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1.
Int J Mol Sci ; 22(21)2021 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-34768958

RESUMO

The development of new laser-driven electron linear accelerators, providing unique ultrashort pulsed electron beams (UPEBs) with low repetition rates, opens new opportunities for radiotherapy and new fronts for radiobiological research in general. Considering the growing interest in the application of UPEBs in radiation biology and medicine, the aim of this study was to reveal the changes in immune system in response to low-energy laser-driven UPEB whole-body irradiation in rodents. Forty male albino Wistar rats were exposed to laser-driven UPEB irradiation, after which different immunological parameters were studied on the 1st, 3rd, 7th, 14th, and 28th day after irradiation. According to the results, this type of irradiation induces alterations in the rat immune system, particularly by increasing the production of pro- and anti-inflammatory cytokines and elevating the DNA damage rate. Moreover, such an immune response reaches its maximal levels on the third day after laser-driven UPEB whole-body irradiation, showing partial recovery on subsequent days with a total recovery on the 28th day. The results of this study provide valuable insight into the effect of laser-driven UPEB whole-body irradiation on the immune system of the animals and support further animal experiments on the role of this novel type of irradiation.


Assuntos
Elétrons/efeitos adversos , Imunidade/efeitos da radiação , Irradiação Corporal Total/efeitos adversos , Animais , Medula Óssea/imunologia , Medula Óssea/patologia , Medula Óssea/efeitos da radiação , Citocinas/biossíntese , Dano ao DNA , Reparo do DNA/efeitos da radiação , Lasers/efeitos adversos , Leucócitos/imunologia , Leucócitos/patologia , Leucócitos/efeitos da radiação , Masculino , Aceleradores de Partículas , Radiobiologia , Ratos , Ratos Wistar
2.
Clin. transl. oncol. (Print) ; 23(9): 1934-1941, sept. 2021. ilus
Artigo em Inglês | IBECS | ID: ibc-222192

RESUMO

Background Pelvic recurrences from previously irradiated gynecological cancer lack solid evidence for recommendation on salvage. Methods A total of 58 patients were included in this clinical analysis. Salvage surgery was performed for locoregional relapse within previously irradiated pelvic area after initial surgery and adjuvant radiotherapy or radical external beam radiotherapy. The primary tumor diagnosis included cervical cancer (n = 47, 81%), uterine cancer (n = 4, 7%), and other types (n = 7, 12%). Thirty-three patients received adjuvant IOERT (1984–2000) at a median dose of 15 Gy (range 10–20 Gy) and 25 patients received adjuvant PHDRB (2001–2016) at a median dose of 32 Gy (range 24–40 Gy) in 6, 8, or 10 b.i.d. fractions. Results The median follow-up was 5.6 years (range 0.5–14.2 years). Twenty-nine (50.0%) patients had positive surgical margins. Grade ≥ 3 toxic events were recorded in 34 (58.6%) patients. The local control rate at 2 years was 51% and remained stable up to 14 years. Disease-free survival rates at 2, 5, and 10 years were 17.2, 15.5, and 15.5%, respectively. Overall survival rates at 2, 5, and 10 years were 58.1, 17.8, and 17.8%, respectively. Conclusions IOERT and PHDRB account for an effective salvage in oligorecurrent gynecological tumors. Patients with previous pelvic radiation suitable for salvage surgery and at risk of inadequate margins could benefit from adjuvant reirradiation in form of IOERT or PHDRB. However, the rate of severe grade ≥ 3 toxicity associated with the entire treatment program is relevant and needs to be closely counterbalanced against the expected therapeutic gain (AU)


Assuntos
Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Braquiterapia/efeitos adversos , Elétrons/uso terapêutico , Neoplasias dos Genitais Femininos/radioterapia , Recidiva Local de Neoplasia/radioterapia , Reirradiação/métodos , Terapia de Salvação/métodos , Elétrons/efeitos adversos , Neoplasias dos Genitais Femininos/mortalidade , Neoplasias dos Genitais Femininos/cirurgia , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/cirurgia , Radioterapia Adjuvante , Reirradiação/efeitos adversos , Terapia de Salvação/efeitos adversos , Taxa de Sobrevida , Resultado do Tratamento
3.
Int J Mol Sci ; 22(15)2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34360644

RESUMO

The complex physical and chemical reactions between the large number of low-energy (0-30 eV) electrons (LEEs) released by high energy radiation interacting with genetic material can lead to the formation of various DNA lesions such as crosslinks, single strand breaks, base modifications, and cleavage, as well as double strand breaks and other cluster damages. When crosslinks and cluster damages cannot be repaired by the cell, they can cause genetic loss of information, mutations, apoptosis, and promote genomic instability. Through the efforts of many research groups in the past two decades, the study of the interaction between LEEs and DNA under different experimental conditions has unveiled some of the main mechanisms responsible for these damages. In the present review, we focus on experimental investigations in the condensed phase that range from fundamental DNA constituents to oligonucleotides, synthetic duplex DNA, and bacterial (i.e., plasmid) DNA. These targets were irradiated either with LEEs from a monoenergetic-electron or photoelectron source, as sub-monolayer, monolayer, or multilayer films and within clusters or water solutions. Each type of experiment is briefly described, and the observed DNA damages are reported, along with the proposed mechanisms. Defining the role of LEEs within the sequence of events leading to radiobiological lesions contributes to our understanding of the action of radiation on living organisms, over a wide range of initial radiation energies. Applications of the interaction of LEEs with DNA to radiotherapy are briefly summarized.


Assuntos
Dano ao DNA , DNA/química , DNA/efeitos da radiação , Elétrons/efeitos adversos , Animais , Humanos
4.
Radiat Res ; 196(3): 250-260, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34107043

RESUMO

Severe radiation-induced skin injury is a complication of tumor radiotherapy and nuclear accidents. Cell therapy is a potential treatment for radiation-induced skin injury. The stromal vascular fraction (SVF) is a newer material in stem cell therapy that is made up of stem cells harvested from adipose tissue, which has been shown to promote the healing of refractory wounds of different causes. In this study, SVF was isolated from patients with radiation-induced skin injury. Adipose-derived stem cells (ADSCs) accounted for approximately 10% of the SVF by flow cytometry. Compared with the control group of rats, administration with SVF attenuated the skin injury induced by electron beam radiation. The effect of SVF on the human skin fibroblast microenvironment was determined by proteomic profiling of secreted proteins in SVF-co-cultured human skin fibroblast WS1 cells. Results revealed 293 upregulated and 1,481 downregulated proteins in the supernatant of SVF-co-cultured WS1 cells. WS1 co-culture with SVF induced secretion of multiple proteins including collagen and MMP-1. In the clinic, five patients with radiation-induced skin injury were recruited to receive SVF transfer-based therapy, either alone or combined with flap transplantation. Autogenous SVF was isolated and introduced into a multi-needle precision electronic injection device, which automatically and aseptically distributed the SVF to the exact layer of the wound in an accurate amount. After SVF transfer, wound healing clearly improved and pain was significantly relieved. The patients' skin showed satisfactory texture and shape with no further wound recurrence. Our findings suggest that transplantation of SVF could be an effective countermeasure against severe radiation-induced skin injury.


Assuntos
Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Radiodermite/terapia , Adulto , Aloenxertos , Animais , Células Cultivadas , Técnicas de Cocultura , Meios de Cultivo Condicionados , Elétrons/efeitos adversos , Feminino , Fibroblastos/metabolismo , Ontologia Genética , Redes Reguladoras de Genes , Traumatismos da Mão/terapia , Xenoenxertos , Humanos , Radioisótopos de Irídio/efeitos adversos , Masculino , Transplante de Células-Tronco Mesenquimais/instrumentação , Transplante de Células-Tronco Mesenquimais/métodos , Pessoa de Meia-Idade , Proteoma , Lesões Experimentais por Radiação/terapia , Radiodermite/etiologia , Radiodermite/patologia , Radiodermite/cirurgia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Pele/efeitos da radiação , Organismos Livres de Patógenos Específicos , Retalhos Cirúrgicos
5.
Int J Mol Sci ; 22(9)2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-33924843

RESUMO

Due to their short-range (2-500 nm), Auger electrons (Auger e-) have the potential to induce nano-scale physiochemical damage to biomolecules. Although DNA is the primary target of Auger e-, it remains challenging to maximize the interaction between Auger e- and DNA. To assess the DNA-damaging effect of Auger e- released as close as possible to DNA without chemical damage, we radio-synthesized no-carrier-added (n.c.a.) [189, 191Pt]cisplatin and evaluated both its in vitro properties and DNA-damaging effect. Cellular uptake, intracellular distribution, and DNA binding were investigated, and DNA double-strand breaks (DSBs) were evaluated by immunofluorescence staining of γH2AX and gel electrophoresis of plasmid DNA. Approximately 20% of intracellular radio-Pt was in a nucleus, and about 2% of intra-nucleus radio-Pt bound to DNA, although uptake of n.c.a. radio-cisplatin was low (0.6% incubated dose after 25-h incubation), resulting in the frequency of cells with γH2AX foci was low (1%). Nevertheless, some cells treated with radio-cisplatin had γH2AX aggregates unlike non-radioactive cisplatin. These findings suggest n.c.a. radio-cisplatin binding to DNA causes severe DSBs by the release of Auger e- very close to DNA without chemical damage by carriers. Efficient radio-drug delivery to DNA is necessary for successful clinical application of Auger e-.


Assuntos
Cisplatino/metabolismo , Elétrons/efeitos adversos , Radioisótopos/efeitos adversos , Linhagem Celular Tumoral , Quebras de DNA de Cadeia Dupla , Humanos , Platina , Radioisótopos/metabolismo
6.
Clin Transl Oncol ; 23(9): 1934-1941, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33835408

RESUMO

BACKGROUND: Pelvic recurrences from previously irradiated gynecological cancer lack solid evidence for recommendation on salvage. METHODS: A total of 58 patients were included in this clinical analysis. Salvage surgery was performed for locoregional relapse within previously irradiated pelvic area after initial surgery and adjuvant radiotherapy or radical external beam radiotherapy. The primary tumor diagnosis included cervical cancer (n = 47, 81%), uterine cancer (n = 4, 7%), and other types (n = 7, 12%). Thirty-three patients received adjuvant IOERT (1984-2000) at a median dose of 15 Gy (range 10-20 Gy) and 25 patients received adjuvant PHDRB (2001-2016) at a median dose of 32 Gy (range 24-40 Gy) in 6, 8, or 10 b.i.d. fractions. RESULTS: The median follow-up was 5.6 years (range 0.5-14.2 years). Twenty-nine (50.0%) patients had positive surgical margins. Grade ≥ 3 toxic events were recorded in 34 (58.6%) patients. The local control rate at 2 years was 51% and remained stable up to 14 years. Disease-free survival rates at 2, 5, and 10 years were 17.2, 15.5, and 15.5%, respectively. Overall survival rates at 2, 5, and 10 years were 58.1, 17.8, and 17.8%, respectively. CONCLUSIONS: IOERT and PHDRB account for an effective salvage in oligorecurrent gynecological tumors. Patients with previous pelvic radiation suitable for salvage surgery and at risk of inadequate margins could benefit from adjuvant reirradiation in form of IOERT or PHDRB. However, the rate of severe grade ≥ 3 toxicity associated with the entire treatment program is relevant and needs to be closely counterbalanced against the expected therapeutic gain.


Assuntos
Braquiterapia , Elétrons/uso terapêutico , Neoplasias dos Genitais Femininos/radioterapia , Recidiva Local de Neoplasia/radioterapia , Reirradiação/métodos , Terapia de Salvação/métodos , Adulto , Idoso , Braquiterapia/efeitos adversos , Intervalo Livre de Doença , Elétrons/efeitos adversos , Feminino , Neoplasias dos Genitais Femininos/mortalidade , Neoplasias dos Genitais Femininos/cirurgia , Humanos , Cuidados Intraoperatórios , Margens de Excisão , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/cirurgia , Dosagem Radioterapêutica , Radioterapia Adjuvante/efeitos adversos , Radioterapia Adjuvante/métodos , Reirradiação/efeitos adversos , Terapia de Salvação/efeitos adversos , Taxa de Sobrevida , Resultado do Tratamento
7.
Commun Biol ; 4(1): 382, 2021 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-33753866

RESUMO

Photosystem II (PSII) plays a key role in water-splitting and oxygen evolution. X-ray crystallography has revealed its atomic structure and some intermediate structures. However, these structures are in the crystalline state and its final state structure has not been solved. Here we analyzed the structure of PSII in solution at 1.95 Å resolution by single-particle cryo-electron microscopy (cryo-EM). The structure obtained is similar to the crystal structure, but a PsbY subunit was visible in the cryo-EM structure, indicating that it represents its physiological state more closely. Electron beam damage was observed at a high-dose in the regions that were easily affected by redox states, and reducing the beam dosage by reducing frames from 50 to 2 yielded a similar resolution but reduced the damage remarkably. This study will serve as a good indicator for determining damage-free cryo-EM structures of not only PSII but also all biological samples, especially redox-active metalloproteins.


Assuntos
Proteínas de Bactérias/ultraestrutura , Microscopia Crioeletrônica , Elétrons/efeitos adversos , Complexo de Proteína do Fotossistema II/ultraestrutura , Proteínas de Bactérias/metabolismo , Modelos Moleculares , Oxirredução , Complexo de Proteína do Fotossistema II/metabolismo , Conformação Proteica , Thermosynechococcus/metabolismo , Thermosynechococcus/ultraestrutura
8.
Sci Rep ; 11(1): 5282, 2021 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-33674709

RESUMO

In this study, we evaluated the effectiveness of palliative breast radiation therapy (RT), with single fraction RT compared with fractionated RT. Our study showed that both RT fractionation schemas provide palliation. Single fraction RT allowed for treatment with minimal interference with systemic therapy, whereas fractionated RT provided a more durable palliative response. Due to equivalent palliative response, at our institution we have increasingly been providing single fraction RT palliation during the COVID-19 pandemic.


Assuntos
Neoplasias da Mama/radioterapia , Elétrons/uso terapêutico , Recidiva Local de Neoplasia/radioterapia , Cuidados Paliativos/métodos , Fótons/uso terapêutico , Radiodermite/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Mama/patologia , Mama/efeitos da radiação , Neoplasias da Mama/patologia , COVID-19/epidemiologia , COVID-19/prevenção & controle , COVID-19/transmissão , Fracionamento da Dose de Radiação , Relação Dose-Resposta à Radiação , Elétrons/efeitos adversos , Feminino , Seguimentos , Humanos , Controle de Infecções/normas , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Pandemias/prevenção & controle , Fótons/efeitos adversos , Radioterapia (Especialidade)/normas , Radiodermite/etiologia , Estudos Retrospectivos , Resultado do Tratamento
9.
Methods Mol Biol ; 2215: 309-319, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33368011

RESUMO

Microcrystal electron diffraction (MicroED) is a technique for structure determination that relies on the strong interaction of electrons with a minuscule, crystalline sample. While some of the electrons used to probe the crystal interact without altering the crystal, others deposit energy which changes the sample through a series of damage events. It follows that the sample cannot be observed without damaging it, and the frames obtained at the beginning of data collection reflect a crystal that differs from the one that yields the last frames of the dataset. Data acquisition at cryogenic temperatures has been found to reduce the rate of damage progression and is routinely used to increase the dose tolerance of the crystal, allowing more useful data to be obtained before the sample is destroyed. Low-dose data collection can further prolong the lifetime of the crystal, such that less damage is inflicted over the course of data acquisition. Ideally, lower doses increase the measurable volume of a single-crystal lattice by reducing the damage caused by probing electrons. However, the information that can be recovered from a diffraction image is directly related to the number of electrons used to probe the sample. The signal from a weakly exposed crystal runs the risk of being lost in the noise contributed by solvent, crystal disorder, and the electron detection process. This work focuses on obtaining the best possible data from a MicroED measurement, which requires considering several aspects such as sample, dose, and camera type.


Assuntos
Microscopia Crioeletrônica/métodos , Elétrons/efeitos adversos , Microscopia Eletrônica de Transmissão/métodos , Microscopia Crioeletrônica/normas , Radiação Eletromagnética , Microscopia Eletrônica de Transmissão/normas , Nanopartículas/química , Conformação Proteica
12.
Sci Rep ; 10(1): 5071, 2020 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-32193504

RESUMO

Despite the tremendous importance of so-called ionizing radiations (X-rays, accelerated electrons and ions) in cancer treatment, most studies on their effects have focused on the ionization process itself, and neglect the excitation events the radiations can induce. Here, we show that the excited states of DNA exposed to accelerated electrons can be studied in the picosecond time domain using a recently developed cathodoluminescence system with high temporal resolution. Our study uses a table-top ultrafast, UV laser-triggered electron gun delivering picosecond electron bunches of keV energy. This scheme makes it possible to directly compare time-resolved cathodoluminescence with photoluminescence measurements. This comparison revealed qualitative differences, as well as quantitative similarities between excited states of DNA upon exposure to electrons or photons.


Assuntos
DNA/efeitos da radiação , Elétrons/efeitos adversos , Medições Luminescentes/métodos , Radiação Ionizante , Fatores de Tempo
13.
J Phys Chem B ; 124(9): 1585-1591, 2020 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-32043891

RESUMO

Low-energy (3-25 eV) electron interactions with multilayers of 2'-deoxyadenosine 5'-monophosphate (dAMP) were probed using X-ray photoelectron spectroscopy (XPS). Understanding how electrons damage the nucleotide dAMP, which is a building block of DNA, can give insight into how the DNA undergoes radiation damage. Chemical modifications to the constituent units of the nucleotide were revealed in situ through monitoring of the O 1s, C 1s, and N 1s elemental transitions. It is shown that direct electron irradiation causes decomposition of both the base and sugar subunits, as well as cleavage of glycosidic and phosphoester bonds. Incident electrons undergo inelastic energy losses, including creation of core-excited resonances above 3-4 eV. In the condensed phase, these resonances decay via autoionization, producing electronically excited targets and <3 eV electrons. The excited states dissociate and the slow (<3 eV) electrons are captured by neighboring molecules, forming molecular shape resonances that can lead to bond rupture. Since the observed chemical changes were similar at all incident electron energies studied, they can be primarily attributed to formation and decay of transient negative ions. Damage enhancements in the energy ranges typical of all scattering resonances are expected, with the damage probability dominated by the low-energy shape resonances.


Assuntos
Nucleotídeos de Desoxiadenina/química , Elétrons/efeitos adversos , Espectroscopia Fotoeletrônica , Dano ao DNA
14.
J Am Acad Dermatol ; 83(1): 78-85, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32004646

RESUMO

BACKGROUND: Low-dose total skin electron beam therapy (TSEBT) for mycosis fungoides is popular because of reduced toxicity with effective palliation. We condensed TSEBT, reducing visits by half and overall treatment length by one third. OBJECTIVE: To determine the efficacy and safety of a novel condensed low-dose TSEBT for mycosis fungoides. METHODS: We conducted a cohort study (2014-2018) with a median follow-up of 22.8 months. We delivered 12 Gy per 6 fractions with the modified Stanford technique, 3 fractions per week, with boosts to shadowed sites at risk between treatments, completing in 2 weeks. Primary outcomes included clinical response, duration of and time to response, and toxicity. Secondary outcomes included patient-reported quality of life (pain, pruritus, and Dermatology Life Quality Index) and physician-scored disease burden (body surface area involvement and Modified Skin Weighted Assessment Tool). RESULTS: Of 25 patients, stage IB was most common at the time of TSEBT (36%). The overall response rate was 88%. Most common was a near complete response (36%), and complete response was achieved in 6 (24%) patients. The median duration of response was 17.5 months (3.5-44.2), and the median time to response was 2 months (range, 0.9-4.1). No patients had toxicity of grade 3 or greater. QOL and disease burden showed significant benefit after TSEBT (P < .001). LIMITATIONS: Cohort study with limited sample size. CONCLUSIONS: Condensed, low-dose TSEBT has favorable outcomes and toxicity with logistical convenience.


Assuntos
Efeitos Psicossociais da Doença , Micose Fungoide/radioterapia , Qualidade de Vida , Adulto , Idoso , Idoso de 80 Anos ou mais , Fracionamento da Dose de Radiação , Elétrons/efeitos adversos , Elétrons/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento
15.
Ann Surg Oncol ; 27(3): 752-762, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31732946

RESUMO

BACKGROUND: The aim of this work is to evaluate pattern of care and clinical outcome in a large series of patients with in-breast recurrence (IBR), after quadrantectomy and intraoperative radiation therapy with electrons (IOERT) as partial breast irradiation. PATIENTS AND METHODS: Patients with IBR after IOERT, treated with salvage surgery ± adjuvant reirradiation (re-RT), were selected from a multiinstitution database. Disease-free survival (DFS), overall survival (OS), cumulative incidence of second IBR, and distant metastases (DM) were estimated. RESULTS: A total of 224/267 patients from seven institutions were included. Primary tumors received 21 Gy. Median time to first IBR was 4.3 years (range 2.6-6.1 years). Salvage mastectomy and repeat quadrantectomy were performed in 135 (60.3%) and 89 (39.7%) patients, followed by adjuvant re-RT in 21/135 (15.5%) and 63/89 (70.8%), respectively. Median follow-up after salvage treatment was 4.1 years. Overall, 5- and 8-year outcomes were as follows: cumulative incidence of second IBR: 8.4% and 14.8%; cumulative incidence of DM: 17.1% and 22.5%; DFS: 67.4% and 52.5%; OS: 89.3% and 74.7%. The risk of second IBR was similar in the salvage mastectomy and repeat quadrantectomy + RT groups [hazard ratio (HR) 1.41, p = 0.566], while salvage mastectomy patients had greater risk of DM (HR 3.15, p = 0.019), as well as poorer DFS (HR 2.13, p = 0.016) and a trend towards worse OS (HR 3.27, p = 0.059). Patients who underwent repeat quadrantectomy alone had worse outcomes (second IBR, HR 5.63, p = 0.006; DFS, HR 3.21, p = 0.003; OS, HR 4.38, p = 0.044) than those adding re-RT. CONCLUSIONS: Repeat quadrantectomy + RT represents an effective salvage approach and achieved local control comparable to that of salvage mastectomy.


Assuntos
Neoplasias da Mama/mortalidade , Elétrons/efeitos adversos , Mastectomia/mortalidade , Recidiva Local de Neoplasia/mortalidade , Lesões por Radiação/mortalidade , Radioterapia Adjuvante/mortalidade , Idoso , Neoplasias da Mama/patologia , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/mortalidade , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/radioterapia , Carcinoma Ductal de Mama/cirurgia , Carcinoma Lobular/mortalidade , Carcinoma Lobular/patologia , Carcinoma Lobular/radioterapia , Carcinoma Lobular/cirurgia , Terapia Combinada , Feminino , Seguimentos , Humanos , Período Intraoperatório , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/radioterapia , Recidiva Local de Neoplasia/cirurgia , Prognóstico , Estudos Prospectivos , Lesões por Radiação/etiologia , Lesões por Radiação/patologia , Dosagem Radioterapêutica , Estudos Retrospectivos , Taxa de Sobrevida
16.
Nucl Med Biol ; 80-81: 37-44, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31706737

RESUMO

INTRODUCTION: Our objective was to evaluate the effectiveness and normal tissue toxicity of nimotuzumab labeled with the Auger electron (AE)-emitter, 111In ([111In]In-Bn-DTPA-nimotuzumab) for radioimmunotherapy (RIT) of human triple-negative breast cancer (TNBC) or trastuzumab-resistant HER2-positive BC tumors overexpressing epidermal growth factor receptors (EGFR) in athymic mice. METHODS: Normal tissue toxicity was studied in non-tumor-bearing Balb/c mice i.v. administered 9.0 or 28.6 MBq (3 mg/kg) of [111In]In-Bn-DTPA-nimotuzumab, unlabeled nimotuzumab (3 mg/kg) or normal saline. A complete blood cell count (CBC) and serum alanine aminotransferase (ALT) and creatinine (Cr) were measured at 14 days. Body weight was monitored. RIT studies were performed in CD-1 athymic mice engrafted s.c. with MDA-MB-468 human TNBC tumors or TrR1 HER2-positive but trastuzumab-resistant BC tumors. Mice were i.v. administered two amounts (15.5 MBq; 3 mg/kg) of [111In]In-Bn-DTPA-nimotuzumab separated by 14 days. Control mice received unlabeled Bn-DTPA-nimotuzumab (3 mg/kg) or anti-HER2 [111In]In-Bn-DTPA-trastuzumab or normal saline. Tumor growth and body weight were measured for 6 weeks. A tumor growth index (TGI) and body weight index (BWI) were calculated to compare the tumor size and body weight post-treatment with the pre-treatment values. A tumor doubling ratio (TDR) was calculated for each treatment group compared to control mice receiving normal saline. RESULTS: There was no loss of body weight or decreased red blood cells (RBC) or platelets (PLT) or increased serum ALT or Cr in Balb/c mice administered 9.0 or 28.6 MBq (3 mg/kg) of [111In]In-Bn-DTPA-nimotuzumab compared to mice treated with unlabeled Bn-DTPA-nimotuzumab (3 mg/kg) or normal saline. There was a significant decrease in white blood cell (WBC) counts in Balb/c mice receiving 28.6 MBq but not 9.0 MBq of [111In]In-Bn-DTPA-nimotuzumab. Based on these results, an administered amount of 15.5 MBq (3 mg/kg) was selected for RIT studies. Administration of two amounts (15.5 MBq; 3 mg/kg) separated by 14 days to CD-1 athymic mice with s.c. MDA-MB-468 xenografts strongly inhibited tumor growth. The TDR for mice treated with [111In]In-Bn-DTPA-nimotuzumab was 2.15 compared to control mice receiving normal saline. In contrast, treatment with unlabeled Bn-DTPA-nimotuzumab or [111In]In-Bn-DTPA-trastuzumab had no significant effect on tumor growth (TDR = 0.96 and 1.08, respectively). RIT with [111In]In-Bn-DTPA-nimotuzumab also strongly inhibited the growth of TrR1 tumors in athymic mice (TDR = 2.13) compared to unlabeled Bn-DTPA-nimotuzumab (TDR = 0.91). There were no losses in body weight over 6 weeks in tumor bearing mice receiving [111In]In-Bn-DTPA-nimotuzumab, unlabeled Bn-DTPA-nimotuzumab, [111In]In-Bn-DTPA-trastuzumab or normal saline. CONCLUSIONS: [111In]In-Bn-DTPA-nimotuzumab was effective for treatment of TNBC or trastuzumab-resistant HER2-positive human BC tumors in mice that overexpress EGFR at administered amounts that caused no decrease in body weight or normal tissue toxicity in non-tumor-bearing Balb/c mice. ADVANCES IN KNOWLEDGE AND IMPLICATIONS FOR PATIENT CARE: Our results suggest that Auger electron RIT with [111In]In-Bn-DTPA-nimotuzumab may provide a novel therapeutic option for patients with TNBC or trastuzumab-resistant HER2-positive BC that overexpresses EGFR. The low normal tissue toxicity of this approach may allow combination with other targeted therapies such as antibody-drug conjugates (ADCs).


Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Resistencia a Medicamentos Antineoplásicos/efeitos da radiação , Receptores ErbB/metabolismo , Radioisótopos de Índio/uso terapêutico , Ácido Pentético/química , Radioimunoterapia/efeitos adversos , Neoplasias de Mama Triplo Negativas/radioterapia , Animais , Anticorpos Monoclonais Humanizados/farmacocinética , Anticorpos Monoclonais Humanizados/uso terapêutico , Linhagem Celular Tumoral , Transformação Celular Neoplásica , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/imunologia , Elétrons/efeitos adversos , Elétrons/uso terapêutico , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Humanos , Imunoconjugados/efeitos adversos , Imunoconjugados/farmacocinética , Imunoconjugados/uso terapêutico , Camundongos , Fenótipo , Distribuição Tecidual , Trastuzumab/farmacologia , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia
17.
Phys Med ; 66: 29-35, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31550531

RESUMO

PURPOSE: To clarify the physical characteristics of a newly developed real time variable shape rubber containing tungsten (STR) with changes in heat and estimate its shielding abilities against electron beams and γ-rays from 192Ir. METHODS: Dynamic mechanical analysis for the STR (density = 7.3 g/cm3) was conducted at a frequency of 1.0 Hz in the temperature range of -60 °C to 60 °C. We evaluated tanδ, defined as the ratio (E″/E') between the storage modulus (E') and loss modulus (E″). The transmission rates were measured against 6- and 12-MeV electron beams and the percentage depth dose and lateral dose profile were compared with low-melting alloy (LMA). For the shielding rate of 192Ir against γ-rays, measurement data and Monte Carlo simulation data were obtained with STR thickness ranging from 1.0 mm to 16.0 mm. RESULTS: At 36 °C, the tanδ value was 0.520, while at 60 °C, this value was 1.016. For 6- and 12-MeV electron beams, the transmission rates decreased with increasing STR thickness and reached plateaus at approximately 1.0% and 4.0% with STR thickness of >7.0 and >12.0 mm, respectively. The dose distributions were almost equal to those for LMA. Against γ-rays, the thickness of STR that obtained a 50% attenuation rate for 192Ir was 5.804 mm. The Monte Carlo calculation results were 2.6% higher on average than the measurement results. CONCLUSION: The STR can be changed shape in real time at 60 °C and maintains its shape at body temperatures. It has adequate shielding abilities against megavoltage electron beams and γ-rays from 192Ir.


Assuntos
Braquiterapia/efeitos adversos , Elétrons/efeitos adversos , Proteção Radiológica/instrumentação , Borracha , Tungstênio , Elétrons/uso terapêutico , Temperatura , Fatores de Tempo
18.
Int J Mol Sci ; 20(16)2019 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-31426385

RESUMO

This review article provides a concise overview of electron involvement in DNA radiation damage. The review begins with the various states of radiation-produced electrons: Secondary electrons (SE), low energy electrons (LEE), electrons at near zero kinetic energy in water (quasi-free electrons, (e-qf)) electrons in the process of solvation in water (presolvated electrons, e-pre), and fully solvated electrons (e-aq). A current summary of the structure of e-aq, and its reactions with DNA-model systems is presented. Theoretical works on reduction potentials of DNA-bases were found to be in agreement with experiments. This review points out the proposed role of LEE-induced frank DNA-strand breaks in ion-beam irradiated DNA. The final section presents radiation-produced electron-mediated site-specific formation of oxidative neutral aminyl radicals from azidonucleosides and the evidence of radiosensitization provided by these aminyl radicals in azidonucleoside-incorporated breast cancer cells.


Assuntos
Dano ao DNA/efeitos da radiação , DNA/genética , Elétrons/efeitos adversos , Animais , DNA/química , Humanos , Modelos Químicos , Modelos Moleculares , Nucleosídeos de Pirimidina/química , Nucleosídeos de Pirimidina/genética , Radiação Ionizante
19.
Int J Radiat Oncol Biol Phys ; 104(4): 877-884, 2019 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-30926576

RESUMO

PURPOSE: To evaluate locoregional control and outcome after mastectomy in patients treated with postmastectomy highly conformal electron radiation therapy (PMERT) with bolus compared with patients treated by highly conformal photon radiation therapy (PMPhRT) without bolus in the adjuvant setting of nonmetastatic breast cancer. METHODS AND MATERIALS: We studied women undergoing PMRT without immediate reconstruction for breast cancer before 2012 in 2 sites of our hospital using 2 different techniques. All patients received 50 Gy in 25 fractions. Patients previously treated by neoadjuvant chemotherapy were excluded. RESULTS: Among the 807 patients, 583 received PMERT and 224 received PMPhRT. The median follow-up was 64 months. Patients in the PMERT group had a median age of 52.7 years (range, 26-91 years), 6.9% were triple-negative, 16.3% were HER2-positive, and 58.6% had multifocal lesions. Patients in the PMPhRT group had a median age of 56.4 years (28-89), 8.5% were triple negative, 12.9% were HER2-positive, and 55.8% had multifocal lesions. Lymph node involvement was observed in 66% and 72.8% of cases (P = .07) treated with PMERT and PMPhRT, respectively. No significant difference in overall survival was observed between the 2 groups (hazard ratio [HR], 1.2; 95% CI, 0.67-2.13; P = .54). The risk of locoregional recurrence, estimated using the Fine-Gray method, was significantly higher with PMPhRT than with PMERT (subdistribution HR, 3.62; 95% CI, 1.07-12.3; P = .04), corresponding to a 5-year LRR rate of 0.53% (95% CI, 0-1.12%) for PMERT and 2.52% (95% CI, 0.05%-4.6%) for PMPhRT. CONCLUSIONS: A higher risk of local recurrence was observed in the PMPhRT without bolus group compared with the PMERT with bolus group. Prospective randomized trials are needed to confirm these findings.


Assuntos
Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Elétrons/uso terapêutico , Mamoplastia , Recidiva Local de Neoplasia , Fótons/uso terapêutico , Radioterapia Conformacional/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/química , Neoplasias da Mama/mortalidade , Fracionamento da Dose de Radiação , Elétrons/efeitos adversos , Feminino , Humanos , Excisão de Linfonodo , Linfonodos/patologia , Irradiação Linfática , Mastectomia , Pessoa de Meia-Idade , Fótons/efeitos adversos , Cuidados Pós-Operatórios , Lesões por Radiação/patologia , Radioterapia Adjuvante , Radioterapia Conformacional/efeitos adversos , Estudos Retrospectivos , Pele/efeitos da radiação
20.
J Cancer Res Ther ; 15(1): 216-222, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30880781

RESUMO

AIM: The purpose of this study is to measure radiation leakage of Siemens Primus Plus and Siemens Artiste linear accelerators in electron mode and to compare the leakage level with that recommended by the International Electrotechnical Commission (IEC) standard. MATERIALS AND METHODS: In this assessment, Siemens Primus Plus linear accelerator with 10 cm × 10 cm, 15 cm × 15 cm, and 25 cm × 25 cm applicators was used. The radiation leakage in lateral and vertical directions was measured for Siemens Primus Plus and Siemens Artiste linear accelerators. RESULTS: Data derived from radiation leakage measurement for Siemens Primus Plus and Siemens Artiste linear accelerators in lateral direction from the field edge and in vertical direction from the applicator were reported. The radiation leakage data were then compared with the IEC standard to evaluate in-air field leakage. CONCLUSION: Comparing the radiation leakage level from fields with the IEC standard for two applicators, the maximum that was occurred for 12 MeV electron beam and applicator size of 10 cm × 10 cm in Siemens Artiste linear accelerator was 2.3%, which is less than the IEC's recommended limit of 10%. It is concluded that the leakage amount is much less than the specified limit and that both of the linear accelerators have high level of safety. Considering the measurement stage, it also needs to be noted that the beam angle affected the radiation leakage level from field edge, and in 25° angle, it is higher than in 0° angle. Comparing radiation leakage from the right side of the field for the two linear accelerators, the amount of leakage for Siemens Primus Plus linear accelerator is more than Siemens Artiste linear accelerator.


Assuntos
Elétrons/efeitos adversos , Neoplasias Induzidas por Radiação/prevenção & controle , Aceleradores de Partículas/normas , Elétrons/uso terapêutico , Humanos , Neoplasias Induzidas por Radiação/etiologia , Imagens de Fantasmas , Dosagem Radioterapêutica/normas
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