Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 64
Filtrar
1.
Front Oncol ; 11: 710245, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34796104

RESUMO

Background: Squamous cell cancers in the hypopharynx (HP) and cervical esophagus (CE) are different diseases with different staging systems and treatment approaches. Pharyngoesophageal junction (PEJ) tumor involves both the hypopharynx and the cervical esophagus simultaneously, but few reports focused on PEJ tumors. This study aimed to clarify clinical characteristics and the treatment approaches of PEJ tumors. Patients and Methods: A total of 222 patients with squamous cell carcinoma in the HP, PEJ, and CE were collected between January 2008 and June 2018 in Fudan University Shanghai Cancer Center. We compared different lymph node metastatic patterns of three diseases above and the survival of different tumor locations, different lymph node metastasis, and different radiotherapy approaches. Results: For HP, PEJ, and CE cancer, the upper and middle cervical lymph node metastatic rates were 85.7%, 47.1%, and 5.8%, respectively; the lower cervical lymph node metastatic rates were 36.7%, 42.9%, and 35.0%, respectively; and the mediastinal lymph node metastatic rates were 2.0%, 72.9%, and 80.6%, respectively. The 3-year overall survival rates were 69.5% in the HP group, 52.0% in the PEJ group, and 69.6% in the CE group (p = 0.024). No survival differences were found between the involved-field-irradiation and elective-node-irradiation subgroups among PEJ tumors (p = 0.717 for OS and p = 0.454 for PFS, respectively). Conclusion: HP cancers had a high prevalence in all cervical lymph node metastases, while CE cancers had a lower prevalence in the cervical and mediastinal lymph node metastases. PEJ cancer had the combined metastatic patterns of both HP and CE cancers. Involved field irradiation was feasible in chemoradiotherapy for PEJ cancers.

2.
Transl Lung Cancer Res ; 10(5): 2172-2192, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34164268

RESUMO

Background: In recent years, immunotherapy has made great progress, and the regulatory role of epigenetics has been verified. However, the role of 5-methylcytosine (m5C) in the tumor microenvironment (TME) and immunotherapy response remains unclear. Methods: Based on 11 m5C regulators, we evaluated the m5C modification patterns of 572 lung adenocarcinoma (LUAD) patients. The m5C score was constructed by principal component analysis (PCA) algorithms in order to quantify the m5C modification pattern of individual LUAD patients. Results: Two m5C methylation modification patterns were identified according to 11 m5C regulators. The two patterns had a remarkably distinct TME immune cell infiltration characterization. Next, 226 differentially expressed genes (DEGs) related to the m5C phenotype were screened. Patients were divided into three different gene cluster subtypes based on these genes, which had different TME immune cell infiltration and prognosis characteristics. The m5C score was constructed to quantify the m5C modification pattern of individual LUAD patients. We found that the high m5C score group had a better prognosis. The role of the m5C score in predicting prognosis was also verified in the dataset GSE31210. Conclusions: Our study revealed that m5C modification played a significant role in TME regulation of LUAD. Investigation of the m5C regulation mode may have some implications for tumor immunotherapy in the future.

3.
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
4.
IDCases ; 23: e00878, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33294369

RESUMO

Pelvic actinomycosis is a rare disease which is hard to be distinguished from other diseases such as malignant tumors and tuberculosis due to its nonspecific clinical signs and symptoms. If pelvic actinomycosis can be diagnosed preoperatively, the patients can be cured with antimicrobial therapy avoiding surgery. It is especially of concern to distinguish pelvic actinomycosis from pelvic mass, if there is a history of intrauterine device use. We report a case of pelvic actinomycosis that was diagnosed after the postoperative pathology of a suspected uterine malignancy.

5.
Cancer Lett ; 483: 114-126, 2020 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-32014456

RESUMO

Radioresistance reduces the success of therapy for patients with ESCC. Enhancing our understanding of the cardinal principles of radioresistance may improve the response of patients to irradiation. MicroRNAs perform a key role in posttranscriptional regulation, which is linked with the response of tumors to irradiation. Here, we successfully constructed a radioresistant cell line model, ECA109R, from parental esophageal cancer cell line ECA109. We used RNA-Seq analysis and qRT-PCR to compare the miRNA expression profiles of the ECA109 and ECA109R cell lines. The results revealed that miR-450a-5p was downregulated in the radioresistant cells. Functional analysis indicated that miR-450a-5p increases cellular radiosensitivity and suppresses autophagy in ESCC cells. We utilized a luciferase reporter assay to identify the target gene, DUSP10, as an indispensable regulator of the p38 and SAPK/JNK signaling pathways. Upregulation or downregulation of DUSP10 expression could reverse the effects of miR-450a-5p overexpression or inhibition. Tumor xenograft experiments verified that miR-450a-5p overexpression could increase sensitivity to radiation therapy in vivo. In general, our findings indicate that miR-450a-5p is a latent radiosensitizer and may represent a potential novel therapeutic target for radioresistance in ESCC.


Assuntos
Fosfatases de Especificidade Dupla/metabolismo , Neoplasias Esofágicas/radioterapia , Carcinoma de Células Escamosas do Esôfago/radioterapia , MicroRNAs/metabolismo , Fosfatases da Proteína Quinase Ativada por Mitógeno/metabolismo , Tolerância a Radiação , Animais , Apoptose/efeitos da radiação , Autofagia/efeitos da radiação , Linhagem Celular Tumoral , Fosfatases de Especificidade Dupla/genética , Neoplasias Esofágicas/enzimologia , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/enzimologia , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/patologia , Regulação Neoplásica da Expressão Gênica , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , Fosfatases da Proteína Quinase Ativada por Mitógeno/genética , Tolerância a Radiação/genética , Transdução de Sinais , Ensaios Antitumorais Modelo de Xenoenxerto , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
6.
Aging Dis ; 11(1): 82-92, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32010483

RESUMO

Non-small cell lung cancer (NSCLC) is the most common cancer and the leading cause of cancer-related deaths worldwide. Age at diagnosis of advanced NSCLC is much older, but studies describing the practice patterns for octogenarians with distant metastasis NSCLC are limited. A retrospective, population-based study using national representative data from the Surveillance, Epidemiology, and End Results (SEER) program was conducted to evaluate 34 882 NSCLC patients with extrathoracic metastases from 2010 to 2013. Patients were classified into three groups (older group: ≥80 yrs, middle-aged group: 60-79 yrs, and younger group: ≤59 yrs). The role of different age at diagnosis of NSCLC in metastasis patterns was investigated, and survival of different age groups of metastatic NSCLC was assessed. The analysis revealed that older patients were more likely to only have bone or liver metastasis (p< 0.001), but less likely to have brain only metastasis (p<0.001) and multiple metastatic sites (p< 0.001) than other two groups. Age at diagnosis was an independent risk factor for different metastasis types. Older group had the worst overall survival (p<0.001) and cancer-specific survival (p<0.001). Furthermore, older age patients with only bone metastasis had the best cancer specific survival (p<0.05) while younger patients with only brain metastasis had the best prognosis (p<0.001). Over 60% octogenarians with metastatic NSCLC did not receive anti-cancer therapy and had the highest rate of cancer deaths among all patients. Our results may help clinicians make positive decisions regarding personalized treatment of metastatic NSCLC in the elderly.

7.
Gene ; 711: 143949, 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31255735

RESUMO

As a transcriptional repressor, Chromobox 8 (CBX8) overexpression is found to be associated with tumorigenesis in several cancers. However, its role in radiotherapy resistance remains poorly characterized. Our study is the first to explore the correlation between CBX8 and radioresistance. We report here that CBX8 is upregulated in Esophageal Squamous Cell Carcinoma (ESCC) tissues and cells and serves as an indicator of poor prognosis for ESCC patients. CBX8 knockdown inhibits cell proliferation, colony formation capability, DNA repair and promotes cell apoptosis. Moreover, the transcriptome sequencing analysis demonstrates that CBX8 downregulates the expression of Apoptotic protease activating factor 1 (APAF1), which is the core protein that mediates mitochondrial apoptotic pathways. APAF1 depletion could abrogate apoptosis induced by CBX8 knockdown in irradiated ESCC cells. Our results provide novel insight into CBX8 as a therapeutic target to improve the radiosensitivity of ESCC.


Assuntos
Fator Apoptótico 1 Ativador de Proteases/genética , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Complexo Repressor Polycomb 1/metabolismo , Tolerância a Radiação , Animais , Fator Apoptótico 1 Ativador de Proteases/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos , Transplante de Neoplasias , Complexo Repressor Polycomb 1/genética , Prognóstico , Regulação para Cima
8.
Ann Transl Med ; 7(8): 176, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31168457

RESUMO

Background: Splicing factor 3b subunit 1 (SF3B1), a splicing factor modulating RNA alternative splicing, is frequently mutated in multiple hematological malignancies including myelodysplastic syndromes and chronic lymphocytic leukemia (CLL). The clinical impact of SF3B1 mutation on CLL remains controversial especially for patients of Asian descent. Methods: We retrospectively analyzed the frequency of SF3B1 mutation by Sanger sequencing in 399 newly diagnosed Chinese CLL patients. Results: SF3B1 mutation was detected in 5.5% (22/399) of the studied cohort with 59.1% of them being c.A2098G (p.K700E). SF3B1 mutation was common in patients with unmutated immunoglobulin heavy chain variable region gene, positive CD38 and positive ZAP-70. Survival analysis showed that SF3B1 mutation was associated with short treatment-free survival (TFS), but not overall survival (OS). We then developed 2 new risk models, named CLL-IPI-S and CLL-PI, according to the SF3B1 mutation status and CLL-international prognostic index (CLL-IPI); CLL-PI showed greater power to predict TFS than CLL-IPI in Chinese CLL patients. Conclusions: Our data suggest a low incidence and adverse clinical significance of SF3B1 mutation in newly diagnosed Chinese CLL patients.

9.
Oncol Lett ; 16(4): 5020-5026, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30250568

RESUMO

At present, chemotherapy and radiotherapy represent the primary modalities of treatment for patients with unresectable esophageal squamous cell carcinoma (ESCC). However, the outcome of patients remains poor owing to radioresistance. The present study aimed to determine the radiosensitizing effect of liriodenine, an aporphine alkaloid derived from Enicosanthellum pulchrum, and investigating the underlying mechanisms in ESCC, using the esophageal cancer ECA-109 cell line. Cellular proliferation was evaluated using the Cell Counting kit-8 assay. Colony formation assay was performed to characterize the radiosensitive effects of liriodenine on ECA-109 cells, and flow cytometry was used to detect the percentage of cells undergoing apoptosis. An immunofluorescence assay was utilized to evaluate the DNA damage repair ability. Western blotting was used to assess the protein levels of caspase-3, B cell lymphoma-2 (Bcl-2) and Bcl-2-associated X (Bax). Liriodenine dose-dependently inhibited ECA-109 cell viability. The clonogenic survival assay demonstrated that liriodenine increased the radiosensitivity of ESCC cells, with a sensitization enhancement ratio of 1.11-1.69. The results of flow cytometry demonstrated that liriodenine induced apoptosis and G2/M arrest. The immunofluorescence assay revealed that liriodenine delays DNA damage repair. The upregulation of Bax and Caspase-3, and the suppression of Bcl-2 confirmed that apoptosis was occurring. Liriodenine radiosensitizes ECA-109 cells by inducing apoptosis and G2/M arrest. The findings of the present study indicated that liriodenine may represent an anticancer agent with promising potential for the treatment of ESCC.

10.
Pathol Oncol Res ; 24(1): 11-18, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28132116

RESUMO

Exosomes are nanovesicles derived from tumor and normal cells that are detectable in human biological fluids, such as plasma, and cell culture supernatants. The function of exosome secretion from "normal" cells is unclear. Although numerous studies have investigated exosomes derived from hematopoietic cells, little is known regarding exosomes fromT cells, even though these cells play significant roles in innate and acquired immunity. A CCK-8 assay was used to examine the ability of exosomes to inhibit TE13 cell proliferation. In vitro invasion and wound healing assays were conducted to explore the effects of exosomes on TE13 cell migration and invasion. A Western blottinganalys is was performed to investigate the effects of exosomes on the expression of the EMT-related moleculesß-catenin, NF-κB and snail. This study aimed to investigate the effects of exosomes from irradiated T cells on the human esophageal squamous cell carcinoma (ESCC) cell line TE13 and revealed that exosomes inhibit the proliferation but promote the metastasis of TE13 cells in a dose-and time-dependent manner. Furthermore, exosomes significantly increased the expression of ß-catenin, NF-κB and snail in TE13 cells. The results of this study suggest an important role for T cell-derived exosomes in the progression of esophageal carcinoma: T cell-derived exosomes promote esophageal cancer metastasis, likely by promoting the EMT through the upregulation of ß-catenin and the NF-κB/snail pathway. Moreover, this study supports the use of exosomes as a nearly perfect example of biomimetic nanovesicles that could be utilized in future therapeutic strategies against various diseases, including cancer.


Assuntos
Carcinoma de Células Escamosas/secundário , Movimento Celular , Transição Epitelial-Mesenquimal , Neoplasias Esofágicas/patologia , Exossomos/patologia , Linfócitos do Interstício Tumoral/patologia , Linfócitos T/patologia , Carcinoma de Células Escamosas/imunologia , Proliferação de Células , Neoplasias Esofágicas/imunologia , Exossomos/imunologia , Exossomos/efeitos da radiação , Humanos , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/efeitos da radiação , Invasividade Neoplásica , Transdução de Sinais , Linfócitos T/imunologia , Linfócitos T/efeitos da radiação , Células Tumorais Cultivadas
11.
Pathol Oncol Res ; 24(1): 75-81, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28341911

RESUMO

Murine double minute 2 (MDM2) negatively regulates the activity of the p53 protein and plays a vital role in cell cycle arrest, apoptosis, and senescence mediated by p53. Nutlin-3, an antagonist of MDM2, is frequently used in anti-cancer studies. In many human tumors, nutlin-3 stabilizes p53 status and enhances p53 expression in cells with wild-type p53. However, the effect of nutlin-3 combined with radiotherapy on esophageal squamous cancer (ESCC) has not been reported. In this study, we examined whether nutlin-3 increases the radiosensitivity of ESCC in vitro and in vivo.We chose two cell lines, ECA-109 (wild-type p53) and TE-13 (p53 mutated), for the following experiments. Cell proliferation and clonogenic survival experiments showed that nutlin-3 inhibits the cell growth and colony formation of ECA-109 cells in a dose-dependent manner. Flow cytometry analysis showed that the apoptosis rate of ECA-109 cells co-treated with nutlin-3 and irradiation(IR) was significantly increased compared with cells treated with irradiation or nutlin-3 alone. Western blotting detected the expression of apoptosis-associated proteins in ECA-109 cells in response to nutlin-3 and irradiation. These effects were not evident in TE-13 cells. Xenograft mouse models indicated that nutlin-3 suppresses tumor growth and promotes radiosensitivity in the ESCC cell line ECA-109 in vivo. We have demonstrated that co-treatment of nutlin-3 with irradiation can significantly inhibit the growth and improve the radiosensitivity of ESCC cells with wild-type p53. The study suggests that nutlin-3 may be a potent therapeutic agent in conjunction with radiotherapy in ESCC.


Assuntos
Carcinoma de Células Escamosas/radioterapia , Neoplasias Esofágicas/radioterapia , Imidazóis/farmacologia , Piperazinas/farmacologia , Proteínas Proto-Oncogênicas c-mdm2/antagonistas & inibidores , Tolerância a Radiação/efeitos dos fármacos , Proteína Supressora de Tumor p53/metabolismo , Animais , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/metabolismo , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Proliferação de Células/efeitos dos fármacos , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Raios gama , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Mutação , Células Tumorais Cultivadas , Proteína Supressora de Tumor p53/genética , Ensaios Antitumorais Modelo de Xenoenxerto
12.
Medicine (Baltimore) ; 96(38): e7946, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28930829

RESUMO

AIM: This meta-analysis was designed to fully assess the curative effects of radiotherapy-based therapies for human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC). METHODS: English articles were retrieved through searching Cochrane library, PubMed, and Embase databases updated to February 2017. Studies were selected based on the inclusion and exclusion criteria. The curative effects of radiotherapy-based therapies forHER2+ BC patients were assessed using hazard rates (HRs) or odds ratios (ORs), as well as their 95% confidence intervals (CIs). In addition, Egger test was used to assess publication bias, followed by sensitivity analysis. All statistic methods were conducted using R 3.12 software. RESULTS: A total of 9 eligible studies were included into this meta-analysis, which involved 2236 HER2+ BC patients. Egger test showed that the eligible studies had no publication bias (t = 2.198, P = .05918). Sensitivity analysis demonstrated that the results were stable. HER2+ BC patients in radiotherapy group had lower locoregional recurrences than those in other groups. Moreover, meta-analysis showed that no significant difference was found between HER2+ BC patients in radiotherapy group and other groups on the 1-year overall survival (P = 0.5263, I = 65.4%), 3-year overall survival (P = 0.4591, I = 0), and 5-year overall survival (P = 0.06277, I = 0). CONCLUSION: Radiotherapy-based therapies might have certain advantages in treating HER2+ BC patients.


Assuntos
Neoplasias da Mama/química , Neoplasias da Mama/radioterapia , Radioterapia/mortalidade , Receptor ErbB-2/efeitos da radiação , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Radioterapia/métodos , Receptor ErbB-2/análise , Taxa de Sobrevida , Resultado do Tratamento
13.
J Cancer ; 8(6): 983-992, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28529610

RESUMO

As a crucial event involved in the metastasis and relapse of esophageal cancer, c-Met overexpression has been considered as one of the culprits responsible for the failure in patients who received radiochemotherapy. Since c-Met has been confirmed to be pivotal for cell survival, proliferation and migration, little is known about its impact on the regulation of radiosensitivity in esophageal cancer. The present study investigated the radiosensitization effects of c-Met inhibitor foretinib in ECA-109 and TE-13 cell lines. Foretinib inhibited c-Met signaling in a dose-dependent manner resulting in decreases in the cell viability of ECA-109 and TE-13. Pretreatment with foretinib synergistically prompted cell apoptosis and G2/M arrest induced by irradiation. Moreover, decreases ability of DNA damage repair was also observed. In vivo studies confirmed that the combinatorial use of foretinib with irradiation significantly diminishes tumor burden compared to either treatment alone. The present findings implied a crucial role of c-Met in the modulation of radiosensitization in esophageal cancer, and foretinib increased the radiosensitivity in ECA-109 and TE-13 cells mainly via c-Met signaling, highlighting a novel profile of foretinib as a potential radiosensitizer for the treatment of esophageal cancer.

14.
Radiother Oncol ; 124(3): 439-447, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28431753

RESUMO

OBJECTIVES: To investigate the biological function of eEF2K in esophageal squamous cell carcinoma (ESCC). MATERIALS AND METHODS: Tissue microarrays containing 100 pairs of ESCC tumor and adjacent normal tissues were completed. Overexpression and knockdown of eEF2K were constructed in ECA-109 and TE-13 ESCC cells. DNA damage, cell viability, migration and invasion, radioresistance, apoptosis and autophagy were determined by immunofluorescence, CCK-8, transwell assay, colony formation assay, flow cytometry and western blot, respectively. Tumor growth and radioresistance were also evaluated using xenograft models created in nude mice. RESULTS: eEF2K expression was higher in ESCC tissues compared with matched non-tumor tissues (P<0.05). Proliferation was increased in eEF2K overexpressing cells compared with controls (P<0.05), while silencing eEF2K reduced cell proliferation (P<0.05). Furthermore, lower levels of eEF2K expression correlated with slower migration and invasion rates (P<0.05), while higher levels of eEF2K expression with faster migration and invasion rates (P<0.05). eEF2K overexpression resulted in radioresistance and radiation-induced autophagy, and reduced radiation-induced apoptosis compared with controls, but silencing eEF2K promoted radiosensitivity and apoptosis, and reduced autophagy. In addition, eEF2K overexpression promoted the tumor growth in vivo (P<0.01). Combined treatment of NH125 (a pharmacological inhibitor of eEF2K) and radiation was more effective at delaying xenograft tumor growth than NH125 and radiation alone (P<0.05). CONCLUSION: eEF2K induced progression and radioresistance in ESCC, which may be a novel therapeutic target for ESCC to increase radiosensitivity.


Assuntos
Carcinoma de Células Escamosas/patologia , Quinase do Fator 2 de Elongação/fisiologia , Neoplasias Esofágicas/patologia , Animais , Apoptose , Autofagia , Carcinoma de Células Escamosas/radioterapia , Linhagem Celular Tumoral , Proliferação de Células , Progressão da Doença , Neoplasias Esofágicas/radioterapia , Carcinoma de Células Escamosas do Esôfago , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Tolerância a Radiação
15.
J Thorac Dis ; 9(3): 610-620, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28449469

RESUMO

BACKGROUND: Cancer stem cells (CSCs) are widely abundant and considered to be an important factor in therapy resistance. They are also promising potential targets for conquering tumors. We explored the effects of radiation on stem cell-like tumor cells via the candidate marker CD90 to provide new ideas for the comprehensive treatment of esophageal squamous cell carcinoma (ESCC). METHODS: We constructed CD90 overexpression ESCC cells by lentiviral transfection and observed differences of toxicity, proliferation, clone number, apoptosis, migration, invasion, and in vivo tumor formation after irradiation. RESULTS: We found that the population of CD90 positive cells showed CSC-like characteristics, including increased tumorigenicity and migration in ESCC cells. We discovered that these capacities were strengthened to varying degrees in remaining cells after irradiation. Further exploration revealed that the genes of ETS-1 and its downstream target MMPs changed significantly, which are correlated with the epithelial mesenchymal transition (EMT). These effects lead to enhanced tumor growth and resistance to radiation. CONCLUSIONS: We show that CD90 overexpressing ESCC cells exhibit CSC-like characteristics and radiation resistance. From a clinical perspective, ESCC patients with tumors that have high CD90 expression, which inhibits apoptosis, could exhibit more local invasion as well as distant metastasis, indicating a poorer prognosis. Research on the mechanism of CD90 may provide a new perspective to therapeutic strategies for patients with ESCC.

16.
J Thorac Dis ; 9(3): 849-859, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28449496

RESUMO

Esophageal cancer is the eighth most common cancer and the sixth leading cause of cancer-related death worldwide. Surgery is the primary form of treatment, but the survival is poor, especially for patients with locally advanced esophageal cancer. Radiotherapy has been a critical treatment option that may be combined with chemotherapy in patients with unresectable esophageal cancer. However, resistance to chemoradiotherapy might result in treatment failures and cancer relapse. This review will mainly focus on the possible cellular mechanisms and tumor-associated microenvironmental (TAM) factors that result in radioresistance in patients with esophageal cancer. In addition, current strategies to increase radiosensitivity, including targeted therapy and the use of radiosensitive biomarkers in clinical treatment, are discussed in this review.

17.
Crit Rev Oncol Hematol ; 107: 128-137, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27823640

RESUMO

PURPOSE: With the advances in radiotracers, positron emission tomography/computed tomography (PET/CT) is recognized as a useful adjunct to anatomic imaging with CT, MRI and endoscopic ultrasonography (EUS). The objective of this review was to comprehensively analyze the roles of PET/CT for the radiotherapy of esophageal cancer. METHODS: In this review, we focused on issues concerning the application of PET/CT in TNM staging, target volume delineation and response to therapy, both for the primary tumor and regional lymph nodes. Furthermore, the following questions were addressed: how does PET/CT guide appropriate treatment protocols, how does it allow accurate tumor delineation and how does it guide prognosis and future treatment decisions. RESULTS AND CONCLUSION: For the staging of esophageal cancer, PET/CT played a crucial role in exploring distant malignant lymph nodes and metastasis with high sensitivity, specificity and accuracy. PET/CT using different radiotracer provided a serial of thresholding methods based on standardized uptake value (SUV) to assist in auto-contouring the gross tumor volume (GTV). The change in SUV may offer a potential paradigm of personalized treatment to definitive chemoradiotherapy (CRT). In total, PET/CT has sought to further optimize radiotherapy treatment planning for patients with esophageal cancer.


Assuntos
Neoplasias Esofágicas/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias Esofágicas/radioterapia , Fluordesoxiglucose F18 , Humanos , Linfonodos , Imageamento por Ressonância Magnética , Estadiamento de Neoplasias
18.
Drug Des Devel Ther ; 10: 2271-8, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27471375

RESUMO

OBJECTIVE: Statins are widely used lipid-lowering drugs, which have pleiotropic effects, such as anti-inflammation, and vascular protection. In our study, we investigated the radioprotective potential of simvastatin (SIM) in a murine model of radiation-induced salivary gland dysfunction. DESIGN: Ninety-six Institute of Cancer Research mice were randomly divided into four groups: solvent + sham irradiation (IR) (Group I), SIM + sham IR (Group II), IR + solvent (Group III), and IR + SIM (Group IV). SIM (10 mg/kg body weight, three times per week) was administered intraperitoneally 1 week prior to IR through to the end of the experiment. Saliva and submandibular gland tissues were obtained for biochemical, morphological (hematoxylin and eosin staining and Masson's trichrome), and Western blot analysis at 8 hours, 24 hours, and 4 weeks after head and neck IR. RESULTS: IR caused a significant reduction of salivary secretion and amylase activity but elevation of malondialdehyde. SIM remitted the reduction of saliva secretion and restored salivary amylase activity. The protective benefits of SIM may be attributed to scavenging malondialdehyde, remitting collagen deposition, and reducing and delaying the elevation of transforming growth factor ß1 expression induced by radiation. CONCLUSION: SIM may be clinically useful to alleviate side effects of radiotherapy on salivary gland.


Assuntos
Radioterapia/efeitos adversos , Glândulas Salivares/efeitos dos fármacos , Glândulas Salivares/fisiopatologia , Sinvastatina/farmacologia , Animais , Masculino , Camundongos , Camundongos Endogâmicos ICR , Glândulas Salivares/metabolismo , Glândulas Salivares/efeitos da radiação , Raios X
19.
Asian Pac J Cancer Prev ; 17(3): 1221-33, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27039752

RESUMO

PURPOSE: To investigate any potential association between wine and breast cancer risk. MATERIALS AND METHODS: We quantitatively assessed associations by conducting a meta-analysis based on evidence from observational studies. In May 2014, we performed electronic searches in PubMed, EmBase and the Cochrane Library to identify studies examining the effect of wine drinking on breast cancer incidence. The relative risk (RR) or odds ratio (OR) were used to measure any such association. RESULTS: The analysis was further stratified by confounding factors that could influence the results. A total of twenty-six studies (eight case-control and eighteen cohort studies) involving 21,149 cases were included in our meta-analysis. Our study demonstrated that wine drinking was associated with breast cancer risk. A 36% increase in breast cancer risk was observed across overall studies based on the highest versus lowest model, with a combined RR of 1.0059 (95%CI 0.97-1.05) in dose-response analysis. However, 5 g/d ethanol from wine seemed to have protective value from our non-linear model. CONCLUSIONS: Our findings indicate that wine drinking is associated with breast cancer risk in a dose-dependent manner. High consumption of wine contributes to breast cancer risk with protection exerted by low doses. Further investigations are needed for clarification.


Assuntos
Neoplasias da Mama/etiologia , Vinho/efeitos adversos , Estudos de Casos e Controles , Relação Dose-Resposta a Droga , Feminino , Humanos , Prognóstico , Fatores de Risco
20.
Onco Targets Ther ; 9: 1759-66, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27042126

RESUMO

BACKGROUND: Radiofrequency ablation (RFA) is a minimally invasive thermal ablation technique. We conducted a meta-analysis based on eligible studies to assess the efficacy and safety of RFA for treating patients with breast cancer. METHODS: A literature search was conducted in PubMed, Embase, and Web of Science databases. Eligible studies were clinical trials that assessed RFA in patients with breast cancer. The outcomes included complete ablation rate, recurrence rate, excellent or good cosmetic rates, and complication rate. A random-effects or fixed-effects model was used to pool the estimate, according to the heterogeneity among the included studies. RESULTS: Fifteen studies, with a total of 404 patients, were included in this meta-analysis. Pooled results showed that 89% (95% confidence interval: 85%-93%) of patients achieved a complete ablation after RFA treatment and 96% of patients reported a good-to-excellent cosmetic result. Although the pooled result for recurrence rate was 0, several cases of relapse were observed at different follow-up times. No RFA-related complications were recorded, except for skin burn with an incidence of 4% (95% confidence interval: 1%-6%). CONCLUSION: This meta-analysis showed that RFA can be a promising alternative option for treating breast cancer since it produces a higher complete ablation rate with a low complication rate. Further well-designed randomized controlled trials are needed to confirm the efficacy and safety of RFA for breast cancer.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...