RESUMO
BACKGROUND: Poly-(ADP-Ribose)-Polymerase inhibitors (PARPi) were reported as radiosensitizers in non-small cell lung cancer (NSCLC) with wide-type epidermal growth factor receptor (EGFR), but the effects of radiation combined with PARPi were not investigated in EGFR-mutated NSCLC. Moreover, the underlying mechanisms were not well examined. This study aimed to study the efficacy of radiation combined with niraparib in EGFR-mutated NSCLC and explore their influence on the immune system. METHODS: Clone formation and apoptosis assay were conducted to explore the effects of niraparib and radiation. Immunofluorescence was conducted to detect the double-strand DNA breaks. Real-time PCR and immunoblotting were employed to evaluate the activation of STING/TBK1/TRF3 pathway and the expression levels of interferon ß, CCL5 and CXCL10. Immunocompetent mice model bearing with subcutaneous Lewis lung cancer was established to confirm the results in vivo. RESULTS: Niraparib and radiation were synergistic to inhibit tumor both in vitro and in vivo. Radiation plus niraparib could activate anti-tumor immunity, which appeared as increased CD8+ T lymphocytes and activated STING/TBK1/IRF3 pathway. CONCLUSION: PARPi not only as a radiosensitizer inhibited EGFR-mutated NSCLC tumor growth, but also cooperated with radiation to promote anti-tumor immune responses.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/terapia , Quimiorradioterapia/métodos , Genes erbB-1 , Indazóis/farmacologia , Neoplasias Pulmonares/terapia , Mutação , Piperidinas/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Radiossensibilizantes/farmacologia , Animais , Linfócitos T CD8-Positivos , Carcinoma Pulmonar de Lewis/imunologia , Carcinoma Pulmonar de Lewis/terapia , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Linhagem Celular Tumoral , Quimiocina CCL5/metabolismo , Quimiocina CXCL10/metabolismo , Quebras de DNA de Cadeia Dupla , Feminino , Imunofluorescência , Humanos , Sistema Imunitário/efeitos dos fármacos , Sistema Imunitário/efeitos da radiação , Imunocompetência , Fator Regulador 3 de Interferon/metabolismo , Interferon beta/metabolismo , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/mortalidade , Linfócitos do Interstício Tumoral , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Nucleares/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Tolerância a Radiação/efeitos dos fármacos , Reação em Cadeia da Polimerase em Tempo Real , Proteínas Semelhantes à Proteína de Ligação a TATA-Box/metabolismo , Ensaio Tumoral de Célula-TroncoRESUMO
Phototherapy in neonates for treatment of pathological jaundice is an effective therapeutic tool that is widely used in neonatal units. Over the past years, a greater concern has emerged about the effects on the immune and inflammatory system and its potential genotoxic and side effects, especially the late ones, possibly associated with childhood diseases, showing that this treatment is not as harmless as previously believed. Numerous studies assessing these possible adverse effects of phototherapy on neonates have been published over the past years. Through this review, we seek to analyze what we know about the side effects of phototherapy in the neonatal period. The main causes of jaundice, phototherapy techniques, acute and late side effects, and effects on the immune and inflammatory system were reviewed. It was concluded that phototherapy is not a treatment free of side effects and further studies need to be conducted to elucidate its harmful effects on neonates.
Assuntos
Icterícia Neonatal/terapia , Fototerapia/efeitos adversos , Permeabilidade do Canal Arterial/etiologia , Humanos , Sistema Imunitário/efeitos da radiação , Recém-Nascido , Recém-Nascido Prematuro , Doenças do Prematuro/etiologia , Doenças do Prematuro/terapia , Fototerapia/instrumentação , Fototerapia/métodos , Pele/efeitos da radiaçãoRESUMO
Technological developments have allowed improvements in radiotherapy delivery, with higher precision and better sparing of normal tissue. For many years, it has been well known that ionizing radiation has not only local action but also systemic effects by triggering many molecular signaling pathways. There is still a lack of knowledge of this issue. This review focuses on the current literature about the effects of ionizing radiation on the immune system, either suppressing or stimulating the host reactions against the tumor, and the factors that interact with these responses, such as the radiation dose and dose / fraction effects in the tumor microenvironment and vasculature. In addition, some implications of these effects in cancer treatment, mainly in combined strategies, are addressed from the perspective of their interactions with the more advanced technology currently available, such as heavy ion therapy and nanotechnology.
Assuntos
Sistema Imunitário/efeitos da radiação , Neoplasias/imunologia , Neoplasias/radioterapia , Radiação Ionizante , Radioterapia/efeitos adversos , Apoptose/imunologia , Apoptose/efeitos da radiação , Morte Celular/efeitos da radiação , Relação Dose-Resposta à Radiação , Humanos , Imunoterapia/métodos , Imunoterapia/tendências , Necrose/etiologia , Radioterapia/tendênciasRESUMO
Technological developments have allowed improvements in radiotherapy delivery, with higher precision and better sparing of normal tissue. For many years, it has been well known that ionizing radiation has not only local action but also systemic effects by triggering many molecular signaling pathways. There is still a lack of knowledge of this issue. This review focuses on the current literature about the effects of ionizing radiation on the immune system, either suppressing or stimulating the host reactions against the tumor, and the factors that interact with these responses, such as the radiation dose and dose / fraction effects in the tumor microenvironment and vasculature. In addition, some implications of these effects in cancer treatment, mainly in combined strategies, are addressed from the perspective of their interactions with the more advanced technology currently available, such as heavy ion therapy and nanotechnology.
Assuntos
Humanos , Radiação Ionizante , Radioterapia/efeitos adversos , Sistema Imunitário/efeitos da radiação , Neoplasias/imunologia , Neoplasias/radioterapia , Radioterapia/tendências , Morte Celular/efeitos da radiação , Apoptose/efeitos da radiação , Apoptose/imunologia , Relação Dose-Resposta à Radiação , Imunoterapia/métodos , Imunoterapia/tendências , Necrose/etiologiaRESUMO
Sunlight, composed of different types of radiation, including ultraviolet wavelengths, is an essential source of light and warmth for life on earth but has strong negative effects on human health, such as promoting the malignant transformation of skin cells and suppressing the ability of the human immune system to efficiently detect and attack malignant cells. UV-induced immunosuppression has been extensively studied since it was first described by Dr. Kripke and Dr. Fisher in the late 1970s. However, skin exposure to sunlight has not only this and other unfavorable effects, for example, mutagenesis and carcinogenesis, but also a positive one: the induction of Vitamin D synthesis, which performs several roles within the immune system in addition to favoring bone homeostasis. The impact of low levels of UV exposure on the immune system has not been fully reported yet, but it bears interesting differences with the suppressive effect of high levels of UV radiation, as shown by some recent studies. The aim of this article is to put some ideas in perspective and pose some questions within the field of photoimmunology based on established and new information, which may lead to new experimental approaches and, eventually, to a better understanding of the effects of sunlight on the human immune system.
Assuntos
Sistema Imunitário/efeitos da radiação , Terapia de Imunossupressão , Pele/efeitos da radiação , Luz Solar , Animais , Humanos , Tolerância Imunológica , Camundongos , Neoplasias Induzidas por Radiação/imunologia , Neoplasias Cutâneas/imunologia , Raios Ultravioleta , Vitamina D/imunologia , Vitamina D/metabolismoRESUMO
The role of complement in the control of the Schistosoma mansoni infection in mice was investigated in vivo. The number of schistosomula recovered from the lung 5 days post-infection was used as a parasitological criterion of immunity. A significant difference in worm burden was observed between normal and immune mice. In contrast, when cobra venom factor (CVF) was injected into normal or immune mice 3 h before challenge, a significant increase in worm burden was noticed compared to untreated mice. We also investigated the protective mechanisms in mice that had been exposed to 650 rads of 60Co gamma radiation before challenge infection. Our results show that gamma-irradiated immune mice, depleted of more than 90% of their circulating or tissue leukocytes, are still able to destroy most of the parasites of a challenge infection with cercariae, suggesting that the radiosensitive leukocytes are not essential in the effector mechanisms of this protective immunity to S. mansoni. These results provide evidence of a role for the complement system, in association with radioresistant effector cells, in protective immunity occurring in the first hours after infection with S. mansoni.