Expression of survivin mRNA in peritoneal lavage fluid from patients with gastric carcinoma

Background Peritoneal dissemination is the most common pattern of metastasis in advanced gastric carcinoma with serosal invasion. In the present study, we reported the clinical relevance of a new diagnostic method involving RT-PCR, using survivin as the target gene, for the detection of free cancer cells in peritoneal washes. Methods Intraoperative peritoneal washes were obtained from 48 patients who underwent surgery for gastric cancer. RT-PCR analysis with primers specific for survivin and conventional cytologicalexaminations were both performed. Results Survivin mRNA was not detected in any peritoneal wash samples from patients with benign disease, but was detected in 28 of 48 samples taken from patients with gastric cancer and in all metastastic nodules. Survivin expression in the peritoneal cavity significantly correlated with depth of cancer invasion, lymph node metastasis, and TNM stage. There were 92% of clinically evident peritoneal metastasis cases showed detectable survivin expression. The combination of survivin RTPCR and cytological examination yielded positive results in 66.7% (32/48) of patients with gastric cancer, much higher than the results produced by cytological method alone. Conclusions Survivin mRNA detected in peritoneal lavage fluid might indicate the presence of free cancer cells in the peritoneal cavity. The high sensitivity of the RT-PCR-based survivin assay suggests that survivin serves as a molecular marker for detecting peritoneal micrometastasis. Its ubiquitous expression in peritoneal cancer cells and metastatic nodules also suggests a promising future therapeutic strategy based on survivin inhibition for cases of gastric cancer involving peritoneal metastasis.     

Aberrant Expression of Kiss-1 and Matrix Metalloproteinase-9 Are Closely Linked to Lymph Node Metastasis of Gastric Cancer

China is one of the countries with the highest risk of gastric cancer over the past century,which is still the leading cause of death worldwide.Because metastatic disease of gastric cancer is the most critical impediment to patient survival,it is necessary to further understand the molecular mechanisms of its metastasis.Kiss-1,mapping to chromosome 1q32,is one of these genes regulated at chromosome 6.Kiss-1 expression was discovered to inhibit metastasis in both in vivo melanoma and breast carcinoma models.     

Lymph node metastasis in early gastric cancer

Objective To discuss the clinicopathological factors for lymph node metastasis （LNM） in early gastric cancer （EGC）,including age,gender,location,size,macroscopic type,depth of invasion,histological type,and lymphatic invasion,and the regulation of LNM in EGC.Data sources The data used in this review were mainly from PubMed articles published in English.The search terms were ＂early gastric cancer＂ and ＂lymph node metastasis.＂ Study selection Articles were selected if they reported the clinicopathological factors and regulation of LNM in EGC.Results The prognosis of EGC is better than advanced gastric cancer,with over 90％ 5-year survival rate.The main risk factors for LNM in EGC are tumor size,macroscopic type,depth of invasion,histological type,ulceration,and lymphatic invasion.Conclusions LNM in EGC is a critical factor for assessment of prognosis and determination of therapeutic strategy.Endoscopic mucosal resection or endoscopic submucosal dissection should be considered when patients have low risk of LNM.     

A preliminary study on correlations of triple-phase multi-slice CT scan with histological differentiation and intratumoral microvascular/lymphatic invasion in gastric cancer

Background  Many studies have shown that cancer cell differentiation and microvascular invasion play a principle role in cancer progression and metastasis, and non-invasive imaging techniques such as CT, MRI and US assessing the differentiation and the surgical resectibility and the prognosis of cancers are now of great importance. This study aimed to explore the correlation of triple-phase multi-slice CT scan with the histological differentiation and intratumor microvascular/lymphatic invasion of progressive gastric cancer.

Methods  The present study included 64 patients with gastric cancer, all of whom underwent routinal and dual-phase contrast enhancement multi-slice CT examinations of the upper abdomen before surgery. The post-operative specimens were used for determination of histological differentiation, cancer cell invasion of intratumoral microvascular/lymphatic vessel identified by CD34 and D2-40 expression. Correlations between contrast enhancement ratio (CER) of triple-phase multi-slice CT scan in gastric cancer and histological differentiation as well as intratumoral microvascular/lymphatic invasion were compared and analyzed.

Results  There was a significant correlation between CER of triple-phase CT scan in gastric cancer and tumor histological differentiation (P <0.05). CER of the arterial phase in gastric cancer with intratumoral microvascular invasion was significantly higher than that without invasion (0.61±0.28 vs. 0.46±0.14, P <0.05); CER of the arterial-parenchymal phase was significantly lower in gastric cancer with intratumoral microvascular invasion than that without invasion (1.81±0.39 vs. 2.28±0.80, P <0.05). However, CER of the parenchymal phase in gastric cancer with intratumoral lymphatic invasion was significantly higher than that without invasion (1.25±0.57 vs. 1.00±0.35, P <0.05).

Conclusions  CER of triple-phase multi-slice CT scan in gastric cancer is closely correlated with intratumoral microvascular and lymphatic invasion, and also could be used as a marker for histological differentiation.

     

Aberrant Expression of Kiss-1 and Matrix Metalloproteinase-9 Are Closely Linked to Lymph Node Metastasis of Gastric Cancer

China is one of the countries with the highest risk of gastric cancer over the past century, which is still the leading cause of death worldwide. Because metastatic disease of gastric cancer is the most critical impediment to patient survival, it is necessary to further understand the molecular mechanisms of its metastasis. Kiss-1, mapping to chromosome 1q32, is one of these genes regulated at chromosome 6. Kiss-1 expression was discovered to inhibit metastasis in both in vivo melanoma and breast carcinoma models. Mounting clinical evidences, particularly the loss of Kiss-1 in metastases, correlates Kiss-1 and metastin receptor expression with human tumor progression.     

Proximal gastric cancer: lymph node metastatic patterns according to different T stages dictate surgical approach

Background As a common form of gastric cancer migration,lymph node metastasis largely affects the surgical treatment and prognosis of gastric cancer.Surgery is the fundamental curative option for gastric cancer that varies depending on different stages.The study aimed to compare the clinicopathological characteristics and lymph node metastatic patterns in patients of proximal gastric cancer with different T stages and investigate a reasonable radical gastrectomy approach in terms of the range of lymphadenectomy for proximal gastric cancer.Methods In our retrospective study,the data of 328 patients of proximal gastric cancer with different T stages were analyzed.By comparing the differences of lymph node metastatic rate and ratio,we investigated the clinicopathological characteristics and metastatic patterns of lymph nodes.Also,we were especially interested in the differences in survival rates between patients with and without No.5 and 6 group metastasis with the same TNM stage.Results The overall lymph node metastatic rate and ratio of advanced proximal gastric cancer were 73.4％ and 23.3％,respectively.The tumors of different T stages were statistically significant in size and differentiation degree （P ＜0.05）,multivariate analysis showed that the depth of tumor invasion was an independent risk factor for lymph node metastasis in proximal gastric cancer （RR,12.025; 95％ CI,2.326 to 62.157; P=0.003）.The overall survival rate of patients with No.5,6 group lymph node metastasis and those without was significantly different,but the differences in survival rates between patients with and without No.5 and 6 group metastasis with the same TNM stage were not statistically significant.Conclusions Different T stages in proximal gastric cancer showed different patterns and characteristics of lymph node metastasis.D2 lymphadenectomy in patients with early gastric cancer had little survival benefit because metastasis to level 2 nodes was rare.Therefore the range of the lymph node dissection in radical gastrectomy     

Endoscopic ultrasonography assessment in preoperative staging for carcinoma of ampulla of Vater and extrahepatic bile duct.

OBJECTIVE To evaluate preoperatively the extent of primary tumor, involvement of regional lymph node, and distant metastasis of ampullary carcinoma and extra hepatic bile duct carcinoma.

METHODS 28 patients with ampullary carcinoma and the 18 patients with extrahepatic bile duct carcinoma were subjected to endoscopic ultrasonography (EUS). The results were compared with those of surgical explorations and pathological findings of the resected specimens for evaluating the accuracy of preoperative staging of EUS. 46 patients underwent surgical explorations. Radical resection with detailed pathological study was done for 22 patients with resectable ampullary carcinoma and 18 patients with extrahepatic bile duct carcinoma. Carcinomas of ampulla of Vater and extrahepatic bile duct were staged according to the tumor, nodes, metastasis (TNM) classification.

RESULTS The accurate rate of EUS in assessing the extent of cancer invasion was 81.8% for ampullary carcinoma, and 72.2% for extrahepatic bile duct carcinoma. The accuracy of EUS in predicting regional lymph node metastasis was 59% for ampullary carcinoma, and 61.1% for extrahepatic bile duct carcinoma. Invasion of portal vein was correctly predicted by EUS in 2 of 3 patients, but the 3 cases of liver metastasis were not detected by EUS.

CONCLUSIONS EUS is an effective method for the evaluation of the extent of invasion of ampullary carcinoma and extrahepatic bile duct carcinoma as well as the involvement of regional lymph node before operation. Because of its limited penetration depth, however, EUS is inadequate in the assessment of liver metastasis.

     

Proteomics in colorectal cancer and hepatic metastasis research

In the current post-genomic era, characterizing the function of genes is a major challenge. Proteomic researchers can translate genome information into useful biological insight. Colorectal cancer represents one of the most common malignancies worldwide. So it is applicable to compare and identify the differentially expressed proteins associated with colorectal cancer and hepatic metastasis. The identification of differentially expressed protein would provide the basis for early diagnosis and detection, as well as clues for understanding the molecular mechanisms governing human colorectal carcinoma carcinogenesis, metastasis and progression, with the final goal to find better solutions to challenges in prevention of the colorectal liver metastasis and kill cancer cells with minimum toxicity maximally and specifically.     

MicroRNAs are implicated in the initiation and progression of gastric cancer

Objective Gastric cancer is a genetically heterogeneous disease that progresses via different oncogenes.MicroRNA （miRNA） can regulate oncogene expression at the post-translational level.In this review,we summarize the most commonly altered miRNAs and their possible roles in cancer initiation and progression in gastric cancer.Data sources Most articles were identified by searching PubMed online resources using the key terms of microRNA and gastric cancer.Study selection Mainly original milestone articles and critical reviews written by major pioneer investigators in the field were selected,and the 69 most important articles were cited finally.Results A set of miRNAs are consistently deregulated in gastric cancer,although there is no clear miRNA expression profiles,such as miR-21 and miR-17 （～92 clusters）.These deregulated miRNAs play important roles in promoting cell proliferation,tumor metastasis,and chemotherapeutic resistance in gastric cancer by targeting different oncogenes.Clinical relevance of these deregulated miRNAs is proved to be associated with TNM stages,metastasis,and prognosis of gastric cancer patients.In addition,circulating miRNAs are promising noninvasive biomarkers for gastric cancer.Conclusions miRNAs have produced a novel paradigm in research in gastric cancer.These small molecules play macroroles in gastric cancer initiation and progression.These results will help us improve management of gastric cancer in future.     

Role of RANTES and its receptor in gastric cancer metastasis

This study examined the role of regulated upon activation normal T cell expressed and secreted(RANTES) and its receptor C-C chemokine receptor type 5(CCR5) in gastric cancer metastasis and the associated mechanism.The expression of RANTES and CCR5 was detected by using immunohistochemical staining and Western blotting in the gastric cancer tissues obtained from 60 gastric cancer patients with or without lymph node metastasis(n=30 in each).The results showed that the expression levels of RANTES and CCR5 were higher in gastric cancer with lymph node metastasis than in that without metastasis(P<0.05).The expression levels of RANTES in 30 lymph nodes with cancerous invasion were higher than in 30 normal lymph nodes(P<0.05).Chemotactic test revealed that the number of migrating gastric cancer cells(n=295.0±54.6) induced by the protein of cancer-invading lymph nodes was greater than that by the protein mixture from cancer-invading lymph nodes and RANTES antibody(n=42.5±11.6)(P<0.05).RT-PCR showed that the expression levels of the main Th1 cytokines(IL-2,γ-IFN) were lower in gastric cancer with lymph node metastasis(2.22±0.90,3.26±1.15 respectively) than in that without metastasis(3.07±1.67,4.77±1.52 respectively)(P<0.05),but the expression level of the main Th 2 cytokine(IL-10) was higher in gastric cancer with lymph nodes metastasis(6.06±2.04) than in that without metastasis(4.88±1.87)(P<0.05).It was concluded that RANTES and its receptor CCR5 may contribute to gastric cancer metastasis through influencing the balance of Th1/Th2.RANTES and CCR5 may become a marker of gastric cancer metastasis.     

RhoC蛋白在胃癌中的表达及其临床意义

目的探讨RhoC在胃癌中的表达及其临床意义.方法收集胃癌手术标本40例和正常胃黏膜组织30例,应用免疫组化SABC法检测RhoC蛋白在上述组织的表达.结果30例正常胃黏膜组织均不表达RhoC.40例胃癌肿瘤细胞中,25例表达RhoC,阳性率为62.5%,两者之间具有显著差异(P=0.001).RhoC的表达与肿瘤细胞分化、浸润深度未见相关性(P=0.977,P=0.141),与淋巴结转移、PTNM分期存在相关性(P=0.014,P=0.039).结论RhoC蛋白在胃癌组织中高表达,RhoC蛋白可作为一项提示胃癌转移潜能的生物学指标.(检测胃癌组织中RhoC的表达对判断预后和指导临床治疗一定参考应用价值.)     

RhoC-siRNA表达载体对肝癌细胞生长速度及侵袭力的影响

目的 构建RhoC-siRNA表达载体,研究其对肝癌细胞生物学行为的影响.方法 构建RhoC-siRNA表达载体,以脂质体转染法将之稳定转染入SK-Hep1肝癌细胞株,Western blot法鉴定转染细胞中RhoC蛋白表达的抑制情况,观察转染前后肝癌细胞形态、生长曲线、黏附、运动及体外侵袭能力的改变.结果 酶切及测序证实RhoC-siRNA真核表达载体构建成功,将之转染入肝癌细胞后,细胞中RhoC蛋白表达水平降低达60%,细胞形态及生长速度无明显改变,但细胞黏附、运动能力及体外侵袭能力均降低.结论 RhoC-siRNA表达载体对肝癌细胞的形态及生长曲线无显著影响,但可抑制其体外侵袭转移能力,可为肝癌的生物学治疗提供新的方法.     

RhoC-shRNA对结肠癌细胞HT-29细胞生物学行为的影响

目的探讨RhoC-shRNA对结肠癌细胞生物学行为的影响。方法构建RhoC-shRNA表达载体,以脂质体转染法将之稳定转染入HT-29结肠癌细胞株,Western blot检测转染细胞中RhoC蛋白表达的抑制情况,观察转染前后结肠癌细胞周期、凋亡和侵袭能力的变化。结果成功构建RhoC-shRNA真核表达载体,并且转染入结肠癌细胞后,细胞中RhoC蛋白表达水平明显受到抑制,并且抑制细胞增殖、促进细胞凋亡,降低肿瘤细胞侵袭能力。结论下调RhoC蛋白的表达可抑制结肠癌细胞HT-29的体外增殖和侵袭能力。     

RhoC mRNA在喉癌中的表达及临床意义

目的:研究RhoC mRNA在喉癌组织、癌旁组织的表达情况,探讨其与喉癌的发生、发展以及转移之间的关系。方法:采用RT-PCR方法检测RhoC mRNA的表达及分布情况。结果:RhoC mRNA在喉癌组织的表达高于癌旁组织的表达(P<0.01)。结论:RhoC蛋白基因的表达在喉癌的发生、浸润以及淋巴结转移的机制中起促进作用。它们可能作为喉癌发生、浸润及局部淋巴结转移的有意义指标,对预测喉癌的发生、局部淋巴结转移以及预后有一定价值。     

SPARC在胃癌组织中的表达

目的检测SPARC在人胃癌组织中的表达，探讨其与胃癌浸润转移的关系。方法运用免疫组化S-P法检测108例胃癌和89例正常胃黏膜组织中SPARC的表达情况。结果SPARC主要表达在胃癌的间质细胞，少数表达在胃癌细胞。SPARC在胃癌组织间质细胞的阳性表达率（88．0％）显著高于正常胃黏膜组织（14．1％）（P〈0．01）。肿瘤细胞SPARC表达与胃癌生物学特性及临床各病理因素均无相关性；而间质细胞SPARC的表达与胃癌的淋巴结转移及临床分期有相关性，与性别、年龄、肿瘤大小、浸润深度、远处转移均无相关性。结论SPARC在胃癌间质过度表达可能促进胃癌的转移，可作为判断胃癌生物学行为的重要指标。     

胃癌组织中RhoC和TERT的表达及其临床意义

目的探讨RhoC和TERT蛋白在胃癌组织中的表达以及在胃癌发生发展过程中的作用。方法采用免疫组织化学方法检测105例胃癌组织中RhoC和TERT蛋白的表达。结果RhoC和TERT蛋白在胃癌组织中的表达与肿瘤浸润深度、组织类型、临床分期及淋巴结转移有明显相关性；RhoC和TERT蛋白在胃癌组织中的表达呈正相关。结论RhoC和TERT蛋白在胃癌的发生发展过程中可能具有一定的协同作用。     

RhoC表达对喉鳞癌Hep2肿瘤细胞凋亡、肿瘤干细胞标志物-ALDH1A1及细胞形态的影响

目的 研究Ras同源类似物C （ras homology C,RhoC）对喉鳞状细胞癌生物学行为的影响。方法 通过脂质体转染技术将外源基因导入喉鳞状细胞癌细胞-Hep2肿瘤细胞,抑制/增强肿瘤细胞中RhoC表达,TUNEL法检测RhoC对Hep2肿瘤细胞凋亡的影响,罗丹明标记的鬼笔环肽染色细胞骨架观察Hep2肿瘤细胞形态变化,实时荧光定量核酸扩增检测（real-time quantitative polymerase chain reaction detecting system,QPCR）方法检测RhoC对Hep2肿瘤细胞肿瘤干细胞标志物乙醛脱氢酶A1（aldehyde dehydrogenase 1 family,member A1,ALDH1A1）的表达的影响。结果 抑制RhoC表达可使Hep2肿瘤细胞凋亡增强,肿瘤细胞群中肿瘤干细胞标志物ALDH1A1 mRNA表达水平降低;改变RhoC表达后,肿瘤细胞形态发生了不同的改变。结论 RhoC在喉鳞癌的转移中具有重要的作用,以RhoC为治疗靶点在控制肿瘤转移方面具有重要的临床应用价值。     

TMPRSS4及Smac在胃癌侵袭和转移中的机制及临床意义的研究

目的:通过检测胃癌组织中TMPRSS4与Smac的表达情况,分析其在胃癌侵袭与转移中的机制,并探讨其在胃癌发生、发展过程中的作用与意义。方法:采用Western blot、RT-PCR及免疫组化的方法检测胃癌组织与正常胃组织的TMPRSS4与Smac的表达。用脂质体转染过表达TMPRSS4胃癌细胞,构建特异性TMPRSS4siRNA表达载体,通过Transwell侵袭实验与划痕愈合实验研究TM-PRSS4表达的胃癌细胞侵袭转移机制;采用脂质体介导转染胃癌细胞MKN-45,用丝裂霉素处理转染前后的胃癌细胞株MKN-45,观察MKN-45的凋亡情况。结果:TMPRSS4mRNA与蛋白在胃癌组织中的表达明显高于正常组织,且以中、高表达占多数,差异有统计学意义(P<0.01);TMPRSS4mRNA与蛋白的表达水平与TNM分期、淋巴结转移个数、肿瘤直径大小、浸润深度有关,差异均有统计学意义(P<0.05～0.01)。在正常胃组织中的Smac表达率明显高于胃癌组织,差异有统计学意义(P<0.01);胃癌细胞的浸润深度、淋巴结转移个数与Samc的表达相关,差异有统计学意义(P<0.05);肿瘤直径大小与TNM分期与Samc表达无明显相关,差异无统计学意义(P>0.05)。转染后的MKN-45对化疗药物的敏感性比转染前明显增强,差异有统计学意义(P<0.05)。随访后发现TMPRSS4与Samc和患者的预后及生存时间相关。结论:TMPRSS4与患者的预后相关,可为患者的预后判断提供一定的依据;Samc的过表达能提高化疗药物的敏感性,为判断临床药物治疗的疗效提供一定的依据。     

胃癌组织中MMP-9的表达及与细胞增殖活性的关系

目的 :研究胃癌组织中基质金属蛋白酶 - 9( MMP- 9)的表达特点 ,探讨其与肿瘤细胞增殖活性之间的关系。方法 :收集 74例胃癌标本 ,采用免疫组织化学 S- P染色技术 ,计算每例切片中癌细胞MMP- 9的阳性率及增殖细胞核抗原阳性指数 ( PLI) ,并结合临床病理参数进行分析。结果 :MMP- 9的表达与癌组织的浸润深度、分化程度、淋巴结转移密切相关 ( P<0 .0 5) ,随着 MMP- 9含量的增加 ,PLI不断增高 ,且具有统计学意义 ( P<0 .0 1)。结论 :具有高增殖活性的肿瘤细胞同时具有较强的分泌MMP- 9的能力 ,MMP- 9可以促进胃癌的浸润和转移     

幽门螺杆菌L型感染与胃癌BGC-823细胞侵袭、转移关系的研究

目的：研究幽门螺杆菌L型（HelicobacterpyloriL—form,Hp—L型）感染对胃癌BGC-823细胞浸润、转移能力的影响,探讨Hp—L型在胃癌发展中的作用和可能机制。方法：将Hp—L型与胃癌BGC-823细胞按不同比例混合培养24h,并设置空白对照组,进行Transwell小室细胞侵袭实验,观察胃癌BGC-823细胞的侵袭能力。应用Western—blotting实验测定胃癌BGC-823细胞中ezrin的表达情况。结果：随胃癌BGC-823细胞与细菌共培养细菌含量增大,穿透重建基底膜的细胞数目明显增多（P〈0．05～P〈0．01）,胃癌BGC-823细胞中ezrin表达量逐渐增加（P〈0．01）。结论：Hp—L型感染增强了胃癌细胞的侵袭和转移能力,其机制可能与胃癌细胞的ezrin表达量增加有关。