RESUMO
In studies of electron and proton radiotherapy, ultrahigh dose rates of FLASH radiotherapy appear to produce fewer toxicities than standard dose rates while maintaining local tumor control. FLASH-proton radiotherapy (F-PRT) brings the spatial advantages of PRT to FLASH dose rates (>40 Gy/second), making it important to understand if and how F-PRT spares normal tissues while providing antitumor efficacy that is equivalent to standard-proton radiotherapy (S-PRT). Here we studied PRT damage to skin and mesenchymal tissues of muscle and bone and found that F-PRT of the C57BL/6 murine hind leg produced fewer severe toxicities leading to death or requiring euthanasia than S-PRT of the same dose. RNA-seq analyses of murine skin and bone revealed pathways upregulated by S-PRT yet unaltered by F-PRT, such as apoptosis signaling and keratinocyte differentiation in skin, as well as osteoclast differentiation and chondrocyte development in bone. Corroborating these findings, F-PRT reduced skin injury, stem cell depletion, and inflammation, mitigated late effects including lymphedema, and decreased histopathologically detected myofiber atrophy, bone resorption, hair follicle atrophy, and epidermal hyperplasia. F-PRT was equipotent to S-PRT in control of two murine sarcoma models, including at an orthotopic intramuscular site, thereby establishing its relevance to mesenchymal cancers. Finally, S-PRT produced greater increases in TGFß1 in murine skin and the skin of canines enrolled in a phase I study of F-PRT versus S-PRT. Collectively, these data provide novel insights into F-PRT-mediated tissue sparing and support its ongoing investigation in applications that would benefit from this sparing of skin and mesenchymal tissues. SIGNIFICANCE: These findings will spur investigation of FLASH radiotherapy in sarcoma and additional cancers where mesenchymal tissues are at risk, including head and neck cancer, breast cancer, and pelvic malignancies.
Assuntos
Epitélio , Tratamentos com Preservação do Órgão , Terapia com Prótons , Sarcoma/patologia , Sarcoma/radioterapia , Animais , Osso e Ossos/patologia , Osso e Ossos/efeitos da radiação , Modelos Animais de Doenças , Cães , Epitélio/efeitos da radiação , Feminino , Perfilação da Expressão Gênica , Humanos , Camundongos , Morbidade , Músculos/patologia , Músculos/efeitos da radiação , Tratamentos com Preservação do Órgão/métodos , Terapia com Prótons/efeitos adversos , Terapia com Prótons/métodos , Lesões por Radiação/diagnóstico , Lesões por Radiação/etiologia , Dosagem Radioterapêutica , Sarcoma/metabolismo , Pele/efeitos da radiação , Resultado do TratamentoRESUMO
Hereditary DNA repair defects affect tissues differently, suggesting that in vivo cells respond differently to DNA damage. Knowledge of the DNA damage response, however, is largely based on in vitro and cell culture studies, and it is currently unclear whether DNA repair changes depending on the cell type. Here, we use in vivo imaging of the nucleotide excision repair (NER) endonuclease ERCC-1/XPF-1 in C. elegans to demonstrate tissue-specific NER activity. In oocytes, XPF-1 functions as part of global genome NER (GG-NER) to ensure extremely rapid removal of DNA-helix-distorting lesions throughout the genome. In contrast, in post-mitotic neurons and muscles, XPF-1 participates in NER of transcribed genes only. Strikingly, muscle cells appear more resistant to the effects of DNA damage than neurons. These results suggest a tissue-specific organization of the DNA damage response and may help to better understand pleiotropic and tissue-specific consequences of accumulating DNA damage.
Assuntos
Proteínas de Caenorhabditis elegans/metabolismo , DNA Helicases/metabolismo , Reparo do DNA , Proteínas de Ligação a DNA/metabolismo , Endonucleases/metabolismo , Animais , Caenorhabditis elegans , Feminino , Músculos/metabolismo , Músculos/efeitos da radiação , Neurônios/metabolismo , Neurônios/efeitos da radiação , Oócitos/metabolismo , Oócitos/efeitos da radiação , Especificidade de Órgãos , Raios UltravioletaRESUMO
Photobiomodulation therapy (PBMT) has been used to improve the physical performance of individuals with advanced age; however, there are no studies in the literature that support the application of light-emitting diode (LED) therapy for the muscular performance of individuals with diabetes mellitus who show a decline in functionality. The aim of the study was to analyze the acute effects of PBMT on strength and functional performance in type 2 diabetic individuals. Sixty-three volunteers were recruited and randomized into five groups: control (C), sham (S), red LED (R), infrared LED (IR), and red LED + infrared LED (R + IR). On the first day, the volunteers were evaluated using the time up and go (TUG), the 6-min walk test (6MWT), and isokinetic dynamometer of the ankle. In the following 3 days, groups R, IR, R + IR, and S returned for application of PBMT bilaterally, with 180 J of energy on each leg. On the fifth day, a reassessment was performed. There was no statistical difference between groups for the variables of the isokinetic dynamometer, TUG, and 6MWT. Analysis of the size of the clinical effect for the isokinetic variables showed that there was no pattern among the effects observed. There is a moderate effect in favor of R, IR, and R + IR in relation to C for the TUG and a moderate effect of R + IR in relation to C for the 6MWT. The PBMT applied for a short period does not bring important gains for the muscular performance and functionality of diabetic individuals.
Assuntos
Diabetes Mellitus/fisiopatologia , Diabetes Mellitus/radioterapia , Terapia com Luz de Baixa Intensidade , Músculos/fisiopatologia , Feminino , Humanos , Masculino , Músculos/efeitos da radiação , Teste de CaminhadaRESUMO
PURPOSE: To assess post-treatment subcutaneous edema, muscle edema, and seroma in MRI after soft-tissue sarcoma (STS) resection with regard to muscle involvement of STS and therapy. METHODS: In all, 177 patients were included and received 1.5-T MRI follow-up examinations after treatment. Post-treatment changes were classified according to type of therapy (therapy 1-surgery; therapy 2-surgery with radiation therapy) and primary tumor localization in soft tissue (localization 1, subcutaneous tissue; localization 2, muscle involvement). Subcutaneous and muscle edema were divided into three grades: grade 0, absence of edema; grade 1, low-to-moderate edema; and grade 2, high-grade edema. RESULTS: The mean age of the patients was 55.7 ± 18.2 years and the mean volume of the resected primary STS was 321.5 cm3. After therapy 1 of a sarcoma in localization 1, patients significantly more often showed low-grade subcutaneous tissue edema and an absence of muscle edema (p < 0.001) than high-grade edema. The risk for grade 2 subcutaneous tissue and muscle edema significantly increased with a tumor in localization 2 (RR = 2.58, p = 0.016 and RR = 15, p = 0.0065/RR = 2.05 , p = 0.021, respectively) and after therapy 2 (RR = 15, p = 0.0087 and RR = 2.05, p < 0.0001, respectively). Of the patients with sarcoma in localization 2, 88% developed grade 2 muscle edema after therapy 2; 40% of the patients developed post-treatment seroma. The risk for seroma is significantly higher after surgery and radiation therapy than after surgery alone (p < 0.001). CONCLUSION: High-grade postoperative subcutaneous and muscle edema are significantly associated with muscle involvement of primary STS both in patients with and without radiation therapy. The risk for seroma is significantly higher after surgery with additional radiation therapy than after surgery alone.
Assuntos
Edema/complicações , Músculos/efeitos dos fármacos , Músculos/efeitos da radiação , Complicações Pós-Operatórias/epidemiologia , Radioterapia/efeitos adversos , Seroma/complicações , Adulto , Idoso , Edema/diagnóstico por imagem , Feminino , Alemanha/epidemiologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Radioterapia/estatística & dados numéricos , Fatores de Risco , Sarcoma/patologia , Sarcoma/radioterapia , Sarcoma/cirurgia , Seroma/diagnóstico por imagem , Seroma/epidemiologia , Índice de Gravidade de Doença , Neoplasias de Tecidos Moles/patologia , Neoplasias de Tecidos Moles/radioterapia , Neoplasias de Tecidos Moles/cirurgiaRESUMO
Linac calibration is done in water, but patients are comprised primarily of soft tissue. Conceptually, and specified in NRG/RTOG trials, dose should be reported as dose-to-muscle to describe the dose to the patient. Historically, the dose-to-water of the linac calibration was often converted to dose-to-muscle for patient calculations through manual application of a 0.99 dose-to-water to dose-to-muscle correction factor, applied during the linac clinical reference calibration. However, many current treatment planning system (TPS) dose calculation algorithms approximately provide dose-to-muscle (tissue), making application of a manual scaling unnecessary. There is little guidance on when application of a scaling factor is appropriate, resulting in highly inconsistent application of this scaling by the community. In this report we provide guidance on the steps necessary to go from the linac absorbed dose-to-water calibration to dose-to-muscle in patient, for various commercial TPS algorithms. If the TPS does not account for the difference between dose-to-water and dose-to-muscle, then TPS reference dose scaling is warranted. We have tabulated the major vendors' TPS in terms of whether they approximate dose-to-muscle or calculate dose-to-water and recommend the correction factor required to report dose-to-muscle directly from the TPS algorithm. Physicists should use this report to determine the applicable correction required for specifying the reference dose in their TPS to achieve this goal and should remain attentive to possible changes to their dose calculation algorithm in the future.
Assuntos
Músculos/efeitos da radiação , Doses de Radiação , Planejamento da Radioterapia Assistida por Computador/normas , Sociedades Científicas , Água , Elétrons/uso terapêutico , Humanos , Fótons/uso terapêutico , Dosagem Radioterapêutica , Padrões de ReferênciaRESUMO
Contamination of the environment after the Chernobyl and Fukushima Daiichi nuclear power plant (NPP) disasters led to the exposure of a large number of humans and wild animals to radioactive substances. However, the sub-lethal consequences induced by these absorbed radiological doses remain understudied and the long-term biological impacts largely unknown. We assessed the biological effects of chronic exposure to ionizing radiation (IR) on embryonic development by exposing zebrafish embryo from fertilization and up to 120 hours post-fertilization (hpf) at dose rates of 0.5 mGy/h, 5 mGy/h and 50 mGy/h, thereby encompassing the field of low dose rates defined at 6 mGy/h. Chronic exposure to IR altered larval behaviour in a light-dark locomotor test and affected cardiac activity at a dose rate as low as 0.5 mGy/h. The multi-omics analysis of transcriptome, proteome and transcription factor binding sites in the promoters of the deregulated genes, collectively points towards perturbations of neurogenesis, muscle development, and retinoic acid (RA) signaling after chronic exposure to IR. Whole-mount RNA in situ hybridization confirmed the impaired expression of the transcription factors her4.4 in the central nervous system and myogenin in the developing muscles of exposed embryos. At the organ level, the assessment of muscle histology by transmission electron microscopy (TEM) demonstrated myofibers disruption and altered neuromuscular junctions in exposed larvae at 5 mGy/h and 50 mGy/h. The integration of these multi-level data demonstrates that chronic exposure to low dose rates of IR has an impact on neuronal and muscle progenitor cells, that could lead to motility defects in free swimming larvae at 120 hpf. The mechanistic understanding of these effects allows us to propose a model where deregulation of RA signaling by chronic exposure to IR has pleiotropic effects on neurogenesis and muscle development.
Assuntos
Desenvolvimento Embrionário/efeitos da radiação , Desenvolvimento Muscular/efeitos da radiação , Músculos/efeitos da radiação , Sistema Nervoso/efeitos da radiação , Radiação Ionizante , Biologia de Sistemas/métodos , Animais , Antineoplásicos/farmacologia , Desenvolvimento Embrionário/efeitos dos fármacos , Desenvolvimento Embrionário/genética , Larva/efeitos dos fármacos , Larva/genética , Larva/efeitos da radiação , Desenvolvimento Muscular/efeitos dos fármacos , Desenvolvimento Muscular/genética , Músculos/efeitos dos fármacos , Músculos/embriologia , Sistema Nervoso/efeitos dos fármacos , Sistema Nervoso/embriologia , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Transcriptoma/efeitos dos fármacos , Transcriptoma/efeitos da radiação , Tretinoína/farmacologia , Peixe-Zebra/embriologia , Peixe-Zebra/genética , Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismoRESUMO
Preoperative radiation is associated with an increased risk of wound complications. However, the influences of radiation on musculofascial wound healing remains unclear. The purpose of the study was to investigate the short-term effects of preoperative local radiation on the musculofascial healing of laparotomy incisions in a rat model. Eighteen Fischer 344 rats received radiation doses of 0, 10, or 20 Gy to the abdominal wall and underwent laparotomy 4 weeks later. Two weeks after laparotomy, samples of irradiated muscle were harvested for mechanical tests, histological (Hematoxylin & Eosin, and Masson's Trichrome) and immunohistochemical analyses using KI67, CD31, TGF-ß, and MYOD1 antibodies. The elastic modulus (EM), maximum strain (MS), and ultimate tensile strength (UTS) in the 20-Gy group were significantly weaker than those in the 0-Gy group. The EM and UTS in the 20-Gy group were significantly lower than those in the 10-Gy group. The UTS and MS in the 10-Gy group were significantly lower than those in the 0-Gy group. The mean number of inflammatory cells per mm2 in the 20-Gy group was significantly larger than those in the 10- and 0-Gy groups. The mean numbers of CD31-, KI67-, and MYOD1-positive cells, the optical density of TGF-ß, and the microvessel density in the 20-Gy group were significantly smaller than those in the 10- and 0-Gy groups. These results indicated that radiation delays musculofascial healing and decreases mechanical strength of the laparotomy incision by creating a chronic inflammatory environment, inhibiting cell proliferation, angiogenesis, granulation maturation, collagen deposition, and muscular regeneration in a dose-dependent manner. The impaired biomechanical, histological and molecular properties may be associated with the higher risk of wound complications in patients who undergo radiotherapy prior to laparotomy.
Assuntos
Fáscia/patologia , Fáscia/efeitos da radiação , Laparotomia , Músculos/patologia , Músculos/efeitos da radiação , Radiação , Cicatrização/efeitos da radiação , Animais , Modelos Animais de Doenças , Antígeno Ki-67/metabolismo , Masculino , Proteína MyoD/metabolismo , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Ratos Endogâmicos F344 , Fatores de Tempo , Aderências Teciduais/patologia , Fator de Crescimento Transformador beta/metabolismoRESUMO
Ultrasound tissue characterization based on the coefficient of nonlinearity, ßn = 1 + B/2A, has been demonstrated to produce added diagnostic value due to its large variation and sensitivity to tissue structure. However, the parameter has been observed to be significantly correlated to the speed of sound and density. These relationships are analyzed empirically as well as theoretically by developing a pressure-density relation based on a thermodynamic model and the Mie intermolecular potential. The results indicate that for many soft tissues, the coefficient of nonlinearity is largely determined by the isentropic compressibility, κs. Consequently, for tissue characterization, estimating the nonlinear response of the medium, given by ßp = ßnκs, appears to be beneficial due to correlated quantities.
Assuntos
Tecido Adiposo/efeitos da radiação , Encéfalo/efeitos da radiação , Rim/efeitos da radiação , Fígado/efeitos da radiação , Modelos Teóricos , Músculos/efeitos da radiação , Ondas Ultrassônicas , Tecido Adiposo/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Humanos , Rim/diagnóstico por imagem , Fígado/diagnóstico por imagem , Músculos/diagnóstico por imagem , Especificidade de Órgãos , Termodinâmica , Ultrassom/métodos , Ultrassonografia/métodosRESUMO
The knowledge of frequency and temperature dependent dielectric properties of tissue is essential to develop ultra-wideband diagnostic technologies, such as a non-invasive temperature monitoring system during hyperthermia treatment. To this end, we characterized the dielectric properties of animal liver, muscle, fat and blood in the microwave frequency range from 0.5 GHz to 7 GHz and in the temperature range between 30 °C and 50 °C. The measured data were modeled to a two-pole Cole-Cole model and a second-order polynomial was introduced to fit the Cole-Cole parameters as a function of temperature. The parametric model provides access to the dielectric properties of tissue at any frequency and temperature in the specified range.
Assuntos
Sangue/efeitos da radiação , Espectroscopia Dielétrica , Micro-Ondas , Temperatura , Algoritmos , Animais , Impedância Elétrica , Gorduras/efeitos da radiação , Humanos , Fígado/fisiologia , Fígado/efeitos da radiação , Modelos Biológicos , Músculos/fisiologia , Músculos/efeitos da radiação , SuínosRESUMO
A new methodology has been proposed to measure optical properties of homogeneous tissue where a laser beam is used to induce heat to a tissue. The induced heat increased the temperature inside the tissue, which is detected by a thermocouple. These readings are compared with that obtained from the solution of the finite element solution that used iterative values of optical properties in determining temperature distribution. The two temperature distributions are used to determine tissue optical properties using the Levenberg-Marquardt iteration. An accurate result is obtained in determining absorption coefficient and reduced scattering coefficient. The work is extended to obtain three parameters (i.e., absorption coefficient, scattering coefficient, and anisotropy). The only limitation is that the temperature readings have to be measured with a high-accuracy thermocouple (i.e., less than 0.4% of maximum-recorded temperature).
Assuntos
Temperatura Alta , Lasers , Músculos/efeitos da radiação , Fenômenos Ópticos , Retina/efeitos da radiação , Animais , Anisotropia , BovinosRESUMO
The aim of the present study was to synthesize mixture solutions which can accurately mimic the dielectric properties of biological tissues, specifically muscle and adipose tissues between 500 MHz and 50 GHz. Mixtures utilizing concentrations of bovine serum albumin (BSA) dissolved in phosphate buffered saline (PBS) and Ringer's solutions were synthesized to mimic in vivo and ex vivo muscle tissues. Solutions consisting of concentrations of peanut oil and Triton X-100 (TX) in PBS and Ringer's solutions were also synthesized to mimic in vivo and ex vivo adipose tissue. Results were then analysed and compared to measured dielectric properties of in vivo and ex vivo biological tissues from another previous study. Good agreement with said dielectric property measurements were obtained since the solutions from this study yielded low RMSE and RMSRE values. This implied that such solutions can be utilized in the construction of human body phantoms for narrowband and ultra-wideband microwave devices for near field breast cancer imaging.
Assuntos
Tecido Adiposo/citologia , Impedância Elétrica , Micro-Ondas , Imagem Molecular/métodos , Músculos/citologia , Imagens de Fantasmas , Tecido Adiposo/efeitos da radiação , Humanos , Músculos/efeitos da radiaçãoRESUMO
It is important to confirm the dose distribution and its biophysiological response in patients subjected to carbon-ion radiotherapy (CIRT) by using medical imaging methods. In this study, the correlation between the signal intensity changes of muscles observed in magnetic resonance imaging (MRI) after CIRT and planned dose distribution was evaluated. Seven patients were arbitrarily selected from among localized prostate cancer patients on whom CIRT was performed in our facilities in 2010. All subjects received the same dose of CIRT, namely, 57.6 Gy relative biological effectiveness (RBE) in 16 fractions. The following two types of images were acquired for each subject: planning computed tomography (CT) images overlaying the dose distribution of CIRT and MRI T2-weighted images (T2WI) taken 1 year after CIRT. The fusion image of the planning CT and MRI images was registered by using a treatment-planning system, and the CIRT dose distribution was compared with changes observed in the MRI of the obturator internus muscles located near the prostate. The signal changes in the axial image passing through the isocenter of the planning target volume were digitized, and a scatter diagram was created showing the relationship between the radiation dose and digitized signal changes. A strong correlation between the radiation dose and the MRI signal intensity changes was observed, and a quadratic function was found to have the best fit. However, estimating the dose distribution from the normalized MRI signal intensity is difficult at this point, owing to the wide variation. Therefore, further investigation is required.
Assuntos
Radioterapia com Íons Pesados , Imageamento por Ressonância Magnética , Músculos/efeitos da radiação , Neoplasias da Próstata/radioterapia , Relação Dose-Resposta à Radiação , Humanos , Masculino , Próstata/diagnóstico por imagem , Próstata/patologia , Próstata/efeitos da radiação , Neoplasias da Próstata/diagnóstico por imagem , Tomografia Computadorizada por Raios XRESUMO
Coaxial sensors are effective for measurement of dielectric properties of biological tissues. Several measurement methods used to derive dielectric properties have been investigated for the measurement with a coaxial sensor at microwave frequencies. While the measurement accuracy depends on the method used, there has been insufficient intercomparison of these methods and their model approximation errors. On the other hand, we have developed a coaxial sensor for the measurement of complex permittivity at millimeter-wave (MMW) frequencies of up to 100 GHz. However, the scarcity of reference data at MMW frequencies makes the validation of the measurement system difficult. Thus, it is essential to clarify the model approximation error of the method used in the measurement system, particularly at MMW frequencies. This study aims to clarify the model approximation errors of methods for dielectric property measurement using a coaxial sensor at MMW frequencies. The model approximation errors were assessed by comparing results obtained by the methods with those based on the theoretical formula of the full-wave modal expression of Maxwell's equations. The measurement uncertainty for the theoretical formula was estimated for a standard liquid sample to clarify the contribution of the model approximation errors to the uncertainty. Furthermore, the methods were applied to the measurement of porcine tissues at body temperature, and the measurement accuracy and usability for measurement at MMW frequencies are discussed.
Assuntos
Impedância Elétrica , Campos Eletromagnéticos/efeitos adversos , Modelos Teóricos , Músculos/efeitos da radiação , Gordura Subcutânea/efeitos da radiação , Animais , Temperatura Corporal , Modelos Biológicos , SuínosRESUMO
Triple negative breast cancer (TNBC) is the most lethal one for all types of breast cancer. Though radiotherapy is an efficient treatment, long-term survival rate of TNBC patients is still suboptimal. Hyprofractionated radiotherapy, an improved radiotherapy, has made an inspiring result in clinic. However, the mechanism underlying TNBC treated with hyprofractionated radiotherapy is not clear. Decorin (DCN) is a small poteoglycan of matrix which has an inhibitory effect on the breast cancer and is secreted by muscle under certain conditions. In this study, we demonstrated that peritumoral muscles secrete more DCN at higher dose irradiation than that at conventional irradiation dose in TNBC tumor-bearing mice. Thus, it indicates that DCN secreted from peritumoral muscle may be one of the reasons why hyprofractionated radiotherapy could inhibit the growth of TNBC more effectively. Moreover, we also indicated that the up-regulated DCN attenuated lung metastasis of TNBC. In conclusion, we demonstrated that hypofractionated radiation promotes the secretion of DCN in peritumoral muscle, thus enhancing the inhibitory effect on TNBC, which might help to optimize the strategy of radiotherapy for TNBC patients in the future.
Assuntos
Decorina/metabolismo , Músculos/efeitos da radiação , Hipofracionamento da Dose de Radiação , Neoplasias de Mama Triplo Negativas/radioterapia , Ensaios Antitumorais Modelo de Xenoenxerto , Animais , Apoptose/genética , Apoptose/efeitos da radiação , Linhagem Celular Tumoral , Decorina/genética , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Músculos/metabolismo , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia , Carga Tumoral/genética , Carga Tumoral/efeitos da radiaçãoRESUMO
High-intensity focused ultrasound (HIFU) under magnetic resonance imaging (MRI) guidance can achieve a noninvasive and precise ablation of the solid tumor. In the study, an MRI-compatible 1-MHz 16-channel ring-shaped transducer was developed to minimize the burn risk of breast skin and perform volumetric ablation for short treatment time. The measured electroacoustic conversion efficiency of the transducer was 50.90% ± 5. The transducer could produce a point and a quasi-hollow-cylinder lesion in a thermal-sensitive phantom or an ex vivo pork by tuning the phase of each element. It may achieve volumetric ablation of 1.5 cm3 when the point lesion is located inside the hollow lesion. Ex vivo ablation experiments showed that the transducer could cause a coagulative necrosis in the pork from the surrounded subcutaneous fat by 5 mm without fat damage. The temperature and region of the pork ablation were quantified by MRI technique. There was no MRI interference from HIFU and vice versa while both systems operated concurrently.
Assuntos
Ablação por Ultrassom Focalizado de Alta Intensidade/métodos , Imageamento por Ressonância Magnética/instrumentação , Neoplasias , Tecido Adiposo/diagnóstico por imagem , Tecido Adiposo/efeitos da radiação , Animais , Desenho de Equipamento , Ablação por Ultrassom Focalizado de Alta Intensidade/efeitos adversos , Imageamento por Ressonância Magnética/métodos , Músculos/diagnóstico por imagem , Músculos/efeitos da radiação , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Imagens de Fantasmas , Suínos , TransdutoresRESUMO
Macrophages play a very important role in the conduction of several regenerative processes mainly due to their plasticity and multiple functions. In the muscle repair process, while M1 macrophages regulate the inflammatory and proliferative phases, M2 (anti-inflammatory) macrophages direct the differentiation and remodelling phases, leading to tissue regeneration. The aim of this study was to evaluate the effect of red and near infrared (NIR) photobiomodulation (PBM) on macrophage phenotypes and correlate these findings with the repair process following acute muscle injury. Wistar rats were divided into 4 groups: control; muscle injury; muscle injury + red PBM; and muscle injury + NIR PBM. After 2, 4 and 7 days, the tibialis anterior muscle was processed for analysis. Macrophages phenotypic profile was evaluated by immunohistochemistry and correlated with the different stages of the skeletal muscle repair by the qualitative and quantitative morphological analysis as well as by the evaluation of IL-6, TNF-α and TGF-ß mRNA expression. Photobiomodulation at both wavelengths was able to decrease the number of CD68+ (M1) macrophages 2 days after muscle injury and increase the number of CD163+ (M2) macrophages 7 days after injury. However, only NIR treatment was able to increase the number of CD206+ M2 macrophages (Day 2) and TGF-ß mRNA expression (Day 2, 4 and 7), favouring the repair process more expressivelly. Treatment with PBM was able to modulate the inflammation phase, optimize the transition from the inflammatory to the regeneration phase (mainly with NIR light) and improve the final step of regeneration, enhancing tissue repair.
Assuntos
Terapia com Luz de Baixa Intensidade , Desenvolvimento Muscular/efeitos da radiação , Músculos/efeitos da radiação , Regeneração/efeitos da radiação , Animais , Antígenos CD/genética , Antígenos de Diferenciação Mielomonocítica/genética , Diferenciação Celular/efeitos da radiação , Humanos , Macrófagos/patologia , Macrófagos/efeitos da radiação , Músculo Esquelético/crescimento & desenvolvimento , Músculo Esquelético/lesões , Músculo Esquelético/efeitos da radiação , Músculos/lesões , Músculos/patologia , Ratos , Receptores de Superfície Celular/genética , Cicatrização/fisiologia , Cicatrização/efeitos da radiaçãoRESUMO
Tendons are mechanosensitive tissues that connect and transmit the forces generated by muscles to bones by allowing the conversion of mechanical input into biochemical signals. These physical forces perform the fundamental work of preserving tendon homeostasis assuring body movements. However, overloading causes tissue injuries, which leads us to the field of tendon regeneration. Recently published reviews have broadly shown the use of biomaterials and different strategies to attain tendon regeneration. In this review, our focus is the use of magnetic fields as an alternative therapy, which has demonstrated clinical relevance in tendon medicine because of their ability to modulate cell fate. Yet the underlying cellular and molecular mechanisms still need to be elucidated. While providing a brief outlook about specific signalling pathways and intracellular messengers as framework in play by tendon cells, application of magnetic fields as a subcategory of physical forces is explored, opening up a compelling avenue to enhance tendon regeneration. We outline here useful insights on the effects of magnetic fields both at in vitro and in vivo levels, particularly on the expression of tendon genes and inflammatory cytokines, ultimately involved in tendon regeneration. Subsequently, the potential of using magnetically responsive biomaterials in tendon tissue engineering is highlighted and future directions in magnetotherapy are discussed.
Assuntos
Campos Magnéticos , Traumatismos dos Tendões/terapia , Tendões/efeitos da radiação , Engenharia Tecidual , Animais , Diferenciação Celular/efeitos da radiação , Homeostase , Humanos , Músculos/efeitos da radiação , Regeneração/efeitos da radiação , Traumatismos dos Tendões/fisiopatologia , Tendões/crescimento & desenvolvimento , Cicatrização/efeitos da radiaçãoRESUMO
BACKGROUND: Muscle abnormalities such as low muscle mass and low muscle radiodensity are well known risk factors for unfavourable cancer prognosis. However, little is known in regard to the degree and impact of longitudinal changes in muscle mass and radiodensity within the context of cancer. Here, we explore the relationship between muscle wasting and mortality in a large population-based study of patients with non-metastatic colorectal cancer (CRC). METHODS: A total of 1924 patients with stage I-III CRC who underwent surgical resection in the Kaiser Permanente Northern California Health System were included. Muscle mass and radiodensity were quantified using computed tomography images obtained at diagnosis and after approximately 14 months. Cox proportional-hazards models were used to estimate hazard ratios for all-cause mortality. RESULTS: The hazard ratio for all-cause mortality among patients with the largest deterioration in muscle mass (≥2 SD; ≥11.4% loss from baseline), as compared with those who remained stable (±1 SD; 0.0 ± 5.7%) was 2.15 [95% confidence interval (CI): 1.59-2.92; P < 0.001]. The hazard ratio for all-cause mortality among patients who experienced the largest deterioration in muscle radiodensity (≥2 SD; ≥20.2% loss from baseline), as compared with those who remained stable (±1 SD; 0.0 ± 10.1%) was 1.61 (95% CI: 1.20-2.15; P = 0.002). CONCLUSIONS: In patients with stage I-III CRC, muscle wasting is a risk factor for mortality, independent of change in body mass and other body composition parameters.
Assuntos
Neoplasias Colorretais/epidemiologia , Músculos/metabolismo , Músculos/efeitos da radiação , Tolerância a Radiação , Adiposidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Composição Corporal , California/epidemiologia , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Neoplasias Colorretais/radioterapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Vigilância em Saúde Pública , Tomografia Computadorizada por Raios X , Adulto JovemRESUMO
The aim of this study was to determine whether oxidative stress markers are influenced by low-intensity laser therapy (LLLT) in rats subjected to a high-intensity resistive exercise session (RE). Female Wistar rats divided into three experimental groups (Ctr: control, 4J: LLLT, and RE) and subdivided based on the sampling times (instantly or 24 h postexercise) underwent irradiation with LLLT using three-point transcutaneous method on the hind legs, which was applied to the gastrocnemius muscle at the distal, medial, and proximal points. Laser (4J) or placebo (device off) were carried out 60 sec prior to RE that consisted of four climbs bearing the maximum load with a 2 min time interval between each climb. Lipoperoxidation levels and antioxidant capacity were obtained in muscle. Lipoperoxidation levels were increased (4-HNE and CL markers) instantly post-RE. LLLT prior to RE avoided the increase of the lipid peroxidation levels. Similar results were also notified for oxidation protein assays. The GPx and FRAP activities did not reduce instantly or 24 h after RE. SOD increased 24 h after RE, while CAT activity did not change with RE or LLLT. In conclusion, LLLT prior to RE reduced the oxidative stress markers, as well as, avoided reduction, and still increased the antioxidant capacity.
Assuntos
Terapia com Luz de Baixa Intensidade , Estresse Oxidativo/efeitos da radiação , Condicionamento Físico Animal , Animais , Feminino , Peroxidação de Lipídeos/efeitos da radiação , Músculos/enzimologia , Músculos/patologia , Músculos/efeitos da radiação , Ratos WistarRESUMO
PURPOSE: To investigate the potential of texture analysis applied on T2-w and postcontrast T1-w images acquired before radiotherapy for prostate cancer (PCa) and 12 months after its completion in quantitatively characterizing local radiation effect on the muscular component of internal obturators, as organs potentially involved in urinary toxicity. METHODS: T2-w and postcontrast T1-w MR images were acquired at 1.5 T before treatment (MRI1) and at 12 months of follow-up (MRI2) in 13 patients treated with radiotherapy for PCa. Right and left internal obturator muscle contours were manually delineated upon MRI1 and then automatically propagated on MRI2 by an elastic registration method. Planning CT images were coregistered to both MRIs and dose maps were deformed accordingly. A high-dose region receiving >55 Gy and a low-dose region receiving <55 Gy were identified in each muscle volume. Eighteen textural features were extracted from each region of interest and differences between MRI1 and MRI2 were evaluated. RESULTS: A signal increase was highlighted in both T2-w and T1-w images in the portion of the obturators near the prostate, i.e., in the region receiving medium-high doses. A change in the spatial organization was identified, as an increase in homogeneity and a decrease in contrast and complexity, compatible with an inflammatory status. In particular, the region receiving medium-high doses presented more significant or, at least, stronger differences. CONCLUSIONS: Texture analysis applied on T1-w and T2-w MR images has demonstrated its ability in quantitative evaluating radiation-induced changes in obturator muscles after PCa radiotherapy.