Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 105
Filtrar
1.
Anticancer Res ; 39(11): 6355-6358, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31704867

RESUMO

BACKGROUND/AIM: Pneumonitis is a serious complication after radiotherapy of breast cancer. This study aimed to identify its prevalence and potential risk factors. PATIENTS AND METHODS: A total of 606 patients irradiated following breast-conserving surgery or mastectomy were retrospectively analyzed. In patients developing pneumonitis, radiation and clinical parameters were investigated to identify potential risk factors. RESULTS: Eleven patients (1.8%) developed a pneumonitis grade ≥2. Mean doses to the ipsilateral lung were >7 Gy in 5 patients (45%). Of the other patients, 5 had a chronic inflammatory disease. Six patients (55%) had another malignancy (4 previous contralateral breast cancers, 1 previous ovarian and thyroid cancer, 1 synchronous carcinoma-in-situ (pTis) at the contralateral breast). Five patients (45%) received chemotherapy including taxanes and 4 patients (36%) received trastuzumab. CONCLUSION: The prevalence of pneumonitis was 1.8%. Potential risk factors included mean radiation dose to ipsilateral lung >7 Gy, systemic treatment with taxanes or trastuzumab, chronic inflammatory disease and history of another malignancy.


Assuntos
Neoplasias da Mama/radioterapia , Pneumonite por Radiação/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Inflamatórios/uso terapêutico , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Carcinoma in Situ/radioterapia , Feminino , Humanos , Pulmão/efeitos da radiação , Mastectomia , Mastectomia Segmentar , Pessoa de Meia-Idade , Neoplasias Primárias Múltiplas , Prednisolona/uso terapêutico , Prevalência , Pneumonite por Radiação/tratamento farmacológico , Pneumonite por Radiação/etiologia , Estudos Retrospectivos , Fatores de Risco , Trastuzumab/administração & dosagem , Trastuzumab/efeitos adversos
2.
Biomed Res Int ; 2019: 6012473, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31341902

RESUMO

Objective: Studying correlative changes of Th1/Th2 (Th, Helper T cells) related factor Interferon-γ (IFN-γ) and Interleukin-4 (IL-4) in the progression of radiation pneumonia (RP) rats and the efficacy of Shashen-Maidong decoction on these indexes to explore the immune mechanism of the decoction on the prevention and treatment of RP. Methods: Male 60 Sprague-Dawley (SD) rats were randomly divided into four groups. In addition to the normal control group taking saline, the other rats were set up RP model treated with Shashen-Maidong decoction or dexamethasone (DXM), respectively. The IFN-γ and IL-4 concentrations in serum and bronchoalveolar lavage fluid (BALF) of rats were tested in the 2nd and 4th week after radiation, and the relative ratio of IFN-γ/IL-4 was calculated. Results: (1) There was significant difference of serum IL-4 concentrations in group B (p<0.01) and extreme difference in groups C and D (p<0.001) compared with group A in 4th week. Compared with group D, IL-4 concentrations in group B increased significantly in both 2nd and 4th week (p<0.01). Group B had significantly decreased IFN-γ concentrations in BALF (p<0.001) compared with group D in the 4th week. And IFN-γ concentrations in BALF in group B were increased compared with group C in the 4th week (p<0.05). (2) There was no difference of the relative ratio of IFN-γ/IL-4 at each time in groups B and A for both serum and BALF, while the ratios in groups C and D in 4th week in BALF were increased (p<0.05) compared to group A. Conclusion: Shashen-Maidong decoction can improve the immune function of RP rats by increasing IFN-γ concentration and decreasing IL-4 concentration, possibly by increasing the relative ratio of IFN-γ/IL-4 to regulate the immune imbalance of Th1/Th2.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Interferon gama/imunologia , Interleucina-4/imunologia , Lesões Experimentais por Radiação/imunologia , Pneumonite por Radiação/imunologia , Células Th1/imunologia , Células Th2/imunologia , Animais , Dexametasona/farmacologia , Masculino , Lesões Experimentais por Radiação/tratamento farmacológico , Lesões Experimentais por Radiação/patologia , Pneumonite por Radiação/tratamento farmacológico , Pneumonite por Radiação/patologia , Ratos , Ratos Sprague-Dawley , Células Th1/patologia , Células Th2/patologia
3.
Health Phys ; 116(4): 558-565, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30624347

RESUMO

Total-body irradiation causes acute and delayed toxicity to hematopoietic, pulmonary, cardiac, gastrointestinal, renal, and other organ systems. Angiotensin-converting enzyme inhibitors mitigate many of the delayed injuries to these systems. The purpose of this study was to define echocardiographic features in rats at two times after irradiation, the first before lethal radiation pneumonitis (50 d) and the second after recovery from pneumonitis but before lethal radiation nephropathy (100 d), and to determine the actions of the angiotensin-converting enzyme inhibitor lisinopril. Four groups of female WAG/RijCmcr rats at 11-12 wk of age were studied: nonirradiated, nonirradiated plus lisinopril, 13-Gy partial-body irradiation sparing one hind leg (leg-out partial-body irradiation), and 13-Gy leg-out partial-body irradiation plus lisinopril. Lisinopril was started 7 d after radiation. Echocardiograms were obtained at 50 and 100 d, and cardiac histology was assessed after 100 d. Irradiation without lisinopril demonstrated echocardiographic transient pulmonary hypertension by 50 d which was largely resolved by 100 d in survivors. Irradiated rats given lisinopril showed no increase in pulmonary artery pressures at 50 d but exhibited left ventricular remodeling. By 100 d these rats showed some signs of pulmonary hypertension. Lisinopril alone had no impact on echocardiographic end points at either time point in nonirradiated rats. Mild increases in mast cells and fibrosis in the heart were observed after 100 d following 13-Gy leg-out partial-body irradiation. These data demonstrate irradiation-induced pulmonary hypertension which was reversed in survivors of pneumonitis. Lisinopril modified cardiovascular remodeling to enhance survival in this model from 41% to 86% (p = 0.0013).


Assuntos
Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Hipertensão Pulmonar/etiologia , Lisinopril/uso terapêutico , Lesões Experimentais por Radiação/tratamento farmacológico , Pneumonite por Radiação/tratamento farmacológico , Remodelação Ventricular/efeitos da radiação , Animais , Ecocardiografia , Feminino , Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/patologia , Hipertensão Pulmonar/prevenção & controle , Miocárdio/patologia , Lesões Experimentais por Radiação/patologia , Lesões Experimentais por Radiação/prevenção & controle , Pneumonite por Radiação/complicações , Pneumonite por Radiação/prevenção & controle , Ratos
4.
Mar Drugs ; 16(10)2018 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-30347679

RESUMO

Purpose: Radiotherapy is a crucial treatment approach for many types of cancer. Radiation pneumonitis (RP) is one of the major complications in chest irradiation. Fucoidan is a sulfated polysaccharide found mainly in various species of brown seaweed. Recent studies have demonstrated the anti-inflammatory effects of fucoidan. However, no study has reported a well-established prophylactic agent for RP. Therefore, we investigated the effects of fucoidan on RP and radiotherapy (RT)-induced lung fibrosis. Materials and Methods: We compared RP and RT-induced fibrosis in lung tissue specimens obtained from irradiated (10 Gy/shot) C57BL/6 mice with or without fucoidan administration (200 mg/kg/day, oral gavage for 14 days). The expression patterns of cytokines in the pleural fluid were determined using a cytokine array and confirmed through enzyme immunoassays. Results: Fucoidan administration attenuated RP and RT-induced fibrosis in lung tissues. Decreased neutrophil and macrophage accumulation was observed in irradiated lung tissues, and radiation-induced lung fibrosis, as demonstrated by Masson trichrome staining, was attenuated. We investigated the expression patterns of inflammatory cytokines in the irradiated lung pleural fluid through the protein array; results revealed that fucoidan administration changed the expression patterns of inflammatory cytokines in irradiated lung tissues. Furthermore, the expression levels of TIMP-1, CXCL1, MCP-1, MIP-2, and interleukin-1Ra were substantially enhanced in the pleural fluid, but fucoidan administration significantly reduced their expression. Conclusions: Fucoidan changes the expression patterns of inflammatory cytokines, which may consequently attenuate RP and RT-induced lung fibrosis.


Assuntos
Citocinas/metabolismo , Mediadores da Inflamação/metabolismo , Pulmão/patologia , Polissacarídeos/farmacologia , Pneumonite por Radiação/tratamento farmacológico , Animais , Modelos Animais de Doenças , Fibrose , Pulmão/efeitos da radiação , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Feófitas/química , Polissacarídeos/uso terapêutico , Pneumonite por Radiação/etiologia , Pneumonite por Radiação/patologia , Alga Marinha/química
5.
Sci Rep ; 8(1): 13316, 2018 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-30190567

RESUMO

Methods to protect against radiation-induced lung injury (RILI) will facilitate the development of more effective radio-therapeutic protocols for lung cancer and may provide the means to protect the wider population in the event of a deliberate or accidental nuclear or radiological event. We hypothesised that supplementing lipid membranes through nebulization of synthetic lamellar lipids would mitigate RILI. Following pre-treatment with either nebulised lamellar lipids or saline, anaesthetised sheep were prescribed fractionated radiotherapy (30 Gray (Gy) total dose in five 6 Gy fractions at 3-4 days intervals) to a defined unilateral lung volume. Gross pathology in radio-exposed lung 37 days after the first radiation treatment was consistent between treatment groups and consisted of deep red congestion evident on the pleural surface and firmness on palpation. Consistent histopathological features in radio-exposed lung were subpleural, periarteriolar and peribronchial intra-alveolar oedema, alveolar fibrosis, interstitial pneumonia and type II pneumocyte hyperplasia. The synthetic lamellar lipids abrogated radiation-induced alveolar fibrosis and reduced alpha-smooth muscle actin (ASMA) expression in radio-exposed lung compared to saline treated sheep. Administration of synthetic lamellar lipids was also associated with an increased number of cells expressing dendritic cell-lysosomal associated membrane protein throughout the lung.


Assuntos
Lipídeos/farmacologia , Alvéolos Pulmonares , Lesões Experimentais por Radiação , Pneumonite por Radiação , Administração por Inalação , Animais , Feminino , Masculino , Alvéolos Pulmonares/metabolismo , Alvéolos Pulmonares/patologia , Lesões Experimentais por Radiação/tratamento farmacológico , Lesões Experimentais por Radiação/metabolismo , Lesões Experimentais por Radiação/patologia , Pneumonite por Radiação/tratamento farmacológico , Pneumonite por Radiação/metabolismo , Pneumonite por Radiação/patologia , Ovinos
6.
Mil Med Res ; 5(1): 30, 2018 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-30185231

RESUMO

AEOL-10150 is a broad-spectrum metalloporphyrin superoxidase dismutase (SOD) mimic specifically designed to neutralize reactive oxygen and nitrogen species. Research has shown that AEOL-10150 is a potent medical countermeasure against national security threats including sulfur mustard (SM), nerve agent exposure and radiation pneumonitis following a radiological/nuclear incident sufficient to cause acute radiation syndrome (ARS). AEOL-10150 performed well in animal safety studies, and two completed phase 1 safety studies in patients demonstrated that the drug was safe and well tolerated, indicating that AEOL-10150 has potential as a new catalytic antioxidant drug. In this article, we review improvements in AEOL-10150 in preclinical pharmacodynamic studies, especially regarding anti-SM, chlorine gas and radiation exposure studies.


Assuntos
Antioxidantes/farmacologia , Lesão Pulmonar/prevenção & controle , Metaloporfirinas/farmacologia , Pneumonite por Radiação/tratamento farmacológico , Animais , Substâncias para a Guerra Química/toxicidade , Humanos , Lesão Pulmonar/induzido quimicamente , Camundongos , Gás de Mostarda/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Lesões Experimentais por Radiação/prevenção & controle
7.
Inflammation ; 41(6): 2196-2205, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30091034

RESUMO

To investigate the effects of aquaporin 4 (AQP4) inhibitor in irradiation-induced pulmonary inflammation in mice. A single dose of 75 Gy was delivered to the left lung of mice to induce radiation pneumonitis. For inhibition of AQP4, 200 mg/kg of TGN-020 was administered i.p. one time per 2 days post-irradiation. Blockade of AQP4 with TGN-020 resulted in the inhibition of inflammatory cell infiltration and the downregulation of inflammatory cytokines (IL-6, IL-17, and TGF-ß), chemokines (MIP1a and MCP1), fibrosis-related (Col3al and Fn1), and M2 macrophage marker (Arg1) post-irradiation. Immunofluorescence staining indicated that there was significant fewer M2 macrophage infiltration in the irradiated lung tissues from mice treated with TGN-020. Additionally, depletion of macrophages with liposome clodronate resulted in alleviated lung injury induced by irradiation. Furthermore, adoptive transfer of M1 or M2 macrophages into clodronate-treated mice was performed. The results showed that the administration of M2 macrophages fully reversed the clodronate-induced beneficial effect on inflammation score, thickness, and fibrosis. However, transfer of M1 macrophages only impacted the inflammation score and thickness and did not affect lung fibrosis. AQP4 blockade alleviated the development and severity of irradiated lung damage. This was associated with attenuated infiltration of inflammatory cell, decreased production of pro-inflammatory cytokines, and inhibited activation of M2 macrophages.


Assuntos
Aquaporina 4/antagonistas & inibidores , Niacinamida/análogos & derivados , Pneumonia/prevenção & controle , Pneumonite por Radiação/tratamento farmacológico , Tiadiazóis/farmacologia , Animais , Movimento Celular/efeitos dos fármacos , Ácido Clodrônico/farmacologia , Citocinas/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/transplante , Camundongos , Niacinamida/farmacologia , Niacinamida/uso terapêutico , Doses de Radiação , Tiadiazóis/uso terapêutico
8.
PLoS One ; 13(5): e0198015, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29847598

RESUMO

BACKGROUND: Radiation pneumonitis is a common and serious complication of radiotherapy. Many published randomized controlled studies (RCTs) reveal a growing trend of using herbal medicines as adjuvant therapy to prevent radiation pneumonitis; however, their efficacy and safety remain unexplored. OBJECTIVE: The aim of this systematic review is to evaluate the efficacy and safety of herbal medicines as adjunctive therapy for the prevention of radiation pneumonitis in patients with lung cancer who undergo radiotherapy. METHODS: We searched the following 11 databases: three English medical databases [MEDLINE (PubMed), EMBASE, The Cochrane Central Register of Controlled Trials (CENTRAL)], five Korean medical databases (Korean Studies Information, Research information Service System, KoreaMed, DBPIA, National Digital Science Library), and three Chinese medical databases [the China National Knowledge Database (CNKI), Journal Integration Platform (VIP), and WanFang Database]. The primary outcome was the incidence of radiation pneumonitis. The risk of bias was assessed using the Cochrane risk-of-bias tool. RESULTS: Twenty-two RCTs involving 1819 participants were included. The methodological quality was poor for most of the studies. Meta-analysis showed that herbal medicines combined with radiotherapy significantly reduced the incidence of radiation pneumonitis (n = 1819; RR 0.53, 95% CI 0.45-0.63, I2 = 8%) and the incidence of severe radiation pneumonitis (n = 903; RR 0.22, 95% CI 0.11-0.41, I2 = 0%). Combined therapy also improved the Karnofsky performance score (n = 420; WMD 4.62, 95% CI 1.05-8.18, I2 = 82%). CONCLUSION: There is some encouraging evidence that oral administration of herbal medicines combined with radiotherapy may benefit patients with lung cancer by preventing or minimizing radiation pneumonitis. However, due to the poor methodological quality of the identified studies, definitive conclusion could not be drawn. To confirm the merits of this approach, further rigorously designed large scale trials are warranted.


Assuntos
Medicina Herbária , Neoplasias Pulmonares/radioterapia , Extratos Vegetais/administração & dosagem , Extratos Vegetais/uso terapêutico , Pneumonite por Radiação/tratamento farmacológico , Administração Oral , Humanos , Pneumonite por Radiação/etiologia
9.
Bull Exp Biol Med ; 165(1): 40-43, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29796814

RESUMO

The efficiency of neomitilan, a polysaccharide isolated from Crenomytilus grayanus mussels, was studied in experimental model of radiation pneumonia (irradiation of the animal lungs with a total dose of 14 and 28 Gy). Histological study showed that an increase in the number of nucleated components in the lungs of animals subjected to neomitilan inhalation prior to irradiation. Proliferation of bronchial epitheliocytes and the formation of additional lymphoid structures were also revealed in these animals. The absence of a tendency to lung tissue recovery in animals irradiated with 28 Gy is due to extreme radiation toxicity.


Assuntos
Bivalves/química , Polissacarídeos/química , Polissacarídeos/uso terapêutico , Lesões Experimentais por Radiação/tratamento farmacológico , Pneumonite por Radiação/tratamento farmacológico , Administração por Inalação , Animais , Relação Dose-Resposta à Radiação , Feminino , Camundongos
10.
Medicine (Baltimore) ; 97(21): e10681, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29794744

RESUMO

RATIONALE: This combination of fluticasone propionate (FP) and the long-acting ß2-agonist salmeterol (Salm) can control the symptoms of asthma and COPD better than FP or Salm on their own and better than the combination of inhaled corticosteroids plus montelukast. FP/Salm has been shown to control symptoms of asthma and COPD better than a double dose of inhaled steroids. The patient in our report had a history of COPD, and suffered relapse of RP when given only steroids. It is possible that COPD history helps explain this patient's more difficult treatment course. Therefore, this combination may be more effective than inhaled steroids for patients with a history of COPD. PATIENT CONCERS: This patient suffered adverse reactions triggered by methylprednisolone: weight gain, hyperglycaemia and sleep disturbance after more than two months of intravenous and oral prednisolone. These reactions disappeared when we switched the patients to FP/Salm maintenance therapy. DIAGNOSES: The patient underwent upper right lobectomy in September 2011. Immunohistochemistry indicated low squamous cell differentiation, and he was diagnosed with stage IIB disease (T2N1M0) according to the Union for International Cancer Control (UICC) (7th edition).One month after repeat radiotherapy, the patient experienced fever (37.6°C), cough, chest distress and shortness of breath. We performed serologic tests, laboratory tests for procalcitonin and C-reactive protein, as well as sputum and blood cultures to rule out bacterial infection. Chest CT showed consolidation with air bronchogram in the hilum of the right lung and ground-glass densities in the right lower lobe and left upper lobe. These radiographic signs are typical of RP. Since the patient required oxygen, he was diagnosed with grade III RP. INTERVENTIONS: After the patinet was diagnosed with grade III RP. The patient was immediately prescribed oxygen, anti-infectives for prophylaxis, treatments to facilitate expectoration and prevent asthma, and most importantly, intravenous methylprednisone at an initial dose of 60  per day. And we cut the steroid dose in half every one week when the patient's symptoms improved obviously, and the patchy shadow on the chest radiograph sharply reduced. Then we give him FP (500 mg)/Salm (50 mg) twice daily for two months. Then the dose was halved for an additional two months. OUTCOMES: The patient showed no signs of tumor or RP relapse by the last follow-up in March 2018. LESSONS: This maintenance therapy of FP/Salm for patient with grade III RP may help avoid relapse when steroid therapy is tapered, particularly for patients with a history of COPD. It may also reduce risk of steroid-associated adverse effects. Based on the results observed with our patient, we intend to design a prospective trial to assess the efficacy of FP/Salm when used as preventive treatment for patients at high risk of RP, and when used as maintenance treatment for patients with grade III RP.


Assuntos
Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Combinação Fluticasona-Salmeterol/uso terapêutico , Neoplasias Pulmonares/terapia , Pneumonite por Radiação/tratamento farmacológico , Glucocorticoides/efeitos adversos , Glucocorticoides/uso terapêutico , Humanos , Pulmão/patologia , Pulmão/efeitos da radiação , Masculino , Metilprednisolona/efeitos adversos , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Pneumonectomia , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Pneumonite por Radiação/diagnóstico , Tomografia Computadorizada por Raios X , Resultado do Tratamento
11.
Intern Med ; 57(9): 1281-1285, 2018 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-29279483

RESUMO

A 59-year-old woman suffering from dry cough and dyspnea was admitted to our hospital. She had undergone concurrent chemo-radiotherapy five months earlier. Chest computed tomography revealed bilateral ground-glass opacities extending outside the irradiated lung field. Her eosinophil numbers were increased in both the peripheral blood and the bronchoalveolar lavage fluid; therefore, she was diagnosed with radiation pneumonitis accompanied by eosinophilic alveolitis. Steroid therapy promptly improved the pneumonitis. Radiation pneumonitis accompanied by eosinophilic alveolitis extending outside the irradiated field is rare. Bronchoalveolar lavage is useful for a diagnosis, and steroid therapy is effective for treatment.


Assuntos
Corticosteroides/uso terapêutico , Alveolite Alérgica Extrínseca/tratamento farmacológico , Alveolite Alérgica Extrínseca/etiologia , Neoplasias Pulmonares/radioterapia , Pneumonite por Radiação/tratamento farmacológico , Pneumonite por Radiação/etiologia , Radioterapia/efeitos adversos , Alveolite Alérgica Extrínseca/diagnóstico por imagem , Eosinófilos/patologia , Feminino , Humanos , Pulmão/patologia , Neoplasias Pulmonares/diagnóstico por imagem , Pessoa de Meia-Idade , Pneumonite por Radiação/diagnóstico por imagem , Resultado do Tratamento
12.
Am J Clin Oncol ; 41(6): 576-580, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27560156

RESUMO

OBJECTIVES: Angiotensin-converting enzyme inhibitors (ACEi) have demonstrated decreased rates of radiation-induced lung injury in animal models and clinical reports have demonstrated decreased pneumonitis in the setting of conventionally fractionated radiation to the lung. We tested the role of ACEi in diminishing rates of symptomatic (grade ≥2) pneumonitis in the setting of lung stereotactic body radiation therapy (SBRT). METHODS: We analyzed patients treated with thoracic SBRT to 48 to 60 Gy in 4 to 5 fractions from 2006 to 2014. We reviewed pretreatment and posttreatment medication profiles to document use of ACEi, angiotensin receptor blockers, bronchodilators, aspirin, PDE-5 inhibitors, nitrates, and endothelin receptor antagonists. Pneumonitis was graded posttreatment based on Common Terminology Criteria for Adverse Events Version 4.0. Univariate and multivariate analysis was performed and time to development of pneumonitis was evaluated by the Kaplan-Meier method. RESULTS: A total of 189 patients were evaluated with a median follow-up of 24.8 months. The overall 1-year rate of symptomatic pneumonitis was 13.2%. The 1-year rate of symptomatic pneumonitis was 4.2% for ACEi users versus 16.3% in nonusers (P=0.03). On univariate analysis, the odds of developing grade 2 or greater pneumonitis were significantly lower for patients on ACEi (P=0.03). On multivariate analysis, after controlling for clinicopathologic characteristics and dosimetric endpoints, there was a significant association between ACEi use and decreased risk of clinical pneumonitis (P=0.04). Angiotensin receptor blockers or other bronchoactive medications did not show significant associations with development of pneumonitis. CONCLUSIONS: Incidental concurrent use of ACEi demonstrated efficacy in diminishing rates of symptomatic pneumonitis in the setting of lung SBRT.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Quimiorradioterapia , Neoplasias Pulmonares/cirurgia , Lesões por Radiação/tratamento farmacológico , Pneumonite por Radiação/tratamento farmacológico , Radiocirurgia/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Lesões por Radiação/diagnóstico , Lesões por Radiação/etiologia , Pneumonite por Radiação/diagnóstico , Pneumonite por Radiação/etiologia , Fatores de Risco , Taxa de Sobrevida
13.
Am J Clin Oncol ; 41(4): 396-401, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-27100959

RESUMO

OBJECTIVES: The primary objective of NRG Oncology Radiation Therapy Oncology Group 0123 was to test the ability of the angiotensin-converting enzyme inhibitor captopril to alter the incidence of pulmonary damage after radiation therapy for lung cancer; secondary objectives included analyzing pulmonary cytokine expression, quality of life, and the long-term effects of captopril. MATERIALS AND METHODS: Eligible patients included stage II-IIIB non-small cell lung cancer, stage I central non-small cell lung cancer, or limited-stage small cell. Patients who met eligibility for randomization at the end of radiotherapy received either captopril or standard care for 1 year. The captopril was to be escalated to 50 mg three times a day. Primary endpoint was incidence of grade 2+ radiation-induced pulmonary toxicity in the first year. RESULTS: Eighty-one patients were accrued between June 2003 and August 2007. Given the low accrual rate, the study was closed early. No significant safety issues were encountered. Eight patients were ineligible for registration or withdrew consent before randomization and 40 patients were not randomized postradiation. Major reasons for nonrandomization included patients' refusal and physician preference. Of the 33 randomized patients, 20 were analyzable (13 observation, 7 captopril). The incidence of grade 2+ pulmonary toxicity attributable to radiation therapy was 23% (3/13) in the observation arm and 14% (1/7) in the captopril arm. CONCLUSIONS: Despite significant resources and multiple amendments, NRG Oncology Radiation Therapy Oncology Group 0123 was unable to test the hypothesis that captopril mitigates radiation-induced pulmonary toxicity. It did show the safety of such an approach and the use of newer angiotensin-converting enzyme inhibitors started during radiotherapy may solve the accrual problems.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Captopril/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/radioterapia , Lesões por Radiação/tratamento farmacológico , Pneumonite por Radiação/tratamento farmacológico , Radioterapia Conformacional/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Qualidade de Vida , Lesões por Radiação/etiologia , Pneumonite por Radiação/etiologia
14.
Int J Mol Sci ; 18(12)2017 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-29186841

RESUMO

Radiation therapy for the treatment of thoracic malignancies has improved significantly by directing of the proton beam in higher doses on the targeted tumor while normal tissues around the tumor receive much lower doses. Nevertheless, exposure of normal tissues to protons is known to pose a substantial risk in long-term survivors, as confirmed by our work in space-relevant exposures of murine lungs to proton radiation. Thus, radioprotective strategies are being sought. We established that LGM2605 is a potent protector from radiation-induced lung toxicity and aimed in the current study to extend the initial findings of space-relevant, proton radiation-associated late lung damage in mice by looking at acute changes in human lung. We used an ex vivo model of organ culture where tissue slices of donor living human lung were kept in culture and exposed to proton radiation. We exposed donor human lung precision-cut lung sections (huPCLS), pretreated with LGM2605, to 4 Gy proton radiation and evaluated them 30 min and 24 h later for gene expression changes relevant to inflammation, oxidative stress, and cell cycle arrest, and determined radiation-induced senescence, inflammation, and oxidative tissue damage. We identified an LGM2605-mediated reduction of proton radiation-induced cellular senescence and associated cell cycle changes, an associated proinflammatory phenotype, and associated oxidative tissue damage. This is a first report on the effects of proton radiation and of the radioprotective properties of LGM2605 on human lung.


Assuntos
Anti-Inflamatórios/uso terapêutico , Butileno Glicóis/uso terapêutico , Glucosídeos/uso terapêutico , Prótons/efeitos adversos , Pneumonite por Radiação/prevenção & controle , Protetores contra Radiação/uso terapêutico , Anti-Inflamatórios/farmacologia , Butileno Glicóis/farmacologia , Pontos de Checagem do Ciclo Celular , Senescência Celular , Glucosídeos/farmacologia , Humanos , Pulmão/efeitos dos fármacos , Pulmão/efeitos da radiação , Estresse Oxidativo , Pneumonite por Radiação/tratamento farmacológico , Pneumonite por Radiação/etiologia , Protetores contra Radiação/farmacologia
15.
Radiat Res ; 188(5): 491-504, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28877030

RESUMO

The threat of exposure to ionizing radiation from a nuclear reactor accident or deliberate terrorist actions is a significant public health concern. The lung is particularly susceptible to radiation-induced injury from external sources or inhalation of radioactive particles from radioactive fallout. Radiation-induced lung disease can manifest with an acute radiation pneumonitis and/or delayed effects leading to pulmonary fibrosis. As prior warning of radiation exposure is unlikely, medical countermeasures (MCMs) to mitigate radiation-induced lung disease that can be given in mass-casualty situations many hours or days postirradiation are needed to prevent both early and late lung damage. In this study, KL4 surfactant (lucinactant) was evaluated as a radiation mitigator in a well-characterized mouse model of targeted thoracic radiation exposure, for its effect on both early (several weeks) and late (18 weeks) lung damage. Here, 120 mg/kg total phospholipid of KL4 surfactant was administered twice daily intranasally, (enabling intrapulmonary inhalation of drug) to C57BL/6 mice 24 h after a single 13.5 Gy dose of thoracic irradiation (LD50 dose). Both early and chronic phase (2 and 4 weeks and 18 weeks postirradiation, respectively) assessments were performed. Mice were evaluated for evidence of reduced arterial blood oxygenation and early and chronic lung and systemic inflammation, lung fibrosis and oxidative stress. Analysis was done by performing lung function/respiration dynamics and measuring cellular protein content of bronchoalveolar lavage fluid (BALF), and levels of cytokines, 8-iso-prostaglandin F2α, hydroxyproline in lung and plasma, along with evaluating lung histology. The results of this study showed that intranasal delivery of KL4 surfactant was able to preserve lung function as evidenced by adequate arterial oxygen saturation and reduced lung inflammation and oxidative stress; total white count and absolute neutrophil count was decreased in BALF, as were plasma pro-inflammatory cytokine levels and biomarker of oxidative stress. KL4 surfactant is a promising MCM for mitigation of lung tissue damage after targeted, thoracic irradiation and has the potential to be developed as a broad-spectrum, multi-use MCM against chemical, biological, radiological or nuclear threat agents with potential to cause lung injury.


Assuntos
Peptídeos/administração & dosagem , Peptídeos/farmacologia , Pneumonite por Radiação/tratamento farmacológico , Administração Intranasal , Animais , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Feminino , Fibrose , Peptídeos e Proteínas de Sinalização Intercelular , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Pulmão/efeitos da radiação , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/efeitos da radiação , Peptídeos/uso terapêutico , Pneumonite por Radiação/etiologia , Pneumonite por Radiação/metabolismo , Pneumonite por Radiação/patologia
16.
Am J Physiol Lung Cell Mol Physiol ; 313(5): L916-L929, 2017 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-28798253

RESUMO

Radiation-induced pulmonary fibrosis (RIPF) is one of the most common side effects of lung cancer radiotherapy. This study was conducted to identify the molecular mechanism responsible for RIPF. We revealed that the transcriptional level of cytochrome P450 2E1 (CYP2E1) was elevated by examining expression profile analysis of RIPF mouse models. We also confirmed that CYP2E1 regulated levels of endoplasmic reticulum (ER) stress and reactive oxygen species (ROS) in alveolar epithelial type II (AE2) cells and lung fibroblasts. Inhibition of CYP2E1 via its siRNA or inhibitor significantly attenuated epithelial-to-mesenchymal transition and apoptosis of AE2 cells, as well as myofibroblast formation induced by radiation. Finally, the effects of a CYP2E1 inhibitor on development of RIPF were evaluated by in vivo studies. Taken together, the results of the present study suggest that CYP2E1 is an important mediator of RIPF development that functions by increasing cellular ER stress and ROS levels.


Assuntos
Citocromo P-450 CYP2E1/farmacologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Fibrose Pulmonar/tratamento farmacológico , Pneumonite por Radiação/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Animais , Apoptose/efeitos dos fármacos , Retículo Endoplasmático/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Humanos , Pulmão/metabolismo , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos
17.
Int J Radiat Oncol Biol Phys ; 99(2): 353-361, 2017 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-28479002

RESUMO

PURPOSE: Ionizing radiation (IR)-induced pulmonary fibrosis (PF) is an irreversible and severe late effect of thoracic radiation therapy. The goal of this study was to determine whether clearance of senescent cells with ABT-263, a senolytic drug that can selectively kill senescent cells, can reverse PF. METHODS AND MATERIALS: C57BL/6J mice were exposed to a single dose of 17 Gy on the right side of the thorax. Sixteen weeks after IR, they were treated with 2 cycles of vehicle or ABT-263 (50 mg/kg per day for 5 days per cycle) by gavage. The effects of ABT-263 on IR-induced increases in senescent cells; elevation in the expression of selective inflammatory cytokines, matrix metalloproteinases, and tissue inhibitors of matrix metalloproteinases; and the severity of the tissue injury and fibrosis in the irradiated lungs were evaluated 3 weeks after the last treatment, in comparison with the changes observed in the irradiated lungs before treatment or after vehicle treatment. RESULTS: At 16 weeks after exposure of C57BL/6 mice to a single dose of 17 Gy, thoracic irradiation resulted in persistent PF associated with a significant increase in senescent cells. Treatment of the irradiated mice with ABT-263 after persistent PF had developed reduced senescent cells and reversed the disease. CONCLUSIONS: To our knowledge, this is the first study to demonstrate that PF can be reversed by a senolytic drug such as ABT-263 after it becomes a progressive disease. Therefore, ABT-263 has the potential to be developed as a new treatment for PF.


Assuntos
Células Epiteliais Alveolares/efeitos dos fármacos , Compostos de Anilina/uso terapêutico , Antineoplásicos/uso terapêutico , Senescência Celular , Pneumonite por Radiação/tratamento farmacológico , Sulfonamidas/uso terapêutico , Proteína X Associada a bcl-2/antagonistas & inibidores , Células Epiteliais Alveolares/patologia , Animais , Antineoplásicos/administração & dosagem , Inibidor p16 de Quinase Dependente de Ciclina/análise , Inibidor p16 de Quinase Dependente de Ciclina/genética , Citocinas/análise , Hidroxiprolina/análise , Mediadores da Inflamação/metabolismo , Pulmão/química , Pulmão/enzimologia , Pulmão/efeitos da radiação , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Reação em Cadeia da Polimerase , Proteínas Proto-Oncogênicas c-bcl-2/análise , Proteínas Proto-Oncogênicas c-bcl-2/genética , RNA Mensageiro/análise , Pneumonite por Radiação/genética , Pneumonite por Radiação/patologia , Radiação Ionizante , Proteína X Associada a bcl-2/metabolismo , beta-Galactosidase/análise
18.
Sci Rep ; 7: 45001, 2017 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-28322297

RESUMO

Radiation therapy is widely used for thoracic cancers. However, it occasionally causes radiation-induced lung injuries, including pneumonitis and fibrosis. Chung-Sang-Bo-Ha-Tang (CSBHT) has been traditionally used to treat chronic pulmonary disease in Korea. PM014, a modified herbal formula derived from CSBHT, contains medicinal herbs of seven species. In our previous studies, PM014 exhibited anti-inflammatory effects in a chronic obstructive pulmonary disease model. In this study, we have evaluated the effects of PM014 on radiation-induced lung inflammation. Mice in the treatment group were orally administered PM014 six times for 2 weeks. Effects of PM014 on radiation pneumonitis were evaluated based on histological findings and differential cell count in bronchoalveolar lavage fluid. PM014 treatment significantly inhibited immune cell recruitment and collagen deposition in lung tissue. Normal lung volume, evaluated by radiological analysis, in PM014-treated mice was higher compared to that in irradiated control mice. PM014-treated mice exhibited significant changes in inspiratory capacity, compliance and tissue damping and elastance. Additionally, PM014 treatment resulted in the downregulation of inflammatory cytokines, chemokines, and fibrosis-related genes and a reduction in the transforming growth factor-ß1-positive cell population in lung tissue. Thus, PM014 is a potent therapeutic agent for radiation-induced lung fibrosis and inflammation.


Assuntos
Extratos Vegetais/farmacologia , Pneumonite por Radiação/patologia , Animais , Biópsia , Modelos Animais de Doenças , Feminino , Imuno-Histoquímica , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/efeitos da radiação , Camundongos , Pneumonite por Radiação/diagnóstico por imagem , Pneumonite por Radiação/tratamento farmacológico , Pneumonite por Radiação/genética , Microtomografia por Raio-X
19.
Int J Radiat Oncol Biol Phys ; 96(4): 857-866, 2016 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-27663762

RESUMO

PURPOSE: Radiation-induced pulmonary fibrosis (RIPF) is a late toxicity of therapeutic radiation. Signaling of the mammalian target of rapamycin drives several processes implicated in RIPF, including inflammatory cytokine production, fibroblast proliferation, and epithelial senescence. We sought to determine if mammalian target of rapamycin inhibition with rapamycin would mitigate RIPF. METHODS AND MATERIALS: C57BL/6NCr mice received a diet formulated with rapamycin (14 mg/kg food) or a control diet 2 days before and continuing for 16 weeks after exposure to 5 daily fractions of 6 Gy of thoracic irradiation. Fibrosis was assessed with Masson trichrome staining and hydroxyproline assay. Cytokine expression was evaluated by quantitative real-time polymerase chain reaction. Senescence was assessed by staining for ß-galactosidase activity. RESULTS: Administration of rapamycin extended the median survival of irradiated mice compared with the control diet from 116 days to 156 days (P=.006, log-rank test). Treatment with rapamycin reduced hydroxyproline content compared with the control diet (irradiation plus vehicle, 45.9 ± 11.8 µg per lung; irradiation plus rapamycin, 21.4 ± 6.0 µg per lung; P=.001) and reduced visible fibrotic foci. Rapamycin treatment attenuated interleukin 1ß and transforming growth factor ß induction in irradiated lungs compared with the control diet. Type II pneumocyte senescence after irradiation was reduced with rapamycin treatment at 16 weeks (3-fold reduction at 16 weeks, P<.001). CONCLUSIONS: Rapamycin protected against RIPF in a murine model. Rapamycin treatment reduced inflammatory cytokine expression, extracellular matrix production, and senescence in type II pneumocytes.


Assuntos
Pneumonite por Radiação/tratamento farmacológico , Tolerância a Radiação/efeitos dos fármacos , Protetores contra Radiação/uso terapêutico , Sirolimo/uso terapêutico , Serina-Treonina Quinases TOR/antagonistas & inibidores , Células Epiteliais Alveolares/efeitos dos fármacos , Animais , Senescência Celular/efeitos dos fármacos , Matriz Extracelular/metabolismo , Feminino , Hidroxiprolina/metabolismo , Interleucina-1beta/metabolismo , Pulmão/metabolismo , Pulmão/efeitos da radiação , Macrófagos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Pneumonite por Radiação/mortalidade , Serina-Treonina Quinases TOR/metabolismo , Fator de Crescimento Transformador beta/metabolismo , beta-Galactosidase/metabolismo
20.
Toxins (Basel) ; 8(5)2016 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-27144583

RESUMO

Bee venom has long been used to treat various inflammatory diseases, such as rheumatoid arthritis and multiple sclerosis. Previously, we reported that bee venom phospholipase A2 (bvPLA2) has an anti-inflammatory effect through the induction of regulatory T cells. Radiotherapy is a common anti-cancer method, but often causes adverse effects, such as inflammation. This study was conducted to evaluate the protective effects of bvPLA2 in radiation-induced acute lung inflammation. Mice were focally irradiated with 75 Gy of X-rays in the lung and administered bvPLA2 six times after radiation. To evaluate the level of inflammation, the number of immune cells, mRNA level of inflammatory cytokine, and histological changes in the lung were measured. BvPLA2 treatment reduced the accumulation of immune cells, such as macrophages, neutrophils, lymphocytes, and eosinophils. In addition, bvPLA2 treatment decreased inflammasome-, chemokine-, cytokine- and fibrosis-related genes' mRNA expression. The histological results also demonstrated the attenuating effect of bvPLA2 on radiation-induced lung inflammation. Furthermore, regulatory T cell depletion abolished the therapeutic effects of bvPLA2 in radiation-induced pneumonitis, implicating the anti-inflammatory effects of bvPLA2 are dependent upon regulatory T cells. These results support the therapeutic potential of bvPLA2 in radiation pneumonitis and fibrosis treatments.


Assuntos
Anti-Inflamatórios/uso terapêutico , Venenos de Abelha/enzimologia , Fosfolipases A2/uso terapêutico , Pneumonite por Radiação/tratamento farmacológico , Linfócitos T Reguladores/imunologia , Animais , Anti-Inflamatórios/farmacologia , Feminino , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/patologia , Pulmão/efeitos da radiação , Camundongos Endogâmicos C57BL , Fosfolipases A2/farmacologia , Pneumonite por Radiação/imunologia , Pneumonite por Radiação/patologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA