RESUMO
BACKGROUND: Advances in the management of multiple myeloma (MM) have extended survival and reduced painful skeletal-related events. As MM is evolving toward a chronic disease, we sought to determine the prevalence of self-reported symptom burden and psychological distress, and to determine the association of distress with survival. METHODS: The CPASS-7 patient-reported outcome instrument was administered to a convenience sample of MM patients at 7 outpatient cancer centers. RESULTS: A total of 239 patients completed the CPASS-7 between September 2015 and October 2016%; 57% of respondents were male, and median age was 67 years. Forty-eight percent were concerned that they could not do the things they wanted to do, with 33% reporting decreased performance status. Financial toxicity concerns were self-reported by 44%, with family burdens noted in 24%. Although depression was reported by only 15%, 41% noted lack of pleasure. Pain was a concern in 36%. With a median follow-up of 316 days since CPASS-7 completion, 13% of patients had died. A high total distress score was noted in 57 (24%) and trended toward an association with a decreased survival rate compared to the 182 patients (76%) with a low total distress score (P = .066). The 6-month survival rates for patients with high and low distress scores were 86% and 96%, respectively, and 12-month survival rates were 76% and 87%, respectively. CONCLUSION: Despite dramatic improvements in survival among patients with MM, symptom, financial, and psychosocial concerns continue to be major patient concerns. As MM becomes a chronic disease, additional attention to addressing these issues is required.
Assuntos
Mieloma Múltiplo/epidemiologia , Mieloma Múltiplo/psicologia , Angústia Psicológica , Autorrelato , Sobreviventes de Câncer/psicologia , Humanos , Mieloma Múltiplo/mortalidade , Cuidados Paliativos , Prevalência , Prognóstico , Qualidade de Vida , Inquéritos e Questionários , Avaliação de SintomasRESUMO
PURPOSE: In this study, we investigated computationally and experimentally a hexagonal-pattern array of spatially fractionated proton minibeams produced by proton pencil beam scanning (PBS) technique. Spatial fractionation of dose delivery with millimeter or submillimeter beam size has proven to be a promising approach to significantly increase the normal tissue tolerance. Our goals are to obtain an optimized minibeam design and to show that it is feasible to implement the optimized minibeams at the existing proton clinics. METHODS: An optimized minibeam arrangement is one that would produce high peak-to-valley dose ratios (PVDRs) in normal tissues and a PVDR approaching unity at the Bragg peak. Using Monte Carlo (MC) code TOPAS we simulated proton pencil beams that mimic those available at the existing proton therapy facilities and obtained a hexagonal-pattern array of minibeams by collimating the proton pencil beams through the 1-3 mm diameter pinholes of a collimator. We optimized the minibeam design by considering different combinations of parameters including collimator material and thickness (t), center-to-center (c-t-c) distance, and beam size. The optimized minibeam design was then evaluated for normal tissue sparing against the uniform pencil beam scanning (PBS) by calculating the therapeutic advantage (TA) in terms of cell survival fraction. Verification measurements using radiochromic films were performed at the Emory proton therapy center (EPTC). RESULTS: Optimized hexagonal-pattern minibeams having PVDRs of >10 at phantom surface and of >3 at depths up to 6 cm were achieved with 2 mm diameter modulated proton minibeams (with proton energies between 120 and 140 MeV) corresponding to a spread-out-Bragg-peak (SOBP) over the depth of 10-14 cm. The results of the film measurements agree with the MC results within 10%. The TA of the 2 mm minibeams against the uniform PBS is >3 from phantom surface to the depth of 5 cm and then smoothly drops to ~1.5 as it approaches the proximal edge of the SOBP. For 2 mm minibeams and 6 mm c-t-c distance, we delivered 1.72 Gy at SOBP for 7.2 × 7.2 × 4 cm3 volume in 48 s. CONCLUSIONS: We conclude that it is feasible to implement the optimized hexagonal-pattern 2 mm proton minibeam radiotherapy at the existing proton clinics, because desirable PVDRs and TAs are achievable and the treatment time is reasonable.
Assuntos
Terapia com Prótons , Prótons , Fracionamento da Dose de Radiação , Método de Monte Carlo , Imagens de Fantasmas , Dosagem RadioterapêuticaRESUMO
New technique is trending in spatially fractionated radiotherapy with protons to utilize the spot scanning together with a physical collimator to obtain minibeams. The primary goal of this study is to quantify ambient neutron dose equivalent (${H}^{\ast }(10)$) due to the secondary neutrons when physical collimator is used to achieve desired minibeams. The ${H}^{\ast }(10)$ per treatment proton dose (D) was assessed using Monte Carlo code TOPAS and measured using WENDI-II detector at different angles (135, 180, 225 and 270 degrees) and distances (11 cm, 58 and 105 cm) from the phantom for two cases: with and without physical collimation. Without collimation $\frac{H^{\ast }(10)}{D}$ varied from 0.0013 to 0.242 mSv/Gy. With collimation $\frac{H^{\ast }(10)}{D}$ varied from 0.017 to 3.23 mSv/Gy. Results show that the secondary neutron dose will increase tenfold when the physical collimator is used. Regardless, it will be low and comparable to the neutron dose produced by conventional passive-scattered proton beams.
Assuntos
Terapia com Prótons , Prótons , Fracionamento da Dose de Radiação , Método de Monte Carlo , Nêutrons , Radiometria , Dosagem RadioterapêuticaRESUMO
This paper presents a cell-by-cell Monte Carlo simulation study that combines charged particle track structure data with an interphase cell nucleus model to quantify DNA double strand breaks (DSBs), spatial distribution of DSBs in a cell nucleus, and resulting potentially lethal or mutagenic events (PLMEs) between DSBs in close proximity. Cell nucleus is simulated according to the chromosome territory-interchromatin compartment (CT-IC) model in that chromatin content is unevenly distributed in chromatin domains (CDs) and IC with a chromatin compaction ratio of 22:1. A particle track structure coordinate (PTSC) library was first generated for each particle type, energy, and dose based on a large number of particle track data obtained by running the Monte Carlo track structure code Geant4-DNA. To assess the DNA DSBs of a cell for a specific particle type, energy, and dose, the corresponding PTSC was selected and "map overlaid" onto 960 unique cell nucleus data sets containing chromatin fiber (CF) locations. Clustering algorithm DBSCAN was next used to identify the clustered energy deposition events occurring inside the CF. These events were then converted to DNA DSBs using a probabilistic approach. The locations of the DSBs thus obtained were, in turn, used to calculate PLMEs within the cell nucleus that can result from DSB proximity and complexity. The results obtained from this simulation study are correctly correlated to the experimental data of DSB yield and the RBE-LET relationships for various types of charged particles and of various energies. The results show agreement with other published radiobiological models.
Assuntos
Quebras de DNA de Cadeia Dupla/efeitos da radiação , Método de Monte Carlo , Núcleo Celular/genética , Núcleo Celular/efeitos da radiação , Transferência Linear de Energia , Mutagênese/genética , Mutagênese/efeitos da radiação , Doses de RadiaçãoRESUMO
BACKGROUND: We conducted a retrospective analysis on 884 patients who were diagnosed with esophageal squamous cell carcinoma (ESCC) and treated with either the neutron brachytherapy in combination with external beam radiotherapy (NBT + EBRT) or 3-dimensional conformal radiation therapy (3D-CRT) to determine the differences in efficacy and morbidity between the two treatment groups. METHODS: The 884 ESCC patients treated with either NBT + EBRT or 3D-CRT between 2002 and 2012 were retrospectively reviewed and analyzed. Multivariable Cox regression was used to compare oncologic outcomes of the two groups of patients in the context of other clinically relevant variables. The acute and chronic toxicities associated with the two groups were compared using Fisher exact and log-rank tests, respectively. RESULTS: Among the 884 patients, 545 received NBT + EBRT and 339 received 3D-CRT (i.e. EBRT-only). The age range is 39-95 years (median 66). The follow-up time range is 3-145 months (median 32). The analysis shows that the NBT + EBRT group has higher overall survival rate and local control rate than that of the 3D-CRT group. The acute toxicity effects were acceptable for both groups of patients with the NBT + EBRT group showing higher rates of leukopenia and thrombocytopenia and the 3D-CRT group showing higher rates on fistula and massive bleeding. CONCLUSIONS: The patients treated with NBT + EBRT showed better oncologic outcomes than those treated with 3D-CRT. The toxicity effects were acceptable for both groups with the NBT + EBRT group showing higher rates on the acute effects and the 3D-CRT group showing higher rates on the late effects.
Assuntos
Braquiterapia/métodos , Carcinoma de Células Escamosas/radioterapia , Neoplasias Esofágicas/radioterapia , Radioterapia Conformacional/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Califórnio/uso terapêutico , Carcinoma de Células Escamosas/mortalidade , Neoplasias Esofágicas/mortalidade , Carcinoma de Células Escamosas do Esôfago , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Nêutrons , Modelos de Riscos Proporcionais , Radioterapia/métodos , Estudos RetrospectivosRESUMO
PURPOSE: The aim of this study was to retrospectively observe and analyze the long-term treatment outcomes for a total of 952 esophageal cancer patients who were treated with (252)Cf neutron brachytherapy (NBT) in combination with external beam radiotherapy (EBRT). METHODS AND MATERIALS: From November 2001 to March 2012, 952 patients with esophageal cancer underwent NBT in combination with EBRT. The patient numbers distributed over various cancer Stages I, IIA, IIB, III, and IVA were 9, 290, 51, 579, and 23, respectively. The total radiation dose to the reference point via NBT was 8-25 Gy-eq in three to five fractions with one fraction/week. The total dose via EBRT was 40-60 Gy delivered over a period of 5-6 weeks with normal fractionation. RESULTS: The overall median survival time was 20.3 months. The 1-, 3-, and 5-year survival rates were 67.1%, 36.3%, and 26.6%, respectively. These results compare favorably with the results obtained from conventional high-dose rate in combination with EBRT. Although a majority of the patients (860 or 90.3%) developed Grades 1 and 2 esophagitis during treatment, the symptoms were effectively relieved after the application of antacid and surface anesthesia. CONCLUSIONS: The clinical data show that NBT in combination with EBRT produced favorable local control and long-term survival rates for patients with esophageal cancer and that the side effects are tolerable. As such, we conclude that this dual-modality method is an effective and safe way for treating esophageal cancer.
Assuntos
Braquiterapia/métodos , Califórnio/uso terapêutico , Carcinoma/radioterapia , Neoplasias Esofágicas/radioterapia , Nêutrons/uso terapêutico , Compostos Radiofarmacêuticos/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma/mortalidade , Terapia Combinada , Fracionamento da Dose de Radiação , Neoplasias Esofágicas/mortalidade , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Doses de Radiação , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do TratamentoRESUMO
PURPOSE: The efficacy of a boron-containing cholesteryl ester compound (BCH) as a boron neutron capture therapy (BNCT) agent for the targeted irradiation of PC-3 human prostate cancer cells was examined. MATERIALS AND METHODS: Liposome-based delivery of BCH was quantified with inductively coupled plasma-mass spectrometry (ICP-MS) and high-performance liquid chromatography (HPLC). Cytotoxicity of the BCH-containing liposomes was evaluated with neutral red, 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS), and lactate dehydrogenase assays. Colony formation assays were utilized to evaluate the decrease in cell survival due to high-linear energy transfer (LET) particles resulting from (10)B thermal neutron capture. RESULTS: BCH delivery by means of encapsulation in a lipid bilayer resulted in a boron uptake of 35.2 ± 4.3 µg/10(9) cells, with minimal cytotoxic effects. PC-3 cells treated with BCH and exposed to a 9.4 × 10(11) n/cm(2) thermal neutron fluence yielded a 20-25% decrease in clonogenic capacity. The decreased survival is attributed to the generation of high-LET α particles and (7)Li nuclei that deposit energy in densely ionizing radiation tracks. CONCLUSION: Liposome-based delivery of BCH is capable of introducing sufficient boron to PC-3 cells for BNCT. High-LET α particles and (7)Li nuclei generated from (10)B thermal neutron capture significantly decrease colony formation ability in the targeted PC-3 cells.
Assuntos
Terapia por Captura de Nêutron de Boro/métodos , Neoplasias da Próstata/radioterapia , Boro/administração & dosagem , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos da radiação , Ésteres do Colesterol/administração & dosagem , Sistemas de Liberação de Medicamentos , Humanos , Isótopos/administração & dosagem , Transferência Linear de Energia , Lipossomos , Masculino , Neoplasias da Próstata/patologiaRESUMO
AIMS AND BACKGROUND: Californium-252 (²5²Cf) neutron brachytherapy is a form of high linear energy transfer radiotherapy, which has proven effective when used in combination with external beam radiotherapy to treat intracavitary cancers of the cervix, colon/rectum and esophagus. No study has been reported for treatment of intracavitary cancers with neutron brachytherapy alone. The aim of the study was to observe and analyze the long-term curative effects and complications for early stage thoracic esophageal cancer patients treated with neutron brachytherapy alone. METHODS: From December 2001 to August 2006, 16 patients of early stage squamous cell carcinoma underwent neutron brachytherapy. The total radiation dose to the reference point was 20-28 Gy-eq in 5 to 7 fractions with 4 Gy-eq/fraction. The 1-, 3-, and 5-year follow-up rates were 100%. RESULTS: The 2-, 3-, 4-, and 5-year survival rates were 100%, 87.5%, 87.5%, and 75%, respectively. The early complication rates for grades 1 and 2 radiation esophagitis were 75% and 25%, respectively. The late complication rates for grades 0 and 1 (according to the RTOG/EORTC standard) were 87.5% and 12.5%, respectively. Barium esophagography after treatments confirmed that the complete response rate was 100%. Fourteen patients were confirmed by endoscopy to have either normal mucosa or inflammation change. CONCLUSIONS: Neutron brachytherapy alone was an effective and safe treatment for early stage esophageal squamous cell cancer.
Assuntos
Braquiterapia/métodos , Califórnio/uso terapêutico , Carcinoma de Células Escamosas/radioterapia , Neoplasias Esofágicas/radioterapia , Nêutrons/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Califórnio/efeitos adversos , Carcinoma de Células Escamosas/patologia , Fracionamento da Dose de Radiação , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Nêutrons/efeitos adversos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Rose geranium (Pelargonium graveolens, Geraniaceae) has anti-cancer and anti-inflammatory properties, and promotes wound healing. Similarly, Ganoderma tsugae (Ganodermataceae), Codonopsis pilosula (Campanulaceae) and Angelica sinensis (Apiaceae) are traditional Chinese herbs associated with immunomodulatory functions. In the present study, a randomised, double-blind, placebo-controlled study was conducted to examine whether the Chinese medicinal herb complex, RG-CMH, which represents a mixture of rose geranium and extracts of G. tsugae, C. pilosula and A. sinensis, can improve the immune cell count of cancer patients receiving chemotherapy and/or radiotherapy to prevent leucopenia and immune impairment that usually occurs during cancer therapy. A total of fifty-eight breast cancer patients who received chemotherapy or radiotherapy were enrolled. Immune cell levels in patient serum were determined before, and following, 6 weeks of cancer treatment for patients receiving either an RG-CMH or a placebo. Administration of RG-CMH was associated with a significant reduction in levels of leucocytes from 31·5 % for the placebo group to 13·4 % for the RG-CMH group. Similarly, levels of neutrophils significantly decreased from 35·6 % for the placebo group to 11·0 % for the RG-CMH group. RG-CMH intervention was also associated with a decrease in levels of T cells, helper T cells, cytotoxic T cells and natural killer cells compared with the placebo group. However, these differences between the two groups were not statistically significant. In conclusion, administration of RG-CMH to patients receiving chemotherapy/radiotherapy may have the capacity to delay, or ease, the reduction in levels of leucocytes and neutrophils that are experienced by patients during cancer treatment.
Assuntos
Antineoplásicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/imunologia , Medicamentos de Ervas Chinesas/uso terapêutico , Imunidade Celular/efeitos dos fármacos , Leucopenia/prevenção & controle , Substâncias Protetoras/uso terapêutico , Anti-Inflamatórios/efeitos adversos , Anti-Inflamatórios/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias da Mama/radioterapia , Carcinoma in Situ/tratamento farmacológico , Carcinoma in Situ/imunologia , Carcinoma in Situ/radioterapia , Estudos de Coortes , Método Duplo-Cego , Medicamentos de Ervas Chinesas/efeitos adversos , Feminino , Humanos , Imunidade Celular/efeitos da radiação , Contagem de Leucócitos , Leucócitos/efeitos dos fármacos , Leucopenia/induzido quimicamente , Leucopoese/efeitos dos fármacos , Leucopoese/efeitos da radiação , Adesão à Medicação , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neutrófilos/efeitos dos fármacos , Substâncias Protetoras/efeitos adversosRESUMO
Radiobiological models are used in modern radiotherapy to evaluate the biological effects of different treatment plans or modalities. A radiobiological model typically converts a physical quantity (e.g. absorbed dose) to a biological quantity (e.g. cell survival fraction). Currently, the linear-quadratic model (LQM) is the most widely used model. Since it is a deterministic model, the LQM naturally ignores the uncertainties arising from the stochastic randomness of energy depositions along radiation tracks and the inherent unpredictable nature of biological systems. Recently, many studies have revealed the detailed spatial and temporal distributions of DNA damages, e.g. the DNA double strand breaks (DSBs), along various types of radiation tracks traversing a cell nucleus. Studies have also been conducted to unravel the biological pathways that involve in how cells and tissues process DNA damages. As such, the author proposes to start developing a new multi-scale radiobiological model based on the "bottom-up" approach. The model includes a Monte Carlo procedure to treat the stochastic randomness of radiation-induced DNA damages, and it also includes the relevant intercellular and intracellular pathways to allow the DNA damages to evolve into higher-order biological endpoints, e.g. chromosome aberrations, cell death, or tumorigenesis. Because of its stochastic nature, the new model inherently addresses the uncertainty issue being ignored by LQM. More importantly perhaps is that the model opens a new way to study radiation effects that involve biological pathways, and therefore, may have a profound impact on radiotherapy in the future.
Assuntos
Modelos Teóricos , Radiobiologia/métodos , Radioterapia , Quebras de DNA de Cadeia Dupla , Previsões , Humanos , Modelos Lineares , Método de Monte CarloRESUMO
Cooking oil fumes (COF) are known to be associated with respiratory diseases and risk of lung cancer. Involvement of trans,trans-2,4-decadienal (tt-DDE), a major component in COF, is suspected. Male CD-1(R) (ICR) mice were intratracheally instilled with either 8 or 24 mg.kg(-1) tt-DDE weekly for 8 weeks. Total numbers and types of cells in bronchoalveolar lavage fluid (BALF), as well as pathological changes, and inflammatory gene modulations in the lung tissues were assessed. We demonstrated that the number of alveolar macrophages in the BALF was significantly increased in tt-DDE-exposed animals. Histologically, there was a dose-correlated increase in epithelial hyperplasia and granulomatous nodules at the bronchioloalveolar junctions (BAJ). Although both Clara and alveolar type II cells were present in the BAJ lesion, only Clara cells were actively proliferative. However, only alveolar type II cells were found in the BAJ granulomatous nodules. Enhanced accumulation of phosphorylated signal transducer and activator of transcription 3 (pSTAT3), a known pro-carcinogenic factor, was also detected in many alveolar type II cells at the BAJ lesions. As both BAJ hyperplasia and enhanced pSTAT3 accumulation are known risk factors associated with increased lung adenocarcinoma development, these findings suggest that tt-DDE may pose a risk in lung carcinogenesis.
Assuntos
Poluentes Atmosféricos/efeitos adversos , Aldeídos/efeitos adversos , Bronquíolos/efeitos dos fármacos , Macrófagos Alveolares/efeitos dos fármacos , Mucosa Respiratória/efeitos dos fármacos , Aldeídos/administração & dosagem , Animais , Bronquíolos/patologia , Líquido da Lavagem Broncoalveolar , Gorduras Insaturadas na Dieta/administração & dosagem , Gorduras Insaturadas na Dieta/efeitos adversos , Hiperplasia/induzido quimicamente , Instilação de Medicamentos , Macrófagos Alveolares/patologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , Estresse Oxidativo , Fator de Transcrição STAT3/efeitos dos fármacos , Compostos Orgânicos VoláteisRESUMO
Kaposiform haemangioendothelioma is a rare soft-tissue tumour of infants and children, and presents as a moderately aggressive malignancy. We present the MRI findings of a histologically proven case of Kaposiform haemangioendothelioma without Kasabach-Merritt phenomenon or typical skin changes. Our case also reveals that the multiple foci of the cutaneous tumour have different MRI morphologies. These findings have not been reported in the literature to date.
Assuntos
Hemangioendotelioma/patologia , Dor/etiologia , Pele/patologia , Neoplasias de Tecidos Moles/patologia , Biópsia , Criança , Diagnóstico Diferencial , Hemangioendotelioma/complicações , Humanos , Imageamento por Ressonância Magnética , Masculino , Neoplasias de Tecidos Moles/complicações , Resultado do TratamentoRESUMO
Tomatoes, which are consumed worldwide, contain abundant phenolics. The objective of this study was to understand the suppression effect of phenolics in fresh and heated tomatoes on the expression of cyclooxygenase 2 (COX-2). Both small and big tomatoes of fresh or heated (in boiling water for 30 min) treatments were used. Sephadex LH-20 gel was used to separate the noncondensed tannin containing and the condensed tannin containing fractions from the crude phenolic extracts of tomatoes. The condensed tannin containing fraction was rich in condensed tannins and simple phenolics. The noncondensed tannin containing fraction contained abundant nontannin flavans. This study explored the effect of tomato phenolic extracts on the regulation of 12-o-teradecanoylphorbol-13-acetate (TPA)-induced inflammatory responses in KB cells. HPLC showed that tomato phenolic profiles were similar between small and big tomatoes either by fresh or heated treatment. Fresh tomato extracts had 70.8 +/- 4.8% (mean +/- SD) noncondensed tannin containing polyphenols (6.68 +/- 0.09 mg/g dry weight), 27.4 +/- 6.9% condensed tannin containing polyphenols (3.52 +/- 0.24 mg/g dry weight), and 1.7 +/- 0.6% other residues. Instead, heated tomato had 53.3 +/- 4.3% noncondensed tannin containing polyphenols (2.70 +/- 0.20 mg/g dry weight), 24.2 +/- 1.7% condensed tannin containing polyphenols (7.37 +/- 0.03 mg/g dry weight), and 22.5 +/- 4.8% other residues. Cell studies showed that phenolic extracts of heated tomatoes resulted in increased suppression of COX-2 expression compared with that of fresh tomato. Noncondensed tannin containing fraction of fresh tomato greatly suppressed COX-2 expression (P < 0.05) that compared to the negative control, but both noncondensed tannin containing and condensed tannin containing fractions of heated tomatoes showed suppression on COX-2 expression. These results suggest that tomato phenolics may play an important role in the chemoprevention of cancer.
Assuntos
Inibidores de Ciclo-Oxigenase 2/farmacologia , Ciclo-Oxigenase 2/metabolismo , Manipulação de Alimentos/métodos , Fenóis/farmacologia , Solanum lycopersicum/química , Adsorção , Análise de Variância , Cromatografia Líquida de Alta Pressão/métodos , Inibidores de Ciclo-Oxigenase 2/análise , Temperatura Alta , Humanos , Células KB , Neoplasias/prevenção & controle , Fenóis/análise , Proantocianidinas/análise , Proantocianidinas/farmacologia , Taninos/análise , Taninos/farmacologiaRESUMO
The new nanodosimetry-based linear-quadratic (LQ) formula has been reviewed for mixed-LET irradiation. V-79 Chinese hamster cells have been irradiated with a mixed-LET field of fission neutrons and gamma rays at the University of Maryland Training Reactor (MUTR). The results show that the experimental survival curve agrees well with that predicted by the new nanodosimetry-based LQ model. The experimental study described in this note, therefore, serves as a validation for the new model to be used for mixed-LET radiotherapies, e.g. 252Cf brachytherapy.
Assuntos
Bioensaio/métodos , Sobrevivência Celular/efeitos da radiação , Modelos Biológicos , Nanotecnologia/métodos , Radiometria/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Animais , Simulação por Computador , Cricetinae , Cricetulus , Relação Dose-Resposta à Radiação , Raios gama , Nêutrons , Doses de RadiaçãoRESUMO
We compared four different skin surface landmarks, the lower margin of the right 2nd costo-sternal junction (point A); the upper margin of the right 3rd costo-sternal junction (point B); the lower margin of the right 3rd costo-sternal junction (point C); and a point 5 cm below the manubrio-sternal junction (point D), in 20 cancer patients undergoing insertion of permanent central venous catheters whose tips were placed near the superior vena cava - right atrium (SVC-RA) junction under transoesophageal echocardiography guidance. The landmark was satisfactory if it was located within 1 cm of the SVC-RA junction. Points C and D were closer to the SVC-RA junction than points A and B (p < 0.0001). However, point C had the highest incidence (C: 70%, A: 0%, B: 20%, D: 30%, p < 0.0001) of being within 1 cm of the SVC-RA junction.
Assuntos
Cateterismo Venoso Central/métodos , Neoplasias/terapia , Pele/anatomia & histologia , Adolescente , Adulto , Idoso , Cateteres de Demora , Ecocardiografia Transesofagiana , Feminino , Átrios do Coração/anatomia & histologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Costelas/anatomia & histologia , Esterno/anatomia & histologia , Veia Cava Superior/anatomia & histologiaRESUMO
This study describes a digital technique for uterine morphometry and its application to endometrial structure during the bovine oestrous cycle. Neither the number nor the size of uterine gland ducts changed during the cycle but a reduction in total endometrial area from days 0 to 8 after oestrus led to an increase in the proportion of the endometrium occupied by gland ducts (gland duct density). This effect on day 8 was maintained to day 16. When endometrial morphology was related to circulating progesterone concentrations on days 5 and 8 of the luteal phase, no relationships were found on day 5, but on day 8, a high progesterone concentration was associated with an increased number of gland ducts. Furthermore, in animals slaughtered on day 8, a high progesterone concentration on day 5 was associated with decreased gland duct size, though a simultaneous decrease in endometrial area led to an increase in gland duct density. The results suggest that contrary to expectation, endometrial glands do not grow and regress during the oestrous cycle, although cyclic changes in endometrial area controlled by progesterone lead to changes in gland duct density.
Assuntos
Bovinos/anatomia & histologia , Decídua/anatomia & histologia , Ciclo Estral/fisiologia , Progesterona/sangue , Animais , Bovinos/sangue , Feminino , Processamento de Imagem Assistida por Computador , Microscopia , Microtomia , Coloração e RotulagemRESUMO
BACKGROUND: When implanting a permanent central venous catheter, the usual aim is to place the tip at the superior vena cava/right atrial (SVC/RA) junction. However, data validating radiographic landmarks of the SVC/RA junction are limited. This investigation was undertaken to compare the radiographic landmarks with the SVC/RA junction as determined by transesophageal echocardiography (TEE). METHODS: In 20 adult oncologic patients undergoing implantation of a permanent subcutaneous central venous catheter, the catheter tip was placed in the SVC/RA junction under TEE guidance. The position of the catheter tip on chest X-ray, which represented the echocardiographic SVC/RA junction, was then compared with a standard radiographic landmark of the SVC/RA junction and with thoracic vertebral levels. RESULTS: In all but two patients radiographic SVC/RA junctions were identified. The echocardiographic SVC/RA junction ranged from 0.6 cm above to 2.8 cm below the radiographic SVC/RA junction. There was a significant difference between the distance from the carina to the radiographic SVC/RA junction and the distance from the carina to the echocardiographic SVC/RA junction. The thoracic vertebral body correlating with the echocardiographic SVC/RA junction ranged from the sixth to the ninth level. CONCLUSION: Both the radiographic SVC/RA junction and the thoracic vertebral bodies are not reliable landmarks for the SVC/RA junction defined by TEE. Physicians should be aware that using the radiographic SVC/RA junction to confirm proper positioning of permanent central venous catheters risks placing the catheter tip in the upper SVC, with subsequent potential long-term complications. More reliable radiographic landmarks for the SVC/RA junction should be investigated.
Assuntos
Cateterismo Venoso Central , Coração/anatomia & histologia , Veia Cava Superior/diagnóstico por imagem , Adulto , Idoso , Ecocardiografia Transesofagiana , Feminino , Átrios do Coração/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Pré-OperatóriosRESUMO
We aimed to produce an estrogen-responsive reporter plasmid that would permit monitoring of estrogen receptor function in the uterus in vivo. The plasmid pBL-tk-CAT(+)ERE was induced by estrogen in bovine endometrial stromal cells. When the CAT gene was replaced by the secreted alkaline phosphatase SeAP, the resulting construct pBL-tk-SeAP(+)ERE remained estrogen responsive. However when the tk promoter was replaced by the cytomegalovirus (cmv) promoter, the resulting plasmid (pBL-cmv-SeAP(+)ERE) was not estrogen responsive. Inhibition of ERE function was not due to an effect in trans or due to lack of estrogen receptor. It was not due to an interaction between the cmv promoter and the SeAP gene. cmv promoter function was dependent on NF-kappaB, and mutagenesis in the NF-kappaB sites reduced basal reporter expression without imparting responsiveness to estrogen. A mutation in the TATA box also failed to impart estrogen responsiveness. Modeling of DNA accessibility indicated the ERE was inserted at a site accessible to transcription factors. We conclude that the cmv promoter inhibits ERE function in cis when the two sequences are located in the same construct, and that this effect does not involve an interaction between cmv and reporter gene, NF-kappaB sites or the TATA box, or DNA inaccessibility.
Assuntos
Citomegalovirus/genética , Estrogênios , Vetores Genéticos , Plasmídeos , Regiões Promotoras Genéticas , Elementos de Resposta , Animais , Bovinos , Células Cultivadas , Engenharia GenéticaRESUMO
The existing dosimetry protocol that uses the concept of RBE for 252Cf brachytherapy contains large uncertainties. A new formula has been developed to correlate the biological effect (i.e. cell survival fraction) resulting from a mixed n + gamma radiation field with two physical quantities and two biological quantities. The formula is based on a pathway model evolved from that of the compound-dual-radiation-action (CDRA) theory, previously proposed by Rossi and Zaider. The new model employs the recently published data on radiation-induced DNA lesions. The new formula is capable of predicting quantitatively the synergistic effect caused by the interactions between neutron events and gamma ray events, and it is intended to be included into a new dosimetry protocol for future 252Cf brachytherapy.
Assuntos
Braquiterapia/métodos , Califórnio/uso terapêutico , DNA/efeitos da radiação , Raios gama/uso terapêutico , Modelos Biológicos , Nêutrons/uso terapêutico , Radiometria/métodos , Algoritmos , Carga Corporal (Radioterapia) , Braquiterapia/efeitos adversos , Califórnio/efeitos adversos , Sobrevivência Celular/efeitos da radiação , Simulação por Computador , Dano ao DNA , Relação Dose-Resposta à Radiação , Raios gama/efeitos adversos , Nêutrons/efeitos adversos , Proteção Radiológica/métodos , Dosagem Radioterapêutica , Eficiência Biológica Relativa , Medição de Risco/métodos , Fatores de RiscoRESUMO
A new cholesterol-carborane conjugate (BCH) has been synthesized as a potential targeting agent for boron neutron capture therapy (BNCT) of cancers. The compound is extremely water insoluble and was formulated in two liposomal formulations to determine if the compound could be adequately taken up by 9L rat glioma cells in cell culture. Several factors potentially affecting the cellular uptake were evaluated, such as concentration of BCH in the incubation medium, incubation time, cell confluence, and the addition of polyethylene glycol (PEG) phospholipids to the liposomal formulation. The studies indicated that the cellular uptakes of BCH in the conventional and PEG liposomal formulations were 49.1 and 45.9 microg boron/g cells, respectively. Therefore, this compound, formulated in both liposomal formulations, delivered sufficient levels of boron to cancer cells in vitro, indicating that BCH is a promising approach for use in BNCT. The uptake appeared to depend upon BCH concentration in the media as well as the confluence of the cells. The greater boron uptake by nonconfluent cells indicated that active growth of cells was a factor in the uptake of this compound.