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。
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.
Objective To observe the expression of Twist in esophageal squamous cell carcinoma (ESCC) and analyze the relationship between positive expression of Twist and disease-free survival, and to provide clinical evidence for reducing tumor recurrence, prolonging disease-free survival and improving prognosis. Methods Retrospective analysis of 70 ESCC patients receiving thoracic surgery from June 2010 to June 2012 in the Department of Thoracic Surgery, Sichuan Cancer Hospital was done, including 39 males and 31 females with an average age of 63.6 years. The expression of Twist in normal esophageal tissue, tumor tissue and vascular tumor emboli was observed by immunohistochemical staining of paraffin specimens. Results The positive rate of Twist in normal esophageal tissues was 42.9%, and in tumor tissue was 77.1% (P<0.05). The positive expression rate of Twist in tumor cells was 74.3% in patients with vascular tumor emboli and 80.0% in patients without vascular tumor emboli (P>0.05). The positive expression rate of Twist in tumor cells and in vascular tumor emboli was 74.3% and 71.4%, respectively (P>0.05). The expression of Twist in lymphatic vessels and blood vessels of patients with vascular tumor emboli was 56.0% and 72.0%, respectively (P>0.05). Conclusion Twist expression in esophageal cancer tissues is significantly higher than that in normal tissues, but there is no significant difference in the positive expression of Twist between tumor cells and the mean disease-free survival (P>0.05). At present, Twist expression can not be used as a prognostic indicator of esophageal cancer, and more researches need be further implemented.
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
Objective To compare short-term quality of life and postoperative complications in esophageal squamous cell carcinoma patients with different routes reconstruction after McKeown esophagectomy. Methods The clinical data of 144 patients with esophageal squamous cell carcinoma who received McKeown esophagectomy in Shanghai Chest Hospital from January 2016 to October 2016 were retrospectively reviewed. Among them 93 patients accepted retrosternal approach (a RR group, 71 males and 22 females at an average age of 63.5±7.7 years) and 51 patients accepted posterior mediastinal approach (a PR group, 39 males and 12 females at an average age of 62.3±8.0 years). Short-term surgical outcomes were compared and a Quality of Life Questionnaire of Patients Underwent Esophagectomy 1.0 was performed at postoperative 1st and 3rd month. Results There was no difference in two groups in sex, age, Body Mass Index (BMI), and location and clinical stage of tumors (P>0.05). The neoadjuvant therapy was more performed in the RR group (16.1%vs. 5.9%, P=0.075). There were more robot-assisted esophagecctomy operations performed in the PR group (52.9% vs. 45.2%, P=0.020). No significant difference was noted in operation duration, intraoperative blood loss or length of ICU stay between the RR and PR groups (251.3±59.1 min vs. 253.1±27.7 min, P=0.862; 223.7±75.1 ml vs. 240.0±75.1 ml, P=0.276; 3.7±6.6 d vs. 2.3±2.1 d, P=0.139). The patients in the PR group had more lymph nodes dissected and shorter hospital stay (P<0.001). Rate of R1/2 resection was higher in the RR group (12.9%vs. 5.9%, P=0.187). No surgery-related mortality was observed in both groups. The anastomotic leak and the anastomotic stricture was higher in the RR group than that in the PR group (25.8% vs. 5.9%, P=0.003). No significant difference was found between the two groups in the quality of life at postoperative 1st and 3rd month. However, the quality of life at postoperative 3rd month significantly improved in both groups (P<0.001). Compared with the PR group, the dysphagia was more severe in the RR group at postoperative 1st month (3.3±1.5 vs. 2.6±1.1, P=0.007), while the reflux symptom was lighter at postoperative 3rd month (3.0±1.8 vs. 3.6±1.6, P=0.045). Conclusion The two different routes reconstruction after McKeown esophagectomy are both safe and feasible. The anterior mediastinal approach increases the risk of anastomotic leak, but with low incidence of reflux symptom.
Objective To evaluate the security and outcomes of thoracolaparoscopic esophagectomy (TLE) versus open approach (OA) for thoracic esophageal squamous cell carcinoma. Methods From June 2014 to June 2015, 125 patients with thoracic esophageal squamous cell carcinoma underwent esophagectomy through McKeown approach, including TLE (a TLE group, 107 patients, 77 males and 30 females) and OA (an OA group, 18 patients, 13 males and 5 females). The data of operation and postoperative complications of the two groups were analyzed retrospectively. Results There was no statistical difference in the duration of operation and ICU stay and resected lymph nodes around laryngeal recurrent nerve between the TLE group and the OA group (333.58±72.84 min vs. 369.17±91.24 min, P=0.067; 2.84±1.44 d vs. 6.44±13.46 d, P=0.272; 4.71±3.87 vs. 3.89±3.97, P=0.408) . There was a statistical difference in blood loss, total resected lymph nodes and resected lymph nodes groups between TLE group and OA group (222.62±139.77 ml vs. 427.78±276.65, P=0.006; 19.62±9.61 vs. 14.61±8.07, P=0.038; 3.70±0.99 vs. 3.11±1.13, P=0.024). The rate of postoperative complications was 32.7% in the TLE group and 38.9% in the OA group (P=0.608). There was a statistical difference (P=0.011) in incidence of pulmonary infection (2.8% in the TLE group and 16.7% in the OA group). Incidences of complications, such as anastomotic leakage, cardiac complications, left-side hydrothorax, right-side pneumothorax, voice hoarse and incision infection, showed no statistical difference between two groups. Conclusion For patients with thoracic esophageal squamous cell carcinoma, TLE possesses advantages of more harvested lymph nodes, less blood loss and less pulmonary infection comparing with open approach, and is complied with the principles of security and oncological radicality of surgery.
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.