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1.
《Biomaterials》2015
Bioreducible heparin (HEP)-based nanogels were prepared by derivatizing HEP with vinyl group followed by copolymerizing with cystamine bisacrylamide in aqueous medium in the absence of surfactant. The hydrodynamic diameter of the HEP nanogels could be tuned in the range from 80 to 200 nm. Doxorubicin (DOX) was loaded into the HEP nanogels, and high drug loading content (30%) and efficiency (90%) were achieved. In vitro drug release test revealed that this drug delivery system exhibited strongly redox-sensitive drug release behavior that would greatly favor the in vivo drug delivery performance of the nanogels. After injected into tumor-bearing mice through tail vein, the DOX-loaded HEP nanogels showed remarkable accumulation in tumors as demonstrated by in vivo near infared fluorescence imaging and ex vivo DOX concentration measurements. The doxorubicin accumulation at tumor site goes beyond 9% injected dose per gram of tumor through such delivery system, making that DOX-loaded HEP nanogels have significantly superior in vivo antitumor activity. 相似文献
2.
《药学学报(英文版)》2020,10(7):1294-1308
A great challenge in multi-targeting drug discovery is to identify drug-like lead compounds with therapeutic advantages over single target inhibitors and drug combinations. Inspired by our previous efforts in designing antitumor evodiamine derivatives, herein selective histone deacetylase 1 (HDAC1) and topoisomerase 2 (TOP2) dual inhibitors were successfully identified, which showed potent in vitro and in vivo antitumor potency. Particularly, compound 30a was orally active and possessed excellent in vivo antitumor activity in the HCT116 xenograft model (TGI = 75.2%, 150 mg/kg, p.o.) without significant toxicity, which was more potent than HDAC inhibitor vorinostat, TOP inhibitor evodiamine and their combination. Taken together, this study highlights the therapeutic advantages of evodiamine-based HDAC1/TOP2 dual inhibitors and provides valuable leads for the development of novel multi-targeting antitumor agents. 相似文献
3.
作者用同位数前体参入法及透射与扫描电镜研究了平阳霉素(博莱霉素A_5)对HeLa细胞大分子生物合成及超微结构的影响。结果显示:平阳霉素能抑制HeLa细胞DNA,RNA和蛋白质的生物合成,对DNA的抑制作用强,ID_(50DNA)为42.77μg/ml。表现为:染色质减少,核内电子密度低,核仁分离及“核仁帽”形成,细胞表面微绒毛消失或变形,最终导致质膜破裂等。作者认为,细胞膜是否为此类药物作用的靶位值得进一步研究。 相似文献
4.
毛喉萜对人肝癌细胞增殖影响的实验研究 总被引:1,自引:0,他引:1
目的 探讨毛喉萜 (Forskolin)的抗肝癌作用。方法 采用克隆形成、MTT比色法观察毛喉萜对SMMC 772 1细胞的作用 ,并利用免疫细胞化学方法检测其对rasp2 1、p5 3蛋白表达的影响。结果 毛喉萜可明显抑制SMMC 772 1细胞的增殖 ,其抑制率与剂量呈正相关 (P <0 .0 1 ) ,经毛喉萜处理后 ,rasp2 1、p5 3蛋白表达均有明显下降。结论 毛喉萜能明显抑制肝癌SMMC 772 1细胞增殖 ,其作用可能与降低rasp2 1、p5 3蛋白表达有关。 相似文献
5.
6.
几种植物来源不同作用机制的抗癌药抗侵袭作用 总被引:4,自引:0,他引:4
用细胞培养法和癌细胞侵袭实验,观察几种植物来源不同作用机理的抗癌药如紫杉醇、三尖杉酯碱、高三尖杉酯碱及喜树碱[1],对黑色素瘤高转移株B16-BL6细胞及人纤维肉瘤细胞HT-1080的细胞毒作用和抗侵袭作用。结果表明紫杉醇、三尖杉酯碱、高三尖杉酯碱及喜树碱对B16-BL6和HT-1080细胞增殖均有很强的抑制作用。紫杉醇、三尖杉酯碱及高三尖杉酯碱对B16-BL6细胞侵袭和运动也有明显的抑制作用,而喜树碱在同样浓度下对B16-BL6细胞侵袭和运动均无明显抑制。 相似文献
7.
M. R. Schneider M. L. Schuderer 《Journal of cancer research and clinical oncology》1988,114(6):583-587
Summary A 1,1,2-triphenylbut-1-ene with a 4-OH group at one C-1 phenyl ring and a chlorocarbamate mustard moiety at the second C-1 ring (compound 3) was synthesized in order to obtain a cytotoxic estrogen with a specific antitumor effect on estrogen-receptor-containing tumors. This compound was tested in comparison to the carrier (compound 1) and a compound (2) having a carbamate mustard group on both C-1 phenyl rings. The estrogen receptor affinity of compound 3 was only about one-quarter lower than that of compound 1, but much higher than that of compound 2. Compounds 2 and 3 showed only partially irreversible binding to the receptor owing to their relatively low alkylating properties. The growth inhibition of the receptor-positive MCF-7 breast cancer cell line by compound 3, but not by compound 1 or 2, was more pronounced than the inhibition of the receptor-negative line MDA. In vivo the hormone-dependent, transplantable mammary tumor MXT M3.2 of the mouse was much better inhibited by compound 3 than its hormone-resistent line MXT OVEX. Compounds 1–3 had no antiestrogenic properties in the mouse, but estrogenic activity was in the order 1>3>2. From these results and because the antitumor activity of compound 3 was superior to that of compounds 1 and 2 in the hormone-dependent tumor models, a selective, receptor-mediated cytotoxic effect of compound 3 on estrogen-receptor-positive tumors in obvious.Supported by the Deutsche Forschungsgemeinschaft, SFB 234 and the Matthias Lackas StiftungDedicated to Prof. Dr. M. F. El Etreby on the occasion of his 50th birthday 相似文献
8.
新城疫病毒pIRHN核酸疫苗构建和表达及对肿瘤细胞的影响 总被引:6,自引:0,他引:6
目的:研究NDV HN基因抗肿瘤作用及其可能机制。方法:以 pIRES1neo为表达载体构建了 NDV HN基因的pIRHN核酸疫苗,在体外转染HeLa细胞,用间接免疫荧光和Western blot检测pIRHN在真核细胞中表达状况,用荧光显微镜、DNA琼脂糖电泳及TUNEL染色等方法,检测HN基因导致细胞死亡的类型;用3,5-二羟基甲苯法测定HeLa细胞唾液酸含量的变化。结果:pIRHN 转染HeLa细胞后,能够在真核细胞中表达,能促进肿瘤细胞死亡,其死亡方式主要以诱导细胞凋亡为主,pIRHN使 HeLa细胞唾液酸含量减少。结论:用 NDV HN基因所构建的核酸疫苗能够在真核细胞中高效表达,表达的 HN蛋白主要位于胞膜,胞浆中亦有 HN蛋白表达;pIRHN具有抗肿瘤作用,可能通过其表达产物与肿瘤细胞唾液酸受体的相互作用,发挥其抗肿瘤作用。本实验为迸一步阐明NDV抗肿瘤作用机制提供了理论依据。 相似文献
9.
Paola Paglia Ivano Arioli Nicole Frahm Trinad Chakraborty Mario P. Colombo Carlos A. Guzmn 《European journal of immunology》1997,27(6):1570-1575
Listeria monocytogenes has been proposed as a carrier to elicit major histocompatibility complex class-I restricted immune responses able to protect against tumor challenge. In this study the properties of the attenuated L. monocytogenes Δmpl2 mutant has been evaluated in vivo against a highly aggressive mouse fibrosarcoma which expresses β-galactosidase (β-gal) as a tumor-associated antigen (TAA). Immunization with the vaccine prototypes resulted in both elicitation of specific antibodies and generation of cytotoxic lymphocytes (CTL). Oral vaccination protected 55–64% of the immunized animals from tumor take (p < 0.01) and strongly reduced the average size of the tumor in the other 34–45% (p < 0.01). Vaccinated mice developed a long-lasting response, which resulted in 100% protection from a subsequent tumor challenge. Substitution of the whole TAA by its CTL-defined immunodominant epitope resulted in 43% protection, suggesting a contribution of the humoral response to the observed antitumor effect. No statistically significant differences were observed in the antitumor response when mice were immunized with strains expressing the immunodominant TAA epitope in the context of carrier proteins which were either exported or restricted to the bacterial cytoplasm. This suggests that the topology of the recombinant antigen does not play a major role in the outcome of the protective response. 相似文献
10.
Yasutake N Matsuzaki T Kimura K Hashimoto S Yokokura T Yoshikai Y 《Medical microbiology and immunology》1999,188(1):9-14
The involvement of several cytokines in the antitumor effect induced by intrapleural (i.pl.) injection of heat-killed cells
of Lactobacillus casei strain Shirota (LC 9018) in mice was investigated. Injection of LC 9018 i.pl. into Meth A fibrosarcoma (Meth A)-bearing mice
not only significantly prolonged the survival of the mice, but also effectively inhibited the accumulation of malignant pleural
fluid in the thoracic cavity. In the thoracic cavity of tumor-bearing mice treated with LC 9018, we observed large amounts
of several cytokines including interleukin (IL)-1β, interferon (IFN)-γ, IL-12 and tumor necrosis factor (TNF)-α. Both anti-IFN-γ
and anti-IL-12 monoclonal antibody (mAb) treatments partially diminished the antitumor activity of LC 9018 in vivo, while
the treatment of anti-IL-1β mAb did not influence the survival of the mice. However, anti-TNF-α mAb treatment completely abolished
the antitumor effect of LC 9018 in vivo, suggesting that in this model LC 9018 has a survival-prolonging effect involving
certain cytokines. Moreover, i.pl. injection of mouse recombinant TNF-α into Meth A-bearing mice pretreated with anti-TNF-α
mAb partially restored the survival-enhancing effect of LC 9018. These results led us to conclude that TNF-α induced by i.pl.
injection of LC 9018 plays an important role in the antitumor effect of LC 9018 in vivo.
Received: 22 February 1999 相似文献