非小细胞肺癌EBUS-TBNA标本中TTF-1、CK7、CK5/6和p63的表达及其意义

目的：探讨在非小细胞肺癌支气管内超声引导针吸活检(EBUS-TBNA)标本中TTF-1、CK7、CK5/6和 p63的表达及其意义。方法采用免疫组化 SP 法检测64例非小细胞肺癌患者EBUS-TBNA标本的TTF-1、CK7、CK5/6和 p63的表达情况。结果 TTF-1和 CK7在肺腺癌患者EBUS-TBNA标本中的表达阳性率分别为75.00%和100.00%,明显高于肺鳞癌(χ2值分别为16.94、32.00,P值均<0.05);CK5/6和 p63在肺鳞癌患者 EBUS-TBNA标本中的表达阳性率分别为91.67%和75.00%,明显高于肺腺癌(χ2值分别为11.45、4.80,P 值均<0.05)。结论检测非小细胞肺癌EBUS-TBNA标本的TTF-1、CK7、CK5/6和 p63对鉴别肺鳞癌和腺癌有重要意义。     

食管鳞状细胞癌组织中RSK4、p63的表达变化及意义

目的 探讨食管鳞状细胞癌（鳞癌）组织中核糖体S6蛋白激酶4(RSK4)、p63的表达变化及意义。方法收集食管鳞癌活检标本72例份,应用免疫组织化学EnVision两步法检测癌组织中RSK4、p63蛋白表达,染色结果采用半定量分析。选取食管鳞状细胞癌细胞系TE-11、TE-10及正常食管细胞Het-1A,分别采用qRT-PCR法、Western blotting法检测RSK4、p63 mRNA及蛋白表达。采用Kaplan-Meier法及Cox风险回归模型对患者进行生存分析。结果食管鳞状细胞癌组织中RSK4蛋白阳性表达率为62.5%(45/72),p63蛋白阳性表达率为83.3%(60/72)。食管鳞状细胞癌细胞系（TE-11、TE-10）中RSK4、p63基因的mRNA和蛋白表达均高于正常食管细胞Het-1A(P均<0.05)。Kaplan-Meier法生存分析结果显示,RSK4阳性表达与食管癌患者预后不良相关（P<0.05）,且分期、组织分化程度、淋巴结转移等均是影响患者生存期的因素（P均<0.05）;p63表达与患者临床病理特征及预后均无关（P均>0.05）。...     

p53蛋白表达与乳腺癌新辅助化疗疗效的关系

采用新辅助化疗TE方案对50例Ⅱa～Ⅲb期乳腺癌患者治疗4个周期，化疗前用粗针穿刺获得乳腺癌组织病理诊断，同时用免疫组化方法检测p53蛋白表达。结果显示，p53蛋白表达阴性者有效率82％，阳性者47％，二者差异有显著性（P〈0．05）。提示p53蛋白表达水平是乳腺癌TE方案新辅助化疗疗效的重要预测因子，阳性者对TE方案疗效欠佳。     

扁桃体鳞状细胞癌中CK7 CK19和p16的表达关系研究

目的 分析细胞角蛋白7(CK7)、细胞角蛋白19(CK19)和p16INK4a蛋白(p16)在扁桃体鳞状细胞癌(TSCC)组织及癌周隐窝上皮和表面上皮中的表达关系,探讨其在人乳头状瘤病毒(HPV)感染相关扁桃体癌变机制中的作用.方法 选择2015-07～2018-01广西医科大学第一附属医院耳鼻喉头颈外科收治的17例T...     

鳞状细胞相关抗原和血管内液生长因子在宫颈浸润癌新辅助化疗前后的改变及临床意义

目的：研究鳞状细胞相关抗原（Scc-Ag）和血管内皮生长因子（VEGF）在宫颈浸润癌新辅助化疗前、后水平的改变,探讨其在宫颈浸润癌诊断和新辅助化疗疗效观察中的临床意义。方法：分别采用化学发光检测技术和酶联免疫（ELISA）法测定89例宫颈浸润癌患者新辅助化疗前后Scc-Ag和VEGF水平,并进行对比分析和观察。结果：①89例宫颈浸润癌患者新辅助化疗前Scc-Ag和VEGF的中位值水平分别为13.61μg/L和393.75μg/L,阳性率为60.67%（54/89）和73.03%（65/89）;新辅助化疗后Scc-Ag和VEGF的中位值水平分别为7.59μg/L和286.37μg/L,阳性率为51.68%（46/89）和65.16%（58/89）。新辅助化疗前、后比较中位值水平差异有统计学意义（P〈0.05）,阳性率差异无统计学意义（P〉0.05）。②宫颈浸润癌患者新辅助化疗后的总反应率为83.15%（74/89）,可手术率为77.52%（69/89）,化疗无反应率为22.47%（20/89）,4例患者新辅助化疗后Scc-Ag和VEGF水平恢复正常;但有10例患者Scc-Ag和VEGF水平较新辅助化疗前增高更为显著（P〈0.05）,且皆为对化疗无反应的手术困难病例。结论：Scc-Ag和VEGF是诊断宫颈浸润癌较为灵敏的指标,接受新辅助化疗后,部分患者Scc-Ag和VEGF恢复到正常水平,少数患者Scc-Ag和VEGF水平增高更明显,且皆为对化疗无反应的手术困难病例,预后差。因此,Scc-Ag和VEGF是宫颈浸润癌较敏感的实验观察指标,在宫颈浸润癌诊断和新辅助化疗疗效观察中有一定的临床应用价值。     

子宫内膜样腺癌组织中p63和CK5/6表达变化及意义

目的 观察子宫内膜癌组织中p63、细胞角蛋白5/6 （CK5/6）的表达变化,并探讨其临床意义.方法 采用免疫组化SP法检测25例（A组）子宫内膜增生、20例（B组）非典型子宫内膜增生及26例（C1组）子宫内膜样腺癌浸润肌层≤ 1/2、14例（C2组）浸润肌层＞1/2组织中的p63和CK5/6.结果 A组p63阳性23例,B组20例,P＞0.05;A组平均阳性指数（ASI）为0.65 ±0.15,B组为0.38 ±0.23,P≤0.05;C1组p63阳性2例,C2组0例,P＞0.05;C1组ASI为0.21 ±0.11,C2组为0,P≤0.05;A组CK5/6阳性22例,B组18例,P＞0.05;A组ASI为0.66±0.15,B组为0.36 ±0.22,P≤0.05;C1组CK5/6阳性3例,C2组0例,P＞0.05;C1组ASI为0.22±0.10,C2组为0,P ≤0.05;C1组p63和CK5/6阳性表达率、ASI均高于B组,P均≤0.05.子宫内膜增生和子宫内膜样腺癌组织中,p63和CK5/6表达的ASI呈正相关（r分别为0.235、0.257,P均≤0.05）.A、B、C1、C2组10年生存率分别为100.0％、75.0％、50.0％、14.3％,P均≤0.05.结论 子宫内膜样腺癌组织中p63和CK5/6表达减少,二者在子宫内膜样腺癌的诊断及病情发展和预后判断中有一定指导作用.     

术前新辅助化疗对小细胞肺癌远期生存的影响

目的揭示术前新辅助化疗对小细胞肺癌（SCLC）长期生存的影响对外科临床十分重要。方法总结1994年1月。2005年1月手术切除263例SCLC的综合治疗效果。分析比较术前新辅助化疗组（A组，n=111例）和术后化疗组（B组，n=96例）的治疗效果。结果A组5年生存率38．25％，B组5年生存46．57％。A组5年生存率Ⅰ期60．15％、Ⅱ期35．70％、Ⅲa期40．16％、Ⅲb期14．29％、Ⅳ期0，5年生存率N0-1和N2组为40，12％和39．22％。B组5年生存率Ⅰ期61．10％、Ⅱ期50．23％、Ⅲa期42．32％、Ⅲb期26．47％、1V期0，5年生存率N0-1和N2组为51．91％和42．69％。结论新辅助化疗病例与术后化疗病例相比预后差：SCLC要取得较好的治疗效果，术后化疗模式不可缺少。     

FXYD6过表达对肝细胞癌SMMC7721细胞5-Fu化疗敏感性的影响

目的 观察FXYD离子转运调节因子6(FXYD6)过表达对肝细胞癌SMMC7721细胞5-氟尿嘧啶(5-Fu)化疗敏感性的影响.方法 将肝细胞癌SMMC7721细胞分为过表达组和对照组,分别转染pcDNA3.1/FXYD6和pcD-NA3.1/Vector真核质粒,培养48 h筛选SMMC7721抗性克隆.取两组转染后...     

新辅助化疗对胃癌组织CD44V6、p21阳性表达及患者预后的影响

目的探讨新辅助化疗对胃癌组织CD44V6、p21阳性表达及患者预后的影响。方法选择胃癌患者60例,随机分为观察组、对照组各30例。两组均行胃癌根治术。观察组先行新辅助化疗2个周期,术后给予常规化疗;对照组仅术后给予常规化疗。两组手术前(观察组新辅助化疗后)经胃镜取胃癌组织,手术后取手术切除的胃癌组织。采用免疫组化SP法检测癌组织中CD44V6、p21表达。术中清扫淋巴结,观察淋巴结阳性率;术后随访3年,观察术后复发率及3年生存率。结果对照组手术前后胃癌组织中CD44V6、p21阳性表达比较差异无统计学意义(P均>0.05),观察组术后胃癌组织中CD44V6阳性表达明显降低、p21阳性表达明显升高(P均<0.05)。观察组淋巴结阳性率、术后3年复发率均低于对照组,术后3年生存率高于对照组(P均<0.05)。结论新辅助化疗能降低胃癌组织CD44V6阳性表达、提高p21阳性表达,继而改善胃癌患者预后,提高患者生存率。     

Efficacy and safety of neoadjuvant chemotherapy and immunotherapy in locally resectable advanced esophageal squamous cell carcinoma

BackgroundEsophageal squamous cell cancer (ESCC) patients with the potentially resectable disease most would experience relapse after surgery. Immunotherapy has been reported to improve the prognosis of advanced esophageal cancer and may be a new strategy to prevent this urgent condition’s recurrence. We first evaluated the efficacy and safety of neoadjuvant chemotherapy combined with immunotherapy in patients with resectable ESCC.MethodsAll patients with resectable locally advanced ESCC (clinical stage III–IVB). Received at least 1 cycle of neoadjuvant chemotherapy combined with immunotherapy (NACI), and the interval between each cycle and the operation should be at least 3 weeks. All patients were treated with standard surgery. The tumor imaginations were obtained at baseline and within a week before surgery. The efficacy endpoint was the rate of major pathologic response (MPR, 10% viable tumor cells). Expression of immunohistochemical-related molecules was investigated in surgical samples.ResultsA total of 38 patients with ESCC were included (36 males, median age 61 years), and most of them used Pembrolizumab (55.26%) and Camrelizumab (31.58%). We analyzed 19 patients and found that 13 patients (68.42%) achieved radiological partial response (PR) by CT images. R0 resection was performed in 35 patients (92.11%), and 10 patients (26.32%) developed postoperative complications. Through postoperative pathology, we found 13 (34.21%) patients had complete pathologic response (cPR), and 16 (42.11%) patients achieved MPR. We also found that none of the factors had a statistically significant impact on MPR. Still, the regression rate of Sum of lesion diameter (SLD) was significantly positively correlated with the pathological remission rate (P=0.012, r=0.565).ConclusionsThe rate of MPR in ESCC patients reached 42.11%. The use of the NACI regimen did not increase the occurrence of complications in neoadjuvant treatment and operation, and the SLD regression rate has a certain guiding significance for the effect of immunotherapy.     

p53蛋白在口腔鳞癌中的表达

目的 通过对突变型p53蛋白在口腔鳞癌组织中表达的观察,分析p53与口腔鳞癌临床病理特征之间的关系,探讨p53在口腔鳞癌发生中的作用机制。方法 利用免疫组化(P-V法)检测116例患者口腔鳞癌组织及10例正常人口腔黏膜组织中突变型p53蛋白的表达情况。结果 p53蛋白在正常人口腔黏膜和口腔鳞癌组织中的表达率分别为20％、63.8％,二者比较差异有统计学意义(X2=5.660 4,P<0.05);口腔鳞癌在不同病理分级时,p53蛋白表达差异有统计学意义(X2=7.536 2,P<0.05);p53蛋白表达与年龄、性别、发生部位及有无淋巴结转移无相关性。结论 突变型p53蛋白表达与口腔鳞癌的发生有关。不同病理分级,p53蛋白表达也不同。     

Assessment of neoadjuvant chemotherapy for patients with advanced squamous cell carcinoma of the esophagus

Background  Neoadjuvant chemotherapy for advanced esophageal cancer is beneficial for responders, whereas it may provide no clinical benefits or even prove harmful in non-responders. Methods  This study retrospectively compared the pathological findings and prognosis of 60 patients with UICC non-T4 stage III and IV, who received chemotherapy followed by surgery, and 96 patients with non-T4 stage III and IV cancer, who underwent surgery alone. The treatment regimen of cisplatin (70 mg/m²/day on day 1), adriamycin (30 mg/m²/day on day 1), and 5-fluorouracil (750 mg/m²/day on days 1–7) was administered for two cycles. Responders represented patients with histological effect of grade 1b-3 following therapy; non-responders represented those with grade 0-1a histological effect. Results  Survival was not significantly different between the neoadjuvant chemotherapy group and the surgery-alone group. Responders showed a tendency of earlier postoperative pStages than preoperative cStages (P = 0.08), better survival (P = 0.10), significantly fewer metastatic nodes, and significantly less extensive lymphatic invasion than the surgery-alone group. However, non-responders showed no significant differences in the degree of downstaging, number of metastatic nodes, extent of lymphatic and venous invasion, and survival rate as compared with the surgery-alone group. Comparison of overall survival between the chemotherapy and surgery-alone groups after matching for pathological stage showed that the survival of pStage II patients of the chemotherapy group was significantly better than the pStage II patients of the surgery-alone group (P = 0.04), whereas that of pStage III and IV patients of the chemotherapy group was not significantly different from the same-stage patients of the surgery-alone group. Conclusions  These results suggest that chemotherapy improves prognosis of responders significantly more than those who show downstaged pathological stage. However, the chemotherapy does not give any clinical benefit for non-responders.     

ZFX promotes tumorigenesis and confers chemotherapy resistance in esophageal squamous cell carcinoma

IntroductionZinc finger X-chromosomal protein (ZFX) has been shown to be essential for the development and progression of multiple types of human cancers. However, its potential roles in esophageal squamous cell carcinoma (ESCC) have not yet been elucidated.Materials and methodsEighty-three pairs of frozen ESCC samples and their para-cancer samples and 24 fresh ESCC samples were collected. In vitro chemosensitivity was tested using the histoculture drug response assay. Quantitative RT-PCR and western blotting were used to measure the expression of functional genes. The effects of ZFX on cell growth, cell apoptosis, and chemosensitivity of the esophageal cancer cells were assessed.ResultsWe found that ZFX was more upregulated in ESCC tissues than in the para-cancer tissues, and its high expression was correlated with inferior clinicopathological characteristics and overall survival. Multivariate analysis revealed that ZFX was an independent prognostic factor in ESCC patients. In ESCC cell lines, ZFX silencing suppressed cell growth and induced cell apoptosis. In addition, ZFX expression was negatively correlated with the sensitivity of fresh ESCC tissues to chemotherapeutic drugs, including cisplatin, docetaxel, fluorouracil, and irinotecan. Furthermore, the depletion of ZFX sensitized ESCC cells to cisplatin, and docetaxel treatment. Mechanistically, ZFX silencing resulted in the inactivation of the MEK/ERK pathway, which mediated the downregulation of P-glycoprotein expression.ConclusionOur study therefore indicates that ZFX possibly plays a critical role in ESCC tumorigenesis and chemotherapy resistance and could be a significant prognostic biomarker and therapeutic target for ESCC.     

食管鳞癌组织p16基因调控区甲基化及其蛋白表达研究

目的探讨p16基因在食管癌变过程中表达缺失与其启动子区甲基化的关系。方法采用MSP免疫组化方法,检测环太行山地区45例食管鳞癌患者癌组织p16基因启动子区甲基化状态及蛋白表达情况。结果p16基因在癌组织中表达异常41例（91．1％）,间变组织中表达异常38例（84．4％）,发生纯合型甲基化的组织分别为33例（73．3％）（癌组织）和32例（71．1％）（间变组织）,而其周围正常组织26例（57．8％）均发生了p16启动子区的杂合型甲基化。p16基因纯合型甲基化与癌组织、间变组织、p16蛋白表达缺失相关（P〈0．05）。结论该地区食管癌组织p16基因在癌前病变中p16启动子区即发生了纯合型甲基化、食管癌变的早期事件。p16基因启动子区甲基化可单独影响p16蛋白的正常表达。     

Association of p53/p21 expression with cigarette smoking and prognosis in esophageal squamous cell carcinoma patients

factors,such as cigarette smoking,in esophageal squamous cell carcinoma(ESCC)in northeastern Iran,a region with a high incidence of ESCC.METHODS:The expression of p53 and p21 proteins was investigated immunohistochemically in tumor tissue from 80 ESCC patients and in 60 available paraffinembedded blocks of adjacent normal specimens from the cases,along with normal esophageal tissue from 80 healthy subjects.RESULTS:Positive expression of p53 protein was detected in 56.2%(45/80)of ESCC cases,and in none of the normal esophageal tissue of the control group(P<0.001).Furthermore,73.8%(59/80)of ESCC cases and 43.8%(35/80)of controls had positive expression of p21 protein(P<0.001).Cigarette smoking was significantly associated with p53 over-expression in ESCC cases(P=0.010,OR=3.64;95%CI:1.32-10.02).p21 over-expression was associated with poorer clinical outcome among the ESCC patients(P=0.009).CONCLUSION:Over-expression of p53 in association with cigarette smoking may play a critical role in ESCC carcinogenesis among this high-risk population of northeastern Iran.Furthermore,p21 over-expression was found to be associated with poor prognosis,specifically in the operable ESCC patients.