Analysis on Ethical Issues in Off-label Use of Antitumor Drugs / 中国医学伦理学

The phenomenon of off-label use of antitumor drugs in the treatment of malignant tumors is relatively common. Although it is conducive to the development of clinical medical practice, but it is still necessary to pay attention to ethical issues such as medication risks and inadequate implementation of informed consent. Therefore, to effectively avoid ethical risks and standardize the rational use of off-label antitumor drugs, this paper proposed that pharmacists should actively participate in the process of off-label use of antitumor drugs, improve the evidence level of evidence-based medicine, implement patients’ right to informed consent, and improve the hospital’s supervision system of off-label drug use, so as to ensure the reasonable and legal use of drugs by patients.

Research progress of BCL-2 family apoptotic regulation and its mediated drug resistance after antitumor drug therapy / 中国胸心血管外科临床杂志

@#Apoptosis is an important means to regulate cell proliferation and maintain homeostasis. Recent researches have shown that the B-cell lymphoma-2 (BCL-2) family not only plays a dominant role in the regulation of normal cell apoptosis, but also plays a crucial role in the formation of tumor genesis, progression and subsequent drug resistance mediated by the escape mode of apoptosis. The phenomenon that BCL-2 family antagonized the apoptosis induced by antitumor drugs and then acquired drug resistance has been reported in the clinical treatment of hematologic lymphatic system tumors, breast cancer, lung cancer, gastric cancer and other diseases. Thus, specific inhibitors targeting anti-apoptotic members of the BCL-2 family have emerged with the development of research. In this paper, we systematically reviewed the regulation of apoptosis mediated by BCL-2 family and the drug resistance mediated by BCL-2 family. Meanwhile, we summarized the research advances of BCL-2 family specific inhibitors to provide new strategy for solving the problems on tumor therapeutic resistance and for finding new therapeutic targets in the future.

Procedures for application of the extended dosing after antitumor drug clinical trials / 中南大学学报(医学版)

New drug clinical trials have been considered as a positive way for treating cancer by cancer patients and doctors, and the extended dosing is a special way for patients' withdrawal from antitumor clinical trials to obtain investigational new drugs. However, neither the regulations of expanded dosing nor the detail documents for expanded dosing have been officially published in China. At present, expanded dosing of investigational drugs is still at the exploratory stage in various medical institutions, and a complete management system has not been established to meet patients' urgent needs for drug use. Based on the practical experience of extended dosing in Hunan Cancer Hospital, this paper preliminarily explored the application procedures and ethical review requirements of extended dosing for subjects in antitumor clinical trials. It is necessary to clarify the responsibilities of all patients in the procedure and establish a patient-medical institution-sponsor joint application system. In the process of ethical review, it is recommended that all parties fully consider the risks and benefits of extended dosing for patients, and then the ethics committee makes a comprehensive assessment to decide whether to approve extended dosing.

Advances of quantitative systems pharmacology in antitumor drug research / 药学学报

The high mortality of tumor is one of the most urgent problems to be solved. However, the current clinical trials provide limited quantitative descriptions on dynamic changes of drug efficacy, which restrict the selection of dosing regimens. Quantitative systems pharmacology (QSP) is a new approach for precise treatment of tumors. It quantifies the network relationship between drug action and diseases by integrating the tumor growth and molecules, cells in vivo, thereby predicting the efficacy, toxicity, and mechanism of antitumor drugs as well as identifying predictive biomarkers. In this review, we provide an overview of definition of QSP, current approaches and typical applications in research of antitumor drugs to enhance our understanding of QSP.

Anti-tumor Drug Delivery and Tumor Therapy Based on Metal-organic Frameworks / 肿瘤防治研究

Metal-organic frameworks (MOFs) are mixed porous materials which are composed of metal clusters or ions and organic pillars. Given their channel tunability, high porosity, large specific surface area, and good biocompatibility, MOFs can be combined with various biological macromolecules. In recent years, they have been widely studied in the field of biomedicine, especially in the loading of anti-tumor drugs, showing great application prospects. Multifunctional anti-tumor MOF combined with different therapeutic methods provides a new idea and method for tumor treatment. On the basis of the structure of MOF, this paper introduces the advantages of using MOF to load anti-tumor drugs and reviews the application of MOF in tumor therapy.

Application of Different Decision Analysis Models in the Economic Evaluation of Antitumor Drugs ：Taking CADTH in Canada as an Example / 中国药房

OBJECTIVE：To provide referenc e for selectin g antitumor drugs economic evaluation models and improving the quality of evidence for antitumor drugs economics evaluation in China. METHODS ：A systematic search of the antitumor drug health technology evaluation （pCODR）reports were conducted on the official website of the Canadian Agency for Drugs and Technologies in Health （CADTH）. The search time was limited to Jan. 1st，2015 to Sep. 6th，2020. The basic information ，model types and structure ，and key limitations were extracted and summarized. RESULTS & CONCLUSIONS ：A total of 185 pCODR reports were finally retrieved ，involving 114 types of tumor indications and 98 types of antitumor drugs. The number of CADTH antitumor drugs economics evaluations in the past 5 years had shown an increasing trend. Among 137 pCODR reports with final economic guidance report ，98 reports（71.5％）adopted the PartSA model ，21 reports（15.3％）used the Markov model ，and some reports（6 reports，4.3％）used both PartSA and Markov models to explore the uncertainty of the model structure. In terms of model health status setting ，86 reports（62.8％）used three-state models to evaluate the economy of different anti tumor drugs ，and 16 reports（11.7％）used no less than four health states to simulate the outcome of disease state. However ，there were still some problems in CADTH models ，such as the unreasonable choice of research time limit ，the unreasonable extrapolation method or uncertain extrapolation results of efficacy （survival）data，the uncertainty of efficacy data obtained by indirect comparison ，and some assumptions or parameter settings did not conform to the actual diagnosis and treatment environment. In view of the advantages of PartSA model ，it is suggested that PartSA model or Markov model combined with PartSA model should be used first to verify the uncertainty of model structure in the future economic evaluation of antitumor drugs ；reasonable settings of key model parameters should be considered to improve the quality of evidence for antitumor drugs economics evaluation in China.

The clinical application and development of traditional antitumor drugs / 药学学报

Traditional antitumor drugs are cytotoxic chemotherapeutic drugs that can directly kill tumor cells and inhibit the growth and proliferation of tumor cells. Modern chemotherapy for tumors was initiated by use of nitrogen mustard to treat lymphomas in 1946, which was derived from mustard gas. Starting with nitrogen mustard, many kinds of anti-tumor drugs, including alkylating agents, anti-metabolism drugs, anti-tumor antibiotics, and anti-tumor plant drugs, have been successively developed for clinical treatment. Traditional antitumor drugs are the cornerstone of tumor chemotherapy and play important roles in the comprehensive treatment and neoadjuvant therapy of malignant tumors. In recent years, the combination of traditional antitumor drugs with molecular targeted therapy, immunotherapy, and radiotherapy has greatly improved the survival rate of tumor patients. With the deepening understanding of tumor genome as well as tumor initiation and promotion, the concepts of precision medicine and individualized treatment have been proposed and achieved success in clinical practice. In this context, the strategies leading to personalized therapy with traditional anti-tumor drugs also need to be further studied and optimized. This review summarized the recent clinical application and research progress of traditional antitumor drugs.

cDNA cloning of a novel lectin that induce cell apoptosis from Artocarpus hypargyreus / 中国天然药物

We isolated a novel lectin (AHL) from Artocarpus hypargyreusHance and showed its immunomodulatory activities. In this study, the amino acid sequence of AHL was determined by cDNA sequencing. AHL cDNA (875bp) contains a 456-bp open reading frame (ORF), which encodes a protein with 151 amino acids. AHL is a new member of jacalin-related lectin family (JRLs), which share high sequence similarities to KM+ and Morniga M, and contain the conserved carbohydrate binding domains. The antitumor activity of AHL was also explored using Jurkat T cell lines. AHL exhibits a strong binding affinity to cell membrane, which can be effectively inhibited by methyl-α-D-galactose. AHL inhibits cell proliferation in a time- and dose-dependent manner through apoptosis, evidenced by morphological changes, phosphatidylserine externalization, poly ADP-ribose polymerase (PARP) cleavage, Bad and Bax up-regulation, and caspase-3 activation. We further showed that the activation of ERK and p38 signaling pathways is involved for the pro-apoptotic effect of AHL.

Recent advances in the development of bispecific antibodies / 生物工程学报

Bispecific antibody (BsAbs) are antibodies (Abs) containing two different antigen-binding sites in one molecule. In the last decade, three BsAbs drugs have been approved for therapeutic use. Meanwhile there are a number of BsAbs in preclinical or clinical studies. In this review, we describe BsAb design, discovery, mechanism of action, and the recent research progress in developing BsAbs.

Investigation on Status of Chemotherapy Drugs for Discharged Patients Under 18 Years Old in Our Hospital and Its Potential Risks / 中国药学杂志

OBJECTIVE: To investigate the actual data of chemotherapy drugs for discharged patients under 18 years old in our hospital, and to firstly provide the real status and risk of chemotherapy drugs during carrying and use at home. METHODS A retrospective research was adopted to statistically analyze 1 955 discharged orders of the patients, under the age of 18, with chemotherapy drugs in our hospital from December 1, 2017 to May 31, 2018. RESULTS: During the sampling period, there were 153 patients with chemotherapy drugs discharged under the age of 18 years old. Thirty kinds of chemotherapy drugs were involved, and 17 drugs with the remaining drug amount regarding to its dosage regimen. CONCLUSION: It was found that it is common and necessary to continue treatment with chemotherapy drugs after discharged. One drug needs to be refrigerated and the other needs to be kept in a shade place, which is difficult to reach the preservation conditions during the journey. There is a residual amount of medications over its usage for young patients, of the total 1 955 medical orders, 898 have the problem of residual amount, which account for 57.11% in cancer patients and 7.09% in non-cancer patients, respectively. For pharmacists,it is time exploring medication education and follow-up for discharged patients, especially for young patients and their guardians.

Research progress of hydrogel in tumor immunotherapy / 中国药理学通报

Cancer immunotherapy has gained increasing atten-tionin recent years, with combination therapy producing good clinical therapeutic effects. However, the response rate of patients to immunotherapy is still not high, which requires attention to drug utilization and systemic side effects at tumor sites. As a drug-loading platform, hydrogel has great advantages,which can directly deliver anti-tumor drugs to tumor sites, reduce sys temic toxicity, and have good degradability. In this review, the latest advances in drug delivery systems bised on hydrogel plat-forms are summarized, including immunochemotherapy, immu-noradiotherapy and immunophotothermal therapy.

Research advancement in vascular endothelial cell metabolism and tumor angiogenesis / 药学学报

Vascular endothelial cells play a major role in maintaining the oxygen and nutrient supply to all tissues in the body. Endothelial cells, together with vascular endothelial growth factor, are also the driving forces of tumor angiogenesis, a process describing the growth of blood vessels from the existing vasculature in tumor tissues. Reprogramming of endothelial cell metabolism satisfied the needs for biomass and energy in the process of tumor angiogenesis, which are known to involve the aspects of glucose metabolism, amino acid metabolism, and fatty acid metabolism. Recently, with the increasing interest to understand the metabolic regulation in cancer, the investigation into the metabolism of endothelial cells has made progress. We herein review the role of endothelial cell metabolism in angiogenesis, with a particular focus on the metabolic regulation of endothelial cells in tumor angiogenesis, which hopes to provide insights for the intervention of tumor angiogenesis in cancer therapy.

Anticancer drug screening: standardization of in vitro wound healing assay / Triagem de drogas anticâncer: padronização do ensaio de ranhura in vitro

ABSTRACT Introduction: Gliomas are characterized by rapid proliferation and aggressive invasion into normal surrounding brain tissue. In medical laboratories, the in vitro wound healing assay stands out as a simple, easy, inexpensive and affordable method to evaluate cell migration and proliferation. Objective: To standardize the in vitro wound healing assay using antimicrotubule drugs as positive controls. Methods: U87MG glioma cells were seeded at different densities and, after 24 h, the monolayer was scratched using different micropipette tip size to create a gap with no cells. The cells were then treated with colchicine and paclitaxel in culture medium with the presence or absence of fetal bovine serum. The wound was photographed with the aid of an inverted microscope and the wound area was measured using the Image J software. Results: Better defined edges scratches and monolayer with approximately 90% confluence were obtained at 1.5 and 2 x 105 cells/well density. The width and area of the scratch were, respectively, 948 pm/2.193221 mm2; 964 pm/2.266 mm2 and 1448 pm/3.221 mm2 to 10. 200 and 1000 pl micropipette tips. Colchicine inhibited wound closure by 12.6% or 3.4%, both in the presence or absence of serum; paclitaxel 2.4 and 6.7% respectively. Conclusion: Under standardized conditions, colchicine and paclitaxel proved to be efficient positive controls into the in vitro wound healing assay.

RESUMEN Introducción: Gliomas se caracterizan por rápida proliferación e invasion agresiva del tejido cerebral normal circundante. En laboratorios médicos, el ensayo de cierre de herida - una prueba in vitro - se destaca por ser un método simple, fácil, de bajo costo y accesiblepara evaluar la migración y la proliferación celular. Objetivo: Estandarizar el ensayo de cierre de herida usando agentes anti-microtúbulos como control positivo. Métodos: Las células de glioma U87MG fueron sembradas en diferentes concentracionesy, después de 24 horas, la monocamadafue rayada con punteras de diferentes tamanos para crear una hendidura sin células. Las células fueron entonces tratadas con colchicina y paclitaxel, en medio con o sin suero fetal bovino. La ranura fue fotografiada con la ayuda de un microscopio invertido, y el área de la ranura fue medida mediante el programa Image J. Resultados: Ranuras con bordes más bien-definidos y monocamada con alrededor de 90% de confluencia se obtuvieron con 1,5 y 2 x 105 células/pozo. La anchura y el área de las ranuras obtenidas fueron, respectivamente, 948 p.m/2,193 mm2; 964p.m/2,266mm2; y 1448p.m/3,221 mm2 para las punteras de 10,200y 1000pl. La colchicina inhibió el cierre de las ranuras en 12,6% o 2,4%, tanto en presencia como en ausencia de suero; el paclitaxel, 3,4% y 6,7%, respectivamente. Conclusión: En condiciones estandarizadas, colchicina y paclitaxel pueden ser usados como control positivo en el ensayo de cierre de herida in vitro.

RESUMO Introdução: Gliomas são caracterizados por terem rápida proliferação e invasão agressiva no tecido cerebral circundante normal. Em laboratórios médicos, o ensaio de ranhura - um teste in vitro - destaca-se por ser um método simples, fácil, barato e acessível para avaliar a migração e a proliferação celular. Objetivo: Padronizar o ensaio de ranhura, utilizando drogas antimicrotúbulos como controles positivos. Métodos: As células de glioma U87MG foram semeadas em diferentes concentrações e, após 24 horas, a monocamada foi arranhada usando ponteiras de diferentes tamanhos para criar uma fenda sem células. As células foram então tratadas com colchicina e paclitaxel, com meio em ausência ou presença de soro fetal bovino. A ranhura foi fotografada com auxílio de microscópio invertido, e a área da ranhura foi medida por meio do programa Image J. Resultados: Ranhuras com bordas mais bem definidas e monocamada com aproximadamente 90% de confluência foram obtidas com 1,5 e 2 x 105 células/poço. A largura e a área das ranhuras obtidasforam, respectivamente, 948pm/2,193 mm2;964pm/2,266mm2; e 1448 pm/3,221 mm2 para as ponteiras de 10, 200 e 1000 pl. A colchicina inibiu o fechamento das ranhuras em 12,6% ou 2,4%, tanto na presença quanto na ausência de soro; o paclitaxel, em 3,4% e 6,7%, respectivamente. Conclusão: Em condições padronizadas, colchicina e paclitaxel podem ser usados como controles positivos eficientes no teste in vitro de ranhura.

Clinical value of an adenosine triphosphate-based chemotherapy response assay in resectable stage III colorectal cancer

PURPOSE: ATP-based chemotherapy response assay (ATP-CRA) is a well-documented and validated technology that can individualize chemotherapy. This study was undertaken to assess the usefulness of ATP-CRA in advanced colorectal cancer (CRC) patients receiving adjuvant chemotherapy. METHODS: A total of 136 patients with curative resection between January 2006 and April 2014 were evaluated using ATP-CRA. Patients received either the FOLFOX or Mayo clinic regimen chemotherapy following assay results. The sensitive-group (S-group) was defined as a drug-producing ≥ 40% reduction in ATP, and the resistant-group (R-group) as an ATP reduction of < 40%. These 2 groups were further subdivided to produce 4 subgroups: the FOLFOX sensitive subgroup (the FS subgroup [n = 65]), the Mayo sensitive subgroup (the MS subgroup [n = 40]), the FOLFOX resistant subgroup (the FR subgroup [n = 10]), and the Mayo resistant subgroup (the MR subgroup [n = 21]). Clinical responses and survival results were compared for both treatment regimens. RESULTS: The FS and MS subgroups showed a better disease-free survival rate (29% vs. 40%, 35% vs. 47.6%) and overall survival rate (92.3% vs. 80.0%, 87.5% vs. 76.2%) than FR and MR subgroups. The FS and MS subgroups showed a longer time to relapse (20.2 months vs. 9.5 months, 17.6 months vs. 16.4 months) than the FR and MR subgroups. CONCLUSION: ATP-CRA tailored-chemotherapy has the potential to provide a survival benefit in resectable advanced CRC.

Advances in research of hyaluronic acid modified nanomicelles for targeting tumor therapy and drug release behavior / 中国药科大学学报

@#Hyaluronic acid, also called hyaluronan(HA)is a biocompatible and biodegradable linear polysaccharide which is of interest for tumor targeting through cell surface CD44 receptors. It is widely applied in the field of tumor therapy as an anticancer drug delivery carrier, and has become a hot spot in the research of tumor targeted drug delivery system. In tumor drug therapy, the key to reduce toxicity is to actively target tumors by using anatomical, pathophysiological and microenvironmental differences between malignant tumors and normal tissues. Differentiation cluster 44(CD44)is a high-affinity receptor for HA, which can be marked as a tumor marker or a targeting receptor because it is overexpressed in tumor cells. The overexpression of CD44 receptors was observed in many tumors such as breast cancer, colorectal cancer, liver cancer and pancreatic cancer. The effect of hyaluronic acid drug nanocarriers on various tumors is briefly described, indicating that the overexpression of CD44 receptor is an ideal choice for the treatment of hyaluronic acid-based drug carriers. The CD44 ligand can increase the affinity of the nanocarrier for tumor cells by binding to the nano drug carrier. The HA structure is known for its potent tumor targeting effect due to the inclusion of CD44 ligand, which enhances uptake of tumor cells by the HA-CD44 receptor-mediated endocytosis pathway. The study reviewed the progression of hyaluronic acid nanomicelles in clinical tumor therapy and its release behavior. The percentage of drug release and release rate are the key factors in the overall efficacy of the treatment strategy. Therefore, a great number of studies have focused on inducing drug release in Cytosol by taking advantage of the difference between the internal and external environments of nanostructured micelles or through external stimulation post-treatment applications. The study proved that an acid environment is more favorable to achieve a greater release and drugs can be quickly and completely released in an oxygen-deficient environment. In addition, the great potential of hyaluronic acid nanomicelles in tumor therapy was also further identified in this article. In vitro and in vivo experimental studies have repeatedly shown that hyaluronic acid-based nanomicelles are a drug- and gene-specific targeting tumor delivery method, in combination with passive targeting, this active targeting strategy is a promising approach to providing chemotherapy drugs to CD44 overexpressing tumors. In conclusion, hyaluronic acid-based nanomicelles are biologically safe with great potential to drug release, blood compatibility and systemic tumor targeting which all implied it has good application prospects in clinical tumor treatment.

Application progress on model organism zebrafish in screening of pharmacodynamic substances of Chinese materia medica / 中草药

Compared with mammals, zebrafish has unique advantages in screening pharmacoactive substance, and has been paid more and more attention in the field of medicine. In recent years, the exploration of zebrafish has been extended and extended to the field of Chinese materia medica (CMM), especially for the screening pharmacoactive substance of the single CMM, the CMM compound and Chinese patent medicines with multi-target, multi-channel and multi-link effects. As a complete animal model, zebrafish can carry out comprehensive and deep research on the effective chemical components that play a role in TCM, and then realize convenient, rapid and high-throughput screening of pharmacodynamics substances in CMM. Combined with the literature reports in recent five years at home and abroad, this paper reviews the latest research progress and unique advantages on the screening of pharmacodynamics substances in CMM in model organism zebrafish, mainly from the screening of cardiovascular drugs, lipid-lowering and liver-protecting drugs, anti-osteoporosis drugs, anti-tumor drugs, anti-inflammatory and other drugs, in order to provide a new idea for the application of model organism zebrafish in CMM and provide reference for the new drugs research of CMM.

Application of Automatic Injection Dispensing System in Antitumor Drug Dispensing in PIVAS / 中国药房

OBJECTIVE： To improve the quality of antitumor drug dispensing in pharmacy intravenous admixture services （PIVAS）， reduce dispensing error and occupational exposure to dispensers by antitumor drugs. METHODS： The composition and functions of automatic injection dispensing system were introduced， and the system was applied in antitumor drug dispensing in PIVAS. Various work indexes were compared 1 month before and after the application of the system. RESULTS： The system included information processing software， equipment control software and drug dispensing machine hardware， and had functions such as automatic counting of medicines， automatic entry into basket， automatic drug dispensing and automatic printing of labels. After applying automatic injection dispensing system， the operation of infusion label printing， basket dividing and dispensing in dispensing process was changed from manual to automatic. It could save human resources， as for each label， the average time of drug dispensing decreased from （33.00±3.31） s to （15.55±1.41） s while no mistakes and damaged label was found. CONCLUSIONS： The application of automatic injection dispensing system achieves automatic operation of antitumor drug dispensing in PIVAS， reduce dispensing error reduces staff’s exposure to antitumor drugs and occupational exposure.

Research progress in toxic effects of antitumor drugs based on drug transporter / 药学学报

Differences of the individual toxic effects of antitumor drugs have been a concern in clinical treatment of cancers. The drug toxicity was not only related to the age, sex, and drug interactions, but also to the expression of protein involved in the metabolism, targets and transporters of drugs. Drug transporter mediates the absorption, distribution and elimination of some drugs, which exhibits a great significance in pharmacology and clinical practice. The purpose of this review is to provide information regarding trans-porter-medicated toxic effects of antitumor drugs in order to reduce or avoid the transporter-medicated toxic effects, and to promote reasonable drug use and individualized application of antitumor drugs in clinics.

Preliminary study of lipid bilayer-coated calcium phosphate nanoparticles as a drug carrier for antitumor drug / 药学学报

This study aims to prepare lipid bilayer-coated calcium phosphate core-shell nanoparticles (LCAPNs), which can dissolve in an acidic environment to improve the tumor cell toxicity of antitumor drug. Paclitaxel (PTX) loaded lipid coated calcium phosphate nanoparticles (PTX-LCAPNs) were prepared by thin-film dispersion method. The morphology, particle size and in vitro release behavior were characterized. Meanwhile, the intracellular uptake, intracellular dissolution, cell toxicity of PTX-LCAPNs and intracellular accumulation of PTX were evaluated in human HCC cell line (Huh-7). The results suggested that the mean diameter of the spherical LCAPNs was 124.73±6.41 nm. The PTX-LCAPNs demonstrated little drug leakage in simulated normal physiological conditions, while a rapid release was observed in simulated intracellular condition in vitro. Moreover, the PTX-LCAPNs achieved 1.7 fold improvement in the intracellular PTX concentration leading to 5-fold reduction in half maximal inhibitory concentration (IC50) values of PTX compared with calcium phosphate nanoparticles loaded with PTX (PTX-CAPNs), demonstrating a stronger cancer cell lethality.

Screening of small molecule inhibitors for PLK1 PBD and evaluation of antitumor activities / 药学学报

With the method of fluorescence polarization (FP), we screened small molecule inhibitors for PLK1 PBD to identify the lead compounds for antitumor drugs. FP led to the identification of a potent hit, F083-0063, whose inhibition rate was (99.7±0.4)% at 10 μg·mL-1. The IC50 was calculated to be 1.9±0.1 μmol·L-1 using Graphpad Prism 5. The effect of the compound on cells' multiplication was measured by MTT assay which showed that F083-0063 inhibited the proliferation of many tumor cell lines. Flow cytometry analysis indicated that the F083-0063 promoted cell apoptosis and induced cell G2/M arrest. Migration abilities of cells, evaluated using scratch test, increased significantly in the presence of F083-0063 with the mi-gration rate as low as (37.6±0.7)% at 20 μmol·L-1. Molecular linkage technique found F083-0063 had good affinity with PLK1 PBD. The results of Western blotting showed that the expression of cyclin-dependent proteins was increased after treatment with F083-0063. In summary, F083-0063 has an antitumor activity and is expected to be an antitumor lead compound targeting PLK1 PBD.