Carbon Chain Length Modulates MDA-MB-231 Breast Cancer Cell Killing Mechanisms by Mitochondrially Targeted Aryl−Urea Fatty Acids

Targeting the tumor cell mitochondrion could produce novel anticancer agents. We designed an aryl−urea fatty acid ( 1 g ; 16({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)hexadecanoic acid) that disrupted the mitochondrion and decreased MDA-MB-231 breast cancer cell viability. To optimize the aryl−ureas the present study evaluated mitochondrial targeting by 1 g analogues containing alkyl chains between 10–17 carbons. Using the dye JC-1, the C12−C17 analogues efficiently disrupted the mitochondrial membrane potential (IC₅₀s 3.5±1.2 to 7.6±1.1 μM) and impaired ATP production; shorter analogues were less active. 7-Aminoactinomycin D/annexin V staining and flow cytometry showed that these agents activated the killing mechanisms of necrosis and apoptosis to varying extents (7-aminoactinomycin D/annexin V staining ratios 4.3–6.0). Indeed, 1 g and its C17 analogue preferentially activated necrosis and apoptosis, respectively (ratios 2.1 and 16). Taken together, alkyl chain length is a determinant of mitochondrial targeting by aryl−ureas and can be varied to develop analogues that activate apoptosis or necrosis in a regulated fashion.     

鸡传染性喉气管炎的药物治疗对比试验

从流行病学、临床症状、病理变化和实验室检验四个方面对鸡传染性喉气管炎进行了诊断，并做了药物治疗对比试验．结果表明，杀病毒药(消毒王)加清热解毒、止咳平喘中草药配合治疗鸡传染性喉气管炎，效果更好，能较快地制止病鸡死亡，显著降低死亡率及减少药物治疗费用．     

Pharmacologic Control of CAR T Cells

Chimeric antigen receptor (CAR) therapy is a promising modality for the treatment of advanced cancers that are otherwise incurable. During the last decade, different centers worldwide have tested the anti-CD19 CAR T cells and shown clinical benefits in the treatment of B cell tumors. However, despite these encouraging results, CAR treatment has also been found to lead to serious side effects and capricious response profiles in patients. In addition, the CD19 CAR success has been difficult to reproduce for other types of malignancy. The appearance of resistant tumor variants, the lack of antigen specificity, and the occurrence of severe adverse effects due to over-stimulation of the therapeutic cells have been identified as the major impediments. This has motivated a growing interest in developing strategies to overcome these hurdles through CAR control. Among them, the combination of small molecules and approved drugs with CAR T cells has been investigated. These have been exploited to induce a synergistic anti-cancer effect but also to control the presence of the CAR T cells or tune the therapeutic activity. In the present review, we discuss opportunistic and rational approaches involving drugs featuring anti-cancer efficacy and CAR-adjustable effect.     

Revisiting Platinum-Based Anticancer Drugs to Overcome Gliomas

Although there are many patients with brain tumors worldwide, there are numerous difficulties in overcoming brain tumors. Among brain tumors, glioblastoma, with a 5-year survival rate of 5.1%, is the most malignant. In addition to surgical operations, chemotherapy and radiotherapy are generally performed, but the patients have very limited options. Temozolomide is the most commonly prescribed drug for patients with glioblastoma. However, it is difficult to completely remove the tumor with this drug alone. Therefore, it is necessary to discuss the potential of anticancer drugs, other than temozolomide, against glioblastomas. Since the discovery of cisplatin, platinum-based drugs have become one of the leading chemotherapeutic drugs. Although many studies have reported the efficacy of platinum-based anticancer drugs against various carcinomas, studies on their effectiveness against brain tumors are insufficient. In this review, we elucidated the anticancer effects and advantages of platinum-based drugs used in brain tumors. In addition, the cases and limitations of the clinical application of platinum-based drugs are summarized. As a solution to overcome these obstacles, we emphasized the potential of a novel approach to increase the effectiveness of platinum-based drugs.     

高黏度头孢菌素C发酵液的超滤研究

利用新型的板式超滤系统对高黏度头孢菌素C发酵液进行了澄清实验研究,通过实验数据与现有系统的运行数据对比,该系统基本解决了目前国内头孢菌素C发酵液超滤提纯中存在的主要过滤问题.     

包结拆分在手性药物分离中的机理与应用

对外消旋体药物进行分离拆分是获取手性药物的重要方法。探讨了环糊精体系包结拆分法的机理，并对运用其机理于手性药物分离中的应用作了探讨。     

2—（2—氨基噻唑—4—基）—2—甲氧基亚氨基乙酸乙酯的合成

以乙酰乙酸乙酯为起始原料,经肟化、甲基化、溴化和缩合四步反应合成2-(2-氨基噻唑-4-基)-2-甲氧基亚氨基乙酸乙酯,总收率63.14％,高于文献报道。     

新型头孢菌素药物及其中间体的合成

介绍了头孢菌素药物的现状及发展,同时综述了一些新型头孢药物。例如:头孢替安、头孢咪唑钠、头孢哌酮、头孢匹罗及重要中间体:1 [2 (N,N 二甲基氨基)乙基] 5 巯基1H 四氮唑、5,10 二氧5H,10H 二咪唑[1,5 α:1',5' α]吡嗪1,6 二碳酰二氯、2 氨基噻唑4 甲基异肟酸的合成方法。     

色谱技术在中药标准品制备中的应用

色谱技术是天然产物研究中重要的分离和纯化方法。本文介绍了色谱法，并综述了其在中药标准品制备中的应用，最后对此进行了展望。