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1.
Br J Radiol ; 92(1103): 20181026, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31529985

RESUMO

OBJECTIVE: To evaluate safety and efficacy of image guided-hypofractionated radiation therapy (IG-HRT) in patients with thoracic nodes oligometastases. METHODS: The present study is a multicenter analysis. Oligometastatic patients, affected by a maximum of five active lesions in three or less different organs, treated with IG-HRT to thoracic nodes metastases between 2012 and 2017 were included in the analysis. Primary end point was local control (LC), secondary end points were overall survival (OS), progression-free survival, acute and late toxicity. Univariate and multivariate analysis were performed to identify possible prognostic factors for the survival end points. RESULTS: 76 patients were included in the analysis. Different RT dose and fractionation schedules were prescribed according to site, number, size of the lymph node(s) and to respect dose constraints for relevant organs at risk. Median biologically effective dose delivered was 75 Gy (interquartile range: 59-86 Gy). Treatment was optimal; one G1 acute toxicity and seven G1 late toxicities of any grade were recorded. Median follow-up time was 23.16 months. 16 patients (21.05%) had a local progression, while 52 patients progressed in distant sites (68.42 %).Median local relapse free survival was not reached, LC at 6, 12 and 24 months was 96.05% [confidence interval (CI) 88.26-98.71%], 86.68% (CI 75.86-92.87) and 68.21% (CI 51.89-80.00%), respectively. Median OS was 28.3 months (interquartile range 16.1-47.2). Median progression-freesurvival was 9.2 months (interquartile range 4.1-17.93).At multivariate analysis, RT dose, colorectal histology, systemic therapies were correlated with LC. Performance status and the presence of metastatic sites other than the thoracic nodes were correlated with OS. Local response was a predictor of OS. CONCLUSION: IG-HRT for thoracic nodes was safe and feasible. Higher RT doses were correlated to better LC and should be taken in consideration at least in patients with isolated nodal metastases and colorectal histology. ADVANCES IN KNOWLEDGE: Radiotherapy is safe and effective treatment for thoracic nodes metastases, higher radiotherapy doses are correlated to better LC. Oligometastatic patients can receive IG-HRT also for thoracic nodes metastases.


Assuntos
Neoplasias do Mediastino/radioterapia , Neoplasias Torácicas/radioterapia , Idoso , Neoplasias da Mama/mortalidade , Progressão da Doença , Intervalo Livre de Doença , Relação Dose-Resposta à Radiação , Estudos de Viabilidade , Feminino , Humanos , Neoplasias Intestinais/mortalidade , Neoplasias Renais/mortalidade , Neoplasias Pulmonares/mortalidade , Metástase Linfática , Masculino , Neoplasias do Mediastino/diagnóstico por imagem , Neoplasias do Mediastino/mortalidade , Pessoa de Meia-Idade , Hipofracionamento da Dose de Radiação , Radioterapia Guiada por Imagem/métodos , Estudos Retrospectivos , Neoplasias Torácicas/diagnóstico por imagem , Neoplasias Torácicas/mortalidade , Tomografia Computadorizada por Raios X/métodos
2.
Medicine (Baltimore) ; 98(37): e17165, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31517868

RESUMO

A thyroid cancer ultrasonography screening for all residents 18 years old or younger living in the Fukushima prefecture started in October 2011 to investigate the possible effect of the radiological contamination after the Fukushima Daiichi Nuclear Power Plant accidents as of March 12 to 15, 2011. Thyroid cancer in 184 cases was reported by February 2017. The question arises to which extent those cancer cases are a biological consequence of the radiation exposure or an artefactual result of the intense screening of a large population.Experiences with the Chernobyl accident suggest that the external dose may be considered a valid surrogate for the internal dose of the thyroid gland. We, therefore, calculated the average external effective dose-rate (µSv/h) for the 59 municipalities of the Fukushima prefecture based on published data of air and soil radiation. We further determined the municipality-specific absolute numbers of thyroid cancers found by each of the two screening rounds in the corresponding municipality-specific exposed person-time observed. A possible association between the radiation exposure and the thyroid cancer detection rate was analyzed with Poisson regression assuming Poisson distributed thyroid cancer cases in the exposed person-time observed per municipality.The target populations consisted of 367,674 and 381,286 children and adolescents for the 1st and the 2nd screening rounds, respectively. In the 1st screening, 300,476 persons participated and 270,489 in the 2nd round. From October 2011 to March 2016, a total of 184 cancer cases were found in 1,079,786 person-years counted from the onset of the exposure to the corresponding examination periods in the municipalities. A significant association between the external effective dose-rate and the thyroid cancer detection rate exists: detection rate ratio (DRR) per µSv/h 1.065 (1.013, 1.119). Restricting the analysis to the 53 municipalities that received less than 2 µSv/h, and which represent 176 of the total 184 cancer cases, the association appears to be considerably stronger: DRR per µSv/h 1.555 (1.096, 2.206).The average radiation dose-rates in the 59 municipalities of the Fukushima prefecture in June 2011 and the corresponding thyroid cancer detection rates in the period October 2011 to March 2016 show statistically significant relationships.


Assuntos
Acidente Nuclear de Fukushima , Neoplasias Induzidas por Radiação/epidemiologia , Doses de Radiação , Neoplasias da Glândula Tireoide/epidemiologia , Adolescente , Criança , Pré-Escolar , Relação Dose-Resposta à Radiação , Detecção Precoce de Câncer , Geografia Médica , Humanos , Incidência , Lactente , Recém-Nascido , Japão/epidemiologia , Modelos Estatísticos , Neoplasias Induzidas por Radiação/diagnóstico por imagem , Prevalência , Exposição à Radiação/efeitos adversos , Glândula Tireoide/diagnóstico por imagem , Glândula Tireoide/efeitos da radiação , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Ultrassonografia
3.
J Environ Radioact ; 208-209: 106035, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31499317

RESUMO

The paper continues study of exposures of luminous marine bacteria to low-dose radiation of tritium; tritiated water (HTO) was applied as a source of the irradiation. Hypothesis on involvement of Reactive Oxygen Species (ROS) to signaling mechanism of bacterial cells under exposure to low-intensity tritium radiation was verified. Bacterial bioluminescence intensity was considered as a tested physiological parameter; it was compared to the ROS production in the bacterial environment of different activity concentrations: 0.03, 4.0, and 500 MBq/L. Exposure of the bacteria to chronic low-dose tritium irradiation (<0.08 Gy) increased bioluminescence intensity and ROS production considerably (up to 300%). Spearman rank correlation coefficients were calculated and confirmed relations between the bioluminescence intensity and ROS production. Additional peculiarities of HTO effect were: independence of the bioluminescence intensity and ROS content on HTO activity concentration; low ROS content in bacteria-free aquatic environment. Effects of HTO on bacterial bioluminescence were attributed to: (1) trigger function of tritium decay products in the bacterial metabolic oxygen-dependent processes, with bioluminescence involved; (2) signaling role of ROS as intercellular messengers in "bystander effect"; (3) fixed amount of bacterial cells (3•107 cells/mL) provided the upper limits of the bioluminescence intensity and ROS content. As an outlook, in spite of low energy of tritium decay, its influence on aquatic biota via ROS production by microorganisms should be taken into consideration.


Assuntos
Bactérias/efeitos da radiação , Espécies Reativas de Oxigênio/metabolismo , Trítio/toxicidade , Poluentes Radioativos da Água/toxicidade , Bactérias/metabolismo , Relação Dose-Resposta à Radiação , Microbiologia da Água
4.
Br J Radiol ; 92(1103): 20190174, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31364397

RESUMO

OBJECTIVE: The effect of functional lung avoidance planning on radiation dose-dependent changes in regional lung perfusion is unknown. We characterized dose-perfusion response on longitudinal perfusion single photon emission computed tomography (SPECT)/CT in two cohorts of lung cancer patients treated with and without functional lung avoidance techniques. METHODS: The study included 28 primary lung cancer patients: 20 from interventional (NCT02773238) (FLARE-RT) and eight from observational (NCT01982123) (LUNG-RT) clinical trials. FLARE-RT treatment plans included perfused lung dose constraints while LUNG-RT plans adhered to clinical standards. Pre- and 3 month post-treatment macro-aggregated albumin (MAA) SPECT/CT scans were rigidly co-registered to planning four-dimensional CT scans. Tumour-subtracted lung dose was converted to EQD2 and sorted into 5 Gy bins. Mean dose and percent change between pre/post-RT MAA-SPECT uptake (%ΔPERF), normalized to total tumour-subtracted lung uptake, were calculated in each binned dose region. Perfusion frequency histograms of pre/post-RT MAA-SPECT were analyzed. Dose-response data were parameterized by sigmoid logistic functions to estimate maximum perfusion increase (%ΔPERFmaxincrease), maximum perfusion decrease (%ΔPERFmaxdecrease), dose midpoint (Dmid), and dose-response slope (k). RESULTS: Differences in MAA perfusion frequency distribution shape between time points were observed in 11/20 (55%) FLARE-RT and 2/8 (25%) LUNG-RT patients (p < 0.05). FLARE-RT dose response was characterized by >10% perfusion increase in the 0-5 Gy dose bin for 8/20 patients (%ΔPERFmaxincrease = 10-40%), which was not observed in any LUNG-RT patients (p = 0.03). The dose midpoint Dmid at which relative perfusion declined by 50% trended higher in FLARE-RT compared to LUNG-RT cohorts (35 GyEQD2 vs 21 GyEQD2, p = 0.09), while the dose-response slope k was similar between FLARE-RT and LUNG-RT cohorts (3.1-3.2, p = 0.86). CONCLUSION: Functional lung avoidance planning may promote increased post-treatment perfusion in low dose regions for select patients, though inter-patient variability remains high in unbalanced cohorts. These preliminary findings form testable hypotheses that warrant subsequent validation in larger cohorts within randomized or case-matched control investigations. ADVANCES IN KNOWLEDGE: This novel preliminary study reports differences in dose-response relationships between patients receiving functional lung avoidance radiation therapy (FLARE-RT) and those receiving conventionally planned radiation therapy (LUNG-RT). Following further validation and testing of these effects in larger patient populations, individualized estimation of regional lung perfusion dose-response may help refine future risk-adaptive strategies to minimize lung function deficits and toxicity incidence.


Assuntos
Neoplasias Pulmonares/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Relação Dose-Resposta à Radiação , Feminino , Humanos , Neoplasias Pulmonares/radioterapia , Masculino , Pessoa de Meia-Idade , Imagem de Perfusão/métodos , Estudos Prospectivos , Planejamento da Radioterapia Assistida por Computador , Tomografia Computadorizada de Emissão de Fóton Único/métodos
5.
Inorg Chem ; 58(16): 11076-11084, 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31393117

RESUMO

Platinum drugs including cisplatin are widely used in clinics to treat various types of cancer. However, the lack of cancer-cell selectivity is one of the major problems that lead to side effects in normal tissues. Luteinizing hormone-releasing hormone (LHRH) receptors are overexpressed in many types of cancer cells but rarely presented in normal cells, making LHRH receptor a good candidate for cancer targeting. In this study, we report the synthesis and cytotoxic study of a novel platinum(IV) anticancer prodrug functionalized with LHRH peptide. This LHRH-platinum(IV) conjugate is highly soluble in water and quite stable in a PBS buffer. Cytotoxic study reveals that the prodrug selectively targets LHRH receptor-positive cancer cell lines with the cytotoxicities 5-8 times higher than those in LHRH receptor-negative cell lines. In addition, the introduction of LHRH peptide enhances the cellular accumulation in a manner of receptor-mediated endocytosis. Moreover, the LHRH-platinum(IV) prodrug is proved to kill cancer cells by binding to the genomic DNA, inducing apoptosis, and arresting the cell cycle at the G2/M phase. In summary, we report a novel LHRH-platinum(IV) anticancer prodrug having largely improved selectivity toward LHRH receptor-positive cancer cells, relative to cisplatin.


Assuntos
Antineoplásicos/farmacologia , Platina/farmacologia , Pró-Fármacos/farmacologia , Receptores LHRH/antagonistas & inibidores , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta à Radiação , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Platina/química , Pró-Fármacos/síntese química , Pró-Fármacos/química , Receptores LHRH/metabolismo , Relação Estrutura-Atividade
6.
Cancer Radiother ; 23(6-7): 674-676, 2019 Oct.
Artigo em Francês | MEDLINE | ID: mdl-31420128

RESUMO

In the last decade, major advances in high precision treatment delivery and multimodal imaging allowed radiotherapy to be more efficient and better tolerated. However, the technology of the accelerators used to generate X-ray beams is outdated and does not allow to explore the tolerance to novel approaches in terms of dose-rate. We have been the first to propose a completely novel modality of irradiation, named Flash radiotherapy, in which the dose per pulse and the instant dose-rate during the pulses is 103 to 104 higher than those used in conventional facilities. Flash has been shown to spare mouse lung from radio-induced fibrosis, whilst leaving unchanged the antitumor potential. Other teams have shown that the advantage of Flash in terms of reduced complications extends to normal brain and intestinal crypts. The goal of this paper is to review the progress of studies dealing with very high dose-rate "Flash" irradiation, describe the theoretical models proposed to explain the underlying mechanisms, and discuss the prospects for clinical applications of this emerging technique.


Assuntos
Dosagem Radioterapêutica , Radioterapia/métodos , Animais , Relação Dose-Resposta à Radiação , Camundongos , Órgãos em Risco/efeitos da radiação , Consumo de Oxigênio , Aceleradores de Partículas , Radioterapia/efeitos adversos , Espécies Reativas de Oxigênio/metabolismo
7.
Int J Nanomedicine ; 14: 5369-5379, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31409993

RESUMO

Purpose: Photothermal therapy (PTT) exploits the light-absorbing properties of nanomaterials such as silica-gold nanoshells (NS) to inflict tumor death through local hyperthermia. However, in in vivo studies of PTT, the heat distribution is often found to be heterogeneous throughout the tumor volume, which leaves parts of the tumor untreated and impairs the overall treatment outcome. As this challenges PTT as a one-dose therapy, this study here investigates if giving the treatment repeatedly, ie, fractionated PTT, increases the efficacy in mice bearing subcutaneous tumors. Methods: The NS heating properties were first optimized in vitro and in vivo. Two fractionated PTT protocols, consisting of two and four laser treatments, respectively, were developed and applied in a murine subcutaneous colorectal tumor model. The efficacy of the two fractionated protocols was evaluated both by longitudinal monitoring of tumor growth and, at an early time point, by positron emission tomography (PET) imaging of 18F-labeled glucose analog 18F-FDG. Results: Overall, there were no significant differences in tumor growth and survival between groups of mice receiving single-dose PTT and fractionated PTT in our study. Nonetheless, some animals did experience inhibited tumor growth or even complete tumor disappearance due to fractionated PTT, and these animals also showed a significant decrease in tumor uptake of 18F-FDG after therapy. Conclusion: This study only found an effect of giving PTT to tumors in fractions compared to a single-dose approach in a few animals. However, many factors can affect the outcome of PTT, and reliable tools for optimization of treatment protocol are needed. Despite the modest treatment effect, our results indicate that 18F-FDG PET/CT imaging can be useful to guide the number of treatment sessions necessary.


Assuntos
Hipertermia Induzida , Fototerapia , Animais , Linhagem Celular Tumoral , Modelos Animais de Doenças , Relação Dose-Resposta à Radiação , Feminino , Glicerol/química , Ouro/química , Temperatura Alta , Raios Infravermelhos , Camundongos Endogâmicos BALB C , Nanoconchas/química , Nanoconchas/ultraestrutura , Neoplasias/patologia , Neoplasias/terapia , Tomografia por Emissão de Pósitrons , Dióxido de Silício/química , Resultado do Tratamento , Carga Tumoral
8.
Ecotoxicol Environ Saf ; 182: 109412, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31295658

RESUMO

Perennial plants and their associated microorganisms grow in the areas that may be contaminated with long-lived gamma-emitting radionuclides. This will induce gamma stress response in plants and their accompanying microorganisms. The present work investigated the growth and physiological responses of Epichloe endophyte infected tall fescue to gamma radiation, as well as whether the endophyte could persist and infect the host plant once exposed to gamma radiation. Seeds of Iranian native genotype of 75B+ of tall fescue were exposed to different doses, including 5.0, 10.0, 15.0, 20.0, 30.0 and 40.0 krad of gamma ray from a 60Co source. Irradiated and unirradiated seeds were sown in pots and grown under controlled conditions in the greenhouse. The growth and physiological parameters associated with plant tolerance to oxidative stress of host plants, as well as endophytic infection frequency (% of plants infected) and intensity (mean number of endophytic hyphae per the field of view), were examined in 3 months-old seedlings. The results indicated that all gamma radiation doses (except 5.0 kr) significantly reduced the height and survival percentage of the host plant. Days to the emergence of seedling increased gradually as gamma doses rose. A dose-rate dependent induction was seen for photosynthetic pigments and proline content. Malondialdehyde (MDA) content grew with elevation of irradiation doses. Depending on the dose and time, the activities of antioxidant enzymes in the host plant responded differently to gamma radiation. Gamma radiation altered the enzyme activities with sever decline in SOD and CAT activities. However, it had barely any effect on in APX and POD activities. The results also revealed that the persistence and intensity of endophyte were affected after gamma-ray irradiation. The initial percentage of tall fescue seeds infected with the endophyte was 91% in un-irradiated seeds. Presence of the viable endophyte started to decline significantly (23%) at 5.0 kr of gamma radiation. A dramatic reduction in the presence and intensity of endophyte occurred at 10.0 to 40.0 kr intensities. Gamma radiation × trait (GT)-biplot analysis indicated positive correlations between the endophyte symbiosis and antioxidant enzyme activities. Also, negative correlations were observed between the endophyte and MDA content in the host plant. Our results suggest that radiation stress (doses over 5.0 kr) caused reduction in the growth and antioxidant enzyme activities of the host plant that accompanied by a dramatic reduction in the persistence and intensity of endophyte fungi. Our findings have provided the basic information for future studies on the effect of gamma irradiation on the interaction between endophytic fungi and its host plant.


Assuntos
Endófitos/efeitos da radiação , Epichloe/efeitos da radiação , Festuca/efeitos da radiação , Raios gama , Relação Dose-Resposta à Radiação , Endófitos/crescimento & desenvolvimento , Epichloe/crescimento & desenvolvimento , Festuca/microbiologia , Festuca/fisiologia , Irã (Geográfico) , Doses de Radiação , Plântula/microbiologia , Plântula/fisiologia , Plântula/efeitos da radiação , Sementes/microbiologia , Sementes/fisiologia , Sementes/efeitos da radiação , Simbiose
9.
Br J Radiol ; 92(1102): 20190317, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31295011

RESUMO

OBJECTIVE: In this study, we used the concept of organ-equivalent dose (OED) to evaluate the excess absolute risk (EAR) for secondary cancer in various organs after radiation treatment for breast cancer. METHODS: Using CT data set of 12 patients, we generated three different whole-breast radiation treatment plans using 50 Gy in 2 Gy fractions: three-dimensional conformal radiotherapy with a field-in-field (FinF) technique, intensity modulated radiation therapy (IMRT), and volumetric modulated arc therapy (VMAT). The OEDs were calculated from differential dose-volume histograms on the basis of the "linear-exponential," "plateau," and "full mechanistic" dose-response models. Secondary cancer risks of the contralateral breast (CB), contralateral lung (CL), and ipsilateral lung (IL) were estimated and compared. RESULTS: The lowest EARs for the CB, CL, and IL were achieved with FinF, which reduced the EARs by 77%, 88%, and 56% relative to those with IMRT, and by 77%, 84%, and 58% relative to those with VMAT, respectively. The secondary cancer risk for FinF was significantly lower than those of IMRT and VMAT. OED-based secondary cancer risks for CB and IL were similar when IMRT and VMAT were used, but the risk for CL was statistically lower when VMAT was used. CONCLUSION: The overall estimation of EAR indicated that the radiation-induced cancer risk of breast radiation therapy was lower with FinF than with IMRT and VMAT. Therefore, when secondary cancer risk is a major concern, FinF is considered to be the preferred treatment option in irradiation of whole-breast. ADVANCES IN KNOWLEDGE: Secondary malignancy estimation after breast radiotherapy is becoming an important subject for comparative treatment planning.When secondary cancer risk a major concern, FinF technique is considered the preferred treatment option in whole breast patients.


Assuntos
Neoplasias da Mama/radioterapia , Neoplasias Induzidas por Radiação/etiologia , Segunda Neoplasia Primária/etiologia , Radioterapia Conformacional/efeitos adversos , Radioterapia de Intensidade Modulada/efeitos adversos , Mama/diagnóstico por imagem , Mama/efeitos da radiação , Fracionamento da Dose de Radiação , Relação Dose-Resposta à Radiação , Feminino , Coração/diagnóstico por imagem , Coração/efeitos da radiação , Humanos , Pulmão/diagnóstico por imagem , Pulmão/efeitos da radiação , Neoplasias Pulmonares/etiologia , Números Necessários para Tratar , Órgãos em Risco/diagnóstico por imagem , Órgãos em Risco/efeitos da radiação , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia Conformacional/métodos , Radioterapia de Intensidade Modulada/métodos , Medição de Risco/métodos , Tomografia Computadorizada por Raios X , Neoplasias Unilaterais da Mama/etiologia
10.
Chem Biol Interact ; 310: 108736, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31278902

RESUMO

The linear non-threshold (LNT) dose response model for cancer risk assessment has been a controversial concept since its initial proposal during the 1930s. It was long advocated by the radiation genetics community in the 1950s, some two decades prior to being generally adopted within the chemical toxicology community. This paper explores possible reasons for such major differences in the acceptance of LNT for cancer risk assessment by these two key groups of scientists.


Assuntos
Modelos Lineares , Neoplasias/etiologia , Radiação Ionizante , Medição de Risco/normas , United States Environmental Protection Agency/normas , Relação Dose-Resposta à Radiação , Humanos , Radiogenética/normas , Toxicologia/normas , Estados Unidos
11.
Radiat Res ; 192(2): 145-158, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31166846

RESUMO

While cutaneous radiation injury (CRI) is generally referenced as a consequence of a nuclear attack, it can also be caused by less dangerous events such as the use of dirty bombs, industrial radiological accidents, or accidental overexposure of beta (ß) particle or gamma (γ) radiation sources in medical procedures. Although the gross clinical consequences of these injuries have been well documented, relatively little is known about the molecular changes underlying the progression of pathology. Here we describe a porcine model of cutaneous radiation injury after skin was exposed to strontium-90 b particle at doses of 16-42 Gy and characterize the anatomical and molecular changes over 70 days. The results show that irradiated sites displayed dosedependent increases in erythema and moist desquamation that peaked between days 35 and 42. Dose-dependent histopathological changes were observed, with higher doses exhibiting increased inflammation and epidermal hyperplasia beyond day 35. Furthermore, immunohistochemistry showed that exposure to 37 Gy ß-particle radiation decreased epidermal cell proliferation and desmosomal junction proteins at day 70, suggesting compromised epidermal integrity. Metabolomic analysis of biopsies revealed dose- and time-dependent changes as high as 252-fold in several metabolites not previously linked to CRI. These alterations were seen in pathways reflecting protein degradation, oxidative stress, eicosanoid production, collagen matrix remodeling, mitochondrial stress, cell membrane composition and vascular disruption. Taken together, these data show that exposure to high doses of ß particle damaged the molecular processes underlying skin integrity to a greater extent and for a longer period of time than has been shown previously. These findings further understanding of radiation-induced skin injury and serve as a foundation for the development and testing of potential therapeutics to treat CRI.


Assuntos
Partículas beta/efeitos adversos , Pele/lesões , Pele/efeitos da radiação , Animais , Proliferação de Células/efeitos da radiação , Relação Dose-Resposta à Radiação , Feminino , Pele/metabolismo , Pele/patologia , Suínos , Transcriptoma/efeitos da radiação
12.
Radiat Res ; 192(2): 159-168, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31188068

RESUMO

In this work, we investigated the change in tumor microenvironment caused by semi-ablative high-dose irradiation and its implication on tumor cell survival, reoxygenation of hypoxic cells and repopulation in FSaII tumors grown subcutaneously in the hind legs of C3H mice. Tumors were exposed to 10-30 Gy of X-ray radiation in a single exposure, and the vascularity and blood perfusion were assessed based on the levels of CD31 expression and Hoechst 33342 perfusion, respectively. The tumor hypoxia was assessed by staining for pimonidazole adduct formation and the expression of hypoxia-inducible factor-1α (HIF-1α) and carbonic anhydrase 9 (CA9). Tumor cell survival was determined using in vivo-in vitro excision assay method. The proportion of hypoxic cells in the tumor was determined from the surviving cell fraction in tumors exposed to a test dose under aerobic and hypoxic conditions. Radiation expsoure markedly reduced the functional vascularity and blood perfusion, and profoundly increased the expression of HIF-1α and CA9 pointing to an increase in tumor hypoxia. The overall clonogenic cell survival progressively decreased during 2-5 days postirradiation, most likely due to the radiation-induced vascular dysfunction. In turn, the proportion of surviving hypoxic cells decreased over several days postirradiation, presumably due to reoxygenation of hypoxic cells. The oxygen supplied through small fractions of blood vessels that survived the high-dose exposure, together with a reduction of oxygen consumption due to massive cell death, appeared to be the cause of the reoxygenation of hypoxic cells. The surviving tumor cells then subsequently repopulated. The findings from this study using a murine tumor model suggest that the efficacy of stereotactic body radiotherapy (SBRT) and stereotactic radiosurgery (SRS) may be significantly improved by allowing an inter-fraction time for reoxygenation while avoiding repopulation.


Assuntos
Fibrossarcoma/patologia , Fibrossarcoma/radioterapia , Oxigênio/metabolismo , Hipofracionamento da Dose de Radiação , Animais , Vasos Sanguíneos/efeitos da radiação , Morte Celular/efeitos da radiação , Relação Dose-Resposta à Radiação , Feminino , Fibrossarcoma/metabolismo , Camundongos , Hipóxia Tumoral/efeitos da radiação , Microambiente Tumoral/efeitos da radiação
13.
Int J Nanomedicine ; 14: 4157-4165, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31239674

RESUMO

Background: During decades, all improvements and developments in radiation therapy technologies have been focused on its main goal: maximize the dose in the tumor and minimize it in surrounding normal tissues. Recently, scientists have some approaches to nanoparticles, especially gold nanoparticles (GNPs), for dose localization. Purpose: Herein, the effect of GNPs in combination with electron brachytherapy in a model of eye tumor has been investigated. Materials and methods: Monte Carlo simulation was utilized and a complete anatomical model of the eye, a tumor with 5 mm thick, and a type of Ruthenium-106 beta emitter ophthalmic plaque were simulated. Simulation results have been validated by a Plexiglas eye phantom and film dosimetry, experimentally. Results: The results showed using GNPs causes the dose amplification in 2 mm from the plaque surface which the higher concentration has the higher enhancement. At more distances, Dose Enhancement Factors (DEFs) have the negative amounts, so that total delivered dose to the tumor has decreased with increasing of Au concentrations and the dose of organ at risk like sclera has increased. Conclusion: Therefore, using of GNPs along with a 106Ru/106Rh ocular plaque, as an electron emitter source, is a good choice only for superficial lesions, and it is not recommended for deeper tumors due to the parameters of radiation treatment and delivered dose to the tissues.


Assuntos
Braquiterapia , Elétrons , Neoplasias Oculares/radioterapia , Ouro/uso terapêutico , Nanopartículas Metálicas/uso terapêutico , Simulação por Computador , Relação Dose-Resposta à Radiação , Olho/patologia , Olho/efeitos da radiação , Humanos , Método de Monte Carlo , Imagens de Fantasmas , Dosagem Radioterapêutica , Reprodutibilidade dos Testes , Rutênio/química , Prata/uso terapêutico
14.
Anticancer Res ; 39(6): 2799-2804, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31177116

RESUMO

BACKGROUND/AIM: Spatially fractionated radiotherapy (grid therapy) can control some bulky tumors which is challenging for conventional radiotherapy. This study aimed to investigate whether a novel tungsten contained rubber (TCR) grid collimator can be employed in electron grid therapy. MATERIALS AND METHODS: The TCR grid collimator placed on a solid water phantom, and percentage depth doses (PDDs) and lateral dose profiles were measured for 9 MeV electron beam with Gafchromic EBT3 films. At the lateral dose profile, the ratios of the dose in the areas with and without shielding (valley-to-peak ratios) were evaluated. RESULTS: The dmax values with the 1, 2 and 3 mm TCR grid collimators were 1.2, 1.1 and 0.7 cm, respectively, while the valley-to-peak ratios at each dmax were 0.566, 0.412 and 0.293, respectively. CONCLUSION: Only the 2 mm TCR grid collimator had adequate dosimetric features compared to the conventional grid collimator and could be substituted.


Assuntos
Neoplasias/radioterapia , Radiometria/métodos , Radioterapia/instrumentação , Tungstênio/química , Relação Dose-Resposta à Radiação , Elétrons , Estudos de Viabilidade , Humanos , Imagens de Fantasmas , Planejamento da Radioterapia Assistida por Computador , Borracha/química
15.
Chemosphere ; 228: 769-777, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31075640

RESUMO

As sulfonated aromatic compounds are widely used in industry, they have frequently been detected in aquatic environments. This study evaluated the degradation and mineralization of 2,6-naphthalenedisulfonic acid disodium salt (2,6-NS), sodium 2-naphthalenesulfonate (2-NS), benzenesulfonic acid sodium salt (BS), and 4-vinylbenzene sulfonate sodium (4-VBS) by exposing aqueous solutions of these compounds to Co60 irradiation. The radiolytic degradation of these pollutants was found to follow pseudo-first-order kinetics. The dose required to achieve 90% degradation (D90) of these four sulfonated compounds was 0.480 (2,6-NS), 0.390 (2-NS), 0.194 (BS), and 0.280 kGy (4-VBS). The chemical radiolytic yield (Gvalue) decreased as the absorbed dose increased; moreover, the chemical structures of these compounds affected their radiolytic efficacy. No significant reduction in radiolytic degradation was observed in the presence of inorganic anions (SO42-, Cl-). The radiolytic degradation efficiency was higher when hydrogen peroxide (H2O2, a hydroxyl radical (OH) promoter) was added. The results also showed that combining H2O2, persulfate anions (S2O82-, a sulfate radical anion (SO4-) promoter), or N2O gas (a OH radical promoter) with the sulfonated compounds enhanced the radiolytic mineralization yield and process by reducing the required irradiation energy. In terms of the Co60/O2 system, at an absorbed dose of 12 kGy, the total organic carbon (TOC) removal efficiency was almost 70%, resulting in the observed release of SO42- anions. In addition, the concentration of dissolved oxygen decreased and the pH was lowered. Based on these results, irradiation with Co60 was found to be a useful tool to remedy wastewater containing sulfonated aromatic compounds.


Assuntos
Sulfonatos de Arila/química , Poluentes Químicos da Água/química , Ânions , Sulfonatos de Arila/efeitos da radiação , Biodegradação Ambiental , Carbono/química , Radioisótopos de Cobalto , Relação Dose-Resposta à Radiação , Peróxido de Hidrogênio/química , Radical Hidroxila/química , Cinética , Naftalenossulfonatos/química , Naftalenossulfonatos/efeitos da radiação , Sulfatos/química , Água/química , Poluentes Químicos da Água/efeitos da radiação
16.
Radiat Res ; 192(1): 28-39, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31058578

RESUMO

Exposures to ionizing radiation can cause depletion in stem cell reservoirs and lead to chronic injury processes that exacerbate carcinogenic and inflammatory responses. Therefore, radioprotective measures, against both acute and chronic biological effects of radiation, require frequent intake of nontoxic natural products, which have practical oral administration. The goal of this study was to characterize the radioprotective, radiomitigative and radiation-induced bystander effect-inhibiting properties of endogenous metabolites: phenylacetate, ursodeoxycholate and tauroursodeoxycholate. Compounds were administered pre- and postirradiation as well as in donor and recipient bystander flasks to analyze whether these might adequately protect against radiation injury as well as facilitate recovery from the exposures. The clonogenic HCT116 p53 wild-type cancer cell line in this study shares characteristics of stem cells, such as high reproductive viability, which is an effective marker to demonstrate compound effectiveness. Clonogenic assays were therefore used to characterize radioprotective, radiomitigative and bystander inhibiting properties of treatment compounds whereby cellular responses to radiation were quantified with macroscopic colony counts to measure cell survival in flasks. The results were statistically significant for phenylacetate and tauroursodeoxycholate when administered preirradiation, conferring radioprotection up to 2 Gy, whereas administration postirradiation and in bystander experiments did not confer radioprotection in vitro. These findings suggest that phenylacetate and tauroursodeoxycholate might be effective radioprotectors, although they possess no radiomitigative properties.


Assuntos
Acetatos/farmacologia , Efeito Espectador/efeitos dos fármacos , Efeito Espectador/efeitos da radiação , Fenóis/farmacologia , Protetores contra Radiação/farmacologia , Transdução de Sinais/efeitos dos fármacos , Ácido Tauroquenodesoxicólico/farmacologia , Ácido Ursodesoxicólico/farmacologia , Acetatos/metabolismo , Sobrevivência Celular/efeitos da radiação , Neoplasias do Colo/patologia , Relação Dose-Resposta à Radiação , Células HCT116 , Humanos , Fenóis/metabolismo , Protetores contra Radiação/metabolismo , Transdução de Sinais/efeitos da radiação , Ácido Tauroquenodesoxicólico/metabolismo , Ácido Ursodesoxicólico/metabolismo
17.
Radiat Res ; 192(1): 40-52, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31059377

RESUMO

The global threat of exposure to radiation and its subsequent outcomes require the development of effective strategies to mitigate immune cell injury. In this study we explored transcriptional and immunophenotypic characteristics of lymphoid organs of a non-human primate model after total-body irradiation (TBI). Fifteen middle-aged adult, ovariectomized, female cynomolgus macaques received a single dose of 0, 2 or 5 Gy gamma radiation. Thymus, spleen and lymph node from three controls and 2 Gy (n = 2) and 5 Gy (n = 2) exposed animals were assessed for molecular responses to TBI through microarray-based transcriptional profiling at day 5 postirradiation, and cellular changes through immunohistochemical (IHC) characterization of markers for B and T lymphocytes and macrophages across all 15 animals at time points up to 6 months postirradiation. Irradiated macaques developed acute hematopoietic syndrome. Analysis of array data at day 5 postirradiation identified transcripts with ≥2-fold difference from control and a false discovery rate (FDR) of Padj < 0.05 in lymph node (n = 666), spleen (n = 493) and thymus (n=3,014). Increasing stringency of the FDR to P < 0.001 reduced the number of genes to 71 for spleen and 379 for thymus. IHC and gene expression data demonstrated that irradiated animals had reduced numbers of T and B lymphocytes along with relative elevations of macrophages. Transcriptional analysis revealed unique patterns in primary and secondary lymphoid organs of cynomolgus macaques. Among the many differentially regulated transcripts, upregulation of noncoding RNAs [MIR34A for spleen and thymus and NEAT1 (NCRNA00084) for thymus] showed potential as biomarkers of radiation injury and targets for mitigating the effects of radiation-induced hematopoietic syndrome-impaired lymphoid reconstitution.


Assuntos
Linfócitos T/metabolismo , Linfócitos T/efeitos da radiação , Transcrição Genética/efeitos da radiação , Irradiação Corporal Total/efeitos adversos , Animais , Relação Dose-Resposta à Radiação , Feminino , Macaca fascicularis
18.
Radiat Res ; 192(1): 1-12, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31081741

RESUMO

We present a comprehensive comparative analysis on the repair of radiation-induced DNA damage ex vivo in 15 strains of mice, including 5 inbred reference strains and 10 collaborative-cross strains, of both sexes, totaling 5 million skin fibroblast cells imaged by three-dimensional highthroughput conventional microscopy. Non-immortalized primary skin fibroblasts derived from 76 mice were subjected to increasing doses of both low- and high-LET radiation (X rays; 350 MeV/n 40Ar; 600 MeV/n 56Fe), which are relevant to carcinogenesis and human space exploration. Automated image quantification of 53BP1 radiation-induced foci (RIF) formation and repair during the first 4-48 h postirradiation was performed as a function of dose and LET. Since multiple DNA double-strand breaks (DSBs) are induced in a dose- and LET-dependent manner, our data suggest that when DSBs are formed within the same discrete nuclear region, referred to as the "repair domain", novel mathematical formalisms used to report RIF allowed us to conclude that multiple DSBs can be present in single RIF. Specifically, we observed that the number of RIF per Gy was lower for higher X-ray doses or higher LET particles (i.e., 600 MeV/n 56Fe), suggesting there are more DSBs per RIF when the local absorbed dose increases in the nucleus. The data also clearly show that with more DSBs per RIF, it becomes more difficult for cells to fully resolve RIF. All 15 strains showed the same dose and LET dependence, but strain differences were preserved under various experimental conditions, indicating that the number and sizes of repair domains are modulated by the genetic background of each strain.


Assuntos
Dano ao DNA , Transferência Linear de Energia , Proteína 1 de Ligação à Proteína Supressora de Tumor p53/metabolismo , Animais , Quebras de DNA de Cadeia Dupla/efeitos da radiação , Reparo do DNA/efeitos da radiação , Relação Dose-Resposta à Radiação , Cinética , Camundongos , Especificidade da Espécie , Fatores de Tempo , Raios X/efeitos adversos
19.
Radiat Res ; 192(1): 63-74, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31095446

RESUMO

Radiotherapy with sparsely ionizing photons is a cornerstone of successful cancer treatment. Age at time of exposure to radiation is known to influence biological outcomes for many end points. The effect of dose and age at exposure upon the occurrence of radiogenic cardiovascular disease is poorly understood. The goal of this work was to determine the response of maleWAG/RijCmcr rats at 6 months of age to gamma rays, and at 6 months or 6 weeks of age to X rays, using clinically relevant biomarkers of cardiovascular disease and kidney injury. Overall, there were significant radiation-induced effects on the levels of bicarbonate (P=0.0016), creatinine (P=0.0002), calcium (P = 0.0009), triglycerides (P = 0.0269) and blood urea nitrogen, albumin, protein, AST, alkaline phosphatase, total cholesterol and HDL (all P < 0.0001). Of those variables with a significant radiation-dose effect, there were significant modifications by age at time of exposure for bicarbonate (P = 0.0033), creatinine (P = 0.0015), AST (P = 0.0040), total cholesterol (P = 0.0006) and blood urea nitrogen, calcium, albumin, protein, alkaline phosphatase and HDL (all P < 0.0001). Cardiac perivascular collagen content was significantly increased in rats that were 8.0 Gy X-ray irradiated at 6 weeks of age (P < 0.047) but not at 6 months of age. While systemic blood pressure was elevated in both cohorts after 8.0 Gy X-ray irradiation (compared to agematched sham-irradiated controls), the magnitude of the increase above baseline was greater in the younger rats (P < 0.05). These findings indicate that dose and age at time of irradiation determine the timeline and severity of cardiac and renal injury.


Assuntos
Cardiopatias/etiologia , Nefropatias/etiologia , Lesões Experimentais por Radiação/etiologia , Fatores Etários , Animais , Relação Dose-Resposta à Radiação , Raios gama/efeitos adversos , Cardiopatias/sangue , Nefropatias/sangue , Masculino , Lesões Experimentais por Radiação/sangue , Ratos , Ratos Wistar , Fatores de Risco
20.
Radiat Res ; 192(2): 135-144, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31141469

RESUMO

Radiotherapy for head and neck cancers can result in extensive damage to the salivary glands, significantly affecting patient quality of life. However, the salivary gland can recover in patients receiving lower doses of radiation. In addition, there is considerable interest in delineating the mechanisms by which stem cells survive radiation exposure and promote tissue regeneration. In this study, we isolated stable radioresistant acinar progenitor cells from the submaxillary gland of the Sprague Dawley rat. Progenitor cells are characterized as c-Kithigh/alpha-amylase+ and are resistant to X rays (≤5 Gy).We further isolated a radiosensitive acinar counterpart, characterized as c-Kitlow/alpha-amylase+, which is effectively killed by exposure to 2 Gy X ray of radiation. Phosphopeptides with homology to the treacle protein (TCOF1) were disproportionately increased in progenitor cells, compared to their radiosensitive counterparts. Silencing of TCOF1 expression (shRNA) radiosensitized progenitor cells, a response conserved in human cells with TCOF1 knockdown. Collectively, these observations indicate that radiation resistance is an intrinsic property of c-Kithigh salivary gland progenitor cells. Since human salivary gland stem cells with c-Kit expression are believed to have enhanced regenerative potencies, our model system provides a stable platform to investigate molecular features associated with c-Kit expression that may contribute to protection or stabilization of the stem cell niche.


Assuntos
Células Acinares/citologia , Proteínas Nucleares/metabolismo , Fosfoproteínas/metabolismo , Tolerância a Radiação , Células-Tronco/efeitos da radiação , Animais , Linhagem Celular , Sobrevivência Celular/efeitos da radiação , Dano ao DNA , Relação Dose-Resposta à Radiação , Técnicas de Silenciamento de Genes , Humanos , Proteínas Nucleares/deficiência , Proteínas Nucleares/genética , Fenótipo , Fosfoproteínas/deficiência , Fosfoproteínas/genética , Transporte Proteico/efeitos da radiação , Ratos , Ratos Sprague-Dawley , Células-Tronco/citologia , Células-Tronco/metabolismo
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