cytotoxic drugs

细胞毒性药物
  • 文章类型: Case Reports
    背景:以铂类为基础的联合化疗,包括顺铂和卡铂,是重要的细胞毒性抗癌剂,其广泛用于治疗各种实体瘤。卡铂对小细胞肺癌的生存有类似的影响,但与顺铂相比,通常毒性较轻。两者都可能导致中度或重度神经毒性,但很少报道卡铂的眼部神经毒性。病例介绍:一名79岁的男性接受了静脉化疗(阿特珠单抗,依托泊苷,和卡铂)用于小细胞肺癌。第二个周期化疗后一周,他报告双侧视力丧失为双眼的手部运动。眼底扩张检查显示视网膜动脉狭窄,无出血,在光学相干断层扫描扫描中观察到弥漫性脉络膜和视网膜变薄。荧光素血管造影显示明显延迟的循环,没有阻塞性病变的证据。30-闪烁视网膜电图测试显示双眼完全没有视锥反应。患者的视力加重到双眼没有光感知,即使在化疗停止后。结论:以治疗剂量给予卡铂联合化疗可导致不可逆的视力丧失,一个没有被广泛承认的副作用。使用卡铂时,医生应该意识到其潜在的眼部毒性.
    Background: Platinum-based combination chemotherapy, including cisplatin and carboplatin, are important cytotoxic anti-cancer agents that are widely used to treat various solid tumors. Carboplatin has a similar effect on survival in small cell lung cancer, but generally has a milder toxicity profile when compared with cisplatin. Both may cause moderate or severe neurotoxicity, but ocular neurotoxicity from carboplatin is rarely reported. Case presentation: A 79-year-old man underwent intravenous polychemotherapy (atezolizumab, etoposide, and carboplatin) for small cell lung cancer. One week after the second cycle of chemotherapy, he reported bilateral visual loss as hand motion in both eyes. Dilated fundus examination showed retinal arterial narrowing without hemorrhage, and diffuse choroidal and retinal thinning was observed in an optical coherence tomography scan. Fluorescein angiography revealed significantly delayed circulation without evidence of obstructive lesions. 30-Flicker electroretinogram testing showed a complete absence of cone response in both eyes. The patient\'s visual acuity aggravated to no light perception in both eyes, even after the cessation of chemotherapy. Conclusions: Carboplatin combination chemotherapy administered at therapeutic doses can result in irreversible visual loss, a side effect that is not widely acknowledged. When using carboplatin, physicians should be aware of its potential ocular toxicity.
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  • 文章类型: Journal Article
    在过去的几十年里,兽医肿瘤学经历了重大的发展,化疗目前应用于几种肿瘤,治疗成功。传统上,化疗方案基于最大耐受剂量(MTD)概念下的经典细胞抑制药物,这与更大的毒性和耐药性风险有关。因此,出现了新的治疗替代方案,如节拍化疗(MC),引入癌症治疗的新模式。MC包括长时间连续施用低剂量的化疗药物,由于细胞毒性的组合,调节肿瘤微环境(TME),抗血管生成和免疫调节作用。自2007年以来,这种多靶向治疗已被描述为几种犬科动物和猫科动物癌症的治疗选择,并已在文献中发表了积极的结果。特别是在狗的乳腺癌和软组织肉瘤中。这篇综述文章的目的是描述有关MC在小动物肿瘤学中使用的最新知识,强调其行动机制,最常用的药物和临床结果。
    Veterinary oncology has experienced significant evolution over the last few decades, with chemotherapy being currently applied to several neoplasms with therapeutic success. Traditionally, chemotherapy protocols are based on classic cytostatic drugs under the concept of maximum tolerated dose (MTD), which has been associated with a greater risk of toxicity and resistance. Thus, new therapeutic alternatives have emerged, such as metronomic chemotherapy (MC), introducing a new paradigm in cancer treatment. MC consists of administering low doses of chemotherapy drugs continuously over a long period of time, modulating the tumour microenvironment (TME) due to the combination of cytotoxic, antiangiogenic and immunomodulatory effects. This multi-targeted therapy has been described as a treatment option in several canine and feline cancers since 2007, with positive results already published in the literature, particularly in mammary carcinomas and soft tissue sarcomas in dogs. The aim of this review article is to describe the current knowledge about the use of MC in small animal oncology, with emphasis on its mechanisms of action, the most commonly used drugs and clinical outcome.
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  • 文章类型: Case Reports
    肠气(PI)是指肠壁内存在空气。它可能与许多原因有关,包括化疗。我们报告了一例70岁的男性转移性舌鳞状细胞癌(SCC),其住院过程因腹泻和PI的发展而复杂化,这是由于5-氟尿嘧啶(5-FU)化疗后,全面的诊断检查和令人放心的体格检查。患者接受抗生素和肠道休息保守治疗。出院前进行的重复成像显示出稳定的发现。患者出院后无并发症发生。我们强调了在确保体检和诊断检查的患者中认识到5-FU是PI的原因的重要性。此外,我们强调,通过保守的措施,它仍然可能得到成功的管理。
    Pneumatosis intestinalis (PI) refers to the presence of air within the bowel wall. It can be associated with many causes including chemotherapy. We report a case of a 70-year-old male with metastatic tongue squamous cell carcinoma (SCC), whose hospital course was complicated by diarrhea and the development of PI, which was attributed to 5-fluorouracil (5-FU) chemotherapy after a comprehensive diagnostic workup and reassuring physical examination. The patient was treated conservatively with antibiotics and a bowel rest. A repeat imaging done before discharge showed stable findings. The patient was discharged afterward without complications. We highlight the importance of recognizing 5-FU as a cause for PI among patients with reassuring physical examination and diagnostic workup. Furthermore, we highlight that it may still be successfully managed with conservative measures.
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  • 文章类型: Journal Article
    抗体-药物缀合物(ADC)是由通过接头与单克隆抗体连接的细胞毒性药物组成的靶向生物制剂。单克隆抗体靶向肿瘤细胞并转运小分子细胞毒性药物,用于特异性递送和最小的脱靶副作用。临床医生有必要了解ADC的分子特征和机制。患者的生存主要取决于适当的剂量和疗程,也取决于不良反应的适当管理。该共识提供了对市售ADC的系统评价,并进一步讨论了ADC的临床应用和管理。
    Antibody-drug conjugates (ADCs) are targeted biological agents composed of a cytotoxic drug linked to a monoclonal antibody through a linker. The monoclonal antibody targets tumor cells and transports small-molecule cytotoxic drugs for specific delivery and minimal off-target side effects. It is necessary for clinicians to understand the molecular characteristics and mechanisms of ADCs. Patients\' survival mainly depends on the appropriate dose and course of treatment and also on proper management of adverse reactions. This consensus provides a systematic review of commercially available ADCs and further discusses the clinical application and management of ADCs.
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  • 文章类型: Journal Article
    乳腺癌是全球诊断最多的实体癌之一。几十年来,广泛的研究一直在进行,以应对用选择性化合物治疗实体瘤的挑战。本文旨在总结美国FDA正在使用或目前批准用于治疗或缓解乳腺癌的治疗剂,到目前为止。探索了以前发表的关于注册分子的同行评审研究论文的书目数据库的结构化搜索,并根据用于乳腺癌不同阶段的一线/辅助治疗的各种药物类别对数据进行了分类。我们收录了300多篇同行评审的论文,包括研究和评论文章,从而为读者提供有用的综合信息。讨论了39种药物的清单及其现状,剂量方案,作用机制,药代动力学,可能的副作用,和市售配方。文章的另一个有趣的方面包括关注这些药物的新制剂,这些药物目前正在临床试验或批准过程中。因此,对于在这些药物的制剂开发领域工作的研究人员来说,这项详尽的审查将是一站式解决方案。
    Breast cancer is one of the most diagnosed solid cancers globally. Extensive research has been going on for decades to meet the challenges of treating solid tumors with selective compounds. This article aims to summarize the therapeutic agents which are either being used or are currently under approval for use in the treatment or mitigation of breast cancer by the US FDA, to date. A structured search of bibliographic databases for previously published peer-reviewed research papers on registered molecules was explored and data was sorted in terms of various categories of drugs used in first line/adjuvant therapy for different stages of breast cancer. We included more than 300 peer-reviewed papers, including both research and reviews articles, in order to provide readers an useful comprehensive information. A list of 39 drugs are discussed along with their current status, dose protocols, mechanism of action, pharmacokinetics, possible side effects, and marketed formulations. Another interesting aspect of the article included focusing on novel formulations of these drugs which are currently in clinical trials or in the process of approval. This exhaustive review thus shall be a one-stop solution for researchers who are working in the areas of formulation development for these drugs.
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  • 文章类型: Journal Article
    近年来,胃肠道癌症的发病率有所增加。目前的治疗提出了许多挑战,包括耐药性,非特异性,和严重的副作用,需要探索新的治疗策略。一个有希望的途径是使用磁性纳米粒子,由于它们在施加外部交变磁场时能够在肿瘤区域产生热量,因此获得了相当大的兴趣,称为热疗的过程。这篇综述对最近十年发表的体外和体内研究进行了系统的搜索,这些研究采用磁性纳米颗粒介导的热疗治疗胃肠道癌症。在应用各种纳入和排除标准后(过去10年中使用替代磁场进行热疗的研究),共分析了40篇文章。结果表明,氧化铁是纳米颗粒中产生磁性的首选材料,大肠癌是研究最多的胃肠道癌症。有趣的是,新的治疗方法采用纳米粒子加载化疗药物,并结合磁性热疗显示出优异的抗肿瘤效果。总之,磁性纳米颗粒介导的热疗治疗似乎是治疗胃肠道癌症的有效方法,提供优于传统疗法的优势。
    The incidence of gastrointestinal cancers has increased in recent years. Current treatments present numerous challenges, including drug resistance, non-specificity, and severe side effects, needing the exploration of new therapeutic strategies. One promising avenue is the use of magnetic nanoparticles, which have gained considerable interest due to their ability to generate heat in tumor regions upon the application of an external alternating magnetic field, a process known as hyperthermia. This review conducted a systematic search of in vitro and in vivo studies published in the last decade that employ hyperthermia therapy mediated by magnetic nanoparticles for treating gastrointestinal cancers. After applying various inclusion and exclusion criteria (studies in the last 10 years where hyperthermia using alternative magnetic field is applied), a total of 40 articles were analyzed. The results revealed that iron oxide is the preferred material for magnetism generation in the nanoparticles, and colorectal cancer is the most studied gastrointestinal cancer. Interestingly, novel therapies employing nanoparticles loaded with chemotherapeutic drugs in combination with magnetic hyperthermia demonstrated an excellent antitumor effect. In conclusion, hyperthermia treatments mediated by magnetic nanoparticles appear to be an effective approach for the treatment of gastrointestinal cancers, offering advantages over traditional therapies.
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  • 文章类型: Journal Article
    操作细胞毒性药物的药学人员处于持续暴露风险中。因此,应始终促进培训和严格遵守建议的做法。这项研究的主要目的是开发和应用一种安全的,有效和低成本的方法,用于培训和评估细胞毒性药物的安全处理,使用市售的补品水。为了评估补品水作为盐酸奎宁的替代标记的潜力,在紫外线(300-400纳米)下分析了1毫升四种不同滋补水(一种有色和三种无色)的故意溢出。着色样品在紫外(UV)光下不产生荧光。通过UV/Vis分光光度法(300-500nm)进一步分析显示荧光的三种市售滋补水。之后,开发了模拟细胞毒性药物操作的方案,并将其应用于12名药学技术人员,根据推荐的常规程序使用补品水制备了24个静脉注射袋。与会者回答了一份简短的问卷,以评估这项活动的充分性和适用性。七个参与者在操纵过程中溢出,其中大部分是在用针头操作期间记录的。为简单起见,所有参与者对滋补水操纵模拟进行了4或5分的评分,效率和可行性。获得的结果表明,补品水可用于模拟训练和评估计划中细胞毒性药物的操作。通过使用这种盐酸奎宁的替代标记,可以执行更具成本效益的,但同样有效,评估。
    Pharmacy personnel that manipulate cytotoxic drugs are under continuous exposure risk. Therefore, training and strict adherence to recommended practices should always be promoted. The main objective of this study was to develop and apply a safe, effective and low-cost method for the training and assessment of the safe handling of cytotoxic drugs, using commercially available tonic water. To evaluate the potential of tonic water as a replacement marker for quinine hydrochloride, deliberate spills of 1 mL of four different tonic waters (one coloured and three non-coloured) were analysed under ultraviolet light (300-400 nm). The pigmented sample did not produce fluorescence under ultraviolet (UV) light. The three commercially available tonic waters that exhibited fluorescence were further analysed by UV/Vis spectrophotometry (300-500 nm). Afterwards, a protocol of simulated manipulation of cytotoxic drugs was developed and applied to 12 pharmacy technicians, that prepared 24 intravenous bags according to recommended routine procedures using tonic water. Participants responded to a brief questionnaire to evaluate the adequacy and applicability of the activity. Seven of the participants had spillages during manipulation, the majority of which recorded during manipulation with needles. All participants scored the tonic water manipulation simulation with 4 or 5 points for simplicity, efficiency and feasibility. The obtained results suggest that tonic water can be used to simulate the manipulation of cytotoxic drugs in training and assessment programs. By using this replacement marker for quinine hydrochloride, it is possible to perform a more cost-effective, yet equally effective, assessment.
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  • 文章类型: Journal Article
    背景技术系统性硬化症(SSc)是一种相对常见的结缔组织疾病,以炎症为特征,进行性皮肤纤维化,和小血管的损伤,特别是在肺和肾。似乎幽门螺杆菌(H.幽门螺杆菌)可能有助于SSc作为胃肠道外自身免疫性疾病的发展。我们调查了幽门螺杆菌感染与SSc患者疾病严重程度之间的关系。方法这是一项横断面研究。本研究中的抽样方法是人口普查方法,其方式是将2015年5月至2016年8月转诊至ImamReza教育与研究大学医学中心的所有SSc患者纳入研究。最后,根据纳入标准选择74例患者。纳入标准为:1.基于美国风湿病学会/欧洲抗风湿病联盟2010(ACR/EULAR)硬皮病分类的最终SSc,这是在过去两年内被诊断出来的。2.不服用任何质子泵抑制剂。3.在最近2个月内未使用任何标准方案进行幽门螺杆菌治疗。由两名风湿病学家根据Medsger疾病严重程度量表(MDSS)评估和确定疾病严重程度。幽门螺杆菌粪便抗原的评价基于检测的敏感性和特异性被证明。所有获得的数据采用SPSS16进行统计分析,采用Fisher精确检验Spearman相关检验(RSpearman)。结果74例患者中41例(55.4%)粪便抗原阳性。我们发现基于MDSS的疾病严重程度与幽门螺杆菌粪便抗原滴度之间存在显着正相关(p≤0.001)。结论本研究表明,幽门螺杆菌感染可能在SSc器官受累的严重程度中起重要作用。
    BACKGROUND Systemic sclerosis (SSc) is a relatively common connective tissue disease, which is characterized by inflammation, progressive skin fibrosis, and injuries of small vessels, particularly in the lung and kidney. It seems that Helicobacter pylori (H. pylori) might contribute to the development of SSc as an extra-gastrointestinal autoimmune disease. We investigated the association between H. pylori infections and disease severity in patients with SSc. METHODS This is a cross-sectional study. Sampling method in this study was census method in such a way that all patients with SSc referred to Imam Reza Education and Research University Medical Center from May 2015 to August 2016 were included in the study. Finally, 74 patients were selected based on the inclusion criteria. Inclusion criteria were: 1. Definitive SSc based on American College of Rheumatology/ European League Against Rheumatism 2010 (ACR/EULAR) classification for scleroderma, which was diagnosed within the last two years. 2. Not taking any proton pump inhibitors. 3. Not taking any H. pylori treatment with a standard regimen within the recent 2 months. Disease severity was assessed and determined by two rheumatologists based on the Medsger\'s Disease Severity Scale (MDSS). H. pylori stool antigen was evaluated based on the test which sensitivity and specificity was proven. All obtained data were statistically analyzed by SPSS 16 using Fisher\'s exact test Spearman correlation test (RSpearman). RESULTS Forty one (55.4%) of the 74 patients had positive stool antigens. We found a significant positive association between the severity of disease based on MDSS and titer of H. pylori stool antigen (p ≤ 0.001). CONCLUSION This study reveals that H. pylori infection may play a significant role in the severity of organ involvement in SSc.
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  • 文章类型: Journal Article
    引言在这项回顾性研究中,分析成人肿瘤患者在超声和透视引导下经颈内静脉移植的安全性和并发症发生率。材料与方法回顾性分析2017年1月1日至2019年12月31日36个月期间在三级肿瘤-抗癌医院植入799名成人肿瘤患者的87个端口。数据采集一直持续到2020年12月31日。所有手术均由两名专业的介入放射科医师在超声和超声引导下进行。静脉通路是通过颈内静脉。导管天数(所有患者在移除之前对端口进行维护的总天数,死亡,或2020年12月31日),技术成功率,根据介入放射学报告和患者病历评估并发症发生率.关于患者的多因素分析,如年龄,性别,体重指数(BMI),婚姻状况,教育水平,癌症类型,插入的一侧,颈内静脉直径,糖尿病,抗凝剂/抗血小板,植入的目的,和导管材料对并发症的风险进行了研究。结果共观察到369,329天的导管维护(457.7±345.0)。技术成功率为99.9%,共发生85例(10.5%)并发症,其中24例(28.2%)出现早期(<30天),其余61例(71.8%)出现晚期(>30天)并发症.具体来说,28例(3.5%)导管相关性血栓形成(CRT),27(3.4%)与感染有关,17(2.1%)是机械性并发症(16个纤维蛋白鞘形成和一个导管阻塞),六个(0.7%)与导管迁移有关,四个(0.5%)与切口愈合问题有关,其余3例(0.4%)与缺血性皮肤坏死有关。由于并发症,取出了47个(5.8%)端口。在多变量分析中,癌症类型被发现是并发症发展的危险因素。此外,有迹象表明恶性血液病与感染有关.结论在超声和透视引导下通过颈内静脉放置港口是一种安全的手术。早期和晚期并发症发生率低。
    Introduction In this retrospective study, the safety and complication rates of port implantations via the internal jugular vein under ultrasound and fluoroscopy guidance in adult oncology patients were analyzed. Material and methods Eight hundred seven ports implanted in 799 adult oncology patients at a tertiary Oncology-Anticancer Hospital during a 36-month period from January 1, 2017 to December 31, 2019 were retrospectively reviewed. Data acquisition was obtained until December 31, 2020. All procedures were performed by two specialized interventional radiologists under ultrasound and fluoroscopy guidance. The vein access was via the internal jugular vein. Catheter days (the total number of days of maintenance of the port by all of the patients until removal, death, or December 31, 2020), technical success rates, and complication rates were evaluated based on the interventional radiological reports and patient medical records. Multivariate analysis regarding patients such as age, sex, body mass index (BMI), marital status, educational level, cancer type, side of insertion, diameter of internal jugular vein, diabetes, anticoagulants/antiplatelets, purpose of implantation, and catheter material as to the risk of complications was conducted. Results A total of 369,329 catheter maintenance days were observed (457.7±345.0). The technical success rate was 99.9%, and a total of 85 (10.5%) complications occurred, of which 24 (28.2%) occurred early (<30 days) and the remaining 61 (71.8%) were late (>30 days) complications. Specifically, 28 (3.5%) were catheter-related thrombosis (CRT), 27 (3.4%) related to infection, 17 (2.1%) were mechanical complications (16 fibrin sheath formation and one catheter occlusion), six (0.7%) related to catheter migration, four (0.5%) related to incision healing problems, and the remaining three (0.4%) related to ischemic skin necrosis. Forty-seven (5.8%) ports were removed due to complications. On multivariate analysis, cancer type was found as a risk factor for the development of a complication. Additionally, there was an indication that hematologic malignancy is related to infection. Conclusion Placement of ports via the internal jugular vein under ultrasound and fluoroscopy guidance is a safe procedure, with low rates of early and late complications.
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  • 文章类型: Journal Article
    药房静脉注射混合物服务(PIVAS)中的细胞毒性药物残留一直是制药工作者和PIVAS环境的主要问题,这不仅污染了PIVAS环境,而且对员工的生命健康造成严重危害。本研究旨在建立超高效液相色谱-四极轨道阱高分辨质谱(UPLC-Q/Orbitrap-HRMS)快速检测和监测15种细胞毒性药物的方法。
    采用UPLC-Q/Orbitrap-HRMS方法建立了阿糖胞苷等15种细胞毒性药物的快速检测方法,吉西他滨等。通过在同一天注射四种浓度的标准溶液,验证了该方法的每日精密度和准确度。3天内分别注射相同浓度的4种标准溶液,以验证该方法的每日精密度。计算10:1的信噪比(SNR)作为数量限制。配置浓度为0.5、1、3、10、30、100、300和1,000ng/mL的15种细胞毒性药物的混合标准溶液,并通过该方法进行线性和范围检测。使用15种药物(15MIX)标准溶液在高浓度(300ng/mL)和低浓度(10ng/mL)的混合物在室温下12和24小时研究了该方法的稳定性,分别。每种药物的标准溶液,15MIX和空白溶液用于验证该方法的排他性。
    结果表明,该方法具有良好的特异性,所有药物的日内精确度均低于10%,日内精确度均低于15%。同时,标准曲线线性良好,R2大于0.99,大多数药物的定量限约为1ng/mL。
    在这项研究中,建立了快速检测15种细胞毒性药物的UPLC-Q/Orbitrap-HRMS方法,为PIVAS细胞毒性药物残留监测提供技术支持,这对环境污染监测和职业暴露预警具有重要意义。
    UNASSIGNED: Cytotoxic drug residues in pharmacy intravenous admixture services (PIVAS) have always been a major problem for pharmaceutical workers and the PIVAS environment,which is not only pollutes the PIVAS environment, but also causes serious harm to the life and health of the staff. This study aimed to establish an ultra-high performance liquid chromatography quadrupole orbitrap high resolution mass spectrometry (UPLC-Q/Orbitrap-HRMS) method for the rapid detection and monitor of 15 cytotoxic drugs.
    UNASSIGNED: UPLC-Q/Orbitrap-HRMS method was used to establish a rapid detection method for 15 cytotoxic drugs such as cytarabine, gemcitabine and so on. The daily precision and accuracy of this method were verified by injecting four concentrations of standard solution on the same day, and the same four concentrations of standard solution were injected within three days respectively to verify the daily precision of this method. The signal-to-noise ratio (SNR) of 10:1 was calculated as the limit of quantity. The mixed standard solution of 15 cytotoxic drugs with concentrations of 0.5, 1, 3, 10, 30, 100, 300, and 1,000 ng/mL was configured and detected by this method for linearity and range.The stability of this method was investigated using a mixture of 15 drugs (15MIX) standard solutions at high concentration (300 ng/mL) and low concentration (10 ng/mL) at room temperature for 12 and 24 hours, respectively. A standard solution of each drug, 15MIX and blank solution were taken to verify the exclusivity of the method.
    UNASSIGNED: The results showed that the method had good specificity, and the intraday precision of all drugs was less than 10% and the intraday precision was less than 15%. At the same time, the standard curve had good linearity, R2 was greater than 0.99, and the limit of quantification of most drugs was about 1 ng/mL.
    UNASSIGNED: In this study, an UPLC-Q/Orbitrap-HRMS method was established for the rapid detection of 15 cytotoxic drugs, providing technical support for the monitoring of cytotoxic drug residues in PIVAS, which is of great significance for environmental contamination mornitoring as well as occupational exposure alert.
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