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1.
AIDS Care ; 34(5): 545-553, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-33779423

RESUMO

The association between patients' confidence in their ability to attend appointments and future retention in care has not previously been studied in a general HIV clinic. A survey of potential and known risk factors for poor retention was developed using validated screening tools and administered to 105 patients at an HIV clinic. Retention in care was assessed prospectively using two definitions: (1) two appointments at least three months apart within one year ("HRSA/HAB retention") and (2) no missed appointments within one year ("missed visits retention"). Most patients were African American (86%) and male (59%). Although most patients were confident they could keep their HIV appointments (89%), fewer were retained (HRSA/HAB: 73%; missed visits: 56%). Patients' confidence in their ability to keep future appointments was not associated with retention. Employment was associated with lower odds of HRSA/HAB retention (aOR 0.26 [95% CI 0.09-0.77]), and childcare was a common barrier that was associated with lower odds of missed visits retention (aOR 0.06 [95% CI 0.006-0.62]). Other known risk factors for poor retention were inconsistently associated with retention in care.


Assuntos
Infecções por HIV , Instituições de Assistência Ambulatorial , Agendamento de Consultas , Humanos , Masculino , Medidas de Resultados Relatados pelo Paciente , Estudos Prospectivos
2.
Brain Behav Immun ; 75: 137-148, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30287389

RESUMO

Environmental and social factors have profound impacts on immune homeostasis. Our work on environmental enrichment (EE) has revealed a novel anti-obesity and anticancer phenotype associated with enhanced activity of CD8+ cytotoxic T lymphocytes in secondary lymphoid tissues. Here we investigated how an EE modulated thymus and thymocyte development. EE decreased thymus mass and cellularity, decreased the double positive thymocyte population, increased the proportion of CD8+ T cells, reduced the CD4:CD8 ratio, and downregulated CD69 expression in T cells. In a model of multiple sclerosis: experimental autoimmune encephalomyelitis (EAE), EE alleviated symptoms, inhibited spinal cord inflammation through regulation of type 1 T-helper cells mediated by glucocorticoid receptor signaling, and prevented EAE-induced thymic disturbance. Our mechanistic studies demonstrated that hypothalamic BDNF activated a hypothalamic-pituitary-adrenal axis mediating the EE's thymic effects. Our results indicate that a lifestyle intervention links the nervous, endocrine, and adaptive immune system, allowing the body to adapt to internal and external environments.


Assuntos
Encefalomielite Autoimune Experimental/imunologia , Meio Ambiente , Timócitos/metabolismo , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Linfócitos T CD8-Positivos/imunologia , Encefalomielite Autoimune Experimental/metabolismo , Encefalomielite Autoimune Experimental/terapia , Feminino , Sistema Hipotálamo-Hipofisário/metabolismo , Hipotálamo/metabolismo , Ativação Linfocitária/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Sistema Hipófise-Suprarrenal/metabolismo , Receptores de Glucocorticoides/metabolismo , Transdução de Sinais/imunologia , Linfócitos T Citotóxicos/imunologia , Células Th1/imunologia , Células Th1/metabolismo
3.
Head Neck ; 46(2): 447-451, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38050748

RESUMO

In the era of free flap reconstruction, mandibular defects are routinely reconstructed with osseous free flaps, and non-free flap bony reconstruction options are limited. A patient with T4N0 mandibular squamous cell carcinoma underwent resection with fibula free flap reconstruction of a parasymphyseal to angle defect. After free flap failure due to venous congestion, the flap was explanted. He declined additional free flap reconstruction and elected to proceed with pedicled osteomyocutaneous pectoralis major with rib. In this case presentation, we discuss the technical details of harvest of this flap using the 6th rib. The pedicled osteomyocutaneous pectoralis major flap with osseous rib harvest, which is infrequently described in the literature, remains a viable option for bony reconstruction, particularly in the salvage setting.


Assuntos
Retalhos de Tecido Biológico , Reconstrução Mandibular , Procedimentos de Cirurgia Plástica , Masculino , Humanos , Músculos Peitorais/transplante , Costelas/transplante
4.
JAMA Otolaryngol Head Neck Surg ; 150(2): 133-141, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38153724

RESUMO

Importance: As the incidence of oropharyngeal squamous cell carcinoma (OPSCC) continues to rise in the US, an increasing number of patients are being treated with transoral robotic surgery (TORS). Readmission following surgery can potentially delay initiation of adjuvant treatment and affect survival outcomes. Objective: To identify risk factors for 30-day postoperative readmission in patients undergoing TORS for OPSCC. Design, Setting, and Participants: This retrospective, population-based cohort study used data from the Nationwide Readmissions Database from 2010 to 2017. All patients undergoing TORS for OPSCC were identified using International Classification of Diseases codes and included. Exclusion criteria were age younger than 18 years or incomplete information regarding index admission or readmission. The analysis was performed from April to October 2023. Exposure: TORS for OPSCC. Main Outcomes and Measures: Univariate and multivariate analyses were performed to determine factors associated with 30-day readmission. Covariates included demographics and medical comorbidities, socioeconomic factors, hospital characteristics, and surgical details. Trends in readmission over time, reasons for readmission, and characteristics of the readmission were also examined. Results: A weighted total of 5544 patients (mean [SD] age, 60.7 [0.25] years; 4475 [80.7%] male) underwent TORS for OPSCC. The overall readmission rate was 17.5% (n = 971), and these rates decreased over the study period (50 of 211 patients [23.7%] in 2010 vs 58 of 633 patients [9.1%] in 2017). Risk factors associated with readmission included male sex (adjusted odds ratio [AOR], 1.54; 95% CI, 1.07-2.20) and a diagnosis of congestive heart failure (AOR, 2.42; 95% CI, 1.28-4.58). Factors associated with decreased rate of readmission included undergoing concurrent selective neck dissection (AOR, 0.30; 95% CI, 0.22-0.41). Among the 971 readmissions, the most common readmission diagnoses were bleeding (151 [15.6%]), electrolyte and digestive problems (44 [4.5%]), pneumonia (44 [4.5%]), and sepsis (26 [2.7%]). Conclusions and Relevance: In this cohort study, readmission rates following TORS for oropharynx cancer decreased over time; however, a subset of patients required readmission most commonly related to bleeding, infection, and electrolyte imbalance. Concurrent neck dissection may be protective against readmission. Elucidation of risk factors for readmission after TORS for OPSCC offers opportunities for evidence-based shared decision-making, quality improvement initiatives, and improved patient counseling.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Orofaríngeas , Procedimentos Cirúrgicos Robóticos , Humanos , Masculino , Pessoa de Meia-Idade , Adolescente , Feminino , Carcinoma de Células Escamosas de Cabeça e Pescoço , Readmissão do Paciente , Carcinoma de Células Escamosas/patologia , Estudos de Coortes , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Eletrólitos
5.
3D Print Med ; 9(1): 4, 2023 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-36813875

RESUMO

BACKGROUND: Complex facial wounds can be difficult to stabilize due to proximity of vital structures. We present a case in which a patient-specific wound splint was manufactured using computer assisted design and three-dimensional printing at the point-of-care to allow for wound stabilization in the setting of hemifacial necrotizing fasciitis. We also describe the process and implementation of the United States Food and Drug Administration Expanded Access for Medical Devices Emergency Use mechanism. CASE PRESENTATION: A 58-year-old female presented with necrotizing fasciitis of the neck and hemiface. After multiple debridements, she remained critically ill with poor vascularity of tissue in the wound bed and no evidence of healthy granulation tissue and concern for additional breakdown towards the right orbit, mediastinum, and pretracheal soft tissues, precluding tracheostomy placement despite prolonged intubation. A negative pressure wound vacuum was considered for improved healing, but proximity to the eye raised concern for vision loss due to traction injury. As a solution, under the Food and Drug Administration's Expanded Access for Medical Devices Emergency Use mechanism, we designed a three-dimensional printed, patient-specific silicone wound splint from a CT scan, allowing the wound vacuum to be secured to the splint rather than the eyelid. After 5 days of splint-assisted vacuum therapy, the wound bed stabilized with no residual purulence and developed healthy granulation tissue, without injury to the eye or lower lid. With continued vacuum therapy, the wound contracted to allow for safe tracheostomy placement, ventilator liberation, oral intake, and hemifacial reconstruction with a myofascial pectoralis muscle flap and a paramedian forehead flap 1 month later. She was eventually decannulated and at six-month follow-up has excellent wound healing and periorbital function. CONCLUSIONS: Patient-specific, three-dimensional printing is an innovative solution that can facilitate safe placement of negative pressure wound therapy adjacent to delicate structures. This report also demonstrates feasibility of point-of-care manufacturing of customized devices for optimizing complex wound management in the head and neck, and describes successful use of the United States Food and Drug Administration's Expanded Access for Medical Devices Emergency Use mechanism.

6.
Head Neck ; 45(6): 1445-1454, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36976815

RESUMO

BACKGROUND: Sinonasal malignancy (SNM) is a heterogeneous group of diseases for which induction chemotherapy (IC) may reduce tumor burden. The purpose of this study was to characterize the response to IC in SNM as a prognostic factor through its effect on survival. METHODS: Retrospective cohort of patients undergoing IC for SNM between 2010 and 2019 at our quaternary referral center. RESULTS: Forty-two patients with advanced SNM were included in the analysis. Patients with a favorable response to IC had higher survival rates than those who had an unfavorable response (5-year OS: 66.8% vs. 9.7%; p < 0.001; PFS: 56.8% vs. 0%; p < 0.001). CONCLUSIONS: Response to IC in our patient cohort was a prognostic indicator of overall response to treatment. Further elucidation of predictors of response is needed for appropriate patient selection.


Assuntos
Quimioterapia de Indução , Neoplasias , Humanos , Estudos Retrospectivos , Prognóstico
7.
Laryngoscope ; 133(11): 2988-2998, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-36974971

RESUMO

OBJECTIVES: To define the role of hypothyroidism and other risk factors for unplanned readmissions after surgery for head and neck cancer. STUDY DESIGN: Retrospective cohort study. METHODS: The Nationwide Readmission Database (NRD) was used to identify patients who underwent surgery for mucosal head and neck cancer (oral cavity, oropharynx, larynx, and hypopharynx) between 2010 and 2017. Univariate and multivariate logistic regression were performed to determine patient, tumor, and hospital related risk factors for 30-day readmission. Readmitted patients were stratified by preoperative diagnosis of hypothyroidism to compare readmission characteristics. RESULTS: For the 131,013 patients who met inclusion criteria, the readmission rate was 15.9%. Overall, 11.91% of patients had a preoperative diagnosis of hypothyroidism. After controlling for other variables, patients with a preoperative diagnosis of hypothyroidism had 12.2% higher odds of readmission compared to those without hypothyroidism (OR: 1.12, 1.03-1.22, p = 0.008). Patients with hypothyroidism had different reasons for readmission, including higher rates of wound dehiscence, fistula, infection, and electrolyte imbalance. Among readmitted patients, the length of stay for index admission (mean 10.5 days vs. 9.2 days, p < 0.001), readmission (mean 7.0 vs. 6.6 days, p = 0.05), and total hospital charge were higher for hypothyroid patients ($137,742 vs. $119,831, p < 0.001). CONCLUSION: Hypothyroidism is an independent risk factor for 30-day readmission following head and neck cancer resection. Furthermore, hypothyroid patients are more likely to be readmitted for wound complications, infection, and electrolyte imbalance. Targeted interventions should be considered for hypothyroid patients to decrease readmission rates and associated patient morbidity, potentially leading to earlier initiation of adjuvant treatment. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:2988-2998, 2023.


Assuntos
Neoplasias de Cabeça e Pescoço , Hipotireoidismo , Humanos , Readmissão do Paciente , Estudos Retrospectivos , Neoplasias de Cabeça e Pescoço/complicações , Neoplasias de Cabeça e Pescoço/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/diagnóstico , Fatores de Risco , Hipotireoidismo/epidemiologia , Eletrólitos
8.
Oral Oncol ; 141: 106402, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37094500

RESUMO

OBJECTIVES: This study investigates the impact of immediate resection of positive margins on local control of oral tongue cancer. MATERIALS AND METHODS: We analyzed 273 consecutive oral tongue cancers resected from 2013 to 2018. Additional resection was performed in cases during the initial operation based on surgeon inspection of the specimen and/or frozen margins. Positive margins were defined as invasive carcinoma/high-grade dysplasia < 1 mm from the inked edge. Patients were grouped as follows: negative margin (Group 1); positive margin with immediate additional tissue resection (Group 2); and positive margin without additional tissue resection (Group 3). RESULTS: Overall, the rate of local recurrence was 7.7 % (21/273), and the rate of positive main specimen margin was 17.9 %. Of these patients, 38.8 % (19/49) underwent immediate additional resection of the presumed positive margin. Group 3 had higher local recurrence rates than Group 1 after adjustment for T-stage (aHR 2.8 [95 % CI 1.0-7.7], p = 0.04). Group 2 had similar rates of local recurrence (aHR 0.45 [95 % CI 0.06-3.6], p = 0.45). Three year local recurrence free survival for Groups 1, 2, and 3 were 91 %, 92 % and 73 %, respectively. Compared to the main specimen margin, sensitivity of intraoperative frozen tumor bed margins was 17.4 %, and specificity was 95 %. CONCLUSION: In patients with positive main specimen margins, anticipation and detection in real-time with immediate additional tissue resection reduced local recurrence to rates similar to those with negative main specimen margins. These findings support the use of technology to provide real-time intraoperative margin data and guide additional resection for improved local control.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Bucais , Neoplasias da Língua , Humanos , Neoplasias da Língua/cirurgia , Neoplasias da Língua/patologia , Prognóstico , Carcinoma de Células Escamosas/patologia , Estudos Retrospectivos , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/prevenção & controle , Recidiva Local de Neoplasia/patologia , Neoplasias Bucais/patologia , Margens de Excisão
9.
Laryngoscope ; 132(2): 478-484, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34324202

RESUMO

OBJECTIVE: Previous studies examining changes in central sleep apnea (CSA) following adenotonsillectomy (T&A) performed for obstructive sleep apnea (OSA) in children have been limited by sample size and analysis of only certain populations. The aim of this study was to determine whether CSA improves following T&A and what factors mediate this change. METHODS: This was a retrospective case series from 1994 to 2020 of children undergoing primary T&A for OSA (obstructive apnea-hypopnea index ≥1) with CSA (central apnea index [CAI] ≥1) and preoperative and postoperative polysomnograms within 12 months of T&A. Polysomnograms were analyzed for improvement in CSA, defined as: 1) if preoperative CAI >5, a postoperative CAI <5; or 2) if preoperative CAI <5, a postoperative CAI <1. RESULTS: One hundred twenty-three patients were included. Median age was 5.5 years (interquartile range, 2.9-8.4). Most patients were overweight/obese (58.5%). Nineteen (15.4%) had a syndromic condition. Preoperative CAI was ≥5 in 21 (17.1%) patients. CAI significantly decreased following T&A (preoperative 2.1, postoperative 0.4; P < .001). Thirty-two (26.0%) patients had CSA postoperatively. Improvement in the microarousal index and older age were significantly associated with improvement in CSA. CONCLUSIONS: T&A led to resolution of CSA in most children with OSA. Improvement in the microarousal index was associated with improvement in CAI, suggesting that preoperative central apneas may be postarousal and thus resolve following T&A. LEVEL OF EVIDENCE: 4 Laryngoscope, 132:478-484, 2022.


Assuntos
Adenoidectomia , Apneia do Sono Tipo Central/cirurgia , Tonsilectomia , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Estudos Retrospectivos , Resultado do Tratamento
10.
Diagn Interv Radiol ; 27(4): 529-533, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34313239

RESUMO

PURPOSE: We aimed to assess the association between complication rate and time to feeding in a cohort of patients undergoing radiologically guided placement of gastrostomy tubes. METHODS: A retrospective study was conducted of all patients receiving pull-type and push-type gastrostomy tubes placed by interventional radiologists between January 1st, 2017 and December 31st, 2018 at a single institution. Primary outcomes included procedural and tube-related complications per medical chart review with a follow-up interval of 30 days. Exclusion criteria were enteral nutrition delayed more than 48 hours, no feeding information, and tubes placed for venting (n=20). Overall, 303 gastrostomy tubes (pull-type, n=184; push-type, n=119) were included. The most common indications for placement included head and neck carcinoma for push-type tubes (n=76, 63.9%) and cerebral vascular accident for pull-type tubes (n=78, 42.4%). RESULTS: In a multiple regression analysis, there was no statistically significant association between complications and time to feeding (p = 0.096), age (p = 0.758), gender (p = 0.127), indication for tube placement (p = 0.206), or type of tube placed (p = 0.437). Average time to initiation of enteral nutrition was 12.3 hours for the pull-type and 21.7 hours for the push-type cohort (p < 0.001). Additional multiple regression analyses of pull-type tubes and push-type tubes separately also did not find any significant association between complications and the above factors (p > 0.05). CONCLUSION: There was no statistically significant correlation between time to feed and complications, suggesting that there is no clinical difference between early and late feeding following gastrostomy tube placement.


Assuntos
Gastrostomia , Neoplasias de Cabeça e Pescoço , Cateterismo , Nutrição Enteral/efeitos adversos , Gastrostomia/efeitos adversos , Humanos , Estudos Retrospectivos
11.
Ann Otol Rhinol Laryngol ; 130(9): 1010-1015, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33511847

RESUMO

OBJECTIVE: Surgery on the ossicular chain may impact its underlying mechanical properties. This study aims to investigate comparative differences in frequency-specific hearing outcomes for ossiculoplasty versus stapedotomy. METHODS: A retrospective chart review was conducted on subjects who underwent ossiculoplasty with partial ossicular replacement prosthesis (PORP) or laser stapedotomy with self-crimping nitinol/fluoroplastic piston, and achieved closure of postoperative pure tone average air-bone gap (PTA-ABG) ≤ 15 dB. 45 PORP and 38 stapedotomy cases were included, with mean length of follow-up of 7.6 months. RESULTS: The mean change in PTA-ABG was similar for the 2 procedures (-17.9 dB vs -18.1 dB, P = .98). Postoperative ABG closure for stapedotomy was superior at 1000 Hz (8.9 dB vs 13.9 dB, P = .0003) and 4000 Hz (11.8 dB vs 18.0 dB, P = .0073). Both procedures also had improved postoperative bone conduction (BC) thresholds at nearly all frequencies, but there was no statistical difference in the change in BC at any particular frequency between the 2 procedures. CONCLUSION: Both procedures achieved a similar mean change in PTA-ABG. Stapedotomy was superior to PORP at ABG closure at 1000 Hz and at 4000 Hz, with 1000 Hz the most discrepant. The exact mechanism responsible for these changes is unclear, but the specific frequencies affected suggest that differences in each procedure's respective impact on the native resonant frequency and mass load of the system could be implicated.


Assuntos
Perda Auditiva Condutiva/cirurgia , Substituição Ossicular/métodos , Cirurgia do Estribo/métodos , Adulto , Audiometria de Tons Puros , Feminino , Perda Auditiva Condutiva/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
12.
Otol Neurotol ; 41(10): 1369-1378, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33492798

RESUMO

OBJECTIVE: To assess the usefulness of numeric grading scales of middle ear risk in predicting ossiculoplasty hearing outcomes. STUDY DESIGN: Retrospective review. SETTING: Tertiary care, academic medical center. PATIENTS: Adults and children undergoing ossiculoplasty between May 2013 and May 2019 including: synthetic ossicular replacement prosthesis, autograft interposition, bone cement repair, and mobilization of lateral chain fixation. INTERVENTION: Cases were scored via middle ear risk index (MERI), surgical prosthetic infection tissue eustachian tube (SPITE) method, and ossiculoplasty outcome scoring parameter (OOPS) scale. Preoperative and postoperative hearing outcomes were recorded. MAIN OUTCOME MEASURE: Statistical correlation between risk score and postoperative pure-tone average air-bone gap (PTA-ABG). RESULTS: The 179 included cases had average pre and postoperative PTA-ABGs of 30.3dB (standard deviation [SD] 12.7) and 20.3dB (SD 11.1), respectively. Mean MERI, SPITE, and OOPS scores were 4.5 (SD 2.3), 2.8 (SD 1.7), and 3.1 (SD 1.8), respectively. Statistically significant correlations with hearing outcome were noted for all three methods (MERI r = 0.22, p = 0.003; OOPS r = 0.19, p = 0.012; SPITE r = 0.27, p < 0.001). No scale predicted poor (PTA-ABG > 30dB) outcomes; only low SPITE scores predicted excellent (PTA-ABG < 10dB) outcomes (odds ratio [OR] 0.74 [Confidence Interval: 0.57 - 0.97], p = 0.032). CONCLUSIONS: Significant weak correlations between each middle ear risk score and hearing outcomes were encountered. Although only the SPITE method predicted postoperative PTA-ABG, it was not overwhelmingly superior. Current grading scale selection may be justified by familiarity or ease of use.


Assuntos
Prótese Ossicular , Substituição Ossicular , Adulto , Criança , Orelha Média/cirurgia , Audição , Perda Auditiva Condutiva/cirurgia , Humanos , Estudos Retrospectivos , Resultado do Tratamento
13.
Cureus ; 11(7): e5207, 2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31565612

RESUMO

Creating visual art to teach and learn histologic concepts is uncommon. A pilot visual art program was developed for use in first-year medical student courses that include histology with the hypothesis that creating visual art would subjectively improve the learning process and lead to learner-based personal incorporation of art into in future learning. Prior to the term, volunteers (n=25) were recruited from 89 first-year medical students. The volunteer group was given art supplies and encouraged to draw histologic images in a free-form setting without restrictions. The control group (n=64) consisted of non-volunteers. Pre- and post-term surveys were distributed to all students, of which 72% and 45% completed the surveys, respectively. Regardless of participation, a majority of students viewed art as a valuable tool to learn medicine prior to and following the term (73% and 82.5%, respectively), however less than half admitted to using art to learn medical concepts (42% and 40%, respectively). In the post-term survey, a higher percentage of students in the experimental group stated they will use art to learn medical concepts in the future (75% vs 40.6%). Most students considered art to be a valuable resource to learn concepts in medicine, including all the students who participated in the art program. Based on the number of students who reported intent to change behavior, the initial hypothesis is supported. Many students favor incorporation of visual art into medical education, we believe that creating visual art may be a worthwhile adjunct tool for histology education.

15.
Cancer Immunol Res ; 4(6): 488-497, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27045020

RESUMO

Macroenvironmental factors, including a patient's physical and social environment, play a role in cancer risk and progression. Our previous studies show that living in an enriched environment (EE) providing complex stimuli confers an anticancer phenotype in mice mediated, in part by a specific neuroendocrine axis, with brain-derived neurotrophic factor (BDNF) as the key brain mediator. Here, we investigated how an EE modulated T-cell immunity and its role in the EE-induced anticancer effects. Our data demonstrated that CD8 T cells were required to mediate the anticancer effects of an EE in an orthotropic model of melanoma. In secondary lymphoid tissue (SLT), an EE induced early changes in the phenotype of T-cell populations, characterized by a decrease in the ratio of CD4 T helper to CD8 cytotoxic T lymphocytes (CTL). Overexpression of hypothalamic BDNF reproduced EE-induced T-cell phenotypes in SLT, whereas knockdown of hypothalamic BDNF inhibited EE-induced immune modulation in SLT. Both propranolol and mifepristone blocked the EE-associated modulation of CTLs in SLT, suggesting that both the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis were involved. Our results demonstrated that enhanced anticancer effect of an EE was mediated at least in part through modulation of T-cell immunity and provided support to the emerging concept of manipulating a single gene in the brain to improve cancer immunotherapy. Cancer Immunol Res; 4(6); 488-97. ©2016 AACR.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/metabolismo , Interação Gene-Ambiente , Hipotálamo/metabolismo , Melanoma Experimental/imunologia , Subpopulações de Linfócitos T/imunologia , Antagonistas Adrenérgicos beta/farmacologia , Animais , Fator Neurotrófico Derivado do Encéfalo/deficiência , Linfócitos T CD8-Positivos/imunologia , Abrigo para Animais , Imunidade Celular/efeitos dos fármacos , Imunidade Celular/genética , Imunidade Celular/imunologia , Imunofenotipagem , Masculino , Melanoma Experimental/genética , Melanoma Experimental/patologia , Camundongos Endogâmicos C57BL , Transplante de Neoplasias , Propranolol/farmacologia , Transdução de Sinais/imunologia , Linfócitos T Citotóxicos/imunologia
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