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1.
Zhonghua Zhong Liu Za Zhi ; 42(2): 105-113, 2020 Feb 23.
Artigo em Chinês | MEDLINE | ID: mdl-32135643

RESUMO

Objective: To explore the expression of microRNA-17-5p (miR-17-5p) in esophageal squamous cell carcinoma (ESCC) and its effects on cell proliferation and invasion ability. Methods: Real-time quantitative PCR (RT-qPCR) was used to detect the miR-17-5p level in ESCC tissues and cells. MiR-17-5p inhibitor and negative control (NC) were transfected into EC9706 and TE1 cells, and miR-17-5p expression was examined by using RT-qPCR. Cell counting kit-8 (CCK-8) and EdU were conducted to detect cell proliferation and Transwell chamber was used to investigate cell invasion ability. Dual-luciferase reporter assay was used to detect the direct interaction of miR-17-5p and retinoblastoma-like protein-2 (RBL2). Western blot and RT-qPCR were used to detect the expression of RBL2 in ESCC tissues, respectively. Finally, the correlation between RBL2 and miR-17-5p was analyzed. Results: The miR-17-5p level in ESCC tissues was 4.222±0.392, significantly higher than 1.081±0.046 in normal esophageal epithelial tissues (P<0.001). The expressions of miR-17-5p in ESCC cells, including EC9706, Eca109, TE1, KYSE450, KYSE70 and KYSE520, were 13.84±1.266, 6.453±0.293, 11.41±0.520, 2.613±0.548, 5.251±0.239 and 4.251±0.195, respectively, all obviously higher than (1.007±0.079) in normal esophageal epithelial cell Het-1A (P<0.05). The miR-17-5p level in patients with ESCC Ⅲ~Ⅳ was 5.094±0.562, markedly higher than 2.934±0.364 in patients with ESCCⅠ~Ⅱ(P<0.01). Moreover, the miR-17-5p level in ESCC patients with lymph node metastasis was 5.523±0.634, markedly higher than 3.533±0.461 in ESCC patients without lymph node metastasis (P<0.05). The survival ratio of ESCC patients with higher miR-17-5p level was evidently lower than that of ESCC patients with lower miR-17-5p level (P<0.05). MiR-17-5p inhibitor significantly downregulated the miR-17-5p expression in EC9706 and TE1, which suppressed cell proliferation and invasion ability. Dual-luciferase reporter assay revealed that co-transfection of 3' untranslated region-wild type (3'UTR-WT) of RBL2 and miR-17-5p mimic significantly reduced luciferase activity in EC9706 and TE1 cells (P<0.01), which implicated that RBL2 was the direct target of miR-17-5p. The result of western blot revealed that RBL2 protein expressions in miR-17-5p group of EC9706 and TE1 cells were 0.936±0.055 and 0.923±0.048, obviously higher than 0.087±0.019 and 0.102±0.010 in control group (P<0.001). The expression of RBL2 in ESCC tissues was 0.219±0.510, markedly lower than 0.983±0.324 in normal esophageal epithelial tissues (P<0.001). The miR-17-5p level exhibited a negative correlation with RBL2 level in ESCC tissues (r=-0.462, P<0.001). Downregulation of RBL2 reversed the miR-17-5p inhibitor induced suppression of cell proliferation and invasion ability. Conclusion: MiR-17-5p participates in the carcinogenesis and development of ESCC, thus may be a potential therapeutic target for ESCC patients.


Assuntos
Neoplasias Esofágicas/metabolismo , Carcinoma de Células Escamosas do Esôfago/metabolismo , MicroRNAs/biossíntese , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Humanos , Invasividade Neoplásica
2.
Zhonghua Zhong Liu Za Zhi ; 42(2): 139-144, 2020 Feb 23.
Artigo em Chinês | MEDLINE | ID: mdl-32135649

RESUMO

Objective: To evaluate the prognostic factors of T1-2N0M0 esophageal squamous cell carcinoma (ESCC) treated with definitive radiotherapy. Methods: The clinical data of 196 patients with T1-2N0M0 ESCC who were treated with definitive radiotherapy in 10 hospitals were retrospectively analyzed. All sites were members of Jing-Jin-Ji Esophageal and Esophagogastric Cancer Radiotherapy Oncology Group (3JECROG). Radiochemotherapy were applied to 78 patients, while the other 118 patients received radiotherapy only. 96 patients were treated with three-dimensional conformal radiotherapy (3DCRT) and 100 treated with intensity-modulated radiotherapy (IMRT). The median dose of plan target volume(PTV) and gross target volume(GTV) were both 60 Gy. The median follow-up time was 59.2 months. Log rank test and Cox regression analysis were used for univariat and multivariate analysis, respectively. Results: The percentage of normal lung receiving at least 20 Gy (V(20)) was (18.65±7.20)%, with average dose of (10.81±42.05) Gy. The percentage of normal heart receiving at least 30 Gy (V(30)) was (14.21±12.28)%. The maximum dose of exposure in spinal cord was (39.65±8.13) Gy. The incidence of radiation pneumonia and radiation esophagitis were 14.80%(29/196) and 65.82%(129/196), respectively. The adverse events were mostly grade 1-2, without grade 4 toxicity. Median overall survival (OS) and progression-free survival (PFS) were 70.1 months and 62.3 months, respectively. The 1-, 3- and 5-year OS rates of all patients were 75.1%、57.4% and 53.2%, respectively. The 1-, 3- and 5-year PFS rates were 75.1%、57.4% and 53.2%, respectively. Multivariate analysis demonstrated that patients'age (HR=1.023, P=0.038) and tumor diameter (HR=1.243, P=0.028)were the independent prognostic factors for OS, while tumor volume were the independent prognostic factor for PFS. Conclusions: Definitive radiotherapy is a promising therapeutic method in patients with T1-2N0M0 ESCC. Patients' age, tumor diameter and tumor volume may impact patients' prognosis.


Assuntos
Neoplasias Esofágicas/radioterapia , Carcinoma de Células Escamosas do Esôfago/radioterapia , Antineoplásicos/uso terapêutico , Quimiorradioterapia , Relação Dose-Resposta à Radiação , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/mortalidade , Carcinoma de Células Escamosas do Esôfago/patologia , Humanos , Prognóstico , Dosagem Radioterapêutica , Radioterapia Conformacional , Radioterapia de Intensidade Modulada , Estudos Retrospectivos
3.
Med Sci Monit ; 26: e919714, 2020 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-32139664

RESUMO

BACKGROUND Esophageal squamous cell carcinoma (ESCC) is a malignant tumor of the gastrointestinal tract. Taurine upregulated gene 1 (TUG1), a long non-coding (lnc) RNA, also known as LIN00080 or TI-227H, was connected with the tumorigenesis of various diseases. Hence, we plumed the role and molecular mechanism of TUG1 in the progression of ESCC. MATERIAL AND METHODS Expression patterns of TUG1, microRNA-498 (miR-498), and cell division cycle 42 (CDC42) mRNA were assessed using quantitative real time polymerase chain reaction (qRT-PCR). The expression level of CDC42 protein was evaluated via western blot analysis. Cell proliferation and invasion were determined with Cell Counting Kit-8 (CCK-8) assay or Transwell assay. The relationship between miR-498 and TUG1 or CDC42 was predicted by online bioinformatics database LncBase Predicted v.2 or microT-CDS and confirmed through dual-luciferase reporter system or RNA immunoprecipitation assay (RIP). RESULTS TUG1 and CDC42 were upregulated while miR-498 was strikingly decreased in ESCC tissues and cells (P<0.0001). Besides, TUG1 suppression blocked the proliferation and invasion of ESCC cells (P<0.001). Importantly, TUG1 decrease restrained CDC42 expression via binding to miR-498 in ESCC cells. Also, the suppressive impacts of TUG1 silencing on the proliferation and invasion of ESCC cells were mitigated by miR-498 reduction. Meanwhile, the repression of proliferation and invasion induced by miR-498 elevation was weakened by CDC42 overexpression. CONCLUSIONS Inhibition of TUG1 hampered cell proliferation and invasion by downregulating CDC42 via upregulating miR-498 in ESCC cells. Thus, TUG1 might be an underlying therapeutic target for ESCC.


Assuntos
Proliferação de Células , Carcinoma de Células Escamosas do Esôfago/patologia , MicroRNAs/genética , RNA Longo não Codificante/genética , Proteína cdc42 de Ligação ao GTP/metabolismo , Linhagem Celular Tumoral , Regulação para Baixo , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Masculino , Pessoa de Meia-Idade
4.
Medicine (Baltimore) ; 99(10): e19440, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32150096

RESUMO

RATIONALE: Although the early detection and treatment of non-metastatic esophageal cancer has improved, these patients' prognoses are still poor. Most patients with radical treatment for esophageal cancer will relapse in 3 years, and the best treatment strategy after recurrence has not been uniformly accepted. Multiform treatments may be beneficial to recurrent patients. PATIENT CONCERNS: A 60-year-old male patient, due to routinely health examination, ulcerated lesions 30 cm away from the incisors were found by gastroscopy, pathology showed esophageal squamous cell carcinoma (ESCC). DIAGNOSIS: Due to the patient's pathology, he was diagnosed with ESCC. INTERVENTIONS: The patient underwent radical surgery for ESCC on June 28, 2015. The left cervical lymph node metastasis occurred after 20 months, and lymph node metastasis carcinoma resection was performed. After that, concurrent chemoradiotherapy was implemented, 40 days after the end of the 4 courses of chemotherapy, the left cervical metastatic lymph nodes relapsed, radioactive particle implantation was carried out, and progressed again after 1 month. The patient took apatinib for 1 week but could not tolerate due to hand-foot syndrome. Immune checkpoint inhibitor (ICI) was administered since October 27, 2017. OUTCOMES: The therapeutic effect of immune checkpoint inhibitor was evaluated as partial response (PR) after 6 courses of treatment and complete response (CR) after 15 courses of treatment. To our knowledge, this is the first case report of successful immunotherapy for refractory esophageal squamous cell carcinoma. LESSONS: The emergence of ICIs promotes the treatment of esophageal cancer to a new era. Our observations suggest that patients for whom schedule to receive anti-programmed cell death protein-1 (anti-PD-1)/programmed cell death-ligand 1 (PD-L1) immunotherapy may require genomic testing to predict whether tumors respond to ICIs. In this case, we also present the predictors for the efficacy of targeted immunotherapy. At present, no matter which predictor of PD-L1 expression, tumor mutational burden (TMB), microsatellite instability (MSI), and tumor-infiltrating lymphocyte (TIL), a single predictor may be unconvincing and cannot accurately estimate the efficacy of immunotherapy. Multiplex detecting methods and combined biomarkers may provide new strategies. Consensus need to be reached in order to be widely applied in future studies.


Assuntos
Vértebras Cervicais , Neoplasias Esofágicas/diagnóstico , Carcinoma de Células Escamosas do Esôfago/diagnóstico , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Quimiorradioterapia , Diagnóstico Diferencial , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas do Esôfago/secundário , Carcinoma de Células Escamosas do Esôfago/terapia , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade
6.
Anticancer Res ; 40(2): 813-823, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32014924

RESUMO

BACKGROUND/AIM: Olaparib was previously shown to synergistically enhance the cytotoxicity of DNA synthesis inhibitors in oesophageal carcinoma (OC) cell lines. However, the mechanisms of this synergy are not fully understood. As P53 binding protein 1 (53BP1) expression was previously shown to potentiate the anticancer effect of olaparib, we investigated the involvement of 53BP1 in the synergetic cytotoxic effects of olaparib and anticancer drugs in KYSE70 cells. MATERIALS AND METHODS: Experiments included small interfering RNA transfection, growth inhibition assays, western blots, immunofluorescence, and flow cytometry. RESULTS: The toxicity of DNA synthesis-inhibiting agents plus olaparib was decreased when 53BP1 was depleted. Olaparib cotreatment significantly increased phosphorylated H2A histone family member X (γH2AX) foci as well as 53BP1/γH2AX co-localisation in anticancer drug-treated cells. Silencing of 53BP1 suppressed anticancer drug-induced apoptosis with or without olaparib. CONCLUSION: Olaparib potentiates the cytotoxicity of anticancer drugs through 53BP1 in OC cells.


Assuntos
Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Ftalazinas/uso terapêutico , Piperazinas/uso terapêutico , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Proteína 1 de Ligação à Proteína Supressora de Tumor p53/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Ftalazinas/farmacologia , Piperazinas/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Transfecção
7.
Crit Rev Oncol Hematol ; 147: 102883, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32014674

RESUMO

Endoscopic resection (ER) combined with adjuvant therapy appears to be a new treatment for esophageal squamous cell cancers (ESCC) invading to deep mucosa (pT1a-m3) or submucosa (pT1b). Adjuvant therapy can take the form of esophagectomy or chemoradiotherapy (CRT), but it is unclear which treatment is better. This review is to explore the outcomes of adjuvant therapy between esophagectomy and CRT for the treatment of pT1a-m3/pT1b ESCC after ER. Ten relevant studies with a total of 285 patients were included. The reported 5-year overall survival rates ranged between 90-100 % for ER-esophagectomy and 75-85 % for ER-CRT. ESCC with the invasion of ≥ sm2 combined with lymphovascular involvement was associated with a high-risk of relapse in patients receiving ER-CRT, but not in ER-esophagectomy. In conclusion, patients with a high-risk of relapse should be treated with ER-esophagectomy; ER-CRT may be used as an alternative treatment for patients with a nonhigh risk of relapse.


Assuntos
Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/cirurgia , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/cirurgia , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/cirurgia , Carcinoma de Células Escamosas/patologia , Quimiorradioterapia , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Esofagectomia , Humanos , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Resultado do Tratamento
8.
Anticancer Res ; 40(2): 1153-1160, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32014968

RESUMO

BACKGROUND/AIM: Neoadjuvant therapy followed by surgery is the standard treatment for advanced esophageal cancer. This study aimed to evaluated the potential of 18F-fluorodeoxyglucose positron-emission tomography to predict the pathological therapeutic effect of neoadjuvant chemotherapy. PATIENTS AND METHODS: We enrolled 68 patients with advanced esophageal squamous cell carcinoma who underwent 18F-fluorodeoxyglucose positron-emission tomography before and after neoadjuvant chemotherapy, followed by surgery. Retrospective analysis of the pathological therapeutic effects was performed. RESULTS: The pathological therapeutic effect of good responders was significantly inversely associated with the maximum standardized uptake value (SUVmax) after neoadjuvant chemotherapy and with SUVmax reduction (both p<0.0001). Univariate and multivariate analyses revealed that lower post therapy SUVmax and reduction in SUVmax were independent prognostic factors for relapse-free (p=0.02) and overall survival (p<0.0001). CONCLUSION: Post-neoadjuvant chemotherapy SUVmax and SUVmax reduction can predict the pathological therapeutic effect of neoadjuvant chemotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas do Esôfago/terapia , Esofagectomia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Terapia Combinada , Carcinoma de Células Escamosas do Esôfago/diagnóstico , Carcinoma de Células Escamosas do Esôfago/mortalidade , Esofagectomia/efeitos adversos , Esofagectomia/métodos , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Imagem Multimodal/métodos , Terapia Neoadjuvante , Gradação de Tumores , Estadiamento de Neoplasias , Curva ROC , Resultado do Tratamento
9.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 51(1): 24-29, 2020 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-31950785

RESUMO

Objective: To investigate the effect of antisense oligodeoxynucleotides (ASODN) of Homeobox A1 gene ( HOXA1) on proliferation, apoptosis, invasion and migration of esophageal carcinoma cells. Methods: The expression of HOXA1 protein in normal esophageal epithelial cells Het-1A and esophageal cancer TE-1, EC9706 and Eca109 cells was detected by Western blot. Screening of highly expressed of HOXA1 protein esophageal squamous cell carcinoma cells for follow-up experiments. HOXA1 antisense oligonucleotide (ASODN) chains, sense oligodeoxynucleotides (SODN) chain, and nonsense oligodeoxy nucleotides (N-ODN) chain were designed. The screened esophageal squamous cell carcinoma cells with high expression were divided into HOXA1 ASODN group (5, 10, 15 µmol/L HOXA1 ASODN transfected Eca109 cells), control group (conventional culture medium, no cell transfection), SODN group (cells transfected with 15 µmol/L of SODN) and N-ODN group (cells transfected with 15 µmol/L N-ODN). Cell viability, apoptosis rate and invasion and migration ability were detected by methylthiazolyldiphenyl-tetrazolium bromide (MTT) method, flow cytometry, transwell chamber respectively; The expression of HOXA1, phosphorylation serine/threonine kinase (p-AKT), proliferating cell nuclear antigen (PCNA), matrix metalloproteinase 2 (MMP-2) and B-cell lymphoma2 (Bcl-2) associated X protein (Bax) protein was detected by Western blot. Results: Compared with normal esophageal epithelial cells Het-1A, the expression of HOXA1 protein in human esophageal squamous cell carcinoma cells TE-1, EC9706 and Eca109 was significantly higher ( P<0.05). The expression of HOXA1 protein was the highest in Eca109 cells, therefore, Eca109 cells were selected for follow-up experiments. The expression of HOXA1 protein in Eca109 cells transfected with HOXA1 ASODN was significantly decreased ( P<0.05). After transfection of Eca109 cells with HOXA1 ASODN, the viability of Eca109 cells decreased with the increase of concentration and time, the difference was significant compared with the control, SODN and N-ODN groups ( P<0.05). 15 µmol/L HOXA1 ASODN significantly inhibited cell viability. After 15 µmol/L HOXA1 ASODN was transfected into Eca109 cells, the invasion and migration abilities of cells were significantly decreased, the apoptosis rate was increased, the expressions of p-AKT, PCNA and MMP-2 were significantly decreased, and the expression of Bax was significantly increased ( P<0.05). Conclusion: Antisense oligodeoxynucleotides of HOXA1 gene can inhibit the proliferation, invasion and migration of esophageal cancer cells, and induce apoptosis. The mechanism is related to the inhibition of PI3K/AKT signaling pathway.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Oligonucleotídeos Antissenso , Apoptose/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Neoplasias Esofágicas/fisiopatologia , Carcinoma de Células Escamosas do Esôfago/fisiopatologia , Humanos , Oligonucleotídeos Antissenso/farmacologia , Transfecção
10.
Medicine (Baltimore) ; 99(4): e18732, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31977864

RESUMO

BACKGROUND: The aim of the study reported here was to evaluate the feasibility and safety of raltitrexed and nedaplatin with concurrent radiotherapy in patients with unresectable, locally advanced esophageal squamous cell carcinoma (ESCC). METHODS: Eligible patients were adults with newly diagnosed untreated, unresectable esophageal cancer in stages I to IV with lymph node metastases or cervical esophageal cancer. Patients received nedaplatin 25 mg/m per day on day 1-3, raltitrexed 3 mg/m on days 1 repeated every 21 days for 2 cycles, and combined concurrent radiotherapy (2 Gy/fraction, total dose of 60 Gy). RESULT: Thirty patients were included with squamous cell carcinoma. The median follow-up duration was 24 months. The overall response rate was 90%. The 1-year and 2-year overall survival rates for all patients were 70.4% and 55.7% with a median survival time of 30 months, and the median progression free survival was 20 month. The major toxicities were leukopenia and thrombopenia, with grade 3 to 4 leukopenia and thrombopenia were 50% and 30% of patients. CONCLUSION: Concurrent chemoradiotherapy with raltitrexed and nedaplatin agents frequently caused myelosuppression but was highly active and suggested to be a promising treatment option for locally advanced ESCC.


Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Quimiorradioterapia/métodos , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas do Esôfago/terapia , Compostos Organoplatínicos/administração & dosagem , Idoso , Antimetabólitos Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Relação Dose-Resposta à Radiação , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/efeitos adversos , Quinazolinas/administração & dosagem , Quinazolinas/efeitos adversos , Estudos Retrospectivos , Tiofenos/administração & dosagem , Tiofenos/efeitos adversos , Resultado do Tratamento
11.
J Surg Oncol ; 121(4): 654-661, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31970776

RESUMO

BACKGROUND AND OBJECTIVES: Lymph node harvest during esophagectomy has been associated with improved survival for esophageal cancer but the value of enhanced lymph node harvest following complete pathologic response (pCR) is debated. This study investigated if increasing lymph node harvest in esophageal cancer patients with a pCR after neoadjuvant therapy and esophagectomy is associated with improved survival. METHODS: We queried the National Cancer Data Base for patients with esophageal cancer between 2004 and 2014 who underwent neoadjuvant chemotherapy or chemoradiation therapy followed by esophagectomy found to have pCR. Multivariable Cox modeling was utilized to evaluate the impact of increasing lymph node counts on overall survival (OS). RESULTS: A total of 1373 patients met inclusion criteria. A National Comprehensive Cancer Network compliant lymphadenectomy of ≥15 nodes was associated with improved survival (66.7% vs 51.1%; P < .001). Cox modeling showed that the first node cutoff to demonstrate a statistically significant improvement in OS was ≥7 nodes (hazard ratio [HR], 95% confidence interval [CI]: 0.81, 0.68-0.97; 5-year OS: 54.2%) with a trend of decreasing and statistically significant HRs until ≥25 nodes (HR, 95% CI: 0.52, 0.37-0.72; 5-year OS: 68.4%). CONCLUSIONS: High negative node counts after neoadjuvant therapy and esophagectomy are associated with improved survival in patients with pCR.


Assuntos
Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/cirurgia , Linfonodos/cirurgia , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adenocarcinoma/terapia , Idoso , Quimiorradioterapia Adjuvante , Quimioterapia Adjuvante , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas do Esôfago/mortalidade , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/cirurgia , Carcinoma de Células Escamosas do Esôfago/terapia , Feminino , Humanos , Estimativa de Kaplan-Meier , Excisão de Linfonodo/estatística & dados numéricos , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Modelos de Riscos Proporcionais
12.
Int J Radiat Oncol Biol Phys ; 106(2): 340-348, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31655197

RESUMO

PURPOSE: Local persistence and relapse of disease in the gross tumor volume (GTV) account for the majority of treatment failures after standard chemoradiation therapy. The primary objective of this phase 1 trial was to define the maximum tolerated dose (MTD) of a hyperfractionated radiation therapy (HFRT) boost to the GTV with concurrent weekly paclitaxel and carboplatin after standard-dose chemoradiation therapy, using image guided intensity modulated radiation therapy techniques. METHODS AND MATERIALS: Eligible patients were given weekly doses of paclitaxel (45 mg/m2) and carboplatin (area under the curve 1.5) for 5 weeks with concurrent radiation therapy (50 Gy), immediately followed by an HFRT boost to the GTV with the same chemotherapy regimen. The boost doses were escalated in increments of 7.2 Gy delivered in 6 twice-daily fractions of 1.2 Gy using a modified Fibonacci design. Once the MTD was established, additional patients were treated at that dose to determine the safety. RESULTS: Thirty-one patients fulfilled the inclusion criteria. The incidence of dose-limiting toxicity was 0 of 3, 0 of 3, 0 of 3, 1 of 6 (grade 4 esophagitis), 0 of 3, and 2 of 3 (1 case each of grade 5 esophageal fistula and grade 3 pneumotitis) at 7.2, 14.4, 21.6, 28.8, 36, and 43.2 Gy, respectively, indicating an MTD of 36 Gy. Ten patients treated with this MTD showed no dose-limiting toxicities. The most common acute grade 3 or greater toxicities were esophagitis (26%) and neutropenia (19%). Late toxicity of grade 2 esophageal stricture occurred in 4 patients. The overall response rate was 84% (95% confidence interval, 42%-93%) in the entire cohort. The 1-year local control rate was 100% among those receiving a cumulative dose of the MTD or greater. CONCLUSIONS: The MTD of the HFRT boost after standard chemoradiation therapy in the setting of concurrent chemotherapy was 36 Gy, resulting in the cumulative tumor dose of 86 Gy in patients primarily with advanced intrathoracic/cervical esophageal squamous cell carcinomas and not adenocarcinomas of the gastroesophageal junction. A phase 2 study to further evaluate this regimen is underway.


Assuntos
Quimiorradioterapia/efeitos adversos , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas do Esôfago/terapia , Dose Máxima Tolerável , Radioterapia de Intensidade Modulada/efeitos adversos , Reirradiação/efeitos adversos , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Área Sob a Curva , Carboplatina/administração & dosagem , Quimiorradioterapia/métodos , Fracionamento da Dose de Radiação , Fístula Esofágica/etiologia , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Esofagite/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neutropenia/etiologia , Paclitaxel/administração & dosagem , Pneumonite por Radiação/etiologia , Radioterapia Guiada por Imagem/métodos , Radioterapia de Intensidade Modulada/métodos , Reirradiação/métodos , Carga Tumoral
13.
Radiol Med ; 125(2): 165-176, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31605354

RESUMO

AIMS: The aim of the study was to predict and assess treatment response by histogram analysis of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to patients with locally advanced esophageal squamous cell carcinoma receiving chemoradiotherapy (CRT). MATERIALS AND METHODS: Seventy-two patients with locally advanced esophageal squamous cell carcinoma who underwent DCE-MRI before and after chemoradiotherapy were enrolled and divided into the complete response (CR) group and the non-CR group based on RECIST. The histogram parameters (10th percentile, 90th percentile, median, mean, standard deviation, skewness, and kurtosis) of pre-CRT and post-CRT were compared using a paired Student's t test in the CR and non-CR groups, respectively. The histogram parameter differences between the CR and the non-CR groups were compared using an unpaired Student's t test. A receiver operating characteristic (ROC) analysis was performed to evaluate the diagnostic performance. RESULTS: The histogram parameters of Ktrans values were observed to have significantly decreased after chemoradiotherapy in the CR group. The CR responders showed significantly higher median, mean, and 10th and 90th percentile of pre-Ktrans values than those of the non-CR group. The histogram analysis indicated the decreased heterogeneity in the CR group after CRT. Esophageal cancer with higher pre-Ktrans and lower post-Ktrans values indicated a good treatment response to CRT. Pre-Ktrans-10th showed the best diagnostic performance in predicting the chemoradiotherapy response. CONCLUSIONS: The histogram parameters of Ktrans are useful in the assessment and prediction of the chemoradiotherapy response in patients with advanced esophageal squamous cell carcinoma. DCE-MRI could serve as an adjunctive imaging technique for treatment planning.


Assuntos
Quimiorradioterapia/métodos , Carcinoma de Células Escamosas do Esôfago/diagnóstico por imagem , Carcinoma de Células Escamosas do Esôfago/terapia , Imagem por Ressonância Magnética/métodos , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Cisplatino/uso terapêutico , Meios de Contraste , Feminino , Gadolínio DTPA , Humanos , Interpretação de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Paclitaxel/uso terapêutico , Dosagem Radioterapêutica , Estudos Retrospectivos
14.
Int J Cancer ; 146(4): 1042-1051, 2020 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-31396961

RESUMO

Esophageal squamous cell carcinoma (ESCC) occurs with highest frequency in China with over 90% mortality, highlighting the need for early detection and improved treatment strategies. We aimed to identify ESCC cancer predisposition gene(s). Our study included 4,517 individuals. The discovery phase using whole-exome sequencing (WES) included 186 familial ESCC patients from high-risk China. Targeted gene sequencing validation of 598 genes included 3,289 Henan and 1,228 moderate-risk Hong Kong Chinese. A WES approach identified BRCA2 loss-of-function (LOF) mutations in 3.23% (6/186) familial ESCC patients compared to 0.21% (9/4300) in the ExAC East Asians (odds ratio [OR] = 15.89, p = 2.48 × 10-10 ). BRCA2 LOF mutation frequency in the combined Henan cohort has significantly higher prevalence (OR = 10.55, p = 0.0035). Results were independently validated in an ESCC Hong Kong cohort (OR = 10.64, p = 0.022). One Hong Kong pedigree was identified to carry a BRCA2 LOF mutation. BRCA2 inactivation in ESCC was via germline LOF mutations and wild-type somatic allelic loss via loss of heterozygosity. Gene-based association analysis, including LOF mutations and rare deleterious missense variants defined with combined annotation dependent depletion score ≥30, confirmed the genetic predisposition role of BRCA2 (OR = 9.50, p = 3.44 × 10-5 ), and provided new evidence for potential association of ESCC risk with DNA repair genes (POLQ and MSH2), inflammation (TTC39B) and angiogenesis (KDR). Our findings are the first to provide compelling evidence of the role of BRCA2 in ESCC genetic susceptibility in Chinese, suggesting defective homologous recombination is an underlying cause in ESCC pathogenesis, which is amenable to therapeutic options based on synthetic lethality approaches such as targeting BRCA2 with PARP1 inhibitors in ESCC.


Assuntos
Proteína BRCA2/genética , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago/genética , Genes BRCA2 , Mutação em Linhagem Germinativa , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático/genética , China , Estudos de Coortes , Exoma , Feminino , Predisposição Genética para Doença , Humanos , Perda de Heterozigosidade , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Linhagem , Penetrância
16.
Gastroenterology ; 158(1): 280-281, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31704298
18.
Cancer Sci ; 111(3): 795-806, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31883400

RESUMO

Esophageal cancer is currently one of the most fatal cancers. However, there is no effective treatment. Increasing evidence suggests that interleukin (IL)-33 has a significant role in tumor progression and metastasis. Currently, the underlying cellular and molecular mechanism of IL-33 in promoting esophageal squamous cell carcinoma (ESCC) remains unclear. In this study, we investigated whether IL-33 could induce the epithelial-mesenchymal transition (EMT) in ESCC. Interleukin-33 expression was examined in ESCC and corresponding adjacent normal tissues by immunohistochemistry and quantitative real-time PCR experiments. Elevated IL-33 levels were observed in ESCC tissues. Further in vitro experiments were undertaken to elucidate the effect of IL-33 on migration and invasion in KYSE-450 and Eca-109 esophageal cancer cells. Knockdown of IL-33 decreased the metastasis and invasion capacity in esophageal cancer cells, whereas IL-33 overexpression showed the opposite effect. We then screened CCL2 which is a downstream molecule of IL-33, and proved that IL-33 could promote tumor development and metastasis by recruiting regulatory T cells (Tregs) through CCL2, and IL-33 regulated the expression of CCL2 through transforming growth factor-ß in Treg cells. Knockdown of IL-33 decreased the development of human ESCC xenografts in BALB/c nude mice. Collectively, we found that the IL-33/nuclear factor-κB/CCL2 pathway played an essential role in human ESCC progress. Hence, IL-33 should be considered as an effective therapy target for ESCC.


Assuntos
Quimiocina CCL2/genética , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago/genética , Interleucina-33/genética , NF-kappa B/genética , Transdução de Sinais/genética , Linfócitos T Reguladores/patologia , Animais , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Progressão da Doença , Transição Epitelial-Mesenquimal/genética , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus
19.
Int J Cancer ; 146(1): 18-25, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30891750

RESUMO

Previous studies have reported an association between hot tea drinking and risk of esophageal cancer, but no study has examined this association using prospectively and objectively measured tea drinking temperature. We examined the association of tea drinking temperature, measured both objectively and subjectively at study baseline, with future risk of esophageal squamous cell carcinoma (ESCC) in a prospective study. We measured tea drinking temperature using validated methods and collected data on several other tea drinking habits and potential confounders of interest at baseline in the Golestan Cohort Study, a population-based prospective study of 50,045 individuals aged 40-75 years, established in 2004-2008 in northeastern Iran. Study participants were followed-up for a median duration of 10.1 years (505,865 person-years). During 2004-2017, 317 new cases of ESCC were identified. The objectively measured tea temperature (HR 1.41, 95% CI 1.10-1.81; for ≥60°C vs. <60°C), reported preference for very hot tea drinking (HR 2.41, 95% CI 1.27-4.56; for "very hot" vs. "cold/lukewarm"), and reported shorter time from pouring tea to drinking (HR 1.51, 95% CI 1.01-2.26; for <2 vs. ≥6 min) were all associated with ESCC risk. In analysis of the combined effects of measured temperature and amount, compared to those who drank less than 700 ml of tea/day at <60°C, drinking 700 mL/day or more at a higher-temperature (≥60°C) was consistently associated with an about 90% increase in ESCC risk. Our results substantially strengthen the existing evidence supporting an association between hot beverage drinking and ESCC.


Assuntos
Ingestão de Líquidos , Neoplasias Esofágicas/epidemiologia , Carcinoma de Células Escamosas do Esôfago/epidemiologia , Temperatura Alta , Chá , Adulto , Idoso , Humanos , Irã (Geográfico) , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco
20.
BMC Complement Altern Med ; 19(1): 358, 2019 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-31822288

RESUMO

BACKGROUND: No previous study has investigated the association between oolong tea consumption and esophageal squamous cell carcinoma (ESCC), we aim to elucidate the association between oolong tea consumption and ESCC and its joint effects with a novel composite index. METHODS: In a hospital-based case-control study, 646 cases of ESCC patients and 646 sex and age matched controls were recruited. A composite index was calculated to evaluate the role of demographic characteristics and life exposure factors in ESCC. Unconditional logistic regression was used to calculate the point estimates between oolong tea consumption and risk of ESCC. RESULTS: No statistically significant association was found between oolong tea consumption and ESCC (OR = 1.39, 95% CI: 0.94-2.05). However, drinking hot oolong tea associated with increased risk of ESCC (OR = 1.60, 95% Cl: 1.06-2.41). Furthermore, drinking hot oolong tea increased ESCC risk in the high-risk group (composite index> 0.55) (OR = 3.14, 95% CI: 1.93-5.11), but not in the low-risk group (composite index≤0.55) (OR = 1.16, 95% CI: 0.74-1.83). Drinking warm oolong tea did not influence the risk of ESCC. CONCLUSIONS: No association between oolong tea consumption and risk of ESCC were found, however, drinking hot oolong tea significantly increased the risk of ESCC, especially in high-risk populations.


Assuntos
Dieta/estatística & dados numéricos , Neoplasias Esofágicas/epidemiologia , Carcinoma de Células Escamosas do Esôfago/epidemiologia , Chá , Estudos de Casos e Controles , Feminino , Temperatura Alta , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances
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