Introduction Head and neck squamous cell carcinoma （HNSCC） is a common cancer worldwide and has a poorprognosis. A biomarker predicting the clinical outcome of HNSCC patients could be useful in guiding treatment pla...Introduction Head and neck squamous cell carcinoma （HNSCC） is a common cancer worldwide and has a poorprognosis. A biomarker predicting the clinical outcome of HNSCC patients could be useful in guiding treatment planning.Overexpression of theT lymphoma invasion and metastasis 1 （Tiaml） protein has been implicated in the migrationand invasion of neoplasms. However, its role in HNSCC progression needs to be further validated. We detectedthe expression of Tiaml in normal and tumor tissues and determined its association with clinical outcomes in patientswith HNSCCMethods： We measured the expression of Tiaml in normal and cancerous tissue samples from the patients withHNSCC treated at Sun Yat-sen University Cancer Center between 2001 and 2008. The Tiaml expression was scoredfrom 0 to 12 based on the percentage of positively stained cells and the staining intensity. We then determined thediagnostic performance of this score in predicting overall survival （OS） and disease-free survival （DFS）.Results： Of the 194 evaluable patients, those with advanced disease, lymph node metastasis at diagnosis, and recurrenceor metastasis during follow-up had a highertendency of having high Tiaml expression as compared with theircounterparts （P 〈 0.05）. The proportion of samples with high Tiaml expression was also higher in cancerous tissuesthan in non-cancerous tissues （57.7% vs. 13.9%, P 〈 0.001）. Cox proportional hazards regression analysis revealed thatTiaml expression scores of 5 and greater independently predicted short OS and DFS.Conclusion： TheTiaml expression is shown as a promising biomarker of clinical outcomes in patients with HNSCCand should be evaluated in prospective trials.展开更多
Objectives: To explore the role of the growth of new nerves (neo-neurogenesis) in the tumorogenesis of squamous cell carcinoma of tongue. Materials and Methods: 10 formalin-fixed specimens were gained from patients di...Objectives: To explore the role of the growth of new nerves (neo-neurogenesis) in the tumorogenesis of squamous cell carcinoma of tongue. Materials and Methods: 10 formalin-fixed specimens were gained from patients diagnosed with tongue squamous cell carcinoma. Animal models were made by subcutaneous injection in the dorsal midline with Tca-8113 cell line. Mice were sacrificed 2, 4, 6 weeks after cell injection, and tumor tissues were fixed in 4% paraformaldehyde, embedded in paraffin, sectioned. Detection of neo-neurogenesis was stained by Neurofila-ment-L antibody (NF-L) using immunohistochemistry method (IHC) in biopsy from both human body and animal model. Results: IHC staining of NF-L is positive in all 10 paraffins of tongue squamous cell carcinoma sections which suggest that newly formed nerves are observed in tumor microenvironment. NF-L staining is also positive in the paraffins from animal models indicating that the tongue cancer recruits newly formed nerves in its tumorogenesis. Conclusions: Tumor neo-neurogenesis may play an important role in the pathogenesis and development of tongue cancer. From a therapeutic perspective, further studies on the topic may provide new clinical opportunity.展开更多
Objective:L1 cell adhesion molecule(L1 CAM)exhibits oncogenic activity in tumors.However,the link between L1 CAM and the tumor microenvironment remains poorly understood in patients with esophageal squamous cell carci...Objective:L1 cell adhesion molecule(L1 CAM)exhibits oncogenic activity in tumors.However,the link between L1 CAM and the tumor microenvironment remains poorly understood in patients with esophageal squamous cell carcinoma(ESCC).In this study,we investigated how L1 CAM expression in ESCC affects the oncogenic characteristics of tumor cells and the tumor microenvironment.Methods:Human ESCC samples were collected,and the m RNA and protein levels of L1 CAM were examined by real-time PCR and immunohistochemistry.Overexpression and knockdown gene expression assays were used for mechanistic studies.The cell proliferation and cell cycle were measured with CCK-8 assays and flow cytometry.Cell migration and invasion ability were measured with Transwell assays.Multiplex bead-based assays were performed to identity the factors downstream of L1 CAM.Xenograft studies were performed in nude mice to evaluate the effects of L1 CAM on tumor growth and regulatory T cell(Treg)recruitment.Results:L1 CAM expression was significantly elevated in ESCC tissues(P<0.001)and correlated with poorer prognosis(P<0.05).Ablation of L1 CAM in ESCC cells inhibited tumor growth and migration,and increased tumor cell apoptosis(P<0.05).In the tumor microenvironment,L1 CAM expression correlated with Treg infiltration in ESCC by affecting CCL22 secretion.Mechanistically,L1 CAM facilitated CCL22 expression by activating the PI3 K/Akt/NF-κB signaling pathway.Furthermore,CCL22 promoted Treg recruitment to the tumor site;the Tregs then secreted TGF-β,which in turn promoted L1 CAM expression via Smad2/3 in a positive feedback loop.Conclusions:Our findings provide new insight into the mechanism of immune evasion mediated by L1 CAM,suggesting that targeting L1 CAM-CCL22-TGF-βcrosstalk between tumor cells and Tregs may offer a unique means to improve treatment of patients with ESCC.展开更多
目的:检测食管鳞癌患者外周血中程序性死亡分子1(programmed cell death 1,PD-1)、程序性死亡分子1配体(programmed cell death ligand 1,PD-L1)及IFN-γ表达情况,并分析其临床意义。方法选取2016年6月至2017年4月河北医科大学第四医院...目的:检测食管鳞癌患者外周血中程序性死亡分子1(programmed cell death 1,PD-1)、程序性死亡分子1配体(programmed cell death ligand 1,PD-L1)及IFN-γ表达情况,并分析其临床意义。方法选取2016年6月至2017年4月河北医科大学第四医院胸外科90例食管鳞状细胞癌患者(其中50例患者行手术治疗)和40例健康对照者为研究对象,收集研究其外周血液标本,采用酶联免疫吸附方法检测血清中可溶性PD-1(sPD-1)、可溶性PD-L1(sPD-L1)及IFN-γ的表达水平。采用SPSS 24.0软件对数据进行检验和相关性分析。结果:食管鳞癌组血清中sPD-1、sPD-L1及IFN-γ水平均明显高于正常对照组(P<0.05);食管鳞癌组手术前血清sPD-L1、IFN-γ水平均明显高于术后(P<0.05),而sPD-1水平两组比较无明显差异(P>0.05)。sPD-1、sPD-L1的表达水平与临床病理特征无明显相关(P>0.05),IFN-γ的表达水平与淋巴结转移情况相关(P<0.05),与T分期、TNM分期、肿瘤体积大小、肿瘤部位、组织分化程度、性别、年龄无明显相关(P>0.05)。血清中sPD-L1表达水平与IFN-γ无明显相关(P>0.05)。结论:食管鳞癌患者血清中sPD-L1较正常人表达升高,且术后表达较术前减少,说明血清中sPD-L1表达水平与病情发展变化有一定相关性。展开更多
Background Patients with esophageal squamous cell carcinoma （ESCC） undergoing definitive chemoradiotherapy （CRT） seem to have a disparity in therapeutic response. The identification of CRT sensitivity-related clin...Background Patients with esophageal squamous cell carcinoma （ESCC） undergoing definitive chemoradiotherapy （CRT） seem to have a disparity in therapeutic response. The identification of CRT sensitivity-related clinicopathological factors would be helpful for selecting patients most likely to benefit from CRT. Cytokeratin 19 fragment antigen 21-1 （CYFRA21-1） and carcinoembryonic antigen （CEA） have been reported as useful tumor markers for esophageal cancer. The aim of this study was to examine the predictive value of CYFRA21-1 in comparison with CEA and other clinicopathological factors in patients with ESCC treated with definitive CRT. Methods Pretreatment serum CYFRA21-1 and CEA levels were measured by immunoradiometric assays. The relationships between pretreatment clinicopathological factors and the efficacy of CRT were analyzed. Overall survival （OS） was estimated by univariate and multivariate analysis. Results The results from a univariate analysis indicated that the efficacy of CRT was significantly associated with the serum levels of CYFRA21-1 and CEA before treatment （P=0.001 and P=0.023, respectively）. It also indicated that the efficacy of CRT was significantly associated with the pretreatment tumor location （P=-0.041）. By Logistic regression analysis, the independent predictive factor associated with efficacy of CRT was CYFRA21-1 （P=0.002）. The OS of the patients with high CYFRA 21-1 levels was worse than that of those with low CYFRA21-1 levels （P=0.001）. In multivariate analysis, a low level of CYFRA21-1 was the most significant independent predictor of good OS （P=0.007）. Conclusions CEA and tumor location may be useful in predicting the sensitivity of ESCC to CRT. CYFRA21-1 may be an independent predictor for definitive CRT sensitivity in ESCC.展开更多
文摘Introduction Head and neck squamous cell carcinoma （HNSCC） is a common cancer worldwide and has a poorprognosis. A biomarker predicting the clinical outcome of HNSCC patients could be useful in guiding treatment planning.Overexpression of theT lymphoma invasion and metastasis 1 （Tiaml） protein has been implicated in the migrationand invasion of neoplasms. However, its role in HNSCC progression needs to be further validated. We detectedthe expression of Tiaml in normal and tumor tissues and determined its association with clinical outcomes in patientswith HNSCCMethods： We measured the expression of Tiaml in normal and cancerous tissue samples from the patients withHNSCC treated at Sun Yat-sen University Cancer Center between 2001 and 2008. The Tiaml expression was scoredfrom 0 to 12 based on the percentage of positively stained cells and the staining intensity. We then determined thediagnostic performance of this score in predicting overall survival （OS） and disease-free survival （DFS）.Results： Of the 194 evaluable patients, those with advanced disease, lymph node metastasis at diagnosis, and recurrenceor metastasis during follow-up had a highertendency of having high Tiaml expression as compared with theircounterparts （P 〈 0.05）. The proportion of samples with high Tiaml expression was also higher in cancerous tissuesthan in non-cancerous tissues （57.7% vs. 13.9%, P 〈 0.001）. Cox proportional hazards regression analysis revealed thatTiaml expression scores of 5 and greater independently predicted short OS and DFS.Conclusion： TheTiaml expression is shown as a promising biomarker of clinical outcomes in patients with HNSCCand should be evaluated in prospective trials.
文摘Objectives: To explore the role of the growth of new nerves (neo-neurogenesis) in the tumorogenesis of squamous cell carcinoma of tongue. Materials and Methods: 10 formalin-fixed specimens were gained from patients diagnosed with tongue squamous cell carcinoma. Animal models were made by subcutaneous injection in the dorsal midline with Tca-8113 cell line. Mice were sacrificed 2, 4, 6 weeks after cell injection, and tumor tissues were fixed in 4% paraformaldehyde, embedded in paraffin, sectioned. Detection of neo-neurogenesis was stained by Neurofila-ment-L antibody (NF-L) using immunohistochemistry method (IHC) in biopsy from both human body and animal model. Results: IHC staining of NF-L is positive in all 10 paraffins of tongue squamous cell carcinoma sections which suggest that newly formed nerves are observed in tumor microenvironment. NF-L staining is also positive in the paraffins from animal models indicating that the tongue cancer recruits newly formed nerves in its tumorogenesis. Conclusions: Tumor neo-neurogenesis may play an important role in the pathogenesis and development of tongue cancer. From a therapeutic perspective, further studies on the topic may provide new clinical opportunity.
基金supported by grants from the National Natural Science Foundation of China(Grant No.81802857)State’s Key Project of Research and Development Plan(Grant No.2016YFC1303501)+1 种基金Henan Science and Technology Research Project(Grant No.172102310143)The Key Research Project of Henan Provincial Colleges and Universities(Grant No.19A320062)。
文摘Objective:L1 cell adhesion molecule(L1 CAM)exhibits oncogenic activity in tumors.However,the link between L1 CAM and the tumor microenvironment remains poorly understood in patients with esophageal squamous cell carcinoma(ESCC).In this study,we investigated how L1 CAM expression in ESCC affects the oncogenic characteristics of tumor cells and the tumor microenvironment.Methods:Human ESCC samples were collected,and the m RNA and protein levels of L1 CAM were examined by real-time PCR and immunohistochemistry.Overexpression and knockdown gene expression assays were used for mechanistic studies.The cell proliferation and cell cycle were measured with CCK-8 assays and flow cytometry.Cell migration and invasion ability were measured with Transwell assays.Multiplex bead-based assays were performed to identity the factors downstream of L1 CAM.Xenograft studies were performed in nude mice to evaluate the effects of L1 CAM on tumor growth and regulatory T cell(Treg)recruitment.Results:L1 CAM expression was significantly elevated in ESCC tissues(P<0.001)and correlated with poorer prognosis(P<0.05).Ablation of L1 CAM in ESCC cells inhibited tumor growth and migration,and increased tumor cell apoptosis(P<0.05).In the tumor microenvironment,L1 CAM expression correlated with Treg infiltration in ESCC by affecting CCL22 secretion.Mechanistically,L1 CAM facilitated CCL22 expression by activating the PI3 K/Akt/NF-κB signaling pathway.Furthermore,CCL22 promoted Treg recruitment to the tumor site;the Tregs then secreted TGF-β,which in turn promoted L1 CAM expression via Smad2/3 in a positive feedback loop.Conclusions:Our findings provide new insight into the mechanism of immune evasion mediated by L1 CAM,suggesting that targeting L1 CAM-CCL22-TGF-βcrosstalk between tumor cells and Tregs may offer a unique means to improve treatment of patients with ESCC.
文摘目的:检测食管鳞癌患者外周血中程序性死亡分子1(programmed cell death 1,PD-1)、程序性死亡分子1配体(programmed cell death ligand 1,PD-L1)及IFN-γ表达情况,并分析其临床意义。方法选取2016年6月至2017年4月河北医科大学第四医院胸外科90例食管鳞状细胞癌患者(其中50例患者行手术治疗)和40例健康对照者为研究对象,收集研究其外周血液标本,采用酶联免疫吸附方法检测血清中可溶性PD-1(sPD-1)、可溶性PD-L1(sPD-L1)及IFN-γ的表达水平。采用SPSS 24.0软件对数据进行检验和相关性分析。结果:食管鳞癌组血清中sPD-1、sPD-L1及IFN-γ水平均明显高于正常对照组(P<0.05);食管鳞癌组手术前血清sPD-L1、IFN-γ水平均明显高于术后(P<0.05),而sPD-1水平两组比较无明显差异(P>0.05)。sPD-1、sPD-L1的表达水平与临床病理特征无明显相关(P>0.05),IFN-γ的表达水平与淋巴结转移情况相关(P<0.05),与T分期、TNM分期、肿瘤体积大小、肿瘤部位、组织分化程度、性别、年龄无明显相关(P>0.05)。血清中sPD-L1表达水平与IFN-γ无明显相关(P>0.05)。结论:食管鳞癌患者血清中sPD-L1较正常人表达升高,且术后表达较术前减少,说明血清中sPD-L1表达水平与病情发展变化有一定相关性。
文摘Background Patients with esophageal squamous cell carcinoma （ESCC） undergoing definitive chemoradiotherapy （CRT） seem to have a disparity in therapeutic response. The identification of CRT sensitivity-related clinicopathological factors would be helpful for selecting patients most likely to benefit from CRT. Cytokeratin 19 fragment antigen 21-1 （CYFRA21-1） and carcinoembryonic antigen （CEA） have been reported as useful tumor markers for esophageal cancer. The aim of this study was to examine the predictive value of CYFRA21-1 in comparison with CEA and other clinicopathological factors in patients with ESCC treated with definitive CRT. Methods Pretreatment serum CYFRA21-1 and CEA levels were measured by immunoradiometric assays. The relationships between pretreatment clinicopathological factors and the efficacy of CRT were analyzed. Overall survival （OS） was estimated by univariate and multivariate analysis. Results The results from a univariate analysis indicated that the efficacy of CRT was significantly associated with the serum levels of CYFRA21-1 and CEA before treatment （P=0.001 and P=0.023, respectively）. It also indicated that the efficacy of CRT was significantly associated with the pretreatment tumor location （P=-0.041）. By Logistic regression analysis, the independent predictive factor associated with efficacy of CRT was CYFRA21-1 （P=0.002）. The OS of the patients with high CYFRA 21-1 levels was worse than that of those with low CYFRA21-1 levels （P=0.001）. In multivariate analysis, a low level of CYFRA21-1 was the most significant independent predictor of good OS （P=0.007）. Conclusions CEA and tumor location may be useful in predicting the sensitivity of ESCC to CRT. CYFRA21-1 may be an independent predictor for definitive CRT sensitivity in ESCC.
