KAI1转移抑制蛋白在宫颈鳞癌中的表达

目的　探讨宫颈鳞癌中KAI1蛋白的表达与宫颈癌病理特征和侵袭转移的关系。方法　采用免疫组织化学SABC法检测12 0例石蜡切片KAI1蛋白表达,宫颈上皮内瘤样病变(CIN)组3 0例,宫颈癌组45例,其中正常宫颈对照组45例。结果　1)在正常宫颈组织,CIN及宫颈癌中KAI1表达阳性率分别为95 .5 6% ,93 .3 3 % ,64 .44 % ,宫颈癌组与前两组差异有显著意义(P <0 .0 5 ) ;2 )KAI1蛋白表达在宫颈鳞癌高、中、低分化组阳性表达率分别为76.47%、66.67%和2 8.5 7% ,三组间差异有显著意义(P <0 .0 5 )。KAI1表达强度与分化程度呈负相关(r =-0 .3 49,P <0 .0 1) ;3 ) ,KAI1蛋白在临床分期≤ⅡA期、ⅡB期、Ⅲ/Ⅳ期表达阳性率分别为78.95 %、70 .5 9%和2 2 .2 2 % ,各期间差异有显著意义(P <0 .0 5 )。KAI1蛋白表达强度与临床分期呈负相关(r =-0 .5 75 ,P <0 .0 1) ;4)KAI1蛋白表达在未转移中的阳性率79.3 1%明显高于淋巴转移组3 7.5 0 % ,差异有显著意义(P <0 .0 5 )。结论　KAI1蛋白与宫颈癌的发展密切相关,有可能从一定程度上预测宫颈癌侵袭转移的潜能。     

KAI1基因转染ATRA诱导对小细胞肺癌细胞株恶性特征的抑制作用

背景与目的:探讨新抑癌基因KAI1与全反式维甲酸(all-trans-retinoic acid,ATRA)对小细胞肺癌NCI-H446细胞株抑制增殖和诱导分化的作用.材料与方法:用脂质体介导的基因转染方法,借助质粒表达载体(PCMV-NEO-XhoI),将抑癌基因KAI1转入小细胞肺癌NCI-H446细胞中,经G418筛选,获得稳定表达的细胞克隆.用10-6mol/L ATRA作用于转染及未转染KAI1基因的小细胞肺癌NCI-H446细胞株,集落形成率检测细胞体外增殖能力,流式细胞仪进行细胞周期和凋亡分析,间接免疫荧光染色结合流式细胞仪检测转染前后细胞CD82蛋白的表达.免疫组化测定MYC的表达,放射免疫测定LN(层连蛋白)表达.结果:ATRA处理脂质体-KAI1基因转染的小细胞肺癌细胞CD82表达降低,细胞增殖能力下降,凋亡增加,更多的细胞被阻止于G1/G0期,MYC及LN表达下降.结论:抑癌基因KAI1与ATRA对抑制小细胞肺癌NCI-H446细胞株的增殖和促分化有协同作用.     

KAI1基因在乳腺癌中的表达及意义

[目的]探讨KAI1基因在人乳腺癌中的表达及意义。[方法]应用免疫组织化学S鄄P法检测87例乳腺癌及30例癌旁正常乳腺组织中的KAI1表达情况。[结果]乳腺癌组织中KAI1阳性率显著低于癌旁正常乳腺组织(P<0.01)。KAI1阳性率在淋巴结转移组和未转移组中分别为34.0%和58.8%,在浸润组和非浸润组中分别为35.9%和77.8%,差异均具有显著性(P<0.05)。[结论]KAI1基因在乳腺癌中表达降低,且与乳腺癌浸润和转移有关。     

乳腺癌中KAI1蛋白表达与临床病理特征的相关性

目的:研究KAI1蛋白在人乳腺癌中的表达及其与临床病理特征的相关性。方法:应用免疫组织化学S-P法检测107例乳腺癌及30例癌旁乳腺组织中的KAI1蛋白表达情况。结果:乳腺癌组中KAI1蛋白高表达率显著低于正常乳腺组织(P<0.05)。正常组织及非侵袭性乳腺癌中,KAI1蛋白呈高表达;反之,在浸润性乳腺癌中KAI1表达减少。伴有腋窝淋巴结转移的61例乳腺癌中,KAI1蛋白高表达率为21.3%(13/61),无腋窝淋巴结转移组46例中,KAI1蛋白高表达率为39.0%(18/46),两者差异有显著性(P<0.05)。同时发现KAI1蛋白表达与肿瘤大小、年龄无相关性。结论:在乳腺癌进展过程中,KAI1蛋白表达降低在乳腺癌浸润和转移过程中起着重要的作用,检测KAI1蛋白表达可能成为监测人乳腺癌进展及临床上判断其预后的重要参考指标。     

宫颈鳞癌组织中转移抑制基因KAl1/CD82的表达及其临床意义

背景与目的转移抑制基因KAI1/CD82在多种肿瘤的浸润、转移中起着重要的作用,但该基因与宫颈癌的关系的研究仍很不充分,因此本研究采用免疫组化方法检测宫颈鳞癌中KAI1基因的表达并探讨其临床意义.方法采用免疫组化LSAB(Labelled streptovidin biotin staining)法检测99例宫颈鳞癌、25例宫颈上皮内瘤变(CIN)Ⅱ～Ⅲ级和18例正常宫颈组织中KAI1/CD82基因的表达,对检测结果与宫颈鳞癌各临床病理因素和预后的关系进行统计学分析.结果宫颈鳞癌中KAI1阴性、弱、中、强表达依次为52.5%(52/99)、16.2%(16/99)、15.2%(15/99)、16.2%(16/99),与正常宫颈和宫颈上皮内瘤变组相比,KAI1在宫颈鳞癌的表达存在显著下调(P=0.000).宫颈鳞癌中KAI1表达与FIGO分期、年龄、盆腔淋巴结转移、肿瘤细胞分化程度、宫颈肌层浸润深度、血清鳞癌抗原水平、宫颈肿瘤大小、大体类型均无相关(P＞0.05).单因素和多因素分析均显示KAI1表达与宫颈鳞癌的预后无相关(P＞0.05).结论KAI1基因在宫颈鳞癌中表达下调,但与宫颈鳞癌临床分期等一系列临床病理因素及预后均无关.     

肿瘤转移抑制基因KAI1/ CD82 和雌孕激素受体在子宫内膜癌组织中的表达及其临床意义

 目的 探讨转移抑制基因KAI1／CD82和雌孕激素受体（ER、PR）在子宫内膜癌组织中的表达及与淋巴结转移的关系，并分析其临床意义。方法 应用SP法对76例子宫内膜癌组织中KAI1、PR、ER的蛋白表达情况进行观察。结果 子宫内膜癌组织中KAI1和PR的阳性表达与手术病理分期、组织学分级、肌层浸润深度呈负相关（ P _{KA H}=0．0089、0．0103、0．0356，P_PR=0．0026、0．000、0．0053）；伴有盆腔淋巴结转移、宫旁或附件受累及的组织KAI1、PR、ER的阳性表达均明显低于无转移的组织（PKAII=0．0091、0．0073，PR=0．0006、0．0074，P _ER=0．0129、0．0073）；ER的阳性表达与FIGO分期呈负相关（P=0．0226）；不同的病理类型中，只有PR表达差异有统计学意义（P=0．0446）；而三者的表达与患者年龄及宫颈是否受累均无关。KAI1、PR、ER表达阴性和阳性的生存率差异均有统计学意义（ P _{KA H}=0．0043，P_PR=0．0010，P _ER=0．0124）。Logistic回归模型分析结果提示：KAI1、PR、ER三个变量中只有KAI1与淋巴结转移有关（P=0．0400，OR=0．245）。COX比例风险回归模型分析结果显示：KAI1、PR、ER表达均不是子宫内膜癌的独立预后因素。结论 KAI1表达与子宫内膜癌的淋巴结转移具有相关性，其可作为临床预测子宫内膜癌患者发生淋巴结转移和评估预后的综合指标之一。KAI1在子宫内膜癌发展中所起的作用可能与PR有关，KAI1、PR、ER的缺失表达与子宫内膜癌的发展、治疗及预后密切相关。     

Evaluation of KISS1 Receptor Gene Expression in Egyptian Female Patients with Breast Cancer

Objective: Breast cancer is the second most common cancer in the world. Many metastasis suppressor genes were identified, including the KISS1 gene which encodes for a 145 amino acid protein (kisspeptin-145), which undergoes proteolytic cleavage resulting in kisspeptin-14, -13 and -10. All of these proteins can activate KISS1 receptor (KISS1R). The role of KP/KISS1R signaling in breast cancer remains controversial. The present study aimed to measure mRNA gene expression of KISS1 receptor in healthy and cancerous breast tissue and to evaluate the association of its level with the available molecular subtypes and the traditional clinico-pathological variables. Methods: The study was done on 41 operable primary breast cancer patients. Biopsies from both tumor tissue and surrounding healthy mammary tissue were taken from all patients. KISS1R mRNA expression level was measured using a quantitative real time PCR.   Results: KISS1R mRNA expression was significantly higher in stage III patients compared to stage II patients. At a cut-off value for KISS1R mRNA expression of 1.75, stage II was discriminated from stage III. A significant positive correlation was found between KISS1R mRNA expression and tumor size as well as lymph nodes metastasis. KISS1R mRNA was highly expressed in ER negative cases compared to ER positive ones, and in PR negative cases compared to PR positive ones. There was a statistically significant difference in KISS1R mRNA expression levels and different molecular subtypes being over-expressed in HER2 and triple negative cancer cases. Conclusion: This study supports other studies suggesting that KISS1/KISS1R may not be acting as a metastasis suppressor in breast cancer. KISS1R mRNA is over expressed in advanced stages of breast cancer and hence it can be used as a prognostic marker for aggressiveness of breast cancer. Also being over expressed in triple negative patients, KISS1R could represent a promising therapeutic target in triple negative cases.     

肿瘤转移抑制基因KAI1/CD82第8内含子剪接区域多态与乳腺癌发病及转移的相关性

 目的 探讨肿瘤转移抑制基因KAI1/CD82第8内含子IVS（8）6C11A /6T11G多态与乳腺癌发病及转移的相关性。方法 提取135例健康人、109例乳腺癌患者的外周血DNA,收集其相应的临床及病理资料,应用PCR-DHPLC和DNA序列分析和病例对照分组研究统计分析KAI1基因第8内含子剪接区域多态与乳腺癌发病及转移的相关关性。结果 KAI1/CD82基因IVS（8）6T11G基因型检出率在健康人群中为30.9%,乳腺癌患者中为32.1%,两者差异无统计学意义（P>0.05）; 在乳腺癌低龄（<50岁）和高龄（≥50岁）患者之间差异无统计学意义(P>0.05),在常见的病理类型,肿瘤大小,病理分级中差异亦无统计学意义(P>0.05),但在有无淋巴结转移之间,两者差异有统计学意义（P<0.05）。结论 肿瘤转移抑制基因KAI1/CD82第8内含子剪接区域多态与乳腺癌的发病、病理分化无关,但可能影响肿瘤的淋巴结转移,提示KAI1/CD82基因IVS（8）6C11A /6T11G多态筛查可能成为乳腺癌患者预后风险评估的指标。     

肺癌转移抑制基因和多药耐药蛋白的表达及意义

目的 :研究肺癌转移抑制基因 (KAI1)和多药耐药蛋白 (MRP)的表达水平及内在联系。方法 :应用逆转录聚合酶链反应 (RT PCR)分别检测肺癌组织中MRP和KAI1。结果 :在肺癌组织中MRP阳性表达率为 4 5 8% (2 2 4 8) ,KAI1阳性表达率为 2 2 9% (11 4 8)。在Ⅰ、Ⅱ期患者中 ,KAI1基因为高表达 ;在Ⅲ期患者中 ,MRP基因为高表达。结论 :早期肺癌患者KAI1基因呈高表达 ,而在晚期患者MRP基因高表达 ,两者之间可能通过p5 3基因来调控     

Hypermethylation of TET1 Promoter Is a New Diagnosic Marker for Breast Cancer Metastasis

Breast cancer metastasis is a major cause of cancer-related death in women. However, markers for diagnosisof breast cancer metastasis are rare. Here, we reported that TET1, a tumor suppressor gene, was downregulatedand hypermethylated in highly metastatic breast cancer cell lines. Moreover, silencing of TET1 in breast cancercells increased the migration and spreading of breast cancer cells. In breast cancer clinical samples, TET1expression was reduced in LN metastases compared with primary tissues. Besides, the methylation level ofthe TET1 promoter was increased significantly in LN metastases. Taken together, these findings indicate thatpromoter hypermethylation may contribute to the downregulation of TET1 and could be used as a promisingmarker for diagnosis in patients with breast cancer metastasis.     

负性情绪相关基因在乳腺癌复发与转移中的检测价值研究

目的 研究与观察负性情绪相关基因在乳腺癌复发与转移中的检测价值.方法 选取48例乳腺癌术后复发转移患者为观察组,同期的48例未发生复发转移的患者为对照组,然后将两组的5-HTTLPR及NPY2R基因型分布频率及血浆氨基酸类神经递质水平进行比较,并比较观察组中不同复发转移情况者的检测结果 ,同时以Logistic分析上述研究指标与乳腺癌复发转移的关系.结果 观察组的5-HTTLPR的SS基因型及NPY2R的TT基因型频率均高于对照组,血浆氨基酸类神经递质水平均低于对照组,且观察组中不同复发转移情况者的检测结果 也存在显著性差异,且经Logistic分析显示,上述研究方面均与乳腺癌复发转移有密切的关系,P均<0.05.结论 负性情绪相关基因在乳腺癌复发与转移中的检测价值较高,应重视对乳腺癌患者进行上述方面的检测.     

Chemotherapy Negates the Effect of SDF1 mRNA to Distant Metastasis and Poor Overall Survival in Breast Cancer Patients

Objective: Investigate the effect of SDF1a, nuclear, and cytoplasmic CXCR4 breast cancer tissue on metastasis and overall survival in patients with complete-chemotherapy and no-chemotherapy. Methods: Cohort ambidirectional design was employed with survival analysis that followed the patient’s diagnosis until obtaining the outcome, distant metastasis, or death. We analyzed samples in three groups (all-patient, no-chemotherapy, and complete-chemotherapy groups).  Breast cancer cell nuclear and cytoplasm expressions of CXCR4 protein were examined using immunohistochemistry. Amplification of mRNA SDF1a of breast cancer tissue was examined using rtPCR on 131 samples from the same initial paraffin block. Results: In the distant metastasis and Overall Survival (OS) analysis, there was no correlation between cytoplasmic and nuclear CXCR4 in all-patient, no-chemotherapy, and complete-chemotherapy groups. SDF1a was significantly correlated to shorter distant metastasis and poor OS in the all-patient (p=0.004 and p=0.04, respectively) and no-chemotherapy group (p=0.008 and p=0.026, respectively). However, in the complete-chemotherapy group, SDF1a was not correlated to either metastasis (p=0.527) or OS (p=0.993), advanced stage demonstrated a strong association on shorter distant metastatic in no-chemotherapy (p=0.021) and complete-chemotherapy group (p=0.004) and also poor OS in both groups (p=0.006 and p=0.002, respectively). The hormone receptor showed a protective effect on the no-chemotherapy group’s OS (p= 0.019). Meanwhile, not undergoing chemotherapy was associated with poor OS in the all-patient group (p= 0.011). Conclusion: SDF1a mRNA amplification has a significant correlation with the occurrence of metastasis and OS in all-patient and no-chemotherapy group. Undergoing chemotherapy negates the effect of SDF1a for distant metastasis and OS.     

Tissue and Serum MUC1 Mucin Detection in Breast Cancer Patients

Tumor MUC1 expression as well as levels of MUC1, MUC1 circulating immune complexes (MUC1-CIC) and free antibodies against MUC1 (IgG and IgM-MUC1) were evaluated in 70 breast cancer patients with different stages of disease. Controls included: 135 serum samples from healthy women, normal mammary tissue samples (n=7) and benign breast disease specimens (n=6). In all assays, pre- and post-vaccination serum samples from breast cancer patients belonging to a vaccination protocol developed at the Memorial Sloan Kettering Cancer Center (New York, USA) were included as controls. Serum MUC1 was measured through Cancer Associated Serum Antigen test and CA15-3 test. Employing ELISA, MUC1-CIC-IgG/M were measured with either C595 or SM3 monoclonal antibodies (MAb) as catchers and also free antibodies against MUC1 (IgG and IgM) using 100mer peptide as catcher. Employing multivariate statistical analysis, results were correlated with age, tumor type, stage of disease and grade of differentiation. By quantitative immunohistochemistry using three anti-MUC1 core protein MAbs (C595, HMFG2 and SM3), tumor MUC1 was detected in 60/70 (86%) breast cancer specimens which reacted with at least one of these MAbs. High MUC1 serum levels were detected in 14/67 (21%); IgG and IgM anti-MUC1 antibodies were found elevated in 32 and 14%, respectively, while IgG-MUC1-CIC-measured with C595 in 42% and IgM-MUC1-CIC in 54%; finally, SM3 was positive in 43 and 18%, respectively. Results of these studies demonstrate that in a group of breast cancer patients, MUC1 was detected both in tissue specimens as well as free in serum samples; furthermore, MUC1 can also circulate complexed with IgG and IgM antibodies; thus an accurate measurement should include free and complexed forms. On the other hand, immunohistochemical studies on breast cancer tissues may contribute to reveal different MUC1 glycoforms.     

Bone Metastasis in Advanced Breast Cancer: Analysis of Gene Expression Microarray

Background

Approximately 30% to 40% of breast cancer recurrences involve bone metastasis (BM). Certain genes have been linked to BM; however, none have been able to predict bone involvement. In this study, we analyzed gene expression profiles in advanced breast cancer patients to elucidate genes that can be used to predict BM.

非小细胞肺癌LVD、MVD、CEAmRNA及KAI1和Kiss-1的表达与患者预后关系的研究

背景与目的目前对非小细胞肺癌(non-small cell lung cancer,NSCLC)患者预后的研究很多,有些临床病理因素已被公认与预后有关,本研究旨在对淋巴管密度(lymphatic vessel density,LVD)、微血管密度(microves-sel density,MVD)及癌胚抗原信使核糖核酸(carcinoembryonic antigen messenger ribonucleic acid,CEAmRNA)和肿瘤转移抑制基因KAI1、Kiss-1的表达与NSCLC患者预后的关系进行探讨。方法选取57例NSCLC患者,采用逆转录巢式聚合酶链反应(nested-RT-PCR)和微流控芯片(micro-fluid chip)技术对外周血CEAmRNA的表达进行检测;采用免疫组织化学技术对肺癌组织LVD、MVD和KAI1、Kiss-1的表达进行检测,并对所有患者进行随访分析。结果全组的5年生存率为18%,中位生存期为34个月;单因素分析显示TNM分期、淋巴结有无转移、CEAmRNA的阳性表达、MVD、LVD和Kiss-1的表达对生存有影响;多因素分析显示TNM分期、淋巴结有无转移和CEAmRNA的表达是影响预后的独立危险因素。结论在NSCLC患者中MVD、LVD和Kiss-1及CEAmRNA的表达可以在一定程度上反映患者的预后。     

Analysis of Oncogenes and Tumor Suppressor Genes in Human Breast Cancer

Oncogenes (c- erb B-2, c- myc , and some genes linked to the 11q13 lesion), tumor suppressor genes (retinoblastoma gene, p53) and an antimetastatic gene ( nm 23/nucleoside diphosphate kinase) play important roles in breast cancer progression. Amplification of c- erb B-2, c- myc , and int -2, and expression of RB, p53 (mutant), and NDP kinase were determined in 77 primary breast cancer specimens. nm 23-H1 allelic loss was also studied. c- erb B-2 and c- myc amplification, loss of RB expression, p53(mutant) expression, and nm 23-H1 allelic loss were also found in non-invasive carcinoma, int -2 amplification was significantly correlated with lymph node status ( P =0.02) and a significant association was found between p53(mutant) expression and tumor size ( P =0.04). c- erb B-2 amplification was strongly associated with disease-free and overall survival in multivariate analysis ( P =0.002). All of the c- erb B-2 amplified cases and all but one of the int -2 amplified cases in node-positive patients had relapsed within 2 years post resection. The cancer cells may acquire new proliferative pathways sequentially as a result of multiple genetic alterations which enable them to bypass the estrogendependent proliferation.     

宫颈鳞癌组织中转移抑制基因KAI1／CD82的表达及其临床意义

背景与目的:转移抑制基因KAI1/CD82在多种肿瘤的浸润、转移中起着重要的作用,但该基因与宫颈癌的关系的研究仍很不充分,因此本研究采用免疫组化方法检测宫颈鳞癌中KAI1基因的表达并探讨其临床意义。方法:采用免疫组化LSAB(Labelled streptovidin biotin staining)法检测99例宫颈鳞癌、25例宫颈上皮内瘤变穴CIN雪Ⅱ～Ⅲ级和18例正常宫颈组织中KAI1/CD82基因的表达,对检测结果与宫颈鳞癌各临床病理因素和预后的关系进行统计学分析。结果:宫颈鳞癌中KAI1阴性、弱、中、强表达依次为52.5%穴52/99雪、16.2%穴16/99雪、15.2%穴15/99雪、16.2%穴16/99雪,与正常宫颈和宫颈上皮内瘤变组相比,KAI1在宫颈鳞癌的表达存在显著下调(P=0.000)。宫颈鳞癌中KAI1表达与FIGO分期、年龄、盆腔淋巴结转移、肿瘤细胞分化程度、宫颈肌层浸润深度、血清鳞癌抗原水平、宫颈肿瘤大小、大体类型均无相关(P>0.05)。单因素和多因素分析均显示KAI1表达与宫颈鳞癌的预后无相关(P>0.05)。结论:KAI1基因在宫颈鳞癌中表达下调,但与宫颈鳞癌临床分期等一系列临床病理因素及预后均无关。