An Investigation of Oxidative DNA Damage in Pharmacy Technicians Exposed to Antineoplastic Drugs in Two Chinese Hospitals Using The Urinary 8-OHdG Assay

Objective To investigate oxidative DNA damage in pharmacy technicians preparing antineoplastic drugs at the PIVAS （Pharmacy Intravenous Admixture Service） in two Chinese hospitals. Methods Urinary 8-OHdG served as a biomarker. 5-Fluorouracil （5-FU） concentrations in air, masks and gloves were determined. The spill exposure of each PIVAS technician to antineoplastic drugs was investigated. Eighty subjects were divided into exposed group t, II, and control group I, II. Results 5-FU concentration ratios for gloves and masks in exposed group I were significantly higher than those in exposed group II （P〈0.05 or P〈0.01）. The average urinary 8-OHdG concentrations in exposed group I, control group I, exposed group II, and control group II were 24.69＋0.93, 20.68＋1.07, 20.57＋0.55, and 12.96_＋0.73 ng/mg Cr, respectively. Urinary 8-OHdG concentration in exposed group I was significantly higher than that in control group I or that in exposed group 11 （P〈0.02）. There was a significant correlation between urinary 8-OHdG concentrations and spill frequencies per technician （P〈0.01）. Conclusion There was detectable oxidative DNA damage in PIVAS technicians exposed to antineoplastic drugs. This oxidative DNA damage may be associated with their spill exposure experience and contamination of their personal protective equipment.

Comparative Study on Antineoplastic Activity of Polysaccharide from Four Kinds of Sea Cucumber

The antineoplastic activity of polysaccharide was investigated in Stichopus chlorontus, Isostichopus badionotus, Stichopus horrens and Holothuria lessoni massin. Crude polysaccharide was prepared with enzyme hydrolyzation method and purified by anion exchange chromatography using DEAE-sepharose fast flow column. The effect of polysaccharide on cells apoptosis of SiHa and U87 was examined with cell counting kit-8 colorimetry method. Western blotting was used to analyze related proteins of cellular apoptosis including p53 and Bcl-2. Results showed that there were two main components in each sea cucumber polysaccharide, which could be eluted down by 1.0 mol/LNaCl solution. The four types of polysaccharide in the second component were named as SC-2, IB-2, HLM-2 and SH-2, respectively. They were used for comparing the antineoplastic activity. Results showed that SC-2, IB-2, HLM-2 and SH-2 could promote apoptosis of U87 and SiHa cells. SH-2 and HLM-2 were selected for the subsequent experiment to explore the additional effect of U87 and SiHa cells, The protein expressions of Bcl-2 and p53 decreased considerably with the increase of polysaccharide concentration in U87 cells. In SiHa cells, protein expressions of Bcl-2 and high dosage group of p53 decreased significantly, whereas no obvious decrease was observed in other groups. The polysaccharides are more effective in promoting apoptosis of U87 and SiHa cells from S. horrens and H. lessoni massin than from the rest species.

Biochemical, Antioxidant and Antineoplastic Properties of Italian Saffron (<i>Crocus sativus L</i>.)

Saffron, the most expensive spice in the world, is got by Crocus sativus L. stigmas. The production of this substance has attracted human interest, since ancient cultures, for its medicinal and culinary properties. Because of saffron high economic value, sometimes, since Middle Ages, it is adulterated with other vegetal materials, dyes or synthetic molecules. Object of this work was the study of one of the best world saffron: Civitaretenga (AQ, Central Italy) C. sativus. Taste, color and aroma of Civitaretenga spice were determined, according to international standards (ISO/Technical Specification 3632), to define its high quality. A biochemical approach was then applied to obtain a secondary metabolite profile of this product. So, crocins, total phenolic content, flavonoids and phenolic acids were detected by HPLC-DAD and spectrophotometric analysis. Moreover, in vitro antioxidant properties and in vivo antineoplastic effects, on highly metastatic murine B16-F10 melanoma cell line, were successfully revealed in Civitaretenga C. sativus extract. All these data confirmed the elevated quality of Civitaretenga saffron and its highly reducing and chemopreventive activity.

Experiment study of Swainsonine's antineoplastic activity

ED50 of Pure Swainsonine (SW) to EMT6 cell strain is 1.2 (0.8-1.6) mg/L and the dose of entire lethal is 6.4 mg/L with MTT method. After ig crude extraction of SW to S180 sareoma rooted in mouse and EMT6 model mice with breast carcinoma for 12 d at dose of 16 mg/kg, the inhibitory rates of weight amounts to 49.7% and 49.4% respectively (P<0.01). Given crude extraction of SW at 4 mg/kg combined with irradiation at 5 Gy60Co-γ, the inhibitory rate of weight of S180 amount to 64.5% (P<0.01). It shows that SW has obviously antineoplastic.

A preliminary analysis of antineoplastic activity ofparvovirus MVMp NS-1 proteins

Human gastric cancer MKN-45 cells were transfectedwith pULB 3238, a plasmid carrying MVMp NS-1 genewith its original P4 promoter replaced by the glucocorticoid inducible promoter MMTV-LTR. After the integration and expression of NS-1 gene, some of the transfectantsdied, while others remained alive, but the growth featuresof survived cells were changed. For further study on theantineoplastic function of parvoviral NS-1 protein in vivo,transgenic mice carrying NS-1 genes were established byconventional method. Among 4 founders, one of them wasfound to be able to transmit the transgene to around 50%of their offsprings. RT-PCR was performed to indicate theexpression of NS-1 gene in transgenic mice and its mRNAappeared in a variety of tissues. The expression of integrated NS-1 gene may correlate with the decreased incidence of tumor induced in vivo by chemical carcinogens.

Studies on Antineoplastic Constituents from Marine Bryozoan Bugula neritina Inhabiting South China Sea (Ⅲ): Isolation and Structural Elucidation of Bryostatins 10,11 and 18

Six active compounds are isolated from the marine bryozoan Bugula neritina,inhabiting the Nanwan Bay in the South China Sea, using the bioassay-guided method with a combination of extraction and partitionation with suitable solvents as well as multiple column chromatographies ( Sephadex LH-20, ODS and preparative HPLC).Their structures are identified as known bryostatins-bryostatins 4, 5, 6, 10, 11 and 18 through intensive analysis of the data of high resolution 2D NMR (600 MHz, DQF-COSY,TOCSY, HMQC and ROESY) and ESI-MS. Among them, bryostatins 10, 11 and 18 are for the first time obtained from this bryozoan in the South China Sea and they show significant antineoplastic activities in vitro.

Effect of Magnetized Water on the Mice Given High Doses of Antineoplastic Drugs

To broaden the applications of magnetized water(MW) in medical science, the possible detoxicative effect of MW to anticancer drugs in vivo were studied. After being given ip with cyclophosphomide (CTX) 500 mg/kg, cisplatin (DDP) 40 mg/kg, harringtonine (HA) 20 mg/kg, mitomycin C (MMC) 8 mg/kg, lycobetaine (Lyc) 200 mg/kg, respectively, the mice were given MW ip 0.2 ml for 7 days. The average life span was calculated for each group. After being given subacutely lower doses of anticancer drugs ( CTX 100 mg/kg, HA 3 mg/kg ) ip 3 times, the mice were given MW ip 0.2 ml for 7 days and the blood white cells were counted as routine. It was shown that the mice in MW groups after ip anticancer drugs survived longer than those without MW. The effects of various anticancer drugs on life span were different. The white cell numbers of groups with MW were higher than that of the groups without MW. So it is possible that MW can remarkably extend the life span of mice and attenuate the leukopenia by mitigating the toxicity of anticancer drugs in vivo .

FIRST STEP VIEW OF THE EFFICACY OF ANTINEOPLASTIC AGENTS

A human K562 leukaemia call and acute adult leudaemia patient samples have been used to test the efficacy of antineoplastic agents with MTT assay.All 18 drugs were invoved.According to the purpose of experiment these durgs were applied at different opportunities or combinations.The drug efficacy has been observed and summarized as four different conditions:1.the change of the time(△ T )closely related with drug effacacy, during the duration the change of drug concentration(△ C) at certain extent has almost no influence; 2the △ C closely related with the efficacy, the △ T has no influence;3. The △ C and △ T effect the results together;and 4.the △ C and △ T effect not the result. And then draw a conclution that the process or drug effacacy has a multiple function with flat distrtct.

Disulfiram’s Antineoplastic Effects on Ovarian Cancer

Objective: Aldehyde dehydrogenase (ALDH) enzymatic activity identifies ovarian cancer stem-like cells. We investigated the antineoplastic activity of the ALDH inhibitor Disulfiram on bulk ovarian cancer cells and CD133+/ALDH+ cancer stem-like cells. Study Design: Ovarian cancer cell lines, human ovarian surface epithelial cells, and mesenchymal stem cells were treated with increasing concentrations of Disulfiram and/or Cisplatin in vitro. Treated cells were assessed for viability or FACS-analyzed for either percentage of ovarian cancer stem-like cells or induction of apoptosis. Disulfiram’s impact on cancer stem-like cells was tested in vitro using tumor sphere formation assays and in vivo using tumor initiation assays with in vitro-treated A2780 cells in NSG mice. Finally, Disulfiram’s in vivo activity was assessed versus CD133+/ALDH+ cell-initiated tumor xenografts. Results: Disulfiram demonstrated antineoplastic activity against multiple ovarian cancer cell lines. While Disulfiram had limited in vitro toxicity against human ovarian surface epithelial cells or mesenchymal stem cells (IC50 of ~15 μM and >30 μM, respectively), its antineoplastic activity against cell lines was comparable to Cisplatin (IC50 ~1.5 μM). Disulfiram-mediated cell death was due, at least in part, to induction of apoptosis. Disulfiram activity was additive with chemotherapy. Disulfiram demonstrated selective depletion of CD44+ cells but not the CD133+ cancer stem-like cells. Disulfiram had no therapeutic impact on tumor initiation studies or in vivo therapy of whole cell line or stem cell-initiated tumor xenografts. Conclusions: In biologically relevant concentrations, Disulfiram has clear antineoplastic activity against ovarian cancer cells in vitro. Disulfiram selectively depleted CD44+ but not CD133+ ovarian cancer stem-like cells in vitro. However, Disulfiram had no significant activity in vivo. Thus, improved and more selective ALDH inhibitors may be required to target ovarian cancer stem cells.

Radiomics in Antineoplastic Agents Development:Application and Challenge in Response Evaluation

The recent spring up of the antineoplastic agents and the prolonged survival bring both challenge and chance to radiological practice.Radiological methods including CT,MRI and PET play an increasingly important role in evaluating the efficacy of these antineoplastic drugs.However,different antineoplastic agents potentially induce different radiological signs,making it a challenge for radiological response evaluation,which depends mainly on one-sided morphological response evaluation criteria in solid tumors(RECIST)in the status quo of clinical practice.This brings opportunities for the development of radiomics,which is promising to serve as a surrogate for response evaluations of anti-tumor treatments.In this article,we introduce the basic concepts of radiomics,review the state-of-art radiomics researches with highlights of radiomics application in predictions of molecular biomarkers,treatment response,and prognosis.We also provide in-depth analyses on major obstacles and future direction of this new technique in clinical investigations on new antineoplastic agents.

Do Antineoplastic Drugs Play an Additional Role in the Progression of Non-Compaction Cardiomyopathy? A Case Report

Non-compaction cardiomyopathy is a rare form of cardiomyopathy;its most common clinical manifestations are heart failure (HF), ventricular arrhythmia, thromboembolism, and sudden cardiac death. We report a rare case of a 63-year-old man with chest tightness, worsening lower leg edema, dyspnea, and decreased exercise tolerance. He had a medical history of gastric cancer treated with subtotal gastrectomy and post-operative chemotherapy with paclitaxel and fluorouracil three years ago. At that time, he was diagnosed with non-compaction cardiomyopathy, and the thickened and reticulated trabecular muscle was exclusively confined to left ventricular apex. Five months ago, he was admitted to our hospital with heart failure and treated for dilated cardiomyopathy, echocardiography revealed severe trabecular noncompact myocardium in both ventricles, which was confirmed by cardiac magnetic resonance imaging (CMR). It is generally accepted that non-compacted myocardium forms in the early embryonic stage, which raises a question in our case whether acquired factors, such as antineoplastic drugs, potentially accelerate the pathological progression of non-compaction cardiomyopathy. Considering there are disparities between current screening tools such as echocardiography and CMR regarding diagnostic criteria, multi-detector CT may be an alternative examination method that could provide a new perspective for diagnosis.

Downregulation of Scar Fibroblasts by Antineoplastic Drugs: A Potential Treatment for Fibroproliferative Disorders

The various fibroproliferative disorders affecting humans have in common excess fibroblast activity and persistent overexpression or dysregulated activity of transforming growth factor beta (TGF-β). Cancer has many similar characteristics. Antineoplastic drugs can downregulate fibroblast activity and cytokine growth factors. This study evaluates the effect of six antineoplastic drugs on keloid and Dupuytren’s disease fibroblasts. Keloid, normal scar, Dupuytren’s affected palmar fascia, and normal palmar fascia fibroblasts were grown and seeded into Fibroblast Populated Collagen Lattices (FPCLs). The FPCLs were treated with one of six antineoplastic drugs or left untreated as controls. At 7 days, supernatants were extracted from all FPCLs and assayed for expression of Transforming Growth Factor beta (TGF)-β1 and TGF-β2. All six antineoplastic drugs significantly inhibited FPCL contraction in both fibroproliferative conditions compared with the untreated controls (p β1 and TGF-β2 expression was downregulated in the supernatants of all FPCLs by the drug exposure. Cytotoxicity did not occur in these studies and was not the reason for the results. Although antineoplastic drugs can have significant side effects when given systemically, these results may be minimized when given to small areas involved in fibroproliferative scarring or when given topically or intralesionally. These in vitro results suggest that antineoplastic drugs may have a utility for treating various fibroproliferative disorders and warrant further investigation.

Nurses’ knowledge, perceptions, and behaviors regarding antineoplastic drugs:the mediating role of protective knowledge

Objective:To explore the relationships between Chinese nurses’knowledge,perceptions,and attitudes and their behavior and actual implementation of safety measures when handling antineoplastic drugs(ADs)in their daily work.Methods:This was a multisite study conducted in 8 public hospitals in China.A self-administered questionnaire was sent to par ticipants querying the degree of contact with ADs.The hypothesized relations were explored using structural equation modelling via the bootstrap method.Mediation analysis was applied to explore the mediating role of protective knowledge regarding AD exposure on the associations among protective training,using warning labels,and using protective masks.Results:A total of 305 nurses were enrolled.The average age of all par ticipants was 30.2(standard deviation[SD]:6.2)years.Nurses who had received protective training for AD exposure were more likely to use labels for ADs after age,body mass index(BMI),length of service,marital status,education,and department were controlled as covariates.The bias-corrected bootstrap of 95%confidence interval(CI)indicated that protective knowledge significantly mediated(23.4%)the association between protective training and using labels(indirect effect=0.202,95%CI:0.009,0.495);the proportion of mediation was 23.4%.Protective knowledge significantly mediated the association between protective training and using protective masks(indirect effect=0.157,95%CI:0.048,0.325);the propor tion of mediation was 27.2%.Conclusions:The findings of this study have provided baseline information on the current state of Chinese nurses’perceptions,knowledge,and preventive behaviors toward ADs as the crisis is happening.Training is also recommended to improve nurses’perceptions of the risks associated with ADs.

《抗肿瘤药物临床应用管理标准》制订与解析

抗肿瘤药物是指通过细胞杀伤、免疫调控、内分泌调节等途径,在细胞、分子水平进行作用,达到抑制肿瘤生长或消除肿瘤的药物,一般包括化学治疗药物、分子靶向治疗药物、免疫治疗药物、内分泌治疗药物等。医疗机构对抗肿瘤药物的管理及合理应用,关系到肿瘤患者的治疗安全。《抗肿瘤药物临床应用管理标准》由中国医院协会药事专业委员会牵头编制,对医疗机构抗肿瘤药物管理工作中涉及的组织管理与制度、用药管理、药品监测与评价三个环节中的18个关键要素进行了规范要求,适用于开展肿瘤诊疗的各级各类医疗机构。该文阐述了该标准制定方法和基本内容,以期为医疗机构开展相关工作提供参考和借鉴。

四联方案预防含顺铂方案多日化疗致恶心呕吐的效果和安全性研究

目的评价四联方案预防含顺铂方案多日化疗所致恶心呕吐(CINV)的有效性和安全性。方法选取以含顺铂药物进行化疗的112例恶性肿瘤患者。以随机数字表法将患者分为试验组与对照组,每组56例。对照组接受含有顺铂的化疗方案时给予三联方案(福沙匹坦双葡甲胺+盐酸昂丹司琼+地塞米松),试验组在对照组基础上给予含奥氮平的四联方案。观察2组恶心及呕吐发生情况、生活质量[呕吐生活功能量表(FILE)]及焦虑抑郁[医院焦虑抑郁量表(HADS)]的变化。结果开始化疗后1~9 d,试验组恶心、呕吐发生率低于对照组,试验组延迟期恶心、呕吐发生率低于对照组(P<0.05);开始化疗后9 d,试验组FILE的恶心、呕吐及总分高于对照组(P<0.05);2组开始化疗后1、9 d焦虑、抑郁评分及不良反应发生率比较差异无统计学意义(P>0.05)。结论四联止吐方案可提高对含顺铂多日化疗方案致CINV的控制率,尤其是针对延迟性恶心、呕吐的控制,改善患者化疗期间的生活质量,且安全性较好。

安罗替尼致高血压文献病例分析

目的探讨安罗替尼相关高血压的临床特点。方法检索中国知网、万方、PubMed、Web of Science数据库(截至2023年7月31日),收集安罗替尼相关高血压文献病例报告类文献,提取患者基本情况、安罗替尼用药情况、高血压情况、干预措施和转归等,进行描述性统计分析。结果纳入分析的文献为16篇,患者18例,男性8例,女性10例;年龄27~76岁,平均58岁;非小细胞肺癌13例,结缔组织和软组织恶性肿瘤2例,肝内胆管癌1例,卵巢癌1例,子宫癌1例。联用其他抗肿瘤药物4例;安罗替尼初始剂量均为12 mg/d。发生的高血压分级为1级3例(17%),2级4例(22%),3级9例(50%),4级2例(11%)。除8例患者从服用安罗替尼至发生高血压的时间不详外,其余10例患者从服用安罗替尼至发生高血压的时间在7 d~6个月内,中位时间36(30,42)d,其中7例(39%)发生在服用安罗替尼2个月内。18例患者中出现不同程度乏力6例(33%),头痛6例(33%),头晕5例(28%),呕吐3例(17%),视物模糊2例(11%),恶心1例(6%),抽搐1例(6%)。13例伴其他不良反应,其中手足综合征7例(39%),蛋白尿3例(17%),高脂血症3例(17%),可逆性后部白质脑病综合征2例(11%),癫痫1例(6%),便血1例(6%),皮疹1例(6%)。1~2级患者安罗替尼未调整(6例)或减量治疗(1例)后耐受良好;3~4级患者中,8例停用安罗替尼且接受降压药治疗,2例减量治疗,1例未调整,随访血压控制平稳。结论安罗替尼相关高血压多发生在用药2个月内,往往伴其他不良反应,3级以上高血压常见,但大多数患者经对症处理、停药或减量后转归良好。

血清miR-345、miR-138及miR-22与晚期胃癌患者化疗敏感性的相关性分析

【目的】探讨血清微小RNA-345(miR-345)、miR-138及miR-22与晚期胃癌患者化疗敏感性的相关性。【方法】100例均接受同一化疗方案治疗的晚期胃癌患者,依据疗效分为有效组(n=69)及无效组(n=31),比较两组临床病理特征及血清相关指标,绘制受试者工作特征(ROC)曲线分析血清miR-345、miR-138及miR-22预测晚期胃癌化疗效果的价值,采用多因素Logistic回归分析影响患者化疗效果的因素。【结果】Ⅲ期患者的血清miR-345相对表达量低于Ⅳ期患者,miR-138及miR-22相对表达量高于Ⅳ期患者(P<0.05);有效组miR-345低于无效组,miR-138、miR-22高于无效组(P<0.05)。经ROC曲线分析证实,血清miR-345、miR-138及miR-22能用于预测晚期胃癌的化疗效果,其敏感度与特异性分别为0.855、0.935、0.971、0.839和0.884、0.903(均P<0.05)。多因素Logistic回归分析显示,病理分期为Ⅳ期、miR-345≥14.5、miR-138≤2及miR-22≤3.12为晚期胃癌患者化疗效果不佳的危险因素(P<0.05)。【结论】血清miR-345≥14.5、miR-138≤2、miR-22≤3.12均为导致化疗效果不佳的危险因素,其可作为评估患者化疗效果的生物学标志物。

免疫检查点抑制剂相关皮肤不良反应管理的证据总结

目的 检索、评价并整合免疫检查点抑制剂(ICIs)相关皮肤不良反应(irAEs)管理的相关证据。方法 系统检索循证决策支持系统BMJ Best Practice、JBI图书馆、Cochrane图书馆、英国国家卫生和临床优化研究所、苏格兰校际指南、Web of science、美国国立综合癌症网络等专业学会网站、PubMed、中国生物医学文献数据库、中国知网、万方中关于ICIs irAEs管理的指南、证据总结、专家共识、系统评价,检索时间限定为2013年1月1月-2022年10月31日。对检索的文献进行质量评价后,再对证据进行提取和整合。结果 共纳入9篇文献,其中包括4篇指南、1篇证据总结、4篇专家共识。经过阅读、提取和归纳,共总结出14条证据,包括培训、健康教育、评估与监测和治疗4个方面。结论 临床医护人员应应用最佳证据对ICIs irAEs进行规范管理,降低irAEs的发生。

西达苯胺联合R-DHAP方案治疗复发/难治性弥漫大B细胞淋巴瘤的临床疗效

【目的】探讨西达苯胺联合R-DHAP方案治疗复发/难治性弥漫大B细胞淋巴瘤(DLBCL)的临床疗效。【方法】78例复发/难治性DLBCL患者,随机分为观察组和对照组。对照组采用R-DHAP方案治疗,观察组采用西达苯胺联合R-DHAP方案治疗。比较两组肿瘤患者体力状况(ECOG)评分,临床疗效,血清血管内皮生长因子(VEGF)、β2-微球蛋白(β2-MG)水平,药物不良反应以及无进展生存时间。【结果】治疗3个疗程后,两组ECOG评分较治疗前均降低(P<0.05),且观察组低于对照组(P<0.05);观察组的客观缓解率高于对照组(P<0.05);两组血清VEGF、β2-MG水平均较治疗前降低(P<0.05),且观察组低于对照组(P<0.05)。两组不良反应发生率比较,差异无统计学意义(P>0.05)。观察组和对照组患者中位无进展生存时间分别为20.60个月和15.18个月,两组比较,差异有统计学意义(P<0.05)。【结论】西达苯胺联合R-DHAP方案治疗复发/难治性DLBCL患者能够改善临床症状,疗效确切,同时可以降低血清VEGF、β2-MG水平,延长患者生存时间,且安全可靠。

血管内皮生长因子及其受体抑制剂相关性高血压病理生理机制及临床诊疗的研究进展

肿瘤治疗相关心血管毒性(CTR-CVT)逐渐成为影响肿瘤幸存者预后的关键因素。以血管内皮生长因子(VEGF)为靶点研发的VEGF及其受体抑制剂(VEGFIs)作为新型抗肿瘤药物现已广泛应用于临床,可延长肿瘤患者的生存周期,改善患者预后,但VEGFIs诱导的高血压作为其最常见的CTR-CVT,可能会限制和影响其应用并引起严重心血管疾病(CVD)。对应用VEGFIs治疗的肿瘤患者应密切监测血压,早期评估,优化管理,使患者获得最佳的抗肿瘤疗效和最低的CTRCVT风险。现就VEGFIs相关性高血压的临床表现、发病机制、诊断和治疗策略进行综述,旨在为临床医生更好地管理和应对VEGFIs相关性高血压提供参考。