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1.
Radiat Oncol J ; 38(1): 60-67, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32229810

RESUMO

PURPOSE: We performed three-dimensional (3D) dose reconstruction-based pretreatment verification to evaluate gamma analysis acceptance criteria in volumetric modulated arc therapy (VMAT) for prostate cancer. MATERIALS AND METHODS: Pretreatment verification for 28 VMAT plans for prostate cancer was performed using the COMPASS system with a dolphin detector. The 3D reconstructed dose distribution of the treatment planning system calculation (TC) was compared with that of COMPASS independent calculation (CC) and COMPASS reconstruction from the dolphin detector measurement (CR). Gamma results (gamma failure rate and average gamma value [GFR and γAvg]) and dose-volume histogram (DVH) deviations, 98%, 2% and mean dose-volume difference (DD98%, DD2% and DDmean), were evaluated. Gamma analyses were performed with two acceptance criteria, 2%/2 mm and 3%/3 mm. RESULTS: The GFR in 2%/2 mm criteria were less than 8%, and those in 3%/3 mm criteria were less than 1% for all structures in comparisons between TC, CC, and CR. In the comparison between TC and CR, GFR and γAvg in 2%/2 mm criteria were significantly higher than those in 3%/3 mm criteria. The DVH deviations were within 2%, except for DDmean (%) for rectum and bladder. CONCLUSIONS: The 3%/3 mm criteria were not strict enough to identify any discrepancies between planned and measured doses, and DVH deviations were less than 2% in most parameters. Therefore, gamma criteria of 2%/2 mm and DVH related parameters could be a useful tool for pretreatment verification for VMAT in prostate cancer.

2.
Int J Med Sci ; 16(11): 1525-1533, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31673245

RESUMO

Radiotherapy, although used worldwide for the treatment of head, neck, and oral cancers, causes acute complications, including effects on vasculature and immune response due to cellular stress. Thus, the ability to diagnose side-effects and monitor vascular response in real-time during radiotherapy would be highly beneficial for clinical and research applications. In this study, recently-developed fluorescence micro-endoscopic technology provides non-invasive, high-resolution, real-time imaging at the cellular level. Moreover, with the application of high-resolution imaging technologies and micro-endoscopy, which enable improved monitoring of adverse effects in GFP-expressing mouse models, changes in the oral vasculature and lymphatic vessels are quantified in real time for 10 days following a mild localized single fractionation, 10 Gy radiotherapy treatments. Fluorescence micro-endoscopy enables quantification of the cardiovascular recovery and immune response, which shows short-term reduction in mean blood flow velocity, in lymph flow, and in transient immune infiltration even after this mild radiation dose, in addition to long-term reduction in blood vessel capacity. The data provided may serve as a reference for the expected cellular-level physiological, cardiovascular, and immune changes in animal disease models after radiotherapy.


Assuntos
Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Vasos Linfáticos/diagnóstico por imagem , Neoplasias Bucais/diagnóstico por imagem , Lesões por Radiação/diagnóstico por imagem , Animais , Fracionamento da Dose de Radiação , Endoscopia , Neoplasias de Cabeça e Pescoço/complicações , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Vasos Linfáticos/patologia , Vasos Linfáticos/efeitos da radiação , Camundongos , Boca/irrigação sanguínea , Boca/diagnóstico por imagem , Boca/patologia , Boca/efeitos da radiação , Neoplasias Bucais/patologia , Neoplasias Bucais/radioterapia , Lesões por Radiação/patologia
3.
PLoS One ; 12(5): e0178204, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28542649

RESUMO

This study was designed to identify potential radiosensitizing (RS) agents for combined radio- and chemotherapy in a murine model of human lung carcinoma, and to evaluate the in vivo effect of the RS agents using diffusion-weighted magnetic resonance imaging (DW-MRI). Radioresistance-associated genes in A549 and H460 cells were isolated on the basis of their gene expression profiles. Celastrol was selected as a candidate RS by using connectivity mapping, and its efficacy in lung cancer radiotherapy was tested. Mice inoculated with A549 carcinoma cells were treated with single ionizing radiation (SIR), single celastrol (SC), or celastrol-combined ionizing radiation (CCIR). Changes in radiosensitization over time were assessed using DW-MRI before and at 3, 6, and 12 days after therapy initiation. The tumors were stained with hematoxylin and eosin at 6 and 12 days after therapy. The percentage change in the apparent diffusion coefficient (ADC) value in the CCIR group was significantly higher than that in the SC and SIR group on the 12th day (Mann-Whitney U-test, p = 0.05; Kruskal-Wallis test, p < 0.05). A significant correlation (Spearman's rho correlation coefficient of 0.713, p = 0.001) was observed between the mean percentage tumor necrotic area and the mean ADC values after therapy initiation. These results suggest that the novel radiosensitizing agent celastrol has therapeutic effects when combined with ionizing radiation (IR), thereby maximizing the therapeutic effect of radiation in non-small cell lung carcinoma. In addition, DW-MRI is a useful noninvasive tool to monitor the effects of RS agents by assessing cellularity changes and sequential therapeutic responses.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Radiossensibilizantes/farmacologia , Triterpenos/farmacologia , Células A549 , Animais , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Quimiorradioterapia , Imagem de Difusão por Ressonância Magnética , Ensaios de Seleção de Medicamentos Antitumorais , Estudos de Viabilidade , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Masculino , Camundongos Nus , Transplante de Neoplasias , Triterpenos Pentacíclicos , Distribuição Aleatória
4.
Cancer Res Treat ; 48(3): 1074-83, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26511800

RESUMO

PURPOSE: We evaluated the role of adjuvant therapy in stage IIIA endometrioid adenocarcinoma patients who underwent surgery followed by radiotherapy (RT) alone or chemoradiotherapy (CTRT) according to risk group. MATERIALS AND METHODS: A multicenter retrospective study was conducted including patients with surgical stage IIIA endometrial cancertreated by radical surgery and adjuvant RT or CTRT. Disease-free survival (DFS) and overall survival (OS) were analyzed. RESULTS: Ninety-three patients with stage IIIA disease were identified. Nineteen patients (20.4%) experienced recurrence, mostly distant metastasis (17.2%). Combined CTRT did not affect DFS (74.1% vs. 82.4%, p=0.130) or OS (96.3% vs. 91.9%, p=0.262) in stage IIIA disease compared with RT alone. Patients with age ≥ 60 years, grade G2/3, and lymphovascular space involvement had a significantly worse DFS and those variables were defined as risk factors. The high-risk group showed a significant reduction in 5-year DFS (≥ 2 risk factors) (49.0% vs. 88.0%, p < 0.001) compared with the low-risk group (< 2). Multivariate analysis confirmed that more than one risk factor was the only predictor of worse DFS (hazard ratio, 5.45; 95% confidence interval, 2.12 to 13.98; p < 0.001). Of patients with no risk factors, a subset treated with RT alone showed an excellent 5-year DFS and OS (93.8% and 100%, respectively). CONCLUSION: We identified a low-risk subset of stage IIIA endometrioid adenocarcinoma patients who might be reasonable candidates for adjuvant RT alone. Further randomized studies are needed to determine which subset might benefit from combined CTRT.


Assuntos
Carcinoma Endometrioide/mortalidade , Carcinoma Endometrioide/terapia , Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/terapia , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/terapia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Carcinoma Endometrioide/patologia , Quimiorradioterapia Adjuvante/métodos , Intervalo Livre de Doença , Neoplasias do Endométrio/patologia , Feminino , Seguimentos , Humanos , Histerectomia , Estimativa de Kaplan-Meier , Excisão de Linfonodo , Metástase Linfática , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Radioterapia Adjuvante/métodos , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Salpingo-Ooforectomia , Falha de Tratamento
5.
Radiat Oncol J ; 33(2): 75-82, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26157676

RESUMO

PURPOSE: We evaluated the prognostic significance of T3 subtypes and the role of adjuvant radiotherapy in patients with resected the American Joint Committee on Cancer stage IIB T3N0M0 non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: T3N0 NSCLC patients who underwent resection from January 1990 to October 2009 (n = 102) were enrolled and categorized into 6 subgroups according to the extent of invasion: parietal pleura chest wall invasion, mediastinal pleural invasion, diaphragm invasion, separated tumor nodules in the same lobe, endobronchial tumor <2 cm distal to the carina, and tumor-associated collapse. RESULTS: The median overall survival (OS) and disease-free survival (DFS) were 55.3 months and 51.2 months, respectively. In postoperative T3N0M0 patients, the tumor size was a significant prognostic factor for survival (OS, p = 0.035 and DFS, p = 0.035, respectively). Patients with endobronchial tumors within 2 cm of the carina also showed better OS and DFS than those in the other T3 subtypes (p = 0.018 and p = 0.016, respectively). However, adjuvant radiotherapy did not cause any improvement in survival (OS, p = 0.518 and DFS, p = 0.463, respectively). Only patients with mediastinal pleural invasion (n = 25) demonstrated improved OS and DFS after adjuvant radiotherapy (n = 18) (p = 0.012 and p = 0.040, respectively). CONCLUSION: The T3N0 NSCLC subtype that showed the most favorable prognosis is the one with endobronchial tumors within 2 cm of the carina. Adjuvant radiotherapy is not effective in improving survival outcome in resected T3N0 NSCLC.

6.
Gynecol Oncol ; 138(3): 519-25, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26115977

RESUMO

OBJECTIVE: To investigate whether combined chemoradiotherapy (CTRT) confers a benefit for survival outcome over radiotherapy (RT) alone after primary surgery in patients with FIGO stage IIIC endometrial adenocarcinoma. METHODS: We conducted a multicenter retrospective study of patients with surgical stage IIIC endometrial cancer from 1990 to 2011. Adjuvant RT alone was performed in 85 patients (40.3%) and adjuvant CTRT in 126 patients (59.7%). Disease-free survival (DFS) and overall survival (OS) were analyzed using Kaplan-Meier method and Cox proportional hazards model. RESULTS: Stage IIIC1 and stage IIIC2 accounted for 63% and 37%, respectively. FIGO IIIC2 had a higher recurrence rate than FIGO IIIC1 (38.5% vs. 29.3%, p=0.172). Five-year OS and DFS were lower in FIGO IIIC2 than FIGO IIIC1 (85.1% vs. 76.9%, p=0.417; 71.0% vs. 59.2%, p=0.108, respectively). Eighteen patients (13.5%) in stage IIIC1 developed PALN recurrence, whereas only one (3.3%) in stage IIIC2 had PALN recurrence (p=0.001). In multivariate analysis, predictors of DFS were parametrial invasion (HR, 3.49; 95% CI, 1.83-6.64; p<0.001), higher grade (HR, 2.78; 95% CI, 1.31-5.89; p=0.008), and >3 positive pelvic nodes (HR, 1.84; 95% CI, 1.11-3.05; p=0.019). Combined CTRT did not affect DFS or OS in IIIC1 and IIIC2 compared with RT alone. CONCLUSION: CTRT showed comparable survival outcome to RT alone. Half of relapses (46%) in stage IIIC1 occurred in PALN region, whereas relapse in stage IIIC2 primarily occurred in distant metastasis (90%). Future randomized studies are needed to determine which subgroup may be most likely to benefit from CCRT.


Assuntos
Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/radioterapia , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/radioterapia , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimiorradioterapia Adjuvante , Intervalo Livre de Doença , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Radioterapia Adjuvante , Estudos Retrospectivos , Adulto Jovem
7.
Brachytherapy ; 14(4): 449-57, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25906951

RESUMO

PURPOSE: We performed a meta-analysis to compare the treatment outcomes between high-dose-rate (HDR) and low-dose-rate (LDR) intracavitary brachytherapy (ICBT) for the treatment of cervical cancer. METHODS AND MATERIALS: We searched the PubMed database for articles and the related referenced articles that compared HDR-ICBT and LDR-ICBT. A total of 15 published articles, 3 prospective randomized trials, and 12 retrospective studies performed between 1966 and December 2013 were selected using predefined inclusion and exclusion criteria for each study. The effect sizes were obtained from the odds ratios of the 5-year overall survival, 5-year disease-free survival (DFS), pelvic (locoregional) recurrence, and rectal and bladder complication rates in each study. The common effect sizes and 95% confidence intervals (CIs) were calculated using either the fixed or the random-effect model, according to the results of the homogeneity tests. RESULTS: We analyzed the outcome data for 18,937 patients, including 10,807 patients in the HDR-ICBT treatment group and 8,130 patients in the LDR-ICBT group. The common effect sizes (95% CI) for the 5-year survival rate, 5-year DFS rate, and pelvic recurrence rate were 1.1350 (0.9231-1.3955), 1.0777 (0.4896-2.3720), and 0.9521 (0.7624-1.1890), respectively. The common effect sizes (95% CI) for moderate-to-severe complication rates of the rectum and the bladder were 0.7645 (0.5099-1.1463) and 0.9051 (0.6140-1.3342), respectively. There were no significant differences between HDR- and LDR-ICBT considering the 5-year survival, 5-year DFS, pelvic recurrence, and the rectal and bladder complication rates. CONCLUSION: The treatment outcome after HDR-ICBT seems to be equivalent to that following LDR-ICBT in terms of survival, pelvic recurrence, and major complications.


Assuntos
Braquiterapia/métodos , Neoplasias do Colo do Útero/radioterapia , Braquiterapia/efeitos adversos , Protocolos Clínicos , Intervalo Livre de Doença , Feminino , Humanos , Recidiva Local de Neoplasia/radioterapia , Órgãos em Risco/efeitos da radiação , Estudos Prospectivos , Lesões por Radiação/etiologia , Dosagem Radioterapêutica , Reto/efeitos da radiação , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Bexiga Urinária/efeitos da radiação
8.
Imaging Sci Dent ; 44(1): 43-52, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24701458

RESUMO

PURPOSE: This study was designed to evaluate whether magnetic resonance imaging (MRI) is appropriate for detecting early changes in the mandibular bone marrow and pulp tissue of rats after high-dose irradiation. MATERIALS AND METHODS: The right mandibles of Sprague-Dawley rats were irradiated with 10 Gy (Group 1, n=5) and 20 Gy (Group 2, n=5). Five non-irradiated animals were used as controls. The MR images of rat mandibles were obtained before irradiation and once a week until week 4 after irradiation. From the MR images, the signal intensity (SI) of the mandibular bone marrow and pulp tissue of the incisor was interpreted. The MR images were compared with the histopathologic findings. RESULTS: The SI of the mandibular bone marrow had decreased on T2-weighted MR images. There was little difference between Groups 1 and 2. The SI of the irradiated groups appeared to be lower than that of the control group. The histopathologic findings showed that the trabecular bone in the irradiated group had increased. The SI of the irradiated pulp tissue had decreased on T2-weighted MR images. However, the SI of the MR images in Group 2 was high in the atrophic pulp of the incisor apex at week 2 after irradiation. CONCLUSION: These patterns seen on MRI in rat bone marrow and pulp tissue were consistent with histopathologic findings. They may be useful to assess radiogenic sclerotic changes in rat mandibular bone marrow.

9.
Oncol Rep ; 31(5): 2365-70, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24626722

RESUMO

Autophagy is known as an important regulatory mediator for cell survival or death and its important role in cancer. Pemetrexed (PTX) has been used in chemotherapy for lung cancer. However, the underlying molecular mechanisms have not been fully clarified. To investigate the role of autophagy induced by PTX in A549 cells, we performed MTT assay, acridine orange staining, western blotting, Annexin V/PI by using the 3-MA autophagy inhibitor. PTX induced autophagy after 48 h treatment in A549 cells. Furthermore, PTX showed acidic vesicular organelles (AVOs) and expressed LC3-II in A549 cells. The induction of autophagy by PTX was inhibited by 3-MA which was confirmed by reduced AVOs. When the autophagy was inhibited, Annexin V was increased. In addition, PARP cleavage was increased as shown by western blotting. Taken together, PTX induced autophagy in A549 cells and these cellular events possibly cause the apoptotic and/or necrotic cell death of A549 cells.


Assuntos
Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Glutamatos/farmacologia , Guanina/análogos & derivados , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Adenina/análogos & derivados , Adenina/farmacologia , Adenocarcinoma de Pulmão , Anexina A5/biossíntese , Antimetabólitos Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular , Guanina/farmacologia , Humanos , Pemetrexede , Poli(ADP-Ribose) Polimerases/metabolismo , Timidilato Sintase/antagonistas & inibidores
10.
Oncol Rep ; 31(1): 248-54, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24173208

RESUMO

The majority of chemotherapy treatments for lung cancer use cisplatin; however, its use is limited as it has several side-effects. Autophagy (or type II cell death) is an important mechanism by which programmed cell death occurs. The purpose of this study was to determine whether low-dose cisplatin treatment induces autophagy in lung cancer cells. We also examined whether autophagy inhibition results in p53-mediated apoptosis. NCI-H460 (wild-type p53) and NCI-H1299 (null-type p53) cells were treated with 5 or 20 µM cisplatin for 12, 24 or 48 h. An MTT assay was performed to measure the cell viability following cisplatin treatment. To detect cisplatin-induced autophagy, cell morphology (autophagic vacuole) and LC3 localization were examined. The outcome of autophagy inhibition was determined using 3-methyladenine (3-MA) to detect Annexin V (+), propidium iodide (PI) (-) and acridine orange (+) cells by FACS analysis. To determine whether cisplatin induced autophagy, we examined the role of p53 as a cell survival regulator in autophagy. Low-doses of cisplatin (5 µM) induced cell death and this was augmented by 3-MA in both cell lines. Autophagic vacuoles and cytoplasmic LC3 formation was more evident in H460 cells than in H1299 cells. The induction of autophagy by low-dose cisplatin was increased by 2-fold in H460 compared to H1299 cells. However, the tests for apoptosis showed no difference between the 2 cell lines. Following 3-MA pretreatment, cisplatin-induced autophagy was found to be markedly reduced (a 3-fold reduction) in wild-type p53 compared to null-type p53 cells. However, cisplatin-induced apoptosis increased in wild-type p53 compared to null-type p53 cells. Autophagy induction and apoptotic shift after autophagy inhibition may be mediated by p53 activation in lung cancer cells treated with low-dose cisplatin.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Cisplatino/farmacologia , Neoplasias Pulmonares/metabolismo , Proteína Supressora de Tumor p53/fisiologia , Adenina/análogos & derivados , Adenina/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Deleção de Genes , Humanos , Proteínas Associadas aos Microtúbulos/biossíntese , Proteína Supressora de Tumor p53/genética
11.
Oncol Rep ; 20(2): 379-84, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18636201

RESUMO

Arsenic trioxide (As2O3) has been introduced to the treatment of acute promyelocytic leukemia (APL), and has also been shown to induce apoptosis in a variety of solid tumor cell lines, including non-small cell lung cancer. However, the prohibitively high concentration required for the induction of apoptotic cell death in many solid tumor cells is unacceptable for clinical utilization due to the excessive toxicity associated with this dose. Sulindac is known to enhance the cellular responsiveness of tumors toward chemotherapeutic drugs. Herein, we demonstrated that combination treatment with As2O3 and sulindac resulted in a synergistic augmentation of cytotoxicity in H157 lung cancer cells, which was revealed by apoptotic induction as demonstrated by an increase in the sub-G0/G1 fraction. In addition, combination treatment with As2O3 and sulindac increased reactive oxygen species (ROS) and oxidative stress, as evidenced by the heme oxygenase-1 (HO-1) expression and mitogen-activated protein kinase (MAPK) phosphorylation. MAPK inhibitors blocked the induction of HO-1 by combination treatment. Inhibitors of p38 and JNK partially inhibited the augmented cell death whereas the ERK inhibitor showed poor inhibition. Combination treatment with As2O3 and sulindac induced oxidative DNA damage in a time-dependent fashion, which was evaluated by H2AX phosphorylation along with HO-1 induction.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias Pulmonares/patologia , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Trióxido de Arsênio , Arsenicais/administração & dosagem , Western Blotting , Dano ao DNA/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Citometria de Fluxo , Fase G1/efeitos dos fármacos , Heme Oxigenase-1/metabolismo , Histonas/metabolismo , Humanos , Peróxido de Hidrogênio/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Proteína Quinase 1 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Óxidos/administração & dosagem , Fosforilação/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Sulindaco/administração & dosagem , Células Tumorais Cultivadas , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
12.
Int J Radiat Oncol Biol Phys ; 71(4): 1230-5, 2008 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-18572086

RESUMO

PURPOSE: To determine whether systemically administered recombinant human epidermal growth factor (rhEGF) accelerates the recovery of mouse small intestinal mucosa after irradiation. METHODS AND MATERIALS: A mouse mucosal damage model was established by administering radiation to male BALB/c mice with a single dose of 15 Gy applied to the abdomen. After irradiation, rhEGF was administered subcutaneously at various doses (0.04, 0.2, 1.0, and 5.0 mg/kg/day) eight times at 2- to 3-day intervals. The evaluation methods included histologic changes of small intestinal mucosa, change in body weight, frequency of diarrhea, and survival rate. RESULTS: The recovery of small intestinal mucosa after irradiation was significantly improved in the mice treated with a high dose of rhEGF. In the mice that underwent irradiation without rhEGF treatment, intestinal mucosal ulceration, mucosal layer damage, and severe inflammation occurred. The regeneration of villi was noticeable in mice treated with more than 0.2 mg/kg rhEGF, and the villi recovered fully in mice given more than 1 mg/kg rhEGF. The frequency of diarrhea persisting for more than 3 days was significantly greater in the radiation control group than in the rhEGF-treated groups. CONCLUSIONS: Systemic administration of rhEGF accelerates recovery from mucosal damage induced by irradiation. We suggest that rhEGF treatment shows promise for the reduction of small intestinal damage after irradiation.


Assuntos
Fator de Crescimento Epidérmico/administração & dosagem , Enteropatias/tratamento farmacológico , Enteropatias/fisiopatologia , Mucosa Intestinal/fisiopatologia , Lesões por Radiação/tratamento farmacológico , Lesões por Radiação/fisiopatologia , Recuperação de Função Fisiológica/efeitos dos fármacos , Animais , Proliferação de Células/efeitos dos fármacos , Fator de Crescimento Epidérmico/genética , Enteropatias/etiologia , Mucosa Intestinal/efeitos dos fármacos , Intestino Delgado , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Lesões por Radiação/etiologia , Protetores contra Radiação/administração & dosagem , Proteínas Recombinantes/administração & dosagem , Resultado do Tratamento
13.
Oral Oncol ; 42(10): 979-86, 2006 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16472552

RESUMO

The Ku protein is essential for the repair of a majority of DNA double-strand breaks in mammalian cells. The purpose of this study was to investigate the relationship between the expression of Ku70/80 and sensitivity to radiation in cancer cell lines of the head and neck. The sensitivity to radiation in various head and neck cancer cell lines (AMC-HN-1 to -9) was analyzed by colony forming assay. Of the nine cell lines examined, the most radiosensitive cell line (AMC-HN-3) and the most radioresistant cell line (AMC-HN-9) were selected for this experiments. The expression of Ku70/80 was examined after irradiation using real time PCR, Western blotting and immunofluorescence in two different cell lines. Cell cycle distribution after irradiation were analysed. A differential radioresponse was demonstrated by expression of Ku70/80 in AMC-HN-3 and AMC-HN-9 cells. While the expression of Ku70 was slightly increased in the radioresistant AMC-HN-9 cell line, the expression of Ku80 was remarkably increased, suggesting a correlation between Ku80 expression and radiation resistance. Overexpression of Ku80 plays an important role in the repair of DNA damage induced by radiation. Ku80 expression may provide an effective predictive assay of radiosensitivity in head and neck cancers.


Assuntos
Antígenos Nucleares/metabolismo , Proteínas de Ligação a DNA/metabolismo , Neoplasias de Cabeça e Pescoço/metabolismo , Proteínas de Neoplasias/metabolismo , Tolerância a Radiação , Apoptose/efeitos da radiação , Western Blotting , Sobrevivência Celular/efeitos da radiação , Dano ao DNA , Reparo do DNA , DNA de Neoplasias/genética , Relação Dose-Resposta à Radiação , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Autoantígeno Ku , Células-Tronco Neoplásicas/patologia , Células-Tronco Neoplásicas/efeitos da radiação , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Células Tumorais Cultivadas
14.
Int J Radiat Oncol Biol Phys ; 65(1): 152-60, 2006 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-16472934

RESUMO

PURPOSE: To present preliminary results of intensity-modulated radiotherapy (IMRT) with the simultaneous modulated accelerated radiotherapy (SMART) boost technique in patients with nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: Twenty patients who underwent IMRT for nondisseminated NPC at the Asan Medical Center between September 2001 and December 2003 were prospectively evaluated. Intensity-modulated radiotherapy was delivered with the "step and shoot" SMART technique at prescribed doses of 72 Gy (2.4 Gy/day) to the gross tumor volume, 60 Gy (2 Gy/day) to the clinical target volume and metastatic nodal station, and 46 Gy (2 Gy/day) to the clinically negative neck region. Eighteen patients also received cisplatin once per week. RESULTS: The median follow-up period was 27 months. Nineteen patients completed the treatment without interruption; the remaining patient interrupted treatment for 2 weeks owing to severe pharyngitis and malnutrition. Five patients (25%) had Radiation Therapy Oncology Group Grade 3 mucositis, whereas 9 (45%) had Grade 3 pharyngitis. Seven patients (35%) lost more than 10% of their pretreatment weight, whereas 11 (55%) required intravenous fluids and/or tube feeding. There was no Grade 3 or 4 xerostomia. All patients showed complete response. Two patients had distant metastases and locoregional recurrence, respectively. CONCLUSION: Intensity-modulated radiotherapy with the SMART boost technique allows parotid sparing, as shown clinically and by dosimetry, and might also be more effective biologically. A larger population of patients and a longer follow-up period are needed to evaluate ultimate tumor control and late toxicity.


Assuntos
Neoplasias Nasofaríngeas/radioterapia , Radioterapia de Intensidade Modulada/métodos , Adulto , Idoso , Antineoplásicos/uso terapêutico , Cisplatino/uso terapêutico , Terapia Combinada/métodos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/tratamento farmacológico , Otite Média/etiologia , Estudos Prospectivos , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/efeitos adversos , Xerostomia/etiologia
15.
Acta Haematol ; 109(2): 95-100, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-12624494

RESUMO

We report a case of aggressive 'nasal type' natural killer (NK)/T cell lymphoma initially presenting as a testicular tumor in a Korean man, which quickly took a fatal course by widespread dissemination. Histologically, the testicular mass showed a diffuse dense infiltrate of medium-sized and atypical large lymphoid cells with angiocentric and angiodestructive infiltration and areas of coagulative necrosis on hematoxylin-eosin stained sections. Immunophenotyping by immunohistochemistry yielded surface markers consistent with NK/T cell lymphoma. The Epstein-Barr virus genome was detected by in situ hybridization. During involved-field irradiation and chemotherapy following radical orchiectomy, the tumor disseminated shortly to the skin and soft tissue of his anterior chest wall and central nervous system (CNS). Identical lymphoid infiltrates were present in the patient's skin. CNS involvement was interpreted as having a leptomeningeal seeding. To the best of our knowledge, this is the 9th reported case of confirmed NK/T cell lymphoma arising from the testis. Relevant literature is reviewed, and the clinicopathologic features, natural history, and treatment options for primary testicular NK/T cell lymphoma are discussed.


Assuntos
Células Matadoras Naturais , Linfoma de Células T/diagnóstico , Neoplasias Testiculares/diagnóstico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Sistema Nervoso Central/patologia , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Evolução Fatal , Herpesvirus Humano 4/genética , Humanos , Imuno-Histoquímica , Imunofenotipagem , Hibridização In Situ , Linfoma de Células T/patologia , Linfoma de Células T/terapia , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Necrose , Metástase Neoplásica , Orquiectomia , Prednisona/uso terapêutico , RNA Viral/análise , Radioterapia , Recidiva , Pele/patologia , Neoplasias Testiculares/patologia , Neoplasias Testiculares/terapia , Parede Torácica/patologia , Tomografia Computadorizada por Raios X , Ultrassonografia , Vincristina/uso terapêutico
16.
Int J Radiat Oncol Biol Phys ; 54(3): 768-79, 2002 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-12377329

RESUMO

PURPOSE: To clarify the role of vascular endothelial growth factor (VEGF) expression as an independent prognostic factor in Stage IB cervical cancer. METHODS AND MATERIALS: A total of 117 patients with Stage IB cervical cancer who had undergone radical hysterectomy and pelvic lymph node dissection with complete histopathologic examination were included. Eighty-eight (75.2%) patients received postoperative radiotherapy and/or chemotherapy. VEGF expression was examined using immunohistochemistry. RESULTS: Of 117 patients, 35 (29.9%) showed high-intensity VEGF expression and 69 (59%) had a high score for area of VEGF expression. Strong correlations were found between high VEGF intensity and both deep stromal invasion (p = 0.01) and positive pelvic lymph nodes (p = 0.03). The area of VEGF expression was significantly associated with tumor size (p = 0.02). In a multivariate analysis, high VEGF intensity (p = 0.009) and tumor size (p = 0.01) were significant prognostic factors for overall survival and disease-free survival (p = 0.001 and p = 0.003, respectively). However, the area of VEGF expression was not a prognostic factor for overall survival or disease-free survival. CONCLUSION: Our findings on the correlation between VEGF expression and prognosis were conflicting. Functional and quantitative tools to assess tumor angiogenesis in addition to the expression of VEGF need to be developed and would be helpful to support the finding that tumor angiogenesis correlates significantly with prognosis in early-stage cervical cancer.


Assuntos
Adenocarcinoma/química , Carcinoma Adenoescamoso/química , Carcinoma de Células Escamosas/química , Fatores de Crescimento Endotelial/análise , Peptídeos e Proteínas de Sinalização Intercelular/análise , Linfocinas/análise , Proteínas de Neoplasias/análise , Neoplasias do Colo do Útero/química , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Análise de Variância , Carcinoma Adenoescamoso/mortalidade , Carcinoma Adenoescamoso/patologia , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Prognóstico , Falha de Tratamento , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/patologia , Fator A de Crescimento do Endotélio Vascular , Fatores de Crescimento do Endotélio Vascular
17.
Clin Oncol (R Coll Radiol) ; 14(3): 241-9, 2002 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12109830

RESUMO

PURPOSE: To explore a static intensity-modulated radiation therapy (IMRT) technique of a more homogeneous isodose distribution to an irregular-shaped tumour of the ethmoid sinus, with concomitantly sparing the adjacent critical normal organs including the orbit. METHODS AND MATERIALS: We conducted a static IMRT technique adding 2 or smaller complementary boost-fields to the underdosed volume in the PTV, which resulted from complete blocking of the orbits in all coplanar or non-coplanar main ports of the standard 3-D CRT. The standard 3-D CRT plans (Plan A) and IMRT plans adding complementary boost fields (Plan B) were established for 10 patients with ethmoid sinus cancer. Two sets of different plans for each patient were compared using isodose distribution, dose statistics, and dose volume histogram (DVH) of the planning target volume (PTV) and also using dose statistics and DVH of the adjacent critical structures. RESULTS: The IMRT plans adding 2 or more complementary boost-fields (Plan B) for each patient demonstrated better coverage and improved dose homogeneity of the PTV compared to the standard 3-D CRT plan (Plan A). Moreover, the radiation doses to adjacent normal tissue organs, such as the orbits, optic nerves, brain stem and optic chiasm were similarly spared in both plans. CONCLUSION: With concomitantly sparing the surrounding visual pathway structures, our IMRT technique using the complementary boost-fields was quantitatively better than current standard 3-D CRT technique with respect to the dose homogeneity within the PTV. Therefore, we believe that our technique, though still not ideal, is thorough enough to be used routinely in treatment of ethmoid sinus tumour.


Assuntos
Seio Etmoidal , Neoplasias dos Seios Paranasais/radioterapia , Radioterapia Conformacional , Adulto , Idoso , Sistema Nervoso Central/efeitos da radiação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Vias Visuais/efeitos da radiação
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