靶向Rad51与肿瘤治疗的研究进展

DNA损伤反应在维持细胞基因组稳定性和机体存活发挥重要作用。DNA双链断裂(Double strand breaks,DSBs)是DNA损伤最严重的形式。同源重组修复是体内参与DSBs损伤修复的重要机制之一,其中Rad51是体内参与同源重组性DNA修复的关键因子。Rad51在人类的多种肿瘤组织中高表达,如乳腺癌、非小细胞肺癌、前列腺癌等,与肿瘤的转移和恶化相关。如何有效下调肿瘤组织中的Rad51的水平,降低肿瘤细胞的DNA损伤修复能力,从而提高肿瘤治疗的疗效具有潜在的临床应用价值。本文对近年来的一个研究热点靶向Rad51在肿瘤治疗研究中的应用进行综述。     

三尖杉酯碱抑制脱氧核糖核酸生物合成机制的研究——Ⅰ.对DNA模板及其合成代谢的影响

本文应用吸收光谱移动法、萤光光谱移动法、~(3)H-药物与DNA 结合实验以及~(3)H-胸腺嘧啶核苷连续标记技术研究了三尖杉酯碱抑制L_(1210)细胞DNA 生物合成的机制。结果表明,DNA合成的受抑可能是由于该药干扰其代谢过程而非直接损伤其模板所致。     

转化细胞及腹水癌细胞对生长调节因子敏感性的研究

 本文~3H-TdR参入细胞DNA为指标研究了EGF等生长调节因子对小鼠腹水癌细胞DNA合成的影响,发现不同癌细胞对EGF等生长因子的敏感性有所差异,考虑到这也许与肿瘤细胞自身特性如恶性度有关。为了进一步探讨恶性度与这一敏感性是否相关,我们观察并比较了C_3H10T1/2CL_8(一种来源于鼠胚的正常成纤维细胞,简称NC_3H_(10)及转化的C_3H_(10)T1/2CL_8(用~3H-TdR转化的上述细胞,简称TC_3H_(10))对EGF等生长因子的敏感性。实验证明,细胞恶性转化后,对EGF的敏感性明显降低,~3H-TdR参入率降至原先的1/4以下。用DBcAMP作用于NC_3H_(10)和TC_3H_(10)均能抑制~3H-TdR参入DNA并可抑制EGF诱导的~3H-TdR参入作用。因此,我们认为,有关物理的致癌因素如放射性同位素,像生物、化学的致癌因素一样,亦能引起其转化细胞对外源性生长调节因子敏感性的改变。     

SUMO化修饰与DNA损伤修复

由于体内外因素的影响,DNA损伤是生物生命周期中的常见现象,如果得不到及时的修复,DNA损伤的积累将导致基因组的不稳定及染色质的异常,并可能导致肿瘤的发生发展。SUMO化修饰是体内一个重要的蛋白质翻译后修饰,越来越多的研究发现SUMO化修饰与多个参与DNA损伤反应、维持基因组稳定的蛋白质相关,有可能参与肿瘤的发生。本文将阐述SUMO化修饰与DNA损伤修复的关系。     

DNA修复酶系统的研究——Ⅰ.紫外线诱发~3H-TdR在着色性干皮病淋巴细胞中的非合成期掺入

本文报告了用液体闪烁计数方法对5例华东地区的着色性干皮病病人外周血淋巴细胞进行DNA切除修复功能的研究。结果发现,这5例病人淋巴细胞中的DNA切除修复功能都有不同程度的缺陷。3例病人为正常人的50％左右,1例为正常人的15％,1例在正常人的5％以下。作者提出了紫外线诱发淋巴细胞非合成期~3H-TdR掺入指数的大小代表DNA切除修复功能的高低,并根据实验结果与临床资料分析,认为DNA修复的程度与着色性干皮病的病情进展可能存在着直接关系。这与Takebe(1978)的结论是一致的。     

中药固真方对ROS17/2.8细胞增殖分化的影响

中药固真方具有补肾益精、延缓衰老等作用。本文主要研究固真方对~3H-TdR参入DNA及碱性磷酸酶活性的影响。实验结果表明,当大鼠成骨肉瘤细胞ROS17/2.8经固真方药处理24h后,其~3H-TdR的参入比对照组增高13.9％至319.2％,而其碱性磷酸酶活性在经固真方药处理2—3天后则增高4.4％至52.8％(平均30.2％),提示固真方药在成骨样细胞中既有增殖作用,也有促分化作用。     

大白菜花药培养中花粉早期DNA的合成

应用显微放射自显影技术,在大白菜(Brassica pekinensis Rupr.)花药离体培养初期观察了~3H-胸腺嘧啶核苷(~3H-TdR)掺入花粉核及其DNA复制类型。花粉去分化进入第一次孢子体分裂主要发生在DNA合成的单核和非均等分裂的营养核的花粉粒中。 实验证明花粉的DNA合成在低温预处理过程中已经开始,离体花药培养后,大大促进花粉DNA的合成。花粉单核在培养后24小时~3H-TdR掺入达到高峰,花粉有丝分裂产生两个均等子核的最大数量是在培养后48小时。 讨论了花药体细胞组织——绒毡层和药内壁对花粉核DNA合成的影响。     

脱氧核糖核酸对机体内超氧化物岐化酶和过氧化物酶活性影响初步研究

超氧化物岐化酶（SOD）和过氧化物酶（POD）是机体内重要的抗氧化酶系之一,其作用在于消除体内的自由基,防止自由基对细胞结构的损伤。它们的活性随增龄而下降,因此自由基不断损伤细胞结构,累积最终导致细胞衰亡和动物机体衰老,老龄小鼠服用DNA一段时间后,其体内SOD和POD的活性均显著提高,因而其衰老速度可能得到一定程度的延缓。     

环磷酰胺致DNA损伤及其防治机制的研究进展

CTX是临床上常用的抗肿瘤药物与免疫抑制剂,其在体内的代谢产物具有很强的烷化作用,可引起DNA链内和链间的交叉连接,干扰转录和复制,造成DNA的损伤。CTX导致DNA损伤的机制与环磷酰胺代谢过程中产生的自由基过量以及代谢产物产生的烷化作用有关,目前减轻CTX造成的DNA损伤的措施主要是提高机体的抗氧化能力和促进机体修复损伤的DNA。DNA损伤会对机体产生一系列变化如导致肿瘤、神经退行性病变、衰老和遗传易感综合症等疾病的发生、发展。本文综述了CTX导致DNA损伤的机制及其防治研究进展,以其为CTX的临床安全用药和今后的科学研究提供思路和依据。     

钙调素拮抗剂小柏胺衍生物对成纤维细胞增殖和功能的影响

为了研究钙调素拮抗剂EBB对成纤维细胞增殖和功能的影响,我们观察了经EBB作用后成纤维细胞的生长曲线、~3H-TdR掺入、钙调素水平的变化以及细胞增殖周期中DNA的改变和~3H-脯氨酸掺入。结果表明EBB直接抑制细胞增殖,使钙调素水平下降,DNA合成受阻,并使细胞停滞于生长周期中的G_0+G_1期。另外,胶原合成也受到阻抑。     

(3R,3′R)-astaxanthin from the yeast Phaffia rhodozyma

Astaxanthin isolated from the yeast Phaffia rhodozyma has the 3R,3′R-configuration, opposite to that of astaxanthin from other sources which have been so far investigated. This is the first example of a naturally occurring carotenoid biosynthesized in different optical forms. A possible explanation is advanced.     

3-Methylthiopropylamine and (R)-3-methylsulphinylpropylamine in Iberis amara

3-Methylthiopropylamine and (R)-3-methylsulphinylpropylamine have been isolated from Iberis amara and identified by PC, high voltage electropho     

Rhamnazin- und rhamnetin-3-O-trioside aus Rhamnus petiolaris

From the fruits of Rhamnus petiolaris two new flavonol-3-O-triosides were isolated and identified as rhamnazin-3-O-[α-l-rhamnopyranosyl (1 → 4)-α-l-rhamnopyranosyl (1 → 6)]-β-d-galactopyranoside and rhamnetin-3-O-α-l-rhamnopyranosyl (1 → 2)-α-l-rhamnopyranosyl (1 → 6)]-β-d-galactopyranoside, respectively.     

3H-cimetidine and the H2-receptor

The H₂-antagonist cimetidine is widely employed in biochemical and pharmacological studies of the H₂-receptor. These studies include the use of ³H-cimetidine in radioligand binding experiments. Confirming our previous finding as to the unsuitability of this ligand in these types of investigations, we now report data showing the lack of correlation between the displacement of specific ³H-cimetidine binding and histamine stimulated adenylate cyclase activity, and the displacement of specific binding by imidazoles devoid of H₂-receptor activity. Results are also presented which question the use of copper ions in ³H-cimetidine binding studies. Our conclusions are discussed in relation to the work carried out by a number of laboratories where ³H-cimetidine is reported to label the H₂-receptor.     

Metal-penicillamine interactions. Part 1. Preparation and crystal structure of a 1:1 complex of mercuric chloride with d-penicillamine, 2[μ3-Cl){HgSC(CH3)2CH(NH3)COO}3·3(μ2-Cl)· 2(H3O)·(H2O·Cl)3

A 1:1 complex of mercuric chloride with D-peniccillamine has been isolated and characterised as 2[(μ₃-Cl){HgSC(CH₃)₂CH(NH₃)COO}3]·3(μ₂-Cl)·2(H₃O)·(H₂O·Cl)₃. The compound crystallises in cubic space group P4₁32, with a = 18.679(5) Å and Z = 4. The structure, refined to R_F = 0.086 for 443 observed Mo-Kα diffractometer data, features a triply bridging chloride ion linking three equivalent [HgSC(CH₃)₂CH(NH₃)COO]⁺ units [Hg-Cl = 2.37(1) Å, Hg-Cl-Hg′ = 98.5(9)°]. The carboxylate groups of a pair of adjacent penicillamine ligands are strongly linked via a symmetrical O?H?O hydrogen bond of length 2.24(8) Å, and neighboring pyramidal trinuclear [μ₃-Cl){HgSC(CH₃)₂CH(NH₃)-COO}₃]²⁺ moieties are further connected by symmetrical chloride bridges [Hg-Cl = 3.06(2) Å; HgClHg′' = 79.6(7)°] to form a three-dimensional network. The voids in the lattice are filled by hydronium ions and novel planar cyclic hydrogen-bonded (H₂O·Cl^?)₃ rings of edge O-H?Cl = 2.46(4) Å.     

Rhamnocitrin-3-glucuronid in Verbesina myricephala

The structure of a new flavonol-glycoside isolated from the herb of Verbesina myricephala Sch. Bip. has been established as the 3-O-β-d-glucopyranuronide of 3,5,4′-trihydroxy-7-methoxy-flavone (rhamnocitrin-3- glucuronide.     

3S,24S,25-Trihydroxytirucall-7-ene from Ailanthus excelsa

A new triterpene has been isolated from the root bark of Ailanthus excelsa (Simaroubaceae) and identified as 3S,24S,25-trihydroxytirucall-7-ene.     

Invivo conversion of 3-ketoceramide to ceramide in rat liver

A doubly labeled 3-ketoceramide, [1-¹⁴C] lignoceroyl [1-³H₂] 3-ketosphingosine ($\text{3H}{}^{14}\text{C}$ ratio, 3.61) was injected into the left ventricle of rat heart. The ceramide isolated from the livers of the animals after 1 hr incubation contained an equal $\text{3H}\text{>}{}^{14}\text{C}$ ratio of 3.60. This finding strongly supports the existence for direct conversion of 3-ketoceramide to ceramide in rat liver.