排序方式: 共有164条查询结果,搜索用时 15 毫秒
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Osnat Bairey MD Alisa Taliansky MD Amir Glik MD Alexandra Amiel MD Shlomit Yust-Katz MD Ronit Gurion MD Miri Zektser MD Tzvika Porges MD Nadav Sarid MD Netanel A. Horowitz MD Tzahala Tzuk Shina MD Eyal Lebel MD Amos Cohen MD Karyn Revital Geiger MD Pia Raanani MD Ofir Wolach MD Tali Siegal MD 《Cancer》2023,129(24):3905-3914
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The US Food and Drug Administration granted acalabrutinib approval as the second Bruton tyrosine kinase (BTK) inhibitor to treat patients with chronic lymphocytic leukemia and small lymphocytic lymphoma as monotherapy or in combination with obinutuzumab. This approval was based on 2 phase 3 trials: ELEVATE-TN and ASCEND. There are several concerns with the design of these trials, including suboptimal treatment of patients in the control arm, expansion of the trial population, and lack of data regarding efficacy or tolerability compared with ibrutinib, a first-in-class drug. The Food and Drug Administration approval of acalabrutinib for patients with chronic lymphocytic leukemia and small lymphocytic lymphoma represents concerning drug approval patterns in the United States and a weakness in evidence generation. 相似文献
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David Chiron Christelle Dousset Carole Brosseau Cyrille Touzeau Sophie Ma?ga Philippe Moreau Catherine Pellat-Deceunynck Steven Le Gouill Martine Amiot 《Oncotarget》2015,6(11):8750-8759
The aggressive biological behavior of mantle cell lymphoma (MCL) and its short response to current treatment highlight a great need for better rational therapy. Herein, we investigate the ability of ABT-199, the Bcl-2-selective BH3 mimetic, to kill MCL cells. Among MCL cell lines tested (n = 8), only three were sensitive (LD50 < 200 nM). In contrast, all primary MCL samples tested (n = 11) were highly sensitive to ABT-199 (LD50 < 10 nM). Mcl-1 and Bcl-xL both confer resistance to ABT-199-specific killing and BCL2/(BCLXL + MCL1) mRNA ratio is a strong predictor of sensitivity. By mimicking the microenvironment through CD40 stimulation, we show that ABT-199 sensitivity is impaired through activation of NF-kB pathway and Bcl-xL up-regulation. We further demonstrate that resistance is rapidly lost when MCL cells detach from CD40L-expressing fibroblasts. It has been reported that ibrutinib induces lymphocytosis in vivo holding off malignant cells from their protective microenvironment. We show here for two patients undergoing ibrutinib therapy that mobilized MCL cells are highly sensitive to ABT-199. These results provide evidence that in situ ABT-199 resistance can be overcome when MCL cells escape from the lymph nodes. Altogether, our data support the clinical application of ABT-199 therapy both as a single agent and in sequential combination with BTK inhibitors. 相似文献
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Chiara Briani Andrea Visentin Federica Cerri Angelo Quattrini 《Journal of the peripheral nervous system : JPNS》2020,25(3):212-221
The peripheral nervous system may be involved at any stage in the course of several hematological diseases, the most common being monoclonal gammopathies (of undetermined significance or malignant) or lymphomas. The underlying pathogenic mechanisms are different and therapies aim at targeting the dangerous either B‐cell or plasma cell clones. Recently, high‐throughput technologies, and next‐generation sequencing have increased our knowledge of hematological diseases pathogenesis by the identification of somatic mutation affecting pivotal signaling pathways. Accordingly, new target therapies are used that may also be borrowed for treatment of neuropathies in hematological diseases. 相似文献
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《Journal of pharmaceutical sciences》2019,108(9):3020-3028
At present, coamorphous systems have attracted increasing interest in the pharmaceutical field owing to their enhanced stabilities, increased solubilities, and improved bioavailabilities compared with those of their pure amorphous and crystalline counterparts. In this study, a novel coamorphous solid form of ibrutinib (IBT) and saccharin (SAC) (1:1 molar ratio) was prepared through rotary vacuum evaporation and then characterized. Differential scanning calorimetry and X-ray powder diffraction indicated the formation of the coamorphous IBT-SAC after rotary vacuum evaporation. Compared with amorphous IBT, coamorphous IBT-SAC exhibited enhanced stability owing to the intermolecular interaction between IBT and SAC. Moreover, the solubility and dissolution of the coamorphous IBT-SAC were increased up to 4.0-7.7 times and 4.3 times, respectively, compared with those of its crystalline Form A. In addition to the superior behaviors of coamorphous IBT-SAC in vitro, the in vivo bioavailability study revealed notable increases in the Cmax and area under the curve0-t of the coamorphous form compared with those of its crystalline Form A. The current study demonstrates that the coamorphization of IBT and SAC presents a promising technology to overcome the limitations of solubility and stability that arise from IBT and can therefore contribute to a major improvement in the bioavailability of IBT. 相似文献
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目的:分析伊布替尼所致不良反应(ADRs)的发生情况及临床特点,为临床安全用药提供参考。方法:检索PubMed、Web of Science、中国知网数据库、维普中文科技期刊数据库、万方数据库、中国医院知识总库关于伊布替尼不良反应的文献并进行分析。结果:伊布替尼致ADRs的个案共41例,多发生在用药30d内(13例,31.7%);伊布替尼致ADRs累及系统-器官以呼吸系统损害(13例,28.9%)、皮肤及附件损害为主(10例,22.2%)为主。结论:临床医师或药师应了解伊布替尼ADRs的发生规律和特点,尽量将ADRs的影响及危害降至最低,最大程度保障用药安全。 相似文献
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《British journal of haematology》2018,182(3):404-411
Ibrutinib has shown significant activity in patients with relapsed or refractory mantle cell lymphoma (RR‐MCL). We report the long‐term outcome and safety profile of a single‐centre, single arm, open‐label, phase 2 study of RR‐MCL treated with IR. Overall, the median follow‐up time was 47 months (range 1–52 months), median duration on treatment was 16 months (range 1–53 months) and median number of treatment cycles was 17 (range 1–56). Twenty‐nine patients (58%) achieved complete remission and of these, 12 patients continue on study. Thirty‐eight patients discontinued treatment, 14 due to disease progression (2 transformed). Patients with blastoid morphology, high risk MCL International Prognostic Index score and high Ki67% had inferior survival. The commonest grade 1–2 toxicities were fatigue, diarrhoea, nausea, arthralgias and myalgias. None had long term toxicities. Median progression‐free survival was 43 months. Eighteen patients (36%) died (14 deaths were MCL‐related). The median overall survival has not been reached. Treatment with IR can provide durable remissions in a subset of patients with RR‐MCL, especially those with low Ki67%. The possible benefit of adding other therapies in combination with IR in RR‐MCL is under exploration. 相似文献
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