肿瘤坏死因子α和γ-干扰素对白血病细胞作用的31PNMR分析

用^31P核磁共振观察了肿瘤坏死因子α（TNF－α）和γ－干扰素（IFN－γ）联合对人淋巴瘤白血病细胞系Molt-4作用后含磷化合物的变化；Molt-4细胞系的^31P谱主要由三磷酸腺苷（ATP）、无机磷（Pi)、磷酸单酯等的共振峰组成；^31P谱显示γ－干扰素、肿瘤坏死因子α及γ－干扰素和肿瘤坏死因子α联合对Molt-4细胞作用后，三磷酸腺式苷的β位磷的共振峰与无机磷的峰高比值（hATP/hPi)不同程度地降低；同时根据Pi的化学位移对Molt-4细胞胞内pH的变化进行了监测。     

31P-NMR研究白血病细胞系Molt-4细胞内pH

用31P-NMR建立了无损伤性测定人淋巴瘤白血病细胞系Molt-4细胞胞内pH的方法.Molt-4细胞的31P核磁共振谱由无机磷(Pi)、ATP等的共振峰组成.通过测定Molt-4细胞内Pi化学位移进而能间接确定细胞内的pH,细胞内无机磷(Pi)的化学位移对pH非常敏感,随pH变化而变化.Molt-4细胞内Pi峰的化学位移为5.65±0.08(n=3),计算得到细胞内pH值为6.68±0.05.31P核磁共振能在测定细胞胞内pH的同时,观测到细胞内多种含磷小分子代谢物,是一种无损伤研究细胞内pH及代谢的有效方法.     

^31P核磁共振观察γ—干扰素对Molt—4细胞作用后含磷代谢物及pH变化

Ｍｏｌｔ＿４细胞的３１Ｐ核磁共振谱由磷酸单酯、无机磷（Ｐｉ）、双磷酸双酯、三磷酸腺苷（ＡＴＰ）的共振峰组成。用３１Ｐ核磁共振观察了γ－干扰素对Ｍｏｌｔ＿４细胞作用后含磷化合物的变化。根据Ｐｉ的化学位移对Ｍｏｌｔ＿４细胞内ｐＨ进行了监测。３１Ｐ核磁共振能一次同时监测细胞内多种含磷代谢物，是一种无损伤研究细胞代谢的有效方法。     

O—糖基—甲氧甲酰基膦酰胺酯的合成及其和生物活性研究

合成了一系列新型Ｏ－糖基－甲氧甲酰基膦酰胺酯，并对Ｏ－糖基亚磷酰胺酯与氯甲酸甲酯的Ａｒｂｕｚｏｖ反应及其它有关反应进行了讨论，产物的结构经ＨＮＭＲ、＾３１ＰＭＲ、ＩＲ及元素分析确定，初步的生物活性测定结果表明，化合３ｃ对人肝癌Ｂｅｌ－７４０２细胞和人白血病ＨＬ－６０细胞有一定的抑制作用，化合３ａ对烟草花叶病毒有一定的抑制活性。     

三苦味酸根·2,2''-二硫代二(N-氧化吡啶)合稀土(Ⅲ) 配合物的合成、表征及其抗肿瘤活性研究

据文献报导,2,2′－二硫代二（N－氧化吡啶）（简称配体L）不仅可以用在农药中抵抗生物疾病^[1],而且有着广泛的抗菌作用^[2]。由于稀土元素具有特殊的药理作用^[3,4],它与配体L形成的配合物,可能表现出更特殊的生理活性。因此,我们合成六种稀土苦味酸盐与2,2′－二硫代二（N－氧化吡啶）的配合物,并对配体及配合物的抗菌活性进行了测试。结果表明,配合物对L1210,HL－60人白血病细胞均有优于配体自身的抗肿瘤活性,其中Eu配合物对于HL－60细胞,La、Eu、Er配合物对于L1210细胞均有较强的杀伤能力,值得进一步做体内抗癌筛选。     

氟喹诺酮均三唑衍生物抗肿瘤活性的CoFMA研究

通过比较分子力场分析方法(CoMFA)研究氟喹诺酮均三唑衍生物对人肝癌细胞(SMMC-7721)、鼠白血病细胞(L1210)和人白血病细胞(HL60)的体外增值抑制活性的三维定量结构-活性相关(3D-QSAR).根据CoMFA模型的立体场和静电场三维等势线图可知,外部苯环的4-位引入的近正远负大体积基团,有利于提高氟喹诺酮均三唑衍生物的抗肿瘤活性.     

含5—氟尿嘧啶生物可降解聚磷酰胺的合成及其抗肿瘤活性研究

通过Ｌ－赖氨酸（Ｎ＾１－５－氟尿嘧啶）烷基酯双盐酸盐与二氯磷酸乙酯，二氯膦甲酸乙酯，二氯膦乙酸乙酯共聚，合成了三类１２种侧链含５－氟尿嘧啶的聚磷酰胺。聚合物的结构经ＵＶ，ＩＲ，ＨＮＭＲ及元纱分析鉴定。聚合物用微量细胞培养四氮唑实验方法（ＭＴＴ法）进行了对人肝癌细胞系Ｂｅｌ－７４０２细胞的微量培养实验。     

C4馏分中微量乙腈的大口径毛细管色谱测定

采用水相萃取富集技术，利用大口径厚液膜HLZ－60石英毛细管色变柱对C4烃抽余液中的微量乙腈进行分析；结果表明LZP－60石英毛细管色谱柱对乙腈化合物具有良好的惰性和色谱选择性；残余烃杂质峰和大量水分不干扰乙腈峰的流出；定量分析结果表明，样品测量的相对标准偏差为15％，其相对误差为7％，色谱分离检测法完全满足实际工作中微量乙腈分析的需要。     

新型汉防己甲素衍生物的合成及其生物活性

以汉防己甲素为原料,经溴代反应制得关键中间体5-溴汉防己甲素(2); 2与硼酸衍生物经Suzuki反应合成了6个新型的汉防己甲素衍生物(4a~4f),其结构经¹H NMR, ¹³C NMR和ESI-MS表征。采用CCK-8法初步考察了4a~4f对人早幼粒白血病细胞(HL60)和人肺癌细胞(A549)的抑制活性;并采用MTT法对活性较好的化合物进行复筛。采用酶联免疫吸附法考察4a~4f对多种受体酪氨酸激酶的抑制活性。结果表明：4b, 4c和4e对HL60和A549有一定的抑制活性; 4b和4c对受体酪氨酸激酶FGFR1的抑制活性大于50%。     

异丙基膦酸单异辛酯负载树脂用萃取色层以分离稀土元素

本文报道异丙基膦酸单异辛酯负载树脂分离稀土（Ⅲ）的性能。实验结果表明采用不同浓度的稀盐酸淋洗可依次分离１５种稀土（Ⅲ）。除钇（Ⅲ）／铒（Ⅲ）对（Ｒｓ１．０）外，其余各相邻稀土（Ⅲ）均达到基线分离。所用酸度不超过２．０ｍｏｌ／Ｌ，低于常用的磷酸双（２－乙已基）酯和２－乙已基磷酸单２－乙基酯所需酸度。     

Decoration of silver nanoparticles on multi-walled carbon nanotubes: Investigation of its anti-acute leukemia property against acute myeloid leukemia and acute T cell leukemia

Recently, the development of carbon nanocomposites composed of carbon nanotubes and metal nanoparticles has attracted many interests because of their large potential for technological applications such as catalysts, sensors, biomedicine, and disinfection. In the present study, we described a simple chemistry method to synthesize multi-walled carbon nanotubes (MWCNTs) decorated with silver nanoparticles (Ag-NPs). Also, we investigated the antioxidant and anti-acute leukemia activities against acute myeloid leukemia and acute T cell leukemia cell lines. Ag NPs-MWCNTs were characterized and analyzed using common nanotechnology techniques including transmission electron microscopy (TEM), X-ray diffraction (XRD), energy dispersive X-ray spectroscopy (EDS), field emission-scanning electron microscopy (FE-SEM) and elemental mapping analysis. Also, 2,2-diphenyl-1-picrylhydrazyl (DPPH) test was performed to assess the antioxidant capacities of AgNO₃, MWCNTs, and Ag NPs-MWCNTs. It revealed similar antioxidant potentials for Ag NPs-MWCNTs and butylated hydroxytoluene. In MTT assay, Ag NPs-MWCNTs had very low cell viability (very high anti-acute leukemia properties) dose-dependently against 32D-FLT3-ITD (Acute myeloid leukemia cell line), Human HL-60/vcr (Acute myeloid leukemia cell line), Jurkat, Clone E6–1 (Acute T cell leukemia cell line), and J.RT3-T3.5 (Acute T cell leukemia cell line) without any cytotoxicity on human umbilical vein endothelial cell line (HUVEC; Normal cell line). In conclusion, the synthesized Ag NPs-MWCNTs revealed excellent antioxidant and cytotoxicity activities against acute myeloid leukemia and acute T cell leukemia cell lines in a dose depended manner. After confirming in the in vivo and clinical trials, these nanoparticles can be administrated in humans for the treatment of acute leukemia especially acute myeloid leukemia and acute T cell leukemia.     

The cellular labeling and pH-sensitive responsive-drug release of celastrol in cancer cells based on Cys-CdTe QDs

As one of the active compounds derived from Traditional Chinese Medicine,Celastrol(CSL)had cytotoxicity for human leukemia cancer cells K562 and its multidrug-resistant cell line K562/A02.Here,we introduced cysteamine-modified CdTe QDs as the labeling and drug carrier into CSL research and found that the self-assembly and conjugation of anticancer molecular CSL with the Cys-CdTe QDs could significantly increase the drug’s cytotoxicity for K562 cells.More important,these CSL-Cys-CdTe nanocomposites could overcome the multidrug resistance of K562/A02 cells and efficiently inhibit the cancer cell proliferation by realizing the pH-sensitive responsive release of CSL to cancer cells.The enhanced cytotoxicity was caused by the increase of the G2/M phase arrest for K562/A02 cells as well as for K562 cells.Cys-CdTe QDs can readily bind on the cell plasma membranes and be internalized into cancer cells to trace and detect human leukemia cancer cells in real time.In addition,these Cys-CdTe QDs can facilitate the inhibition of the multidrug resistance of K562/A02 cells and readily induce apoptosis.As a good photosensitizer for the therapy,labeling,and tracing of cancer cells,the combination of CSL with Cys-CdTe QDs can optimize the use of and a new potential therapy method for CSL and yield new tools to explore the mechanisms of active compounds from Traditional Chinese Medicine.     

Targeting Human C‐Type Lectin‐like Molecule‐1 (CLL1) with a Bispecific Antibody for Immunotherapy of Acute Myeloid Leukemia

Acute myeloid leukemia (AML), which is the most common acute adult leukemia and the second most common pediatric leukemia, still has a poor prognosis. Human C‐type lectin‐like molecule‐1 (CLL1) is a recently identified myeloid lineage restricted cell surface marker, which is overexpressed in over 90 % of AML patient myeloid blasts and in leukemic stem cells. Here, we describe the synthesis of a novel bispecific antibody, αCLL1‐αCD3, using the genetically encoded unnatural amino acid, p‐acetylphenylalanine. The resulting αCLL1‐αCD3 recruits cytotoxic T cells to CLL1 positive cells, and demonstrates potent and selective cytotoxicity against several human AML cell lines and primary AML patient derived cells in vitro. Moreover, αCLL1‐αCD3 treatment completely eliminates established tumors in an U937 AML cell line xenograft model. These results validate the clinical potential of CLL1 as an AML‐specific antigen for the generation of a novel immunotherapeutic for AML.     

Green formulation,chemical characterization and anti-acute leukemia effects of vanadium nanoparticles containing Foeniculum vulgare extract

In this study, vanadium nanoparticles (VNPs) were green synthesized using Foeniculum vulgare extract. VNPs were characterized using chemical analysis techniques including FT-IR, XRD, FE-SEM, TEM and EDS. The microscopy techniques revealed a spherical morphology for the particles with size less than 50 nm. According to XRD data V₂O₅ was confirmed for VNPs. Maybe significant anti-human acute leukemia potentials of the synthesized nanoparticles against common human acute leukemia cell lines are linked to their antioxidant activities. MTT assay was used on common acute leukemia cell lines i.e., 32D-FLT3-ITD, MOLT-3 and Jurkat, Clone E6-1 to survey the cytotoxicity and anti-acute leukemia effects of the synthesized nanoparticles. The synthesized nanoparticles had very low cell viability and high anti-acute leukemia activities dose-dependently against 32D-FLT3-ITD, MOLT-3 and Jurkat, Clone E6-1 cell lines without cytotoxicity on the normal cell line (HUVEC). To determine the antioxidant properties of the synthesized nanoparticles, the DPPH test was used in the presence of butylated hydroxytoluene as the positive control. The IC₅₀ of VNPs were 25, 33 and 26 µg/mL against 32D-FLT3-ITD, MOLT-3 and Jurkat, Clone E6-1 cell lines, respectively. The synthesized nanoparticles inhibited half of the DPPH molecules in the concentration of 28 µg/mL.     

Cytotoxic and apoptotic activities of novel Pd(II) complexes against human leukemia cell lines in vitro

In the investigation for alternative chemotherapeutic strategies against leukemia, Pd(II) complexes were synthesized and investigated for cytotoxic and apoptotic properties on two human leukemia cell lines (HL-60 and K562). Pd(II) complexes (Pd-5a and Pd-6a) with 5a and 6a as ligands were synthesized and characterized by ¹H-NMR and F-TIR. The cytotoxicity of the compounds was quantified using MTT method. Bax, Bcl-2, and caspase 3 gene expression levels were estimated using RT-qPCR. Here we show that Pd(II) complexes have important cytotoxic activity on human leukemia cell lines. RT-qPCR indicated that Bax and caspase 3 gene expression levels were increased after 24 h treatment with Pd-5a and Pd-6a complexes in both HL-60 and K562 cells at some selected dose. Furthermore, Bcl-2 gene expression level decreased after 24 h treatment with Pd-5a and Pd-6a complexes in K562 cells at all selected dose. In HL-60 cells, only one selected Pd-5a dose (25 µM) decreased the gene expression level of Bcl-2. The results obtained in the present investigation indicate that these two newly synthesized Pd(II) complexes have apoptotic effects at appropriate doses through caspase 3 and Bax genes and might represent a novel potentially active agents for the management of human leukemia cell lines.     

STUDY ON INDUCTION OF DIFFERENTIATION OF A HUMAN MEGAKARYOBLASTIC LEUKEMIA CELL LINE (HIMeg) BY 1,25-DIHYDROXYVITAMIN D_3

It is reported that 1,25-dihydroxyvitamin D_3(1,25(OH)_2D_3), a physiological factor, has aninductive effect on the differentiation of a novel human megakaryoblastic leukemia cell line(HIMeg) in vitro. At the concentrations ranging from 10~(-9) to 10~(-6) mol/L, 1,25(OH)_2D_3 showedinhibition of proliferation on HIMeg cells which was demonstrated by count of survivalcells and cloning efficiency. Meanwhile, using light/electron microscopy, stain of cytochem-istry (including immunoenzymatic technique) and flow cytometry, we found that HIMeg cellscould be further induced into more mature cells in megakaryocytic lineage confirmed by aseries of evidence, including the changes of cell morphology/structure and cytochemistry,increased expression of differentiation antigens on the cell surface, and polyploidization.So, it is possible for 1,25(OH)_2D_3 to promote the differentiation of the cells in megakaryo-cytic lineage in vivo and to be used to treat acute megakaryoblastic leukemia and other di-seases with mal     

Design,Synthesis and Antitumor Activity of a Novel Series of PAC-1 Analogues

A novel series of first procaspase activating compound(PAC-1) analogues was designed, synthesized and evaluated for antitumor activity towards two cell lines[human promyelocytic leukemia cell line(HL60) and human embryonic lung fibroblast cell line(HLF)] by the MTT[3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazo-liumromide] method in vitro. The structures of all the compounds were confirmed by ¹H NMR, MS and elemental analysis. Among the compounds synthesized,(E)-2-[(3-{[4-(tert-butyl)benzyl](methyl)amino}propyl)(methyl)amino]-N'-[4-(diethylamino)-2-hydroxybenzylidene]acetohydrazide(compound 6n) exhibits a good anti-proliferative activity to the majority of tumor cells tested, and selectively cleaves cancer cells. Thus, compound 6n was identified as promising lead compound for further structural modification.     

Hypericin-induced photocytotoxicity is connected with G2/M arrest in HT-29 and S-phase arrest in U937 cells

Susceptibility of the HT-29 human colon adenocarcinoma cell line and human myeloid leukemia cell line U937 to hypericin-mediated photocytotoxicity was investigated and compared in this study. Cellular parameters as viability, cell number, metabolic activity and total protein amount were monitored in screening experiments with subsequent cell-cycle analysis and apoptosis detection to determine the cellular response of the different tumor types to various concentrations of photoactivated hypericin. The results show concentration dependence of the photosensitizer's cytotoxicity on the studied cell lines, with higher sensitivity of U937 cells. Whereas the two extreme hypericin concentrations (1 x 10(-9) M and 1 x 10(-6) M) resulted in similar changes in all tested cellular parameters on the two studied cell lines, 1 x 10(-8) M and 1 x 10(-7) M hypericin treatment resulted in different responses of the cell lines in all monitored parameters except for viability. Although leukemic cells proved sensitive to both 1 x 10(-8) M and 1 x 10(-7) M hypericin, significant changes on HT-29 cells were detected only after the 1 x 10(-7) M hypericin concentration. Cell-cycle arrest was related to simultaneously occurring apoptosis in colon cancer. Remarkable is the difference in cell-cycle profile where G2/M arrest in colon cancer cells versus accumulation of leukemic cells in the S phase appears. This suggests that hypericin treatment affecting the cell-cycle machinery of different cancer cells is not universal in effect.