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排序方式: 共有180条查询结果,搜索用时 15 毫秒
1.
Ruichong Ma Margarida Rei Isaac Woodhouse Katherine Ferris Sophie Kirschner Anandhakumar Chandran Uzi Gileadi Ji-Li Chen Mariana Pereira Pinho Yoanna Ariosa-Morejon Skirmantas Kriaucionis Nicola Ternette Hashem Koohy Olaf Ansorge Graham Ogg Puneet Plaha Vincenzo Cerundolo 《Neuro-oncology》2022,24(12):2093
2.
目的 制备地西他滨温度敏感聚乙二醇化脂质体,对处方进行筛选及优化,并且对制剂进行初步评价。方法 选用逆相蒸发法制备地西他滨温度敏感长循环聚乙二醇化脂质体,采用微柱离心-HPLC测定包封率,以包封率为评价指标,考察磷脂浓度、磷脂胆固醇质量比、药脂比、水化介质等因素对脂质体的影响,在此基础上运用正交设计对处方进行优化。 结果 正交设计结果表明,磷脂质量浓度为5 g·L-1,磷脂与胆固醇的质量比为4∶1,药物磷脂质量比为40∶1,水相pH7.0为最佳处方,制得的脂质体包封率为(44.50±1.08)%,Zeta电位为-8.34 mV,平均粒径为(140.25±2.40)nm,药物在42~43 ℃有突释。结论 优选出最佳处方,制得到地西他滨温度敏感聚乙二醇化脂质体,在相变温度时,体外释药明显。 相似文献
3.
《British journal of haematology》2017,176(4):609-617
Although azanucleoside DNA‐hypomethylating agents (HMAs) are routinely used for the treatment of myelodysplastic syndrome/acute myeloid leukaemia (MDS/AML), very few outcome predictors have been established. Expression of the β‐like globin gene locus is tightly regulated by DNA methylation, is HMA‐sensitive in vitro, and fetal haemoglobin (HbF) expression is under study as a potential biomarker for response of MDS patients to azacitidine. We determined HbF expression in 16 MDS and 36 AML patients receiving decitabine (DAC). Pre‐treatment HbF was already elevated (>1·0% of total haemoglobin) in 7/16 and 12/36 patients, and HbF was induced by DAC in 81%/54% of MDS/AML patients, respectively. Elevated pre‐treatment HbF was associated with longer median overall survival (OS): 26·6 vs. 8·6 months for MDS (hazard ratio [HR] 8·56, 95% confidence interval [CI] 1·74–42·49, P = 0·008, with similarly longer progression‐free and AML‐free survival), and 10·0 vs. 2·9 months OS for AML (HR 3·01, 95% CI 1·26–7·22, P = 0·014). In a multivariate analysis, the prognostic value of HbF was retained. Time‐dependent Cox models revealed that the prognostic value of treatment‐induced HbF induction was inferior to that of pre‐treatment HbF. In conclusion, we provide first evidence for in vivo HbF induction by DAC in MDS/AML, and demonstrate prognostic value of elevated pre‐treatment HbF, warranting prospective, randomized studies. 相似文献
4.
《British journal of haematology》2017,176(4):600-608
To identify the molecular signatures that predict responses to decitabine (DAC ), we examined baseline gene mutations (28 target genes) in 109 myelodysplastic syndrome (MDS ) patients at diagnosis. We determined that TP 53 mutations predicted complete response (CR ), as 10 of 15 patients (66·7%) who possessed TP 53 mutations achieved a CR . Univariate and multivariate analyses showed that TP 53 mutations are the only molecular signatures predictive of a CR to DAC in MDS . Among the ten patients with TP 53 mutations who achieved a CR , nine presented with complex karyotypes due to abnormalities involving chromosome 5 and/or chromosome 7, and eight possessed monosomies. Although TP 53 mutations were associated with a higher frequency of CR s, they were not associated with improved survival. Poor outcomes were attributed to early relapses and transformation to acute myeloid leukaemia after CR . Post‐DAC therapy patient gene mutation profiles showed that most CR patients exhibited fewer gene mutations after achieving a CR . It seems that suppression of these gene mutations was facilitated by DAC , resulting in a CR . In summary, TP 53 mutations might predict decitabine‐induced complete responses in patients with MDS . DAC ‐induced responses may result from partial suppression of malignant clones containing mutated TP 53 genes. 相似文献
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目的 分析探讨低剂量地西他滨与支持治疗对骨髓增生异常综合征低危患者预后的影响。方法 选取2016年10月-2018年10月于西安市中心医院收治的110例骨髓增生异常综合征患者,根据治疗方案的不同将所有患者分为对照组和观察组,每组各55例。对照组患者均给予支持治疗,而观察组患者则在对照组基础上给予低剂量地西他滨进行治疗。第1~5天为1个疗程,每个疗程至少间隔3周,治疗至少2个疗程。比较两组患者的临床疗效和不良反应发生情况。结果 治疗后,观察组患者的总有效率为67.27%,显著优于对照组患者的34.55%(P<0.05)。治疗后,观察组患者中出现3级以上感染和因不良反应死亡的不良情况发生率分别为32.73%和3.64%,均显著低于对照组患者的60.00%和29.09%(P<0.05)。结论 对骨髓增生异常综合征低危患者采用低剂量地西他滨治疗能够有效改善患者的临床预后,在降低其不良反应发生率的同时大大提升了治疗效果,值得在临床上加以推广运用。 相似文献
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8.
Hassan Awada Reda Z. Mahfouz Ashwin Kishtagari Teodora Kuzmanovic Jibran Durrani Cassandra M. Kerr Bhumika J. Patel Valeria Visconte Tomas Radivoyevitch Alan Lichtin Hetty E. Carraway Jaroslaw P. Maciejewski Yogen Saunthararajah 《British journal of haematology》2020,188(6):924-929
The nucleoside analogue decitabine can deplete the epigenetic regulator DNA methyltransferase 1 (DNMT1), an effect that occurs, and is saturated at, low concentrations/doses. A reason to pursue this molecular-targeted effect instead of the DNA damage/cytotoxicity produced with high concentrations/doses, is that non-cytotoxic DNMT1-depletion can cytoreduce even p53-null myeloid malignancies while sparing normal haematopoiesis. We thus identified minimum doses of decitabine (0·1–0·2 mg/kg) that deplete DNMT1 without off-target anti-metabolite effects/cytotoxicity, and then administered these well-tolerated doses frequently 1–2X/week to increase S-phase dependent DNMT1-depletion, and used a Myeloid Malignancy Registry to evaluate long-term outcomes in 69 patients treated this way. Consistent with the scientific rationale, treatment was well-tolerated and durable responses were produced (~40%) in genetically heterogeneous disease and the very elderly. 相似文献
9.
La-Wei Yang Xian-Jin Wu Yi Liang Guang-Qing Ye Yuchuan Che Xue-Zhen Wu Xiao-Jie Zhu Huo-Liang Fan Xiang-Ping Fan Jun-Fa Xu 《Molecular carcinogenesis》2020,59(4):447-461
Effective therapeutic targets for triple-negative breast cancer (TNBC), a special type of breast cancer (BC) with rapid metastasis and poor prognosis, are lacking, especially for patients with chemotherapy resistance. Decitabine (DCA) is a Food and Drug Administration-approved DNA methyltransferase inhibitor that has been proven effective for the treatment of tumors. However, its antitumor effect in cancer cells is limited by multidrug resistance. Cancer stem cells (CSCs), which are thought to act as seeds during tumor formation, regulate tumorigenesis, metastasis, and drug resistance through complex signaling. Our previous study found that miR-155 is upregulated in BC, but whether and how miR-155 regulates DCA resistance is unclear. In this study, we demonstrated that miR-155 was upregulated in CD24−CD44+ BC stem cells (BCSCs). In addition, the overexpression of miR-155 increased the number of CD24−CD44+ CSCs, DCA resistance and tumor clone formation in MDA-231 and BT-549 BC cells, and knockdown of miR-155 inhibited DCA resistance and stemness in BCSCs in vitro. Moreover, miR-155 induced stemness and DCA resistance by inhibiting the direct target gene tetraspanin-5 (TSPAN5). We further confirmed that overexpression of TSPAN5 abrogated the effect of miR-155 in promoting stemness and DCA resistance in BC cells. Our data show that miR-155 increases stemness and DCA resistance in BC cells by targeting TSPAN5. These data provide a therapeutic strategy and mechanistic basis for future possible clinical applications targeting the miR-155/TSPAN5 signaling axis in the treatment of TNBC. 相似文献
10.
Xinping Zhou Chen Mei Jin Zhang Ying Lu Jianping Lan Shengyun Lin Yuefeng Zhang Yuemin Kuang Yanling Ren Liya Ma Juying Wei Li Ye Weilai Xu Kongfei Li Chenxi Lu Jie Jin Hongyan Tong 《Hematological oncology》2020,38(4):531-540
Patients with acute myeloid leukemia (AML) evolving from myelodysplastic syndrome (MDS) or higher-risk MDS have limited treatment options and poor prognosis. Our previous single-center study of decitabine followed by low dose idarubicin and cytarabine (D-IA) in patients with myeloid neoplasms showed promising primary results. We therefore conducted a multicenter study of D-IA regimen in AML evolving from MDS and higher-risk MDS. Patients with AML evolving from MDS or refractory anemia with excess blasts type 2 (RAEB-2) (based on the 2008 WHO classification) were included. The D-IA regimen (decitabine, 20 mg/m2 daily, days 1 to 3; idarubicin, 6 mg/m2 daily, days 4 to 6; cytarabine 25 mg/m2 every 12 hours, days 4 to 8; granulocyte colony stimulating factor [G-CSF], 5 μg/kg, from day 4 until neutrophil count increased to 1.0 × 109/L) was administered as induction chemotherapy. Seventy-one patients were enrolled and treated, among whom 44 (62.0%) had AML evolving from MDS and 27 (38.0%) had RAEB-2. Twenty-eight (63.6%) AML patients achieved complete remission (CR) or complete remission with incomplete blood count recovery (CRi): 14 (31.8%) patients had CR and 14 (31.8%) had CRi. Six (22.2%) MDS patients had CR and 15 (55.6%) had marrow complete remission. The median overall survival (OS) was 22.4 months for the entire group, with a median OS of 24.2 months for AML and 20.0 months for MDS subgroup. No early death occurred. In conclusion, the D-IA regimen was effective and well tolerated, representing an alternative option for patients with AML evolving from MDS or MDS subtype RAEB-2. 相似文献