Evaluation of drugs for elimination of leukemic cells from the bone marrow of patients with acute leukemia

Relatively nonmyelotoxic drugs and drug combinations were investigated for their ability to eliminate malignant cells from human bone marrow. In vitro 90% inhibitory concentration (IC90) doses were established on granulocyte macrophage colony-forming units (GM-CFU) in culture of bone marrow by using the GM-CFU assay for the following drugs: 4- hydroperoxycyclophosphamide (4-HC), Adriamycin, L-asparaginase, bleomycin, hydrocortisone, VP-16, spirogermanium, Taxol, and vincristine. The leukemic cell kill efficiency of these drugs at IC90 doses was compared with that of 4-HC on acute lymphoid leukemia (ALL) cell lines by using the limiting-dilution assay. Under these conditions, no single drug was superior to 4-HC. To increase the in vitro effect in leukemic cell kill, combinations of vincristine with hydrocortisone, Adriamycin, VP-16, and 4-HC were investigated. Vincristine at 1 to 5 micrograms/mL increased the marrow cytotoxicity of hydrocortisone, Adriamycin, and VP-16, but it was protective (subadditive) with 4-HC. Vincristine and 4-HC in combination was additive to supraadditive on ALL cell lines, increased the leukemic cell kill by one to two logs above 4-HC alone at IC90 doses (P less than .05), and was not affected by the addition of excess marrow cells. The recommended doses for chemopurging in clinical studies are vincristine, 1 to 5 micrograms/mL, plus 4-HC, 5 micrograms/mL.     

前列腺特异抗原研究进展与挑战(摘要)

前列腺特异抗原(ＰＳＡ)发现四分之一世纪以来,已成为诊断前列腺癌最有价值的肿瘤标志物。前列腺癌在男性癌症发病中占首位。自从80年代中期第一代检测ＰＳＡ的方法问世以来,前列腺癌的发病率有了显著改变。这部分归功于ＰＳＡ检测的增加,从而使前列腺癌得到早期诊断,这有利于将癌症控制在发病早期,增加治愈的可能性。虽然ＰＳＡ是一个有效的肿瘤标志物,并具有器官特异性,但其癌症特异性不高。ＰＳＡ升高也可见于其他良性前列腺疾病,尤其当ＰＳＡ浓度在4～10μｇ/Ｌ时。这个浓度范围被称为“诊断灰色区域”。对ＰＳＡ分子结构的研究主要集中…     

Study on liver injury models induced by CCl4 D-Gal and ANIT in mice

ＳｔｕｄｙｏｎｌｉｖｅｒｉｎｊｕｒｙｍｏｄｅｌｓｉｎｄｕｃｅｄｂｙＣＣｌ４ＤＧａｌａｎｄＡＮＩＴｉｎｍｉｃｅＹＡＮＧＸｉｎＢｏ１，ＨＵＡＮＧＺｈｅｎｇＭｉｎｇ１，ＣＡＯＷｅｎＢｉｎ１，ＺＨＥＮＧＭｉｎｇ１，ＣＨＥＮＨｏｎｇＹａｎ１，ＺＨＡＮ...     

Effects of sera from burn patients on human hepatocytic viscoelasticity

ＥｆｅｃｔｓｏｆｓｅｒａｆｒｏｍｂｕｒｎｐａｔｉｅｎｔｓｏｎｈｕｍａｎｈｅｐａｔｏｃｙｔｉｃｖｉｓｃｏｅｌａｓｔｉｃｉｔｙＷＡＮＧＸｉａｏＪｕｎ，ＬＵＯＸｉａｎｇＤｏｎｇ，ＬＵＯＱｉｎａｎｄＹＡＮＧＺｏｎｇＣｈｅｎｇＢｕｒｎＲｅｓｅａｒｃｈＩｎ...     

多聚二磷酸腺苷核糖合成酶抑制剂对血管紧张素Ⅱ刺激培养心肌细胞异常基因表达的阻止作用

目的:观察多聚二磷酸腺苷(ADP)核糖合成酶(PARP)抑制剂对血管紧张素Ⅱ(AngⅡ)刺激的乳鼠心脏心肌重构的预防作用.方法:新生大鼠心肌细胞原代培养,传代,用PARP抑制剂3-AB预处理细胞,观察PARP抑制剂对AngⅡ诱导心肌细胞PARP激活、PARPl表达,细胞内ROS产生和c-fos,ANP,β/aMHC基因表达的影响.结果:AngⅡ显著诱导心肌细胞PARP激活,ROS产生增加,PARPl、c-los、β/a-MHC、ANP基因表达增加.给予3-AB预处理可显著抑制AngⅡ诱导的上述变化.结论:AngⅡ可以诱导培养的心肌细胞内PARP激活,PARPl蛋白表达增加,3-AB预处理可以明显降低AngⅡ诱导的心肌细胞内异常基因表达增加,提示PARPl参与了心室重构的发生发展过程.     

Transfected leukocyte integrin CD11b/CD18 (Mac-1) mediates phorbol ester-activated, homotypic cell:cell adherence in the K562 cell line

The CD11b/CD18 leukocyte integrin molecule mediates diverse neutrophil adherence-related functions, including cell:cell and cell:extracellular matrix attachments. To study the individual role of this leukocyte integrin in cell adherence in hematopoietic cells, we expressed the CD11b/CD18 complex on the surface of K562 cells, a cell line derived from an individual with chronic myelogenous leukemia in blast crisis. We used an amphotrophic retroviral vector designated LCD18SN, harboring the complete coding sequence for the CD18 subunit, to transfer the CD18 cDNA into K562 cells and select stable cell lines. The CD11b subunit in the expression plasmid pREP4 was transfected into these K562/CD18 cells by electroporation and stable cell clones were selected. These K562 cells possessed RNA and intracellular protein for each subunit, and they expressed the CD11b/CD18 heterodimer on the cell surface. When CD11b/CD18 expressing K562 cells were stimulated with phorbol myristate acetate (50 ng/mL) for 24 to 48 hours, these K562 cells formed dense cell:cell aggregates. This homotypic aggregation required both activation of the CD11b/CD18 complex and the induction of the counter- receptor for CD11b/CD18 on the conjugate cell. This cell line will (1) enable the structure-function relationships between cell activation and homotypic adherence to be assessed, (2) provide the opportunity to identify accessory molecules required for activation of the CD11b/CD18 complex, and (3) facilitate the identification of novel ligands for the CD11b/CD18 complex.