CY, Cyclophosphamide

CY,环磷酰胺
  • 文章类型: Journal Article
    化疗引起的副作用影响癌症患者的生活质量和治疗效果。目前用于治疗化疗副作用的方法效果不佳,并且可能引起许多有害的副作用。因此,开发来自天然无毒化合物的新的有效药物来治疗化疗引起的副作用是必要的。体内和体外实验表明,人参(PG)及其人参皂苷无疑是治疗化疗引起的副作用的无毒和有效的选择,如肾毒性,肝毒性,心脏毒性,免疫毒性,和造血抑制。机制集中在抗氧化上,抗炎,和抗凋亡,以及信号通路的调节,如核因子-2相关因子2(Nrf2)/血红素加氧酶-1(HO-1),P62/keap1/Nrf2,c-junN末端激酶(JNK)/P53/caspase3,丝裂原活化蛋白激酶(MEK)/细胞外信号调节激酶(ERK),AMP激活蛋白激酶(AMPK)/哺乳动物雷帕霉素靶蛋白(mTOR),丝裂原活化蛋白激酶激酶4(MKK4)/JNK,和磷脂酰肌醇3-激酶(PI3K)/AKT。由于尚未对PG及其人参皂苷对化疗引起的副作用的作用和机制进行系统综述,我们为此目的提供了全面的总结,并为PG的未来研究提供了启示。
    Chemotherapy-induced side effects affect the quality of life and efficacy of treatment of cancer patients. Current approaches for treating the side effects of chemotherapy are poorly effective and may cause numerous harmful side effects. Therefore, developing new and effective drugs derived from natural non-toxic compounds for the treatment of chemotherapy-induced side effects is necessary. Experiments in vivo and in vitro indicate that Panax ginseng (PG) and its ginsenosides are undoubtedly non-toxic and effective options for the treatment of chemotherapy-induced side effects, such as nephrotoxicity, hepatotoxicity, cardiotoxicity, immunotoxicity, and hematopoietic inhibition. The mechanism focus on anti-oxidation, anti-inflammation, and anti-apoptosis, as well as the modulation of signaling pathways, such as nuclear factor erythroid-2 related factor 2 (Nrf2)/heme oxygenase-1 (HO-1), P62/keap1/Nrf2, c-jun N-terminal kinase (JNK)/P53/caspase 3, mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinases (ERK), AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR), mitogen-activated protein kinase kinase 4 (MKK4)/JNK, and phosphatidylinositol 3-kinase (PI3K)/AKT. Since a systemic review of the effect and mechanism of PG and its ginsenosides on chemotherapy-induced side effects has not yet been published, we provide a comprehensive summarization with this aim and shed light on the future research of PG.
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  • 文章类型: Journal Article
    UNASSIGNED: Post-transplant cyclophosphamide (PT-Cy) has become a standard of care in haploidentical hematopoietic stem cell transplantation (HSCT) to reduce the risk of graft-versus-host disease. However, data on cardiac events associated with PT-Cy are scarce.
    UNASSIGNED: This study sought to assess the incidence and clinical features of cardiac events associated with PT-Cy.
    UNASSIGNED: The study compared clinical outcomes between patients who received PT-Cy (n = 136) and patients who did not (n = 195), with a focus on early cardiac events (ECE) occurring within the first 100 days after HSCT. All patients had the same systematic cardiac monitoring.
    UNASSIGNED: The cumulative incidence of ECE was 19% in the PT-Cy group and 6% in the no-PT-Cy group (p < 0.001). The main ECE occurring after PT-Cy were left ventricular systolic dysfunction (13%), acute pulmonary edema (7%), pericarditis (4%), arrhythmia (3%), and acute coronary syndrome (2%). Cardiovascular risk factors were not associated with ECE. In multivariable analysis, the use of PT-Cy was associated with ECE (hazard ratio: 2.7; 95% confidence interval: 1.4 to 4.9; p = 0.002]. Older age, sequential conditioning regimen, and Cy exposure before HSCT were also associated with a higher incidence of ECE. Finally, a history of cardiac events before HSCT and ECE had a detrimental impact on overall survival.
    UNASSIGNED: PT-Cy is associated with a higher incidence of ECE occurring within the first 100 days after HSCT. Patients who have a cardiac event after HSCT have lower overall survival. These results may help to improve the selection of patients who are eligible to undergo HSCT with PT-Cy, especially older adult patients and patients with previous exposure to Cy.
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  • 文章类型: Journal Article
    目的:伴有神经系统受累的肾上腺脑白质营养不良(ALD)的预后通常是令人沮丧的;然而,异基因干细胞移植(SCT)被认为是稳定或改善ALD临床症状的有效方法。在这里,我们报告了ALD患者的临床结局,这些患者在我们的机构连续接受了同种异体干细胞移植并降低了预处理强度.
    方法:16例ALD患者,有症状(n=14)或症状前(n=2),2010年至2016年收到SCT。干细胞来源为脐带血(n=14),或来自相同同胞的人类白细胞抗原的骨髓(n=2)。移植前的预处理方案强度降低,由氟达拉滨(125mg/m2)组成,美法仑(140mg/m2)和4Gy(n=15)或3Gy(n=1)的低剂量全身照射(TBI)。
    结果:在11例患者中获得了一次植入,5例失去初次移植物的患者中有4例接受了第二次脐带血移植并进行了移植。5年总生存率和无事件生存率分别为90.9%和61.1%。中位数为45个月(范围16-91)。除内囊受累患者外,Loes评分在移植后18个月稳定或改善。
    结论:对ALD患者进行强度降低的同种异体SCT是安全的,即使在有症状的患者中也没有重大的移植相关并发症,对无内囊受累的患者进行SCT后神经系统症状稳定。
    OBJECTIVE: The prognosis of adrenoleukodystrophy (ALD)with neurological involvement is generally dismal; however, allogeneic stem cell transplantation (SCT) is recognized as effective to stabilize or improve the clinical symptoms of ALD. Herein, we report the clinical outcomes of patients with ALD who consecutively underwent allogeneic stem cell transplantation with reduced intensity conditioning at our institution.
    METHODS: Sixteen patients with ALD, who were symptomatic (n = 14) or presymptomatic (n = 2), received SCT from 2010 to 2016. The stem cell source was cord blood (n = 14), or bone marrow from a human leukocyte antigen identical sibling (n = 2). The conditioning regimen prior to transplantation was reduced intensity and consisted of fludarabine (125 mg/m2), melphalan (140 mg/m2) and low dose total body irradiation (TBI) of 4Gy (n = 15) or 3Gy (n = 1).
    RESULTS: Primary engraftment was obtained in 11 patients, and 4 of the 5 patients who lost the primary graft received a second cord blood transplantation and were engrafted. Five years overall and event-free survival were 90.9% and 61.1% respectively, with a median of 45 months (range 16-91). Loes score stabilized or improved by 18 months after transplantation except for patients with internal capsule involvement.
    CONCLUSIONS: Allogeneic SCT with reduced intensity conditioning for patients with ALD was safely performed without major transplant-related complications even in symptomatic patients and neurological symptoms were stabilized after SCT in patients without internal capsule involvement.
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  • 文章类型: Journal Article
    尽管通过最近引入靶向药物如多激酶抑制剂在晚期肾癌的治疗方面取得了重大改善,这种疾病的长期获益仍然有限,且仍有大量未满足的医疗需求.通过在一小部分患者中诱导持久的反应,癌症免疫疗法显示了其潜力。然而,迄今为止使用的非特异性免疫干预(高剂量)细胞因子与显著的副作用相关.特异性癌症免疫疗法可以通过攻击肿瘤细胞同时保留正常组织来规避这些问题,其中使用多肽疫苗接种是最有前途的策略之一。我们在这里总结了研究IMA901的I期和II期试验的临床和翻译数据。临床获益与针对IMA901肽的可检测T细胞反应的显着关联,以及在治疗患者中令人鼓舞的生存数据,促使开始了一项随机研究,一线晚期RCC的III期对照试验,预计到2015年底生存结果。还讨论了与最近发现的所谓检查点抑制剂的潜在组合策略。
    Despite a major improvement in the treatment of advanced kidney cancer by the recent introduction of targeted agents such as multi-kinase inhibitors, long-term benefits are still limited and a significant unmet medical need remains for this disease. Cancer immunotherapy has shown its potential by the induction of long-lasting responses in a small subset of patients, however, the unspecific immune interventions with (high dose) cytokines used so far are associated with significant side effects. Specific cancer immunotherapy may circumvent these problems by attacking tumor cells while sparing normal tissue with the use of multi-peptide vaccination being one of the most promising strategies. We here summarize the clinical and translational data from phase I and II trials investigating IMA901. Significant associations of clinical benefit with detectable T cell responses against the IMA901 peptides and encouraging survival data in treated patients has prompted the start of a randomized, controlled phase III trial in 1st line advanced RCC with survival results expected toward the end of 2015. Potential combination strategies with the recently discovered so-called checkpoint inhibitors are also discussed.
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  • 文章类型: Clinical Trial
    先前未治疗的患者(n=34),用抗原特异性癌症免疫治疗剂tecemotide(L-BLP25)反复免疫接种缓慢进展的无症状I/II期多发性骨髓瘤或常规抗肿瘤治疗后处于稳定反应/平台期的II/III期多发性骨髓瘤.此外,患者被随机分配给单次或多次低剂量环磷酰胺以抑制调节性T细胞(Treg).用tememotide免疫导致47%的患者诱导/增强粘蛋白1特异性免疫反应。免疫应答似乎涉及涉及CD4和CD8T细胞的Th1样细胞免疫应答。单次给药与多次给药环磷酰胺以及与没有预先存在的粘蛋白1免疫力。在45%的可评估患者中观察到M蛋白浓度随时间的斜率降低(但未达到常规抗肿瘤药物反应的临床标准)。主要是那些没有与预先存在的粘蛋白1免疫和早期疾病的患者。在接受单次或多次环磷酰胺给药的患者中没有发现差异。用替莫肽治疗通常耐受性良好。重复vs.单次给药环磷酰胺对Treg数量无影响,在一例致死性脑炎被评估为可能与研究相关后停止给药.替考莫肽免疫疗法在相当一部分患者中诱导粘蛋白1特异性细胞免疫反应,初步证据表明部分患者的M蛋白浓度时间曲线发生了变化。
    Patients (n = 34) with previously untreated, slowly progressive asymptomatic stage I/II multiple myeloma or with stage II/III multiple myeloma in stable response/plateau phase following conventional anti-tumor therapy were immunized repeatedly with the antigen-specific cancer immunotherapeutic agent tecemotide (L-BLP25). Additionally, patients were randomly allocated to either single or multiple low doses of cyclophosphamide to inhibit regulatory T cells (Treg). Immunization with tecemotide resulted in the induction/augmentation of a mucin 1-specific immune response in 47% of patients. The immune responses appeared to involve a Th1-like cellular immune response involving CD4 and CD8 T cells. The rate of immune responses was similar with single versus multiple dosing of cyclophosphamide and in patients with vs. without pre-existing mucin 1 immunity. On-treatment reductions in the slope of M-protein concentration over time (but not fulfilling clinical criteria for responses with conventional anti-tumor agents) were observed in 45% of evaluable patients, predominantly in those without versus with pre-existing mucin 1 immunity and in patients with early stage disease. No differences were seen in patients receiving single or multiple cyclophosphamide dosing. Treatment with tecemotide was generally well tolerated. Repeated vs. single dosing of cyclophosphamide had no impact on Treg numbers and was stopped after a case of fatal encephalitis that was assessed as possibly study-related. Tecemotide immunotherapy induces mucin 1-specific cellular immune responses in a substantial proportion of patients, with preliminary evidence of changes in the M-protein concentration time curve in a subset of patients.
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