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1.
Int J Mol Sci ; 22(19)2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34638817

RESUMO

Local radiotherapy (RT) is important to manage metastatic triple-negative breast cancer (TNBC). Although RT primarily reduces cancer cells locally, this control can be enhanced by triggering the immune system via immunotherapy. RT and immunotherapy may lead to an improved systemic effect, known as the abscopal effect. Here, we analyzed the antitumor effect of combination therapy using RT with an anti-programmed cell death-1 (PD-1) antibody in primary tumors, using poorly immunogenic metastatic mouse mammary carcinoma 4T1 model. Mice were injected subcutaneously into both flanks with 4T1 cells, and treatment was initiated 12 days later. Mice were randomly assigned to three treatment groups: (1) control (no treatment with RT or immune checkpoint inhibitor (ICI)), (2) RT alone, and (3) RT+ICI. The same RT dose was prescribed in both RT-alone and RT+ICI groups as 10Gy/fx in two fractions and delivered to only one of the two tumor burdens injected at both sides of flanks. In the RT+ICI group, 200 µg fixed dose of PD-1 antibody was intraperitoneally administered concurrently with RT. The RT and ICI combination markedly reduced tumor cell growth not only in the irradiated site but also in non-irradiated sites, a typical characteristic of the abscopal effect. This was observed only in radiation-sensitive cancer cells. Lung metastasis development was lower in RT-irradiated groups (RT-only and RT+ICI groups) than in the non-irradiated group, regardless of the radiation sensitivity of tumor cells. However, there was no additive effect of ICI on RT to control lung metastasis, as was already known regarding the abscopal effect. The combination of local RT with anti-PD-1 blockade could be a promising treatment strategy against metastatic TNBC. Further research is required to integrate our results into a clinical setting.


Assuntos
Inibidores de Checkpoint Imunológico/farmacologia , Neoplasias Pulmonares/prevenção & controle , Neoplasias Mamárias Experimentais/terapia , Tolerância a Radiação/efeitos dos fármacos , Animais , Linhagem Celular Tumoral , Feminino , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/secundário , Neoplasias Mamárias Experimentais/imunologia , Neoplasias Mamárias Experimentais/patologia , Camundongos , Camundongos Endogâmicos BALB C , Metástase Neoplásica , Tolerância a Radiação/imunologia , Tolerância a Radiação/efeitos da radiação
2.
Int J Clin Oncol ; 2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34677738

RESUMO

BACKGROUND: We evaluated whether there is a difference in the local recurrence and survival after pelvic external radiotherapy (ERT) with and without boost vaginal brachytherapy (VB) in cervical cancer patients with positive or close vaginal resected margins (RM). METHODS: We retrospectively reviewed FIGO stage IA-IIB cervical cancer patients treated with postoperative ERT between 1997 and 2018. The sixty patients showing close (safety margin < 5 mm) or positive vaginal RM were included. ERT was delivered with median 50.4 Gy in 28 fractions to the pelvis and VB with median 30 Gy in 6 fractions. RESULTS: The median follow-up duration was 46 months. Five out of 30 patients treated with ERT alone experienced vaginal recurrence within 2 years after surgery. The 5-year local control (LC) was 100% in patients receiving ERT + VB compared with 81.3% in patients receiving ERT alone (log rank p = 0.022). The 5-year pelvic control (PC) was 95.8% for patients receiving ERT + VB and 76.8% for ERT alone (p = 0.041). The 5-year overall survival and recurrence-free survival (RFS) were not significantly different between treatment groups. In multivariate analysis, perineural invasion was a significant risk factor for PC (p = 0.024). Parametrial involvement (p = 0.044) and vascular invasion (p = 0.032) were unfavorable prognostic factors for RFS. Late toxicity occurrences were not significant in both groups. CONCLUSION: VB after ERT improved LC and PC in cervical cancer patients with close or positive RM after hysterectomy. The toxicities were not increased after VB was added to ERT.

3.
Molecules ; 26(17)2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34500557

RESUMO

In this study, we aimed to evaluate the anticancer effect of benzimidazole derivatives on triple-negative breast cancer (TNBC) and investigate its underlying mechanism of action. Several types of cancer and normal breast cells including MDA-MB-231, radiotherapy-resistant (RT-R) MDA-MB-231, and allograft mice were treated with six benzimidazole derivatives including mebendazole (MBZ). Cells were analyzed for viability, colony formation, scratch wound healing, Matrigel invasion, cell cycle, tubulin polymerization, and protein expression by using Western blotting. In mice, liver and kidney toxicity, changes in body weight and tumor volume, and incidence of lung metastasis were analyzed. Our study showed that MBZ significantly induced DNA damage, cell cycle arrest, and downregulation of cancer stem cell markers CD44 and OCT3/4, and cancer progression-related ESM-1 protein expression in TNBC and RT-R-TNBC cells. In conclusion, MBZ has the potential to be an effective anticancer agent that can overcome treatment resistance in TNBC.


Assuntos
Antineoplásicos/farmacologia , Benzimidazóis/farmacologia , Mebendazol/farmacologia , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Animais , Biomarcadores Tumorais/metabolismo , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Feminino , Humanos , Rim/efeitos dos fármacos , Rim/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Neoplasias Pulmonares/metabolismo , Células MCF-7 , Camundongos , Camundongos Nus , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , Neoplasias de Mama Triplo Negativas/metabolismo
4.
Eur J Cancer ; 157: 31-39, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34474218

RESUMO

PURPOSE: To evaluate the role of adjuvant radiotherapy (RT) after curative resection in patients with extrahepatic bile duct (EHBD) cancer. METHODS: Between January 2000 and December 2015, 1475 patients with EHBD cancer who underwent curative resection were accrued from 14 institutions in Korea. Among these, 959 patients did not receive any adjuvant therapy (RT(-) group), while 516 underwent postoperative RT with or without chemotherapy (RT(+) group). RESULTS: The median age was 67 years. Nodal involvement was present in 482 patients (32.7%), and resection margin was involved in 293 patients (19.9%). RT(+) group had more patients with proximal tumours, advanced tumours, nodal involvement, perineural invasion, and involved resection margin than RT(-) group (all p < 0.001). With a median follow-up of 36 months, there were 211 locoregional recurrences, 307 distant metastases and 322 combined locoregional and distant failures. On multivariate analysis incorporating age, tumour location, differentiation, pT classification, pN classification, perineural invasion and resection margin, adjuvant RT was associated with improved overall survival (hazard ratio, 0.74; 95% confidence interval, 0.63-0.86; p < 0.001). When RT(+) group was separated into RT alone, concurrent chemoradiotherapy (CCRT) and CCRT followed by chemotherapy, the greatest benefit was observed in patients treated with CCRT followed by chemotherapy (hazard ratio, 0.52; 95% confidence interval, 0.41-0.68). CONCLUSIONS: Adjuvant RT combined with chemotherapy improved survival outcomes of resected EHBD cancer patients. Considering the greatest benefit observed in patients receiving CCRT followed by chemotherapy, a randomised controlled trial comparing chemotherapy alone and CCRT followed by chemotherapy is urgently needed.

5.
Int J Mol Sci ; 22(9)2021 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-34066541

RESUMO

Breast cancer is one of the major causes of deaths due to cancer, especially in women. The crucial barrier for breast cancer treatment is resistance to radiation therapy, one of the important local regional therapies. We previously established and characterized radio-resistant MDA-MB-231 breast cancer cells (RT-R-MDA-MB-231 cells) that harbor a high expression of cancer stem cells (CSCs) and the EMT phenotype. In this study, we performed antibody array analysis to identify the hub signaling mechanism for the radiation resistance of RT-R-MDA-MB-231 cells by comparing parental MDA-MB-231 (p-MDA-MB-231) and RT-R-MDA-MB-231 cells. Antibody array analysis unveiled that the MAPK1 protein was the most upregulated protein in RT-R-MDA-MB-231 cells compared to in p-MDA-MB-231 cells. The pathway enrichment analysis also revealed the presence of MAPK1 in almost all enriched pathways. Thus, we used an MEK/ERK inhibitor, PD98059, to block the MEK/ERK pathway and to identify the role of MAPK1 in the radio-resistance of RT-R-MDA-MB-231 cells. MEK/ERK inhibition induced cell death in both p-MDA-MB-231 and RT-R-MDA-MB-231 cells, but the death mechanism for each cell was different; p-MDA-MB-231 cells underwent apoptosis, showing cell shrinkage and PARP-1 cleavage, while RT-R-MDA-MB-231 cells underwent necroptosis, showing mitochondrial dissipation, nuclear swelling, and an increase in the expressions of CypA and AIF. In addition, MEK/ERK inhibition reversed the radio-resistance of RT-R-MDA-MB-231 cells and suppressed the increased expression of CSC markers (CD44 and OCT3/4) and the EMT phenotype (ß-catenin and N-cadherin/E-cadherin). Taken together, this study suggests that activated ERK signaling is one of the major hub signals related to the radio-resistance of MDA-MB-231 breast cancer cells.


Assuntos
Neoplasias da Mama/enzimologia , Neoplasias da Mama/radioterapia , Sistema de Sinalização das MAP Quinases , Tolerância a Radiação , Apoptose/efeitos dos fármacos , Fator de Indução de Apoptose/metabolismo , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Forma Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Clonais , Ciclofilina A/metabolismo , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Feminino , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Necroptose/efeitos dos fármacos , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Fenótipo , Poli(ADP-Ribose) Polimerases/metabolismo , Mapas de Interação de Proteínas/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Proteômica , Tolerância a Radiação/efeitos dos fármacos
6.
Int J Radiat Oncol Biol Phys ; 110(5): 1396-1406, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-33677048

RESUMO

PURPOSE: To evaluate the feasibility and efficacy of involved-field irradiation in definitive chemoradiation therapy for locoregional esophageal squamous cell carcinoma. METHODS AND MATERIALS: Patterns in recurrence and elective nodal failure were analyzed in patients from the previously published ESO-Shanghai 1 trial, who received definitive chemoradiation therapy with involved-field irradiation to 61.2 Gy in 34 fractions using intensity modulated radiation therapy planning. Nodal regions were delineated using the lymph node map from the sixth edition of the American Joint Committee on Cancer staging system. Elective nodal failure was defined as recurrence in the regional nodal area outside the planning target volume. Extensive elective nodal failure, defined as an extensive nodal area regardless of tumor location, was calculated for additional analysis. The incidental (ie, mean) irradiation dose of each node and each region was evaluated. RESULTS: With a median follow-up of 48.7 months among survivors, the 3-year actuarial rate for overall survival was 53.6%, and the median overall survival was 44.8 months (95% confidence interval, 34.6-55.0). Of the 436 patients included in this study, 258 patients (59.2%) experienced treatment failure. Elective nodal failure was experienced by 37 patients (8.5%), 7 (1.6%) of whom encountered nodal-only failure. The 3-year actuarial rates of elective nodal control and elective nodal-only control were 89.7% and 97.9%, respectively. The median incidental dose of these nodes was 33.2 Gy (interquartile range [IQR], 1.3-50.7 Gy). The median distance of each node to the planning target volume was 1.4 cm (IQR, 0.6-4.9 cm). Extensive elective nodal failure was experienced by 51 patients (11.6%), and 20 (4.6%) patients had nodal-only failure. The 3-year extensive elective nodal control and extensive elective nodal control-only rates were 86.0% and 94.3%, respectively. The median incidental dose of these nodes was 23.2 Gy (IQR, 1.1-53.5 Gy). The median distance of each node to the planning target volume was 2.0 cm (IQR, 0.6-5.5 cm). CONCLUSION: Involved-field irradiation can achieve a low rate of isolated nodal failure and a satisfactory survival outcome. The use of elective nodal irradiation may be unnecessary in definitive chemoradiation therapy for the treatment of locoregional esophageal squamous cell carcinoma.


Assuntos
Quimiorradioterapia/métodos , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas do Esôfago/terapia , Radioterapia de Intensidade Modulada/métodos , Idoso , China , Cisplatino/uso terapêutico , Intervalos de Confiança , Fracionamento da Dose de Radiação , Esquema de Medicação , Neoplasias Esofágicas/diagnóstico por imagem , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/radioterapia , Carcinoma de Células Escamosas do Esôfago/diagnóstico por imagem , Carcinoma de Células Escamosas do Esôfago/mortalidade , Carcinoma de Células Escamosas do Esôfago/radioterapia , Estudos de Viabilidade , Feminino , Fluoruracila/uso terapêutico , Humanos , Linfonodos/diagnóstico por imagem , Irradiação Linfática , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Paclitaxel/uso terapêutico , Estudos Prospectivos , Fatores de Tempo , Falha de Tratamento
7.
J Clin Med ; 10(4)2021 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-33670117

RESUMO

The immunologic aspects of radiation pneumonitis (RP) are unclear. We analyzed variations in cytokine profiles between patients with grade (Gr) 0-1 and Gr ≥ 2 RP. Fifteen patients undergoing concurrent chemoradiotherapy for non-small cell lung cancer were included. Blood samples of 9 patients with Gr 0-1 and 6 with Gr ≥ 2 RP were obtained from the Biobank. Cytokine levels were evaluated using an enzyme linked immunosorbent assay at before radiotherapy (RT) initiation, 1, 3, and 6 weeks post-RT initiation, and 1 month post-RT completion. Concentrations of granulocyte colony-stimulating factor (G-CSF), interleukin (IL)-6, IL-10, IL-13, IL-17, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and transforming growth factor (TGF)-ß were analyzed; none were related to the occurrence of Gr ≥ 2 RP at pre-RT initiation. At 3 weeks, relative changes in the G-CSF, IL-6, and IFN-γ levels differed significantly between the groups (p = 0.026, 0.05 and 0.026, respectively). One month post-RT completion, relative changes of IL-17 showed significant differences (p = 0.045); however, relative changes in TNF-α, IL-10, IL-13, and TGF-ß, did not differ significantly. Evaluation of changes in IL-6, G-CSF, and IFN-γ at 3 weeks after RT initiation can identify patients pre-disposed to severe RP. The mechanism of variation in cytokine levels in relation to RP severity warrants further investigation.

8.
Asia Pac J Clin Oncol ; 17(3): 209-215, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32757461

RESUMO

AIM: Stereotactic-body radiotherapy (SBRT) is a treatment option for portal vein tumor thrombosis (PVTT) in patients with hepatocellular carcinoma (HCC). Here, we report on our experience of treating PVTT using SBRT in patients with concomitant underlying chronic liver disease. METHODS: This study included 24 patients. The initial prescription dose was 45 Gy in three fractions in 17 (70.8%) patients, but it was modified in the remaining seven (29.2%) patients, with the dose ranging from 39 to 42 Gy in 3-4 fractions. After SBRT, transarterial chemoembolization (TACE) was performed in 16 (66.7%) patients. RESULTS: Of the 24 patients, 2 (8.3%) showed complete response, while 11 (45.8%) showed partial response. After a median follow-up of 8.4 months (range: 2.6-56.5 months), the 1-year overall survival (OS) and the median survival were 67.5% and 20.8 months, respectively. Both combined SBRT and TACE and grade ≥3 hepatic toxicity affected the 1-year OS (SBRT alone vs SBRT + TACE: 14.6% vs 71.4%, P < .001; presence of hepatic toxicity vs absence: 0% vs 81.1%, P = .002). CONCLUSIONS: Overall, SBRT, especially in combination with TACE, is an effective treatment for patients with HCC and PVTT. An optimal dose schedule must be followed to reduce hepatic toxicity while maintaining tumor response.


Assuntos
Carcinoma Hepatocelular/mortalidade , Quimioembolização Terapêutica/mortalidade , Doença Hepática Terminal/mortalidade , Neoplasias Hepáticas/mortalidade , Veia Porta/patologia , Radiocirurgia/mortalidade , Trombose Venosa/mortalidade , Adulto , Idoso , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/terapia , Terapia Combinada , Doença Hepática Terminal/complicações , Doença Hepática Terminal/patologia , Doença Hepática Terminal/terapia , Feminino , Humanos , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Trombose Venosa/complicações , Trombose Venosa/patologia , Trombose Venosa/terapia
9.
Radiother Oncol ; 154: 179-186, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32980384

RESUMO

PURPOSE: To investigate the safety and efficacy of intensity-modulated radiation therapy (IMRT) for early breast cancer compared with 3-dimensional conformal radiotherapy (3D-CRT) in a prospective and randomized trial. METHODS AND MATERIALS: From March 2015 to February 2018, 693 patients with pT1-2N0M0 early breast cancer who underwent breast-conserving surgery were enrolled and randomly assigned into IMRT and 3D-CRT. The primary endpoint was 3-year locoregional recurrence-free survival (LRRFS). The secondary endpoints were recurrence-free survival, overall survival, acute toxicity, target coverage index, irradiation dose to organs at risk, and fatigue inventory. The radiation dose for the 3D-CRT arm was 59.4 Gy in 33 fractions for 6.5 weeks. It was 57.4 Gy in 28 fractions with simultaneous integrated boost for 5.5 weeks for the IMRT arm. RESULTS: Of 693 patients, 349 and 344 patients received 3D-CRT and IMRT, respectively. There was no significant difference in LRRFS between the two arms. Conformity index of planning target volume was significantly superior in the IMRT arm than the 3D-CRT arm (p < 0.001). The mean lung dose and V5-V50 for the ipsilateral lung were significantly lower in the IMRT arm than the 3D-CRT arm (all p < 0.05). The incidence of grade 2 or higher dermatitis was significantly lower in the IMRT arm (p = 0.009). CONCLUSION: Compared to 3D-CRT, IMRT showed similar results in locoregional tumor control but superior results in planning target volume coverage. When IMRT is used in breast cancer, the irradiation dose to an ipsilateral lung and skin toxicity can be reduced.


Assuntos
Neoplasias da Mama , Radioterapia Conformacional , Radioterapia de Intensidade Modulada , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Humanos , Estudos Prospectivos , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Radioterapia Conformacional/efeitos adversos , Radioterapia de Intensidade Modulada/efeitos adversos
10.
Cancer Res Treat ; 53(3): 685-694, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33321563

RESUMO

PURPOSE: Radiotherapy (RT) is one of main strategies of cancer treatment. However, some cancer cells are resistant to radiation-induced cell death, including apoptosis. Therefore, alternative approaches targeting different anti-tumor mechanisms such as cell senescence are required. This study aimed to investigate the synergistic effect of alpha-lipoic acid (ALA) on radiation-induced cell death and senescence in MDA-MB-231 human breast cancer cells. MATERIALS AND METHODS: The cells were divided into four groups depending on the cell treatment (control, ALA, RT, and ALA+RT). Cells were analyzed for morphology, apoptotic cell death, mitochondrial reactive oxygen species, membrane potential, cellular senescence, and cell cycle. RESULTS: Our data showed that ALA significantly promoted apoptotic cell death when combined with RT, as reflected by Annexin V staining, expression of apoptosis-related factors, mitochondrial damages as well as cell morphological changes and reduction of cell numbers. In addition, ALA significantly enhanced radiation-induced cellular senescence, which was shown by increased HMGB1 expression in the cytosol fraction compared to the control, increased p53 expression compared to the control, activation of p38 as well as nuclear factor кB, and G2/M cell cycle arrest. CONCLUSION: The current study is the first report showing a new mode of action (senescence induction) of ALA beyond apoptotic cell death in MDA-MB-231 cancer cells known to be resistant to RT.

11.
Cancer Res Treat ; 52(4): 1188-1198, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32718145

RESUMO

PURPOSE: In pulmonary oligometastases from colorectal cancer (POM-CRC), the primarily recommended local therapy is metastasectomy. Stereotactic body radiotherapy (SBRT) is another local therapy modality that is considered as an alternative option in patients who cannot undergo surgery. The purpose of this meta-analysis is to demonstrate the effects of SBRT on POM-CRC by integrating the relevant studies. Materials and Methods: The authors explored MEDLINE, EMBASE, Cochrane Library, Web of Science, and SCOPUS, and selected studies including patients treated with SBRT for POM-CRC and availability of local control (LC) or overall survival (OS) rate. In this meta-analysis, the effect of SBRT was presented in the form of the LC and OS rates for 1, 2, 3, and 5 years after SBRT as pooled estimates, and the frequency of pulmonary toxicity of grade 3 or higher after SBRT (PTG3-SBRT). RESULTS: Fourteen full texts among the searched 4,984 studies were the objects of this meta-analysis. The overall number of POM-CRC patients was 495 as per the integration of 14 studies. The pooled estimate LC rate at 1, 2, 3, and 5 years after SBRT was 81.0%, 71.5%, 56.0%, and 61.8%, and the OS rate was 86.9%, 70.1%, 57.9%, and 43.0%, respectively. The LC and OS rates gradually declined until 3 years after SBRT in a similar pattern. Among the 14 studies, only two studies reported PTG3-SBRT as 2.2% and 10.8%, respectively. CONCLUSION: For POM-CRC, SBRT is an ablative therapy with a benefit on LC and OS rates and less adverse effects on the lung.


Assuntos
Neoplasias Colorretais/radioterapia , Neoplasias Pulmonares/radioterapia , Pneumonite por Radiação/epidemiologia , Radiocirurgia/efeitos adversos , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Humanos , Pulmão/patologia , Pulmão/efeitos da radiação , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/secundário , Pneumonite por Radiação/diagnóstico , Pneumonite por Radiação/etiologia , Índice de Gravidade de Doença , Taxa de Sobrevida , Resultado do Tratamento
12.
Qual Life Res ; 29(12): 3353-3361, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32705458

RESUMO

PURPOSE: We investigated the relationship of physical activity with dietary habits and quality of life (QoL) in breast cancer survivors in accordance with the recommendations of the American Cancer Society. METHODS: Data of 928 breast cancer survivors were obtained from the KROG 14-09 study to measure QoL in early phase after adjuvant radiotherapy. According to the extent of physical activity, survivors were divided into four groups: inactivity (0-149 min/week, N = 144), regular activity (150-450 min/week, N = 309), moderate activity (451-900 min/week, N = 229), and marked activity (901-1800 min/week, N = 164) excluding hyperactivity (> 1800 min/week, N = 82) as it is a difficult condition to recommend to survivors. Global physical activity questionnaire, 5-dimensional questionnaire by EuroQoL (EQ-5D-3L), QoL Questionnaire-breast cancer (QLQ-BR23) from EORTC, and dietary habits were surveyed. A linear-to-linear association test for EQ-5D-3L and Kruskal-Wallis analysis for QLQ-BR23 and dietary habit were conducted. RESULTS: Overall, 15.5% respondents (144/928) were classified as physically inactive. The trends of frequent intake of fruits (p = 0.001) and vegetable (p = 0.005) and reluctance toward fatty food (p < 0.001) were observed in physically active groups. Mobility (p = 0.021) and anxiety (p = 0.030) of EQ-5D-3L, and systemic therapy side effect (p = 0.027) and future perspective (p = 0.008) of QLQ-BR23 were better in physically active groups besides body image (p = 0.003) for the survivors with breast-conserving surgery. However, moderate and marked activities did not further improve QoL than regular activity. CONCLUSION: Physicians and care-givers have to pay attention to inactive survivors to boost their physical activity, thereby facilitating a better QoL and dietary habit.


Assuntos
Neoplasias da Mama/psicologia , Neoplasias da Mama/terapia , Exercício Físico/psicologia , Comportamento Alimentar/psicologia , Qualidade de Vida/psicologia , Adolescente , Adulto , Sobreviventes de Câncer , Feminino , Humanos , Inquéritos e Questionários , Adulto Jovem
13.
Thorac Cancer ; 11(8): 2163-2169, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32530138

RESUMO

BACKGROUND: A significant proportion of lung cancer patients suffer from malignant airway obstruction (MAO). Palliative external beam radiotherapy (EBRT) is often used to control the symptoms caused by MAO. In this study, we report the effect of palliative EBRT on lung cancer with MAO and analyze the factors that influence it. METHODS: This study included 75 patients with MAO in lung cancer who underwent palliative EBRT, between 2009 and 2018 and were analyzed retrospectively. Change of dyspnea, tumor response, and overall survival (OS) were recorded. Univariate and multivariate analyses were performed to determine the prognostic factors for treatment outcomes. RESULTS: The median follow-up duration was 2.5 months, and median OS was 2.3 months. Out of 75 patients, dyspnea was improved in 46 patients (61.3%), and tumor was partially decreased in 39 patients (52%). Symptoms improved in all tumor responding patients. The symptom improvement was significantly affected by radiation dose and time to EBRT. The tumor response was significantly affected by pathology, radiation dose, and time to EBRT. CONCLUSIONS: Palliative EBRT is an effective and safe treatment option for patients with MAO in lung cancer. In particular, high-dose irradiation and prompt treatment can improve treatment results. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: In MAO patients, tumor response is an important factor for resolving dyspnea and improving survival rate. In order to increase the tumor response, high-dose irradiation and prompt treatment after symptoms occur are necessary. WHAT THIS STUDY ADDS: Our study reported the effects of EBRT and prognostic factors in MAO patients. We emphasize that palliative EBRT is a relatively safe and effective treatment in MAO patients, which is a complement to previous studies.


Assuntos
Obstrução das Vias Respiratórias/radioterapia , Neoplasias Pulmonares/radioterapia , Dosagem Radioterapêutica/normas , Idoso , Idoso de 80 Anos ou mais , Obstrução das Vias Respiratórias/patologia , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
14.
Int J Mol Sci ; 21(11)2020 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-32531940

RESUMO

Radioiodine (RI) therapy is known to cause salivary gland (SG) dysfunction. The effects of antioxidants on RI-induced SG damage have not been well described. This study was performed to investigate the radioprotective effects of alpha lipoic acid (ALA) administered prior to RI therapy in a mouse model of RI-induced sialadenitis. Four-week-old female C57BL/6 mice were divided into four groups (n = 10 per group): group I, normal control; group II, ALA alone (100 mg/kg); group III, RI alone (0.01 mCi/g body weight, orally); and group IV, ALA + RI (ALA at 100 mg/kg, 24 h and 30 min before RI exposure at 0.01 mCi/g body weight). The animals in these groups were divided into two subgroups and euthanized at 30 or 90 days post-RI treatment. Changes in salivary 99mTc pertechnetate uptake and excretion were tracked by single-photon emission computed tomography. Salivary histological examinations and TUNEL assays were performed. The 99mTc pertechnetate excretion level recovered in the ALA treatment group. Salivary epithelial (aquaporin 5) cells of the ALA + RI group were protected from RI damage. The ALA + RI group exhibited more mucin-containing parenchyma and less fibrotic tissues than the RI only group. Fewer apoptotic cells were observed in the ALA + RI group compared to the RI only group. Pretreatment with ALA before RI therapy is potentially beneficial in protecting against RI-induced salivary dysfunction.


Assuntos
Lesões Experimentais por Radiação/prevenção & controle , Protetores contra Radiação/farmacologia , Glândulas Salivares/efeitos da radiação , Sialadenite/prevenção & controle , Ácido Tióctico/farmacologia , Animais , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Aquaporina 5/metabolismo , Peso Corporal/efeitos dos fármacos , Peso Corporal/efeitos da radiação , Senescência Celular/efeitos dos fármacos , Senescência Celular/efeitos da radiação , Ensaio de Imunoadsorção Enzimática , Feminino , Radioisótopos do Iodo/efeitos adversos , Camundongos Endogâmicos C57BL , Lesões Experimentais por Radiação/etiologia , Radioterapia/efeitos adversos , Radioterapia/métodos , Saliva/efeitos dos fármacos , Saliva/efeitos da radiação , Glândulas Salivares/efeitos dos fármacos , Glândulas Salivares/fisiopatologia , Sialadenite/etiologia , Testes de Função Tireóidea
15.
Molecules ; 25(8)2020 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-32326231

RESUMO

Artemisia annua L. has been reported to show anti-cancer activities. Here, we determined whether polyphenols extracted from Artemisia annua L. (pKAL) exhibit anti-cancer effects on radio-resistant MDA-MB-231 human breast cancer cells (RT-R-MDA-MB-231 cells), and further explored their molecular mechanisms. Cell viability assay and colony-forming assay revealed that pKAL inhibited cell proliferation on both parental and RT-R-MDA-MB-231 cells in a dose-dependent manner. The anti-proliferative effects of pKAL on RT-R-MDA-MB-231 cells were superior or similar to those on parental ones. Western blot analysis revealed that expressions of cluster of differentiation 44 (CD44) and Oct 3/4, matrix metalloproteinase-9 (MMP-9) and signal transducer and activator of transcription-3 (STAT-3) phosphorylation were significantly increased in RT-R-MDA-MB-231 cells compared to parental ones, suggesting that these proteins could be associated with RT resistance. pKAL inhibited the expression of CD44 and Oct 3/4 (CSC markers), and ß-catenin and MMP-9 as well as STAT-3 phosphorylation of RT-R-MDA-MB-231. Regarding upstream signaling, the JNK or JAK2 inhibitor could inhibit STAT-3 activation in RT-R-MDA-MB-231 cells, but not augmented pKAL-induced anti-cancer effects. These findings suggest that c-Jun N-terminal kinase (JNK) or Janus kinase 2 (JAK2)/STAT3 signaling are not closely related to the anti-cancer effects of pKAL. In conclusion, this study suggests that pKAL exhibit anti-cancer effects on RT-R-MDA-MB-231 cells by suppressing CD44 and Oct 3/4, ß-catenin and MMP-9, which appeared to be linked to RT resistance of RT-R-MDA-MB-231 cells.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Artemisia annua/química , Metaloproteinase 9 da Matriz/metabolismo , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , Extratos Vegetais/farmacologia , Polifenóis/farmacologia , beta Catenina/metabolismo , Antineoplásicos Fitogênicos/química , Biomarcadores , Biomarcadores Tumorais , Neoplasias da Mama , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Feminino , Expressão Gênica , Humanos , Imunofenotipagem , Janus Quinase 2/metabolismo , Extratos Vegetais/química , Polifenóis/química , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos
16.
Int J Mol Sci ; 21(7)2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-32218158

RESUMO

Radiation therapy is a standard treatment for patients with head and neck cancer. However, radiation exposure to the head and neck induces salivary gland (SG) dysfunction. Alpha lipoic acid (ALA) has been reported to reduce radiation-induced toxicity in normal tissues. In this study, we investigated the effect of ALA on radiation-induced SG dysfunction. Male Sprague-Dawley rats were assigned to the following treatment groups: control, ALA only (100 mg/kg, intraperitoneally), irradiation only, and ALA administration 24 h or 30 min prior to irradiation. The neck area, including SGs, was irradiated evenly at 2 Gy/min (total dose, 18 Gy) using a photon 6 MV linear accelerator. The rats were sacrificed at 2, 6, 8, and 12 weeks after irradiation. Radiation decreased SG weight, saliva secretion, AQP5 expression, parasympathetic innervation (GFRα2 and AchE expression), regeneration potentials (Shh and Ptch expression), salivary trophic factor levels (brain-derived neurotrophic factor and neurturin), and stem cell expression (Sca-1). These features were restored by treatment with ALA. This study demonstrated that ALA can rescue radiation-induced hyposalivation by preserving parasympathetic innervation and regenerative potentials.


Assuntos
Lesões Experimentais por Radiação/tratamento farmacológico , Glândulas Salivares/efeitos dos fármacos , Ácido Tióctico/farmacologia , Animais , Peso Corporal/efeitos dos fármacos , Masculino , Tamanho do Órgão/efeitos dos fármacos , Lesões Experimentais por Radiação/patologia , Ratos Sprague-Dawley , Glândulas Salivares/patologia
17.
Int J Radiat Biol ; 96(6): 759-766, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31977276

RESUMO

Purpose: Hepatocellular carcinoma (HCC) involving the inferior vena cava (IVC) and/or right atrium (RA) can affect systemic circulation, causing fatal complications. Standard treatment is yet to be established due to its rarity and intractability. We sought to determine the clinical efficacy of external beam radiotherapy (EBRT) in HCC treatment.Patients and methods: Our group designed this multicenter trial and recruited patients with HCC and IVC and/or RA involvement. Forty-nine patients from six institutions received EBRT with median dose of 46.7 (range: 35.4-71.5) Gy during 2009-2016. The primary outcome was overall survival (OS), and relevant predictors were evaluated.Results: Median follow-up length was 9.3 (range: 1.1-119) months. Median survival, 1-, and 2- year OS rates were 10.1 months (95% confidence interval [CI]: 7.5-12.7 months), 43.5%, and 30.1%, respectively. Significant factors affecting OS were alpha-fetoprotein level ≥300 ng/mL (risk ratio [RR]: 2.34, p = .025), tumor multiplicity (RR: 2.56, p = .028), and patient volume of institutions (high- vs. middle volume centers) (RR: 3.58, p = .001). Local control rates were 88.7% and 74.5% at 1 and 2 years, respectively. The most common first failure site was the lung (21/49, 42.9%) followed by liver outside the EBRT field (17/49, 34.7%). One case of possible radiation-induced liver disease was noted, with transient alkaline phosphatase elevation.Conclusion: EBRT can yield favorable local control in HCC with IVC and/or RA involvement. Systemic treatment may be more indicated as factors reflecting tumor aggressiveness were significant, and first distant failure is common.


Assuntos
Carcinoma Hepatocelular/irrigação sanguínea , Carcinoma Hepatocelular/radioterapia , Átrios do Coração/efeitos da radiação , Neoplasias Hepáticas/irrigação sanguínea , Neoplasias Hepáticas/radioterapia , Veia Cava Inferior/efeitos da radiação , Intervalo Livre de Doença , Estudos de Viabilidade , Feminino , Átrios do Coração/patologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , República da Coreia , Veia Cava Inferior/patologia
18.
Int J Mol Sci ; 20(22)2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31766286

RESUMO

Dry eye syndrome related to radiation therapy is relatively common and can severely impair a patient's daily life. The nuclear factor of activated T cells 5(NFAT5) is well known for its osmoprotective effect under hyperosmolar conditions, and it also has immune-modulating functions. We investigated the role of NFAT5 and the protective effect of α-lipoic acid(ALA) on radiation-induced lacrimal gland (LG) injuries. Rats were assigned to control, ALA only, radiation only, and ALA administered prior to irradiation groups. The head and neck area, including the LG, was evenly irradiated with 2 Gy/minute using a photon 6-MV linear accelerator. NFAT5 expression was enhanced and localized in the LG tissue after irradiation and was related to cellular apoptosis. ALA had a protective effect on radiation-induced LG injury through the inhibition of NFAT5 expression and NFAT5-dependent signaling pathways. Functional radiation-induced damage of the LG and cornea was also restored with ALA treatment. NFAT5 expression and its dependent signaling pathways were deeply related to radiation-induced dry eye, and the condition was improved by ALA treatment. Our results suggest a potential role of NFAT5 and NF-κB in the proinflammatory effect in LGs and cornea, which offers a target for new therapies to treat dry eye syndrome.


Assuntos
Aparelho Lacrimal/efeitos dos fármacos , Lesões por Radiação/tratamento farmacológico , Protetores contra Radiação/uso terapêutico , Ácido Tióctico/uso terapêutico , Fatores de Transcrição/metabolismo , Animais , Aparelho Lacrimal/metabolismo , Aparelho Lacrimal/patologia , Aparelho Lacrimal/efeitos da radiação , Masculino , Lesões por Radiação/metabolismo , Lesões por Radiação/patologia , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/efeitos da radiação
19.
Medicine (Baltimore) ; 98(40): e17390, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31577744

RESUMO

Stereotactic radiosurgery (SRS) is considered the initial treatment for lung cancer patients with small-sized and limited number of brain metastases. The objective of this study was to assess clinical outcomes of SRS treatment using CyberKnife (CK) for recursive partitioning analysis (RPA) class II/III patients with 1 to 3 brain metastases from lung cancer and identify which patients in the high RPA class could benefit from SRS.A total of 48 lung cancer patients who received CK-based SRS for their metastatic brain lesions from 2010 to 2017 were retrospectively analyzed. Radiographic response was evaluated during follow-up period. Overall survival (OS) and intracranial progression-free survival (IPFS) were calculated and prognostic variables associated with OS and IPFS were evaluated.Median follow-up time was 6.6 months. Local control rates at 6 months and 1-year following SRS were 98% and 92%, respectively. The median OS of all patients was 8 months. One-year and 2-year OS rates were 40.8% and 20.9%, respectively. In multivariate analysis, uncontrolled primary disease (P = .01) and Eastern Cooperative Oncology Group performance status of 2 or 3 (P = .001) were independent prognostic factors for inferior OS. These 2 factors were also significantly associated with inferior IPFS. In subgroup analysis according to RPA class, primary disease status was the only prognostic factor, showing statistically significant OS differences in both RPA class II and III (controlled vs uncontrolled: 41.1 vs 12.3 months in RPA class II, P = .03; 26.9 vs 4.1 months in RPA class III, P = .01).Our results indicated that SRS could be an effective treatment option for RPA class II/III patients with brain metastases from lung cancer in the modern treatment era. SRS might be particularly considered for patients with controlled primary disease.


Assuntos
Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/cirurgia , Neoplasias Pulmonares/patologia , Radiocirurgia/métodos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida
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