Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 656
Filtrar
1.
Adv Exp Med Biol ; 1287: 59-68, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33034026

RESUMO

Esophageal squamous cell carcinoma (ESCC) is a deadly disease that requires extensive research on its mechanisms, prevention, and therapy. Recent studies have shown that NOTCH mutations are commonly seen in human ESCC. This chapter summarizes our current understanding of the NOTCH pathway in normal esophagus and in ESCC. In normal esophagus, NOTCH pathway regulates the development of esophageal squamous epithelium, in particular, squamous differentiation. Exposure to extrinsic and intrinsic factors, such as gastroesophageal reflux, alcohol drinking, and inflammation, downregulates the NOTCH pathway and thus inhibits squamous differentiation of esophageal squamous epithelial cells. In ESCC, NOTCH plays a dual role as both a tumor suppressor pathway and an oncogenic pathway. In summary, further studies are warranted to develop NOTCH activators for the prevention of ESCC and NOTCH inhibitors for targeted therapy of a subset of ESCC with activated NOTCH pathway.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Receptores Notch/metabolismo , Carcinogênese , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/metabolismo , Carcinoma de Células Escamosas do Esôfago/patologia , Humanos , Transdução de Sinais
2.
Medicine (Baltimore) ; 99(45): e21850, 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33157909

RESUMO

INTRODUCTION: Esophageal subepithelial lesions (SELs) are rare, and the majority of them are benign. SELs are often covered with normal mucosa, thereby resulting in some malignant SELs to be easily missed or misdiagnosed. We report 2 cases of esophageal intramural squamous cell carcinomas (SCCs) that presented as SELs and were endoscopically removed. PATIENT CONCERNS: Case 1 is a 63-year-old man with abdominal distension; case 2 is a 65-year-old man with increasing dysphagia for 2 months. DIAGNOSIS: In case 1, endoscopy showed a 1.5-cm mucosal eminence with normal overlying mucosa. Endoscopic ultrasound (EUS) revealed that it might be derived from the muscularis mucosa or submucosa. In case 2, endoscopy revealed a 1.2-cm hemispherical lesion covered with smooth mucosa. Furthermore, EUS revealed that this lesion might be derived from the submucosa. INTERVENTIONS: In both cases, the lesions were removed by endoscopic submucosal dissection (ESD). Pathological examination revealed esophageal SCC nests with intramural growth patterns. OUTCOMES: The first patient underwent postoperative radiotherapy, whereas the second patient did not receive any additional treatment. Both patients agreed to regular follow-up, and no tumor recurrence or metastasis was observed. CONCLUSION: First, not all esophageal SELs are benign, and a small number of SELs can be malignant. Second, these cases illustrate the value of newer endoscopic techniques, especially ESD. Thus, it is important to be alert when visualizing the esophagus for the possibility of a subtle SEL so that further evaluation and treatment, if necessary, can be undertaken, ideally with a less invasive approach afforded by ESD.


Assuntos
Ressecção Endoscópica de Mucosa , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/cirurgia , Idoso , Carcinoma de Células Escamosas do Esôfago/radioterapia , Humanos , Masculino , Pessoa de Meia-Idade
3.
Zhonghua Zhong Liu Za Zhi ; 42(8): 635-643, 2020 Aug 23.
Artigo em Chinês | MEDLINE | ID: mdl-32867454

RESUMO

Objective: To investigate the effects of microRNA-182-5p (miR-182-5p) on cell proliferation and invasion of esophageal squamous cell carcinoma (ESCC) and its related molecular mechanisms. Methods: Real-time quantitative polymerase chain reaction (RT-qPCR) was employed to detect the miR-182-5p expression in ESCC tissues and cells. MiR-182-5p inhibitor, miR-182-5p mimic and negative control (NC) were transfected into ESCC Eca109 and TE1 cells, and miR-182-5p expression after transfection was examined using RT-qPCR. Cell counting kit-8 (CCK-8) was utilized to investigate the cell proliferation and Transwell chamber was used to detect the cell invasion ability. Dual-luciferase reporter assay was used to detect the direct interaction of miR-182-5p and cell adhesion molecule 2 (CADM2), RT-qPCR was employed to detect CADM2 expression in ESCC tissues, the correlation between CADM2 and miR-182-5p was also examined. Finally, western blot was used to detect the protein expressions of CADM2, focal adhesion kinase (FAK), p-Akt and Akt after transfection. Results: The miR-182-5p level in ESCC tissues was (2.180±1.295), significantly higher than (0.890±0.284) in normal esophageal epithelial tissues (P<0.001). The survival ratio of ESCC patients with high miR-182-5p level was evidently lower than that of ESCC patients with low miR-182-5p level (P<0.05). MiR-182-5p expression was significantly associated with TNM staging and lymph node metastasis (P<0.05). The expressions of miR-182-5p in ESCC cells including EC9706, Eca109, TE1, KYSE450 and KYSE70 were (2.449±0.082), (2.965±0.088), (4.873±0.258), (1.338±0.045) and (1.999±0.082), respectively, obviously higher than (0.989±0.087) in normal esophageal epithelial cell Het-1A (all P<0.01). Besides, miR-182-5p inhibitor significantly downregulated the miR-182-5p expression in Eca109 and TE1, and suppressed cell proliferation and invasion ability. Conversely, miR-182-5p mimic significantly upregulated the miR-182-5p expression in Eca109 and TE1, and promoted cell proliferation and invasion ability. Dual-luciferase reporter assay revealed that co-transfection of CADM2-3'UTR-WT and miR-182-5p mimic significantly reduced the luciferase activities in Eca109 and TE1 cells (P<0.01), and CADM2 was the direct target of miR-182-5p. The expression of CADM2 in ESCC tissues was (0.190±0.143), markedly lower than (0.845±0.327) in normal esophageal epithelial tissues (P<0.001). The miR-182-5p level exhibited negative correlation with CADM2 level in ESCC tissues (r=-0.5004, P<0.001). In addition, CADM2 expression was closely correlated with TNM staging and lymph node metastasis (P<0.05). The survival ratio of ESCC patients with high CADM2 level was evidently higher than that of ESCC patients with low CADM2 level (P<0.05). MiR-182-5p inhibitor significantly upregulated the expression of CADM2 protein, but suppressed the protein expressions of FAK, p-Akt and Akt, whereas miR-182-5p mimic markedly downregulated the expression of CADM2 protein, but promoted the protein expressions of FAK, p-Akt and Akt. Conclusion: MiR-182-5p is implicated in the carcinogenesis and development of ESCC, and thus may be a potential molecular target for ESCC patients.


Assuntos
Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Regulação Neoplásica da Expressão Gênica , MicroRNAs , Invasividade Neoplásica , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Humanos
4.
Zhonghua Zhong Liu Za Zhi ; 42(8): 676-681, 2020 Aug 23.
Artigo em Chinês | MEDLINE | ID: mdl-32867461

RESUMO

Objective: To evaluate the survival and prognostic factors of radiotherapy in patient with Ⅳ stage esophageal squamous carcinoma treated with radiation or chemoradiation. Methods: The medical records of 608 patients with stage Ⅳ esophageal squamous cell carcinoma who met the inclusion criteria in 10 medical centers in China from 2002 to 2016 were retrospectively analyzed. The overall survival and prognostic factors of all patients at 1, 3 and 5 years were analyzed. Results: The 1-, 3-, 5- year overall survival (OS) rates was 66.7%, 29.5% and 24.3% in stage ⅣA patients, and 58.8%, 29.0% and 23.5% in stage ⅣB patients. There was no statistical difference between the two groups (P=0.255). Univariate analysis demonstrated that the length of lesion, treatment plan, planned tumor target volume (PGTV) dose, subsequent chemotherapy, and degrees of anemia, radiation esophagitis, radiation pneumonia were related to the prognoses of patients with Ⅳ stage esophageal carcinomas after radiotherapy and chemotherapy (P<0.05). Multivariate analysis demonstrated that PGTV dose (OR=0.693, P=0.004), radiation esophagitis (OR=0.867, P=0.038), and radiation pneumonia (OR=1.181, P=0.004) were independent prognostic factors for OS. Conclusions: For patients with stage Ⅳ esophageal squamous cell carcinoma, chemoradiotherapy followed by sequential chemotherapy is recommended, which can extend the total survival and improve the prognosis of the patients. PGTV dose more than 60 Gy has better efficacy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia/métodos , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/radioterapia , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/radioterapia , China/epidemiologia , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/mortalidade , Carcinoma de Células Escamosas do Esôfago/patologia , Humanos , Estadiamento de Neoplasias , Radioterapia de Intensidade Modulada/métodos , Estudos Retrospectivos , Resultado do Tratamento
5.
PLoS Biol ; 18(9): e3000825, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32886690

RESUMO

Microbial dysbiosis in the upper digestive tract is linked to an increased risk of esophageal squamous cell carcinoma (ESCC). Overabundance of Porphyromonas gingivalis is associated with shorter survival of ESCC patients. We investigated the molecular mechanisms driving aggressive progression of ESCC by P. gingivalis. Intracellular invasion of P. gingivalis potentiated proliferation, migration, invasion, and metastasis abilities of ESCC cells via transforming growth factor-ß (TGFß)-dependent Drosophila mothers against decapentaplegic homologs (Smads)/Yes-associated protein (YAP)/Transcriptional coactivator with PDZ-binding motif (TAZ) activation. Smads/YAP/TAZ/TEA domain transcription factor1 (TEAD1) complex formation was essential to initiate downstream target gene expression, inducing an epithelial-mesenchymal transition (EMT) and stemness features. Furthermore, P. gingivalis augmented secretion and bioactivity of TGFß through glycoprotein A repetitions predominant (GARP) up-regulation. Accordingly, disruption of either the GARP/TGFß axis or its activated Smads/YAP/TAZ complex abrogated the tumor-promoting role of P. gingivalis. P. gingivalis signature genes based on its activated effector molecules can efficiently distinguish ESCC patients into low- and high-risk groups. Targeting P. gingivalis or its activated effectors may provide novel insights into clinical management of ESCC.


Assuntos
Infecções por Bacteroidaceae/complicações , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Porphyromonas gingivalis/fisiologia , Fator de Crescimento Transformador beta/fisiologia , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adulto , Idoso , Animais , Infecções por Bacteroidaceae/metabolismo , Infecções por Bacteroidaceae/mortalidade , Infecções por Bacteroidaceae/patologia , Células Cultivadas , Progressão da Doença , Drosophila , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/microbiologia , Neoplasias Esofágicas/mortalidade , Carcinoma de Células Escamosas do Esôfago/metabolismo , Carcinoma de Células Escamosas do Esôfago/microbiologia , Carcinoma de Células Escamosas do Esôfago/mortalidade , Feminino , Seguimentos , Células HCT116 , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Transdução de Sinais/fisiologia , Proteínas Smad/metabolismo , Análise de Sobrevida , Fatores de Transcrição/metabolismo , Fator de Crescimento Transformador beta/metabolismo
6.
PLoS One ; 15(9): e0238113, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32886924

RESUMO

Esophageal endoscopic submucosal dissection (ESD) can be a curative treatment for superficial esophageal squamous cell carcinoma (SESCC). However, it is unclear whether the development of metachronous recurrence after ESD may be explained based on several risk factors. This study aimed to assess the incidence and the risk factors of metachronous recurrence of SESCC after ESD. This retrospective analysis was conducted at Samsung Medical Center, Seoul, Korea, from April 2007 to May 2018. Two hundred and fifty-three SESCC patients treated with ESD were followed using surveillance endoscopy after the procedure. Risk factors for metachronous esophageal SCC were analyzed using the Kaplan-Meier method and Cox's proportional hazards model. Metachronous esophageal SCCs were found in 21 (8.3%) of the 253 patients. Six patients (2.4%) with extraesophageal recurrence such as lymph node metastasis confirmed by imaging were excluded from patients with metachronous recurrence and data were censored from the recurrence date. Univariate analysis revealed that the presence of many (>10) irregularly shaped multiform Lugol-voiding lesions (LVLs) around the main lesion, margin of the main LVL, and tumor differentiation were risk factors for the development of metachronous cancer. Multivariate analysis also revealed that many (>10) LVLs (hazard ratio [HR], 6.32; 95% confidence interval [CI], 1.62-24.72; p = 0.047) and unclear or spiculated margin of the main LVL (HR, 6.51; 95% CI, 1.44-29.42; p = 0.029) were associated with the risk of metachronous recurrence. Metachronous esophageal SCC develops in patients treated with ESD for SESCC. A risk assessment is important for surveillance before and after ESD for SESCC. Number of LVLs and tumor edge type are associated with an increased risk of metachronous cancer in SESCC. Patients will benefit from careful endoscopic surveillance when endoscopists pay attention to these tumor characteristics.


Assuntos
Ressecção Endoscópica de Mucosa , Carcinoma de Células Escamosas do Esôfago/cirurgia , Idoso , Estudos de Coortes , Carcinoma de Células Escamosas do Esôfago/patologia , Feminino , Humanos , Masculino , Recidiva , Fatores de Risco
7.
Medicine (Baltimore) ; 99(37): e22173, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32925786

RESUMO

Angiogenic factor with G-patch and FHA domain 1 (AGGF1) is a newly initiator of angiogenesis. Forkhead box C2 (FOXC2) that is a member of the winged spiral transcription factor family plays an important role in epithelial-mesenchymal transition (EMT). Epithelial-cadherin (E-cad) that is an adhesion molecule is also involved in EMT. The purpose of this study is to investigate the expression of AGGF1, FOXC2, and E-cad in esophageal squamous cell carcinoma (ESCC) and their clinical significance.Immunohistochemistry was performed to investigate the expression of AGGF1, FOXC2, and E-cad in 170 ESCC specimens and corresponding normal esophageal mucosa tissues. Follow-up data was also collected.The positive rates of AGGF1 and FOXC2 expression were significantly higher in ESCC group when compared with the control group; the positive rate of E-cad expression was significantly lower in ESCC group when compared with the control group. Positive rates of AGGF1, FOXC2, and E-cad expression were significantly associated with grades of differentiation, tumor grades, lymph node metastasis stages, as well as tumor-node-metastasis stages. Kaplan-Meier analysis demonstrated that positive expression of AGGF1 or FOXC2 for ESCC patients had significantly unfavorably overall survival time when compared with patients with negative expression of AGGF1 or FOXC2; and positive expression of E-cad for ESCC patients had significantly longer overall survival time when compared with patients with negative expression of E-cad. Multivariate analysis indicated that AGGF1, FOXC2, and E-cad expression and tumor-node-metastasis stages were postoperative independent prognostic factors for ESCC patients.AGGF1, FOXC2, and E-cad may be considered promising biomarkers of ESCC patients' prognosis.


Assuntos
Proteínas Angiogênicas/biossíntese , Antígenos CD/biossíntese , Caderinas/biossíntese , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Fatores de Transcrição Forkhead/biossíntese , Idoso , Biomarcadores Tumorais , Feminino , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neovascularização Patológica , Prognóstico
8.
Toxicol Lett ; 333: 62-70, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32739445

RESUMO

Cigarette smoking is a factor capable of inducing esophageal squamous cell carcinoma (ESCC). However, the biological pathways that are responsible for tumor development and are directly affected by cigarette smoking remain unknown. To explore the role of cigarette smoking in ESCC, we developed a long-term cigarette smoke extract (CSE) exposed cell model using the normal immortalized SHEE esophageal epithelial cell line, which would malignantly transform after long-term cultivation without carcinogens. CSE-exposed cells displayed higher malignancy and differently expressed several lncRNAs. Among them, H19, a lncRNA responsible for proliferation and invasion, was upregulated in CSE-exposed SHEE cells. In tumors from ESCC patients, H19 was significantly increased in smoking ESCC patients compared to non-smoking patients, and H19 was overexpressed and correlated with pathological tumor size in smokers. These results indicated that cigarette smoking lead to a different biological change from non-smoking induced ESCC and H19 related to cancer development during CSE-induced carcinogenesis.


Assuntos
Carcinogênese/efeitos dos fármacos , Neoplasias Esofágicas/induzido quimicamente , Carcinoma de Células Escamosas do Esôfago/induzido quimicamente , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , RNA Longo não Codificante/genética , Tabaco/toxicidade , Animais , Carcinogênese/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Transformação Celular Neoplásica/efeitos dos fármacos , Transformação Celular Neoplásica/genética , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/patologia , Feminino , Humanos , Masculino , Camundongos Nus , Fumaça/efeitos adversos , Fumar/efeitos adversos
9.
Medicine (Baltimore) ; 99(32): e21470, 2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32769880

RESUMO

Esophageal cancer is a common malignant tumor of the digestive system with a high incidence and a poor prognosis. At the present, CT-based radiomics is providing more and more valuable information. However, the heterogeneity of the study and the poor repeatability of the texture feature parameters have limited its wider clinical application. In the present study, we focused on comparing the differences in the texture features of T3 stage esophageal squamous cell carcinoma at different locations and normal esophageal wall, aiming to provide some pieces of useful information for future research on esophageal squamous cell carcinoma.Fifty seven cases with throat CT imaging, including esophageal cancer contrast enhanced CT and conventional CT of healthy control group. The texture characteristics in control group and tumor group among different parts were compared. Using Univariable analysis, we compared the difference and conducted receiver-operator curve analysis to evaluate the performance of tumor grade diagnosis model.53 radiomic features were significantly different in control group and so as 93 features for tumor group. The upper section was the mostly different from the other 2 sections. Run-length matrix (RLM) features in tumor group accounted for the highest proportion, only Surface Volume Ratio was different.There are differences in the texture features of the tube wall in different parts of the esophagus of healthy adults, and this difference is more obvious in pT3 stage esophageal squamous cell carcinoma. In the future radiomics study of esophageal squamous cell carcinoma, we need to pay attention to this to avoid affecting the accuracy of the results.


Assuntos
Neoplasias Esofágicas/diagnóstico por imagem , Carcinoma de Células Escamosas do Esôfago/diagnóstico por imagem , Radiometria/estatística & dados numéricos , Tomografia Computadorizada por Raios X/estatística & dados numéricos , Idoso , Estudos de Casos e Controles , Meios de Contraste , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Esôfago/diagnóstico por imagem , Esôfago/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Curva ROC , Radiometria/métodos , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Tomografia Computadorizada por Raios X/métodos
10.
Medicine (Baltimore) ; 99(27): e21099, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32629742

RESUMO

RATIONALE: Intramural esophageal squamous cell carcinoma (ESCC) without mucosal invasion is extremely rare. Endoscopic mucosal biopsy results are often negative, making diagnosis difficult. In these cases, endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) biopsy is a useful diagnostic method. PATIENT CONCERNS: A 78-year-old female was admitted to hospital due to dysphagia, and gastroscopy showed a concentric narrowing of the esophageal lumen with a smooth and undamaged esophageal mucosa. DIAGNOSES: Endoscopic ultrasound (EUS) revealed that the esophageal mucosa was thickened with a low echo, and the layers of the esophageal wall could not be clearly distinguished. Cytologic and pathologic diagnoses were obtained through EUS-FNA, which suggested ESCC. INTERVENTIONS: According to the pathologic diagnosis obtained by EUS-FNA, surgery or radiotherapy were recommended for this patient. Eventually, this patient elected to seek treatment at another medical institution. OUTCOMES: This type of disease cannot be diagnosed according to gastroscopic biopsy alone, and the diagnosis was eventually confirmed through EUS-FNA. LESSONS: When an imaging examination suggests a possible malignant lesion of the oesophagus, EUS-FNA may be considered if the surface mucosa contains no endoscopic damage. EUS-FNA has high diagnostic value with high sensitivity, minimal invasiveness, and high safety.


Assuntos
Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/métodos , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/diagnóstico por imagem , Carcinoma de Células Escamosas do Esôfago/patologia , Idoso , Transtornos de Deglutição/diagnóstico , Transtornos de Deglutição/etiologia , Feminino , Gastroscopia/métodos , Hospitalização , Humanos , Membrana Mucosa/patologia , Pacientes Desistentes do Tratamento/psicologia , Radioterapia/normas , Procedimentos Cirúrgicos Operatórios/normas
11.
Anticancer Res ; 40(8): 4387-4394, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32727767

RESUMO

BACKGROUND/AIM: Intensive trimodal therapy is needed for locally advanced esophageal squamous cell carcinoma (ESCC). The prediction of recurrence is especially required for patients with pathological residual tumors in the resected primary sites and/or lymph nodes [non-pathological complete response (pCR)] who have a high possibility of recurrence after trimodal therapy. We aimed to determine the risk factors for cancer recurrence in ESCC patients diagnosed with non-pCR after trimodal therapy. PATIENTS AND METHODS: We evaluated the risk factors for recurrence-free survival (RFS) using the multivariate Cox proportional hazards analysis, based on data from 105 ESCC patients diagnosed with non-pCR after neoadjuvant chemoradiotherapy followed by esophagectomy. RESULTS: Univariate analysis revealed that RFS was significantly associated with postoperative complications, pathological T, N, M stage after therapy (ypT, ypN, ypM), tumor differentiation, lymphovascular invasion (LVI), and pathological response of the primary tumor. Subsequent multivariate analysis revealed postoperative complications ypN, tumor differentiation, and LVI as independent variables for RFS. The RFSs significantly differed between patients with and without these risk factors. CONCLUSION: Severe postoperative complications, ypN 2/3, poor tumor differentiation, and LVI were significantly associated with poor RFS. These factors may be used as prognostic factors in patients with non-pCR after trimodal therapy.


Assuntos
Quimiorradioterapia/métodos , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas do Esôfago/terapia , Esofagectomia/métodos , Recidiva Local de Neoplasia/diagnóstico , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Terapia Neoadjuvante , Estadiamento de Neoplasias , Fatores de Risco , Análise de Sobrevida , Resultado do Tratamento
12.
Medicine (Baltimore) ; 99(29): e21306, 2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32702926

RESUMO

The aim of this study was to investigate the prognostic value of neutrophils-to-lymphocyte ratio in peripheral blood (NLR) and in cancer nest (iNLR) in patients with esophageal squamous cell carcinoma (ESCC).Totally 103 patients with ESCC treated with surgical radical surgery in the Shuyang People's Hospital from February 2010 to November 2014 were collected retrospectively. Peripheral blood routine test and immunohistochemistry examination of carcinoma nest were mainly performed. Survival rates were analyzed with Kaplan-Meier curves. Univariate analysis and multivariate analysis were also performed to explore potential prognostic factors of ESCC.The median survival time after surgery of low NLR group and high NLR group were 48 months and 30 months, respectively. The difference of overall survival between the 2 groups was statistically significant (χ = 7.435, P = .006). The median survival time after surgery of low iNLR group and high iNLR group were 37 months and 24.5 months, respectively. The difference between the 2 groups was also statistically significant (χ = 33.640, P = .000). Univariate analysis showed influence factors of postoperative survival in patients with ESCC included tumor-node-metastasis staging, NLR, iNLR, and grade of NLR score + iNLR score (P ≤ .05). Multivariate analysis confirmed NLR, iNLR, and tumor-node-metastasis staging were independent influence factors of postoperative survival in patients with ESCC (P ≤ .05).High level of NLR and iNLR implies a poor prognosis of ESCC. The application of both NLR and iNLR could guide clinicians to take aggressive treatments for high risk population.


Assuntos
Neoplasias Esofágicas/diagnóstico , Carcinoma de Células Escamosas do Esôfago/diagnóstico , Linfócitos , Neutrófilos , Adulto , Idoso , Neoplasias Esofágicas/imunologia , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/imunologia , Carcinoma de Células Escamosas do Esôfago/mortalidade , Carcinoma de Células Escamosas do Esôfago/patologia , Esôfago/imunologia , Esôfago/patologia , Feminino , Humanos , Contagem de Leucócitos , Linfócitos/patologia , Masculino , Pessoa de Meia-Idade , Neutrófilos/patologia , Prognóstico
13.
Nat Commun ; 11(1): 3675, 2020 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-32699215

RESUMO

Epigenetic landscapes can shape physiologic and disease phenotypes. We used integrative, high resolution multi-omics methods to delineate the methylome landscape and characterize the oncogenic drivers of esophageal squamous cell carcinoma (ESCC). We found 98% of CpGs are hypomethylated across the ESCC genome. Hypo-methylated regions are enriched in areas with heterochromatin binding markers (H3K9me3, H3K27me3), while hyper-methylated regions are enriched in polycomb repressive complex (EZH2/SUZ12) recognizing regions. Altered methylation in promoters, enhancers, and gene bodies, as well as in polycomb repressive complex occupancy and CTCF binding sites are associated with cancer-specific gene dysregulation. Epigenetic-mediated activation of non-canonical WNT/ß-catenin/MMP signaling and a YY1/lncRNA ESCCAL-1/ribosomal protein network are uncovered and validated as potential novel ESCC driver alterations. This study advances our understanding of how epigenetic landscapes shape cancer pathogenesis and provides a resource for biomarker and target discovery.


Assuntos
Biomarcadores Tumorais/genética , Epigênese Genética , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago/genética , Regulação Neoplásica da Expressão Gênica , Idoso , Linhagem Celular Tumoral , Sequenciamento de Cromatina por Imunoprecipitação , Estudos de Coortes , Ilhas de CpG , Metilação de DNA , Conjuntos de Dados como Assunto , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/cirurgia , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/cirurgia , Esofagectomia , Esôfago/patologia , Esôfago/cirurgia , Feminino , Genômica , Heterocromatina/metabolismo , Histonas/genética , Histonas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Regiões Promotoras Genéticas/genética , Proteômica , RNA-Seq , Sequenciamento Completo do Genoma
15.
J Cancer Res Ther ; 16(2): 269-275, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32474512

RESUMO

Background: Hypoxia-inducible factor 1α (HIF-1α), p53, and vascular endothelial growth factor (VEGF) are important factors that facilitate tumor progression. The aims of our study were to investigate the expression of HIF-1α, p53, and VEGF in esophageal squamous cell carcinoma (ESCC) treated by curative surgery and to analyze their association with clinicopathological parameters and clinical outcome. Materials and Methods: The surgical specimens from 120 patients who had undergone potentially curative resection for ESCC were immunohistochemically assessed using monoclonal antibodies against HIF-1α, p53, and VEGF. Results: Positive rates of HIF-1α, p53, and VEGF expression were 61.7%, 56.7%, and 78.3%, respectively. No significant relationship was found between HIF-1α, p53, VEGF expression, and the analyzed clinicopathological parameters. There was no significant correlation between the expression of HIF-1α, p53, and VEGF. Univariate analysis revealed that overexpression of HIF-1α was associated with poor disease-free and overall survival (P = 0.023 and 0.01, respectively). Multivariate analysis demonstrated that upregulation of HIF-1α is an independent predictor for poor overall survival (P = 0.044). Conclusions: HIF-1α was a useful independent prognostic factor for surgically treated ESCC. Further studies with larger sample size are required to determine the relationship between the expression of HIF-1α, p53, VEGF, and clinicopathological parameters.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Idoso , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/cirurgia , Carcinoma de Células Escamosas do Esôfago/metabolismo , Carcinoma de Células Escamosas do Esôfago/cirurgia , Feminino , Humanos , Hipóxia/patologia , Metástase Linfática , Masculino , Gradação de Tumores , Estadiamento de Neoplasias , Taxa de Sobrevida
16.
Cancer Sci ; 111(9): 3132-3141, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32579769

RESUMO

Esophageal squamous cell carcinoma (ESCC) is the main prevalent histological type of esophageal cancer, predominantly constituting 90% of cases worldwide. Despite the development of multidisciplinary therapeutic approaches, its prognosis remains unfavorable. Recently, the development of monoclonal antibodies inhibiting programmed death 1 (PD-1) or programmed death-ligand 1 (PD-L1) has led to marked therapeutic responses among multiple malignancies including ESCC. However, only a few patients achieved clinical benefits due to resistance. Therefore, precise and accurate predictive biomarkers should be identified for personalized immunotherapy in clinical settings. Because the tumor immune microenvironment can potentially influence the patient's response to immune checkpoint inhibitors, tumor immunity, such as PD-L1 expression on tumors, tumor-infiltrating lymphocytes, tumor-associated macrophages, and myeloid-derived suppressor cells, in ESCC should be further investigated. In this review, accumulated evidence regarding the tumor immune microenvironment and immune checkpoint inhibitors in ESCC are summarized.


Assuntos
Antineoplásicos Imunológicos/farmacologia , Neoplasias Esofágicas/etiologia , Neoplasias Esofágicas/metabolismo , Carcinoma de Células Escamosas do Esôfago/etiologia , Carcinoma de Células Escamosas do Esôfago/metabolismo , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologia , Animais , Antineoplásicos Imunológicos/uso terapêutico , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/metabolismo , Biomarcadores Tumorais , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/patologia , Humanos , Imunomodulação/efeitos dos fármacos , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Linfócitos do Interstício Tumoral/patologia , Macrófagos/imunologia , Macrófagos/metabolismo , Macrófagos/patologia , Mutação , Células Supressoras Mieloides/imunologia , Células Supressoras Mieloides/metabolismo , Células Supressoras Mieloides/patologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Linfócitos T/metabolismo
17.
J Surg Oncol ; 122(3): 412-421, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32462769

RESUMO

BACKGROUND: Esophageal adenocarcinoma (AC) and squamous cell carcinoma (SCC) have distinct outcomes, treatment strategies, and response profiles to therapy. Adenosquamous carcinoma (ASC) is thought to behave more aggressively than each of its counterparts. The aim of this study is to determine ifASC is best managed as AC or SCC. METHODS: National Cancer Database (2004-2015) was queried for patients with nonmetastatic esophageal ASC. The analysis was stratified by clinical node-negative (cN0) or clinical node-positive (cN1-3). Treatment was categorized into chemoradiation alone, surgery alone, or preoperative chemoradiation followed by surgery. The primary outcome was 5-year overall survival (OS). RESULTS: Among 352 patients, 43% were cN0 (n = 151), 57% were cN1-3 (n = 201) and 55% had chemoradiation alone (n = 194), 15% surgery alone (n = 53), and 30% preoperative chemoradiation (n = 105). Among patients who had preoperative chemoradiation, 20% had pathologic complete response (n = 17). For either cN0 or cN1-3, Charlson-Deyo Comorbidity Index did not differ among the treatment groups(all p > 0.05). On Kaplan-Meier analysis for cN0, treatment with surgery alone had comparable OS to preoperative chemoradiation (47% vs 34%; P = .5) and each had improved OS compared to chemoradiation alone (30%; P = .02; P = .06). On univariate analysis for cN0, clinical T category was not associated with OS. For cN1-3, however, preoperative chemoradiation was associated with improved OS when compared to chemoradiation alone or surgery alone (27% vs 19% vs 0%; P < .001). This persisted when accounting for age and clinical T category (hazard ratio: 0.45; P < .001). CONCLUSION: Esophageal ASC behaves more like AC in response to chemoradiation and survival based on treatment modality. A complete response to chemoradiation is only 20% unlike what has been shown for SCC, where chemoradiation is an acceptable definitive therapy. Esophageal ASC should be managed more like AC.


Assuntos
Adenocarcinoma/terapia , Carcinoma Adenoescamoso/terapia , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas do Esôfago/terapia , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Idoso , Carcinoma Adenoescamoso/mortalidade , Carcinoma Adenoescamoso/patologia , Quimiorradioterapia/estatística & dados numéricos , Terapia Combinada , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/mortalidade , Carcinoma de Células Escamosas do Esôfago/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Cuidados Pré-Operatórios , Sistema de Registros , Estados Unidos/epidemiologia
18.
Technol Cancer Res Treat ; 19: 1533033820920967, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32356485

RESUMO

BACKGROUND: In recent studies, microRNAs have been demonstrated as stable detectable biomarkers in blood for cancer. In addition, computer-aided biomarker discovery has now become an attractive paradigm for precision diagnosis. METHODS: In this study, we identified and evaluated miR-139-3p as a biomarker for screening of esophageal squamous cell carcinoma using the Cancer Genome Atlas and Gene Expression Omnibus database analyses. We identified possible miR-139-3p target genes through the predicted database and esophageal squamous cell carcinoma upregulated genes from the Cancer Genome Atlas and Gene. Bioinformatics analysis was performed to determine key miR-139-3p targets and pathways associated with esophageal carcinoma. Finally, the expression and expected significance of hub genes were evaluated via the Genotype-Tissue Expression project. RESULTS: MiR-139-3p was significantly downregulated in patients with esophageal squamous cell carcinoma/esophageal carcinoma. In GSE 122497, the area under the curve-receiver operating characteristic value, sensitivity, and specificity for serum miR-139-3p were 0.754, 67.49%, and 80.00%, respectively. The pattern specification process, skeletal system development, and regionalization process were the most enriched interactions in esophageal carcinoma. In addition, Epstein-Barr virus infection, human T-cell leukemia virus 1 infection, and human cytomegalovirus infection were identified as crucial pathways. Six hub genes (CD1A, FCGR2A, ANPEP, CD1B, membrane metalloendopeptidase, and TWIST1) were found, and FCGR2A and membrane metalloendopeptidase were further confirmed by genotype-tissue expression. High expression of membrane metalloendopeptidase correlated with a better overall survival but not with disease-free survival of patients with esophageal carcinoma. CONCLUSIONS: MiR-139-3p was identified as a candidate biomarker for predicting esophageal squamous cell carcinoma based on network analysis. MiR-139-3p acted as a tumor suppressor by targeting membrane metalloendopeptidase in esophageal carcinoma, and low expression of membrane metalloendopeptidase may indicate a better prognosis of patients with esophageal carcinoma.


Assuntos
Neoplasias Esofágicas/sangue , Carcinoma de Células Escamosas do Esôfago/sangue , MicroRNAs/sangue , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Biologia Computacional/métodos , Bases de Dados Genéticas , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/patologia , Perfilação da Expressão Gênica/métodos , Redes Reguladoras de Genes , Humanos , MicroRNAs/genética , Prognóstico , Mapas de Interação de Proteínas , Taxa de Sobrevida
19.
Anticancer Res ; 40(5): 2941-2946, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32366446

RESUMO

BACKGROUND/AIM: The spliceosome pathway, including Splicing Factor 3b Subunit 4 (SF3B4), plays an important role in carcinogenesis and progression in various cancers; however, the clinical relevance of SF3B4 in esophageal squamous cell carcinoma (ESCC) remains unknown. PATIENTS AND METHODS: SF3B4 expression was evaluated by real-time reverse transcription polymerase chain reaction in 80 ESCC patients. In order to explore the mechanism of SF3B4 in ESCC, the mRNA expression and copy number of SF3B4 were obtained from TCGA and we also implemented gene set enrichment analysis (GSEA). RESULTS: The high SF3B4 expression group (n=33) showed significantly more lymphatic permeation and poorer prognosis than the low SF3B4 expression group (n=47). GSEA revealed that high SF3B4 expression was correlated with genes associated with the transcription factor E2F and the G2/M checkpoint. SF3B4 expression was positively correlated with SF3B4 DNA copy number. CONCLUSION: Over-expression of SF3B4 may play a crucial role in the lymphatic progression of ESCC.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas do Esôfago/genética , Fatores de Processamento de RNA/genética , Carcinoma de Células Escamosas do Esôfago/mortalidade , Carcinoma de Células Escamosas do Esôfago/patologia , Feminino , Humanos , Masculino , Prognóstico , Análise de Sobrevida
20.
J Cancer Res Clin Oncol ; 146(8): 1979-1992, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32447483

RESUMO

PURPOSE: Esophageal cancer (EC) is one of the most lethal gastrointestinal malignancies. Immunotherapy is a promising treatment modality for this disease. However, broader implementation of EC immunotherapy has been discouraged because of insufficient understanding of tumor interactions with the immune system. As with other malignancies, the current research on EC focuses on deciphering the immune cell signatures within the tumor microenvironment. However, the disease-elicited immune cell profiles in the paratumoral compartments are largely unknown. METHODS: We examined the immune cell signatures in 62 tissue samples from 16 EC patients in different esophageal tissue compartments: tumor tissue, peritumoral tissue, healthy esophageal tissue, and adjacent lymph nodes. We analyzed the proportions and distribution patterns of NK cells and CD4+ and CD8+ T cells as well as their death receptor (FasR, FasR/DR3)-expressing subpopulations. The analyzed data were then compared and correlated with the patients' clinicopathological data. RESULTS: We found that the FasR+ NK cells, CD4+ and CD8+ T cells infiltrated lymph nodes at the lowest levels and that the FasR+DR3+ CD4+ T cells were enhanced in tumors. The comparisons with the clinicopathological data revealed a major impact of active smoking on the reduction in paratumoral NK cells and the upregulation of FasR in tumor-infiltrating NK and CD8+ T cells. The lymph node metastatic stage, tumor stage, and Mandard grade correlated with the compartmental proportions of the evaluated immune cells. CONCLUSION: The novel association of the disease state with tumoral and paratumoral immune cell signatures suggests new possibilities for personalized immunotherapy for EC patients.


Assuntos
Neoplasias Esofágicas/imunologia , Neoplasias Esofágicas/terapia , Linfócitos/imunologia , Adenocarcinoma/imunologia , Adenocarcinoma/patologia , Adenocarcinoma/terapia , Idoso , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/patologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/patologia , Estudos de Casos e Controles , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/imunologia , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/terapia , Feminino , Humanos , Imunoterapia/métodos , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/patologia , Linfonodos/imunologia , Linfonodos/patologia , Linfócitos/patologia , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/patologia , Masculino , Pessoa de Meia-Idade , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/patologia , Receptor fas/imunologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA