Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 15 de 15
Filtrar
1.
Am J Otolaryngol ; 45(4): 104288, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38640811

RESUMO

PURPOSE: There is sparse literature discussing the impact of smoking on postoperative outcomes following surgical treatment of Zenker's diverticulum. In this study, we seek to characterize differences in the management and outcomes of open Zenker's diverticulectomy based on patient smoking status. METHODS AND MATERIALS: This paper is a retrospective cohort review. The 2005-2018 American College of Surgeons National Surgical Quality Improvement (ACS-NSQIP) database was queried for patients undergoing open Zenker's diverticulectomy. Chi-square and multivariable logistic regression were performed to determine statistical associations between postoperative outcomes and smoking status. RESULTS: Of the 715 identified patients, 70 (9.8 %) were smokers and 645 (91.2 %) were non-smokers. Smokers were younger than non-smokers (mean 63.9 vs. 71.7 years, p < 0.001) and more likely to have a prolonged operative time (20.0 % vs. 11.6 %, p = 0.044). On multivariable regression analysis controlling for demographics and comorbidities, smokers had greater odds than non-smokers for developing overall postoperative complications (OR: 2.776, p = 0.013), surgical infections (OR: 3.194, p = 0.039), medical complications (OR: 3.563, p = 0.011), and medical infections (OR: 1.247, p = 0.016). Smokers also had greater odds for requiring ventilation/intubation (OR: 8.508, p = 0.025) and having a prolonged postoperative stay (OR: 2.425, p = 0.030). CONCLUSION: In a cohort of patients undergoing transcervical Zenker's diverticulectomy, smokers are at increased risk for overall complications, medical complications, medical infections, surgical infections, prolonged postoperative stay, and ventilation/intubation.

2.
Otolaryngol Head Neck Surg ; 168(6): 1338-1345, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36939404

RESUMO

OBJECTIVE: This study reviews the presentation, management, and outcomes of patients with rhinolithiasis. DATA SOURCES: An electronic database search of PubMed, SCOPUS, CINAHL, and the Cochrane Library was performed in accordance with the PRISMA 2020 updated guidelines for reporting systematic reviews. REVIEW METHODS: Case reports and case series published from 2004 to 2020 were included. Data collected included patient demographics, clinical symptoms at presentation, diagnosis, treatment, complications, and follow-up. Relevant descriptive statistics were computed using Microsoft Excel 2013 (Microsoft Corp). RESULTS: Fifty-five case reports and five case series were included (n = 122). The majority were female (60.7%). The mean age was 29.4 years (range, 4-80 years). The most common symptoms were rhinorrhea (81.1%), nasal obstruction (79.5%), nasal malodor (38.5%), and headache (27.9%). Computed tomography imaging was obtained in 109 (91.5%) cases. Concurrent rhinosinusitis (35.2%) and deviated nasal septum (28.7%) were commonly identified. Rhinoliths were commonly found in the right nostril (52.5%) and in between the inferior turbinate and nasal septum (26.9%). All rhinoliths were fully excised using endoscopic sinonasal surgery, accompanied by a septoplasty (9.2%). The nidus was identified in 27 (22.2%) patients. There were no recurrences or complications over an average follow-up of 8.5 months (range, 0.25-36 months). CONCLUSION: Rhinolithiasis is an uncommon entity of the nasal cavity and should be suspected in patients with long-standing unilateral nasal obstruction, rhinorrhea, and nasal malodor. Rigid nasal endoscopy and endoscopic sinonasal surgery are the most important methods for diagnosis and treatment, respectively.


Assuntos
Litíase , Obstrução Nasal , Doenças Nasais , Humanos , Masculino , Feminino , Adulto , Doenças Nasais/cirurgia , Obstrução Nasal/etiologia , Rinorreia , Endoscopia/métodos
4.
Head Neck ; 45(3): 685-696, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36584171

RESUMO

BACKGROUND: Our study investigates the prognostic significance of spindle cell histology on overall survival (OS) of conventional head and neck squamous cell carcinoma (HNSCC). METHODS: The 2004 to 2017 National Cancer Database was queried for patients with head and neck spindle cell carcinoma (HNSpCC) (n = 1572) or HNSCC (n = 242 697) of the oral cavity, major salivary glands, sinonasal tract, oropharynx, hypopharynx, and larynx treated with curative intent. RESULTS: Patients with HNSpCC presented more frequently with higher-grade tumors and cN0 disease than those with HNSCC (p < 0.001). In the oral cavity, the HR for death for SpCC compared with SCC was 1.33 (p < 0.001). In the oropharynx, the HR for death for SpCC compared with SCC was 1.47 (p = 0.028). CONCLUSIONS: After adjusting for patient, tumor, and treatment characteristics, SpCC histology had an independent adverse prognostic effect on OS in the oral cavity and oropharynx. SpCC histology does not necessarily portend poorer survival in all HNSCC.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Humanos , Prognóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Carcinoma de Células Escamosas/patologia , Neoplasias de Cabeça e Pescoço/terapia
5.
Am J Rhinol Allergy ; 37(3): 247-252, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36343940

RESUMO

BACKGROUND: Preoperative laboratory tests (PLTs) are often obtained prior to outpatient surgical procedures. The objective of this study is to examine the current practice of routine PLT in low-risk patients undergoing ambulatory endoscopic sinonasal surgery (ESS) and to assess whether such testing impacts surgical outcomes. METHODS: Patients undergoing ambulatory ESS were identified from the 2011 to 2018 NSQIP database. Low-risk patients were defined as American Society of Anesthesiologist class 1 or 2. PLTs were grouped into hematologic, chemistry, coagulation, and liver function tests. Chi-square analyses and independent samples t-tests were conducted to compare categoric and continuous variables, respectively. RESULTS: A total of 664 cases met the inclusion criteria, of which 419 (62.1%) underwent at least one PLT. Of these, the most frequent PLT obtained was a complete blood cell count (92.4%). Major complications occurred in 1.5% of patients. There were no statistically significant differences in overall postoperative complications between those with and without PLT (P = .264). Specifically, no significant difference was seen in the incidence of postoperative bleeding (P = .184), urinary tract infection (P = .444), pulmonary embolism (P = .444), or wound infection (P = .701). On multivariable analyses, PLT status was not significantly associated with any complication (P = .097) or unplanned readmission (P = .898). CONCLUSIONS: Our analysis did not reveal an association between the use of PLT and postoperative morbidity or unplanned readmission in low-risk patients undergoing outpatient ESS.


Assuntos
Endoscopia , Complicações Pós-Operatórias , Humanos , Estados Unidos , Risco , Incidência , Endoscopia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Fatores de Risco
6.
Laryngoscope ; 133(6): 1402-1408, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-35869847

RESUMO

OBJECTIVES: Hypoalbuminemia has been used as a proxy for poor nutrition, and has been associated with poor postoperative outcomes in varying surgical procedures. This study investigates the association between albumin status and complications following transcervical Zenker diverticulectomy. STUDY DESIGN: Retrospective database review. METHODS: The National Surgical Quality Improvement Program database was queried for patients who underwent transcervical Zenker diverticulectomy between 2005 and 2018. Univariate and multivariable analyses were conducted to determine associations between albumin status and postoperative complications. RESULTS: 318 patients undergoing transcervical Zenker diverticulectomy with available albumin values were queried. The mean serum albumin was 3.90 g/dL (SD = 0.56). Univariate analysis showed that hypoalbuminemia was associated with increased age (77.68 vs. 70.03 years) and female gender (54.4% vs. 45.6%), as well as sepsis (p = 0.045), reintubation (p = 0.040), urinary tract infection (p = 0.017), any medical complication (p < 0.001), any life-threatening complication (p = 0.017), and mortality (p = 0.012). Multivariable analyses found no associations between hypoalbuminemia and mortality (OR 33.136, 95% CI N/A, p = 1.000), any medical complication (OR 1.154, 95% CI 0.326-4.079, p = 0.824), any life-threatening complication (OR 0.604, 95% CI 0.079-4.586, p = 0.604), and length of stay (p = 0.249). CONCLUSIONS: This study suggests no association between hypoalbuminemia and postoperative complications in transcervical Zenker diverticulectomy. Hypoalbuminemia and malnutrition may not be a contraindication for surgery correcting Zenker diverticulectomy. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:1402-1408, 2023.


Assuntos
Hipoalbuminemia , Desnutrição , Humanos , Feminino , Estudos Retrospectivos , Hipoalbuminemia/complicações , Resultado do Tratamento , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Desnutrição/epidemiologia , Desnutrição/etiologia , Albumina Sérica/análise , Fatores de Risco
7.
Otolaryngol Head Neck Surg ; 168(3): 413-421, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-35608906

RESUMO

OBJECTIVE: To examine factors associated with hospital safety net burden and its impact on survival for patients with sinonasal squamous cell carcinoma (SNSCC). STUDY DESIGN: Retrospective database study. SETTING: National Cancer Database from 2004 to 2016. METHODS: SNSCC cases were identified in the National Cancer Database. Hospital safety net burden was defined by percentage of uninsured/Medicaid patients treated, namely ≤25% for low-burden hospitals, 26% to 75% for medium-burden hospitals, and >75% for high-burden hospitals (HBHs). Univariate and multivariate analyses were used to investigate patient demographics, clinical characteristics, and overall survival. RESULTS: An overall 6556 SNSCC cases were identified, with 1807 (27.6%) patients treated at low-burden hospitals, 3314 (50.5%) at medium-burden hospitals, and 1435 (21.9%) at HBHs. On multivariate analysis, Black race (odds ratio [OR], 1.39; 95% CI, 1.028-1.868), maxillary sinus primary site (OR, 1.31; 95% CI, 1.036-1.643), treatment at an academic/research program (OR, 20.63; 95% CI, 8.868-47.980), and treatment at a higher-volume facility (P < .001) resulted in increased odds of being treated at HBHs. Patients with grade III/IV tumor (OR, 0.70; 95% CI, 0.513-0.949), higher income (P < .05), or treatment modalities other than surgery alone (P < .05) had lower odds. Survival analysis showed that hospital safety net burden status was not significantly associated with overall survival (log-rank P = .727). CONCLUSION: In patients with SNSCC, certain clinicopathologic factors, including Black race, lower income, treatment at an academic/research program, and treatment at facilities in the West region, were associated with treatment at HBHs. Hospital safety net burden status was not associated with differences in overall survival.


Assuntos
Hospitais , Neoplasias dos Seios Paranasais , Estados Unidos/epidemiologia , Humanos , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Medicaid , Neoplasias dos Seios Paranasais/terapia
8.
Otolaryngol Head Neck Surg ; 168(4): 643-657, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-35349383

RESUMO

OBJECTIVE: To offer pragmatic, evidence-informed guidance on the use of systemic corticosteroids (SCS) for common otolaryngologic disorders. DATA SOURCES: PubMed, Cochrane Library, and American Academy of Otolaryngology-Head and Neck Surgery Foundation clinical practice guidelines. REVIEW METHODS: A comprehensive search of published literature through November 2021 was conducted on the efficacy of SCS, alone or in combination with other treatments, for managing disorders in otolaryngology and the subdisciplines. Clinical practice guidelines, systematic reviews, and randomized controlled trials, when available, were preferentially retrieved. Interventions and outcomes of SCS use were compiled to generate summary tables and narrative synthesis of findings. CONCLUSIONS: Evidence on the effectiveness of SCS varies widely across otolaryngology disorders. High-level evidence supports SCS use for Bell's palsy, sinonasal polyposis, and lower airway disease. Conversely, evidence is weak or absent for upper respiratory tract infection, eustachian tube dysfunction, benign paroxysmal positional vertigo, adenotonsillar hypertrophy, or nonallergic rhinitis. Evidence is indeterminate for acute laryngitis, acute pharyngitis, acute sinusitis, angioedema, chronic rhinosinusitis without polyps, Ménière's disease, postviral olfactory loss, postoperative nerve paresis/paralysis, facial pain, and sudden sensorineural hearing loss. IMPLICATIONS FOR PRACTICE: Clinicians should bring an evidence-informed lens to SCS prescribing to best counsel patients regarding the risks, anticipated benefits, and limited data on long-term effects. Alternate routes of corticosteroid administration-such as sprays, drops, inhalers, and intralesional injections-may be preferable for many disorders, particularly those that are self-limited or require a prolonged duration of therapy. Prudent use of SCS reduces the risk of medication-related adverse effects. Clinicians who are conversant with high-level evidence can achieve optimal outcomes and stewardship when prescribing SCS.


Assuntos
Paralisia de Bell , Otolaringologia , Otorrinolaringopatias , Sinusite , Humanos , Esteroides , Corticosteroides/uso terapêutico , Otorrinolaringopatias/tratamento farmacológico , Otorrinolaringopatias/cirurgia , Paralisia de Bell/tratamento farmacológico , Sinusite/tratamento farmacológico , Sinusite/cirurgia
9.
Otolaryngol Head Neck Surg ; 168(2): 227-233, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-35380889

RESUMO

OBJECTIVES: To investigate the impact of facility volume on Patient Safety Indicator (PSI) events following transsphenoidal pituitary surgery (TSPS). STUDY DESIGN: Retrospective database review. SETTING: National Inpatient Sample database (2003-2011). METHODS: The National Inpatient Sample was queried for TSPS cases from 2003 to 2011. Facility volume was defined by tertile of average annual number of TSPS procedures performed. PSIs, based on in-hospital complications identified by the Agency of Healthcare Research and Quality, and poor outcomes, such as mortality and tracheostomy, were analyzed. RESULTS: An overall 16,039 cases were included: 804 had ≥1 PSI and 15,235 had none. A greater proportion of male to female (5.8% vs 4.3%) and Black to White (7.0% vs 4.5%) patients experienced PSIs. There was an increased likelihood of poor outcome (odds ratio [OR], 3.1 [95% CI, 2.5-3.7]; P < .001) and mortality (OR, 30.1 [95% CI, 18.5-48.8]; P < .001) with a PSI. The incidence rates of PSIs at low-, intermediate-, and high-volume facilities were 5.7%, 5.1%, and 4.2%, respectively. Odds of poor outcome with PSIs were greater at low-volume facilities (OR, 3.3 [95% CI, 2.4-4.4]; P < .001) vs intermediate (OR, 3.1 [95% CI, 2.1-4.2]; P < .001) and high (OR, 2.5 [95% CI, 1.7-3.8]; P < .001). Odds of mortality with PSIs were greater at high-volume facilities (OR, 43.0 [95% CI, 14.3-129.4]; P < .001) vs intermediate (OR, 40.0 [95% CI, 18.5-86.4]; P < .001) and low (OR, 17.3 [95% CI, 8.0-37.7]; P < .001). CONCLUSION: PSIs were associated with a higher likelihood of poor outcome and mortality following TSPS. Patients who experienced PSIs had a lower risk of poor outcome but increased mortality at higher-volume facilities.


Assuntos
Hospitais , Segurança do Paciente , Humanos , Masculino , Feminino , Estudos Retrospectivos
10.
Int Forum Allergy Rhinol ; 12(10): 1225-1231, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35730163

RESUMO

Absorbable steroid-eluting sinus implants provide targeted corticosteroid release over a sustained period and are designed to prevent both undesirable adhesion formation and sinus ostia restenosis. Here, we highlight the key evidence of these implants to date and query a group of experts via a Delphi process on the indications and optimal timing for intraoperative or in-office placement of these implants. Six of a total of 12 statements reached consensus and were accepted. Overall, experts largely agree that intraoperative or in-office use of steroid-eluting stents could be considered for patients: (1) who are diabetic or intolerant of oral steroids, (2) undergoing extended frontal sinus surgery, and (3) with recurrent stenosis. Given the lack of expert consensus on other key statements, clinicians should carefully consider these treatment options on a case-by-case basis after shared decision-making.


Assuntos
Rinite , Sinusite , Implantes Absorvíveis , Corticosteroides , Doença Crônica , Técnica Delphi , Endoscopia , Humanos , Rinite/cirurgia , Sinusite/cirurgia , Esteroides/uso terapêutico , Resultado do Tratamento
11.
Otolaryngol Head Neck Surg ; 167(4): 760-768, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35133910

RESUMO

OBJECTIVE: This study aims to provide an age-stratified analysis of associations with patient sex in pediatric inpatients with acute rhinosinusitis (ARS). STUDY DESIGN: Retrospective cohort study. SETTING: National administrative database. METHODS: The 2016 Kids' Inpatient Database was queried for pediatric inpatients (<21 years old) with ARS (ICD-10 J01). Orbital and intracranial sequelae were selected via ICD-10 codes. Statistical associations by sex were determined via univariate and multivariable analyses. Weighted measures are reported to provide national estimates. RESULTS: Of the 5882 patients identified with ARS, 2404 (40.9%) were female and 3478 (59.1%) were male. Male patients were younger than female patients (mean, 9.3 vs 9.9 years; P < .001). Multivariable analysis indicated that males and females had similar total charges ($71,094 vs $66,892, P = .464) and length of stay (5.8 vs 6.1 days, P = .263). However, male patients underwent more procedures (1.8 vs 1.5, P < .001). Mortality was similar between male and female patients (odds ratio [OR], 0.91; P = .664). Male patients also had increased odds for having orbital (OR, 1.58; P < .001) and intracranial (OR, 1.99; P < .001) complications. Differences in sex-dependent sequela risk were starkest in patients aged 14 to 20 years, with male patients being more likely to have orbital (OR, 2.91; P < .001) and intracranial (OR, 3.86; P < .001) complications. CONCLUSION: In a cohort of pediatric inpatients with ARS, males have increased odds for orbital and intracranial sequelae and undergo more procedures than females. However, males and females have similar charges and length of stay. Our study highlights age-stratified differences in ARS across patient sex.


Assuntos
Sinusite , Doença Aguda , Adulto , Criança , Feminino , Humanos , Pacientes Internados , Tempo de Internação , Masculino , Estudos Retrospectivos , Sinusite/cirurgia , Adulto Jovem
12.
Otolaryngol Head Neck Surg ; 165(5): 626-635, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-33528314

RESUMO

OBJECTIVE: To systematically review the current literature regarding the operative outcomes of stapes surgery for stapes fixation via the endoscopic and microscopic approaches. DATA SOURCES: PubMed, Embase, and Web of Science. REVIEW METHODS: An electronic search was conducted with the keywords "endoscop* or microscop*" and "stapes surgery or stapedectomy or stapedotomy or otosclerosis or stapes fixation." Studies were included if they compared endoscopy with microscopy for stapes surgery performed for stapes fixation and evaluated hearing outcomes and postoperative complications. Articles focusing on stapes surgery other than for stapes fixation were excluded. RESULTS: The database search yielded 1317 studies; 12 remained after dual-investigator screening for quantitative analysis. The mean MINORS score was 18 of 24, indicating a low risk of bias. A meta-analysis demonstrated no statistically significant difference between the groups with regard to operative time, chorda tympani nerve manipulation or sacrifice, or postoperative vertigo. There was a 2.6-dB mean improvement in the change in air-bone gap in favor of endoscopic stapes surgery and a 15.2% increased incidence in postoperative dysgeusia in the microscopic group, but the studies are heterogeneous. CONCLUSIONS: Endoscopic stapes surgery appears to be a reasonable alternative to microscopic stapes surgery, with similar operative times, complications, and hearing outcomes. Superior visibility with the endoscope was consistently reported in all the studies. Future studies should have standardized methods of reporting visibility, hearing outcomes, and postoperative complications to truly establish if endoscopic stapes surgery is equivalent or superior to microscopic stapes surgery.


Assuntos
Endoscopia/métodos , Microscopia/métodos , Microcirurgia/métodos , Otosclerose/cirurgia , Cirurgia do Estribo/métodos , Humanos
13.
Int J Pediatr Otorhinolaryngol ; 124: 190-192, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31202037

RESUMO

OBJECTIVES: Upper lip tie, without concomitant tongue tie, can prevent proper flanging of the upper lip during breastfeeding, resulting in a poor seal and suck for the infant with nipple pain and maternal dissatisfaction. Due to the lack of published studies on this subject, we report our technique and outcomes for in-office release of isolated upper lip tie. METHODS: Using CPT Code 40,806 for 'incision of labial frenulum', 22 mother-infant dyads with infant age under 60 days with breastfeeding problems and a restrictive upper lip frenum were identified. These infants underwent in-office release of upper lip tie as detailed below. Outcomes of the procedure were assessed by a telephone survey to mothers within the 4-week period post-procedure. RESULTS: 82% of mothers reported an improved latch and 73% noted increased satisfaction with breastfeeding. Lip pain, if present, resolved within 24 h for most children. Recurrence was reported by 9% of mothers; no infection or other complications occurred. CONCLUSION: Upper lip frenotomy, in properly selected infants, has favorable short-term outcomes with mild transient discomfort and a low rate of recurrence. Since our study was short-term and did not include a control group, we are unable to comment on procedure efficacy or long-term impact.


Assuntos
Procedimentos Cirúrgicos Ambulatórios , Aleitamento Materno , Freio Labial/cirurgia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Mucosa Bucal/cirurgia , Recidiva , Comportamento de Sucção , Resultado do Tratamento
14.
Otolaryngol Head Neck Surg ; 156(5): 809-815, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28168892

RESUMO

Objective To provide aggregate data regarding the ability of functional rhinoplasty to improve nasal obstruction as measured by the Nasal Obstruction Symptom Evaluation (NOSE) score. Data Sources PubMed, EMBASE, Cochrane databases. Review Methods A search was performed with the terms "nasal obstruction" and "rhinoplasty." Studies were included if they evaluated the effect of functional rhinoplasty on nasal obstruction with the NOSE score. Case reports, narratives, and articles that did not use the NOSE score were excluded. Functional rhinoplasty was defined as surgery on the nasal valve. This search resulted in 665 articles. After dual-investigator independent screening, 16 articles remained. Study results were pooled with a random effects model of meta-analysis. Change in NOSE score after surgery was assessed via the mean difference between baseline and postoperative results and the standardized mean difference. Heterogeneity was assessed and reported through the I2 statistic. Results Patients in the included studies had moderate to severe nasal obstructive symptoms at baseline. The NOSE scores were substantially improved at 3-6, 6-12, and ≥12 months, with absolute reductions of 50 points (95% CI, 45-54), 43 points (95% CI, 36-51), and 49 points (95% CI, 39-58), respectively. All of these analyses showed high heterogeneity. Conclusions Nasal obstruction as measured by the NOSE survey is reduced by 43 to 50 points (out of 100 points) for 12 months after rhinoplasty. Our confidence in these results is limited by heterogeneity among studies, large variability in outcomes beyond 12 months, and the inherent potential for bias in observational studies.


Assuntos
Obstrução Nasal/cirurgia , Recuperação de Função Fisiológica/fisiologia , Rinoplastia/métodos , Feminino , Humanos , Masculino , Obstrução Nasal/diagnóstico , Septo Nasal/cirurgia , Nariz/fisiologia , Qualidade de Vida , Índice de Gravidade de Doença , Avaliação de Sintomas , Resultado do Tratamento
15.
J Biol Chem ; 287(33): 27703-14, 2012 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-22711540

RESUMO

The focal adhesion adapter protein p130(cas) regulates adhesion and growth factor-related signaling, in part through Src-mediated tyrosine phosphorylation of p130(cas). AND-34/BCAR3, one of three NSP family members, binds the p130(cas) carboxyl terminus, adjacent to a bipartite p130(cas) Src-binding domain (SBD) and induces anti-estrogen resistance in breast cancer cell lines as well as phosphorylation of p130(cas). Only a subset of the signaling properties of BCAR3, specifically augmented motility, are dependent upon formation of the BCAR3-p130(cas) complex. Using GST pull-down and immunoprecipitation studies, we show that among NSP family members, only BCAR3 augments the ability of p130(cas) to bind the Src SH3 domain through an RPLPSPP motif in the p130(cas) SBD. Although our prior work identified phosphorylation of the serine within the p130(cas) RPLPSPP motif, mutation of this residue to alanine or glutamic acid did not alter BCAR3-induced Src SH3 domain binding to p130(cas). The ability of BCAR3 to augment Src SH3 binding requires formation of a BCAR3-p130(cas) complex because mutations that reduce association between these two proteins block augmentation of Src SH3 domain binding. Similarly, in MCF-7 cells, BCAR3-induced tyrosine phosphorylation of the p130(cas) substrate domain, previously shown to be Src-dependent, was reduced by an R743A mutation that blocks BCAR3 association with p130(cas). Immunofluorescence studies demonstrate that BCAR3 expression alters the intracellular location of both p130(cas) and Src and that all three proteins co-localize. Our work suggests that BCAR3 expression may regulate Src signaling in a BCAR3-p130(cas) complex-dependent fashion by altering the ability of the Src SH3 domain to bind the p130(cas) SBD.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteína Substrato Associada a Crk/metabolismo , Complexos Multiproteicos/metabolismo , Transdução de Sinais/fisiologia , Quinases da Família src/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Motivos de Aminoácidos , Animais , Células COS , Linhagem Celular Tumoral , Chlorocebus aethiops , Proteína Substrato Associada a Crk/genética , Fatores de Troca do Nucleotídeo Guanina , Humanos , Complexos Multiproteicos/genética , Mutação , Fosforilação/genética , Ligação Proteica , Domínios de Homologia de src , Quinases da Família src/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA