番荔枝内酯抗肿瘤作用研究进展

番荔枝内酯(ACG)是一类从多种番荔枝科植物中提取的长碳链脂肪酸内酯,具有广谱抗肿瘤作用.番荔枝内酯来源丰富,具有广阔开发应用前景.动物实验发现,番荔枝内酯毒性较大.目前通过化学修饰或结构改造,提高其抗肿瘤活性、生物利用度并降低毒性,是番荔枝内酯药物的研发方向.     

阿蒂莫耶番荔枝总内酯体外抗肿瘤作用

番荔枝内酯是从番荔枝科植物中得到一类具有抗癌活性令人鼓舞的新型天然产物。同时其毒性低，活性高，极有希望成为新型的天然抗癌剂，阿蒂莫耶植物种子中番荔枝总内酯含有多种抗癌力强的成份，本文拟探讨这种番荔枝总内酯的体外抗肿瘤作用。方法；以阿莫耶番荔枝内酯对多种人的体外培养的细胞株进行细胞毒测定。     

番荔枝内酯抗肿瘤作用研究进展

自１９８２年Ｊｏｌａｄ等从番荔枝科紫玉盘属植物Ｕｖａｒｉａａｃｕｍｉｎａｔａ根中第一次分离得到第一个番荔枝内酯并证明具有抗肿瘤活性以来，对番荔枝内酯抗肿瘤作用的研究进展很快，至今已发现这类化合物共有２００多种。目前，番荔枝内酯就其化学结构主要分为四类...     

番荔枝科植物抗癌活性成分研究的新结果

番荔枝科植物在全世界有 12 0个属约 2 0 0 0种 ,分布在热带和亚热带地区。中国有 2 4个属 10 3个种和 6个变种。以往对番荔枝科的植物化学研究主要集中在生物碱方面。自从 1982年第一个抗肿瘤活性高的番荔枝内酯 (annona ceousacetogenin)被发现以来 ,番荔枝科植物中抗癌化学成分番荔枝内酯的研究已经成为国内外植物化学和肿瘤药理学研究继紫杉醇后又一个热点。与此同时 ,从番荔枝科哥纳香属植物中还分离到了具有抗癌活性的另一类化学成分———番荔枝苯乙烯内酯 (styryllactones)。本文结合自己的工作介绍了目前对番荔枝内酯及番荔枝苯乙…     

抗肿瘤核糖核酸酶研究进展

核糖核酸酶(RNase)是一类广泛存在于动植物体内的核酸水解酶,近年来一系列研究表明核糖核酸酶及其结构类似物具有抗肿瘤活性,通过破坏RNA发挥抗肿瘤作用.有一些因素决定RNase的细胞毒性,了解这些因素有助于改造Rnase,以增强其细胞毒性,更好地发挥抗肿瘤治疗作用.RNase的研究为临床治疗肿瘤提供了新的前景,有望成为一类新型的抗肿瘤药物.     

姜黄素抗肿瘤机制研究进展

姜黄素是一种植物多酚,具有抗氧化、抗凝、降血脂、抗动脉粥样硬化、抗人类免疫缺陷病毒、抗菌、抗寄生虫、镇痉、抗肿瘤、抗突变等多种药理作用,且毒性很低,其抗肿瘤作用及其机制的研究日益受到重视,具有广阔的开发前景.现介绍近年来有关姜黄素抗肿瘤作用及其机制、临床试验研究方面的进展.     

雷公藤内酯醇抗肿瘤研究进展

雷公藤内酯醇抗肿瘤作用因具有广谱、高效等突出的优越性而受到国内外医学工作者的关注，近年众多研究认为雷公藤内酯醇通过抑制NF—κB的活化、促进p53表达等从而使肿瘤细胞发生凋亡，同时能抑制实体肿瘤生长及转移，其治疗效果优于紫杉醇。因而雷公藤内酯醇有望成为新一代的抗肿瘤药物。     

亚硝基脲对钙调素的体内体外作用

由于抗肿瘤药物存在着多种毒性,因而临床应用受到限制。这些毒性包括胃肠上皮细胞损害和骨髓的破坏。因此,新的抗肿瘤药物应考虑到已知的或潜在的毒性和作用机制来设计.亚硝基脲是具活性的抗肿瘤药物,将DNA 烷基化为其机制。此类药中,还有几种可使细胞蛋白质氨甲酰基化的.由于氨甲酰基化与抗肿瘤效果无关,因而,人们认为临床上产生的副作用是由此而产生的.另一方面,迄今已有报道表明,有几种抗肿瘤药     

右丙亚胺对蒽环类抗肿瘤药心脏毒性防护研究

右丙亚胺是作用位点专一的心脏防护药物.能够有效预防蒽环类抗肿瘤药引起的心脏毒性.右丙亚胺已被广泛应用于接受蒽环类抗肿瘤药化疔的患者.临床研究表明,静脉应用右丙亚胺能够显著降低葸环类抗肿瘤药引起的充血性心力衰竭和严重心脏意外.其不良反应非常小,患者易于耐受.到目前为止,是唯一有效地能够预防蒽环类抗肿瘤药引起的心脏毒性的药物,推荐临床使用.     

肿瘤抗原致敏树突状细胞协同CD3AK细胞的抗肿瘤作用

目的:观察雷公藤内酯醇是否能抑制肿瘤细胞增殖,并探讨其是否通过诱导肿瘤细胞凋亡发挥抗肿瘤作用.方法:选择人宫颈癌细胞株HeLa为研究对象,以MTr实验检测肿瘤细胞的增殖,以AnnexinV/PI染色检测细胞的凋亡,R123染色检测线粒体膜电势的变化.Hoechst 33258荧光染色法观察细胞形态学改变,琼脂糖凝胶电泳检测染色体DNA断裂.结果:雷公藤内酯醇能明显抑制HeLa细胞的增殖;AnnexinV/PI染色结果证明雷公藤内酯醇能诱导HeLa细胞凋亡,R123染色结果说明雷公藤内酯醇诱导的细胞凋亡与线粒体膜电势的变化有关.雷公藤内酯醇处理的HeLa细胞可见凋亡特有的形态学及生物化学改变,DNA电泳呈梯状条带.结论:雷公藤内酯醇可以通过诱导肿瘤细胞凋亡而发挥抗肿瘤作用.     

Newcastle disease virus activates macrophages for anti-tumor activity

Newcastle Disease Virus (NDV), an agent with interesting immune stimulatory and anti-tumor activity, was investigated for its capacity to activate anti-tumor activity in murine macrophages in vitro and in vivo. Direct macrophage activation was seen under a variety of experimental conditions using two different strains of NDV, different sources of macrophages (spleen and peritoneum) and different strains of mice (DBA/2, C57BL/6, 615). Various macrophage enzymes (ADA, iNOS, lysozyme, acid phosphatase) became upregulated and anti-tumor effector molecules such as nitric oxide (NO) and TNF-alpha were found in the supernatant. NDV activated macrophages performed anti-tumor activity in vitro such as anti-tumor cytostasis and anti-tumor cytotoxicity. The cytotoxic anti-tumor activity was broad and active against all tumor lines tested including mammary carcinoma, lung carcinoma, mastocytoma and immune escape variants (lymphoma). Macrophage activation via BCG/LPS also caused a broad range anti-tumor cytotoxic activity while activation via mixed lymphocyte culture conditioned medium had restricted anti-tumor activity. Anti-tumor activity of NDV activated macrophages could be transfered in vivo. Transfer of macrophages which had not been appropriately activated exerted either no effect or a tumor growth augmenting effect. Repeated intravenous transfer of NDV activated macrophages exerted a significant suppressive effect on pulmonary metastases in a mammary carcinoma tumor model as well as in a lung carcinoma model. Taken together these results demonstrate that NDV can strongly activate macrophages to perform anti-tumor activities in vitro and in vivo.     

In vitro antitumor SAR of threo/cis/threo/cis/erythro bis-THF acetogenins: correlations with their inhibition of mitochondrial Complex I

Annonaceous acetogenins (ACG) are a large family of natural products that have been described as the most potent in vitro inhibitors of the mitochondrial respiratory chain Complex I. During the last two decades a large number of related structures have been discovered, increasing the number of members of this family. The large diversity of structural moieties and the general trends observed for inhibiting both growth of tumor cell lines and mitochondrial respiratory chain activity have resulted in the classification of these compounds into several structural groups according to their potency. Among them, the adjacent bis-tetrahydrofuranic acetogenins (bis-THF ACG) with a threo/cis/threo/cis/erythro relative configuration, have been described as the most potent subgroup, the prototypical member of which, rolliniastatin-1, was originally isolated from Rollinia membaranacea seeds. In this report we describe the different structure-activity relationships (SAR) observed for some natural ACG and semisynthetic derivatives as growth inhibitors of human tumor breast, lung, liver, and colon cell lines. All the compounds assayed showed potencies in the micromolar range. Trends observed in the cytotoxicity assay have been compared with previous data reported for these compounds as inhibitors of mitochondrial respiratory chain.     

The use of molecular markers in farnesyltransferase inhibitor (FTI) therapy of breast cancer

The hypothesis that pharmacologic inhibitors of Ras can be effective anti-cancer agents has led to the development of Farnesyltransferase inhibitors (FTIs). These agents inhibit the requisite processing of a number of cellular proteins including Ras. FTIs have shown good anti-tumor efficacy and little toxicity in preclinical models and based on these results, numerous clinical trials are currently underway to evaluate the clinical potential of these agents in patients with cancer. However, contrary to the ideas that led to their design, mechanistic studies have not confirmed that they inhibit tumors through the inhibition of Ras. FTIs inhibit the growth of a broad variety of human tumor cells in vitro and studies to date have not identified cellular characteristics that predict the anti-tumor efficacy of this class of agents. We have studied a panel of breast cancer cell lines that differ widely in their sensitivity to FTI in order to determine which molecular characteristics may determine sensitivity to this class of agents. In these cells we find that FTI sensitivity does not correlate with the relative expression of Ras isoforms or the inhibition of Ras processing, growth factor signaling, expression of estrogen receptor or the overexpression of growth factor receptors. Looking for other molecular correlates of FTI sensitivity we have compared the activity of farnesylprotein transferase (FPTase) among these cells and although we find no overall correlation with FTI sensitivity, we find that two cell lines with unusually low FPTase activity are sensitive. Comparing p53 genotype with FTI-sensitivity we find that although most cell lines in our panel have mutant p53, all three cell lines with wild-type p53 are quite sensitive to FTI. In fact, MCF-7 cells which have both wild-type p53 and the lowest FPTase activity are the most FTI-sensitive cell type we have ever seen. Although these studies do not identify any single molecular marker that can accurately predict FTI sensitivity in breast tumors, they highlight the potential roles of FPTase activity and p53 function for further analysis.     

白细胞介素-15与肿瘤的相关性

白细胞介素-15 (IL-15)是一种多功能的细胞因子,是T细胞、B细胞、自然杀伤(NK)细胞、淋巴因子激活杀伤(LAK)细胞等细胞活化因子及诱导分泌细胞因子,有刺激造血干细胞增殖分化、增强免疫和抗肿瘤等作用.IL-15具有与白细胞介素-2(IL-2)类似的结构和功能,但许多活性作用强于IL-2,其与肿瘤的发生发展密切...     

Phase II study of uracil-tegafur in patients with metastatic pancreatic cancer

OBJECTIVE: Uracil-tegafur (UFT) has been reported to have a broad anti-tumor activity in a variety of malignancies including colorectal cancer and breast cancer. However, its activity in pancreatic cancer has not been fully evaluated. The aim of the present study was to evaluate the anti-tumor activity and toxicity of UFT in patients with metastatic pancreatic cancer. METHODS: All patients were required to have a pathologic diagnosis of pancreatic adenocarcinoma with measurable metastatic lesions, and no prior chemotherapy. A dose of 360 mg/m2/day of UFT was administered orally until the appearance of disease progression or unacceptable toxicity. RESULTS: Twenty-two patients were entered into this study. Of 21 patients evaluable for response, no patient achieved an objective tumor response; one showed no change, and the remaining 20 showed progressive disease. The median survival time for all patients was 4.2 (range: 0.9-9.0) months. The most common toxicities were nausea/vomiting and anorexia. Five patients (23%) had to discontinue UFT treatment because of gastrointestinal toxicity. CONCLUSION: This schedule of UFT did not demonstrate a significant anti-tumor activity against metastatic pancreatic cancer.     

Biological mechanisms of bevacizumab-associated adverse events

The perception that inhibition of cancer-associated angiogenesis would be an effective treatment strategy was based on the fundamental difference in cell cycle activity between neoplastic and normal endothelial cells. Selective targeting of tumor vessels could have additional benefits, such as circumventing development of acquired resistance to these types of agents, overcoming intrinsic tumor resistance, exhibiting broad anti-tumor activity and decreasing normal tissue toxicity. Successful translation of anti-angiogenic therapy into the clinical setting was achieved only 5 years ago with the approval of bevacizumab for metastatic colorectal cancer. Although the benefits demonstrated in clinical trials led to the approval of bevacizumab for treatment of colorectal, lung and breast cancers, and most recently glioblastoma, a number of serious soft-tissue and vascular toxicities have also been observed in patients receiving this anti-angiogenic agent. This review assesses the relationship between inhibition of VEGF and toxicity, and proposes the pathogenic mechanisms that lead to the adverse events.     

人类Runt相关转录因子3及其在肿瘤细胞质中的异位表达

人类Runt相关转录因子3(RUNX3)属于Runt转录因子家族成员,在某些肿瘤中RUNX3蛋白在肿瘤细胞质中异位表达,被认为是导致肿瘤发生发展的另一重要机制.目前认为RUNX3蛋自发挥何种作用取决于其在细胞中的表达部位,当在细胞核中表达时发挥抑癌作用,而在细胞质中表达时则发挥致癌作用.     

干扰素在胆系肿瘤治疗中的作用及其研究进展

干扰素是一种具有广泛生物活性的细胞因子,具有多方面的抗肿瘤作用。干扰素家族包括Ⅰ、Ⅱ、Ⅲ 3种类型。研究表明,Ⅰ型干扰素尤其是INF-α2b联合单药氟尿嘧啶（5-FU）或以其为基础的化疗方案对胆系肿瘤有效, 联合HELF方案（羟基喜树碱+足叶乙甙+亚叶酸钙+5-FU）对晚期胆囊癌疗效较好;Ⅱ型干扰素除有较好的免疫调节作用外,可有效抑制胆系肿瘤细胞生长和促进细胞凋亡,在与钙调素（CaM）拮抗剂、米非司酮及中药等联合运用时可增效;Ⅲ型干扰素目前仅用于病毒性疾病的治疗,但基础研究证实其抗肿瘤作用明确,值得进一步研究。本文就干扰素在胆系肿瘤治疗中的作用及其研究进展作一综述。     

Increase in tissue inhibitor of metalloproteinase-2 (TIMP-2) levels and inhibition of MMP-2 activity in a metastatic breast cancer cell line by an anti-invasive small molecule SR13179

Tissue inhibitor of metalloproteinase-2 (TIMP-2), the endogenous inhibitor of matrix metalloproteinase-2 (MMP-2), regulates tumor invasion by modulating the activity of MMP-2. In addition, TIMP-2 is involved in the direct regulation of cell growth and angiogenesis, independent of MMP inhibition. Therefore, the development of therapeutic agents that increase TIMP-2 levels may offer a novel and broad approach to anti-neoplastic therapy. We report that a novel small molecule synthetic flavanoid SR13179, which inhibits the invasion of a highly metastatic human breast cancer cell line MCF-10CA1a through Matrigel, significantly increases protein and mRNA levels of TIMP-2 in a time- and dose-dependent manner. SR13179 inhibits the gelatinolytic activity of MMP-2 by >50% but has no effect on MMP-2 protein expression. SR13179 also possesses potent anti-tumor activity in several tumor cell lines regardless of their hormone receptor, p53 or multi-drug resistance status. Given the multifunctional inhibitory activity of TIMP-2 on tumor growth and invasion, the observed increase in TIMP-2 expression by SR13179 may play a central role in the anti-tumor and anti-invasive activity of this novel small molecule. Modulation of TIMP-2 protein expression may be a new molecular target for anti-metastatic adjuvant therapy for breast and other cancers.