目的 探讨基质金属蛋白酶3（MMP-3）及其抑制因子2（TIMP-2）在肺鳞癌中的表达及临床意义。 方法 采用免疫组织化学方法（SP法），分别检测96例肺鳞癌组织和20例正常支气管黏膜上皮组织中MMP-3及TIMP-2的蛋白表达。 结果 MMP-3及TIMP-2在96例肺鳞癌组织中的阳性表达率（分别为81.3%、51.0%）明显高于正常支气管黏膜上皮组织（分别为25.0%、15.0%）；与无淋巴结转移的肺鳞癌组织相比，伴淋巴结转移的肺鳞癌组织中MMP-3、TIMP-2的阳性表达率明显升高，且差异均有显著的统计学意义（P＜0.01）。MMP-3的阳性表达随临床分期增加而有增高趋势，且差异有非常显著的统计学意义(P＜0.01)；TIMP-2在中晚期肺鳞癌组织（Ⅲ）的阳性表达率较早期肺鳞癌组织（Ⅰ+Ⅱ）有下降趋势，但差异无统计学意义（P＞0.05），二者之间表达也无明显相关性（r=−0.095，P＞0.05）。与无淋巴结转移肺鳞癌组织比较，有淋巴结转移肺鳞癌组织中，MMP-3的表达增高，TIMP-2的表达明显下降，二者之间表达呈负相关（r=−0.294，P＜0.05）。 结论 MMP-3与TIMP-2的过度表达与肺鳞癌的发展、淋巴结转移及临床TNM分期关系密切。MMP-3和TIMP-2在肺鳞癌组织中的表达情况，对预测肺鳞癌的浸润、转移，判断复发危险等方面具有重要意义，并有望成为判断肺鳞癌预后的生物学标志物。
Objective To analyze the Podoplanin expression in patients with esophageal squamous cell carcinoma and to find out the relationship between Podoplanin expression and tumor embolus, lymph node metastasis, tumor differentiation as well as prognosis, and to provide clinical evidence for reducing the recurrence of esophageal squamous cell carcinoma and prolonging the disease-free survival and overall survival. Methods A retrospective analysis of 70 patients with esophageal squamous cell carcinoma in our hospital from June 2010 to June 2012 was conducted, including 39 males and 31 females, with a mean age of 63.6 years. Positive diagnosis of tumor thrombus was achieved in 35 patients and negative in 35 patients. Postoperative pathological specimens were examined and normal esophageal tissues (esophageal tissue more than 5 cm from the edge of the tumor) of patients were excised as a control group. Results The positive rate of Podoplanin was 34.2% in normal esophageal tissues and 62.8% in tumor tissues. The positive rate of Podoplanin expression was 77.1% and 48.6% in esophageal squamous cell carcinoma patients with or without tumor embolus, respectively. The positive rate of Podoplanin expression in tumor cells of patients with positive and negative lymph node metastasis was 71.9% and 23.1%, respectively (P<0.05). The mean disease-free survival of patients with Podoplanin expression-negative esophageal squamous cell carcinoma was 15.2 months, which was significantly longer than that of patients with Podoplanin expression-positive esophageal squamous cell carcinoma (P<0.05). Conclusion Podoplanin expression in the tumor cells and vessels can be an important reference index to the prognosis of patients with esophageal squamous cell carcinoma.
ObjectiveTo investigate whether adjuvant therapy can bring survival benefits to patients with esophageal squamous cell carcinoma (ESCC) who have received neoadjuvant therapy plus esophagectomy. MethodsStudies were identified by searching databases including PubMed, EMbase, Web of Science, The Cochrane Library and CNKI from inception to November 2022 to collect studies which conformed to the objective of this study. Clinical outcomes including overall survival (OS) and recurrence-free survival (RFS) were extracted from eligible studies after screening. RevMan 5.4 and Stata 14.0 were used to perform the meta-analysis. ResultsA total of 9 studies were selected including 1 340 patients. Compared with the neoadjuvant therapy plus surgery (NS) group, the neoadjuvant therapy plus surgery+adjuvant therapy (NS+A) group had no significant benefit in the OS [HR=0.88, 95%CI (0.75, 1.02), P=0.09], but had remarkable benefit in the RFS [HR=0.75, 95%CI (0.58, 0.97), P=0.03]. Subgroup analysis by nodal status showed that adjuvant therapy could improve the RFS of patients with node-positive disease. Prolonged OS was observed in the patients with both positive and negative nodes but not in the patients with only positive nodes. In terms of the subgroup analysis by prescription, it revealed that triple agents exhibited advantages in improving RFS but not OS. However, dual agents did not bring additional survival benefits to the NS+A group compared with the NS group. Subgroup analysis by adjuvant therapy indicated that neither postoperative chemoradiotherapy nor chemotherapy improved OS, whereas postoperative chemoradiation elongated RFS. ConclusionAdjuvant therapy can improve the prognosis of patients with ESCC after neoadjuvant therapy followed by esophagectomy.
ObjectiveTo explore the effects and molecular mechanisms of histone methylase G9a inhibitor BIX-01294 on apoptosis in esophageal squamous cell carcinoma (ESCC).MethodsMTT assay and Colony-forming Units were adopted to determine the effects of BIX-01294 on the growth and proliferation of ESCC cell lines EC109 and KYSE150. Flow cytometry was used to analyze the apoptosis status of ESCC cells after the treatment of BIX-01294. The effects of BIX-01294 treatment on the expressions of G9a catalytic product H3K9me2, DNA double-strand break (DSB) markers, and apoptosis-related proteins were detected by Western blotting.ResultsBIX-01294 inhibited the growth of EC109 and KYSE150 cells in a dose-dependent manner (P<0.05), and BIX-01294 with the inhibitory concentration 50% (IC50) significantly inhibited the formation of colony (P<0.05). After 24 hours treatment of BIX-01294 (IC50), the apoptosis rate of EC109 cells increased from 11.5%±2.1% to 42.5%±5.4%, and KYSE150 cells from 7.5%±0.9% to 49.2%±5.2% (P<0.05). The expression level of the G9a catalytic product, H3K9me2, significantly decreased (P<0.05); while the expression of the DSB marker γH2AX was dramatically enhanced (P<0.05). We also found that the mitochondrial apoptosis pathway was activated and the expression levels of cleaved caspase3 and cleaved PARP were significantly elevated (P<0.05).ConclusionBIX-01294, the inhibitor of methyltransferase G9a, prompted apoptosis in ESCC cells by inducing DSB damage and activating mitochondrial apoptosis pathway.
Abstract:Objective To investigate the clinicopathological features and prognostic aspect of basaloid squamous carcinoma （BSC）. Methods From July 2000 to May 2003, the clinical data of 1 257 documented cases that underwent potentially curative resection on esophageal carcinoma in our department were retrospectively analysed, and 18 cases of BSC （BSC group） were detected. And 54 cases of typical squamous carcinoma of esophagus（ESC） were randomly selected as control （ESC group）, to analyse the clinicopathological and prognostic parameters of BSC patients. Results The age of BSC group patients was higher than that of ESC group （61. 56 ± 7. 62 years vs. 56.11± 10. 58 years; t=-2. 012,P=0. 048）, and the ratio of T4 stage was much higher than that in ESC group （27.8% vs. 5.6%;x2= 6. 750, P= 0. 020）. The follow-up showed that, comparing with ESC group, the ratio of metastasis was higher（62.5% vs. 25.0%, P=0. 047）, and mean survival time（P〈0.05） was significantly shorter in patients of BSC group after curative resection. There were no statisticaly differences in patient gender （P = 0. 494）, or ratio of recurrence （P=0. 887） between two groups. Conclusion The BSC is a rare carcinoma involving esophagus, which occurs in elder patients. Both invasiveness and metastasis of BSC are more usual than those of typical ESC.
目的：研究小鼠头颈鳞癌细胞株SCCⅦ体外放射敏感性，并探讨其与细胞周期阻滞的可能关系。方法：利用细胞克隆形成试验及MTT法检测SCCⅦ细胞受X射线照射后细胞存活能力及细胞生长趋势的变化，通过流式细胞学检测X射线照射后细胞周期分布的变化。结果：相同剂量照射后的SCCⅦ细胞存活分数高于Hela细胞（Plt;0.05）；4 Gy照射后的SCCⅦ细胞在96 h内细胞生长速度仍高于Hela细胞（Plt;0.05）；4 Gy照射后SCCⅦ细胞G1期和G2期细胞比例明显升高（Plt;0.05）。结论：SCCⅦ细胞对放射线不敏感性，放射线导致的细胞周期阻滞是SCCⅦ细胞放射抵抗的可能原因之一
ObjectiveTo explore the effect of DDX46 silencing on growth and apoptosis in esophageal squamous cell carcinoma cell TE-1 by the shRNA. MethodsThe relative expression of DDX46 mRNA in TE-1 cells was detected by real-time quantitative polymerase chain reaction (qRT-PCR) and compared with immortalized human esophageal squamous cell Het-1A. DDX46 shRNA-expressing lentivirus was applied to silence DDX46 (experimental group), and non-silencing control lentivirus was added (control group) with a multiplicity of infection of 5 in TE-1 cells. In both groups, cell growth was monitored using high content screening, cell colony-forming capacity was measured by colony formation assay, cell apoptosis were determined by flow cytometry. Further, the Stress and Apoptosis Signaling Antibody Array Kit was used to detect the changes of signaling molecules in TE-1 cells after DDX46 knockdown. ResultsCompared with the control group, cell counting after DDX46 silencing showed that TE-1 cell growth was significantly inhibited (P<0.001). Colony formation assay showed that cell colony-forming capacity was significantly inhibited (P<0.01). Annexin V-APC flow cytometry showed a significant increase in apoptosis (P<0.001). In PathScan® Antibody Array, the expression levels of Akt (Ser473, phosphorylation) and IκBα (Total, N/A) significantly decreased (P<0.01), and the expression of Caspase-3 (Asp175, cleaved) increased (P<0.05). ConclusionDDX46 is overexpressed in TE-1 cells. Targeted gene silencing of DDX46 inhibits cell growth, and induces cell apoptosis. DDX46 silencing probably by negative regulation of Akt/NF-κB signaling pathway, to play a role in inhibiting TE-1 cells growth and inducing apoptosis.
ObjectiveTo investigate the expression of MicroRNA 155 (miR-155) in esophageal squamous cell carcinoma (ESCC) and analyze its correlation with clinicopathological features of ESCC. MethodsThis study included 54 patients with primary ESCC who underwent radical esophagectomy in Department of Thoracic Surgery, Henan Cancer Hospital of Zhengzhou University between January 2010 and November 2012. There were 47 males and 7 females with median age of 61 years (range, 45 to 82 years). Forty patients were in stage Ⅰ or Ⅱ and 14 patients in stage Ⅲ a+b. Expression of miR-155 was determined by SYBR Green qRT-PCR in ESCC tissue and corresponding adjacent normal mucosa in surgical samples from the 54 patients, and its correlation with clinicopathological features was analyzed. ResultsExpression of miR-155 was significantly lower in ESCC tissue than that in adjacent normal mucosa (Z=-4.258, P=0.000).Expression level of miR-155 was significantly correlated with lymph node metastasis (P=0.040), but not significantly correlated with smoking (P=0.430), drinking (P=0.429), age (P=0.769), gender (P=0.671), depth of invasion (P=0.230), differentiation degree (P=0.896) or pTNM (P=0.407) of ESCC. ConclusionUnder-regulation of miR- 155 expression in ESCC tissue may lead to disorders of inflammation response, immune response and relevant tumor suppressor, and may play a significant role in carcinogenesis and progression of ESCC.
Objective To observe the growth of xenografted tumor in nude mice after DDX46 expression decreased, and to further study the role of DDX46 in the development and progression of esophageal squamous cell carcinoma. Methods DDX46-shRNA mediated RNAi was applied to silencing DDX46 in Eca-109 cells. Twenty-five female BALB/c nude mice were divided into 3 groups: an experiment group (DDX46-shRNA-LV, n=10), a control group (Control-LV, n=10) and a blank control group (Het-1A, n=5). The prepared Eca-109 cells of DDX46-shRNA-LV and Control-LV were subcutaneously injected into the right armpit of mice (4×106 cells per mouse), while Het-1A cells were subcutaneously injected into the bilateral armpits of mice (4×106 cells per side). Tumor growth was monitored twice a week on the 14th day after injection. Tumor volume was measured with calipers, in vivo imager to observe the fluorescence of each group. Further, western blotting analysis was used to detect the changes of apoptosis signaling molecules in xenografted tumor after DDX46 silence. Results The growth of xenografted tumor in nude mice was significantly slower in the DDX46-shRNA-LV group than that in the Control-LV group throughout the study period (P<0.001). Western blotting analysis showed that silencing DDX46 effectively suppressed the expression of DDX46, and upregulated the expression of cleaved Caspase-3 and cleaved PARP-1 in xenografted tumor (P<0.01). Conclusion DDX46 is involved in the development and progression of esophageal squamous cell carcinoma, and the silence of DDX46 expression can inhibit the growth of esophageal squamous cell carcinoma, which probably by positive regulation of apoptosis signaling pathway.