Etoposide: four decades of development of a topoisomerase II inhibitor

Podophyllin-containing materials have been used as folk medicines for centuries. In the 1950s, scientists began a search to identify a more effective podophyllotoxin derivative. These efforts eventually resulted in the development of a new class of antineoplastic agents which target the DNA unwinding enzyme, topoisomerase II. The history of the development of one of the first identified topoisomerase II inhibitors, etoposide, is reviewed in this paper. Critical developments in etoposide's mechanism of action, pharmacology and administration schedule are summarised. The clinical benefits of the recently marketed etoposide prodrug, etoposide phosphate (Etopophos) are also detailed. The current status of other clinically approved anticancer agents which target topoisomerase II is briefly reviewed.     

Clinical applications of anticancer drugs targeted to topoisomerase II

Agents which 'poison' the enzyme topoisomerase II, have proven to be useful drugs for cancer treatment. Six antineoplastic drugs, which target topoisomerase II (doxorubicin, daunorubicin, idarubicin, mitoxantrone, etoposide and teniposide) are currently approved for clinical use in the United States. In this paper, the strategies and goals of cancer chemotherapy are summarized for the non-clinician. The use, pharmacology and toxicity of each of the six currently approved topoisomerase II inhibiting agents are reviewed.     

食糖市场营销战略分析

2005/06年制糖期全国食糖产量881.5万t,消费量估计达到1070万t,主产区白糖平均售价达到4500元/t,制糖企业取得很好效益.新形势下制糖行业将发生转变,一是食糖流通企业经过整合力量不断壮大,二是市场化、国际化程度逐步提高,三是食糖价格将总体走高,四是甜菜糖和淀粉糖将加速发展.在新形势下制糖企业必须努力提高市场竞争力,制定市场营销战略,重视销售网络渠道建设,不断扩大市场份额.     

The effect of magnetic field on the impurity binding energy of shallow donor impurities in a Ga1?xInxNyAs1?y/GaAs quantum well

Using a variational approach, we have investigated the effects of the magnetic field, the impurity position, and the nitrogen and indium concentrations on impurity binding energy in a Ga_1−xIn_xN_yAs_1−y/GaAs quantum well. Our calculations have revealed the dependence of impurity binding on the applied magnetic field, the impurity position, and the nitrogen and indium concentrations.     

Dark fermentative hydrogen production from sucrose and molasses

There are many factors affecting the dark fermentative hydrogen production. The interaction of these factors, that is, their combined effects, should be investigated for better design of the systems with stable and higher hydrogen yields. This study aimed to investigate the combined effects of initial substrate, pH, and biomass (or initial substrate to biomass) values on hydrogen production from sucrose and sugar‐beet molasses. Therefore, optimum initial chemical oxygen demand (COD), pH, and volatile suspended solids (VSS) or initial substrate to biomass (VSS) ratio (S/X_o) values leading to the highest dark fermentative hydrogen production were investigated in batch reactors. An experimental design approach (response surface methodology) was used. Results revealed that when sucrose was the substrate, maximum hydrogen production yield (HY) of 2.3 mol H₂/mol sucrose_added was obtained at initial pH of 7 and COD of 10 g/L. Initial S/X_o values studied (4–20 g COD/g VSS) had no effect on HY, while the initial pH was found as the parameter mostly affecting both HY and hydrogen production rate (HPR). When substrate was molasses, initial COD concentration was the only variable affecting HY and HPR. Maximum of both was achieved at 10 g/L initial COD. Initial VSS values studied (2.5–7.5 g/L) had no effect on HPR and HY. This study also indicated that molasses leads to homoacetogenesis for potentially containing intrinsic microorganism and/or natural constituents; thus, sucrose is more advantageous for hydrogen production via fermentation. Homoacetogenesis should be prevented for effective optimization via response surface methodology, if substrate is a natural carbon source potential to have intrinsic microorganisms. Copyright © 2017 John Wiley & Sons, Ltd.     

Determination of optimum hazelnut roasting conditions

The objective of this study was to test the hypothesis that the roasting conditions used for hazelnuts, such as the air temperature, air velocity and roasting time (independent variables), could be optimized by using Response Surface Methodology. Effects of independent variables on sensory and physical characteristics were determined. A consumer test was used to determine the acceptable samples. Very dark and very light roasted samples, corresponding to 165 °C, 3 m/s, 25 min and 125 °C, 1 m/s, 15 min process conditions, respectively, were unacceptable. Superimposed contour plots were used to determine the values of independent variables and these showed the process conditions where all product characteristics were acceptable to consumers. At low velocity (0.3 m/s), acceptable products were produced at about 165–179 °C for 20–25 min. When air velocity increased, air temperature shifted to lower temperatures. Samples roasted at 145 °C, 2 m/s, 28 min, 165 °C, 1 m/s, 25 min and 145 °C, 3.7 m/s, 20 min produced the most acceptable products. The sample roasted at 165 °C, 1 m/s, 25 min required the least air velocity and was the most economical in terms of energy consumed among the samples rated most acceptable by consumers.     

纳秒级d－T聚变反应的16．7MeVγ测量

ｄ－Ｔ聚变反应产生的１６７ＭｅＶγ射线很弱，必须从很强的γ、中于混合场中筛选出来，故要求探测系统有高的信噪比，快的时间响应和宽的动态范围。利用高能γ与介质相互作用的康普顿效应及其定量对应关系，由扇形聚焦磁场一次偏转，用ＣＯ２气体切连科夫探测器（ＧＣＤ）探测电子束，或由扇形聚焦磁场（ＳＣＤ）二次偏转，用有机玻璃切连科夫探测器测电子束。仔细考虑了探测装置的辐射屏蔽和探测系统的电磁屏蔽。分别在“闪光－１”装置、ＤＨＪ－２５回旋加速器和２ＭＶ直线加速器上对探测装置进行了模拟检验实验和标定实验。在实际测试中，首次获得了纳秒级ｄ－Ｔ聚变反应产生的１６７ＭｅＶγ波形。     

Induction of telomerase activity by UV-irradiation in Chinese hamster cells

Telomerase is a ribonucleoprotein whose activity has been detected in germline cells and in neoplastic and immortal cells. Telomerase compensates the telomere loss arising by the end replication problem by synthesizing telomeric repeats at the 3' end of the eukaryotic chromosomes. Telomerase is reactivated during cancer progression in human and mice. In order to determine whether the telomerase activity can be upregulated in vitro in response to DNA damaging agents, we examined the telomerase activity in five Chinese hamster cell lines following exposure to 5 J/m2 or 40 J/m2 UV-C radiation. All the cell lines tested showed an increase in telomerase activity in the PCR-based telomeric repeat amplification protocol (TRAP) in a dose dependent manner. This increase in telomerase activity correlated well with the number of cells being in the S and G2/M phase after UV exposure. However, in unirradiated control cells, similar levels of telomerase activity were observed in different phases of the cell cycle. Furthermore, telomeric signals were clustered in one or more parts of the disintegrating nuclear particles of the apoptotic cell as detected by fluorescence in situ hybridization (FISH). This is the first study to demonstrate the induction of telomerase activity following exposure to DNA-damaging agents like UV radiation in Chinese hamster cells in vitro.