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.

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.

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。

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.

淋巴细胞活化基因-3在妇科肿瘤中的研究进展

妇科肿瘤是女性死亡的重要原因之一,尽管经过规范治疗部分患者的病情可以得到改善,但仍有很大一部分患者病情恶化,预后不佳。早期诊断及治疗是改善妇科肿瘤预后、减轻疾病负担的重要方法,因此需寻找更有效的治疗靶点。淋巴细胞活化基因-3(lymphocyte activation gene-3,LAG-3)是一个新兴的免疫检查点分子,高表达于多种类型的肿瘤浸润淋巴细胞表面,通过抑制免疫细胞功能参与免疫抑制并造成肿瘤免疫逃逸。近年研究发现,LAG-3在妇科肿瘤中高表达,与肿瘤的发生发展密切相关,有望成为妇科肿瘤免疫治疗的新靶点。阐述LAG-3的结构及功能,并就LAG-3与三大妇科肿瘤的相关性研究进展进行综述,以期为妇科肿瘤的后续治疗研究提供新的思路。

工程化间充质干细胞来源外泌体在靶向递送抗肿瘤药物中的应用与问题

背景:间充质干细胞来源外泌体具有免疫原性低且肿瘤归巢能力强等优点,在靶向递送药物方面备受关注。但外泌体在到达靶细胞前易被体内循环迅速清除,此外,由于外泌体表面性质和摄取机制复杂,其靶向性并不十分明显,需要一定的工程化策略提高递送效率。目的:通过综述间充质干细胞来源外泌体工程化修饰的不同策略,了解提高外泌体递送效率的相关机制、临床前应用和面临的问题,为进一步临床应用提供理论依据。方法:检索中国知网、维普、万方、PubMed数据库从建库至2024年的相关文献,检索词为“间充质干细胞,外泌体,工程化外泌体,靶向递送,抗肿瘤药物”和“mesenchymal stem cells,exosomes,engineered exosomes,targeted delivery,antineoplastic agents”,筛选工程化间充质干细胞来源外泌体靶向递送抗肿瘤药物的文献,共计纳入85篇文献进行综述分析。结果与结论:(1)间充质干细胞来源外泌体的工程化修饰复杂多样,可通过显著增强外泌体对器官或组织靶向能力,增加血液循环中停留时间,以及降低外泌体中促肿瘤分子的表达,以此达到提高外泌体递送效率的效果;(2)间充质干细胞外泌体在目前的抗肿瘤治疗研究中递送传统和新型药物具有巨大前景;(3)当前仍然存在一些安全问题不能将其转化在临床中,未来的研究将进一步改进和深入研究递送机制,有望开发出更为高效和安全的治疗策略。

卵巢癌铂耐药及其治疗研究进展

卵巢癌是恶性程度最高的妇科恶性肿瘤之一。以铂为基础的化疗是卵巢癌治疗的重要组成部分,因此铂耐药也是卵巢癌治疗中棘手的问题。铂耐药是一个复杂的过程,涉及多种机制。本文就卵巢癌细胞铂耐药的分子机制及治疗进展作一综述,以期为该病的临床治疗提供借鉴。

Potential of four marine-derived fungi extracts as anti-proliferative and cell death-inducing agents in seven human cancer cell lines

Objective:To evaluate the in vitro anticancer activity of crude ethyl acetate extracts of the culture of four marine-derived fungi Aspergillus similanensis KUFA 0013(E1),Neosartorya paulistemis KUFC 7897(E2),Neosartorya siamensis KUFA 0017(E4) and Talaromyces trachyspermus KUFC 0021(E3) on a panel of seven human cancer cell lines.Methods:Effects on cell proliferation,induction of DNA damage and cell death were assessed by MTT and clonogenic assays,comet assay and nuclear condensation assay,respectively.Results:The proliferation of HepG2,HCTl 16 and A375 cells decreased after incubation with the extracts E2 and E4.The anti-proliterative effect was confirmed by morphologic alterations and by clonogenic assay.Both extracts also induced cell death in HepG2 and HCT116 cells.Doxorubicin was used as a positive control and showed in vitro anticancer activity.Conclusions:This study demonstrated,for the first time,that extracts of Neosartorya paulistensis and Neosartorya siamensis have selective anti-proliferative and cell death activities in HepG2,HCT16 and A375 cells.The bioactivity of these extracts suggests a potential for biotechnological applications and substantiates that both should be further considered for the elucidation of the molecular targets and signal transduction pathways involved.

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.

基于网络药理学和分子对接探讨康艾注射液治疗乳腺癌的作用机制

目的利用网络药理学和分子对接探讨康艾注射液治疗乳腺癌的分子机制。方法该研究起止时间为2021年3—6月。资料来源是通过中药系统药理学数据库与分析平台(TCMSP)、Swiss Target Prediction数据库挖掘康艾注射液的化学成分及靶点,借助Uniprot数据库进行基因名称校正,在GeneCards、OMIM数据库中检索乳腺癌疾病的相关靶点,利用Venny 2.1在线软件获取药物与疾病的共同靶点,由Cytoscape 3.7.2绘制药物-成分-靶点-疾病网络,STRING数据库在线绘制蛋白互作网络,基于DAVID数据库对靶点进行基因本体(GO)和京都基因与基因组百科全书(KEGG)富集分析,运用AutoDock Vina软件对康艾注射液的关键的活性成分和作用靶点进行分子对接验证。结果康艾注射液的32个有效成分通过调控125个靶点和104条通路对乳腺癌产生作用,4个关键的化合物分别为异鼠李素、槲皮素、山柰酚、氧化苦参碱,可通过肿瘤抑制蛋白(TP53)、外消旋-α丝氨酸/苏氨酸蛋白激酶(AKT1)、核转录因子激活蛋白-1(JUN)、丝裂原活化蛋白激酶1(MAPK1)、肿瘤坏死因子(TNF)等关键靶蛋白介导癌症途径、TNF、低氧诱导因子-1(HIF-1)、磷脂酰肌醇-3-激酶-丝氨酸/苏氨酸蛋白激酶(PI3K-Akt)、凋亡途径、核苷酸结合寡聚化结构域(NOD)样受体、T细胞受体等信号通路发挥抗乳腺癌作用。分子对接表明筛选的靶点蛋白与有效活性成分具有较好的结合活性。结论康艾注射液治疗乳腺癌具有多成分、多靶点、多途径的作用特点,该研究结果为康艾注射液的临床应用及其机制研究提供了理论依据。

某医院血液科24种抗肿瘤药超说明书用药评价

目的 回顾性调查某院血液科抗肿瘤药物超说明书用药现状并进行循证医学评价,为制定超说明书用药政策提供基线数据,为临床超说明书用药提供合理用药依据。方法 收集昆明医科大学第二附属医院血液科2019年7—12月出院病人的病历资料,依据药品说明书,判断其抗肿瘤药用药医嘱是否超说明书,通过Micromedex的Thomson分级系统对超说明书用药进行评价,Micromedex数据库检索不到的,临床药师进一步查询证据后进行Thomson分级评价。结果 2019年7—12月该院血液科共有24种药品存在超说明书用药,375条超说明书用药医嘱,共有36项不同类型超说书用药,其中有效性等级Class Ⅰ(治疗有效)有2项、Class Ⅱa(证据支持有效)24项、Class Ⅱb(有效性具有争议)9项、Class Ⅲ(治疗无效)1项;推荐等级Class Ⅰ(治疗有效)有2项、Class Ⅱa(证据支持有效)2项、Class Ⅱb(有效性具有争议)30项、Class Ⅲ(治疗无效)2项、Indeterminate(不明确)0项;证据等级Catagory A 0项、Catagory B 35项、Catagory C 1项、No Evidence 0项。结论 该院血液科抗肿瘤药物超说明书用药情况较为常见,超说明书用药均有循证医学证据,但个别证据等级低、有效性有限。医疗机构应加强超说明书用药管理,构建超说明书用药循证评价系统,规范超说明书用药行为,促进临床合理用药。

宫颈神经内分泌癌治疗的新进展

宫颈神经内分泌癌(neuroendocrine carcinoma of the cervix,NECC)是一种罕见的恶性程度极高的妇科肿瘤。临床上对NECC的组织来源、发病机制并不明确。NECC没有标准的治疗方案,多是结合宫颈鳞状细胞癌、腺癌和小细胞肺癌的治疗经验制定治疗方案。近年来大样本队列基因组研究显示,NECC与宫颈外神经内分泌癌具有不同的基因组学特征,对NECC与宫颈外神经内分泌癌之间的生物学和治疗相关性提出了质疑。由于NECC的罕见性,获得足够数量的患者进行疗效试验的可能性很低,这阻碍了NECC标准治疗方案的制定。基因检测能为NECC靶向药物的个体化治疗提供策略。多项研究结果显示,NECC具有潜在的可调控的治疗靶点,免疫疗法与放射疗法结合可以延长晚期复发性NECC患者的长期生存。综述NECC的分子特征、靶向药物及免疫治疗的研究进展。

他汀类药物在卵巢癌中的研究进展

他汀类药物是3-羟基-3-甲基戊二酰辅酶A还原酶(3-hydroxy-3-methylglutaryl-coenzyme A reductase,HMGCR)抑制剂,可通过减少胆固醇生物合成和诱导低密度脂蛋白受体表达而降低血浆胆固醇水平,广泛应用于高脂血症的治疗和心脑血管疾病的预防;此外,他汀类药物可能通过阻断细胞周期进展、诱导细胞凋亡、抑制血管生成、抑制肿瘤生长和转移而具有潜在的抗癌作用。卵巢癌预后较差,给患者造成了严重的经济和心理负担。他汀类药物通过抑制甲羟戊酸(mevalonic acid,MVA)途径、促进铁死亡、调节细胞自噬和调节肿瘤微环境(tumor microenvironment,TME)等多种途径发挥抗肿瘤作用和改善卵巢癌化疗耐药现象,同时在某种程度上可抑制卵巢癌细胞增殖,降低卵巢癌患病风险,改善预后,协同并增强化疗药物抗肿瘤作用,降低复发率。综述他汀类药物在卵巢癌的预防和治疗中的研究新进展,以期对未来临床实践提供帮助。

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.

Adeno-associated virus mediated endostatin gene therapy in combination with topoisomerase inhibitor effectively controls liver tumor in mouse model

AIM:rAAV mediated endostatin gene therapy has been examined as a new method for treating cancer.However, a sustained and high protein delivery is required to achieve the desired therapeutic effects.We evaluated the impact of topoisomerase inhibitors in rAAV delivered endostatin gene therapy in a liver tumor model. METHODS:rAAV containing endostatin expression cassettes were transduced into hepatoma cell lines.To test whether the topoisomerase inhibitor pretreatment increased the expression of endostatin,Western blotting and ELISA were performed.The biologic activity of endostatin was confirmed by endothelial cell proliferation and tube formation assays. The anti-tumor effects of the rAAV-endostatin vector combined with a topoisomerase inhibitor,etoposide,were evaluated in a mouse liver tumor model. RESULTS:Topoisomerase inhibitors,including camptothecin and etoposide,were found to increase the endostatin exPression level in vitro.The over-expressed endostatin, as a result of pretreatment with a topoisomerase inhibitor, was also biologically active.In animal experiments,the combined therapy of topoisomerase inhibitor,etoposide with the rAAV-endostatin vector had the best tumor- suppressive effect and tumor foci were barely observed in livers of the treated mice.Pretreatment with an etoposide increased the level of endostatin in the liver and serum of rAAV-endostatin treated mice.Finally,the mice treated With rAAV-endostatin in combination with etoposide showed the longest survival among the experimental models. CONCLUSION:rAAV delivered endostatin gene therapy in combination with a topoisomerase inhibitor pretreatment is an effective modality for anticancer gene therapy.

抗肿瘤药物的心脏毒性及预防

心脏毒性,是抗肿瘤药物严重的并发症。近年来,随诊抗肿瘤药物的发展,多药联合治疗可显著延长患者的生存期,但此方式加重心脏毒性。了解心脏毒性的发生机制,及时发现并进行预防,可减少心血管意外的发生。本文就抗肿瘤药物的心脏毒性预防及管理进行综述。

miR-141-3p、miR-200a在卵巢癌患者外周血中的表达及其对化疗敏感性的预测价值

【目的】探讨微小核糖核酸-141-3p(miR-141-3p)、微小核糖核酸-200a(miR-200a)在卵巢癌患者外周血中的表达及其对化疗敏感性的预测价值。【方法】选取2015年10月至2020年9月延安大学附属医院收治的82例卵巢癌患者,根据卵巢癌患者化疗效果分为无应答组和敏感组,比较两组患者临床资料,采用Logistic回归分析影响卵巢癌患者化疗敏感性的危险因素;绘制受试者工作特征(ROC)曲线,以曲线下面积(AUC)评价外周血miR-141-3p、miR-200a对卵巢癌患者化疗敏感性的预测效能。【结果】本研究82例卵巢癌患者化疗后,共有27例(32.93%)患者对化疗无应答。无应答组临床分期为Ⅳ期占比、有淋巴结转移占比、残留肿瘤直径及miR-141-3p表达水平均高于敏感组(P<0.05),无应答组miR-200a表达水平则低于敏感组(P<0.05)。Logistic回归分析结果显示:临床分期Ⅳ期及外周血miR-141-3p、miR-200a表达水平均是影响卵巢癌患者化疗敏感性的危险因素(OR=2.732、3.241、3.277,P<0.05)。ROC曲线分析显示:外周血miR-141-3p、miR-200a预测卵巢癌患者化疗敏感性的最佳截断点分别为1.55、1.84,AUC分别为0.757、0.790。【结论】外周血miR-141-3p、miR-200a表达水平与卵巢癌患者化疗敏感性有关,可作为预测卵巢癌患者化疗敏感性的重要参考指标。

构建掺杂铕(Eu)的二氧化硅(SiO2)纳米粒子载药平台

目的构建掺杂铕(Eu)的中空介孔二氧化硅(SiO2)纳米粒子载药平台,并观察其特性。方法采用水热法制备掺杂Eu的SiO2空心微球,在其表面修饰靶向物质透明质酸(HA),以浸润法将紫杉醇(PTX)负载于介孔氧化硅纳米颗粒(MSN)中,得到HA-Eu-hMSNs-PTX,观察其形态、荧光特性等性状,以及载药量、生物安全性及细胞毒性。结果所获HA-Eu-hMSNs直径(61.33±8.94)nm;以PTX修饰后成功制备HA-Eu-hMSNs-PTX,其PTX负载量为52.33µg/mg。加入Eu-hMSNs和HA-Eu-hMSNs后,SW1990细胞的细胞核均被DAPI染为蓝色并可见红色荧光信号,但加入Eu-hMSNs后该信号较弱。加入HA-Eu-hMSNs 24 h后,最高浓度(200μg/ml)组SW1990细胞存活率仍在90%以上。PTX、Eu-hMSNs-PTX和HA-Eu-hMSNs-PTX均对SW1990细胞具有浓度依赖性细胞毒性;相同PTX浓度下,HA-Eu-hMSNs-PTX的细胞毒性高于游离PTX和Eu-hMSNs-PTX。结论所制备HA-Eu-hMSNs-PTX粒径均匀、生物安全性佳,靶向能力和肿瘤细胞杀伤能力良好。