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1.
Anticancer Res ; 40(1): 459-464, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892601

RESUMO

BACKGROUND/AIM: This study compared the dose distributions of carbon ion radiotherapy (C-ion RT) and intensity-modulated radiotherapy (IMRT) in patients with locally advanced hepatocellular carcinoma (LAHCC). PATIENTS AND METHODS: A retrospective analysis was conducted in 10 consecutive patients with LAHCC who had undergone C-ion RT. The dose-volume histogram parameters of clinical plans using C-ion RT at 60 Gy and simulated plans using IMRT at 60 Gy and 50 Gy were compared. We measured the percentage of the normal liver volume that received at least 5 Gy (V5), 10 Gy (V10), 20 Gy (V20), 30 Gy (V30), 40 Gy (V40), and 50 Gy (V50). RESULTS: The V5, V10, V20, and the mean liver dose were significantly lower in patients who received 60 Gy of C-ion RT than in those who received 50 or 60 Gy of IMRT. CONCLUSION: C-ion RT exhibits a better liver dose distribution than IMRT in patients with LAHCC.


Assuntos
Carcinoma Hepatocelular/radioterapia , Radioterapia com Íons Pesados , Neoplasias Hepáticas/radioterapia , Radioterapia de Intensidade Modulada , Carcinoma Hepatocelular/diagnóstico por imagem , Relação Dose-Resposta à Radiação , Humanos , Fígado/patologia , Fígado/efeitos da radiação , Neoplasias Hepáticas/diagnóstico por imagem , Estadiamento de Neoplasias , Dosagem Radioterapêutica , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Carga Tumoral
2.
Cancer Invest ; 38(1): 61-84, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31791151

RESUMO

Cancer treatment by magnetic hyperthermia offers numerous advantages, but for practical applications many variables still need to be adjusted before developing a controlled and reproducible cancer treatment that is bio-compatible (non-damaging) to healthy cells. In this work, Fe3O4 and CoFe2O4 were synthesized and systematically studied for the development of efficient therapeutic agents for applications in hyperthermia. The biocompatibility of the materials was further evaluated using HepG2 cells as biological model. Colorimetric and microscopic techniques were used to evaluate the interaction of magnetic nano-materials (MNMs) and HepG2 cells. Finally, the behavior of MNMs was evaluated under the influence of an alternating magnetic field (AMF), observing a more efficient temperature increment for CoFe2O4, a desirable behavior for biomedical applications since lower doses and shorter expositions to alternating magnetic field might be required.


Assuntos
Hipertermia Induzida/métodos , Nanopartículas de Magnetita/administração & dosagem , Nanomedicina/métodos , Neoplasias/terapia , Animais , Materiais Biocompatíveis/administração & dosagem , Materiais Biocompatíveis/química , Materiais Biocompatíveis/toxicidade , Cobalto/administração & dosagem , Cobalto/química , Cobalto/toxicidade , Colorimetria , Terapia Combinada/efeitos adversos , Terapia Combinada/métodos , Compostos Férricos/administração & dosagem , Compostos Férricos/química , Compostos Férricos/toxicidade , Óxido Ferroso-Férrico/administração & dosagem , Óxido Ferroso-Férrico/química , Óxido Ferroso-Férrico/toxicidade , Células Hep G2 , Humanos , Hipertermia Induzida/efeitos adversos , Fígado/efeitos da radiação , Terapia de Campo Magnético/efeitos adversos , Terapia de Campo Magnético/métodos , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/toxicidade , Masculino , Teste de Materiais/métodos , Ratos , Fatores de Tempo , Testes de Toxicidade/métodos
3.
Parasitol Int ; 74: 101921, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31026594

RESUMO

Cystic echinococcosis (CE) is a global public health problem associated with a high overall disease burden. Multiple organ systems are involved in approximately 20% of cases, and treatment is challenging and rarely reported. In this study, we described microwave ablation (MWA) combining surgery for the treatment of a multiorgan CE patient. The patient underwent percutaneous MWA for a hepatic CE3b lesion and exploratory resection of the pelvic cavity lesions. The hepatic lesion was effectively treated by MWA, and invasiveness was reduced by avoiding hepatectomy. The patient had a favorable prognosis at a 20-month's follow-up. More studies are needed to evaluate its usefulness in CE treatment.


Assuntos
Técnicas de Ablação , Equinococose/cirurgia , Equinococose/terapia , Fígado/efeitos da radiação , Micro-Ondas/uso terapêutico , Adulto , Equinococose/diagnóstico , Feminino , Humanos , Fígado/parasitologia , Fígado/patologia , Resultado do Tratamento
4.
Clin Nucl Med ; 45(2): 100-104, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31876805

RESUMO

PURPOSE: The complication profile following repeat Y-radioembolization (RE) is not well understood, and repeat RE is sometimes avoided because of concerns for RE-induced liver disease (REILD) and liver toxicity. The purpose of this study was to examine the incidence of REILD and liver toxicity following repeat Y-RE and to identify potential risk factors. METHODS: A retrospective analysis of patients undergoing repeat RE to the same hepatic lobe between 2013 and 2018 was performed. Baseline factors were evaluated as predictors of liver toxicity, mortality, and REILD, which was defined as the presence symptomatic ascites or jaundice in the absence of biliary obstruction within 8 weeks following RE. Post-RE complications were graded according to the Common Terminology Criteria for Adverse Events version 5. RESULTS: A total of 39 patients underwent repeat RE with 14 (35.9%) experiencing Common Terminology Criteria for Adverse Events toxicity of grade 2 or greater, 3 (10.3%) grade 3, and no grade 4 or greater. A Model for End Stage Liver Disease score of 8 or greater was associated with grade 2 toxicity or greater (26.7% vs 75%; P = 0.013). Only 3 patients (7.7%) experienced REILD due to symptomatic ascites without jaundice. Greater than 2 REs were associated with a greater rate of 6-month mortality (12% vs 58.3%, P = 0.003), 12-month mortality (28% vs 75%, P = 0.007), and REILD (0% vs 21.4%, P = 0.016). Age, sex, microsphere type, cirrhosis, Child-Pugh, and Eastern Cooperative Oncology Group status were not significantly associated with complications, REILD, or survival. CONCLUSIONS: Repeat Y-RE appears to be well tolerated with a low rate of high-grade adverse events and REILD.


Assuntos
Embolização Terapêutica/efeitos adversos , Hepatopatias/etiologia , Fígado/efeitos da radiação , Lesões por Radiação/etiologia , Centros de Atenção Terciária , Radioisótopos de Ítrio/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Incidência , Fígado/fisiopatologia , Hepatopatias/fisiopatologia , Masculino , Microesferas , Pessoa de Meia-Idade , Lesões por Radiação/fisiopatologia , Estudos Retrospectivos , Radioisótopos de Ítrio/uso terapêutico
5.
Radiat Oncol ; 14(1): 223, 2019 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-31822293

RESUMO

BACKGROUND: The addition of regional nodal radiation (RNI) to whole breast irradiation for high risk breast cancer improves metastases free survival and new data suggests it contributes additional benefit to overall survival. Deep inspiration breath hold (DIBH) has been shown to reduce cardiac and pulmonary dose in the context of left-sided disease treated with or without RNI, yet few studies have investigated its utility for right-breast cancer. This study investigates the potential advantages of DIBH in local and locoregional radiotherapy for right-sided breast cancer. METHODS: Free-breathing (FB) and DIBH computed tomography datasets were obtained from twenty patients who previously underwent radiotherapy for left-sided breast cancer. Ten patients were retrospectively planned for whole right breast only irradiation and ten patients were planned for irradiation to the whole breast plus ipsilateral supra-clavicular (SC) nodes, with and without irradiation of the ipsilateral internal mammary nodes (IMN). Dose-volume metrics for the clinical target volume, lungs, heart, left anterior descending artery, right coronary artery (RCA) and liver were recorded. Differences between FB and DIBH plans were analysed using Wilcoxon signed-rank tests, with P < 0.05 considered statistically significant. RESULTS: DIBH increased the average total lung volume compared to FB in both breast only and breast plus RNI cohorts (P = 0.001). For the breast only group, there was no significant improvement in any ipsilateral lung dose-volume metric between FB and DIBH. However, for the breast plus RNI group, there was an improvement in ipsilateral lung mean dose (18.9 ± 3.2 Gy to 15.9 ± 2.3 Gy, P = 0.002) and V20Gy (45.3 ± 13.3% to 32.9 ± 9.4%, P = 0.002). In addition, DIBH significantly reduced the maximum dose to the RCA for RNI (11.6 ± 7.2 Gy to 5.6 ± 2.9 Gy, P = 0.03). Significant reductions in the liver V20Gy and maximum dose were observed in all cohorts during DIBH compared to FB. CONCLUSIONS: DIBH is a promising approach for right-breast radiotherapy with considerable sparing of normal tissue, particularly when the ipsilateral IMNs are also irradiated.


Assuntos
Suspensão da Respiração , Órgãos em Risco/efeitos da radiação , Lesões por Radiação/prevenção & controle , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/métodos , Neoplasias Unilaterais da Mama/radioterapia , Feminino , Coração/efeitos da radiação , Humanos , Inalação , Fígado/efeitos da radiação , Pulmão/efeitos da radiação , Prognóstico , Dosagem Radioterapêutica , Estudos Retrospectivos
6.
Probl Radiac Med Radiobiol ; 24: 220-234, 2019 Dec.
Artigo em Inglês, Ucraniano | MEDLINE | ID: mdl-31841469

RESUMO

OBJECTIVE: Rat liver stem-like epithelial cells (WB-F344) that under certain conditions may differentiate into hepa- tocyte and biliary lineages were subjected to acute X-irradiation with the aim to examine cell cycle peculiarities dur- ing the course of survival. MATERIALS AND METHODS: Suspensions of WB-F344 cells that grew as a monolayer and reached sub-confluence were irradiated with 1, 5, and 10 Gy of X-rays (2 Gy/min). As an intact control, sham-irradiated cells were used. After irra- diation, cells were plated into 25-cm2 tissue culture flasks to culture them for over several days without reaching contact inhibition. On days 1, 2, 3, and 5 post-irradiation, cells were harvested and examined for nuclear morpholo- gy and DNA ploidy by stoichiometric toluidine blue reaction and image cytometry. On days 7 and 9 post-irradiation, only heavily irradiated (10 Gy) cells were examined. Also, 10 Gy-irradiated cells were chosen for immunofluorescence staining to monitor persistence of DNA lesions (γ-H2AX), cell proliferation (Ki-67), and self-renewal factors charac- teristic for stem cells (OCT4 and NANOG). RESULTS: Radioresistance of WB-F344 cells was evidenced by the findings that they do not undergo rapid and mas- sive cell death that in fact was weakly manifested as apoptotic even in heavily irradiated cells. Instead, there was cell cycle progression delay accompanied by polyploidization (via Ki-67-positive mitotic slippage or via impaired cytokinesis) and micronucleation in a dose-dependent manner, although micronucleation to some extent went ahead of polyploidization. Polyploid cells amenable for recovering from DNA damage can mitotically depolyploidize. Many micronuclei contained γ-H2AX clusters, suggesting isolation of severely damaged DNA fragments. Both factors, OCT4 and NANOG, were expressed in the intact control, but became enhanced after irradiation. CONCLUSIONS: Although the fact of micronucleation is indicative of genotoxic effect, WB-F344 cells can probably escape cell death via sorting of damaged DNA by micronuclei. Induction of polyploidy in these cells can be adaptive to promote cell survival and tissue regeneration with possible involvement of self-renewal mechanism.


Assuntos
Dano ao DNA , Células Epiteliais/efeitos da radiação , Fígado/efeitos da radiação , Micronúcleos com Defeito Cromossômico/efeitos da radiação , Poliploidia , Tolerância a Radiação , Raios X/efeitos adversos , Animais , Técnicas de Cultura de Células , Linhagem Celular , Relação Dose-Resposta à Radiação , Células Epiteliais/patologia , Fígado/patologia , Doses de Radiação , Ratos , Células-Tronco/patologia , Células-Tronco/efeitos da radiação
7.
Phys Med ; 68: 10-16, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31726265

RESUMO

In this study, the image quality of in-treatment four-dimensional cone-beam computed tomography (In-4D-CBCT) obtained with various prescription doses (PDs) were quantitatively evaluated in volumetric-modulated arc therapy (VMAT) for stereotactic body radiation therapy (SBRT) of the lungs and liver. To assess image quality, we used a dynamic thorax phantom and three-dimensional (3D) abdominal phantom; In-4D-CBCT images were acquired with various PDs (from 5 to 12 Gy). The In-4D-CBCT with various PDs were compared with the reference images (pre-4D-CBCT). The image quality was evaluated using the signal-to-noise ratio (SNR), the contrast-to-noise ratio (CNR), and the Dice similarity coefficient (DSC). The fiducial marker positions with various PDs were compared with those of the reference images. For the dynamic thorax phantom, the difference between pre- and In-4D-CBCT in terms of SNR and CNR decreased, as the PD increased from 6 to 12 Gy. The median DSC ranged from 0.7 to 0.74, and showed good similarity. For the 3D abdominal phantom, the difference between pre- and In-4D-CBCT in terms of SNR and CNR decreased as the PD increased from 5 to 6 Gy; conversely, it increased as the PD increased from 7 to 8 Gy. The fiducial marker positions were within 1.0 mm for all PDs. We concluded that the image quality of In-4D-CBCT degraded compared with the reference image; however, it was sufficiently accurate for assessing the intra-fractional tumor position in VMAT for SBRT of the lungs and liver both in terms of the target volume similarity and accuracy of the fiducial marker position.


Assuntos
Tomografia Computadorizada Quadridimensional , Radiocirurgia , Radioterapia de Intensidade Modulada , Fígado/diagnóstico por imagem , Fígado/efeitos da radiação , Pulmão/diagnóstico por imagem , Pulmão/efeitos da radiação , Imagens de Fantasmas , Controle de Qualidade
8.
J BUON ; 24(4): 1390-1401, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31646782

RESUMO

PURPOSE: To compare the survival of American Joint Committee on Cancer (AJCC) stage I hepatocellular carcinoma (HCC) treated with surgery versus external beam radiation therapy (EBRT). METHODS: Surveillance, Epidemiology, and End Results (SEER) database was used to identify the patients diagnosed with HCC between 2004 and 2013. Overall survival (OS) and liver-specific survival (LSS) were compared between patients treated with surgery and EBRT. A 1:1 propensity score matching (PSM) analysis was employed by matching age, sex, and race. RESULTS: Among the 1553 patients with HCC ≤2cm, there was no significant difference in OS (p=0.605, before PSM; p=0.891, after PSM) and LSS (p=0.281, before PSM; p=0.346, after PSM) between patients treated with surgery and EBRT. Among the 1752 patients with HCC >2cm and ≤3cm, patients treated with surgery had significantly better OS (p=0.001) than those treated with EBRT, but statistically similar LSS (p=0.072) before PSM; however, there was no significant difference in OS (p=0.139) and LSS (p=0.722) between patients treated with surgery and EBRT after PSM. Additionally, 1157, 723, and 1331 patients had HCC >3cm and ≤4cm, HCC >4cm and ≤5cm, and HCC >5cm, respectively; among them, patients treated with surgery had significantly better OS and LSS than those treated with EBRT regardless of PSM. CONCLUSIONS: At the AJCC stage I, the survival after EBRT might be comparable to that after surgery for HCC ≤3cm, but the survival after EBRT was inferior to that after surgery for HCC >3cm.


Assuntos
Carcinoma Hepatocelular/radioterapia , Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Braquiterapia/métodos , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/patologia , Criança , Pré-Escolar , Terapia Combinada , Intervalo Livre de Doença , Feminino , Humanos , Lactente , Fígado/patologia , Fígado/efeitos da radiação , Fígado/cirurgia , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pontuação de Propensão , Programa de SEER , Adulto Jovem
9.
J BUON ; 24(4): 1402-1407, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31646783

RESUMO

PURPOSE: To compare the efficacy of transcatheter arterial chemoembolization (TACE) combined with radiofrequency ablation (RFA) in primary hepatocellular carcinoma and recurrence of hepatocellular carcinoma after hepatectomy, and analysis the prognostic factors affecting therapeutic outcomes. METHODS: A total of 132 hepatocellular carcinoma patients treated with TACE combined with RFA were divided into primary group (n=89) and recurrent group (n=43). Their clinical date were reviewed. The overall survival (OS), tumor-free survival (TFS) and safety between 2 groups were compared. Prognostic factors were analyzed with univariate and multivariate analyses. RESULTS: OS rates at 1 and 3 years were 94.4% (84/89) and 70.8% (63/89) in the primary group, and TFS were 76.4% (68/89) and 37.1% (33/89), respectively. The OS rates in the recurrent group were 93.0% (40/43) and 65.1% (28/43), and TFS rates were 41.9% (18/43) and 13.9% (6/43), respectively. The OS rates had no significant difference between 2 groups (x2=0.0068, 0.4353, p=0.9342, 0.5094), but the TFS rates in primary group were significantly higher than in the recurrent group (x2=15.2378, 7.4483, p=0.0001, 0.0063). Multivariate analysis identified presence of portosystemic collaterals, AFP level, total bilirubin and Child-Pugh grading as factors affecting OS, and the presence of portosystemic collaterals and AFP level were two unfavorable prognostic factors influencing TFS. CONCLUSIONS: TACE combined with RFA is helpful in improving the survival rate of patients with primary and recurrent hepatocellular carcinoma. Presence of portosystemic collaterals, AFP level,ptotal bilirubin and Child-Pugh grading were the factors affecting OS.


Assuntos
Ablação por Cateter , Quimioembolização Terapêutica , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/radioterapia , Terapia Combinada , Feminino , Hepatectomia , Humanos , Fígado/patologia , Fígado/efeitos da radiação , Fígado/cirurgia , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Resultado do Tratamento
10.
Artigo em Russo | MEDLINE | ID: mdl-31626159

RESUMO

BACKGROUND: Experimental studies have established that that low-intensity ultrahigh frequency (UHF) electromagnetic radiation (EMR) has a preventive effect under the action of radiation and other pathogenic factors, which manifests itself in the accelerated development of adaptation, in the predominance of anabolic reactions over catabolic ones, and in the strengthening of the body' structural reserves. At the same time, from the standpoint of studying the mechanisms of primary prevention, it is very important not only to identify the overall adaptation effect, but also to have an idea on the specific contribution of a physical factor used in the development of adaptation. AIM: To identify metabolic and ultrastructural adaption parameters under the action of low-intensity UHF EMR on healthy animals and to determine their stability (safety), by using a model of radiation exposure. MATERIAL AND METHODS: The experiments were carried on 42 mature male rats weighing 180-200g. All the rats were divided into 5 groups: 2 experimental groups of 8 animals each for the comparative study of the specific features of adaptation developed under the preliminary action of UHF EMR in healthy animals and under radiation; 2 control groups of 8 animals each, and one intact group of 10 animals. The lumbar region (the area of the projection of the adrenal glands) was exposed to UHF EMP for 2 min daily (a cycle of 10 sessions). The animals were once irradiated at 2 Gy 60Co gamma ray doses, by using an Agat-R apparatus. The investigation objects were the liver, adrenal glands, testes, and thymus. The investigators used biochemical assays (the levels of RNA and DNA, antioxidant activity, specific activity in the thymocyte genome), transmission electron microscopy of adrenocorticocytes in the adrenal bundle zone and Sertoli cells in the testis. Mitochondria (number, average and total area, number of cristae) were morphometrically analyzed. RESULTS: The metabolic and ultrastructural adaption changes induced by UHF EMR in healthy animals were ascertained to be able to withstand the pathogenic effect of radiation and at the same time showed both stability (safety) and certain variability (plasticity) in their reactions. In this case, there were increases in the synthesis of nucleic acids and in the activity of the antioxidant system; there was also mitochondrial structural stability that was more manifested in the adrenocorticocytes in the adrenal bundle zone. At the same time, there was also a decrease in the intensity (magnitude) of a number of adaptive indicators, although by and large they were significantly higher than the level of control (the effect of radiation). DISCUSSION: Thus, the effect of UHF EMR on healthy animals contributed to the development of adaptive rearrangements in the organs studied. The essence of these changes was mainly the enhancement of synthetic reactions, as indicated by a larger amount of RNA and DNA, the activation of cellular and intracellular regeneration with the increased processes of hyperplasia of the mitochondrial cristae and the higher levels of ribosomes and polysomes. In addition, it can be assumed that the use of UHF EMR has laid the physicochemical foundations of its antioxidant action as conformational rearrangements in the membranes, which increased their structural stability. The findings are indicative of the increased level of morphofunctional reserves in the studied cells and tissues due to their increased bioenergetic and plastic potential. CONCLUSION: This study has provided new data that expand our understanding of the features of the development of adaptive mechanisms and the formation of the body's structural and functional reserves under the primary prophylactic action of low-intensity UHF EMR, by using the model of radiation exposure.


Assuntos
Glândulas Suprarrenais/efeitos da radiação , Radiação Eletromagnética , Fígado/efeitos da radiação , Testículo/efeitos da radiação , Timo/efeitos da radiação , Animais , Masculino , Ratos
11.
Anticancer Res ; 39(10): 5495-5504, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570443

RESUMO

BACKGROUND/AIM: Most patients with hepatocellular carcinoma (HCC) cannot be treated using traditional therapies. Boron neutron capture therapy (BNCT) may provide a new treatment for HCC. In this study, the therapeutic efficacy and radiobiological effects of boric acid (BA)-mediated BNCT in a VX2 multifocal liver tumor-bearing rabbit model are investigated. MATERIALS AND METHODS: Rabbits were irradiated with neutrons at the Tsing Hua Open Pool Reactor 35 min following an intravenous injection of BA (50 mg 10B/kg BW). The tumor size following BNCT treatment was determined by ultrasonography. The radiobiological effects were identified by histopathological examination. RESULTS: A total of 92.85% of the tumors became undetectable in the rabbits after two fractions of BNCT treatment. The tumor cells were selectively eliminated and the tumor vasculature was collapsed and destroyed after two fractions of BA-mediated BNCT, and no injury to the hepatocytes or blood vessels was observed in the adjacent normal liver regions. CONCLUSION: Liver tumors can be cured by BA-mediated BNCT in the rabbit model of a VX2 multifocal liver tumor. BA-mediated BNCT may be a breakthrough therapy for hepatocellular carcinoma.


Assuntos
Ácidos Bóricos/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/radioterapia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/radioterapia , Animais , Vasos Sanguíneos/efeitos dos fármacos , Vasos Sanguíneos/efeitos da radiação , Terapia por Captura de Nêutron de Boro/métodos , Hepatócitos/efeitos dos fármacos , Hepatócitos/efeitos da radiação , Fígado/efeitos dos fármacos , Fígado/efeitos da radiação , Masculino , Coelhos
12.
Pak J Pharm Sci ; 32(4): 1589-1597, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31608878

RESUMO

The current study was designed to estimate the effect of υ-radiation on male rats pretreated with Levetiracetam (LEV) and/or Oxcarbazepine (OXC). Poly-treatment of rats with LEV, OXC and υ-radiation showed a significant elevation in the activity of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and isoenzyme creatinine kinase-MB (CK-MB) along with, an increase in the level of creatinine, urea, cardiac troponin (cTnI) and glutamate. These increases were associated with a decrease in acetylcholine (Ach) and υ-aminobutyric acid (GABA) levels. The data further revealed a significant increase of the apoptotic mediators tumor necrosis factor alpha (TNF-α) and brain caspase3 as well as, alterations in the oxidative stress parameters. The Results of the histopathological examination of liver, kidney, heart and brain tissues indicated coincidence with those recorded by the biochemical analysis. It seems promising to conclude that the exposure to υ-radiation intensified the deleterious and detrimental effect of dual treatment of LEV and OXC in rats.


Assuntos
Anticonvulsivantes/farmacologia , Raios gama/efeitos adversos , Levetiracetam/efeitos adversos , Oxcarbazepina/efeitos adversos , Acetilcolina/metabolismo , Alanina Transaminase/sangue , Animais , Anticonvulsivantes/efeitos adversos , Aspartato Aminotransferases/sangue , Biomarcadores/sangue , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Encéfalo/efeitos da radiação , Quimioterapia Combinada , Coração/efeitos dos fármacos , Rim/efeitos dos fármacos , Rim/patologia , Rim/efeitos da radiação , Levetiracetam/farmacologia , Fígado/efeitos dos fármacos , Fígado/patologia , Fígado/efeitos da radiação , Masculino , Malondialdeído/metabolismo , Neurotransmissores/metabolismo , Oxcarbazepina/farmacologia , Ratos
13.
Appl Radiat Isot ; 154: 108891, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31536909

RESUMO

Zingerone (ZO) is an ingredient of ginger (Zingiber officinale) which has different pharmacological properties. The objective of this research was to evaluate the protective effect of ZO against Cisplatin (Cis) or γ-Irradiation (IR)-induced hepatotoxicity in rats. ZO was given orally for consecutive 14 days prior to the treatment with Cis or exposure to IR at 15th day. Animals were sacrificed at the 23rd day. Cis or IR induced a marked increase in MAPK signal transduction as evidenced by increased p38 MAPK, JNK and ErK1/2. CYP2E1 and NADPH oxidase were significantly up-regulated. Inflammatory markers (TLR4, iNOS, COX-2 and MPO) and liver enzymes (AST, ALT and ALP) activities were also increased. Administration of ZO significantly ameliorated the above mentioned parameters.


Assuntos
Cisplatino/antagonistas & inibidores , Cisplatino/toxicidade , Guaiacol/análogos & derivados , Fígado/efeitos dos fármacos , Fígado/efeitos da radiação , Protetores contra Radiação/farmacologia , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Animais , Aspartato Aminotransferases/sangue , Citocromo P-450 CYP2E1/genética , Raios gama/efeitos adversos , Expressão Gênica/efeitos dos fármacos , Expressão Gênica/efeitos da radiação , Guaiacol/administração & dosagem , Guaiacol/farmacologia , Mediadores da Inflamação/metabolismo , Fígado/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos da radiação , Masculino , Terapia de Alvo Molecular , Substâncias Protetoras/administração & dosagem , Substâncias Protetoras/farmacologia , Protetores contra Radiação/administração & dosagem , Ratos
14.
Phys Med Biol ; 64(20): 205006, 2019 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-31519018

RESUMO

Magnetic-resonance linear-accelerator (MR-LINAC) systems integrating in-room magnetic-resonance-imaging (MRI) guidance are a currently emerging technology. Such systems address the need to provide frequent imaging at optimal soft-tissue contrast for treatment guidance. However, the use of MRI-guidance in radiotherapy should address imaging-related spatial distortions, which may hinder accurate geometrical characterization of the treatment site. Since spatial encoding relies on well-defined magnetic fields, accurate modeling of the magnetic field alterations due to [Formula: see text]-inhomogeneities, gradient nonlinearities, and susceptibilities is needed. In this work, the modeling of susceptibility induced distortions is considered. Dedicated susceptibility measurements are reported, aiming at extending the characterization of different tissues for MRI-guided extra-cranial radiotherapy applications. A digital 4D anthropomorphic phantom, providing time-resolved anatomical changes due to breathing, is exploited as reference anatomy to quantify spatial distortions due to variations in tissue susceptibility. Sub-millimeter values can be attributed to susceptibility-induced distortions, with maximum values up to 2.3 mm at a gradient strength of 5 mT m-1. Improvements in susceptibility simulation for extra-cranial sites are shown when including specifically the contributions from lung, liver and muscular tissues.


Assuntos
Imagem por Ressonância Magnética/métodos , Imagem por Ressonância Magnética/normas , Imagens de Fantasmas , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia Guiada por Imagem/métodos , Neoplasias de Tecidos Moles/radioterapia , Algoritmos , Animais , Fígado/efeitos da radiação , Pulmão/efeitos da radiação , Campos Magnéticos , Músculo Esquelético/efeitos da radiação , Aceleradores de Partículas , Respiração , Suínos
15.
J Radiat Res ; 60(6): 747-758, 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31504707

RESUMO

This study examines the ability of arabinoxylan rice bran (MGN-3/Biobran) to enhance the anti-cancer effects of fractionated X-ray irradiation of Ehrlich solid tumor-bearing mice. Swiss albino mice bearing tumors were exposed to the following: (i) Biobran treatment (40 mg/kg/day, intraperitoneal injections) beginning on day 11 post-tumor cell inoculation until day 30; (ii) ionizing radiation (Rad) 2 Gy at three consecutive doses on days 12, 14 and 16; or (iii) Biobran + Rad. Final tumor weight was suppressed by 46% for Biobran, 31% for Rad and 57% for the combined treatment (Biobran + Rad) relative to control untreated mice. Biobran and Rad also arrested the hypodiploid cells in the sub-G1-phase, signifying apoptosis by +102% and +85%, respectively, while the combined treatment induced apoptosis by +123%, with similar results in the degree of DNA fragmentation. Furthermore, Biobran + Rad upregulated the relative gene expression and protein level of p53 and Bax in tumor cells, down-regulated Bcl-2 expression, and increased the Bax/Bcl-2 ratio and caspase-3 activity, with the combined treatment greater than for either treatment alone. Additionally, the combined treatment modulated the decrease in body weight, the increase in liver and spleen weight, and the elevation of liver enzymes aspartate aminotransferase, alanine aminotransferase and gamma-glutamyl transferase to be within normal values. We conclude that Biobran enhances radiation therapy-induced tumor regression by potentiating apoptosis and minimizing toxicities related to radiation therapy, suggesting that Biobran may be useful in human cancer patients undergoing radiotherapy and warranting clinical trials.


Assuntos
Carcinoma de Ehrlich/tratamento farmacológico , Carcinoma de Ehrlich/radioterapia , Xilanos/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Peso Corporal/efeitos dos fármacos , Peso Corporal/efeitos da radiação , Carcinoma de Ehrlich/genética , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/efeitos da radiação , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Terapia Combinada , Dano ao DNA , Fragmentação do DNA/efeitos dos fármacos , Fragmentação do DNA/efeitos da radiação , Feminino , Regulação da Expressão Gênica , Fígado/efeitos dos fármacos , Fígado/enzimologia , Fígado/patologia , Fígado/efeitos da radiação , Camundongos , Tamanho do Órgão/efeitos dos fármacos , Tamanho do Órgão/efeitos da radiação , Baço/efeitos dos fármacos , Baço/patologia , Baço/efeitos da radiação , Carga Tumoral/efeitos dos fármacos , Carga Tumoral/efeitos da radiação , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Raios X , Xilanos/farmacologia , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo
16.
Cells ; 8(9)2019 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-31489941

RESUMO

Liver damage upon exposure to ionizing radiation, whether accidental or because of therapy can contribute to liver dysfunction. Currently, radiation therapy is used for various cancers including hepatocellular carcinoma; however, the treatment dose is limited by poor liver tolerance to radiation. Furthermore, reliable biomarkers to predict liver damage and associated side-effects are unavailable. Here, we investigated fibrinogen-like 1 (FGL1)-expression in the liver and plasma after radiation exposure. We found that 30 Gy of liver irradiation (IR) induced cell death including apoptosis, necrosis, and autophagy, with fibrotic changes in the liver occurring during the acute and subacute phase in mice. Moreover, FGL1 expression pattern in the liver following IR was associated with liver damage represented by injury-related proteins and oxidative stress markers. We confirmed the association between FGL1 expression and hepatocellular injury by exposing human hepatocytes to radiation. To determine its suitability, as a potential biomarker for radiation-induced liver injury, we measured FGL1 in the liver tissue and the plasma of mice following total body irradiation (TBI) or liver IR. In TBI, FGL1 showed the highest elevation in the liver compared to other major internal organs including the heart, lung, kidney, and intestine. Notably, plasma FGL1 showed good correlation with radiation dose by liver IR. Our data revealed that FGL1 upregulation indicates hepatocellular injury in response to IR. These results suggest that plasma FGL1 may represent a potential biomarker for acute and subacute radiation exposure to the liver.


Assuntos
Fibrinogênio/metabolismo , Cirrose Hepática/sangue , Fígado/efeitos da radiação , Lesões Experimentais por Radiação/sangue , Animais , Apoptose , Autofagia , Biomarcadores/sangue , Células Cultivadas , Hepatócitos/metabolismo , Hepatócitos/efeitos da radiação , Humanos , Fígado/metabolismo , Cirrose Hepática/etiologia , Cirrose Hepática/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Lesões Experimentais por Radiação/patologia , Radiação Ionizante
17.
Radiology ; 293(1): 223-231, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31453767

RESUMO

Background Overall survival (OS) for patients with uveal melanoma (UM) hepatic metastases is extremely poor. Therefore, stabilization of hepatic metastases is essential to prolonging OS. Purpose To assess the safety and effectiveness of radioembolization (RE) for treatment of UM hepatic metastases. Materials and Methods Enrollment for this prospective phase II trial began November 2011 and concluded January 2017. Treatment-naïve participants (group A) and participants who progressed after immunoembolization (group B) with hepatic tumor burden less than 50% underwent RE. Participants were followed for 1 month and every 3 months for acute and delayed toxicities, respectively. MRI, CT, and PET were performed every 3 months to evaluate for tumor response and extrahepatic disease. Participants were followed for at least 2 years or until death. Kaplan-Meier method and multivariable Cox proportional hazard models were used for data analysis. Results In group A, 24 participants (mean age ± standard deviation, 59 years ± 13; 13 men and 11 women) underwent unilobar (n = 7), fractionated whole-liver (n = 1), or sequential lobar (n = 16) RE. One participant was excluded from the trial. Complete response (n = 0), partial response (n = 9), or stable disease (n = 11) was achieved in 20 of 23 (87.0%; 95% confidence interval [CI]: 66.4%, 97.2%) participants. Median progression-free survival from liver metastasis was 8.1 months (95% CI: 6.4, 11.8; range, 3.3-33.7 months). Median OS was 18.5 months (95% CI: 11.3, 23.5; range, 6.5-73.7 months). In group B, 24 participants (mean age, 58 years ± 10; nine men and 15 women) underwent unilobar (n = 5) or sequential lobar (n = 19) RE. Complete response (n = 0), partial response (n = 8), or stable disease (n = 6) was achieved in 14 of 24 (58.3%; 95% CI: 36.3%, 77.9%) participants. Median progression-free survival from liver metastasis was 5.2 months (95% CI: 3.7, 9.8; range, 2.9-22.0 months). Median OS was 19.2 months (95% CI: 11.5, 24.0; range, 4.8-76.6 months). Grade 3 treatment-related toxicities included transient lymphopenia (group A, n = 1; group B, n = 1), pain (group A, n = 2) and nausea or vomiting (group A, n = 1). Conclusion Radioembolization is a promising treatment for patients with uveal melanoma hepatic metastases. © RSNA, 2019 Online supplemental material is available for this article.


Assuntos
Embolização Terapêutica/métodos , Neoplasias Hepáticas/radioterapia , Melanoma/patologia , Segunda Neoplasia Primária/radioterapia , Neoplasias Uveais/patologia , Radioisótopos de Ítrio/uso terapêutico , Diagnóstico por Imagem/métodos , Feminino , Humanos , Fígado/diagnóstico por imagem , Fígado/efeitos da radiação , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Segunda Neoplasia Primária/diagnóstico por imagem , Estudos Prospectivos , Resultado do Tratamento
18.
Phys Med ; 65: 33-39, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31430584

RESUMO

PURPOSE: To quantitatively evaluate and compare the image recognition performance of multiple fiducial markers available in real-time tumor-tracking radiation therapy (RTRT). METHODS: Clinically available markers including sphere shape, coil shape, cylinder shape, line shape, and ball shape (folded line shape) were evaluated in liver and lung models of RTRT. Maximum thickness of the polymethyl metacrylate (PMMA) phantom that could automatically recognize the marker was determined by template-pattern matching. Image registration accuracy of the fiducial marker was determined using liver RTRT model. Lung RTRT was mimicked with an anthropomorphic chest phantom and a one-dimensional motion stage in order to simulate marker motion in heterogeneous fluoroscopic images. The success or failure of marker tracking and image registration accuracy for the lung model were evaluated in the same manner as that for the liver model. RESULTS: All fiducial markers except for line shape and coil shape of thinner diameter were recognized by the PMMA phantom, which is assumed to have the typical thickness of an abdomen, with two-dimensional image registration accuracy of <2 pixels. Three-dimensional calculation error with the use of real-time stereoscopic fluoroscopy in RTRT was thought to be within 1 mm. In the evaluation using the lung model, the fiducial markers were recognized stably with sufficient accuracy for clinical application. The same was true for the evaluation using the liver model. CONCLUSIONS: The image recognition performance of fiducial markers was quantified and compared. The results presented here may be useful for the selection of fiducial markers.


Assuntos
Marcadores Fiduciais , Fluoroscopia , Processamento de Imagem Assistida por Computador , Neoplasias/diagnóstico por imagem , Neoplasias/radioterapia , Radioterapia Guiada por Imagem/normas , Fígado/diagnóstico por imagem , Fígado/efeitos da radiação , Pulmão/diagnóstico por imagem , Pulmão/efeitos da radiação , Imagens de Fantasmas , Polimetil Metacrilato , Fatores de Tempo
19.
Eur J Radiol ; 119: 108626, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31430661

RESUMO

PURPOSE: To investigate the image quality, diagnostic accuracy, and dose reduction potential of a split-bolus protocol(SBP) compared with a multiphasic protocol(MPP) in the detection of recurrent or progressive pancreatic ductal adenocarcinoma(PDAC) or cholangiocarcinoma(CC) using contrast- enhanced computed tomography(CECT). MATERIALS AND METHODS: This prospective study included 56 patients who underwent CECT, 28 with our institutional standard MPP(100 ml contrast bolus) and 28 with a novel SBP(110 ml). Radiation exposure was determined in terms of total dose- length product(DLP) and computed tomography dose index(CTDI). Image quality was measured objectively by analysis of attenuation in Hounsfield units(HU) in regions of interest(ROIs) and subjectively by two blinded readers using a Likert scale. Diagnostic accuracy and interreader variability were tested. RESULTS: The total DLP of the SBP group(498.1 ± 43.7 mGy*cm) was significantly lower than in the MPP group(1,092.5 ± 106.9 mGy*cm; p < 0.001). The SBP showed higher contrast enhancement of all critical anatomical structures including portal vein, liver, and pancreas compared with the MPP, except for the aorta(SBP: 326.9 ± 15.7 HU vs. MPP: 246.7 ± 12.2 HU; p < 0.001). Subjective analysis revealed poorer image quality ratings for important landmarks with the MPP (resection surface: p = 0.624, portal vein: p = 0.395, liver p = 0.361). The two blinded readers correlated significantly. Sensitivity, specificity, positive and negative predictive values (PPV/NPV), and overall interreader variabilities correlated significantly. Furthermore, significantly fewer slices per exam were required for the SBP(1,823 vs. 3,235; p < 0.001). CONCLUSION: The SBP provides the same image quality and diagnostic accuracy as an MPP while significantly lowering radiation exposure in CT follow-up of PDAC or CC.


Assuntos
Neoplasias dos Ductos Biliares/diagnóstico por imagem , Carcinoma Ductal Pancreático/diagnóstico por imagem , Colangiocarcinoma/diagnóstico por imagem , Meios de Contraste/administração & dosagem , Neoplasias Pancreáticas/diagnóstico por imagem , Idoso , Ductos Biliares/diagnóstico por imagem , Ductos Biliares/efeitos da radiação , Protocolos Clínicos , Feminino , Humanos , Iohexol/administração & dosagem , Iohexol/análogos & derivados , Iopamidol/administração & dosagem , Iopamidol/análogos & derivados , Fígado/diagnóstico por imagem , Fígado/efeitos da radiação , Masculino , Tomografia Computadorizada Multidetectores/métodos , Recidiva Local de Neoplasia/diagnóstico por imagem , Pâncreas/diagnóstico por imagem , Pâncreas/efeitos da radiação , Veia Porta/diagnóstico por imagem , Veia Porta/efeitos da radiação , Estudos Prospectivos , Doses de Radiação , Exposição à Radiação , Sensibilidade e Especificidade
20.
Cancer Radiother ; 23(6-7): 636-650, 2019 Oct.
Artigo em Francês | MEDLINE | ID: mdl-31444078

RESUMO

Liver stereotactic body radiotherapy is a developing technique for the treatment of primary tumours and metastases. Its implementation is complex because of the particularities of the treated organ and the comorbidities of the patients. However, this technique is a treatment opportunity for patients otherwise in therapeutic impasse. The scientific evidence of liver stereotactic body radiotherapy has been considered by the French health authority as insufficient for its widespread use outside specialized and experienced centers, despite a growing and important number of retrospective and prospective studies, but few comparative data. This article focuses on the specific features of stereotactic body radiotherapy for liver treatments and the results of published studies of liver stereotactic body radiotherapy performed with classic linear accelerators and dedicated radiosurgery units.


Assuntos
Carcinoma Hepatocelular/radioterapia , Neoplasias Hepáticas/radioterapia , Radiocirurgia/instrumentação , Carcinoma Hepatocelular/diagnóstico por imagem , Humanos , Fígado/efeitos da radiação , Cirrose Hepática/complicações , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/secundário , Movimentos dos Órgãos , Aceleradores de Partículas , Guias de Prática Clínica como Assunto , Tolerância a Radiação , Radiocirurgia/métodos , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia Guiada por Imagem/métodos , Respiração , Resultado do Tratamento
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