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.

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 .

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.

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.

Advances in the Researches on the Blocking Effect of Chinese Drugs on Tumors

Malignant tumors are caused by multiple carcinogenic factors undergoing several stages. The occurrence and development of tumors may be prevented and blocked if some effective interference factors are brought into play.1 At present, there are two main subjects for the researches, that is, blocking the precancerous lesions and blocking the develop-ment of tumors. The former focuses on the removing of carcinogenic factors and on the chemoprophylaxis of cancer, while the latter on the inhibition of cancer cell infiltration and cancerometastasis. These are summarized as follows.

THE EFFECTS OF CHINESE DRUGS FOR SUPPORTING HEALTHY ENERGY AND REMOVING BLOOD STASIS ON POSTOPERATIVE METASTASIS OF GASTRIC CARCINOMA AND ORNITHINE DECARBOXYLASE

32 postoperative cases of gastric carcinoma were treated by traditional Chinese medicine (TCM) drugs for supporting healthy energy and removing blood stasis, and their therapeutic results were compared with those in the control group treated by western medicine. After 6 months of treatment, in the TCM group, the rate of metastatic recurrence was significantly reduced, and the level of ornithine decarboxylase was also markedly lowered. Therefore, it is considered that the action of anti-metastatic recurrence of TCM drugs in postoperative cases of gastric carcinoma is probably related to the lowered activity of ornithine decarboxylase.

Suppression of P-gp induced multiple drug resistance in a drug resistant gastric cancer cell line by overexpression of Fas

AIM To observe the drug sensitizing effect andrelated mechanisms of fas gene transduction onhuman drug-resistant gastric cancer cellSGC7901/VCR(resistant to Vincristine).METHODS The cell cycle alteration wasobserved by FACS.The sensitivity of gastriccancer cells to apoptosis was determined by invitro apoptosis assay.The drug sensitization ofcells to several anti-tumor drugs was observedby MTT assay.Immunochemical method wasused to show expression of P-gp and Topo Ⅱ ingastric cancer cells.RESULTS Comparing to SGC7901 and pBK-SGC7901/VCR,fas-SGC7901/VCR showeddecreasing G2 cells and increasing S cells,theG2 phase fraction of pBK-SGC7901/VCR wasabout 3.0 times that of fas-SGC7901/VCR,but Sphase fraction of fas-SGC7901/VCR was about1.9 times that of pBK-SGC7901/VCR,indicatingS phase arrest of fas-SGC7901/VCR.FACS alsosuggested apoptosis of fas-SGC7901/VCR,fas-SGC7901/VCR was more sensitive to apoptosisinducing agent VM-26 than pBK-SGC7901/VCR.MTT assay showed increased sensitization offas-SGC7901/VCR to DDP,MMC and 5-FU,butsame sensitization to VCR according to pBK-SGC7901/VCR.SGC7901,pBK-SGC7901/ VCRand fas-SGC7901/VCR had positively stainedTopo Ⅱ equally.P-gp staining in pBK- SGC7901/VCR was stronger than in SG07901,but there was little staining of P-gp in fas.SGC7901/VCR.CONCLUSION fas gene transduction couldreverse the MDR of human drug-resistant gastriccancer cell SGC7901/VCR to a degree,possiblybecause of higher sensitization to apoptosis anddecreased expression of P-gp.

Activation of STAT3 signaling in human stomach adenocarcinoma drug-resistant cell line and its relationship with expression of vascular endothelial growth factor

AIM: To investigate the difference in activation of STAT3 signaling between two human stomach adenocarcinoma cell lines: 5-fluorouracil resistant cell line and its parental cell line, and to evaluate its relationship with the expression of vascular endothelial growth factor (VEGF). METHODS: Western blot and electrophoretic mobility shift assay (EMSA) were used to detect the expression of phospho-STAT3 protein and constitutive activation of STAT3 in two human stomach adenocarcinoma cell lines, 5-fluorouracil resistant cell line SGC7901/R and its parental cell line SGC7901, respectively. The mRNA expression of VEGF was analysed by semi-quantitative RT-PCR. The expressive intensity of VEGF protein was measured by immunocytochemistry. RESULTS: The expressions of phospho-STATS protein and constitutive activation of STAT3 between two human stomach adenocarcinoma cell lines were different. Compared with the parental cell line SGC7901, the STAT3DNA binding activity and the expressive intensity of phospho-STAT3 protein were lower in the drug-resistant cell line SGC7901/R. The expression levels of VEGF mRNA and its encoded protein were also decreased in drugresistant cell line. CONCLUSION: Over-expression of VEGF may be correlated with elevated STAT3 activation in parental cell line. Lower VEGF expression may be correlated with decreased STAT3 activation in resistant cell line, which may have resulted from negative feedback regulation of STAT signaling.

pH-responsive mesoporous silica nanoparticles employed in controlled drug delivery systems for cancer treatment

In the fight against cancer, controlled drug delivery systems have emerged to enhance the therapeutic efficacy and safety of anti-cancer drugs. Among these systems, mesoporous silica nanoparticles （MSNs） with a functional surface possess obvious advantages and were thus rapidly developed for cancer treatment. Many stimuli-responsive materials, such as nanopartides, polymers, and inorganic materials, have been applied as caps and gatekeepers to control drug release from MSNs. This review presents an overview of the recent progress in the production of pH-responsive MSNs based on the pH gradient between normal tissues and the tumor microenvironment. Four main categories of gatekeepers can respond to acidic conditions. These categories will be described in detail.

Effects of Taxotere on invasive potential and multidrug resistance phenotype in pancreatic carcinoma cell line SUIT-2

INTRODUCTIONDevelopment of drug-resistance to chemotherapyand subsequent metastasis of tumor are primarilyresponsible for treatment failure and the death fromcancer. There have been many previous studies onthe relationship between expression of multidrugresistance (MDR) phenotype P-glycoprotein (P-gp)and the malignant properties of tumors, but theresults are often conflicting[1-8]. The difference intumor types or MDR phenotype induced by specificagents might account for this discrepancy. Taxotere(TXT), a member of the family of taxanes, hasantitumor activity through its effect of promotingthe polymerization of tubulin[9,10].

龙寿丹胶囊对脑梗死患者TCD影响

为探讨龙寿丹胶囊对脑梗死患者ＴＣＤ 的影响及近期疗效。采用双盲对照法观察７８ 例脑梗死患者口服龙寿丹和安慰剂治疗前后ＴＣＤ 改变及近期疗效，观察期为１ 个月。结果龙寿丹能够提高脑梗死患者脑血流速度，改善脑循环，其近期疗效显著，为治疗脑梗死的抗栓溶栓良药。

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。

我院静脉配置中心抗肿瘤药不合理用药分析

目的分析我院静脉用药调配中心抗肿瘤药不合理用药情况,为临床抗肿瘤静脉用药提供参考,促进临床合理用药,保障肿瘤患者用药安全。方法我院2022年度住院静脉用药调配中心抗肿瘤用药医嘱10098份,依据药品说明书、相关文献等相关资料对87份不合理医嘱进行统计分析。结果我院2022年度住院静脉用药调配中心医嘱10098份,其中有不合理用药医嘱87份,每个科室均存在不合理用药情况,妇科的不合理医嘱数最多,其占比23.08%;静脉用药调配中心抗肿瘤药不合理用药情况主要包括溶媒错误(40.23%)、药物剂量不合理(29.89%)、给药顺序不合理(18.39%)、给药时间不合理(11.49%)。结论应加强我院的静脉用药调配中心抗肿瘤药不合理用药情况和抗肿瘤药溶媒管理,加强医师对抗肿瘤药物性质的认知,合理规范选择药物,同时药剂师应严格审核医嘱,以最大幅度减少不合理用药情况。

《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。

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。

95例新型抗肿瘤药物不良反应分析

目的 分析我院上报的新型抗肿瘤药物药品不良反应(ADR)的特点和发生规律,为ADR监测和合理用药提供参考。方法 收集我院2020年1月~2023年12月上报的95例新型抗肿瘤药物ADR,对患者基本情况、报告类型、发生时间、给药途径、涉及药品、ADR累及系统、转归情况等方面进行分析。结果 95例ADR中,男女比例为1∶0.83;≥50岁人群超过80%;给药途径以静脉滴注为主。ADR涉及28种药品,新的和严重的ADR 60例(63.16%);程序性死亡蛋白1(PD-1)抑制剂占比最高(31例,32.63%);其中卡瑞利珠单抗例数最多(11例);ADR可累及多个系统,皮肤及其附件损害最常见(32例,33.68%)。结论 临床应重视新型抗肿瘤药物ADR监测,关注此类药物新的和严重的ADR,加强患者的用药宣教,确保治疗的安全性和持续性。

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。