anticancer chemotherapy

  • 文章类型: Case Reports
    我们报告了一例晚期睾丸癌,即使在诱导化疗期间感染COVID-19后,也通过早期适当恢复化疗治愈。
    患者是一名健康的36岁男性。诊断为IIIB期非精原细胞瘤(pT2N2M1a)。在第一个化疗周期的第14天,患者被诊断为轻度COVID-19。第二个化疗周期延迟1天开始(在COVID-19诊断后第10天)。患者在最小程度推迟化疗的情况下获得缓解。
    只有少数病例报告描述了COVID-19患者恢复抗癌化疗。在决定COVID-19感染后何时恢复化疗时,必须考虑癌症类型等因素,programming,和COVID-19的严重程度,应根据个体患者的需求量身定制。
    UNASSIGNED: We report a case of advanced testicular cancer cured by early and appropriate resumption of chemotherapy even after COVID-19 infection during induction chemotherapy.
    UNASSIGNED: The patient was a healthy 36-year-old male. The diagnosis was a stage IIIB nonseminoma (pT2N2M1a). On day 14 of the first chemotherapy cycle, the patient was diagnosed with mild COVID-19. The second chemotherapy cycle was initiated with a 1-day delay (on day 10 after the COVID-19 diagnosis). The patient achieved remission with minimal postponement of chemotherapy.
    UNASSIGNED: Only a few case reports have described the resumption of anticancer chemotherapy in patients with COVID-19. In deciding when to resume chemotherapy after COVID-19 infection, it is essential to consider factors such as cancer type, progression, and severity of COVID-19 and should be tailored to individual patient needs.
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  • 文章类型: Journal Article
    背景:对抗癌化疗和单克隆抗体的超敏反应可能导致一线治疗方案的终止。这些反应的鉴定可以通过快速药物脱敏提供特定的诊断和治疗。
    目的:为了确定抗癌化疗和单克隆抗体的超敏反应,以及快速药物脱敏的安全性和有效性。
    方法:我们在墨西哥对抗癌化疗和单克隆抗体给药后出现的超敏反应进行了观察性研究。我们记录了最初反应的症状及其严重程度,还有皮肤测试的结果.我们还报告了在这些患者中进行12步(轻度-中度反应)和16步(严重反应)脱敏方案的经验。
    结果:总体而言,93例患者接受了336例快速药物脱敏;105例紫杉烷,115铂类药物,101单克隆抗体,和其他15种抗癌化疗。紫杉烷类的过敏反应发生在第一次或第二次给药,第六周期后的铂类药物,和利妥昔单抗在第一个周期。卡铂最常见的症状是荨麻疹,紫杉醇背痛,奥沙利铂和多西他赛呼吸困难,和单克隆抗体的心血管症状。75%的卡铂组皮肤试验呈阳性,多西他赛中只有16.7%。药物快速脱敏成功率为99.4%,85.7%未出现任何相关的超敏反应。
    结论:对抗癌化疗和单克隆抗体的超敏反应的诊断为肿瘤疾病的治疗提供了一个全景图。我们的标准化脱敏方案是安全有效的,可以在其他中心复制,以治疗需要维持一线治疗的患者。
    BACKGROUND: Hypersensitivity reactions to anticancer chemotherapy and monoclonal antibodies may lead to discontinuation of first-line treatment options. Identification of these reactions can provide specific diagnosis and treatment by rapid drug desensitizations.
    OBJECTIVE: To determine the hypersensitivity reactions involved in anticancer chemotherapy and monoclonal antibodies, and the safety and efficacy of rapid drug desensitization.
    METHODS: We conducted an observational study of hypersensitivity reaction presented after the administration of anticancer chemotherapy and monoclonal antibodies in Mexico. We documented the symptoms of initial reaction and their severity, and the results of skin tests. We also report our experience of the administration of 12-step (mild-moderate reactions) and 16-step (severe reactions) desensitization protocols in these patients.
    RESULTS: Overall, 93 patients received 336 rapid drug desensitization; 105 to taxanes, 115 to platinum drugs, 101 to monoclonal antibodies, and 15 other anticancer chemotherapy. Hypersensitivity reaction to taxanes occurred in the first or second administration, platinum drugs after the sixth cycle, and rituximab in the first cycle. The most common symptom in carboplatin was urticaria, paclitaxel back pain, oxaliplatin and docetaxel dyspnea, and in the monoclonal antibodies cardiovascular symptoms. Skin tests were positive in 75% of the carboplatin group, and only 16.7% in docetaxel. There was a rapid drug desensitization success rate of 99.4% and 85.7% did not present any related hypersensitivity reaction.
    CONCLUSIONS: The diagnosis of hypersensitivity reaction to anticancer chemotherapy and monoclonal antibodies offers a panorama in the management of oncological diseases. Our standardized desensitization protocol is safe and effective and can be reproduced in other centers to treat patients who need to maintain first-line treatment.
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  • 文章类型: Journal Article
    金属基络合物在许多慢性疾病的治疗中占据了开创性的地位,包括各种类型的癌症。尽管顺铂治疗许多实体恶性肿瘤取得了惊人的成功,迄今为止,临床上用于抗癌化疗的金属药物数量有限。虽然许多其他突出的铂和非铂基金属药物(例如NAMI-A,KP1019,卡铂,奥沙利铂,二氯化二茂钛,casiopeinas®等)已进入临床试验,由于有害的毒性作用,许多人在研发的后期阶段失败了,固有耐药性和不良的药代动力学反应以及低疗效。尽管如此,多年来,药物无机化学领域的研究呈指数级增长,采用新的基于靶标的药物设计策略,旨在改善药理学结果,同时减轻这些药物实体的副作用。在过去的几十年里,天然产物成为抗癌药物开发的关键结构基序之一。药物化学领域的许多杰出研究人员致力于开发新的3d过渡金属基抗癌药物/重新利用现有的生物活性化合物,这些化合物来自多种药效团,如香豆素,黄酮类化合物,色原,生物碱等.天然生物碱及其类似物的金属配合物,jatrorrhizine,小檗碱,氧杂吗啡,8-羟基喹啉等.在抗癌药物开发过程中获得了突出的地位,因为天然存在的生物碱可以抗增殖,诱导细胞凋亡,抑制血管生成,具有较好的愈合效果。虽然它们中的一些是ERK信号调节激酶的抑制剂,其他显示基于环氧合酶-2(COX-2)和端粒酶抑制的活性。然而,这些生物碱复合物的靶标仍不清楚,尽管已经确定它们通过在体外和体内干扰肿瘤发生和肿瘤进展的多种途径而证明了抗癌效力。在过去的十年里,在开发基于天然生物碱的金属药物治疗以干预癌症化疗方面取得了许多重大进展,这些进展总结如下,并在本文中进行了综述。
    Metal-based complexes have occupied a pioneering niche in the treatment of many chronic diseases, including various types of cancers. Despite the phenomenal success of cisplatin for the treatment of many solid malignancies, a limited number of metallo-drugs are in clinical use against cancer chemotherapy till date. While many other prominent platinum and non‑platinum- based metallo-drugs (e.g. NAMI-A, KP1019, carboplatin, oxaliplatin, titanocene dichloride, casiopeinas® etc) have entered clinical trials, many have failed at later stages of R&D due to deleterious toxic effects, intrinsic resistance and poor pharmacokinetic response and low therapeutic efficacy. Nonetheless, research in the area of medicinal inorganic chemistry has been increasing exponentially over the years, employing novel target based drug design strategies aimed at improving pharmacological outcomes and at the same time mitigating the side-effects of these drug entities. Over the last few decades, natural products became one of the key structural motifs in the anticancer drug development. Many eminent researchers in the area of medicinal chemistry are devoted to develop new 3d-transition metal-based anticancer drugs/repurpose the existing bioactive compounds derived from myriad pharmacophores such as coumarins, flavonoids, chromones, alkaloids etc. Metal complexes of natural alkaloids and their analogs such as luotonin A, jatrorrhizine, berberine, oxoaporphine, 8-oxychinoline etc. have gained prominence in the anticancer drug development process as the naturally occurring alkaloids can be anti-proliferative, induce apoptosis and exhibit inhibition of angiogenesis with better healing effect. While some of them are inhibitors of ERK signal-regulated kinases, others show activity based on cyclooxygenases-2 (COX-2) and telomerase inhibition. However, the targets of these alkaloid complexes are still unclear, though it is well-established that they demonstrate anticancer potency by interfering with multiple pathways of tumorigenesis and tumor progression both in vitro and in vivo. Over the last decade, many significant advances have been made towards the development of natural alkaloid-based metallo-drug therapeutics for intervention in cancer chemotherapy that have been summarized below and reviewed in this article.
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  • 文章类型: Journal Article
    癌细胞中谷胱甘肽(GSH)水平升高导致对化疗的反应不佳,因此需要使用最大耐受剂量的药物。导致无数的副作用。我们开发了一种生物相容性和荧光可跟踪的纳米系统,铁(III)结合纳米碳质多酚(FeNCP),为了调节癌细胞中可用的GSH库,在细胞毒性抗癌药物的治疗中发挥协同作用,多柔比星(Dox)。使用纳米级碳系统作为平台来设计该纳米系统以产生GSH响应性没食子酸-铁络合物。使用UV-Vis在PBS(pH7.4)和细胞裂解物中探测了FeNCP和GSH之间的有效相互作用,荧光分光光度法,1HNMR,流式细胞术,以及共聚焦和透射电子显微镜研究。用亚细胞毒性FeNCP和Dox同时治疗癌细胞导致HepG2(肝细胞癌)的Dox剂量减少指数为6.1,B16F0(黑色素瘤)为6.7,杀死50%的细胞群,这表明需要多倍低剂量的Dox。值得注意的是,与模型正常细胞系相比,这种组合对癌细胞系的细胞毒性相对更大,Vero.在组合治疗中增加的活性氧物质水平表明FeNCP是调节谷胱甘肽活性和增强Dox细胞毒性作用的潜在候选者。这种纳米系统的智能多重设计可能使未来在GSH的光学检测和成像辅助手术中的适用性,除了有可能推进抗癌化疗的治疗方案。
    The elevated glutathione (GSH) level in cancer cells contributes to the poor response to chemotherapy and necessitates the use of maximum tolerated drug doses, leading to myriad side effects. We have developed a biocompatible and fluorescently trackable nanosystem, iron(III)-bound nanocarbonaceous polyphenol (FeNCP), to modulate the available GSH pool in cancer cells for synergistic effects in treatments with a cytotoxic anticancer drug, doxorubicin (Dox). This nanosystem was designed using a nanoscale carbon system as a platform to generate a GSH-responsive gallic acid-iron complex. The effective interaction between FeNCP and GSH was probed in PBS (pH 7.4) and cell lysates using UV-Vis, fluorescence spectrophotometry, 1H NMR, flow cytometry, and confocal and transmission electron microscopic studies. The concurrent treatment of cancer cells with subcytotoxic FeNCP and Dox leads to dose reduction indices of Dox of ∼6.1 for HepG2 (hepatocellular carcinoma) and 6.7 for B16F0 (melanoma) to kill ∼50% of the cell population, which is suggestive of the requirement of a multifold lower dose of Dox. Notably, this combination was relatively more cytotoxic toward cancer cell lines than the model normal cell line, Vero. The increased reactive oxygen species levels in combinatorial treatment reveal that FeNCP serves as a potential candidate for modulating glutathione activity and potentiating cytotoxic effects of Dox. The intelligent multifold design of this nanosystem might enable the applicability in optical detection of GSH and imaging-assisted surgery in the future, in addition to the potential to advance treatment regimens in anticancer chemotherapy.
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  • 文章类型: Journal Article
    活性氧(ROS)在体内发挥重要作用,例如氧化磷酸化和稳态信号转导中能量的产生。由于各种环境因素,生物系统中的氧化还原平衡逐渐崩溃,包括衰老和疾病,并诱导体内氧化应激。天然或合成抗氧化剂均未获得临床批准,由于其不利影响。在这里,我们开发了基于L-半胱氨酸(Cys)的聚合物胶束作为新的自组装抗氧化剂,以减少常规抗氧化剂的不利影响。通过阴离子开环聚合合成了聚乙二醇-嵌段-聚L-半胱氨酸(PEG-block-PCys)。因为PCys片段侧链中的游离SH基团被二硫键保护,所获得的嵌段共聚物是两亲性的并且在水性介质中形成数十纳米大小的聚合物胶束(NanoCyss)。NanoCyss在牛血清白蛋白(BSA)存在下的稳定性通过增加PCys片段的分子量(MW)而增加,使用动态光散射(DLS)进行分析。还使用DLS测量通过改变pH和NaCl浓度来分析NanoCyss的尺寸和凝结趋势。NanoCyss被证实在体外和体内都比N-乙酰半胱氨酸(NAC)毒性更低,因为它们的大小和生物相容性PEG表面层。向肿瘤异种移植小鼠模型腹膜内(i.p.)施用NanoCyss成功地抑制了肿瘤生长。有趣的是,这种影响取决于PCys段的MW。
    Reactive oxygen species (ROS) play essential roles in the body, such as the production of energy in oxidative phosphorylation and signal transduction for homeostasis. Redox balance in biological systems gradually collapses due to various environmental factors, including aging and disease, and induces oxidative stress in the body. None of the natural or synthetic antioxidants have been approved clinically, owing to their adverse effects. Herein, we developed L-cysteine (Cys)-based polymer micelles as new self-assembling antioxidants to reduce the adverse effects of conventional antioxidants. Poly(ethylene glycol)-block-poly(L-cysteine) (PEG-block-PCys) was synthesized via anionic ring-opening polymerization. Because the free SH groups in the side chains of the PCys segment were protected by disulfide bonds, the obtained block copolymers were amphiphilic and formed polymer micelles (NanoCyss) of tens of nanometers in size in aqueous media. The stability of NanoCyss in the presence of bovine serum albumin (BSA) was increased by increasing the molecular weight (MW) of the PCys segments, which was analyzed using dynamic light scattering (DLS). The size and coagulation tendency of NanoCyss were also analyzed using DLS measurements by changing the pH and NaCl concentration. NanoCyss were confirmed to be less toxic both in vitro and in vivo than N-acetylcysteine (NAC) because of their size and biocompatible PEG surface layer. Intraperitoneal (i.p.) administration of NanoCyss to the tumor xenograft mouse model successfully suppressed tumor growth. Interestingly, this effect depended on the MW of the PCys segments.
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  • 文章类型: Journal Article
    铜是一种内源性金属离子,已被研究用于制备副作用较小的新型抗肿瘤剂。铜作为辅助因子参与几种酶,在ROS生产中,在促进肿瘤进展中,转移,和血管生成,并且在几种类型的人类癌症的血清和组织中发现了高水平。在这种情况下,在新型抗癌铜基药物的开发中,通常遵循两种策略:游离铜离子的螯合和触发细胞死亡的铜络合物的合成。在过去的40年中,后一种策略得到了遵循,许多评论涵盖了广谱铜配合物的抗癌特性,表明这些化合物的活性通常是多方面的。在这项工作中,我们希望关注带有取代或未取代的1,10-菲咯啉基配体和不同类别的无机和有机辅助配体的混合Cu(II)配合物的抗癌性质。对于每种金属络合物,将报告和讨论有关测试细胞系和机理研究的信息。根据辅助配体的作用机理,金属中心,和日益复杂的复合结构。
    Copper is an endogenous metal ion that has been studied to prepare a new antitumoral agent with less side-effects. Copper is involved as a cofactor in several enzymes, in ROS production, in the promotion of tumor progression, metastasis, and angiogenesis, and has been found at high levels in serum and tissues of several types of human cancers. Under these circumstances, two strategies are commonly followed in the development of novel anticancer Copper-based drugs: the sequestration of free Copper ions and the synthesis of Copper complexes that trigger cell death. The latter strategy has been followed in the last 40 years and many reviews have covered the anticancer properties of a broad spectrum of Copper complexes, showing that the activity of these compounds is often multi factored. In this work, we would like to focus on the anticancer properties of mixed Cu(II) complexes bearing substituted or unsubstituted 1,10-phenanthroline based ligands and different classes of inorganic and organic auxiliary ligands. For each metal complex, information regarding the tested cell lines and the mechanistic studies will be reported and discussed. The exerted action mechanisms were presented according to the auxiliary ligand/s, the metallic centers, and the increasing complexity of the compound structures.
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  • 文章类型: Case Reports
    A 51-year-old woman was admitted to our hospital because of pneumonia after chemotherapy with doxorubicin and cyclophosphamide for left breast cancer. The patient was diagnosed with Mycobacterium abscessus pulmonary infection by the detection of M. abscessus complex (MABC) in sputum cultures. However, MABC is intrinsically resistant to most of the antibacterial agents, and MABC pulmonary disease outcomes with modern antibiotic treatment are currently the worst among all mycobacterial species. We herein report the successful treatment of M. abscessus pulmonary infection by a combination treatment with antibiotics and surgical lung resection.
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  • 文章类型: Journal Article
    Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent complication in patients receiving anticancer chemotherapy, but no effective treatment is yet available. Objective: To evaluate the efficacy and safety of a tramadol/acetaminophen combination tablets for CIPN. Design: This is a single-arm phase II study of tramadol/acetaminophen. Setting/subjects: Eligible patients had received oxaliplatin, paclitaxel, or nab-paclitaxel, and were experiencing CIPN. The patients were given one tablet (37.5 mg tramadol plus 325 mg acetaminophen) twice a day for 7 days, then four times a day for 21 days. Measurements: The primary endpoint was the numerical rating scale of neuropathic pain. Other endpoints included the potential of CYP2D6 genetic variants to effective response or toxicity. Results: Of the 34 patients enrolled, 23 completed the protocol treatment. The mean neuropathic pain score decreased insignificantly from 5.53 at baseline to 5.00 at 28 days (95% confidence interval -0.21 to 1.43; p = 0.139). However, 13 of the 23 (56.5%) patients who completed the protocol treatment showed improvement of the neuropathic pain score by at least 1 point. No severe adverse events were observed. Tramadol/acetaminophen may be more effective in patients with the intermediate metabolizer phenotype of the CYP2D6 single nucleotide polymorphisms (SNPs) although at the cost of increased toxicity. Conclusions: Although tramadol/acetaminophen tablets did not reduce neuropathic pain to a statistically significant degree, the neuropathic pain severity reduced in more than a half of the patients.
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  • 文章类型: Editorial
    暂无摘要。
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  • 文章类型: Journal Article
    背景:癌症患者尤其面临药物相互作用的风险。然而,在肿瘤学中,这种风险在法国尚未得到深入研究。这项研究的主要目的是描述肺癌或消化道肿瘤患者中药物相互作用的比例。
    方法:对5月27日以来93例患者的药物处方进行分析,2019年7月07日,2019年在我们的综合癌症中心住院的肿瘤患者中使用两个软件程序(Thériaque™和DDIPredictor™)。
    结果:在纳入研究的88例患者中,已经确定了544种药物相互作用,66例患者(75.0%,95%CI:64.6-83.6)。对于20/88例患者(22.7%CI:14.5-32.9),报告了非推荐组合或理论禁忌症。依托泊苷是在禁忌或不推荐的组合中最涉及的抗癌分子。在住院期间接受化疗的49例患者中,没有观察到定义为不推荐或禁忌的组合。最常见的毒性是警觉和代谢紊乱,包括高钾血症.使用三种或更多种药物是药物相互作用的危险因素(83vs.23%,P<0.001)。
    结论:药物相互作用仍然是癌症住院患者的主要问题。重要的是继续和加强医生和药剂师之间的合作,以便更好地防止它们的发生。
    BACKGROUND: Cancer patients are particularly at risk for drug interactions. However, in oncology, this risk has not been studied in depth in France. The main objective of this study was to describe the proportion of drug interactions in patients with lung or digestive cancer.
    METHODS: The drug prescriptions of 93 patients were analyzed from may 27th, 2019 to July 07th, 2019 using two software programs (Thériaque™ and DDI Predictor™) in oncology patients hospitalized in our comprehensive cancer center.
    RESULTS: Of the 88 patients included in the study, 544 drug interactions were identified, in 66 patients (75.0%, 95% CI: 64.6-83.6). For 20/88 patients (22.7% CI: 14.5-32.9) a non-recommended combination or a theoretical contraindication was reported. Etoposide was the anticancer molecule most involved in combinations that are contraindicated or not recommended. No combinations defined as not recommended or contraindicated were observed in any of the 49 patients treated with chemotherapy during their hospitalization. The most common toxicities were alertness and metabolic disorders, including hyperkalemia. The use of three or more drugs was a risk factor for drug interactions (83 vs. 23%, P<0.001).
    CONCLUSIONS: Drug interactions remain a major concern in cancer hospitalized patients. It is important to continue and strengthen the collaboration between physicians and pharmacists in order to better prevent their occurrence.
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