土槿乙酸衍生物的合成及其抗肿瘤活性

目的:研究土槿乙酸抗肿瘤作用的构效关系。方法:以土槿乙酸为原料,合成8个土槿乙酸衍生物,其结构经1H-NMR,MS证实。经MTT法筛选了衍生物的抗肿瘤活性。结果:8个化合物均为新化合物,除Ⅱc所有化合物均具有抗肿瘤活性,其中Ⅱf,Ⅱg的抗肿瘤活性显著高于土槿乙酸。结论:某些土槿乙酸酯和酰胺可提高抗肿瘤活性。     

葫芦素B抗肿瘤作用及其机制研究进展

葫芦素是从葫芦科等植物中分离的三萜类天然产物,具有多种药理作用。葫芦素B是葫芦素家族的重要成员,对多种肿瘤具有抑制作用,是潜在的抗肿瘤药物。葫芦素B能够抑制肿瘤细胞STAT3转录因子的活化,干扰丝裂原活化蛋白激酶信号转导通路,诱导细胞周期阻滞于G2/M期,诱导肿瘤细胞凋亡,引起细胞骨架变化。越来越多的研究表明,葫芦素B的抗肿瘤作用可能与其破坏肌动蛋白细胞骨架的活性密切相关。本文综述了葫芦素B的抗肿瘤作用及其可能的机制。     

Activity of safracins A and B, heterocyclic quinone antibiotics, on experimental tumors in mice

Safracins A and B, new antibiotics produced by Pseudomonas fluorescens A2-2, were tested for antitumor activity against mouse tumors. Structurally, these antibiotics belong to the saframycin family of antibiotics, and safracin B is 21-hydroxysafracin A. They showed antitumor activity against L1210 and P388 leukemias and B16 melanoma. The toxic and effective doses of safracin B were much lower than those of safracin A. Safracin B also prolonged the life span of tumor-bearing mice to a greater extent than safracin A. These results indicate that the alpha-carbinolamine structure plays an important role in the antitumor action of this type of antibiotic. Both safracins were, however, ineffective when their administration route differed from that used for inoculating tumor cells.     

白桦三萜类物质抗黑色素瘤B16、S180肉瘤作用及其机制的实验研究

目的　研究白桦三萜类物质 (triterpenesofbetulaplatyphyllasuk .TBP)抗黑色素瘤B16、S180肉瘤及其诱导细胞调亡作用和对细胞周期的影响。方法　建立小鼠体内荷黑色素瘤B16和腹水型S180肉瘤模型 ,测定TBP的抑瘤率和生命延长率。用形态学检测方法 (Giemsa染色法 )和流式细胞光度术检测TBP诱导的细胞调亡和对细胞周期的影响。结果　TBP具有明显的抗肿瘤作用 ,1 2 g·kg-1TBP对黑色素瘤B16的抑瘤率为 5 1 40 % ,对荷S180肉瘤小鼠生命延长率为 41 0 4%。可诱导B16和S180肿瘤发生细胞调亡 ,G0 /G1期细胞比例增加 ,S期细胞比例下降。结论　TBP可明显抑制黑色素瘤B16和S180肉瘤生长 ,其机制与诱导细胞调亡和阻断细胞生长于G0 /G1期有关。     

国产云芝多糖对小鼠抗肿瘤免疫反应的促进作用

本文采用观察同一个体多种指标的方法,研究国产云芝胞内多糖对C57BL/6J/J小鼠体内的黑色素瘤B16的抗瘤作用及其促进荷瘤鼠抗肿瘤免疫反应的作用.结果表明,这种云芝多糖对黑色素瘤B16的抑瘤率为40.8%,与环磷酰胺合用对黑色素瘤B16人工肺转移的抑制率达84.4%;其抗瘤作用机理以拮抗肿瘤的免疫抑制作用,多方面有效地促进行瘤鼠的非特异性抗肿瘤免疫反应为主,对正常机体的免疫反应也有一定促进作用.     

The double-edge role of B cells in mediating antitumor T-cell immunity: Pharmacological strategies for cancer immunotherapy

Emerging evidence reveals the controversial role of B cells in antitumor immunity, but the underlying mechanisms have to be explored. Three latest articles published in the issue 521 of Nature in 2015 reconfirmed the puzzling topic and put forward some explanations of how B cells regulate antitumor T-cell responses both positively and negatively. This paper attempts to demonstrate that different B-cell subpopulations have distinct immunological properties and that they are involved in either antitumor responses or immunosuppression. Recent studies supporting the positive and negative roles of B cells in tumor development were summarized comprehensively. Several specific B-cell subpopulations, such as IgG(+), IgA(+), IL-10(+), and regulatory B cells, were described in detail. The mechanisms underlying the controversial B-cell effects were mainly attributed to different B-cell subpopulations, different B-cell-derived cytokines, direct B cell-T cell interaction, different cancer categories, and different malignant stages, and the immunological interaction between B cells and T cells is mediated by dendritic cells. Promising B-cell-based antitumor strategies were proposed and novel B-cell regulators were summarized to present interesting therapeutic targets. Future investigations are needed to make sure that B-cell-based pharmacological strategies benefit cancer immunotherapy substantially.     

几类重要的海洋抗肿瘤药物研究进展

目前对海洋抗肿瘤药物的研究已经成为全世界普遍关注的热点。近年来，苔藓抑素、ecteinascidin-743、海兔毒肽、膜海鞘素、psammaplin、软海绵素B等六类化合物的研究取得了较大进展。本文综述这几类海洋抗肿瘤药物及其衍生物的研究进展，并探讨海洋抗肿瘤药物发展的趋势。     

肿瘤组织中的CYP1B1及其抑制剂的抗肿瘤活性

综述细胞色素P450酶（CYP）1B1在肿瘤组织中的表达、在肿瘤的发生发展和诊断与干预中的作用以及其抑制剂的研发和抗肿瘤活性。CYP1B1在正常组织中低表达,而在许多肿瘤组织中则特异性高表达,可激活和代谢产生致癌物质,并可致多种抗癌药物代谢失活而使肿瘤耐药,因此它既可用于早期癌症的诊断,又可作为理想的抗肿瘤作用靶点而用于药物研发。     

Combretastatin A4类似物研究新进展

Combretastatin A4(CA4)为非洲灌木矮柳树(Combretum caffrum)树皮植物中分离的一种具有抗肿瘤活性的化合物,为微管蛋白抑制剂。本文综述了近几年来对CA4类似物研究的新进展,其主要方法集中在对CA4中的A环、B环及其骨架结构的修饰。     

epothilone类构效关系及生物合成、转化的研究进展

epothilone类化合物大多数具有明显的抗肿瘤作用，并且在来源、合成方法、亲水性、抗肿瘤活性和抗肿瘤谱等方面均优于紫杉醇类药物，是一类新型抗肿瘤药物。近年来，对大量epothilone及其类似物进行了生物活性测定及药效学试验，并借助计算机分析，进行三维定量构效关系研究。在大规模发酵条件下，主要得到epothilone A和B以及C，D，E等少量成分，其中epothilone B和D被普遍认为是目前比较有效的抑瘤剂。这些化合物之间存在着某些生物转化关系，有可能会产生新的活性物质。本文主要叙述了该类化合物的构效关系、生物合成及相关转化的研究进展。     

黄疣海参皂苷 hillaside A 和 hillaside B 的体外抗真菌及抗肿瘤活性

目的阐明黄疣海参hillasideA和hillasideB的抗肿瘤及体外抗真菌活性。方法对黄疣海参的总提取物采取硅胶柱色谱及半制备高效液相色谱（HPLC）法等分离手段进行活性成分追踪分离,通过理化性质及波谱学手段进行化学结构鉴定,以磺酰罗丹明B蛋白染色（SRB）法评价化合物的抗肿瘤活性。结果分离得到了2个新的三萜皂苷元类化合物,命名为hillasideA和hillasideB。2个新化合物均显示了较强的体外抗真菌及抗肿瘤活性。结论研究为研制新的抗肿瘤药物提供了先导化合物,为充分开发利用我国的海洋生物资源提供了一定的物质基础和科学依据。     

Antitumoractive Endoperoxides from Triterpenes

A series of triterpene endoperoxides was synthesized and screened for antitumor activity in a panel of 15 human cancer cell lines by a sulforhodamine‐B (SRB) assay. The compounds induce apoptosis and show excellent antitumor activity.     

An ent-kaurene diterpene enhances apoptosis induced by tumor necrosis factor in human leukemia cells

Some antitumor agents, including tumor necrosis factor-alpha (TNF-alpha) and camptothecin (CPT), often cause resistance of tumor cells to antitumor agents through activation of the nuclear factor-kappa B (NF-kappa B) pathway that leads to up-regulation of anti-apoptotic proteins. Therefore, co-treatment of an inhibitor of the NF-kappa B pathway with antitumor agents is a useful strategy for chemotherapy. Here we report that ent-11 alpha-hydroxy-16-kauren-15-one (KD) selectively inhibits NF-kappa B-dependent gene expression due to treatment with TNF-alpha. KD in combination with TNF-alpha caused a dramatic increase in apoptosis in human leukemia cells accompanied by activation of caspases. A broad-spectrum inhibitor of caspases decreased the apoptosis induced by treatment with KD and TNF-alpha. KD in combination with CPT also caused an increase in apoptosis. These results suggest that the apoptotic potency of co-treatment of KD with TNF-alpha or CPT is elicited through selective inhibition of NF-kappa B-dependent anti-apoptotic proteins and thus may provide a basis for the development of useful approaches to the treatment of leukemia.     

Sultriecin, a new antifungal and antitumor antibiotic from Streptomyces roseiscleroticus. Production, isolation, structure and biological activity.

Streptomyces roseiscleroticus L827-7 (ATCC 53903) produced a novel antifungal and antitumor antibiotic, sultriecin. It exhibited in vitro antifungal activity and potent in vivo antitumor activity against P388 and L1210 leukemias, and B16 melanoma. Sultriecin is composed of several unique structural units; a conjugated triene, an alpha,beta-unsaturated delta-lactone, and a sulfate functionality.     

跨膜型超抗原金黄色葡萄球菌肠毒素A融合蛋白的抗肿瘤作用

目的　为扩大超抗原金黄色葡萄球菌肠毒素A(SEA)的抗瘤谱 ,制备跨膜型SEA融合蛋白 ,研究该蛋白制备的肿瘤疫苗的抗肿瘤作用。方法　在荷B16黑色素瘤的C5 7BL/ 6小鼠上 ,观察跨膜型SEA融合蛋白制备的肿瘤疫苗对荷瘤小鼠的免疫治疗作用和免疫保护作用 ,并通过乳酸脱氢酶 (LDH)释放法检测治疗组和免疫组小鼠脾细胞的天然杀伤细胞(NK)和细胞毒性T细胞 (CTL)活性。结果　融合蛋白制备的肿瘤疫苗能够显著抑制荷瘤小鼠肿瘤的生长 ,并延长其生存期 ,其脾细胞的NK和CTL活性显著增强。同时 ,该肿瘤疫苗对同种肿瘤细胞攻击可产生较强的免疫保护作用。结论　跨膜型SEA融合蛋白制备的肿瘤疫苗具有显著的抗肿瘤作用 ,可有效激发荷瘤小鼠机体的特异性和非特异性抗肿瘤免疫应答 ,增强CTL和NK活性。     

2014—2016年辽宁省肿瘤医院抗生素类抗肿瘤药的使用情况分析

目的 分析2014—2016年辽宁省肿瘤医院抗生素类抗肿瘤药物的使用情况,为临床合理应用抗肿瘤药物提供参考.方法 对2014—2016年辽宁省肿瘤医院抗生素类抗肿瘤药物的使用金额、用药频度(DDDs)、日均费用(DDC)及药品排序比(B/A)进行统计与分析.结果 2014—2016年抗生素类抗肿瘤药物的总使用金额和DDDs未出现逐年增长的趋势.吡柔比星的使用金额逐年递增.表柔比星、多柔比星脂质体、多柔比星使用金额逐年递减.从排序来看,表柔比星、吡柔比星与多柔比星脂质体的使用金额连续3年排前3位.表柔比星与吡柔比星的DDDs排名持续居于前2位.抗生素类抗肿瘤药物的DDC及其排序相对稳定,多柔比星脂质体的DDC持续居于首位.大部分抗生素类抗肿瘤药物的B/A值接近于1.00.结论 辽宁省肿瘤医院抗生素类抗肿瘤药物使用基本合理,符合安全、有效、经济、方便的原则.     

Tallysomycin, a new antitumor antibiotic complex related to bleomycin. III. Antitumor activity of tallysomycins A and B.

The antitumor activity of tallysomycins A and B was determined in five experimental tumor systems in mice. Tallysomycins A and B were highly active against B16 melanoma, sarcoma 180 ascites tumor and Lewis lung carcinoma, and moderately active against P388 leukemia but were without effect on lymphoid leukemia L1210. The antitumor activity of tallysomycin A was 2 to 3 times that of tallysomycin B and 3 to 17 times that of bleomycin. Tallysomycin A was about 1.5 and 4 times more toxic for mice than tallysomycin B and bleomycin, respectively, in terms of subacute LD50 values.     

A new antitumor antibiotic, FR900840. III. Antitumor activity against experimental tumors

FR900840 [2S)-2-amino-2-carboxyethyl (3R)-2-diazo-3-hydroxybutyrate), a new antibiotic with antitumor activity was isolated from the fermentation broth of Streptomyces sp. No. 8727. Its antitumor activity was examined in three mouse tumor systems and ten human tumor systems. FR900840 had no clear effect on mouse ascitic tumors, P388 and L1210, and the B16 melanoma line, but had prominent antitumor effects on several human solid tumors. Its antitumor activity against A549 human lung adenocarcinoma was stronger than those of vinblastine, doxorubicin and cisplatin. These results suggest that FR900840 may become a useful prototype antitumor drug.     

Polyamine transporter recognization and antitumor effects of anthracenymethyl homospermidine

This study was conducted to examine the polyamine transporter (PAT) recognization and antitumor effects of anthracenymethyl homospermidine (ANTMHspd) and its apoptotic mechanism in B16 melanoma cells. ANTMHspd promoted a dose-dependent apoptosis in B16 melanoma cells and the apoptosis was associated with the excellent PAT recognization, externalization of cell membrane phosphatidylserine and the disruption of mitochondria, these processes were correlated with up-regulation of polyamine oxidase, an increase in intracellular reactive oxygen species (ROS) production and oxidative stress. In addition, reduction of MMP, release of cytochrome c, up-regulation of Bax protein expression, down-regulation of Bcl-2 protein expression, and activation of caspase-3, caspase-9 were also observed in B16 cells after treatment with ANTMHspd. Furthermore, N-acetylcysteine obviously antagonized ANTMHspd-induced apoptosis. Importantly, ANTMHspd was found to be better tolerated and revealed potent antitumor effect on inhibiting tumor growth in situ and suppressing pulmonary metastasis in xenograft mice model. These data demonstrate that ANTMHspd is an excellent PAT recognization and potent antitumor agent.     

Correlation of the in vitro cytotoxic and in vivo antitumor activities of gold(I) coordination complexes

A series of gold(I) coordination complexes including analogues of the antiarthritic agent auranofin 1 were evaluated for in vitro cytotoxic potency against both B16 melanoma cells and P388 leukemia cells and in vivo antitumor activity against P388 leukemia in mice. A number of the complexes showed potent cytotoxic activity in vitro and antitumor activity in vivo, with the phosphine-coordinated gold(I) thiosugar complexes demonstrating the greatest in vitro and in vivo activity. The data compiled for 63 complexes of the general structural formula LAuX provide the basis for the following observations: potent in vitro cytotoxic activity is observed for substituted (phosphine) gold complexes, lack of potency in vitro correlates well with lack of antitumor activity, potent cytotoxicity in vitro is not necessarily predictive of activity in vivo, in vivo antitumor activity is generally optimized by ligation of Au(I) with a substituted phosphine and a thiosugar.