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排序方式: 共有1509条查询结果,搜索用时 273 毫秒
1.
Tycel J. Phillips Jean-Marie Michot Vincent Ribrag 《Clinical Lymphoma, Myeloma & Leukemia》2021,21(1):8-20.e3
Although outcomes after first-line therapy for patients with indolent or aggressive non-Hodgkin lymphoma (NHL) are continually improving, relapse is still common. Current treatment options for patients with relapsed or refractory disease have limited efficacy, and various targeted therapies are under investigation to help improve outcomes in this patient population. The phosphatidylinositol 3-kinase (PI3K) pathway was identified as being involved in hematologic malignancies, leading to significant research for potential therapeutic agents. This has led to 3 PI3K inhibitors (idelalisib, copanlisib, and duvelisib) being approved for the treatment of patients with relapsed or refractory follicular lymphoma who have received at least 2 prior systemic therapies, with reported response rates of 40% to 59%. With potential class-specific and PI3K isoform–related toxicities that may limit clinical utility, the safety of the approved PI3K inhibitors has been carefully evaluated to weigh the risk/benefit ratio of therapy. Currently, there are no approved PI3K inhibitors for patients with aggressive NHL. A number of newer PI3K inhibitors are in clinical development for the treatment of relapsed or refractory NHL, aiming to improve treatment benefit for patients. We discuss a number of attributes that are important to increase the therapeutic potential of newer PI3K inhibitors. More promising results may come from combination trials with these newer PI3K inhibitors, developed to limit toxicities (including long-term adverse events), and other antitumor agents. 相似文献
2.
《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
3.
《Journal of Pharmaceutical Analysis》2020,10(4):376-384
5-Dimethylaminopropylamino-8-hydroxytriazoloacridinone (C-1305) is a promising antitumor compound developed in our laboratory. A better understanding of its metabolic transformations is still needed to explain the multidirectional mechanism of pharmacological action of triazoloacridinone derivatives at all. Thus, the aim of the current work was to predict oxidative pathways of C-1305 that would reflect its phase I metabolism. The multi-tool analysis of C-1305 metabolism included electrochemical conversion and in silico sites of metabolism predictions in relation to liver microsomal model. In the framework of the first approach, an electrochemical cell was coupled on-line to an electrospray ionization mass spectrometer. The effluent of the electrochemical cell was also injected onto a liquid chromatography column for the separation of different products formed prior to mass spectrometry analysis. In silico studies were performed using MetaSite software. Standard microsomal incubation was employed as a reference procedure. We found that C-1305 underwent electrochemical oxidation primarily on the dialkylaminoalkylamino moiety. An unknown N-dealkylated and hydroxylated C-1305 products have been identified. The electrochemical system was also able to simulate oxygenation reactions. Similar pattern of C-1305 metabolism has been predicted using in silico approach. Both proposed strategies showed high agreement in relation to the generated metabolic products of C-1305. Thus, we conclude that they can be considered as simple alternatives to enzymatic assays, affording time and cost efficiency. 相似文献
4.
β-紫罗兰酮(β-Ionone,BI)是一类环化异戊二烯,广泛分布于水果和蔬菜中。BI具有多种生物活性,其抗癌活性是当前研究的热点,并可成为一种潜在的癌症化学预防剂。为更好地理解其抑制肿瘤方面的作用及其机制,本文对BI近年来研究进展进行简要地综述。 相似文献
5.
《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
6.
目的 综述目前pH敏感纳米递药系统用于肿瘤靶向治疗中的国内外研究进展。方法 在Pubmed和Google上检索近年国内外资料,阐明pH敏感纳米递药系统靶向肿瘤治疗的作用机制,对超顺磁性纳米粒、胶束、树状大分子等相关研究成果进行总结和评价。结果 传统肿瘤化疗药物普遍存在疗效低、副作用大等问题,而近年来研发的pH响应的纳米载体可通过EPR效应积聚于肿瘤组织,并在弱酸性的肿瘤细胞外液或经内吞作用后在细胞质或溶酶体中释放药物。该pH敏感型载体能促进药物的靶向递送,在减少系统性副作用的同时提高肿瘤化疗疗效。结论 pH敏感纳米递药系统在肿瘤靶向治疗中具有广阔的应用前景,开发具有靶向性、高效性、安全性的递药系统是目前该领域研究主要方向之一。 相似文献
7.
Marı́a I. Rodrı́guez Tulio Chávez-Gil Yasiris Colón Naomi Dı́az Enrique Meléndez 《Journal of electroanalytical chemistry (Lausanne, Switzerland)》2005,576(2):315-322
The binding interactions of molybdenocene dichloride (Cp2MoCl2) and [Cp2Mo(L)n]Cl2 (n = 1, L = 6-mercaptopurine, 6-mercaptopurineribose, 2-amine-6-mercaptopurine and 2-amine-6-mercaptopurineribose and n = 2, L = d-penicillamine) complexes with calf-thymus DNA have been investigated by cyclic voltammetry. Cp2MoCl2 belongs to a group of metallocene antitumor agents and [Cp2Mo(L)n]Cl2 complexes are structural modifications of molybdenocene dichloride that have also been shown to possess antitumor properties. From the mechanistic point, there is interest in discovering whether molybdenocene dichloride binds DNA or not. To investigate this issue in more detail, we carried out molybdenocene–DNA titrations monitored by cyclic voltammetry. The changes in oxidation potentials (Epa) allowed us to determine the degree of Mo–DNA interaction. (Cp2MoCl2) and [Cp2Mo(L)n]Cl2 (n = 1, L = 2-amine-6-mercaptopurine and 2-amine-6-mercaptopurineribose and n = 2, L = d-penicillamine) complexes showed weak DNA bindings (3.2–10.1%) while the complexes containing the ligands 6-mercaptopurine and 6-mercaptopurineribose showed negligible interactions. ICP-AES was used to corroborate the CV results. 相似文献
8.
【摘要】 目的 探讨达卡巴嗪长循环脂质体(PEGylated dacarbazine liposome,PEG-DTIC-LP)的制备及体内抗肿瘤效应。 方法 采用硫酸铵梯度法制备PEG-DTIC-LP,考察其包封率、载药量、形态、粒径、Zeta电位、稳定性、体外释药性等性质。建立荷黑色素瘤小鼠模型,将小鼠分为生理盐水组、空白脂质体组、DTIC溶液组、PEG-DTIC-LP组4组,每组6只,雌雄各半。于第1、3、5、7、9天按10 mg/kg给药剂量给生理盐水组小鼠尾静脉注射生理盐水,空白脂质体组尾静脉注射空白脂质体混悬液,DTIC溶液组尾静脉注射1mg/mL DTIC溶液,PEG-DTIC-LP组尾静脉注射1 mg/mL PEG-DTIC-LP混悬液。以肿瘤体积、小鼠体重、中位生存时间为评价指标,研究PEG-DTIC-LP的抗肿瘤效应。 结果 制备的PEG-DTIC-LP为半透明乳白色有蓝色乳光的液体;包封率为(60.41±2.47)%,载药量为(5.95±0.24)%;平均粒径为190nm,Zeta电位为-53.8mV;放置7天后PEG-DTIC-LP包封率无显著变化(P>0.05),放置14天后包封率下降明显(P<0.05);PEG-DTIC-LP组荷瘤小鼠的肿瘤体积显著小于DTIC组与生理盐水组(P<0.05),但与空白脂质体组比较差异无统计学意义(P>0.05);中位生存时间PEG-DTIC-LP组>空白脂质体组>生理盐水组>DTIC溶液组(P<0.05);PEG-DTIC-LP组体重低于其余三组(P<0.05)。 结论 将达卡巴嗪制备成长循环脂质体有利于提高其抗肿瘤效应。 相似文献
9.
10.
基因工程肿瘤细胞融合疫苗诱导Th1应答抗肿瘤 总被引:5,自引:0,他引:5
目的 探讨基因工程肿瘤细胞融合疫苗的抗肿瘤作用。方法 将鼠源性IL 12 (mIL 12 )基因转染J5 5 8细胞制备工程瘤细胞 ,再与树突状细胞进行融合后免疫BALB c小鼠 ,14d后再以不同剂量的瘤细胞攻击小鼠以观察其保护效力。结果 制备的工程瘤细胞J5 5 8经测试其培养上清中mIL 12表达量为 (870± 6 0 )pg·(10 5细胞 ) - 1 ·ml- 1 ;与树突状细胞体外融合后 ,镜下测得细胞融合率约为 30 % ;收集免疫小鼠腹股沟及月国窝淋巴结细胞与肿瘤细胞共培养 ,其上清IFN γ含量较对照组高 ;体内、外特异性抗肿瘤实验均显示该型瘤苗具有良好的抗瘤作用。结论 免疫小鼠体内诱导Th1应答 ,其明显的抗肿瘤功效为临床应用提供了可能性 相似文献