抗氧化剂与大肠癌细胞MMP-3表达关系研究

核因子-kB(nuclear factor kappa B,NF-κB) 是一种重要的细胞转录因子,参与多种细胞增殖、凋亡和癌基因等的转录调控.细胞核因子-kB通过上调与侵袭和转移有关的多个基因蛋白表达,从而参与肿瘤的侵袭和转移.因此,通过抑制NF-κB的活化,间接下调相关下游基因蛋白表达,从而抑制肿瘤的侵袭和转移正成为一种新的抗肿瘤治疗方法.本实验旨在探讨大肠癌MMP-3蛋白表达及NF-kB抑制剂二硫氨基甲酸吡啶PDTC(pyrrolidine dithiocarbamate)对大肠癌MMP-3蛋白表达的影响,为大肠癌转移的治疗提供新的理论依据.     

胃癌侵袭与转移相关分子的研究进展

胃癌转移是一个非常复杂的多环节、多步骤的连续过程,此过程受黏附分子、蛋白降解酶、转移抑制因子等多种基因的调控。胃癌侵袭转移相关的分子包括黏附分子及其受体、蛋白水解酶类、转移抑制因子、凋亡相关的分子标记、癌基因和抑癌基因和cDNA芯片技术发现的侵袭转移相关分子。     

c－erbB－2、ras癌基因产物在大肠癌及癌前病变中表达

ｃ－ｅｒｂＢ－２、ｒａｓ癌基因产物在大肠癌及癌前病变中表达殷智榕，张云汉，刘复兴，郝志芳，李新荣，黄孝立ｃ－ｅｒｂＢ－２、Ｈ－ｒａｓ基因产物是调控细胞增殖或分化的两个重要因子。为了探讨这两种癌基因产物与大肠癌发生发展的关系，以及其对大肠癌早期诊断、预...     

大肠癌的基因诊断

大肠癌的早期诊断相当重要,常规的检查方法均难以达到此目的.基因诊断技术为大肠癌早期诊断提供了可能性.分子生物学研究显示:大肠癌的发生涉及多种癌基因的激活及抑癌基因的失活,在肿瘤克隆形成过程中,基因改变早于形态改变,对这些基因及其产物进行检查,将有助于早期诊断.本文概括了近年来人们从分子水平诊断大肠癌的多种尝试,主要包括常见的癌基因、抑癌基因和细胞周期产物、端粒和端粒酶,DNA损伤修复系统等方面的研究.     

大肠癌分子遗传学的研究进展

大肠癌是研究肿瘤进展的良好模型,腺瘤息肉是大肠癌的癌前病变,可以作为系统研究大肠癌演变的分子遗传学变化。研究大肠癌演变过程中各种不同的等位基因缺失,亦是研究其他实体瘤,特别是研究肿瘤抑制基因(又称抗癌基因)的突破口。本文提出了癌基因及肿瘤抑制基因在肿瘤进展中可能的作用机理。     

利用基因芯片筛查大肠癌肿瘤相关基因

目的探讨大肠癌肿瘤相关基因的差异表达。方法采用含有8064个人类靶基因的基因表达谱芯片筛选大肠癌组织同正常大肠黏膜的差异表达基因,并用逆转录聚合酶链反应（RT-PCR）技术对其中4条差异表达基因加以验证。结果大肠癌差异表达基因有1807条,发现上调表达的基因有936条,下调表达的基因有871条,其中癌基因及抑癌基因共57条。这57条基因中,36条基因表达上调．21条基因表达下调。结论大肠癌的发生发展与多个原癌基因及抑癌基因的差异表达有关。     

三种反义c-myc RNA对肿瘤细胞凋亡的影响

c-myc是癌基因家族中最重要的成员之一，其编码产物属核蛋白类。c-Myc作为转录因子，在细胞周期调控、细胞增殖、分化、凋亡及肿瘤发生、转移等生理病理过程中发挥重要作用。近期研究还发现，c-myc与增生性心血管疾病的发生、发展密切相关。鉴于c-myc是一个在结构、功能和基因调节上都极具特色的转录因子编码基因，     

c-myc的结构和功能

c－myc是myc癌基因家族中最重要的一员，并编码产物c－myc蛋白属核蛋白类．其基因结构具有独特性，可作为转录因子在细胞周期、细胞增殖、分化、凋亡、肿瘤发生、转移等生理病理过程中发挥重要作用，近期研究还发现该基因与增生性心血管病的发生发展和肝糖酵解等代谢活动息息相关，并可能作为复制因子影响DNA复制过程，业已引起学者们的广泛注意。本文将就上述进行综述．     

大肠肿瘤中Tiam1的表达及临床意义

目的探讨T淋巴瘤侵袭转移诱导因子1(T lymphom a invasion and m etastasis induc ing factor 1,Tiam1)表达与大肠癌发生、发展和转移的关系。方法应用免疫组化方法检测大肠正常组织、大肠腺瘤、大肠癌和大肠淋巴结转移癌石蜡组织标本中Tiam1蛋白的表达情况。应用RT-PCR和免疫组化方法检测大肠癌细胞株中Tiam1 mRNA和蛋白的表达情况。结果Tiam1蛋白在大肠正常组织、腺瘤、癌及淋巴结转移癌中表达差异有显著性(2χ=23.561,P<0.01);两两比较发现,腺瘤Tiam1表达比大肠正常组织高(Z=-2.423,P<0.05),淋巴结转移癌组织Tiam1表达比大肠癌组织高(Z=-2.051,P<0.05),而大肠癌组织与腺瘤组织Tiam1表达差异无显著性(Z=-0.938,P>0.05)。在大肠癌组织中,伴发转移的大肠癌组织比未发生转移的大肠癌组织Tiam1表达明显增强,差异具有显著性(Z=-3.176,P<0.01)。RT-PCR结果显示Tiam1基因在高转移的LoVo和SW 620中呈高表达,在低转移的LS174T和HT29中呈低或不表达,在SW 480、HCT116等呈中度表达。结论Tiam1表达与大肠癌转移存在密切关系,Tiam1表达可作为大肠癌转移过程中一个有价值的指标。     

肿瘤细胞中基因选择性剪接的研究进展

选择性剪接是高等真核细胞在转录后水平调控基因表达以及产生蛋白质组多样性的重要机制。选择性剪接过程受多种顺式作用元件和反式作用因子相互作用调节。肿瘤癌基因、抑癌基因、肿瘤转移抑制基因可发生选择性剪接，与肿瘤发生发展关系密切，其蛋白异构体参与基因转录、细胞周期和凋亡等生命过程，对肿瘤生长有一定作用。以选择性剪接蛋白异构体为靶点或干预选择性剪接过程，可望进行肿瘤的分子治疗。     

结直肠癌组织多基因甲基化的检测及其临床意义

目的： 检测结直肠癌组织中脾酪氨酸激酶（Syk）、E-钙黏附素（E-cadherin,CDH1）和组织金属蛋白酶抑制因子-3(TIMP-3)多基因甲基化水平,并探讨多基因甲基化在结直肠癌发病机制中的作用与复发转移和术后预后的关系。方法: 采用巢式甲基化特异性PCR(n-MSP)方法检测120例结直肠癌肿瘤组织Syk的甲基化水平, 及其中100例结直肠癌肿瘤组织CDH1和TIMP-3的甲基化水平。结果: 1个及以上基因共甲基化率为74%,2个基因同时甲基化率为21%, 3个基因共同甲基化为8%。3个基因同时甲基化阳性与淋巴结转移无关（2=0.725,P>0.05）;CDH1基因甲基化与肝肺转移显著相关（2=6.938,P<0.01）,Syk和TIMP-3基因甲基化与肝肺转移无关;Syk甲基化、TIMP-3甲基化、CDH1及TIMP-3同时甲基化是结直肠癌术后生存的相对危险因素,而3个基因同时甲基化则是非相对危险因素。结论: 结直肠癌组织中存在多基因共同甲基化率,多基因共同甲基化在结直肠癌发病机制、侵袭复发机制及影响预后生存中并非必需条件。     

A five‐gene signature as a potential predictor of metastasis and survival in colorectal cancer

To understand the molecular mechanisms of metastasis and prognosis of colorectal cancer (CRC), we isolated single cell‐derived progenies (SCPs) from SW480 cells in vitro and compared their metastatic potential in an orthotopic CRC tumour model in vivo. Two groups of SCPs with the capability of high and low metastasis, respectively, were obtained. By analysing the gene expression profiles of high (SCP51), low (SCP58) metastatic SCPs, and their parental cell line (SW480/EGFP), we demonstrated that 143 genes were differentially expressed either between SCP51 and SCP58 or between SCP58 and SW480/EGFP. Gene‐annotation enrichment analysis of DAVID revealed 80 genes in the top ten clusters of the analysis (gene enrichment score > 1). Of the 80‐gene set, 32 genes are potentially involved in metastasis, as revealed by Geneclip. Five putative metastatic genes (LYN, SDCBP, MAP4K4, DKK1, and MID1) were selected for further validations. Immunohistochemical analysis in a cohort of 181 CRC clinical samples showed that the individual expression of LYN, MAP4K4, and MID1, as well as the five‐gene signature, was closely correlated with lymph node metastasis in CRC patients. More importantly, the individual expression of LYN, MAP4K4, SDCBP, and MID1, as well as the five‐gene signature, was significantly correlated with overall survival in CRC patients. Thus, our five‐gene signature may be able to predict metastasis and survival of CRC in the clinic, and opens new perspectives on the biology of CRC. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Down‐regulated expression of SATB2 is associated with metastasis and poor prognosis in colorectal cancer

To identify novel biomarkers of metastasis of colorectal cancer (CRC), we developed an orthotopic implantation model of murine CRC and selected in vivo M5, a subclone of the SW480 CRC cell line with enhanced potential for metastasis to the liver. We compared the differences in the gene expression profiles between M5 and SW480 cells using gene expression profiling. We found that expression of special AT‐rich sequence‐binding protein 2 (SATB2) was down‐regulated in M5 cells. Immunohistochemical analysis of 146 colorectal tumour samples showed that underexpression of SATB2 was strongly correlated with poor prognosis, tumour invasion, lymph node metastasis, distant metastasis, and Dukes' classification for CRC. Univariate and multivariate survival analyses further showed that SATB2 expression was a potential favourable prognostic factor for CRC. These results demonstrated not only that SATB2 is a potential novel prognostic factor for CRC, but also that selection of a highly metastatic clone of SW480 in vivo coupled with gene expression profiling is a powerful approach to identifying prognostic markers for CRC. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Prevention of colorectal cancer liver metastasis by exploiting liver immunity via chitosan-TPP/nanoparticles formulated with IL-12

The development of effective therapies for the prevention of colorectal cancer (CRC) liver metastasis is of great importance. Recently, chitosan (CS) nanoparticles have been utilized as carriers of interluekin-12 (IL-12) administered locally to deliver therapeutic proteins and genes. In this study, we encapsulated IL-12 by incorporation using tripolyphosphate (TPP) as the coacervated crosslinking agent to form CS-TPP/IL-12 nanoparticles. We further characterized the association efficiency, rate of release, liver-targeting, and toxicity, which were predominantly dependent on the factors of particle size, zeta potential, pH of solution, and whether or not modified with TPP. Systemic delivery of CS-TPP/IL-12 nanoparticles significantly reduced the number and volume of CRC liver metastasis foci compared to the CS-TPP treated mouse group. Although delivery of IL-12 alone also inhibited the number of CRC liver metastasis observed, further study of the change in hepatic metastasis volume demonstrated no significant differences between the groups treated with CS-TPP or IL-12 alone. Mechanistically, CS-TPP nanoparticles blocked the toxicity of IL-12 and induced infiltration of NK cells and some T cells, which are most likely the effector cells that mediate tumor metastasis inhibition during CS-TPP/IL-12 immunotherapy. The results obtained from this study demonstrate the potential benefit of using chitosan modification technology as a cytokine delivery system for the successful prevention of CRC liver metastasis by exploiting liver immunity.     

Expression of TUSC3 and its prognostic significance in colorectal cancer

Background

Colorectal cancer (CRC) is one of the most common cancers worldwide. Tumor suppressor candidate 3 (TUSC3) has been reported be associated with embryogenesis and metabolism. The aim of this study is to investigate the expression of TUSC3 in CRC tissues, and to evaluate the clinical pathological characters and prognostic significance.

RETRACTED: PIM3 Functions as Oncogenic Factor and Promotes the Tumor Growth and Metastasis in Colorectal Cancer

Colorectal cancer (CRC) is one of the common human malignancies. Discovery and identification of novel therapeutic target is imperative to improve the prognosis of CRC patients. As a member of the PIM family, PIM3 has been found to be overexpressed in a variety of cancerous tumors. In this study, we evaluated the expression of PIM3 in CRC tissues and analyzed the role of PIM3 in CRC. Our results showed that PIM3 expression was significantly higher in CRC tissues compared with adjacent noncancerous tissues. The PIM3 expression level was found to be correlated with advanced disease stage and lymph node metastasis. Moreover, PIM3 was found to be able to predict poor prognosis in CRC patients as an independent factor. In vitro studies also showed that knockdown of PIM3 exhibited inhibitory effect on cell growth, promoted cell apoptosis and dampened invasive capability of HCT116 and SW620 cells. Moreover, PIM3 knockdown was able to delay tumor growth and suppress lung metastasis in xenograft model. Our results indicated that PIM3 is a potential therapeutic target for CRC. Anat Rec, 302:1552–1560, 2019. © 2018 American Association for Anatomy