terapia , Doença Aguda , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Obstrução das Vias Respiratórias/classificação , Antibacterianos/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Dexametasona/administração & dosagem , Feminino , Humanos , Infusões Intravenosas , Intubação Intratraqueal , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Supraglotite/classificação , Resultado do Tratamento , Adulto Jovem
14.
Acta Otolaryngol ; 131(12): 1293-8, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21905793

RESUMO

CONCLUSION: Even though the use of TachoComb does not decrease pain after tonsillectomy, it is safe and useful to reduce bleeding after tonsillectomy. OBJECTIVES: Sealing the post-tonsillectomy wound would be expected to reduce pain and bleeding by decreasing the exposure of the traumatized tissue and sensory nerves. TachoComb is a powerful topical hemostatic agent. The objectives of this study were to evaluate the effect of TachoComb on reduction of pain and bleeding after tonsillectomy. METHODS: A prospective randomized double-blind study was performed on 120 pediatric patients undergoing adenotonsillectomy. The patients were randomized into two groups: use/non-use of TachoComb. In the study group, each tonsillar bed was covered with a TachoComb strip at the end of operation. No hemostatic agents were used in the control group. After surgery, patients were monitored for pain, bleeding, oral intake, medication administration, activity, and complications using a 10-day diary. RESULTS: In all, 110 patients returned and filled in the diary. The use of TachoComb did not decrease pain, reduce the use of analgesic drugs or speed recovery to normal everyday life. Post-surgery bleeding was not experienced by any of the TachoComb patients, but occurred in five of the control patients. The result had borderline statistical significance (p < 0.1).


Assuntos
Adenoidectomia , Materiais Revestidos Biocompatíveis/uso terapêutico , Adesivo Tecidual de Fibrina/uso terapêutico , Hemostáticos/uso terapêutico , Hemorragia Pós-Operatória/prevenção & controle , Tonsilectomia , Analgésicos/uso terapêutico , Criança , Método Duplo-Cego , Feminino , Humanos , Masculino , Medição da Dor , Estudos Prospectivos
15.
Auris Nasus Larynx ; 35(2): 291-4, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17881169

RESUMO

Carcinoma ex pleomorphic adenoma (CXPA) is a rare, aggressive, poorly understood malignancy that usually occurs in the salivary glands. CXPA has been reported to account for 3.6% of all salivary neoplasms and 11.7% of salivary malignancies. CXPA not only has a low incidence rate but there are few papers or case reports reporting perineural invasion rates. We report a case of CXPA which occurred in the parotid gland, showing retrograde perineural invasion along the facial nerve back to the internal auditory canal (IAC).


Assuntos
Adenoma Pleomorfo/diagnóstico , Neoplasias dos Nervos Cranianos/diagnóstico , Nervo Facial/patologia , Neurilemoma/diagnóstico , Neoplasias Parotídeas/diagnóstico , Adulto , Diagnóstico Diferencial , Humanos , Masculino
16.
Int J Cancer ; 122(3): 672-80, 2008 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-17955488

RESUMO

Cisplatin is a chemotherapeutic agent that is widely used to treat cancers such as head and neck squamous cell carcinoma (HNSCC). Previously, we have reported that cisplatin induced an early caspase-dependent apoptosis (8 hr) in a HNSCC cell, HN4. In this study, we examined a late caspase-independent apoptosis as well as an early caspase-dependent apoptosis in cisplatin-treated HN4 cells. While z-VAD-fmk, a pan-caspase inhibitor, blocked the caspase activities and protected cells from the early apoptosis, it did not provide protection against delayed apoptosis occurring after extended exposure (16 hr) to cisplatin, suggesting that the delayed apoptotic response in the presence of z-VAD-fmk was caspase-independent. Cisplatin treatment induced reactive oxygen species (ROS) generation, loss of the mitochondrial membrane potential (MMP) and nuclear translocation of endonuclease G (EndoG). Small interfering RNA mediated-knockdown of EndoG significantly protected cells from the delayed apoptosis induced by cisplatin in the presence of z-VAD-fmk. Overexpression of Bcl-2 in HN4 cells prevented loss of MMP, nuclear translocation of EndoG and protected cells from the delayed apoptosis induced by cisplatin in the presence of z-VAD-fmk. Pretreatment with N-acetyl-L-cysteine (NAC), a ROS scavenger, prevented both ROS generation, loss of the MMP and nuclear translocation of EndoG. Together, our data indicate that cisplatin treatment induced ROS-mediated loss of the MMP, and, then, the nuclear translocation of EndoG, which played a crucial role in caspase-independent apoptosis of HN4 cells in the presence of z-VAD-fmk. This is the first report about the involvement of EndoG in cisplatin-induced caspase-independent apoptosis of cells.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma de Células Escamosas/metabolismo , Caspases/metabolismo , Cisplatino/farmacologia , Endodesoxirribonucleases/metabolismo , Neoplasias de Cabeça e Pescoço/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Western Blotting , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Citocromos c/metabolismo , Endodesoxirribonucleases/genética , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Marcação In Situ das Extremidades Cortadas , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Transporte Proteico , RNA Interferente Pequeno/farmacologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Frações Subcelulares
17.
J Pharmacol Exp Ther ; 311(3): 1062-70, 2004 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-15273254

RESUMO

The failure to treat metastatic cancer with multidrug resistance is a major problem for successful cancer therapy, and the molecular basis for the association of metastatic phenotype with resistance to therapy is still unclear. In this study, we revealed that various metastatic cancer cells showed consistently higher levels of antiapoptotic proteins, including Bcl-2, nuclear factor-kappaB, MDM2, DNA-dependent protein kinase (DNA-PK), and epidermal growth factor receptor (EGFR), and lower levels of proapoptotic proteins, including Bax and p53 than low metastatic parental cells. This was followed by chemo- and radioresistance in metastatic cancer cells compared with their parental cells. EGFR and DNA-PK activity, which are known to be associated with chemo- and radioresistance, were demonstrated to be mutually regulated by each other. Treatment with PKI166, an EGFR inhibitor, suppressed etoposide-induced activation of DNA-PK in A375SM metastatic melanoma cells. In addition, PKI166 enhanced markedly the chemosensitivities of metastatic cancer cell sublines to various anticancer drugs in comparison with those of low metastatic cancer cells. These results suggest that the activities of DNA-PK and EGFR, which is positively correlated with each other, may contribute to metastatic phenotype as well as therapy resistance, and the EGFR inhibitor enhances the effect of anticancer drugs against therapy-resistant metastatic cancer cells via suppression of stress responses, including activation of DNA-PK.


Assuntos
Antineoplásicos/farmacologia , Apoptose/fisiologia , Proteínas de Ligação a DNA/metabolismo , Receptores ErbB/antagonistas & inibidores , Metástase Neoplásica/fisiopatologia , Proteínas Serina-Treonina Quinases/metabolismo , Animais , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Western Blotting , Linhagem Celular Tumoral , Proteína Quinase Ativada por DNA , Sinergismo Farmacológico , Ensaio de Desvio de Mobilidade Eletroforética , Etoposídeo/farmacologia , Genes MDR/genética , Humanos , Indicadores e Reagentes , Melanoma/patologia , Metástase Neoplásica/tratamento farmacológico , Metástase Neoplásica/radioterapia , Proteínas Nucleares , Pirimidinas/farmacologia , Pirróis/farmacologia , Radiossensibilizantes/farmacologia , Ratos
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