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排序方式: 共有366条查询结果,搜索用时 46 毫秒
1.
Yu-Jiao Liu Xiao-Yang Fan Dr. Dong-Dong Zhang Yin-Zheng Xia Dr. Yan-Jun Hu Feng-Lei Jiang Prof. Fu-Ling Zhou Prof. Yi Liu 《ChemMedChem》2020,15(6):552-558
Based on the potential therapeutic value in targeting mitochondria and the fluorophore tracing ability, a fluorescent mitochondria-targeted organic arsenical PDT-PAO-F16 was fabricated, which not only visualized the cellular distribution, but also exerted anti-cancer activity in vitro and in vivo via targeting pyruvate dehydrogenase complex (PDHC) and respiratory chain complexes in mitochondria. In details, PDT-PAO-F16 mainly accumulated into mitochondria within hours and suppressed the activity of PDHC resulting in the inhibition of ATP synthesis and thermogenesis disorder. Moreover, the suppression of respiratory chain complex I and IV accelerated the mitochondrial dysfunction leading to caspase family-dependent apoptosis. In vivo, the acute promyelocytic leukemia was greatly alleviated in the PDT-PAO-F16 treated group in APL mice model. Our results demonstrated the organic arsenical precursor with fluorescence imaging and target-anticancer efficacy is a promising anticancer drug. 相似文献
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Prof. Dr. Hans-René Bjørsvik Prof. Dr. Bjørn Tore Gjertsen Dr. Vijayaragavan Elumalai 《ChemMedChem》2020,15(10):862-870
A previously designed and developed 12-step total synthesis that includes [1,1′-biphenyl]-2-amine and carbazole intermediates and that ultimately produces the carbazole alkaloid carbazomycin G was exploited as a screening compound library with the goal of identifying potential lead compound(s) with cytotoxic effect. These compounds were investigated by using in-vitro tests involving the two human cell lines HL-60 and MOLM-13, which both model acute myeloid leukaemia (AML). The in-vitro biological test results were used together with the molecular structures of the various intermediates in a concise SAR analysis. Several of the intermediates revealed cytotoxicity (IC50<10−4 M), although the final natural product carbazomycin G did not reveal cytotoxicity versus the two said human cell lines. 相似文献
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Gleevec是抑制致癌的融合蛋白BCR-ABL的一种分子靶向治疗药物,BCR-ABL是一种与慢性髓细胞性白血病(CML)有关的酪氨酸激酶抑制剂。用Gleevec选择性地抑制BCR-ABL活性在治疗CML中显示出很好的效果,特别是在CML慢性期,因此,监测疗效非常重要。现就Gleevec的研究进展及如何监测其在CML中的疗效作一简单综述。 相似文献
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以姊妹染色体互换为观察指标.观察了干扰素对慢性粒细胞白血病骨髓细胞DNA损伤修复的影响,探讨了干扰素对慢性粒细胞白血病的治疗机理,对指导临床治疗具有重要的意义。 相似文献
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Karolina Bukowska-Strakova Joanna Wodek Ewelina Pitera Magdalena Kozakowska Anna Konturek-Ciela Maciej Ciela Monika Goka Witold Nowak Aleksandra Wieczorek Katarzyna Pawiska-Wsikowska Alicja Jzkowicz Maciej Siedlar 《International journal of molecular sciences》2021,22(3)
Whilst the survival rates of childhood acute lymphoblastic leukemia (ALL) have increased remarkably over the last decades, the therapy resistance and toxicity are still the major causes of treatment failure. It was shown that overexpression of heme oxygenase-1 (HO-1) promotes proliferation and chemoresistance of cancer cells. In humans, the HO-1 gene (HMOX1) expression is modulated by two polymorphisms in the promoter region: (GT)n-length polymorphism and single-nucleotide polymorphism (SNP) A(−413)T, with short GT repeat sequences and 413-A variants linked to an increased HO-1 inducibility. We found that the short alleles are significantly more frequent in ALL patients in comparison to the control group, and that their presence may be associated with a higher risk of treatment failure, reflecting the role of HO-1 in chemoresistance. We also observed that the presence of short alleles may predispose to develop chemotherapy-induced neutropenia. In case of SNP, the 413-T variant co-segregated with short or long alleles, while 413-A almost selectively co-segregated with long alleles, hence it is not possible to determine if SNPs are actually of phenotypic significance. Our results suggest that HO-1 can be a potential target to overcome the treatment failure in ALL patients. 相似文献
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Guadalupe Rosario Fajardo-Ordua Edgar Ledesma-Martínez Itzen Aguiiga-Snchez María de Lourdes Mora-García Benny Weiss-Steider Edelmiro Santiago-Osorio 《International journal of molecular sciences》2021,22(9)
Acute myeloid leukemia (AML), the most common type of leukemia in older adults, is a heterogeneous disease that originates from the clonal expansion of undifferentiated hematopoietic progenitor cells. These cells present a remarkable variety of genes and proteins with altered expression and function. Despite significant advances in understanding the molecular panorama of AML and the development of therapies that target mutations, survival has not improved significantly, and the therapy standard is still based on highly toxic chemotherapy, which includes cytarabine (Ara-C) and allogeneic hematopoietic cell transplantation. Approximately 60% of AML patients respond favorably to these treatments and go into complete remission; however, most eventually relapse, develop refractory disease or chemoresistance, and do not survive for more than five years. Therefore, drug resistance that initially occurs in leukemic cells (primary resistance) or that develops during or after treatment (acquired resistance) has become the main obstacle to AML treatment. In this work, the main molecules responsible for generating chemoresistance to Ara-C in AML are discussed, as well as some of the newer strategies to overcome it, such as the inclusion of molecules that can induce synergistic cytotoxicity with Ara-C (MNKI-8e, emodin, metformin and niclosamide), subtoxic concentrations of chemotherapy (PD0332991), and potently antineoplastic treatments that do not damage nonmalignant cells (heteronemin or hydroxyurea + azidothymidine). 相似文献
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Transmission electron microscopy, scanning electron microscopy, and ultrastructural cytochemistry were utilized to study megakaryoblastic cells from four patients suffering from megakaryoblastic leukemia. The results show that megakaryoblastic leukemic cells have a unique ultrastructural appearance, surface architecture, and cytochemical activity. The cells are positive for platelet peroxidase cytochemical reaction, which is localized in the perinuclear space and endoplastic reticulum, but not in the Golgi apparatus and cytoplasmic granules. They have a rather smooth surface and display blebs or tuberculi which are different from those in other types of leukemic cells as seen under the scanning electron microscope. The megakaryoblastic leukemic cells also show a special appearance under the transmission electron microscope, such as a cytoplasm which contains numerous small mitochondria, mostly concentrated in one pole of the cell. These ultrastructural and cytochemical characteristics of the megakaryoblastic leukemic cells revealed by the combined techniques are very useful in the diagnosis of megakaryoblastic leukemia. 相似文献