Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 16 de 16
Filtrar
1.
World J Surg ; 47(10): 2587-2593, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37353714

RESUMO

BACKGROUND: Elastofibroma dorsi (EFD) is a pseudotumor of the thoracic wall that can be difficult to diagnose due to its rarity. Prompt recognition can limit unnecessary workup and expedite treatment. This study retrospectively analyzed patients with a diagnosis of EFD, discussing clinical presentations and surgical outcomes. METHODS: This is an IRB-approved single-center retrospective study of all patients with a diagnosis of elastofibroma at our institution between 2000 and 2022. RESULTS: Ten patients were identified to have a pathologic diagnosis of EFD since 2000, with half presenting in the last 5 years. Our cohort had an average age of 56.8 years and was 50% female. The average age of male subjects was younger than females, 49.6-64.0 years, respectively (p = 0.10). Eighty percent (8/10) of patients had unilateral EFDs and symptoms lasted 27.1 months on average prior to diagnosis. Surgical resection was performed on 66.67% (8/12) of masses, with 87.5% (7/8) of patients who underwent surgery reporting complete resolution of their symptoms and none reporting recurrence. CONCLUSIONS: Although EFD is a rare pseudotumor, its incidence may be increasing. As such, surgeons should be aware of the typical clinical presentation; specifically, a slow growing, predominantly unilateral, painful, subscapular mass with an inhomogeneous pattern on imaging. Originally thought to predominantly affect elderly women, our study shows that younger men may be at risk as well. If patients present with EFD, complete surgical resection should be performed to achieve favorable outcomes and resolution of symptoms.


Assuntos
Fibroma , Neoplasias de Tecidos Moles , Parede Torácica , Humanos , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Parede Torácica/diagnóstico por imagem , Parede Torácica/cirurgia , Estudos Retrospectivos , Fibroma/diagnóstico por imagem , Fibroma/cirurgia , Neoplasias de Tecidos Moles/diagnóstico por imagem , Neoplasias de Tecidos Moles/cirurgia , Pesquisa
2.
Clin Lung Cancer ; 23(4): 333-344, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35256282

RESUMO

INTRODUCTION: Therapeutic options for stage III non-small-cell lung cancer (NSCLC) consist of definitive chemoradiation, surgery combined with neoadjuvant/adjuvant chemotherapy, and trimodality therapy. More recently, biologically driven systemic therapy options, including immunotherapy and targeted therapy, have become increasingly available. METHODS: A customized, case-based survey was designed and distributed to members of the International Association for the Study of Lung Cancer (IASLC) to determine practice habits and preferences for NSCLC patients with stage III disease and N2 to N3 nodal involvement. RESULTS: Data were compiled from 87 respondents from 31 countries, including medical oncologists (49%), surgical oncologists (24%), and radiation oncologists (21%). Definitive chemoradiation was more likely to be recommended for stage IIIC (98.2%) or stage IIIB (75.8%) scenarios compared with stage IIIA (59.6%) without actionable driver alterations (P < .0001 and .0003, respectively); and chemoradiation was more likely for stage IIIB (57.7%) compared to stage IIIA (39.9%) with actionable EGFR/ALK alterations (P = .008). Surgery was more likely to be recommended in the presence of an actionable alteration (38.7% vs. 19%, P < .0001). Surgeons were more likely than medical oncologists to recommend surgical approaches in scenarios without actionable alterations (25.6% vs. 11.2%, P < .0001) or with actionable alterations (57.5% vs. 31.1%, P = .0001). DISCUSSION: The dominant recommended strategy for stage III NSCLC was chemoradiation, although respondents were more likely to recommend surgical approaches in the presence of actionable alterations. Despite the lack of reported clinical trial data, many IASLC lung cancer experts favored targeted therapy when actionable driver alterations were present.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Terapia Combinada , Efeitos Psicossociais da Doença , Humanos , Neoplasias Pulmonares/patologia , Estadiamento de Neoplasias
3.
AACE Clin Case Rep ; 4(5): e375-e378, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-31897433

RESUMO

OBJECTIVE: Ectopic Cushing's syndrome secondary to thymic carcinoid is a rare disorder that may be difficult to diagnose and manage. METHODS: We describe a case of severe Cushing's syndrome secondary to a large adrenocorticotropic hormone (ACTH) producing thymic carcinoid in a patient with history of primary hyperaldosteronism. RESULTS: A 43-year-old female with a 20-year history of an aldosterone-secreting adrenocortical adenoma status post right adrenalectomy presented with acute onset of proximal muscle weakness, swelling, facial hirsutism, and severe hypokalemia. Ectopic Cushing's Syndrome was suspected based on the sudden symptom onset and markedly elevated 24-hr urine cortisol and ACTH levels. MRI revealed an empty pituitary sella and a large (7.3 cm) mediastinal mass visible on chest CT. The mass was resected by video-assisted thoracoscopic surgery, resulting in resolution of symptoms and cortisol levels. Pathology assessment confirmed well-differentiated thymic carcinoid with positive ACTH staining. CONCLUSION: The case highlights clinical features, challenges in diagnostic work up, treatment modalities, and associated endocrine findings in a thymic carcinoid abutting the heart and presenting with ectopic ACTH secretion.

4.
A A Case Rep ; 3(2): 15-9, 2014 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-25611017

RESUMO

A 74-year-old man presented for outpatient endoscopy because of dysphagia and the sensation of a mass in the back of his throat. Esophagogastroduodenoscopy demonstrated a soft tissue mass in the proximal esophagus that prolapsed into the hypopharynx on withdrawal of the endoscope. Complete airway obstruction ensued, requiring emergent tracheotomy. The patient was transferred to the hospital for further treatment. Surgical resection revealed a rare giant fibrovascular polyp, which may be associated with asphyxiation and sudden death.

5.
J Cardiothorac Surg ; 6: 19, 2011 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-21352550

RESUMO

BACKGROUND: This study was designed to assess the prevalence of smoking at time of lung cancer diagnosis in a surgical patient cohort referred for cardiothoracic surgery. METHODS: Retrospective study of lung cancer patients (n = 626) referred to three cardiothoracic surgeons at a tertiary care medical center in Southern California from January 2006 to December 2008. Relationships among years of smoking cessation, smoking status, and tumor histology were analyzed with Chi-square tests. RESULTS: Seventy-seven percent (482) had a smoking history while 11.3% (71) were current smokers. The length of smoking cessation to cancer diagnosis was <1 year for 56 (13.6%), 1-10 years for 110 (26.8%), 11-20 years for 87 (21.2%), 21-30 years for 66 (16.1%), 31-40 years for 44 (10.7%), 41-50 years for 40 (9.7%) and 51-60 years for 8 (1.9%). The mean cessation was 18.1 ± 15.7 years (n = 411 former smokers). Fifty-nine percent had stage 1 disease and 68.0% had adenocarcinoma. Squamous cell carcinoma was more prevalent in smokers (15.6% vs. 8.3%, p = 0.028); adenocarcinoma was more prevalent in never-smokers (79.9% versus 64.3%, p = 0.0004). The prevalence of adenocarcinoma varied inversely with pack year (p < 0.0001) and directly with years of smoking cessation (p = 0.0005). CONCLUSIONS: In a surgical lung cancer cohort, the majority of patients were smoking abstinent greater than one decade before the diagnosis of lung cancer.


Assuntos
Neoplasias Pulmonares/epidemiologia , Pneumonectomia , Abandono do Hábito de Fumar/estatística & dados numéricos , Fumar/efeitos adversos , Idoso , California/epidemiologia , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/cirurgia , Masculino , Prevalência , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo
6.
J Card Surg ; 23(4): 378-81, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18384575

RESUMO

Migration of a fractured strut of an inferior vena cava (IVC) filter to the heart is a rare complication. We report the case of a 40-year-old woman who had this complication eight months after infrarenal IVC filter placement. She presented with chest pain. The broken arm of the IVC filter had migrated to the heart and penetrated the free wall of the right ventricle. It was removed successfully by cardiac surgery without the aid of cardiopulmonary bypass.


Assuntos
Migração de Corpo Estranho/diagnóstico , Ventrículos do Coração/lesões , Filtros de Veia Cava/efeitos adversos , Ferimentos Penetrantes/diagnóstico , Adulto , Falha de Equipamento , Feminino , Migração de Corpo Estranho/cirurgia , Humanos , Ferimentos Penetrantes/etiologia , Ferimentos Penetrantes/cirurgia
7.
Ann Thorac Surg ; 85(5): e24-6, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18442525

RESUMO

Photodynamic therapy is an effective technique for debulking endobronchial tumors over an acceptably short time-course; however, to be effective, numerous treatment cycles may be required to achieve the desired results. We present a case in which photodynamic therapy was used with curative intent to downsize an obstructing endobronchial non-small cell lung cancer in advance of resection via video-assisted thoracoscopic surgery with right upper lobe sleeve lobectomy.


Assuntos
Carcinoma Adenoescamoso/tratamento farmacológico , Carcinoma Adenoescamoso/cirurgia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/cirurgia , Terapia Neoadjuvante , Fotoquimioterapia/métodos , Pneumonectomia/métodos , Cirurgia Torácica Vídeoassistida/métodos , Broncoscopia , Carcinoma Adenoescamoso/patologia , Terapia Combinada , Desbridamento/métodos , Feminino , Humanos , Pulmão/patologia , Neoplasias Pulmonares/patologia , Excisão de Linfonodo , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Tomografia Computadorizada por Raios X
8.
Ann Thorac Surg ; 85(2): S729-32, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18222205

RESUMO

BACKGROUND: As thoracic surgery moves towards more minimally invasive procedures, such as video-assisted thoracic surgery (VATS) lobectomy, conversion from a VATS to open thoracotomy has been required for a sleeve resection. This article reports a large experience of VATS sleeve lobectomy. METHODS: We reviewed our thoracic surgery database of more than 1500 VATS lobectomies for VATS sleeve resections. Preoperative, operative, and perioperative outcome variables, including morbidity and mortality were examined. RESULTS: Identified were 13 patients (median age, 59 years; range, 16 to 82 years) who underwent VATS sleeve lobectomy. There were no conversions to thoracotomy. Diagnoses included non-small cell lung cancer in 8 patients, typical carcinoid in 4, and metastatic sarcoma in 1 patient. Median tumor size was 2.1 cm (range, 0 to 6.6 cm). Median data were operative time, 167 minutes (range, 90 to 300 minutes); blood loss, 250 mL (range, 75 to 800 mL); chest tube drainage, 692 mL (range, 459 to 1590 mL); and chest tube duration, 3 days (range, 2 to 6 days). Median intensive care unit stay was 0 days (range, 0 to 4 days), and median hospital stay was 3 days (range, 2 to 8 days). No complications occurred in 9 patients (69%). Morbidity in the remaining 4 patients included 1 patient each with atrial fibrillation, anastomotic stricture, reintubation, and bronchial tear requiring repair. There were no deaths at 30 days. CONCLUSIONS: In experienced centers, VATS sleeve lobectomy is possible with acceptable morbidity and mortality as well as short length of stay.


Assuntos
Mortalidade Hospitalar/tendências , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/cirurgia , Pneumonectomia/métodos , Cirurgia Torácica Vídeoassistida/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia por Agulha , Estudos de Coortes , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Tempo de Internação , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pneumonectomia/mortalidade , Complicações Pós-Operatórias/mortalidade , Sistema de Registros , Estudos Retrospectivos , Medição de Risco , Análise de Sobrevida , Cirurgia Torácica Vídeoassistida/mortalidade , Fatores de Tempo , Resultado do Tratamento
9.
Ann Thorac Surg ; 85(2): S733-6, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18222206

RESUMO

BACKGROUND: Although lobectomy is the standard for lung cancer because a wedge resection has a 3 to 5 times greater incidence of local recurrence, poor pulmonary function may preclude lobectomy. For these patients, low-dose-rate brachytherapy has recently been used to decrease local recurrence after sublobar resection. Current techniques expose operating room personnel and patient contacts to unnecessary radioactivity risks. We present our technique of sublobar resection combined with afterload catheters for high-dose-rate brachytherapy for patient benefit with minimal risk to others. METHODS: Forty-eight patients (25 women, 23 men) underwent wedge resection, node dissection, and brachytherapy. A remote-afterloading high-dose-rate unit for radiation produced a median dose of 2450 cGy (350 cGy per fraction over 7 fractions twice daily for 4 days). The dose was prescribed to 1 cm deep to the stapled line. Biologically, this dose is approximately 5000 cGy and above (180 cGy/d equivalent) at the depth of 5 mm in reference to the resection margin. RESULTS: Two patients died. The length of mean stay was 5.5 days (median, 5 days). Complications included prolonged air leak in 5 patients, atrial fibrillation in 5, pneumonia in 3, trapped lung in 2, and 1 each with empyema, bleeding, and recurrent laryngeal nerve injury. Three patients required a blood transfusion. Within the follow-up of 1 to 27 months, there were four recurrences. CONCLUSIONS: Wedge resection and brachytherapy appears to be a reasonable treatment for patients with lung cancer and pulmonary function that prohibits a lobectomy.


Assuntos
Braquiterapia/métodos , Mortalidade Hospitalar/tendências , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/cirurgia , Invasividade Neoplásica/patologia , Pneumonectomia/métodos , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Terapia Combinada , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Complicações Pós-Operatórias/mortalidade , Radioterapia Adjuvante , Testes de Função Respiratória , Estudos Retrospectivos , Medição de Risco , Análise de Sobrevida , Técnicas de Sutura , Suturas , Resultado do Tratamento
10.
Ann Thorac Surg ; 84(5): 1663-7; discussion 1667-8, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17954081

RESUMO

BACKGROUND: In the era of cost containment, a fast-tracking protocol was developed to reduce cost and shorten the length of stay after a lobectomy. The purpose of our study was to see whether a fast-tracking protocol provided a short length of stay without compromising morbidity and mortality or leading to readmission to the hospital. METHODS: The protocol was to perform lobectomies by means of video-assisted thoracoscopic surgery with no routine postoperative laboratory work or chest roentgenograms. The chest tubes were discontinued once the output was less than 300 mL in a 24-hour period and there was no air leak present. If the chest tube output was low, but there was an air leak, the patient was discharged home with a Heimlich valve. RESULTS: Two hundred eighty-two consecutive video-assisted thoracoscopic surgery lobectomies were performed by a single surgeon during 18 months in 158 women (56%) and 124 men (44%), with a mean age of 71.2 years. Following this protocol, the mean length of stay was 3.26 days, and the median was 3 days. Seven of 282 patients (2.5%) were discharged with a Heimlich valve. There was 1 mortality. There were no complications in 251 patients (89%). Two patients were readmitted to the hospital. No chest tubes were reinserted. CONCLUSIONS: Using a fast-tracking protocol, video-assisted thoracoscopic surgery lobectomy with anatomic dissection can be performed with minimal complication, a short postoperative length of stay, and reduced costs.


Assuntos
Pneumonectomia/métodos , Cirurgia Torácica Vídeoassistida/métodos , Idoso , Análise Custo-Benefício , Feminino , Humanos , Tempo de Internação , Masculino , Pneumonectomia/economia , Pneumonectomia/mortalidade , Cirurgia Torácica Vídeoassistida/economia , Cirurgia Torácica Vídeoassistida/mortalidade , Toracotomia
11.
Thorac Surg Clin ; 17(2): 223-31, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17626400

RESUMO

The literature shows that, in the hands of experienced thoracoscopic surgeons, VL is a safe operation that offers patients at least comparable complication and survival rates compared with lobectomy by thoracotomy. VL can be performed safely with proven advantages over conventional thoracotomy for lobectomy: smaller incisions, decreased postoperative pain, decreased LOS, decreased chest tube output and duration, decreased blood loss, better preservation of pulmonary function, and earlier return to normal activities. These results are obtained without sacrificing the oncologic principles of thoracic surgery, and, in fact, the evidence in the literature is mounting that VATS may offer reduced rates of complications and better survival.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/cirurgia , Estadiamento de Neoplasias , Pneumonectomia/métodos , Cirurgia Torácica Vídeoassistida , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Neoplasias Pulmonares/patologia , Complicações Pós-Operatórias , Cirurgia Torácica Vídeoassistida/instrumentação , Cirurgia Torácica Vídeoassistida/métodos , Resultado do Tratamento
12.
J Thorac Cardiovasc Surg ; 126(5): 1609-17, 2003 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-14666041

RESUMO

OBJECTIVE: Many tumors are poorly immunogenic and resistant to cytotoxic T-lymphocyte-mediated cell lysis. Because cisplatin has been demonstrated to increase tumor cell Fas receptor expression, we hypothesized that cisplatin will enhance cytotoxic T-lymphocyte tumor cell killing and augment the antitumor effect of an active immunotherapy strategy in a poorly immunogenic murine lung cancer model. METHODS: Lewis lung carcinoma cells were exposed to cisplatin in vitro, and Fas receptor expression and apoptosis in response to an agonistic anti-Fas antibody were quantified using flow cytometry. Wild-type and Fas ligand-deficient mice bearing Lewis lung carcinoma flank tumors were then treated with intraperitoneal cisplatin as well as an intratumoral injection of an adenovirus gene transfer vector encoding CD40 ligand. End points included tumor size, animal survival, and Fas expression (determined using immunofluorescence). Cytotoxicity assays were performed using splenocytes from adenovirus gene transfer vector encoding CD40 ligand-treated animals as effectors and cisplatin-treated Lewis lung carcinoma cells as targets. RESULTS: Cisplatin induced heightened expression of Fas receptor on Lewis lung carcinoma cells in vitro and in vivo and enhanced apoptosis in cells exposed to an agonistic anti-Fas antibody. In vivo, the combination of 1 dose of intraperitoneal cisplatin and intratumoral adenovirus gene transfer vector encoding CD40 ligand inhibited tumor growth and prolonged survival compared with adenovirus gene transfer vector encoding CD40 ligand alone, resulting in a higher cure rate. This effect was lost in Fas ligand-deficient mice. Splenocytes from adenovirus gene transfer vector encoding CD40 ligand-treated wild-type mice lysed cisplatin-treated Lewis lung carcinoma cells more efficiently than untreated Lewis lung carcinoma cells, an effect lost in splenocytes from Fas ligand-deficient mice. CONCLUSION: Cisplatin augments the antitumor effect of a cytotoxic T-lymphocyte-mediated immunotherapy strategy, resulting in a higher cure rate than seen with immunotherapy alone. This effect is associated with the enhanced ability of cytotoxic T lymphocytes to lyse tumor cells that have been exposed to cisplatin through Fas/Fas ligand interactions.


Assuntos
Carcinoma Pulmonar de Lewis/imunologia , Carcinoma Pulmonar de Lewis/terapia , Cisplatino/farmacologia , Imunoterapia Adotiva/métodos , Linfócitos T Citotóxicos/efeitos dos fármacos , Adenoviridae , Animais , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Ligante de CD40 , Feminino , Citometria de Fluxo , Imunofluorescência , Técnicas de Transferência de Genes , Vetores Genéticos , Injeções Intraperitoneais , Camundongos , Camundongos Endogâmicos C57BL , Probabilidade , Sensibilidade e Especificidade , Estatísticas não Paramétricas , Taxa de Sobrevida , Linfócitos T Citotóxicos/imunologia , Células Tumorais Cultivadas , Regulação para Cima , Receptor fas/efeitos dos fármacos , Receptor fas/imunologia
13.
J Thorac Cardiovasc Surg ; 126(1): 28-38, 2003 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12878936

RESUMO

OBJECTIVE: Pigment epithelium-derived factor is known to be an inhibitor of angiogenesis. We hypothesized that in vivo gene transfer of pigment epithelium-derived factor may inhibit tumor angiogenesis and growth in syngeneic models of thoracic malignancies. METHODS: An adenovirus vector encoding the human pigment epithelium-derived factor cDNA (AdPEDF) was used to transduce human lung cancer cells in vitro. Transgene expression was assessed using Western analysis. Three different murine flank tumors (2 lung, 1 colon) were then established in syngeneic mice and treated intratumorally with phosphate-buffered saline, AdPEDF, or an empty vector (AdNull). Endpoints measured included transgene expression, tumor size, and animal survival, as well as microvessel density within the tumor. Additionally, a murine pulmonary metastasis model was established by intravenous injection of a syngeneic colon adenocarcinoma cell line expressing a marker gene (beta-galactosidase). One day later, treatment (phosphate-buffered saline, AdNull, or AdPEDF) was administered intrapleurally. Tumor burden (gross and histologic inspection, lung weight, and beta-galactosidase expression) was then evaluated 13 days after vector dosing, and survival was recorded. RESULTS: AdPEDF-derived expression of pigment epithelium-derived factor was demonstrated in vitro and in vivo. In syngeneic murine lung cancer flank tumors, intratumoral administration of AdPEDF significantly inhibited tumor growth (P <.01), prolonged mouse survival (P <.01), and decreased microvessel density (P <.01) compared with control groups. In the pulmonary metastasis model, AdPEDF-treated mice exhibited significantly reduced lung lesions, lung weight (P <.0005), beta-galactosidase expression (P <.05), and animal survival was prolonged (P <.05). CONCLUSION: Gene transfer of pigment epithelium-derived factor suppresses tumor vascularization and growth, while prolonging survival in syngeneic murine models of thoracic malignancies.


Assuntos
Proteínas do Olho , Técnicas de Transferência de Genes , Fatores de Crescimento Neural , Proteínas/genética , Serpinas/genética , Neoplasias Torácicas/genética , Adenovírus Humanos/genética , Animais , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/mortalidade , Modelos Animais de Doenças , Feminino , Expressão Gênica/genética , Vetores Genéticos/administração & dosagem , Vetores Genéticos/antagonistas & inibidores , Vetores Genéticos/genética , Injeções Intravenosas , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/secundário , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Modelos Cardiovasculares , Biossíntese de Proteínas , Proteínas/antagonistas & inibidores , Serpinas/biossíntese , Análise de Sobrevida , Neoplasias Torácicas/metabolismo , Neoplasias Torácicas/mortalidade , Células Tumorais Cultivadas
14.
J Immunother ; 26(2): 117-29, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-12616103

RESUMO

Macrophage-derived chemokine is chemotactic for a variety of leukocytes, and has been shown to be involved in T 2-mediated cellular immunity. To evaluate the role of this chemokine in tumor immunity in vivo, an adenovirus vector encoding the human macrophage-derived chemokine cDNA (AdMDC) was administered to established murine tumors. Gene transfer with AdMDC significantly inhibited tumor growth and prolonged animal survival. AdMDC was not directly cytotoxic to tumor cells, but splenocytes from animals that received intratumoral AdMDC were able to lyse syngeneic tumor cells, and purified splenic CD8 cells secreted interferon-gamma in a tumor-specific manner. The antitumor activity of AdMDC was lost in mice lacking CD8 T lymphocytes, but surprisingly, it was preserved in animals lacking CD4 cells, as was the systemic cytotoxic T lymphocyte response. Systemic NK cells did not play a role in the antitumor immune response induced by AdMDC. Experiments using knockout mice demonstrated that host expression of MHC Class I, but not Class II, IL-4, or IL-12, was necessary for AdMDC to exert its antitumor effect, and immunohistochemistry demonstrated infiltrates of CD8 and CD86 cells, but not CD4 cells in treated tumors. These studies highlight a new function for macrophage-derived chemokine by demonstrating that it possesses in vivo antitumor activity with CD8 T cells as the effector cells, and interestingly, that the CD4 cell/MHC II pathway of CD8 cell activation is not required for the antitumor effects of this chemokine.(H)


Assuntos
Adenocarcinoma/terapia , Linfócitos T CD4-Positivos/imunologia , Quimiocinas CC/genética , Quimiocinas CC/farmacologia , Neoplasias do Colo/terapia , Terapia Genética/métodos , Adenocarcinoma/imunologia , Adenoviridae/genética , Animais , Quimiocina CCL22 , Neoplasias do Colo/imunologia , Modelos Animais de Doenças , Regulação Neoplásica da Expressão Gênica , Vetores Genéticos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias Experimentais/terapia , Probabilidade , Ratos , Estatísticas não Paramétricas , Taxa de Sobrevida , Transfecção , Resultado do Tratamento
15.
Clin Cancer Res ; 8(11): 3561-9, 2002 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-12429647

RESUMO

PURPOSE: The purpose of this study was to evaluate the effect of the Rel homology domain (RHD) of the transcription factor, nuclear factor kappa B (NF kappa B), on proinflammatory gene expression in bone marrow-derived dendritic cells (BMDCs). EXPERIMENTAL DESIGN: We used an adenovirus vector encoding only the RHD of the NF kappa B (p65 family member) cDNA (AdRHD) to transduce murine BMDCs ex vivo. Endpoints measured included BMDC expression of activation markers, cytokine secretion, peptide antigen presentation, and the ability of these transduced cells to induce antitumor immunity in vivo. RESULTS: AdRHD-transduced BMDCs secreted higher levels of the cytokines interleukin (IL) 1 beta, IL-6, and IL-12 (p40) compared with sham-transduced BMDCs or those transduced with an empty vector. AdRHD induced heightened surface expression of the activation markers CD40, B7.1, B7.2, and MHC class II on BMDCs, and these cells were able to present a peptide antigen to a T-lymphocyte hybridoma more efficiently than controls in vitro. Growth of syngeneic, established tumors (CT26 and B16.F10) was inhibited, and survival was prolonged in the mice that received intratumoral AdRHD-modified BMDCs compared with controls. Splenocytes from CT26 tumor-bearing animals that received intratumoral AdRHD-modified BMDCs were able to lyse CT26 target cells more efficiently than controls. Similar experiments using host mice harboring targeted mutations in CD4 and CD8, as well as BMDCs from mice lacking MHC class I, MHC class II, or IL-12 revealed that this tumor immunity was dependent on the presence of CD4+ and CD8+ cells in the tumor-bearing host, as well as MHC class I, MHC class II, and IL-12 expression by the administered BMDCs. Furthermore, induction of IL-12 (p40) expression by AdRHD was completely abrogated in BMDCs lacking the c-Rel NF kappa B family member. CONCLUSIONS: We made the following conclusions: (a) gene transfer-mediated overexpression of the RHD of NF kappa B activates BMDCs; (b) AdRHD-transduced BMDCs induce antitumor immunity when administered intratumorally, an effect mediated by both the CD4+ T cell/MHC class II and the CD8+ T cell/MHC class I pathways, as well as IL-12; and (c) IL-12 (p40) up-regulation by the RHD transgene in BMDCs is dependent on the presence of the c-Rel NF kappa B family member.


Assuntos
Adenoviridae/genética , Células Dendríticas/metabolismo , Vetores Genéticos , NF-kappa B/genética , Animais , Antígeno CD11c/biossíntese , Complexo CD3/biossíntese , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Citocinas/metabolismo , Citometria de Fluxo , Técnicas de Transferência de Genes , Genes MHC Classe I , Genes MHC da Classe II , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , NF-kappa B/química , Transplante de Neoplasias , Peptídeos/química , Estrutura Terciária de Proteína , Fatores de Tempo , Fator de Transcrição RelA , Transfecção , Células Tumorais Cultivadas , Regulação para Cima
16.
Mol Ther ; 5(3): 307-15, 2002 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11863421

RESUMO

To address the effect of adenovirus (Ad) gene transfer vector transduction on the diverse functions of dendritic cells, we used an Ad vector encoding no transgene (AdNull) to transduce mouse bone-marrow-derived dendritic cells (BMDC). Initial experiments using an Ad vector encoding a marker gene (AdGFP, jellyfish green fluorescent protein) showed that the optimal ratio of infectious Ad particles to each cell was 100, when both transgene expression and resultant BMDC viability were taken into account. Exposure to AdNull resulted in upregulation of both surface activation markers (CD40, MHC class II, B7.1, B7.2, ICAM-1) and IL-12 expression by BMDC. AdNull activation of BMDC was observed in multiple strains of mice. Despite this, AdNull-transduced BMDC displayed only modestly impaired antigen uptake ability, as demonstrated in macropinocytosis and phagocytosis assays, in vitro. However, Ad-modified BMDC migrated to regional lymph nodes five times more efficiently than sham-transduced BMDC in vivo. In addition, Ad transduction significantly enhanced the ability of BMDC to present a model peptide antigen to T-lymphocyte hybridoma cells at low BMDC:T cell ratios. We conclude that Ad modification, in and of itself, induces a state of activation in mouse BMDC. This activation, albeit mild compared with that induced by other stimuli, produces measurable effects of the specific immunological functions of these antigen-presenting cells.


Assuntos
Adenoviridae , Células Dendríticas/imunologia , Vetores Genéticos , Transgenes/imunologia , Animais , Apresentação de Antígeno/imunologia , Movimento Celular/imunologia , Células Cultivadas , Células Dendríticas/fisiologia , Regulação da Expressão Gênica/imunologia , Camundongos , Fagocitose/imunologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...