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.

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.

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.

PERCUTANEOUS INJECTING ANTINEOPLASTIC AGENT INTO TRANSPLANTED TUMORS OF MICE BY CT－GUIDED

Antineoplastic agent and contrast medium were injected into transplanted tumors of mice under guidance with CT, site and range of the intratumoural drug were shown on CT image immediately. It was value of multipoint injections, concentration of 0.1 mg/0.l ml MMC every point, 1 cm interval of injection. After the injections, the tumor size of mice reduced and at last disappeared (ratio of inhibited tumor 59.32% in 0.05 mg MMC group, 43.86% in 0.1 mg MMC group).The pathologic examination showed coagulatic necrosis of the tumor tissues. The higher concentration of antineoplastic agent (0.2 mg MMC) could make the tumors enlarged (ratio of inhibited tumor -15.3%). The tissues and vessels around the tumors were not injured, if MMC overflow out off the tumor.

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.

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.

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.

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.

Chemotherapy combined with bevacizumab for small cell lung cancer with brain metastases:A case report

BACKGROUND Small cell lung cancer(SCLC)is a common and aggressive subtype of lung cancer.It is characterized by rapid growth and a high mortality rate.Approximately 10%of patients with SCLC present with brain metastases at the time of diagnosis,which is associated with a median survival of 5 mo.This study aimed to summarize the effect of bevacizumab on the progression-free survival(PFS)and overall survival of patients with brain metastasis of SCLC.CASE SUMMARY A 62-year-old man was referred to our hospital in February 2023 because of dizziness and numbness of the right lower extremity without headache or fever for more than four weeks.The patient was diagnosed with limited-stage SCLC.He received 8 cycles of chemotherapy combined with maintenance bevacizumab therapy and achieved a PFS of over 7 mo.CONCLUSION The combination of bevacizumab and irinotecan effectively alleviated brain metastasis in SCLC and prolonged PFS.

Evaluation of the Efficiency of the Magicramp® Device for Reducing Cramps Resulting from Oncological Treatments: “Double-Blind, Randomized Clinical Trial”

We identified that oncological treatments in general (chemotherapies, immunotherapies and radiotherapies) frequently cause peripheral neuropathy, including cramps, characterized by excess protons due to metabolic and neuronal factors, such as sudden changes in pH, uremia and aspects that affect neuromotor functions. Such situations and others like them are often neglected in treatment, which naturally concerns itself with the main problem: Cancer. Sometimes toxic solutions are implemented that have comorbid side effects, such as duloxetine (standard treatment). Based on monitoring of cancer patients who used the non-toxic product, called “Magicramp® Electrostatic Charge Reduction Cushion” (MECRC), approved in Europe more than 10 years ago, we carried out a controlled test in Brazil. In this clinical trial, we hypothesized that reducing excessive ionic charges (electrostatic charge), which is one of the side effects often described in the literature as “Chemotherapy-Induced Peripheral Neuropathy” (CIPN), would decrease or eliminate cramping, under the hypothesis that such elimination would prevent or attenuate muscular vulnerability to action impulses, and increase the power of relaxation through the same mechanism. In this double-blind and randomized clinical trial, 40 (forty) adult patients with muscle cramps caused by oncological treatments were tested, evaluating the degree of efficiency of the product that aims to reduce muscle cramps, by eliminating and/or reducing excess loads electrostatic ionic. Data from the clinical research conducted in this study are available online at https://doi.org/10.7910/DVN/QUS94U.

Studies on Antineoplastic Effect by Adjusting Ratios of Targeted-ligand and Antitumor Drug

A series of drug delivery systems based on a sodium alginate derivative were prepared by mixing glycyrrhetinic acid （GA） and doxorubicin （DOX） conjugates at different ratios. GA （a liver-targeting ligand） and DOX （an antitumor drug） were both conjugated to oligomeric glycol monomethyl ether-modified sodium alginate （ALG-mOEG） for prolonged duration of action. These NP-based delivery systems exhibited active cell uptake and cytotoxicity in vitro and liver-targeted distribution and anti-tumor activity in vivo. In addition, nanoparticles with a 1：1 （W：W） ratio of GA-ALG-mOEG and DOX-ALG-mOEG （NPs-3） showed the highest cellular uptake and cytotoxicity in vitro and liver-targeted distribution and anti-tumor activity in vivo. Specifically, when mixed nanoparticles defined as NPs-3 were injected in mice, liver DOX concentration reached 61.9 μg/g 3 h after injection, and AUC0-∞ and t1/2 of DOX in liver reached 4744.9 μg·h/g and 49.5 h, respectively. In addition, mice receiving a single injection of NPs-3 exhibited much slower tumor growth （88.37% reduction in tumor weight） 16 days after injection compared with placebo. These results indicate that effective cancer treatment may be developed using mixed NP delivery systems with appropriate ratio of targeted ligand and drug.

Targeting the“undruggable”cancer driver genes:Ras,myc,and tp53

The term“undruggable”is to describe molecules that are not targetable or at least hard to target pharmacologically.Unfortunately,some targets with potent oncogenic activity fall into this category,and currently little is known about how to solve this problem,which largely hampered drug research on human cancers.Ras,as one of the most common oncogenes,was previously considered“undruggable”,but in recent years,a few small molecules like Sotorasib(AMG-510)have emerged and proved their targeted anti-cancer effects.Further,myc,as one of the most studied oncogenes,and tp53,being the most common tumor suppressor genes,are both considered“undruggable”.Many attempts have been made to target these“undruggable”targets,but little progress has been made yet.This article summarizes the current progress of direct and indirect targeting approaches for ras,myc,two oncogenes,and tp53,a tumor suppressor gene.These are potential therapeutic targets but are considered“undruggable”.We conclude with some emerging research approaches like proteolysis targeting chimeras(PROTACs),cancer vaccines,and artificial intelligence(AI)-based drug discovery,which might provide new cues for cancer intervention.Therefore,this review sets out to clarify the current status of targeted anti-cancer drug research,and the insights gained from this review may be of assistance to learn from experience and find new ideas in developing new chemicals that directly target such“undruggable”molecules.

Inhibitory Effects of Propolis Water Extract on the Proliferation of Cervical Cancer Cells

[Objectives]To investigate the effects of propolis extract on HeLa cells to provide theoretical guidance for facilitating clinical treatment.[Methods]The effects of propolis on inflammation,and proliferation were analyzed based on the levels of DNA transcriptional regulation and mRNA and protein expression levels.[Results]Propolis water extract(PWE)could inhibit the cell proliferation and production of DNA damage in a dosedependent manner.Moreover,the propolis water extract could significantly downregulate the expression of iNOS-Luc,PTGS-2-Luc,and IL-8-Luc,and that it was related to the expression of the NF-κB family protein.After the induction of HeLa cells by propolis,the expression of the cell cycle inhibitor gene p21 was increased,while that of the cell proliferation gene Ki67 was decreased.[Conclusions]Propolis water extract could significantly inhibit the cell proliferation and production of DNA damage,suggesting propolis as a potential candidate for the development of adjunctive therapy against cervical cancer.

喉癌喉咽癌的辅助与综合治疗

喉癌喉咽癌的辅助与综合治疗在喉癌喉咽癌治疗中占有越来越重要的位置。其主要目的是补充外科手术的缺点和不足,增强外科手术的治疗效果;提高喉器官功能保留率和患者的生存质量;作为晚期喉癌喉咽癌治疗的姑息性方法,延长患者的生存时间。本文系统论述了放疗、化疗、联合放化疗(包括同步放化疗)和分子靶向治疗在喉癌喉咽癌治疗中的作用及近年的发展和现状。

Zebularine对人鼻咽癌细胞CNE-2Z增殖的抑制作用

某些抑癌基因转录起始区域的启动子发生异常超甲基化，会导致抑癌基因表达失活引发肿瘤，因此有关去甲基化药物的研究正在成为肿瘤治疗领域的热点。在国外研究中已证实抗肿瘤药——Zebularine（Zeb）可以抑制多种肿瘤细胞生长，并上调因甲基化失活的相应抑癌基因表达。但Zeb对鼻咽癌细胞的影响在国内、外还未见报道，鉴于鼻咽癌在我国华南地区的高发率，我们对此进行初步探讨，以期为鼻咽癌的综合治疗提供新的思路。

喉神经内分泌癌临床病理学分析

神经分泌癌是一种由神经内分泌细胞分化而来的特殊的恶性肿瘤，尤其是喉神经内分泌癌（1aryngeal neuroendocrine carcinoma．LNEC）发生率极低。本病首先由Goldman（1969年）报道，目前国外共报道650例。近20年来随着诊疗技术的进步，本病的相关报道有所增多，但多属于个例报道．目前国内外对本病仍无系统的认识。