食管鳞癌组织中SPARC蛋白表达的临床意义

目的：探讨基质蛋白SPARC在食管鳞癌的增殖、侵润和转移中的作用。方法：应用免疫组化技术研究SPARC在食管鳞癌组织和其相邻的正常粘膜组织的表达差异，同时对蛋白表达进行定位。结果：36例食管鳞癌手术标本中30例SPARC蛋白表达阳性，正常食管上皮组织表达阴性（P〈0．01）。SPARC蛋白在不同分化程度的食管鳞癌组织中的表达阳性率基本相同（P〉0.05），有淋巴结转移的食管鳞癌组织与无淋巴结转移癌组织的表达间有显著差异（P〈0.05）。4例癌组织细胞核有表达，其余均为细胞浆表达。结论：SPARC和食管癌的发生与发展密切相关。食管癌出现转移时SPARC蛋白表达升高。     

组织蛋白酶B表达与食管鳞癌浸润转移的关系

目的：探讨组织蛋白酶B（cathepsin B，CB）表达与食管鳞癌发生、发展及浸润转移的关系。方法：应用免疫组化SP法和原位杂交方法检测49例食管癌组织及其相应的癌旁非典型增生组织和正常组织中CB蛋白及mRNA的表达。结果：正常食管粘膜CB蛋白及mRNA均阴性表达，转移组癌组织及非典型增生组织CB蛋白及mRNA阳性表达率明显高于无转移组。两组间相比差异有显著性（P〈0．05）。浸润至外膜组癌组织、非典型增生组织中CB蛋白和CBmRNA的阳性表达率均高于浅肌层组、深肌层组，差异有显著性（P〈0．05）；深肌层与浅肌层相比，差异无显著性（P〉0．05）。转移组及无转移组癌组织CB蛋白及mRNA阳性表达率均高于相应的癌旁非典型增生组织，差异有显著性（P〈0．01）。结论：人食管鳞癌组织CB蛋白及mRNA均呈高表达，CB表达与食管癌的发生、发展及浸润转移有关。     

食管鳞癌组织中P-selectin的表达与淋巴结转移的关系

目的　探讨P selectin在食管鳞癌中的表达水平及其与食管癌病理分级和淋巴结转移的关系。方法　应用原位杂交及免疫组化SP技术研究了P selectinmRNA及蛋白在有转移的和无转移的食管鳞癌中的表达。结果　癌组织中P selectinmRNA及蛋白的阳性率在有转移的食管鳞癌中的表达分别为 76.2 % ( 16/2 1)和 85 .7% ( 18/2 1) ,在无转移的食管鳞癌中的表达分别为 48.5 % ( 16/3 3 )和5 4.5 % ( 18/3 3 )。它们的表达与浸润深度和淋巴结转移呈正相关 (P <0 .0 5 )。P selectinmRNA与P selectin蛋白的表达呈明显负相关(r =0 .0 0 5 )。结论　P selectin与食管癌浸润深度和淋巴结转移关系密切     

层粘连蛋白在食管鳞癌的表达及其与临床特征的关系

目的:探讨细胞外基质中层粘连蛋白(Laminin,LN)在食管鳞癌的表达情况与临床病理关系。方法:采用免疫组织化学SABC法对70例食管鳞癌原发灶进行了检测。结果:LN在食管鳞癌中的表达率为64.3%。中高分化组及淋巴结无转移组中LN表达明显强于低分化组及有转移组(P<0.05)。结论:基底膜中LN的分布和含量与肿瘤浸润转移有关,可作为评价食管鳞癌侵袭性及恶性程度的指标之一。     

食管鳞癌中ICAM-1蛋白的表达及意义

目的 研究细胞间粘附分子-1(ICAM-1)在食管鳞癌组织中的表达及意义.方法 采用免疫组织化学S-P法检测49例食管鳞癌组织及38例正常食管黏膜组织中ICAM-1蛋白的表达.结果 食管鳞癌组织中ICAM-1蛋白表达率为46.9%(23/49),显著高于其在正常食管黏膜组织中的表达0.0%(0/38);ICAM-1蛋白表达率在有淋巴结转移组明显高于无淋巴结转移组;其表达率随癌组织浸润深度的加深而增加;在不同分化程度的癌组织中其阳性率也有一定差异,Ⅰ级与Ⅱ、Ⅲ级之间差异有统计学意义(P＜0.05).结论 ICAM-1在食管鳞癌的发生发展中起重要作用,与肿瘤的浸润转移密切相关.     

食管鳞癌中PTEN蛋白的表达及意义

目的　通过对PTEN在食管鳞癌中表达的研究,探讨其与食管鳞癌的发生、浸润、转移的关系。方法　应用免疫组织化学S P法检测49例食管鳞癌组织及40例正常食管黏膜组织中PTEN的表达。结果　食管鳞癌组织中PTEN蛋白表达率为5 3 0 6% (2 6/4 9)。显著低于正常食管黏膜组织的表达10 0 % (4 0 /4 0 ) ,在不同分化程度的癌组织中其阳性表达率有显著性差异(P <0 0 5 ) ,且PTEN蛋白表达率随癌组织浸润深度的加深而明显降低(P <0 0 5 ) ,有淋巴结转移组明显低于无淋巴结转移组(P <0 0 5 )。结论　PTEN基因缺失或蛋白表达降低在食管鳞癌的发生发展中可能起重要作用,且与肿瘤的分化程度、浸润转移密切相关。     

食管鳞癌p16和p53蛋白的表达及其意义

目的 :探讨 p16、p5 3蛋白在食管鳞癌 (ESC)中的表达及其意义。方法 :利用 S- P法检测 5 6例 ESC中 p16和 p5 3蛋白的表达。结果 :5 6例食管鳞癌中 ,p16蛋白表达阳性 2 1例 ,占 37.5 % ,p5 3蛋白表达阳性 35例 ,占 6 2 .5 % ,p16和 p5 3蛋白表达与肿瘤分化程度关系密切 ,随分化程度的降低 ,p16蛋白阳性率逐渐降低 (P<0 .0 2 5 ) ,p5 3蛋白阳性率逐渐增加 (P<0 .0 5 ) ,p16阳性表达组 p5 3表达显著低于 p16阴性组 (P<0 .0 1) ,且与淋巴结转移有一定的关系。结论 :联合检测食管鳞癌组织中 p16和 p5 3蛋白的表达有助于综合判断食管鳞癌的恶性程度和转移潜能。     

微管不稳定蛋白Stathmin在食管鳞癌组织中的表达及意义

目的 探讨Stathmin蛋白在食管鳞癌组织中的表达及意义.方法 收集新乡医学院2006年4月至9月期间食管鳞癌切除标本及其相应癌旁组织31例,以免疫组织化学法检测Stathmin蛋白在所取标本中的表达情况.结果 在31例食管鳞癌标本中,Stathmin蛋白表达阳性的标本为23例,阳性率为74.2%,阳性颗粒可见于细胞质;分别按年龄、性别、组织类型、分化程度、淋巴结转移、肿瘤浸润深度及TNM分期将31例食管癌标本分组,Stathmin蛋白表达差异有统计学意义的因素有分化程度、淋巴结转移、肿瘤浸润深度及TNM分期(P＜0.05).结论 食管鳞癌组织中Stathmin蛋白高表达,其表达与食管鳞癌的分化程度、淋巴结转移、肿瘤浸润深度及TNM分期显著相关,Stathmin蛋白可能为人食管癌的生物治疗提供一个新靶点.     

Increased expression of HSP27 inhibits invasion and metastasis in human esophageal squamous cell carcinoma

Previous studies have indicated that heat shock protein 27 (HSP27) had high correlation with the development and progression in several tumors. However, the roles of HSP27 in esophageal squamous cell carcinoma (ESCC) were uncertain. The aim in this study is to investigate the potential roles of HSP27 in the metastasis of ESCC. The expression of HSP27 in ESCC tissues and four human esophageal cancer cell lines were examined by immunohistochemistry and Western blotting, respectively. Wound healing assays, transwell assays, and in vivo assays were used to identify the differences of metastasis potential between normal and HSP27 overexpressed cells. HSP27 expression was downregulated in cancer tissue compared to the matched normal tissue. And the positive staining was mainly located in the cytoplasm. Statistical analyses showed that the expression of HSP27 in ESCC was significantly correlated with the tumor differentiation (P?=?0.023), the patient’s TNM stage (P?=?0.013), lymph metastasis (P?=?0.020), and distant metastasis (P?=?0.017). HSP27 expression was significantly lower in highly metastatic cells than the less ones. The metastatic potentials of EC9706-H and EC109-H cells were higher than EC9706-L and EC109-L cells. In vitro and in vivo assays showed that overexpression of HSP27 in highly metastatic cells dramatically decreased their metastatic capacity. This study indicated that the expression level of HSP27 may be inversely correlated with the metastasis behavior of ESCC, and HSP27 may play an important role in this progression. HSP27 may be a potential molecular target for the therapy and prognosis of patients with ESCC.     

ILK及E-钙黏蛋白的表达在宫颈鳞癌发病中的意义

目的 研究整合素连接激酶(ILK)、E-钙黏蛋白(E-cadherin)在宫颈上皮内瘤变(CIN)及宫颈鳞癌组织中的表达情况,分析其与临床病理资料的关系。方法 采用免疫组化方法检测ILK及E-cadherin在54例CIN、38例宫颈鳞癌及20例正常宫颈组织中的表达。结果 ILK在正常宫颈、CINⅠ、CINⅡ~Ⅲ及宫颈鳞癌中的阳性表达率分别为25.0%、68.8%、78.9%、97.3%。ILK在CIN及宫颈鳞癌中的阳性表达率显著高于正常宫颈(P＜0.05)。E-cadherin在正常宫颈、CINⅠ、CINⅡ~Ⅲ及宫颈鳞癌中的阳性表达率分别为100.0%、75.0%、55.3%、36.8%。E-cadherin在CIN及宫颈鳞癌中的阳性表达率显著低于正常宫颈(P＜0.05)。在宫颈鳞癌组织中ILK的表达与E-cadherin呈负相关(r=-0.531,P＜0.01)。E-cadherin阳性表达还与宫颈鳞癌临床分期、分化程度、淋巴结转移有关(P＜0.05)。结论 ILK、E-cadherin可作为区分正常宫颈组织与CIN及宫颈鳞癌的标记物,E-钙黏蛋白还与宫颈癌恶性生物学行为有关。     

MicroRNA-373 promotes migration and invasion in human esophageal squamous cell carcinoma by inhibiting TIMP3 expression

Esophageal squamous cell carcinoma (ESCC) is the predominant pathological type of esophageal carcinoma in Asia. MicroRNAs (miRNAs) are a class of 19-22-nucleotide non-coding RNAs acting on target mRNAs that function as either oncogenes or anti-oncogenes. It has been confirmed that miR-373 expression varies among different tumor types. However, its mechanism is still unclear in ESCC. In our current study, we found that miR-373 expression was upregulated in ESCC tissues compared with matched adjacent normal tissues, as well as in the plasma of ESCC patients compared with that of healthy volunteers. Overexpression of miR-373 in ECA109 cells enhanced proliferation, G1-phase cell proportion, migration, and invasion. On the other hand, suppression of miR-373 in KYSE410 cells decreased proliferation, G1-phase cell proportion, migration, and invasion and also improved cell apoptosis. Moreover, we found that TIMP3, which was reported to suppress invasion and metastasis of ESCC, was a direct target of miR-373. Overexpression of miR-373 in ECA109 caused a reduction of TIMP3 mRNA and protein, whereas suppression of miR-373 in KYSE410 led to an increase of TIMP3 mRNA and protein. Introducing TIMP3 in miR-373 over-expressed cells or knocking down TIMP3 in miR-373 suppressed cells could partially abrogate the effect of miR-373 on migration and invasion. Therefore, these results prove that as an oncogene, miRNA-373 would be an important and reliable biomarker for ESCC diagnosis and treatment by targeting TIMP3.     

Significance of COX-2 expression in human esophageal squamous cell carcinoma

Cyclooxygenase-2 (COX-2) is well established to play an important role in the tumorigenesis of a variety of human cancers; however, the function of COX-2 in the development of esophageal squamous cell carcinoma (ESCC) remains less clear. Here, we determined, first, the pattern of COX-2 expression in normal esophageal mucosa, dysplasia, carcinoma in situ (CIS) and invasive SCC. Immunohistochemical analysis showed that, while COX-2 was weakly expressed, if at all, in normal squamous epithelium, strong COX-2 expression was detected as early as the stage of dysplasia and frequently in 20 of 26 (77%) CIS and 86 of 111 (77%) invasive SCC. Upregulation of COX-2 in ESCC was found to be significantly associated with tumor progression (R = 0.493, P < 0.01). Further, treatment of human ESCC cell lines (KYSE450 and KYSE510) with NS-398, a COX-2 specific chemical inhibitor, suppressed the production of prostaglandin E2 (PGE2) and induced cell growth inhibition, cell cycle arrest at the G1-S checkpoint, and the expression of cyclin-dependent kinase inhibitors p21waf1/cip1 and p27kip1. Finally, knockdown expression of COX-2 in KYSE450 cells by a specific COX-2 siRNA dramatically inhibited PGE2 production, cell growth and, more importantly, colony formation and tumorigenesis in nude mice. Together, this study suggested that COX-2 may be involved in an early stage of squamous cell carcinogenesis of the esophagus and has a non-redundant role in the regulation of cellular proliferation and tumorigenesis of esophageal epithelial cells.     

PRAF3 induces apoptosis and inhibits migration and invasion in human esophageal squamous cell carcinoma

Background

Diet has long been suspected to impact on breast cancer risk. In this study we evaluated whether the degree of adherence to a Mediterranean diet pattern modifies breast cancer risk amongst Greek-Cypriot women.

Methods

Subjects included 935 cases and 817 controls, all participating in the MASTOS case-control study in Cyprus. The study was approved by the Cyprus National Bioethics Committee. Information on dietary intakes was collected using an interviewer administered 32-item Food Frequency Questionnaire. Information on demographic, anthropometric, lifestyle, and other confounding factors was also collected. Adherence to the Mediterranean Diet pattern was assessed using two a-priory defined diet scores. In addition, dietary patterns specific to our population were derived using Principal Component Analysis (PCA). Logistic regression models were used to assess the association between the dietary patters and breast cancer risk.

Results

There was no association with breast cancer risk for either score, however, higher consumptions of vegetables, fish and olive oil, were independently associated with decreased risk. In addition, the PCA derived component which included vegetables, fruit, fish and legumes was shown to significantly reduce risk of breast cancer (ORs across quartiles of increasing levels of consumption: 0.89 95%CI: 0.65-1.22, 0.64 95%CI: 0.47-0.88, 0.67 95%CI: 0.49-0.92, P trend < 0.0001), even after adjustment for relevant confounders.

Conclusions

Our results suggest that adherence to a diet pattern rich in vegetables, fish, legumes and olive oil may favorably influence the risk of breast cancer. This study is the first investigation of dietary effects on breast cancer risk in Cyprus, a country whose population has traditionally adhered to the Mediterranean diet.     

Proteoglycans and their functions in esophageal squamous cell carcinoma

Esophageal squamous cell carcinoma (ESCC) is a highly malignant disease that has a poor prognosis. Its high lethality is mainly due to the lack of symptoms at early stages, which culminates in diagnosis at a late stage when the tumor has already metastasized. Unfortunately, the common cancer biomarkers have low sensitivity and specificity in esophageal cancer. Therefore, a better understanding of the molecular mechanisms underlying ESCC progression is needed to identify novel diagnostic markers and therapeutic targets for intervention. The invasion of cancer cells into the surrounding tissue is a crucial step for metastasis. During metastasis, tumor cells can interact with extracellular components and secrete proteolytic enzymes to remodel the surrounding tumor microenvironment. Proteoglycans are one of the major components of extracellular matrix. They are involved in multiple processes of cancer cell invasion and metastasis by interacting with soluble bioactive molecules, surrounding matrix, cell surface receptors, and enzymes. Apart from having diverse functions in tumor cells and their surrounding microenvironment, proteoglycans also have diagnostic and prognostic significance in cancer patients. However, the functional significance and underlying mechanisms of proteoglycans in ESCC are not well understood. This review summarizes the proteoglycans that have been studied in ESCC in order to provide a comprehensive view of the role of proteoglycans in the progression of this cancer type. A long term goal would be to exploit these molecules to provide new strategies for therapeutic intervention.     

Clinicopathological significance of human macrophage metalloelastase expression in esophageal squamous cell carcinoma

OBJECTIVE: Human macrophage metalloelastase is referred to as matrix metalloproteinase (MMP-12), its function in tumors is contradictory. The current study was undertaken to investigate the role of MMP-12 in esophageal squamous cell carcinoma (SCC). PATIENTS AND METHODS: We analyzed the levels of MMP-12 mRNA expression in 67 patients with primary esophageal SCC by Northern blot analysis and the tissues were subjected to in situ hybridization analysis for MMP-12. Immunohistochemical staining was performed to detect the macrophages infiltrated in esophageal SCCs. RESULTS: MMP-12 mRNA was detected in 27 of 67 esophageal SCC samples by Northern blot analysis. In situ hybridization and immunohistochemical staining revealed that MMP-12 mRNA signals are located mainly in tumor cells. The frequency of lymph node metastasis was significantly higher in the MMP-12-positive (MMP-12(+)) subgroup than MMP-12-negative (MMP-12(-)) subgroup (p < 0.05); furthermore, invasion was significantly deeper in the MMP- 12(+) subgroup than in the MMP-12(-) subgroup (p < 0.01). MMP-12 mRNA was inversely correlated with prognosis (p < 0.05). However, Cox multivariate analysis revealed that upregulation of MMP-12 was not related to prognosis. CONCLUSIONS: MMP-12 gene expression was associated with the progression of esophageal SCC; however, it was not an independent prognostic factor.     

miR -22抑制食管鳞状细胞癌细胞侵袭和转移

目的:探讨微小RNA-22(miR-22)对食管鳞状细胞癌细胞侵袭和转移的影响。方法:采用实时定量RT-PCR检测miR-22在食管鳞状细胞癌细胞系中的表达。过表达miR-22后应用Transwell小室、MTT增殖及划痕试验分析对食管鳞状细胞癌细胞侵袭和转移能力的影响。结果:在食管鳞状细胞癌细胞系中miR-22的表达比正常对照明显降低。此外,过表达miR-22可明显抑制食管鳞状细胞癌细胞系Eca109和TE-1细胞增殖、侵袭和转移能力。结论:miR-22作为肿瘤抑制小片段RNA可以抑制食管癌细胞的侵袭和转移。本研究有助于了解miR-22在食管鳞状细胞癌中的功能,为食管鳞状细胞癌治疗提供新靶点。     

Dysregulated expression of HOX and ParaHOX genes in human esophageal squamous cell carcinoma

Homeobox genes function as master regulators in embryonic morphogenesis. We hypothesized that homeobox genes are essential to maintain tissue- or organ-specificity even in adult body and that the dysregulated expression of homeobox genes results in tumor development and progression. To better understand the roles of homeobox genes in development and progression of esophageal cancer, we analyzed the expression patterns of 39 HOX genes and 4 ParaHOX (CDX1, CDX2, CDX4 and PDX1) genes in esophageal squamous cell carcinoma (ESCC) and normal esophageal mucosa tissues. A total of 48 primary ESCC tissues and 7 normal esophageal mucosa tissues were resected from patients who underwent radical surgery without any preoperative chemotherapy or radiotherapy. The expression of HOX and ParaHOX genes were analyzed by a quantitative real-time RT-PCR method and immunohistochemistry. The expression levels of 24 HOX genes, CDX1, CDX2 and PDX1 were significantly higher in ESCC compared to normal mucosa (p<0.01, Mann-Whitney U test). The Immunohistochemical study revealed that HOXA5 and D9 proteins were more cytoplasmic in ESCC than normal mucosa cells. Our data indicate that the disordered expression of HOX and ParaHOX genes are involved in the development of ESCC or its malignancy.