长链非编码RNA CASC2抑制肿瘤发生发展的研究概况

长链非编码RNA(lncRNA)包括大部分人类DNA的非编码信息,占整个基因组的90%以上。lncRNA由超过200个核苷酸组成,通常缺乏开放阅读框并参与肿瘤的病理生理过程。lncRNA能调控各种肿瘤基因表达、印记、转录和翻译后修饰等。2004年在子宫内膜癌(EC)中首次发现lncRNA癌易感性候选基因2(Cancer susceptibility candidate 2,CASC2)可能是潜在的抑癌基因。而后发现CASC2在诸如宫颈癌、大肠癌、胃癌、肝癌、非小细胞肺癌、肾细胞癌、膀胱癌、神经胶质瘤和甲状腺癌等中都表达下调,而CASC2过表达时能抑制肿瘤细胞增殖,这说明CASC2有抑癌作用。在肾上腺癌等其他肿瘤中CASC2的转录水平不变,表明CASC2的抑癌作用具有组织特异性。本文对CASC2在肿瘤中的抑癌作用及相关机制做一综述。     

抑癌复方对大鼠肝癌前病变的抑制作用

目的　研究抑癌复方的抗促癌作用。　方法　采用二乙基亚硝胺(diethylnitrosamineDEN)诱癌观察该方法对大鼠肝癌癌前变的影响。　结果　抑癌复方有以下功能:①明显保护大鼠肝脏功能(P<001)。②降低大鼠血清碱性磷酸酶(AKP)和肝组织匀浆γ谷氨酰转肽酶(GGT)的水平(P<001);③降低血清肿瘤坏死因子α(TNFα)的水平(P<001);④使甲胎蛋白(AFP)免疫组织化学阳性细胞数各组间有明显差异(P<005)。　结论　抑癌复方对DEN所致大鼠肝癌前病变有明显的防治作用     

微RNA-126与肿瘤

微RNA(miRNA)-126通过靶向作用于表皮生长因子域7(EGFL7)、同源框A9(HOXA9)、胰岛素受体底物-1(IRS-1)、p85-β基因等,在转录后水平调控靶基因表达,在肿瘤形成中起重要作用.miRNA-126作为抑癌因子,在多种肿瘤中均下调,其抑癌作用及机制在肺癌、白血病、乳腺癌、宫颈癌等中均已得到证实.     

逆癌酮抗小鼠肺癌作用的初步研究

背景与目的　研究发现丹参酮具有抗肿瘤作用,逆癌酮是以丹参酮为主要成分并加入其它抗肿 瘤成分的中药制剂。本研究拟探讨逆癌酮对小鼠Lewis肺癌的抑癌作用及其机制。方法　用逆癌酮进行体 内抑癌实验,并用流式细胞术检测肿瘤组织中细胞凋亡指数和细胞周期分布。结果　共进行两次实验,每次 实验单一性别小鼠。逆癌酮组与5 Fu组的瘤重与对照组比较均有显著性差异(P<0.05),逆癌酮对小鼠 Lewis肺癌的抑瘤率分别为38.9%和32.2%,5 Fu对小鼠Lewis肺癌的抑瘤率分别为59.6%和53.9%;各 组间肺部转移率均无显著性差异(P>0.05)。流式细胞仪分析表明,逆癌酮组细胞凋亡指数(11.22%)明显 高于对照组(5.43%)(P<0.05),而细胞周期分布与对照组比较无显著性差异(P>0.05)。结论　逆癌酮对 小鼠Lewis肺癌有抑癌作用,它可能是通过诱导肿瘤细胞凋亡实现的。     

细胞周期调控基因p21WAF1／CIP1与肿瘤

肿瘤细胞区别于正常细胞的基本特征是细胞生长失控和分化受阻。细胞生长和分化受两类信号调控：正性信号(即癌基因)阻止分化，促使细胞生长；负性信号(即抑癌基因)则与正性信号相反。近几年来，在抑癌基因、抑癌基因与细胞周期调控关系方面的研究均取得明显的进展。抑癌基因的改变既在正常体细胞转化为恶性肿瘤细胞中发挥重要作用，又涉及种系细胞改变，这就成为肿瘤易感性的基础。……     

从大肠癌免疫核糖核酸(IRNA)中分离信使核糖核酸(mRNA)

目前对免疫核糖核酸(IRNA)的抗癌机理存在着两种主要见解,一种认为IRNA的抗癌作用与其他免疫刺激剂(例B.C.G和C.P.等)一样,仅引起机体的非特异性免疫水平的升高,起一种非特异的免疫应答抑癌作用;另一种看法是,在IRNA中携带(或蓄藏)有针对肿瘤抗原(细胞)的特异性免疫信息,且此特异免疫抗癌信息存在于IRNA中的mRNA部分,最近已有实验室证明IRNA的特异抗癌作用正是基于mRNA所含有的特异密码免疫     

低密度脂蛋白受体相关蛋白1B基因在消化系统肿瘤中的研究进展

低密度脂蛋白受体相关蛋白1B(LRP1B)自被发现以来便被定义为潜在抑癌因子。肿瘤中LRP1B基因多处于表达沉默状态, 其主要致病机制包括基因突变、启动子表观遗传修饰和微RNA(miRNA)调控。最近研究表明, LRP1B与消化系统肿瘤发生、发展存在重要联系。现结合国内外研究进展, 总结LRP1B结构、功能及在消化系统肿瘤中的作用, 揭示LRP1B作为消化道恶性肿瘤免疫治疗标志物的潜在价值, 并探讨其在不同肿瘤中从抑癌到促癌的角色转换, 旨在为后续机制研究提供帮助。     

FHIT基因与肝癌的研究进展

肿瘤发生过程中,原癌基因激活、抑癌基因功能丧失、以及一些修饰基因功能改变等起了重要作用。对抑癌基因的研究已成为目前肿瘤研究领域内的一个热点。近年在染色体3p区域新发现的脆性组氨酸三体(FHIT)基因是将脆性位点与肿瘤基因的变异联系起来的抑癌基因。它在人类许多肿瘤组     

珠子参体外诱导人肝癌细胞凋亡效应及机制研究

目的观察珠子参体外诱导人肝癌细胞凋亡效应并初探其分子机制。方法体外细胞培养采用人肝癌细胞株SMMC-7721,分为对照(BL)组、珠子参(PJ)组、二甲基亚砜(DMSO)组及5-FU组,采用电镜观察作用后肝癌细胞超微结构改变;流式细胞仪检测肝癌细胞周期和凋亡率;RT-PCR法检测癌基因c-myc、c-fos和抑癌基因p53、p21表达的变化。结果与对照组比较,电镜下珠子参组SMMC-7721细胞染色质浓缩,分解成大小不一有膜包绕团块,内含有新月形DNA物质及细胞器,形成凋亡小体;周期分析可见G0/G1期细胞阻滞,阻止了细胞向S期的转换,并引起细胞凋亡,凋亡率达38.34%;RT-PCR半定量分析珠子参能降低癌基因c-myc表达(P<0.05),增高抑癌基因p53和p21表达(P<0.05)。结论珠子参能诱导人肝癌细胞SMMC-7721凋亡,部分作用机制可能与阻滞细胞停留在G0/G1,降低癌基因c-myc和c-fos表达,增高抑癌基因p53和p21表达有关。     

NDR蛋白激酶家族调控肿瘤发生发展机制的研究进展

NDR（nuclear Dbf2-related）蛋白激酶家族是蛋白激酶AGC家族的一个亚家族,属于进化上高度保守的丝氨酸/苏氨酸(Ser／Thr)蛋白激酶家族成员,目前发现的人类NDR激酶家族包括NDR1/STK38(serine/threonine kinase 38)、NDR2/STK38L(serine/threonine kinase 38-like protein)、LATS1 (large tumor suppressor-1) 和LATS2四个成员。NDR蛋白激酶表达较为广泛,其主要通过激酶活性来调节细胞的功能,参与细胞增殖与分化。NDR蛋白激酶活化异常可导致其下游基因的异常活化,尤其调控一些原癌基因,如LATS1/2可通过经典HIPPO信号通路调控原癌基因Yorkie转录活性,发挥抑癌作用;NDR1/2一方面通过调控中心体复制、染色体校正参与稳定染色体组、凋亡信号等发挥抑癌作用,另一方面通过增强原癌基因C-myc的稳定性发挥促癌作用,值得关注的是NDR1/2亦可通过调节P21的稳定性而发挥抑癌和促癌的双重作用。本文主要综述近年来NDR蛋白激酶家族在肿瘤研究领域中的研究进展,以期为靶向蛋白激酶的抗肿瘤治疗策略提供新的靶标。     

Anthocyanins and their role in cancer prevention

Anthocyanins are the most abundant flavonoid constituents of fruits and vegetables. The conjugated bonds in their structures, which absorb light at about 500 nm, are the basis for the bright red, blue and purple colors of fruits and vegetables, as well as the autumn foliage of deciduous trees. The daily intake of anthocyanins in residents of the United States is estimated to be about 200 mg or about 9-fold higher than that of other dietary flavonoids. In this review, we summarize the latest developments on the anti-carcinogenic activities of anthocyanins and anthocyanin-rich extracts in cell culture models and in animal model tumor systems, and discuss their molecular mechanisms of action. We also suggest reasons for the apparent lack of correlation between the effectiveness of anthocyanins in laboratory model systems and in humans as evidenced by epidemiological studies. Future studies aimed at enhancing the absorption of anthocyanins and/or their metabolites are likely to be necessary for their ultimate use for chemoprevention of human cancer.     

Antitumor effect of hydrolyzed anthocyanin from grape rinds and red rice

When Balb/C mice that were fed with red glutinous rice, white ordinary rice, or commercially available standard food were inoculated with syngeneic Meth/A lymphoma cells i.p., the group fed the red rice survived longer than the other two groups. In order to determine if the anthocyanins contained in red-coloured seeds and fruit rinds were responsible for the tumor suppressive effect, we added anthocyanins extracted from grape rinds and glutinous red rice to petri dishes that had been seeded with HCT-15 cells. After 4 days of culture, cell counts were made. These anthocyanins were not effective in suppressing the tumor growth. However, anthocyanidins, which were generated by keeping anthocyanins in 5 to 6% HC1 methanol for 5 to 6 hours, were effective in the suppression of tumor growth. Flowcytometric histograms were made after 2 days of culture with these bioflavonoids. The histogram of cells treated with crude anthocyanin was similar to that of the control. Hydrolyzed anthocyanidins gave the elevation of S phase, suggesting a block in the step from S-phase to G2-phase. It seemed that the anthocyanidins contained in the grape rinds and red rice were effective on the suppression of cell growth as observed previously for anthocyanins extracted from the petals of higher plants.     

Anthocyanins: Targeting of Signaling Networks in Cancer Cells

It is becoming progressively more understandable that phytochemicals derived from edible plants haveshown potential in modelling their interactions with their target proteins. Rapidly accumulating in-vitroand in- vivo evidence indicates that anthocyanins have anticancer activity in rodent models of cancer. Moreintriguingly, evaluation of bilberry anthocyanins as chemopreventive agents in twenty-five colorectal cancerpatients has opened new window of opportunity in translating the findings from laboratory to clinic. Confluenceof information suggests that anthocyanins treated cancer cells reveal up-regulation of tumor suppressor genes.There is a successive increase in the research-work in nutrigenomics and evidence has started to shed lighton intracellular-signaling cascades as common molecular targets for anthocyanins. In this review we bring tol imelight how anthocyanins induced apoptosis in cancer cells via activation of extrinsic and intrinsic pathways.     

Cyanidin 3-O-beta-D-glucoside isolated from skin of black Glycine max and other anthocyanins isolated from skin of red grape induce apoptosis in human lymphoid leukemia Molt 4B cells

Cyanidin 3-O-beta-D-glucoside (CG) was purified from black bean seed coat and other anthocyanins were prepared from red grape skin. These anthocyanins were identified by Mass, and 1H- and 13C-NMR. The effects of four anthocyanins on cell viability in human leukemia Molt 4B cells were investigated. The anthocyanins displayed strong growth inhibitory effects against human leukemia Molt 4B cells. Morphological changes showing apoptotic bodies were observed in the Molt 4B cells treated with these anthocyanins. The fragmentations by these anthocyanins of DNA to oligonucleosomal-sized fragments, that is a characteristic of apoptosis, were observed to be concentration-dependent. N-acetyl-L-cysteine, an antioxidant, suppressed the fragmentation of DNA by these anthocyanins. These findings suggest that growth inhibition of Molt 4B cells by these anthocyanins result from the induction of apoptosis by these compounds and that active oxygen is involved in the induction of apoptosis in the Molt 4B cells.     

Antimutagenic activity of anthocyanins isolated from Aronia melanocarpa fruits

Anthocyanins belong to the flavonoid family and are ubiquitous in plants, especially in flower petals and fruit peels. We established that anthocyanins isolated from fruits of Aronia melanocarpa markedly inhibited the mutagenic activity of benzo(a)pyrene and 2-amino fluorene in the Ames test. In the Sister Chromatid Exchanges (SCEs) test with human blood-derived lymphocytes cultured in vitro, a significant decrease of SCEs frequency induced by benzo(a)pyrene was observed in the presence of anthocyanins. In the case of mitomycin C the effect of anthocyanins on SCEs frequency was smaller but still noticeable. Anthocyanins markedly inhibited the generation and release of superoxide radicals by human granulocytes. The results suggest that the antimutagenic influence of anthocyanins is exerted mainly by their free-radicals scavenging action as well as by the inhibition of enzymes activating promutagens and converting mutagens to the DNA-reacting derivatives. These preliminary data seem to be important in the aspect of a possible antimutagenic and anticarcinogenic potency of anthocyanins commonly present in fruits and vegetables.     

Anti-metastasis Activity of Black Rice Anthocyanins Against Breast Cancer: Analyses Using an ErbB2 Positive Breast Cancer Cell Line and Tumoral Xenograft Model

Background: Increasing evidence from animal, epidemiological and clinical investigations suggest that dietary anthocyanins have potential to prevent chronic diseases, including cancers. It is also noteworthy that human epidermal growth factor receptor 2 (ErbB2) protein overexpression or ErbB2 gene amplification has been included as an indicator for metastasis and higher risk of recurrence for breast cancer. Materials and Methods: The present experiments investigated the anti-metastasis effects of black rice anthocyanins (BRACs) on ErbB2 positive breast cancer cells in vivo and in vitro. Results: Oral administration of BRACs (150 mg/kg/day) reduced transplanted tumor growth, inhibited pulmonary metastasis, and decreased lung tumor nodules in BALB/c nude mice bearing ErbB2 positive breast cancer cell MDA-MB-453 xenografts. The capacity for migration, adhesion,motility and invasion was also inhibited by BRACs in MDA-MB-453 cells in a concentration dependent manner, accompanied by decreased activity of a transfer promoting factor, urokinase-type plasminogen activator (u-PA). Conclusions: Together, our results indicated that BRACs possess anti-metastasis potential against ErbB2 positive human breast cancer cells in vivo and in vitro through inhibition of metastasis promoting molecules.     

Anti-invasive activities of anthocyanins through modulation of tight junctions and suppression of matrix metalloproteinase activities in HCT-116 human colon carcinoma cells

Claudins are a family of proteins that are the most important components of the tight junctions. Recently it has been reported that these proteins are overexpressed in cancers and there is a positive correlation between suppression of the expression of these proteins and anti-invasive activity. Matrix metalloproteinases (MMPs) have been implicated as important mediators in cancer invasion. Here, we investigated the effects of anthocyanins on tight junctions (TJs) and the expression of claudins as well as MMPs. The inhibitory effects of the anthocyanins on cell proliferation, motility and invasiveness were found to be associated with tightening TJs, which was demonstrated by an increase in transepithelial electrical resistance (TER). The expression of claudin proteins was suppressed by anthocyanins. Furthermore, the activities of MMP-2 and -9 were dose-dependently suppressed by anthocyanin treatment. These effects were related to activation of 38-MAPK and suppression of the PI3K/Akt pathway in HCT-116 human colon cancer cells.     

Berberine induces cell death in human hepatoma cells in vitro by downregulating CD147

The isoquinoline plant alkaloid berberine has anti-tumor effects on a variety of carcinoma cells, mainly through inhibition of cell proliferation, apoptosis induction and cell cycle arrest. However, the mechanisms underlying its role in tumor progression are unknown. In the present study, we investigated the molecular mechanisms involved in berberine-induced cell death in human hepatoma carcinoma cell (HCC) lines HepG2 and SMMC7721. Our results showed that berberine inhibited tumor cell viability in a dose- and time-dependent manner, and induced cell death via apoptosis and autophagy. Moreover, berberine treatment significantly inhibited CD147 expression by HCC cells in a dose-dependent manner. Overexpression of CD147 protein markedly reduced berberine-induced cell death. Our data provide the first experimental evidence that berberine induces cell death in HCC cells via downregulation of CD147 and suggest a new mechanism to explain its anti-tumor effects.     

Anthocyanins are novel AMPKα1 stimulators that suppress tumor growth by inhibiting mTOR phosphorylation

AMP-activated protein kinase (AMPK) has emerged as a therapeutic target of cancer. AMPK functions as an upstream regulator of proliferative signals such as mammalian target of rapamycin (mTOR), tuberous sclerosis complex (TSC), p70S6 and elongation factor-2, indicating that AMPK can be applied for the inhibition of cancer cell proliferation via modulating the proliferative signaling network. The Akt/mTOR signaling pathway is activated in colon cancer. The well known mTOR inhibitor rapamycin has a disadvantage of feedback stimulation of Akt. Anthocyanins are naturally-occurring mTOR inhibitor possessing Akt inhibitory activities. We have investigated the mTOR inhibitory effect of anthocyanins through the activation of AMPK. In this study, anthocyanins were applied to colon cancer cells and tumor-bearing xenograft models to investigate their anti-proliferative and pro-apoptotic effects, and elucidate the mechanisms that link AMP-activated protein kinase (AMPK) α1 activation to the survival signal of mTOR. Our results indicated that anthocyanins significantly decreased phospho-mTOR comparable to rapamycin, a synthetic mTOR inhibitor, and this inhibitory effect of anthocyanins on mTOR was completely abrogated by inactivating AMPKα1. Furthermore, suppression of cell growth with anthocyanins was also alleviated in the absence of noticeable AMPKα1 activities. For the first time we have found anthocyanins as novel AMPKα1 activators, and in conditions of AMPKα1 inactivation, anthocyanins lost their ability to inhibit mTOR in HT-29 colon cancer cells. The activation of AMPKα1, and the deactivation of mTOR and Akt were observed in anthocyanins-treated tumor-bearing xenograft models. The results from this study suggest that there is a complex interaction between AMPKα1 and mTOR signaling, and anthocyanins are powerful AMPKα1 activators that inhibit cancer cell growth by inhibiting mTOR phosphorylation.     

放射性皮炎的防治研究现状

放射性皮炎是肿瘤放射治疗最常见的并发症，其预防和治疗一直是放疗界关注的问题。放射性皮炎的评价目前主要基于医生的主观评价，一些客观评价方法用于临床实践还需要进一步的研究。许多因素影响放射性皮炎的发生及其严重程度，包括内在因素和外在因素。除常规的护理以外，药物是放射性皮炎防治很重要的手段，如植物提取物（包括芦荟凝胶和植物油类）、维生素类（包括维生素C、维生素B12和维生素E等）、乳膏类（激素类乳膏和比亚芬等）、重组人表皮生长因子和中药等。许多学者对以上药物的防治效果进行了研究，但评价不一，期待更为有效的防治措施和方法出现。