核糖核苷酸还原酶抑制剂治疗肿瘤的研究进展

核糖核苷酸还原酶（RR）是生物细胞中唯一催化二磷酸核糖核苷酸还原为二磷酸脱氧核糖核苷酸（dNTPs）的酶，调节dNTPs含量，在DNA合成及细胞增殖中至关重要，其过表达与肿瘤的发生发展有着明确的联系。目前RR抑制剂已应用于临床治疗肿瘤，以RR及其亚单位为潜在靶点开发新型抗癌药物，可望为临床治疗肿瘤提供新的选择。本综述从RR的结构和功能、RR在癌症发展中的作用、RR抑制剂的应用及研究前景几方面进行探讨。     

全反式维甲酸抗肿瘤作用的研究进展

 维甲酸类药物包括维生素A的天然及人工合成的衍生物。维生素A（视黄醇）进入人体后转变成视黄醛，再经氧化变成维甲酸。维甲酸是维持生长发育不可缺少的物质，尤其在促进上皮组织分化生长及维持其正常功能方面起重要作用。     

肿瘤与止血的相互作用——血小板抑制剂和抗凝剂应用于肿瘤治疗的理论基础

临床和实验研究表明,某些肿瘤在体内能激活血小板和凝血机制,血小板和纤维蛋白会参与肿瘤的生长和转移。对血小板抑制剂和抗凝剂作为肿瘤辅助治疗的效果,已经或正在进行大量的临床和实验研究。对不同的药物和肿瘤,抗血小板药物可产生不同的效果。宿主和肿瘤两者的前列腺素合成途径似乎是血小板功能抑制剂起作用的重要因素。在试验的各种抗凝剂中,香豆素衍生物对某些人类和实验性肿瘤能产生较为一致的抗肿瘤效果。口服抗凝剂的抗肿瘤效果看来不是药物的直接作用,似与其作为维生素K拮抗剂有关。应当强调,尽管     

维生素缺乏与恶性肿瘤

一、B族维生素与肿瘤 B族维生素包括：B1、B2、B4、B6、B12烟酸等。有研究发现,食管癌高发地区（中国林州、南非、伊朗等地）的共同膳食特点之一,是B族维生素（特别是维生素B2和烟酸）的摄入严重缺乏。因为动物实验发现维生素B2缺乏可导致亚硝胺的代谢改变,促进食管上皮增生。     

RGD肽在肿瘤显像和治疗中的应用研究进展

介绍精氨酸（Arg）—甘氨酸（Gly）—天冬氨酸（Asp）肽（RGD肽）在肿瘤诊治领域应用研究新进展．内源性RGD肽存在于多种生物细胞外基质中，参与多条信号传导通路的活化，在多种生理和病理过程中发挥重要作用。外源性RGD肽与肿瘤细胞表面整合素结合后，可作为体内RGD肽类物质的竞争性抑制剂，从而能抑制肿瘤细胞与细胞外基质的黏附与迁移、抑制肿瘤血管形成、诱导肿瘤细胞凋亡。RGD肽能与肿瘤高表达的整合素受体结合，并从多个环节对肿瘤起到抑制作用，其具有靶向性进行肿瘤显像及肿瘤治疗的潜在应用价值。     

DNA错配修复基因的遗传变异/突变与肿瘤治疗反应

DNA错配修复（mismatch repair,MMR）是一个复杂的生物学过程,在维持基因组完整性方面起着重要作用。微卫星不稳定性（microsatellite instability,MSI）由MMR蛋白功能缺陷导致。MMR基因的遗传变异或突变对肿瘤的发生、发展以及预后起到关键作用,其相关研究已取得显著成果。目前国内外多个指南建议对晚期实体瘤患者检测MMR/MSI,其结果可以预测肿瘤患者的预后,并可预测肿瘤辅助化疗及免疫治疗疗效,对治疗方案的选择具有指导意义。     

维生素E琥珀酸酯抗肿瘤作用的研究进展

维生素E（vitamin E,VE）是人体内具有多种生理功能的重要脂溶性维生素和天然抗氧化剂,除了维持机体正常的生理功能外,其潜在的肿瘤预防和治疗作用也被公认。在VE抗肿瘤作用中,以其同型衍生物维生素E琥珀酸酯（RRR-α-tocopher-yl succinate,α-TOS,vitamin Esuccinate,VES）的活性最强,1995年,Turiey等首先报道VES具有诱导人B淋巴瘤细胞凋亡的作用,随后研究发现,VES在体内和体外均可有效地抑制多种肿瘤细胞生长而对机体正常细胞无毒性。本文就VES抗肿瘤作用的最新进展进行综述。     

BCAR1／p130Cas蛋白与乳腺癌抗雌激素药物耐药的相关研究

研究表明，雌激素在诱导乳腺癌发生和细胞增殖方面起到重要的作用。雌激素及其受体组成的蛋白复合体作用于乳腺细胞，促进多种基因的转录调节。临床上，大约2／3的乳腺癌雌激素受体（ER）阳性，且具备生物活性功能，能促进和维持乳腺肿瘤细胞的生长。因此，临床上通过检查乳腺癌细胞是否含有ER，和ER对雌激素的应答性来决定是否应用抗雌激素药物。     

泛素特异性蛋白酶39的生物学功能及在肿瘤中的研究进展

泛素特异性蛋白酶39（ubiquitin-specific protease 39，USP39）是泛素特异性蛋白酶家族的成员之一，在多种肿瘤细胞中高表达。USP39不仅能够参与剪接体的形成，参与pre-mRNAs的剪接过程，在维持纺锤体的稳定、调节细胞周期方面也起着重要的作用。USP39可以通过多种信号通路调节细胞的增殖、迁移、细胞周期阻滞、增加肿瘤细胞对化疗药物和放射的耐受性，导致肿瘤的恶性进展等。本文就USP39的生物学功能及其在肿瘤发生发展中的作用进行综述，为基于USP39的肿瘤诊断和治疗提供理论依据。     

维甲酸受体在乳腺癌中表达的研究

维生素Ａ族化合物包括维生素Ａ及其衍生物,维甲酸属于此族化合物的一种。它们在预防肿瘤包括乳腺癌的发生及各种细胞的分化中起着重要的作用［１］。它们主要是通过与甾体激素同属核受体家族的维甲酸受体（ＲＡＲｓ）和相关受体（ＲＸＲｓ）起作用,两类受体各分α、β、...     

Detoxifying cancer causing agents to prevent cancer

Different vitamins and other micronutrients in vegetables, fruits, and other natural plant products may prevent cancer development (carcinogenesis) by interfering with detrimental actions of mutagens, carcinogens, and tumor promoters. The goal of current studies in cancer prevention is to determine the mechanisms of synergistic action of the natural source compounds known to inhibit one or more stages of carcinogenesis, that is, initiation and promotion/progression. Many natural cancer preventive agents are effective inhibitors of tumor initiation, promotion, and/or progression. The mechanism of action is related to their abilities to prevent critical carcinogen metabolism and to increase detoxification of carcinogens and tumor promoters. The authors review here the potential role of the detoxification system and, in particular, the roles of D-glucaric acid and the enzyme beta-glucuronidase in early detection and prevention of cancer. There is now growing evidence for the possible control of different stages of the cancer induction by inhibiting beta-glucuronidase with D-glucaric acid derivatives, especially with its salts (D-glucarates). D-Glucaric acid has been found in many vegetables and fruits. Therefore, the consumption of fruits and vegetables naturally rich in D-glucaric acid or self-medication with D-glucaric acid derivatives such as calcium D-glucarate offers a promising cancer prevention approach.     

Future directions for research on Silybum marianum for cancer patients

Silymarin (Silybum marianum [L.] Gaertn. [Asteraceae]) is a promising agent for cancer prevention, adjuvant cancer treatment, and reduction of iatrogenic toxicity. Although it is safe and free of serious adverse side effects, few studies have evaluated its use alongside conventional cytotoxic therapies, and adverse events associated with long-term administration are uncertain. Although it may prevent some types of cancer, its promotion of tissue regeneration and its potential estrogen activity could promote the growth of some tumors. Further clinical trials using authenticated fractions of silymarin as simple and complex derivatives are required prior to any general recommendations. Future research should focus on authentication of active chemicals, pharmacokinetics, adverse interactions and quality control, prevention of cancer initiation and progression, adjuvant therapy for specific cancers, and prevention of toxicity from anticancer therapies.     

肿瘤相关成纤维细胞在结直肠癌发生发展中的作用研究进展

肿瘤相关成纤维细胞（CAFs）是间质的主要细胞成分,在结直肠癌（colorectal cancer,CRC）的发生发展中发挥重要作用。CAFs通过细胞与细胞间的直接接触以及旁分泌的方式分泌各种细胞因子、生长因子和趋化因子,通过不同的信号通路促进CRC的发生、生长以及血管生成、侵袭和转移。CAFs还为CRC的早期诊断和治疗提供新的标记和新的靶点,为CRC的综合治疗提供新的思路。本文主要就近年来CAFs在结直肠癌发生发展以及诊治中作用的研究进展作一综述。     

阿司匹林在乳腺癌防治中应用研究进展

目的 总结国内外对阿司匹林与乳腺癌防治研究的最新进展,并就阿司匹林抗乳腺癌的机制、安全性及风险获益分析进行综述.方法 应用PubMed、Web of Science及CNKI期刊全文数据库检索系统,以“阿司匹林(aspirin)、非甾体类抗炎药(non-steroidal anti-inflammatory drugs,NSAIDs)、癌(cancer,tumor,neoplasm,carcinoma)、乳腺癌(breastcancer)”等为关键词,检索2000-2016的相关文献,共检索到英文文献1 759条,中文文献231条.纳入标准:(1)阿司匹林或非甾体类抗炎药与癌症防治或乳腺癌防治相关的基础研究、临床研究、荟萃分析等;(2)长期服用阿司匹林的安全性、风险获益分析;(3)发表年限较近的文章.剔除标准:(1)文献中所研究的非甾体类抗炎药不包含阿司匹林;(2)发表年限较久远的文章;(3)重复性文献.根据纳入及排除标准,最后纳入分析40篇文献.结果 阿司匹林主要通过抑制体内环氧化酶活性发挥抗乳腺癌作用,长期服用阿司匹林增加了溃疡、出血等风险,但对于低出血风险及高乳腺癌风险的患者来说获益大于风险.大量研究证明,阿司匹林具有抗乳腺癌作用,但目前各研究结果结论不一,其是否可以降低乳腺癌的发病率和死亡率以及抑制乳腺癌的复发和转移尚存在争议.结论 阿司匹林是癌症防治的新策略,有望成为乳腺癌的有效防治措施,但仍需要更多大型多中心临床研究进行进一步研究和论证.     

长链非编码RNA在食管癌中的研究进展

随着分子生物学研究的技术革新和计算机生物信息学的蓬勃发展,长链非编码RNA（lncRNA）的作用和生物学功能得到了深入研究,其在细胞周期进程、细胞生长和凋亡等过程中具有重要的调控作用。lncRNA的异常表达与肿瘤的增殖、迁移及侵袭均密切相关。本文总结了近2年有关食管癌lncRNA的相关研究进展,介绍影响食管癌生物学特性的lncRNA调控机制,尤其是lncRNA作为竞争性内源RNA（ceRNA）的调控机制,以期为食管癌的诊断和治疗提供新思路。     

维生素D防治胰腺癌的研究进展

胰腺癌是一种致死率较高的恶性肿瘤,具有转移早、诊断晚、治疗耐药等特征,且手术根治率低,预后较差,目前针对胰腺癌的一线联合化疗方案整体治疗效果不佳,治疗后患者生存率仍较低,亟需开发有效的干预治疗策略.维生素D对多种恶性肿瘤的发生和发展具有积极的预防和治疗作用,近年来,维生素D防治胰腺癌已成为研究热点之一.维生素D及其衍生...     

Ascorbic acid suppresses drug-induced apoptosis in human colon cancer cells by scavenging mitochondrial superoxide anions

Although a high alimentary intake of antioxidant vitamins such as ascorbic acid may play an important role in cancer prevention, a high level of antioxidants may have quite different effects at different stages of the transformation process. In cancer development, the resistance of cells to apoptosis is one of the most crucial steps. We have tested the effects of ascorbic acid on apoptosis in HT-29 human colon carcinoma cells when induced by two potent apoptosis inducers, the classical antitumor drug camptothecin or the flavonoid flavone. Apoptosis was assessed based on caspase-3-like activity, plasma membrane disintegration and finally nuclear fragmentation and chromatin condensation. Ascorbic acid dose-dependently inhibited the apoptotic response of cells to camptothecin and flavone. RT-PCR analysis and western blot analysis revealed that ascorbic acid specifically blocked the decrease of bcl-X(L) by camptothecin or flavone. An increased generation of mitochondrial O(2)(-.) precedes the down-regulation of bcl-X(L) by camptothecin and flavone and ascorbic acid at a concentration of 1 mM prevented the generation of this reactive oxygen species. In conclusion, ascorbic acid functions as a potent antioxidant in mitochondria of human colon cancer cells and thereby blocks drug-mediated apoptosis induction allowing cancer cells to become insensitive to chemotherapeutics.     

COX inhibitors and breast cancer

There is considerable evidence to suggest that prostaglandins play an important role in the development and growth of cancer. The enzyme cyclo-oxygenase (COX) catalyses the conversion of arachidonic acid to prostaglandins. In recent years, there has been interest in a possible role for COX inhibitors in the prevention and treatment of malignancy. Cyclo-oxygenase-2 (COX-2) is overexpressed in several epithelial tumours, including breast cancer. Preclinical evidence favours an antitumour role for COX inhibitors in breast cancer. However, the epidemiological evidence for an association is conflicting. Trials are being conducted to study the use of COX inhibitors alone and in combination with other agents in the chemoprevention of breast cancer, and in the neo-adjuvant, adjuvant, and metastatic treatment settings. In evaluating the potential use of these agents particularly in cancer chemoprophylaxis, the safety profile is as important as their efficacy. Concern over the cardiovascular safety of both selective and nonselective COX-inhibitors has recently been highlighted.     

Inhibition of cutaneous ultraviolet light B-mediated inflammation and tumor formation with topical celecoxib treatment

Inflammation, which includes the release of growth factors, proinflammatory cytokines and prostaglandins, the infiltration and activation of inflammatory cells, and the induction of oxidative DNA damage, is known to play a role in cancer development. The combination of damage to the skin resulting from chronic ultraviolet light B (UVB) exposure itself and the inflammatory response it induces is a major source of skin cancer development. Cyclooxygenase-2 (COX-2), an inflammatory enzyme responsible for the production of prostaglandins, is now implicated in the development of epithelial cancers, including squamous cell carcinoma in the skin. Previous work conducted in our laboratory has shown that topical treatment with celecoxib following UVB irradiation inhibits several parameters of acute inflammation, including vascular permeability, the infiltration and activation of neutrophils, and the production of prostaglandin E(2) (PGE(2)). The present studies expanded these observations, demonstrating the ability of topical celecoxib to inhibit acute oxidative damage. In addition, long-term studies illustrate the effectiveness of topical treatment with this drug in reducing chronic inflammation and UVB-induced papilloma/carcinoma formation. This data provides compelling evidence to explore the clinical efficacy of topically applied COX-2 inhibitors for the prevention of human skin cancers.     

哺乳动物雷帕霉素靶蛋白及其信号通路在胃癌中的研究进展

哺乳动物雷帕霉素靶蛋白(mTOR)及其信号通路控制着蛋白质合成、细胞的生长和代谢以及血管的生成等.其信号通路在胃癌中常被高度激活,与胃癌进展及预后密切相关.雷帕霉素及其衍生物可通过阻断mTOR通路的信号传递,抑制胃癌细胞生长,促进肿瘤坏死,并能与其他化疗药物产生协同作用,有望为胃癌预防和治疗提供有效的方法.