Factors Influencing Compliance with Safe Handling Requirements of Anticancer Agents by Nurses in a Tertiary Hospital-A Secondary Publication

Purpose:This research aimed to identify leading factors that affect nurses’compliance with the safe handling of anticancer agents.Methods:Data were collected from 114 nurses working in the university hospital and were analyzed through independent t-test,one-way ANOVA,Pearson’s correlation coefficient,and multiple regression analysis using SPSS25.0.Results:The average level of compliance with the safe handling of anticancer agents was 3.73±0.33 out of 5 points.Workplace safety culture(β=0.40,P<0.001)and knowledge of safe handling(β=0.18,P=0.030)had significant influences on nurses’compliance with the safe handling of anticancer agents.The explained variance for compliance was 28.3%.Conclusion:To enhance the implementation of safety management for anticancer agents,each institution should strive to support human and material resources and enhance specialization in the workplace safety culture through system improvement.Based on the results of this study,we suggest research for the development of a training program for anticancer agent safety management.

Hetero-bimetallic transition metal-substituted Krebs-type polyoxometalate with N-chelating ligand as anticancer agents

A novel hetero-bimetallic transition metal(Sb^(Ⅴ)/Mn^(Ⅱ))-substituted Krebs-type polyoxometalate(POM)with N-chelating ligand H_(4)Na_(4)[Mn_(4)(H_(2)O)_(4)(trz)_(2)(SbO_(2))_(2)(SbW_(9)O_(33))_(2)]-20H_(2)O(Sb_(2)Mn_(2))(1)(trz=1,2,4-triazole)built from trilacunary Keggin POM unitα-B-[SbW_(9)O_(33)]^(9-){SbW_(9)]has been synthesized and characterized by single-crystal/powder X-ray diffraction and a wide range of analytical methods,including powder X-ray diffraction,Fourier transform infrared spectroscopy,Raman,ultraviolet-visible spectroscopy,electrospray ionization-mass spectroscopy,and thermogravimetric analysis.To further investigate the antitumor activity of the(Sb_(2)Mn_(2))(1)in human gastric cancer Human Gastric Adenocarcinoma Cells and Human Gastric Cancer Cell lines,in vitro cytotoxicity assay and flow cytometry analysis was performed.The results indicated that the IC_(50) values of(Sb_(2)Mn_(2))(1)on Human Gastric Adenocarcinoma(AGS)and Human Gastric Cancer(BGC-823)Cell Lines were 1.86±0.05μmol·L^(-1) and 14.61±0.55μmol·L^(-1),respectively.(Sb_(2)Mn_(2))(1)also exhibited high cytotoxicity on Human Gastric Cancer Cells and could induce cell apoptosis by inhibiting S and G_(2)/M cell cycles.Therefore,the result not only shows that this new POM-based inorganic-organic hybrid compound has high selectivity and low toxicity,but also provides an effective method for the development of potential transition metal-substituted POMs based antitumor drugs.

Novel anticancer agents from plant sources

植物仍然是新药，新药领先和新化学实体的重要来源。植物基于的药发现主要导致了 anticancer 和反传染的代理人的发展，并且继续在临床的试用贡献新领先。自然产品药在药品的照顾起一个主导的作用。几导出植物的混合物成功地当前在癌症治疗被采用。有为药的进一步的改进和开发学习的导出植物的细胞毒素的自然产品的许多类。从关于植物 antitumor 代理人的研究导出的新 anticancer 药将连续地被发现。这评论的基本目的是从药用的植物探索最新发现的 anticancer 混合物的潜力，作为为 anticancer 药开发的领先。在地球附近为研究人员和科学家从他们探索植物并且为新药发现的药用的价值将是有用的。

In vitro studies of polyethyleneimine coated miRNA microspheres as anticancer agents

RNA plays important roles as a gene-silencing agent, a therapeutic agent for clinical treatment, and in the differentiation, proliferation, and development of cells. However, RNA is very difficult to work with due to its sensitivity and fragility. Another obstacle in using RNA for gene delivery/silencing is its negative charge, which causes its repulsion by cell membranes, which are also negatively charged. Our recent study showed that miR-125b is upregulated in glioblastoma （GMB） and plays an oncogenic role in GMB cells by promoting cell proliferation and inhibiting apoptosis. Endogenous miR-125b can be blocked by transfection of its antisense RNA molecule, miR-125b antisense （miR-125b-AS）. Thus, miR- 125b-AS can be developed as an RNA-based agent for cancer treatment. However, instability during storage and difficulty in delivery into cells has limited the use of RNA-based therapies thus far. In the current work, we demonstrate a short and simple one-step technique for the preparation of positively charged RNA nanospheres （miR-125b-RNS and miR-125b-AS-RNS） coated with a bioavailable polymer, polyethylenimine （PEI）. These RNA nanospheres are able to penetrate the cell directly without the use of liposomes. Our study confirmed that converting miR-125b and miR-125b-AS into nanospheres is a viable approach for storing RNA. In addition, this study provides evidence that PEI-coated RNA nanospheres have the potential to be used as a novel class of anticancer a^ents.

Alkylating anticancer agents and their relations to microRNAs

Alkylating agents represent an important class of anticancer drugs.The occurrence and emergence of tumor resistance to the treatment with alkylating agents denotes a severe problem in the clinics.A detailed understanding of the mechanisms of activity of alkylating drugs is essential in order to overcome drug resistance.In particular,the role of non-coding microRNAs concerning alkylating drug activity and resistance in various cancers is highlighted in this review.Both synthetic and natural alkylating agents,which are approved for cancer therapy,are discussed concerning their interplay with microRNAs.

Anticancer Activities and QSAR Study of Novel Agents with a Chemical Profile of Benzimidazolyl-Retrochalcone

The present pharmacochemical and modelling work focused on a benzimidazolyl-chalcone series. These previously synthesized compounds were evaluated in vitro for their anticancer activities against a panel of seven human cancer cell lines and normal fibroblasts. Among the new benzimidazole-supported chalcones, nine (9) compounds (compounds 1 - 4, 6 - 8 and compounds 10 and 11) showed promising anticancer activities with IC50s ranging from 0.83 to 2.58 μM. Compounds 2 and 6 with IC50s of 0.83 and 0.86 μM, respectively, were shown to be potent inhibitors of HCT-116 colon cancer cell proliferation. It was therefore necessary, for a development of this new series of chalcones, to establish through a QSAR study, their quantum descriptors according to the DFT calculation method and following the B3LYP/6-31+G (d,p) theory. These descriptive and predictive studies focused on the colon HCT 116 cell line which was found to be more sensitive to the anticancer action of our benzimidazolyl-retrochalcones. QSAR study showed that the electronic energy (Eelec), lipophilicity (logP), chemical softness (S) and chemical hardness (η) of benzimidazolyl-retrochalcones play an important role in inhibiting cancer cell proliferation.

ANTICANCER AGENTS FROM TRADITIONAL CHINESE MEDICINE AND NATURAL PRODUCTS

Chemotherapy is still the effective strategy for treating cancer.It is important to explore anticancer agents from Traditional Chinese Medicine and Natural products.Different cancer cell lines were included in our research,such as HL60,K562,K562/ADR,KB,KBv200 cells.Cell growth inhibition assay,Annexin V-FITC/PI double-staining assay,measurement of reactive

Anticancer and cytotoxic properties of the latex of Calotropis procera in a transgenic mouse model of hepatocellular carcinoma

AIM： To evaluate the anticancer property of the dried latex （DL） of Calotropis procera, a tropical medicinal plant, in the X15-myc transgenic mouse model of hepatocellular carcinoma and to elucidate its mechanism of action in cell culture. METHODS： The young transgenic mice were orally fed with the aqueous suspension of DL （400 mg/kg for 5 d/wk） for 15 wk and their liver was examined for histopathological changes at 20 wk. Serum levels of vascu- lar endothelial growth factor （VEGF） were also measured in these animals. To characterize the active fraction, DL was extracted with petroleum ether followed by methanol. The methanolic extract was sub-fractionated on a silica gel G column using a combination of non-polar and polar solvents and eleven fractions were obtained. Each fraction was analysed for cytotoxic effect on hepatoma （Huh7） and non-hepatoma （COS-1） cell lines and nontransformed hepatocytes （AML12） using tetrazolium （MTT） assay. Finally, the mechanism of cell death was investigated by measuring the levels of Bcl2, caspase 3 and DNA fragmentation. RESULTS： DL treatment of mice showed a complete protection against hepatocarcinogenesis. No adverse effect was observed in these animals. The serum VEGF level was significantly lowered in the treated mice as compared to control animals. Cell culture studies revealed that the methanolic extract of DL as well as its fraction 8 induced extensive cell death in both Huh-7 and COS-1 cells while AML12 cells were spared. This was accompanied by extensive fragmentation of DNA in Huh-7 and COS-1 cells. No change in the levels of canonical markers of apoptosis such as Bcl2 and caspase 3 was observed. CONCLUSION： DL of C. procera has the potential for anti-cancer therapy due to its differentJable targets and non-interference with regular pathway of apoptosis.

Anticancer Activities of Plant Secondary Metabolites:Rice Callus Suspension Culture as a New Paradigm

Plant natural products including alkaloids,polyphenols,terpenoids and flavonoids have been reported to exert anticancer activity by targeting various metabolic pathways.The biological pathways regulated by plant products can serve as novel drug targets.Plant natural compounds or their derivatives used for cancer treatment and some novel plant-based compounds which are used in clinical trials were discussed.Callus suspension culture with secondary metabolites can provide a continuous source of plant pharmaceuticals without time and space limitations.Previous research has shown that rice callus suspension culture can kill>95%cancer cells with no significant effect on the growth of normal cells.The role of candidate genes and metabolites which are likely to be involved in the process and their potential to serve as anticancer and anti-inflammatory agents were discussed.Large scale production of plant callus suspension culture and its constituents can be achieved using elicitors which enhance specific secondary metabolites combined with bioprocess technology.

Identification of a dihydroorotate dehydrogenase inhibitor thatinhibits cancer cell growth by proteomic profiling

Dihydroorotate dehydrogenase(DHODH)is a central enzyme of the de novo pyrimidine biosynthesis pathway and is a promising drug target for the treatment of cancer and autoimmune diseases.This study presents the identification of a potent DHODH inhibitor by proteomic profiling.Cell-based screening revealed that NPD723,which is reduced to H-006 in cells,strongly induces myeloid differentiation and inhibits cell growth in HL-60 cells.H-006 also suppressed the growth of various cancer cells.Proteomic profiling of NPD723-treated cells in ChemProteoBase showed that NPD723 was clustered with DHODH inhibitors.H-006 potently inhibited human DHODH activity in vitro,whereas NPD723 was approximately 400 times less active than H-006.H-006-induced cell death was rescued by the addition of the DHODH product orotic acid.Moreover,metabolome analysis revealed that H-006 treatment promotes marked accumulation of the DHODH substrate dihydroorotic acid.These results suggest that NPD723 is reduced in cells to its active metabolite H-006,which then targets DHODH and suppresses cancer cell growth.Thus,H-006-related drugs represent a potentially powerful treatment for cancer and other diseases.

Inhibition of Probimane on Lipid Peroxidation of Rabbit and Human Erythrocytes

Lipid peroxide (LPO) plays pivotal roles in the process and development of many diseases. In this work, we studied the inhibitory effect of probimane (Pro), a Chinese anticancer agent, on erythrocyte LPO and the interaction of Pro with sialic acids (sia). Malondialdehyde (MDA) of erythrocytes activated by hydrogen peroxide was measured. Pro was found to inhibit the product of LPO induced by hydrogen peroxide in a non-enzyme system of both rabbit and human erythrocytes in the absence of doxorubicin. Sia were found to enhance LPO production and the activity of N-glycolylneuraminic acid (NeuGc) was about 5 times higher than that of N-acetylneuraminic acid (5AcNeu) at equivalent concentrations. Pro inhibited the increased LPO production induced by sia and the activity of Pro against LPO with 5AcNeu was almost twofold higher than that of Pro alone. It suggests that Pro be an inhibitor of LPO (free radicals) and as a functional modulator of sia in body.

Synthesis and Cytotoxic Activity of Novel Tetrahydrocurcumin Derivatives Bearing Pyrazole Moiety

Tetrahydrocurcumin(THC)is a major metabolite of curcumin and plays an important role in curcumin-induced biological effects.THC is a promising preventive and chemotherapeutic agent for cancer.A series of new pyrazole derivatives of THC have been synthesized as potent anticancer agents.Direct condensation of THC with various substituted hydrazines leads to new pyrazole derivatives of THC(1-18).The prepared compounds have been evaluated via in vitro MTT(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide)assay for their cell proliferation-inhibitory activity against human lung adenocarcinoma(A549),human cervical carcinoma(HeLa)and human breast carcinoma(MCF-7)cells.Most derivatives show significantly higher anticancer activity against all three tested cancer cell lines than the parent compound THC.Several compounds(7,8,12,13 and 15)display promising anticancer activity against MCF-7 cell line with IC50 values ranging from 5.8 to 9.3 iM.The most active compound(8)is substituted with 4-bromophenyl group at the pyrazole ring and inhibits the growth of all three tested cancer cell lines with an IC50 values of(8.0 iM,A549),(9.8 iM,HeLa)and(5.8 iM,MCF-7).The obtained compounds can be a good starting point for the development of new lead molecules in the fight against cancer.

A Systematic Review of Anticancer Effects of Radix Astragali

Objective： To review the anticancer effects of Radix astragali （RA）, one of the most commonly used herbs to manage cancer in East Asia, and its constituents and to provide evidence of clinical usage through previously performed clinical studies. Methods： Preclinical and clinical studies related to the anticancer effects of RA were searched from inception to November 2013 in electronic databases. Two reviewers independently investigated 92 eligible studies, extracted all the data of studies and appraised methodological quality of clinical trials. The studies were categorized into in vitro and in vivo experimental studies and clinical studies, and analyzed by saponins, polysaccharides, and flavonoids of RA constituents, RA fraction, and whole extract. Results： In preclinical studies, RA was reported to have tumor growth inhibitory effects, immunomodulatory effects, and attenuating adverse effects by cytotoxic agents as well as chemopreventive effects. Saponins seemed to be the main constituents, which directly contributed to suppression of tumor growth through the activation of both intrinsic and extrinsic apoptotic pathway, modulation of intracellular signaling pathway, and inhibition of invasion and angiogenesis. Flavonoids suppressed tumor growth through the similar mechanisms with saponins. Polysaccharides showed immunomodulatory effects, contributing tumor shrinkages in animal models, despite the low cytotoxicity to cancer cells. Most of the clinical studies were performed with low evidence level of study designs because of various limitations. RA whole extracts and polysacchaddes of RA were reported to improve the quality of life and ameliorate myelosuppression and other adverse events induced by cytotoxic therapies. Coaclusion： The polysaccharides, saponins, and flavonoids of RA, and the whole extract of RA have been widely reported with their anticancer effects in preclinical studies and showed a potential application as a adjunctive cancer therapeutics with the activities of irnmunomodulation, anti-proUferation and attenuation of adverse effects induced by cytotoxic therapy.

Auranofin and its analogs as prospective agents for the treatment of colorectal cancer

Today colorectal cancer(CRC)is one of the leading causes of cancer death worldwide.This disease is poorly chemo-sensitive toward the existing medical treatments so that new and more effective therapeutic agents are urgently needed and intensely sought.Platinum drugs,oxaliplatin in particular,were reported to produce some significant benefit in CRC treatment,triggering the general interest of medicinal chemists and oncologists for metal-based compounds as candidate anti-CRC drugs.Within this frame,gold compounds and,specifically,the established antiarthritic drug auranofin with its analogs,form a novel group of promising anticancer agents.Owing to its innovative mechanism of action and its favorable pharmacological profile,auranofin together with its derivatives are proposed here as novel experimental agents for CRC treatment,capable of overcoming resistance to platinum drugs.Some encouraging results in this direction have already been obtained.A few recent studies demonstrate that the action of auranofin may be further potentiated through the preparation of suitable pharmaceutical formulations capable of protecting the gold pharmacophore from unselective reactivity or through the design of highly synergic drug combinations.The perspectives of the research in this field are outlined.

Rational design of multi-targeting ruthenium-and platinum-based anticancer complexes

Platinum-based anticancer drugs, including cisplatin and its analogues, have played important roles in the clinical treatment of solid tumors over the past 38 years. However, poor selectivity, high toxicity and intrinsic or acquired drug resistance profoundly limit their application, which encourages the development of novel transition metal-based anticancer agents with different mechanisms of action. To this end, transition metal complexes that can simultaneously act on more than one target, termed as single-molecule multi-targeting complexes, have attracted increasing attention because of their enhanced efficacy and diminished chance of drug resistance. In this review, we systematically discuss the recent progress in the development of platinum- and ruthenium-based anticancer agents, in particular the rational design of platinum and ruthenium complexes with multi-targeting features.

Efficient synthesis of ethyl 4-[N-methyl-N-(2,3-aziridinyl)amino]benzoate and diethyl N-{4-[N-methyl-N-(2,3-aziridinyl)amino]benzoyl}-L-glutamate

Aziridine and its N-substituted derivatives could undergo nucleophilic ring opening reaction with biological molecules, leading to their alkylation and the loss of their biological activities. For this purpose, ethyl 4-[N-methyl-N-（2,3-aziridinyl）amino] benzoate and diethyl N-{4-[N-methyl-N-（2,3-aziridinyl）amino]benzoyl}-L-glutamate, as the key intermediates in the synthesis of new anticancer agents, were designed and synthesized via four steps of reactions in good yields.

Euphorbia factor L2 induces apoptosis in A549 cells through the mitochondrial pathway

Euphorbia factor L2, a lathyrane diterpenoid isolated from caper euphorbia seed(the seeds of Euphorbia lathyris L.), has been traditionally applied to treat cancer. This article focuses on the cytotoxic activity of Euphorbia factor L2 against lung carcinoma A549 cells and the mechanism by which apoptosis is induced. We analyzed the cytotoxicity and related mechanism of Euphorbia factor L2 with an MTT assay, an annexin V-FITC/PI test, a colorimetric assay, and immunoblotting. Euphorbia factor L2 showed potent cytotoxicity to A549 cells. Euphorbia factor L2 led to an increase in reactive oxygen species(ROS) generation,a loss of mitochondrial electrochemical potential, release of cytochrome c, activation of caspase-9 and caspase-3, and cleavage of poly(ADP-ribose) polymerase, suggesting that Euphorbia factor L2 induced apoptosis through a mitochondrial pathway. The cytotoxic activity of Euphorbia factor L2 in A549 cells and the related mechanisms of apoptotic induction provide support for the further investigation of caper euphorbia seeds.

The Role of Chinese Medicine in Clinical Oncology

Chinese Medicine（CM）has been used for several thousand years,playing an important role in the prevention and treatment of diseases including cancer.In the recent four decades,a number of CM herbs have aroused extreme interest in the world-isolating anticancer components from medicinal herbs,using them as biological response modifiers,and most recently as angiogenesis inhibitors.The present review reports both the experimental and clinical results obtained in the field of clinical oncology,especially conducted by our group.The review also presents the possible future of integration of CM and modern medicine in basic research and clinical practice,especially when CM used as adjuvant and maintenance therapy.

In vitro cytotoxicity and antimicrobial activity of Talaromyces flavus SP5 inhabited in the marine sediment of Southern Coast of India

Marine sediment samples were collected from the coastal areas of Southern India, particularly in Kanyakumari District. Twenty-eight different fungal strains were isolated. The screening of fungi from marine sediment was done to isolate a potent fungus that can produce bioactive compounds for biomedical applications. Only three strains viz Trichoderma gamsii SP4, Talaromyces flavus SP5 and Aspergillus oryzae SP6 were screened for further studies. The intracellular bioactive compounds were extracted using solvent extraction method. The crude extracts were tested for its anti-microbial and anti-cancer properties and analytically characterized using Gas Chromatography Mass Spectrometry(GC-MS). All the three extracts were active, but the extract from T. flavus SP5 was found to be more active against various human pathogens, viz., Pseudomonas aeruginosa ATCC 27853(17.8 ± 0.1), Escherichia coli ATCC 52922(18.3 ± 0.3), and Candida tropicalis ATCC 750(17.7 ± 0.4). It also exhibited cytotoxic activity against HEp2 carcinoma cell line with the LC_(50) value of 25.7 μg·mL^(-1). The GC-MS data revealed the presence of effective bioactive compounds. These results revealed that the extract from isolated fungus T. flavus SP5 acted as a potent antimicrobial, antifungal, and anticancer agent, providing basic information on the potency of marine fungi towards biomedical applications; further investigation may lead to the development of novel anticancer drugs.

Synthesis of Chlorin-enediyne Dyads by Palladium-catalyzed Coupling Reaction

Methyl 9 ethylenedioxpyropheophorbide d was prepared from methyl pyropheophorbide a by protection of cyclic ketone with ethylene glycol, and oxidation with OsO 4 in vinyl group at 2 position. The terminal alkyne was introduced into chlorin chromophore by Grignard reaction, and the enediyne moiety was constructed by a palladium catalyzed coupling reaction with (Z) chloroenynes.