Microfluidics:Emerging prospects for anti-cancer drug screening

Cancer constitutes a heterogenic cellular system with a high level of spatio-temporal complexity.Recent discoveries by systems biologists have provided emerging evidence that cellular responses to anti-cancer modalities are stochastic in nature.To uncover the intricacies of cell-to-cell variability and its relevance to cancer therapy,new analytical screening technologies are needed.The last decade has brought forth spectacular innovations in the field of cytometry and single cell cytomics,opening new avenues for systems oncology and high-throughput real-time drug screening routines.The up-and-coming microfluidic Lab-on-a-Chip(LOC)technology and micrototal analysis systems(μTAS)are arguably the most promising platforms to address the inherent complexity of cellular systems with massive experimental parallelization and 4D analysis on a single cell level.The vast miniaturization of LOC systems and multiplexing enables innovative strategies to reduce drug screening expenditures while increasing throughput and content of information from a given sample.Small cell numbers and operational reagent volumes are sufficient for microfluidic analyzers and,as such,they enable next generation high-throughput and high-content screening of anticancer drugs on patient-derived specimens.Herein we highlight the selected advancements in this emerging field of bioengineering,and provide a snapshot of developments with relevance to anti-cancer drug screening routines.

HPLC Method Research of Picoplatin-a New Platinum Anti-cancer Drug and Its Impurities

Purpose: To establish a HPLC testing method of the content of bulk picoplatin and its impurities. Method: the separation was perform on a C18 column(4.6 mm×250 mm, 5 m) with potassium dihydrogen phosphate-aceton-itrile as the mobile phase at a flow rate of 1.0 mL/min. The detecting wavelength was set at 210 nm, and the column temperature was set at 30℃. Result: in the method validation, the linear relationship modulus of picoplatin is 0.9999, the systemic precision is 0.44%, the method precision is 0.74%, the average recovery rate is 99.62%, the LOD and LOQ of picoplatin is 0.2 ng and 1.0 ng. The average resolution of picoplatin and its impurities is more than 2. Conclusion: The established method is good specificity, high sensitivity, and good repeatability which could provide scientific evidence for the quality control of picoplatin and its impurities.

Carbohydrate-associated epitope-based anti-cancer drugs and vaccines

RP215 is one of the three thousand monoclonal antibodies (Mabs) which were generated against the OC-3-VGH ovarian cancer cell line. RP215 was shown to react with a carbohydrate-associated epitope located specifically on glycoproteins, known as CA215, from cancer cells. Further molecular analysis by matrix adsorption laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) revealed that CA215 consists mainly of immunoglobulin super-family (IgSF) proteins, including immunoglobulins, T-cell receptors, and cell adhesion molecules, as well as several other unrelated proteins. Peptide mappings and glycoanalysis were performed with CA215 and revealed high-mannose and complex bisecting structures with terminal sialic acid in N-glycans. As many as ten O-glycans, which are structurally similar to those of mucins, were also identified. In addition, two additional O-linked glycans were exclusively detected in cancerous immunoglobulins but not in normal B cell-derived immunoglobulins. Immunizations of mice with purified CA215 resulted in the predominant generation of RP215-related Mabs, indicating the immunodominance of this carbohydrate-associated epitope. Anti-idiotype (anti-id) Mabs of RP215, which were generated in the rat, were shown to contain the internal images of the carbohydrate-associated epitope. Following immunizations of these anti-id Mabs in mice, the resulting anti-anti-id (Ab3) responses in mice were found to be immunologically similar to that of RP215. Judging from these observations, anti-id Mabs, which carry the internal image of the RP215-specific epitope, may be suitable candidates for anticancer vaccine development in humans.

Control the Silver Content in the Preparation Process of Platinum Group Anti-cancer Drugs

In order to control the silver content in the preparation process of platinum group anti-cancer drugs, we put two kinds of color reagent to color in the production process of the platinum anti-cancer drugs by UV spectra measurement to control drugs production of platinum anticancer, thus we could control the silver content in the drugs so that it meets the pharmacopoeia standards of US and

Regulation of “Checkpoint Molecule” Sheds New Light on Anti-Cancer Drug Development

The rivalry between T cells and tumor cells somewhat mimics the scene of 'Tom and Jerry,' an animated series in which Tom (a house cat) rarely succeeds in catching Jerry (a mouse), mainly because of Jerry’s cleverness and cunning abilities. In a way, tumor cells are like Jerry, in terms of their crafty and sneaky features.

Bridging academic science and clinical research in the search for novel targeted anti-cancer agents

This review starts with a brief history of drug discovery & development, and the place of Asia in this worldwide effort discussed. The conditions and constraints of a successful translational R&D involving academic basic research and clinical research are discussed and the Singapore model for pursuit of open R&D described. The importance of well-characterized, validated drug targets for the search for novel targeted anti-cancer agents is emphasized, as well as a structured, high quality translational R&D. Furthermore, the characteristics of an attractive preclinical development drug candidate are discussed laying the foundation of a successful preclinical development. The most frequent sources of failures are described and risk management at every stage is highly recommended. Organizational factors are also considered to play an important role. The factors to consider before starting a new drug discovery & development project are described, and an example is given of a successful clinical project that has had its roots in local universities and was carried through preclinical development into phase I clinical trials.

Drug-Drug Interactions in Patients with Breast Cancer

The research paper investigates the intricate landscape of drug-drug interactions (DDIs) within the context of breast cancer treatment, with a particular focus on the elderly population and the use of complementary and alternative medicine (CAM). The study underscores the heightened susceptibility of elderly patients to DDIs due to the prevalence of polypharmacy and the widespread utilization of CAM among breast cancer patients. The potential ramifications of DDIs, encompassing adverse drug events and diminished treatment efficacy, are elucidated. The paper accentuates the imperative for healthcare providers to comprehensively understand both conventional and CAM therapies, enabling them to provide patients with informed guidance regarding safe and efficacious treatment options, culminating in enhanced patient outcomes.

Utilization of kinase inhibitors as novel therapeutic drug targets:A review

Kinase inhibitors are a significant and continuously developing division of target therapeutics.The drug discovery and improvement efforts have examined numerous attempts to target the signaling pathway of kinases.The Kinase inhibitors have been heralded as a game-changer in cancer treatment.For developing kinase inhibitors as a treatment for various non-malignant disorders like auto-immune diseases,is currently undergoing extensive research.It may be beneficial to investigate whether cell-specific kinase inhibitor administration enhances therapeutic efficacy and decreases adverse effects.The goal of the current review is to gain insight into the role of kinase inhibitors in facilitating effective target drug delivery for the treatment of various anti-inflammatory,auto-immune,and anticancer disorders.The aim of this review is also to shed light on drug discovery approaches for kinase inhibitors,their mode of action,and delivery approaches.The variation in the binding of kinases bestows different target approaches in drug design,which can be employed for designing the targeted molecules.Several target sites have been studied,exceeding the design of drugs for various diseases like cancer,Alzheimer’s,rheumatoid arthritis,etc.Diverse delivery approaches have also been studied for the targeted application of kinase inhibitors.

国医大师王晞星辨治肺腺癌靶向相关性药疹经验采菁

王晞星教授认为少阳枢机不利,风湿热毒之邪侵袭为靶向药酪氨酸酶抑制剂所致药疹之核心病机。治法上强调以“和解”为本,通过和枢机、解郁结、清热利湿解毒之法治疗本病,并在此基础上创制柴胡土茯苓合剂方。临床中若治疗得当,病邪可从少阳经外出入太阳表经;若失治误治,病邪可内传少阴出现少阴热化证。强调应重视疾病所处病机阶段,准确辨证,方能取得佳效。

Targeting SAMHD1: To overcome multiple anti-cancer drugs resistance in hematological malignancies

Sterile α motif and histidine/aspartic acid domain containing protein 1 (SAMHD1) is a deoxynucleoside triphosphate (dNTPs) triphosphohydrolase that can hydrolyze dNTPs into deoxynucleosides and triphosphates to keep the balance of the intracellular dNTPs pool. Moreover, it has been reported that SAMHD1 plays a role in regulating cell proliferation and the cell cycle, maintaining genome stability and inhibiting innate immune responses. SAMHD1 activity is regulated by phosphorylation, oxidation, SUMOylation, and O-GlcNAcylation. SAMHD1 mutations have been reported to cause diseases, including chronic lymphocytic leukemia and mantle cell lymphoma. SAMHD1 expression in acute myeloid leukemia predicts inferior prognosis. Recently, it has been revealed that SAMHD1 mediates the resistance to anti-cancer drugs. This review will focus on SAMHD1 function and regulation, the association between SAMHD1 and hematological malignancies and will provide updated information on SAMHD1 mediating resistance to nucleoside analogue antimetabolites, topoisomerase inhibitors, platinum-derived agents and DNA hypomethylating agents. Furthermore, histone deacetylase inhibitors and tyrosine kinase inhibitors indirectly increase anti-cancer drug resistance by increasing SAMDH1 activity. We herein highlight the importance of the development of novel agents targeting SAMHD1 to overcome treatment resistance of hematological malignancies, which would be an opportunity to improve the outcome of patients with refractory hematological malignancies.

周恩超教授治疗抗肿瘤药物相关性肾损害经验

抗肿瘤药物相关性肾损害是恶性肿瘤治疗过程中的常见不良反应之一。中医的整体观念和辨证论治对于抗肿瘤药物相关性肾损害有着独特的优势。周恩超教授认为,“肾元亏虚”和“肾毒”在本病的发生发展过程中起着十分重要的作用。他提倡在整个治疗过程中运用益肾解毒的方法,并在临床实践中取得了显著的治疗效果。

清热解毒药与活血药相配伍的实验研究

观察了清热解毒药与活血药相配伍对内毒素血症和非特异性炎症动物模型的作用。两药配伍使ＰＧＥ＿２、内毒素血浓度、全血还原粘度降低，伊文斯蓝渗出量减少，足爪肿胀百分率下降，血浆皮质醇含量增加，纤溶活性增强。其中多数测定结果均优于两药单独使用。表明两药相配伍更有利于解毒、消炎和炎症的恢复。

清热解毒药与泻火药相配伍的实验研究

清热解毒药和泻火药配伍防止了内毒素造型家兔ＨＣＴ、血液粘度、ＰＴＴ、纤溶活性的异常变化，降低内毒素、ＰＧＥ＿２含量。并使大鼠踝关节肿胀率、小鼠伊文斯蓝惨出量明显减少。但二药苦寒又可伤正，值得临床注意。

解毒活血配伍方药对载脂蛋白E基因敲除小鼠血清超敏C反应蛋白的影响

目的观察解毒活血配伍方药对载脂蛋白E基因敲除[apolipoprotein E gene knock-out,ApoE(-/-)mice]小鼠血清超敏C反应蛋白(hs-CRP)的影响。方法13周龄110只ApoE(-/-)小鼠分为高脂饲料组(98只,给予高脂饲料),普通饲料组(12只,给予普通饲料),同时设13周龄C57BL/6J小鼠作为正常对照组(12只,给予普通饲料)。19周后随机抽取高脂饲料ApoE(-/-)小鼠2只确认易损斑块形成后,剩余96只随机分为8组(模型组、解毒组、活血组、解毒活血配伍高、中、低剂量组、洛伐他汀组和血脂康组),每组12只。造模成功后每天给予药物干预,解毒组予虎杖提取物26·6mg/kg;活血组予芎芍胶囊110mg/kg;配伍高剂量组予虎杖提取物53·2mg/kg,芎芍胶囊220mg/kg;配伍中剂量组给予虎杖提取物26·6mg/kg,芎芍胶囊110mg/kg;配伍低剂量组给予虎杖提取物13·3mg/kg,芎芍胶囊55mg/kg;洛伐他汀组给予洛伐他汀3·3mg/kg;血脂康组给予血脂康0·2g/kg;以上药物根据剂量蒸馏水溶解,混匀后灌胃,每次0·4mL。模型组、普通饲料组、C57BL/6J小鼠对照组均灌服生理盐水0·4mL。用药17周后,下腔静脉取血,全自动酶标仪检测血清hs-CRP浓度。结果模型组血清hs-CRP水平显著高于正常对照组和普饲组(P<0·05,P<0·01);各给药组中,洛伐他汀组、解毒组和配伍高剂量组hs-CRP水平下降,与模型组比较,差异有统计学意义(P<0·01);配伍高剂量组hs-CRP水平低于洛伐他汀组、血脂康组、单纯解毒或活血组及配伍中、低剂量组;解毒组hs-CRP水平低于活血组(P<0·01)。结论解毒活血配伍方药可降低ApoE(-/-)小鼠血清hs-CRP水平。

中药注射剂常见联合用药类型及其配伍禁忌文献研究

目的通过文献研究探索中药注射剂联合用药过程中产生配伍禁忌的规律性和特殊性,为中药注射剂配伍禁忌研究提供指导,也为临床安全合理地使用中药注射剂提供参考。方法基于功能主治将中药注射剂分为抗肿瘤类、活血化瘀类、清热解毒类、急救类和其他类型,总结各类中药注射剂常见联合用药类型。选择36种临床常用中药注射剂,基于联合用药类型对其配伍禁忌情况进行归纳和分析。结果抗肿瘤类中药注射剂常与基础化疗药物联合使用;相对于心脑血管类和清热解毒类中药注射剂,抗肿瘤类中药注射剂配伍禁忌研究相对较少。清热解毒类中药注射剂常与抗菌药联合使用;清热解毒类中药注射剂与抗菌药混合后,普遍会发生不溶性微粒增加、产生沉淀等配伍禁忌现象。活血化瘀类中药注射剂常与循环系统药物联合使用;此外,活血化瘀类中药注射剂+抗菌药也是常见的联合用药类型。结论中药注射剂配伍禁忌具有一定的规律性和特殊性,但是,当前中药注射剂配伍禁忌研究内容简单粗放,研究水平参差不齐。

解毒化瘀中药对急性淋巴细胞白血病模型小鼠的改善作用

背景:研究表明,白血病患者需要及早行化疗延缓病情进展,中草药对该病治疗效果甚微,还有研究持相反意见,认为中草药联合化疗可以一定程度提高患者的治愈率。由于中草药成分复杂,治疗的机制尚不明确。目的:探究解毒化瘀中药对急性淋巴细胞白血病模型小鼠的影响。方法:将白血病细胞株L1210和白血病耐药细胞分别从小鼠尾静脉注入体内制备急性淋巴细胞白血病模型,随机分为白血病模型组、解毒化瘀中药低浓度组、解毒化瘀中药高浓度组,另设正常对照组。造模成功后第2天按照10,50 mg/kg给药,连续7 d,于每周一早晨7点取尾静脉血,连续5周,采用MTT检测白血病耐药细胞生存率,分析血细胞种类及血象;Westernblot法检测小鼠骨髓中NF-κB/P65、NF-κB/P50、IκBα、PTEN、Akt、Bcl-2及p-Akt蛋白的表达。结果与结论:①与白血病模型组比较,解毒化瘀中药低、高浓度组白血病耐药细胞存活率显著降低,差异有显著性意义(P <0.01);②与模型组比较,解毒化瘀中药低、高浓度组小鼠骨髓中NF-κB/P65、NF-κB/P50、IκBα、Bcl-2、Akt、p-Akt蛋白表达量显著降低,PTEN蛋白表达量显著升高,差异有显著性意义(P <0.01);③与模型组相比,解毒化瘀中药低、高浓度组白细胞、淋巴细胞、L1210细胞显著降低,中性粒细胞显著升高,差异有显著性意义(P<0.01);④结果表明,解毒化瘀中药通过阻断PI3K/Akt及NF-κB信号通路实现抑制L1210细胞增殖效应,从而缓解和治疗急性淋巴细胞白血病。

中西医结合若干问题的比较思考

讨论中西医结合对西医临床思维的影响。对于慢性病中医注意病人的主观症状,与病人就医的缘由一致;西医重视客观的功能和结构异常,其判断结果有时未必能被病人接受。近年来西医开始重视病人的生活质量,其实中医的辨证指标有很多就是针对病人的生活质量。中医的整体观念同样体现在急性感染的治疗中,现代研究显示,清热解毒法除祛邪外也兼顾扶正。中西医结合促进了中西药合用,但须注意合理应用,避免合用的不良效果。

清瘟解毒方治疗流感B病毒上呼吸道感染的观察护理

目的:探讨清瘟解毒方治疗流感B病毒上呼吸道感染的效果。方法:将 60例流感B病毒感染的患者随机分为观察组 30例和对照组 30例;观察组服用清瘟解毒方,每日 1剂,分 2次服,对照组服用病毒唑, 3次 /d,比较两组患者服药后体温及症状的变化。结果:观察组在体温恢复效果上显著优于对照组 (P<0.005),治愈率明显高于对照组。结论:清瘟解毒方治疗流感B病毒上呼吸道感染效果显著,副作用少。

我国《禁毒法》对艾滋病减少危害战略的含义

通过对比《全国人大常委会关于禁毒的决定》和《中华人民共和国禁毒法》的不同之处及其对减少伤害政策的含义,分析在我国预防和控制艾滋病时实施减少伤害政策中的伦理问题,认为推行美沙酮的新政策,对于控制吸毒和艾滋病的作用都是巨大的。

清热解毒药在“以痈论治”消化性溃疡中现代临床应用

近年来我国消化系统疾病患者逐年增多,其中消化性溃疡为临床上常见疾病之一。周学文教授认为“胃毒热证”为其基本证候,“以痈论治”为其基本治则。清热解毒药物因其具有显著疗效而作为治疗消化性溃疡的常用药物,该文主要通过讨论“毒热”与消化性溃疡之间的关系、古代医家对于使用清热解毒药物治疗消化性溃疡的经验以及清热解毒药物治疗消化性溃疡的理论依据,从根本上提出两者之间的关联,为日后消化性溃疡的临床治疗提出理论性参考。