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抗肿瘤药物--格列卫 总被引:3,自引:0,他引:3
格列卫为人工合成的酪氨酸激酶抑制剂,已成功用于血液系统肿瘤,尤其是慢性髓细胞白血病的治疗,并正试用于胃肠基质瘤、小细胞肺癌以及胶质母细胞瘤等实体肿瘤的治疗。本文就格列卫的作用机制、适应证以及不良反应作简要的探讨。 相似文献
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新型蛋白酪氨酸激酶抑制剂类抗肿瘤药物的研究进展 总被引:6,自引:0,他引:6
目的探讨蛋白酪氨酸激酶抑制剂抗肿瘤作用机理及其研究进展。方法综述了最新发现的小分子酪氨酸激酶抑制剂的化学结构、抗肿瘤作用及其作用机制及其发展方向等内容。结果结论蛋白酪氨酸激酶与细胞的增殖、分化、迁移和凋亡有着密切的关系,在细胞生命活动的信号转导途径中扮演着十分关键的角色,筛选酪氨酸激酶抑制剂已经成为开发抗肿瘤药物的新途径。 相似文献
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134例抗肿瘤药物的不良反应回顾性分析 总被引:1,自引:0,他引:1
目的分析抗肿瘤药物的不良反应(ADR)规律及其特点,为临床合理用药提供参考。方法对我院2009年收集的134例抗肿瘤药物的不良反应报告进行回顾性分析。结果抗肿瘤药物涉及的不良反应以中老年为多,吉非替尼、厄洛替尼、索拉非尼所致不良反应居前三位,皮肤及其附件损害最常见。结论临床上应加强对抗肿瘤药物的监测,以减少或避免不良反应的发生。 相似文献
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蛋白酪氨酸激酶抑制剂类抗肿瘤药物的不良反应及疗效性价比 总被引:1,自引:0,他引:1
目的:探讨蛋白酪氨酸激酶抑制剂抗肿瘤的不良反应与疗效性价比。方法:回顾性分析2007年1月1日-2008年12月30日的抗肿瘤蛋白酪氨酸激酶抑制剂的不良反应报告。结果:VEGFR引起的不良反应数最好;主要的不良反应的临床表现都是变态反应与消化系统反应;多靶点酪氨酸激酶抑制剂的价值相对较高。结论:蛋白酪氨酸激酶与细胞的增殖、分化、迁移和凋亡有着密切的关系,筛选出合理酪氨酸激酶抑制剂已经成为开发抗肿瘤药物的新途径。 相似文献
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蛋白酪氨酸激酶信号转导途径与抗肿瘤药物 总被引:3,自引:0,他引:3
细胞信号转导(signal transduction)在细胞的代谢、分裂、分化、生物功能及死亡过程中起着重要作用,肿瘤的发生和发展与细胞信号转导过度激活有关。本文简要阐述了蛋白酪氨酸激酶(protein tyrosine kinases,PTKs)介导的信号转导途径,分别介绍了受体酪氨酸激酶介导的Ras/Raf/MAPK和PI-3K/Akt途径,非受体酪氨酸激酶介导的Src、Bcr-Abl和JAK/STAT途径。以此5条信号转导通路中参与的重要蛋白分子为靶点,统计和介绍了相关的已经上市或处于临床研究的抗肿瘤药物。 相似文献
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抗肿瘤药L in ifan ib 总被引:1,自引:0,他引:1
血管生成是毛细血管从已存在的血管网络中生长出来的生理过程,可满足组织生成时的营养供给,对于肿瘤的维持或生长至关重要,因此,血管生成抑制剂被认为是癌症治疗的有效手段。 相似文献
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Abbas R Hug BA Leister C Burns J Sonnichsen D 《British journal of clinical pharmacology》2011,71(4):522-527
AIM
The primary objective was to evaluate the pharmacokinetics of a single dose of neratinib, a potent, low-molecular-weight, orally administered, irreversible pan-ErbB (ErbB-1, -2, -4) receptor tyrosine kinase inhibitor, during co-administration with ketoconazole, a potent CYP3A4 inhibitor.METHODS
This was an open-label, randomized, two-period, crossover study. Fasting healthy adults received a single oral dose of neratinib 240 mg alone and with multiple oral doses of ketoconazole 400 mg. Blood samples were collected up to 72 h after each neratinib dose. Plasma concentration data were analyzed using a noncompartmental method. The least square geometric mean ratios [90% confidence interval (CI)] of Cmax(neratinib+ketoconazole) : Cmax(neratinib alone), and AUC(neratinib+ketoconazole) : AUC(neratinib alone) were assessed.RESULTS
Twenty-four subjects were enrolled. Compared with neratinib administered alone, co-administration of ketoconazole increased neratinib Cmax by 3.2-fold (90% CI: 2.4, 4.3) and AUC by 4.8-fold (3.6, 6.5). Median tmax was 6.0 h with both regimens. Ketoconazole decreased mean apparent oral clearance of neratinib from 346 l h−1 to 87.1 l h−1 and increased mean elimination half-life from 11.7 h to 18.0 h. The incidence of adverse events was comparable between the two regimens (50% neratinib alone, 65% co-administration with ketoconazole).CONCLUSION
Co-administration of neratinib with ketoconazole, a potent CYP3A inhibitor, increased neratinib Cmax by 3.2-fold and AUC by 4.8-fold compared with administration of neratinib alone. These results indicate that neratinib is a substrate of CYP3A and is susceptible to interaction with potent CYP3A inhibitors and, thus, dose adjustments may be needed if neratinib is administered with such compounds. 相似文献12.
《Expert opinion on investigational drugs》2013,22(11):1735-1751
Background: The revolutionary success of imatinib, a specific inhibitor of the BCR-ABL tyrosine kinase (TK) in the treatment of chronic myelogenous leukemia ushered in the era of targeted therapies in cancer. The erythroblastic leukemia viral oncogene homolog family of receptor TKs, to which EGFR (HER1) and human epidermal growth factor receptor 2 (HER2)/neu TKs belong, has been implicated in a variety of cancers, and several agents that inhibit these TKs are in clinical use, with many more in various stages of development. Objectives: To summarize current knowledge about neratinib (HKI-272), an oral, irreversible dual inhibitor of EGFR and HER2 and to define its future clinical role, especially in the context of related agents that are either available or in the pipeline. Methods: A Medline search using Pubmed was conducted using the keywords neratinib, HKI-272, EGFR, HER2, lapatinib, trastuzumab, erlotinib, gefitinib, cetuximab and panitumumab. Relevant abstracts presented at the American Society of Clinical Oncology and San Antonio Breast Cancer Symposium meetings were also reviewed. Conclusions: Both preclinical and human studies have shown that neratinib has promising activity in both advanced breast cancer and NSCLC with an acceptable safety profile. The data support its continued clinical development. 相似文献
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樊艳 《中国医院药学杂志》2015,35(17):1571-1574
目的:探讨来那替尼对人乳腺癌细胞增殖、凋亡的影响及其作用机制。方法:以0,0.5,1和2 μmol·L-1四种浓度的来那替尼处理人乳腺癌细胞BT474,MTT法检测其对细胞增殖的影响;流式细胞术检测其对细胞生长周期及凋亡的影响;蛋白免疫印迹法检测其对细胞凋亡信号通路相关蛋白的表达水平。结果:MTT实验结果表明来那替尼可显著抑制人乳腺癌细胞的增殖,2 μmol·L-1来那替尼处理96 h后,其细胞存活率为31%;流式细胞分析结果表明来那替尼可将BT474细胞阻滞在G0/G1期,2 μmol·L-1来那替尼阻滞效果最为明显,处于G0/G1期的细胞百分比为76%;来那替尼也可促进细胞凋亡,2 μmol·L-1剂量时凋亡率为19.3%。蛋白免疫印迹结果表明来那替尼可减弱细胞内AKT、mTOR的磷酸化蛋白表达水平。结论:来那替尼可能通过抑制细胞内PI3K-AKT-mTOR信号通路促进乳腺癌细胞凋亡,为乳腺癌的治疗提供理论依据。 相似文献
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抗肿瘤药物苹果酸舒尼替尼的合成 总被引:1,自引:0,他引:1
目的 合成抗肿瘤药物苹果酸舒尼替尼。方法 以乙酰乙酸叔丁酯为起始原料,通过Knorr吡咯合成法、脱叔丁氧羰基、Vilsmeier甲酰化、酯水解反应得中间体5-甲酰基-2,4-二甲基-1H-吡咯-3-羧酸(6),6与碳酰二咪唑反应生成酰基咪唑,不经分离直接用“一锅煮”方法与5-氟吲哚啉-2-酮和2-(二乙氨基)乙二胺缩合,最后成盐得到苹果酸舒尼替尼。 结果与结论 合成的苹果酸舒尼替尼经核磁共振、质谱和元素分析确证结构,总收率达28%。 相似文献
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Roccaro AM Hideshima T Richardson PG Russo D Ribatti D Vacca A Dammacco F Anderson KC 《Current pharmaceutical biotechnology》2006,7(6):441-448
The ubiquitin-proteasome pathway (UPP) is the major non-lysosomal proteolytic system in the cytosol and nucleus of all eukaryotic cells. Bortezomib (also known as PS-341 and Velcade) is a proteasome inhibitor, a novel class of cancer therapies. Bortezomib blocks multi-ubiquitinated protein degradation by inhibiting 26S proteasome activity, including regulating cell cycle, anti-apoptosis, and inflammation, as well as immune surveillance. In multiple myeloma (MM) cells, bortezomib directly induces cell stress response followed by activation of c-Jun NH(2) terminal kinase (JNK)/stress-activated protein kinase (SAPK), and triggers caspase-dependent apoptosis of tumor cells. Recent clinical studies demonstrated that bortezomib had remarkable anti-tumor activity in refractory and relapsed MM, providing the basis to approval by FDA. Its anti-tumor activities earlier in the course, in combination therapies, and in other malignancies is ongoing. 相似文献
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Moheno PB;SRI International;Arizona Cancer Center University of Arizona Health Sciences Center;San Diego Research 《International journal of pharmaceutics》2004,271(1-2):293-300
A series of in vivo studies are reported that provide evidence for an immunologically mediated mechanism for the antitumor response from a calcium pterin (CaPterin) suspension. Strong antitumor efficacy was demonstrated in fully immunocompetent female C3H/HeN-MTV+ mice (retired breeders) presenting spontaneous mammary gland adenocarcinomas. Comparison of results obtained by testing CaPterin in either nude or SCID mice (severely compromised immunodeficient) implanted with MDA-MB-231 human cancer cells showed a significant antitumor response in the nudes and no response in the SCIDs. This comparison argues for B-cell immunological involvement in the mechanism of CaPterin antitumor activity since nude mice possess B-cell capability while SCID mice do not. This comparison also indicates that there is no measurable direct cancer cell toxicity from the CaPterin. Results showing no CaPterin antitumor efficacy against EMT6 tumor cells implanted in Balb/c mice also suggest an antitumor mechanism involving B-cells, since transforming growth factor beta (TGF-beta), produced by EMT6 cells, is known to cause B-cell apoptosis. Taken together, these results, along with those of other researchers, indicate that CaPterin's antitumor mechanism involves antibody-dependent cellular cytotoxicity (ADCC) mediated, for example, by natural killer (NK) cells, interlukin-2, and CaPterin. 相似文献
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Alice Glover Hoo G. Chun Larry M. Kleinman David A. Cooney Jacqueline Plowman Charles K. Grieshaber Louis Malspeis Brian Leyland-Jones 《Investigational new drugs》1987,5(2):137-143
Summary Merbarone was developed to clinical trial stage on the basis of its curative activity against P388 and L1210 leukemias and moderate activity against B16 melanoma and M5076 sarcoma. Its activity appears to be schedule-dependent favoring a longer duration of administration. The mechanism of action of merbarone is not yet established but it does induce single strand breaks in DNA apparently without binding to DNA.The pharmacokinetic data in the dog indicate that clearance mechanisms may be saturable. Merbarone is hydroxylated at the 4 position in the rat, mouse and dog, and glucuronidated in the dog. Parent drug and the hydroxy metabolite are excreted in the urine. If saturable clearance mechanisms also pertain to man, this will mean that infusion rate (and therefore steady state concentrations reached) may be a significant factor in determining acute toxicity.Preclinical toxicology studies revealed that major target tissues are in the lymphoid organs, bone marrow, gastrointestinal tract and kidney. Some behavioral signs of reversible central nervous system toxicity were observed.Phase I trials have commenced using only a 5-day continuous intravenous infusion schedule based on the preclinical data. The pharmacokinetic information from these trials will be crucial for further clinical development of the compound, including selection of the optimal schedule(s) for phase II/III evaluation. 相似文献
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Solid-state phase transitions of AG337, an antitumor agent 总被引:1,自引:0,他引:1
Rastogi S Zamansky I Roy S Tyle P Suryanarayanan R 《Pharmaceutical development and technology》1999,4(4):623-632
The object of this investigation was to perform detailed solid-state characterization studies on the different solid forms of AG337 and to determine the conditions of their interconversions. Solid-state characterization was done using differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), hot stage microscopy, Karl Fischer titrimetry, ambient and variable temperature X-ray powder diffractometry (XRD) and TGA coupled with FTIR (TGA/FTIR). In addition to five polymorphic forms of the anhydrate (I alpha to I epsilon), a hemihydrate (C14H12N4OS.2HCl.0.5H2O, II), a monohydrate (C14H12N4OS.2HCl.H2O; III), as well as a dihydrate (C14H12N4OS.2HCl.2H2O; IV) were identified. The 'as is' anhydrate, I alpha, resisted water uptake until stored at 98% RH (room temperature), where it transformed directly to IV, II and III transformed to IV at RH values > or = 7.6 and 84% respectively. Heating II and III to 130 degrees C in the variable temperature XRD resulted in the formation of I beta and I gamma respectively. On the other hand, I delta and I epsilon were obtained when II and III were respectively stored at 60 degrees C under vacuum. Variable temperature XRD, by providing information about the solid-state as a function of temperature, assisted in the interpretation of the DSC and TGA results. TGA/FTIR provided direct evidence that the thermal events observed in the temperature ranges of 25-150 degrees C and 200-250 degrees C were due to loss of water and loss of hydrogen chloride respectively. In addition to the conventional analytical techniques such as XRD, DSC, TGA and KFT, two other techniques, (variable temperature XRD and TGA/FTIR), were very useful in these solid-state characterization studies. 相似文献