Matrine Enhances the Antitumor Efficacy of Chidamide in CTCL by Promoting Apoptosis.

BACKGROUND: Cutaneous T-cell Lymphoma (CTCL) is a rare group of non-Hodgkin lymphoma originating from the skin, which is characterized by T-cell lymphoproliferative disorders. Chidamide, a Chinese original antineoplastic agent with independent intellectual property rights, and matrine, an extract of Chinese herbal medicine, both have been reported to exert effects on the treatment of tumors individually. However, chidamide combined with matrine has not been tested for the treatment of CTCL. METHODS: Both HH and Hut78 CTCL cell lines were treated with chidamide (0.4 µmol/L), matrine (0.6 g/L), or chidamide combined with matrine for 24, 48, and 72 h. Cell viability was estimated by MTS assay at each time point. Flow cytometry was then conducted to detect cell apoptosis. The exact mechanism of chidamide combined with matrine on CTCL cells was detected by Western blotting and further validated in xenograft models of NOD/SCID mice. RESULTS AND DISCUSSION: Compared to the single drug, chidamide combined with matrine showed a more significant effect on proliferation inhibition and apoptosis induction on CTCL cells both in vitro and in vivo. The results from the in vitro and in vivo studies suggested that matrine could enhance the anti-tumor effect of chidamide by increasing the protein expression of cleaved caspase- 3 and decreasing the expression of E-cadherin, NF-κB, p-Bad, and Bcl-2 to activate apoptosis. CONCLUSION: Our data have demonstrated chidamide combined with matrine to exhibit elevated antitumor activity in both CTCL cells and xenograft models of NOD/SCID mice, which may be a potential treatment option for CTCL.

Advancements in pH-responsive nanocarriers: enhancing drug delivery for tumor therapy.

INTRODUCTION: Tumors pose a significant global economic and health burden, with conventional cancer treatments lacking tumor specificity, leading to limited efficiency and undesirable side effects. Targeted tumor therapy is imminent. Tumor cells produce lactate and hydrogen ions (H+) by Warburg effect, forming an acidic tumor microenvironment (TME), which can be employed to design targeted tumor therapy. Recently, progress in nanotechnology has led to the development of pH-responsive nanocarriers, which have gathered significant attention. Under acidic tumor conditions, they exhibit targeted accumulation within tumor sites and controlled release profiles of therapeutic reagents, enabling precise tumor therapy. AREAS COVERED: This review comprehensively summarize the principles underlying pH-responsive features, discussing various types of pH-responsive nanocarriers, their advantages, and limitations. Innovative therapeutic drugs are also examined, followed by an exploration of recent advancements in applying various pH-responsive nanocarriers as delivery systems for enhanced tumor therapy. EXPERT OPINIONS: pH-responsive nanocarriers have garnered significant attention for their capability to achieve targeted accumulation of therapeutic agents at tumor sites and controlled drug delivery profiles, ultimately increasing the efficiency of tumor eradication. It is anticipated that the employment of pH-responsive nanocarriers will elevate the effectiveness and safety of tumor therapy, contributing to improved overall outcomes.

The mechanism and treatment of targeted anti-tumour drugs induced cardiotoxicity.

As the intensive anti-tumour therapy and combination of multiple anti-tumour drugs, cardiotoxicity events caused by anti-tumour drugs have also increased significantly, and the incidence of cardiotoxicity also increased with survival time. Different types of anti-tumour drugs could cause all kinds of cardiotoxicity which increase the difficulties in treatment and even live threatening. In this review, we concentrated in the targeted anti-tumour drugs such as human epidermal growth factor receptor-2 (HER2) inhibitors, tyrosine kinase inhibitors (TKIs), immune checkpoint inhibitors (ICIs), and proteasome inhibitors (Pls). The molecular mechanism of how these drugs induce cardiotoxicity is introduced which includes several signal pathways. These drugs induced cardiotoxicity involved heart failure, hypertension, atherosis and thrombosis, QT interval prolongation, and myocarditis. Some of the cardiotoxicity could be moderate and reversible but others could have happened severely.The aim of this review is to summarise the targeted anti-tumour drugs induced cardiotoxicity and treatment strategies.

Analysis of ethical review issues of informed consent form for clinical trials of registered anti-tumor drugs in our hospital / 中国药房

OBJECTIVE To promote the standardization and integrity of the informed consent form for clinical trials of registered anti-tumor drugs， and to protect the legitimate rights and interests of the subjects. METHODS The ethical review resolutions of clinical trial projects of registered anti-tumor drugs that were initially reviewed by the Ethics Committee of our hospital from July 1st， 2020 to July 1st， 2022 were summarized to statistically analyze the problematic items according to the “Quality Analysis Form of Informed Consent” prepared by our hospital. RESULTS Of the 316 clinical trials of registered anti- tumor drugs that were initially reviewed， 257 （81.3%） had problems with the contents of informed consent form， mainly domestic multi-center trials and phase Ⅲ trials. The main problems included the vague notification of the test fee bearer （68.5%）， the incomplete notification of the test content （59.1%）， the insufficient notification of rights and interests and risks （58.4%）， the insufficient notification of personal information protection （56.0%）， and the nonstandard expression of the informed consent form （52.5%）. CONCLUSIONS There is still a gap between the informed consent form of the clinical trials of registered anti-tumor drugs in our hospital and the requirements of the new version of Good Clinical Practice for Drugs （GCP）. The parties involved in the test can take a number of measures to improve the standardization and integrity of the informed consent form， and the research team should design the informed consent form in strict accordance with the requirements of the new GCP and pay attention to the comprehensive notification about the test. The Ethics Committee can provide the sponsor and researcher with the template of informed consent form and the key points of writing， continue to strengthen the examination ability， improve the examination quality， and effectively protect the safety and interests of the subjects.

Practice of refined management of anti-tumor drugs based on value healthcare / 中华医院管理杂志

In recent years, the rapid increase in cancer treatment costs in China had brought a huge economic burden to society, and it was urgent to standardize the rational application of anti-tumor drugs. In the context of the reform of group payment related to disease diagnosis, a tertiary first-class hospital focused on the needs of patients and guided by value-based healthcare, established a professional and normalized refined anti-tumor drug management system, setted up a multidisciplinary diagnosis and treatment team, and promoted " Internet plus pharmaceutical services" in December 2018.From 2019 to 2021, the proportion of hospital drugs were 30.8%, 30.1%, and 27.3%, respectively. The amount of money spent on anti-tumor drugs were 83.25 million yuan, 76.41 million yuan, and 62.48 million yuan, respectively, showing a decreasing trend year by year. The practice of refined management of anti-tumor drugs fully reflected the core concept of value based healthcare, achieving closed-loop management of the entire process of drugs, improving the level of rational drug use, reducing the economic burden on patients, and providing reference for improving the level of rational use of anti-tumor drugs in public hospitals.

Pharmacoepitranscriptomic landscape revealing m6A modification could be a drug-effect biomarker for cancer treatment.

RNA chemical modifications are a new but rapidly developing field. They can directly affect RNA splicing, transport, stability, and translation. Consequently, they are involved in the occurrence and development of diseases that have been studied extensively in recent years. However, few studies have focused on the correlation between chemical modifications and drug effects. Here, we provide a landscape of six RNA modifications in pharmacogene RNA (pharmacoepitranscriptomics) to fully clarify the correlation between chemical modifications and drugs. We performed systematic and comprehensive analyses on pharmacoepitranscriptomics, including basic characteristics of RNA modification and modification-associated mutations and drugs affected by them. Our results show that chemical modifications are common in pharmacogenes, especially N6-methyladenosine (m6A) modification. In addition, we found a very close relationship between chemical modifications and anti-tumor drugs. More interestingly, the results demonstrate the importance of m6A modification for anti-tumor drugs, especially for drugs in triple-negative breast cancer (TNBC), ovarian cancer, and acute myelocytic leukemia (AML). These results indicate that pharmacoepitranscriptomics could be a new source of drug-effect biomarkers, especially for m6A and anti-tumor drugs.

Mathematical modeling and dynamical analysis of anti-tumor drug dose-response.

Cancer is a serious threat to human health and life. Using anti-tumor drugs is one of the important ways for treating cancer. A large number of experiments have shown that the hormesis appeared in the dose-response relationship of various anti-tumor drugs. Modeling this phenomenon will contribute to finding the appropriate dose. However, few studies have used dynamical models to quantitatively explore the hormesis phenomenon in anti-tumor drug dose-response. In this study, we present a mathematical model and dynamical analysis to quantify hormesis of anti-tumor drugs and reveal the critical threshold of antibody dose. Firstly, a dynamical model is established to describe the interactions among tumor cells, natural killer cells and M2-polarized macrophages. Model parameters are fitted through the published experimental data. Secondly, the positivity of solution and bounded invariant set are given. The stability of equilibrium points is proved. Thirdly, through bifurcation analysis and numerical simulations, the hormesis phenomenon of low dose antibody promoting tumor growth and high dose antibody inhibiting tumor growth is revealed. Furthermore, we fit out the quantitative relationship of the dose-response of antibodies. Finally, the critical threshold point of antibody dose changing from promoting tumor growth to inhibiting tumor growth is obtained. These results can provide suggestions for the selection of appropriate drug dosage in the clinical treatment of cancer.

One-Pot Synthesis of Multifunctional Carbon-Based Nanoparticle-Supported Dispersed Cu2+ Disrupts Redox Homeostasis to Enhance CDT.

In chemodynamic therapy (CDT), the levels of reactive oxygen species (ROS) production plays an important role for evaluating the therapeutic efficacy. However, the high levels of glutathione (GSH) in tumor cells consume the ROS, directly reducing the therapeutic efficiency. Herein, we synthesized carbon-based nanoparticle (Cu-cys CBNPs) using one-pot strategy, which consume GSH via redox reactions to produce Cu+ that catalyze H2 O2 to produce . OH, thus the ROS level was observably increased through this synergistic effect. In vivo experiments further revealed that Cu-cys CBNPs could effectively inhibit tumor growth. Additionally, Cu-cys CBNPs can affect the activity of some protein sulfhydryl groups in cells, which was assessed by rdTOP-ABPP assay. In general, this study not only provides a potential CDT drug, but also provides a strategy for one-pot synthesis of multifunctional nanomaterials.

Research progress and coping strategy of the drug resistant mechanism of platinum anti-tumor drugs / 药学实践杂志

Platinum anti-tumor drugs are currently the most widely used first-line chemotherapeutic drugs in clinical practice, and their curative effects are remarkable. However, the problems of platinum drug resistance in non-small cell lung cancer, breast cancer, ovarian cancer and others seriously limit effectiveness and clinical application of platinum drugs. The occurrence of platinum drug resistance is caused by many factors. At present, the resistance mechanism of platinum drugs mainly includes the following aspects: decreasing the accumulation of platinum in cells, increasing the inactivation of platinum in cells, repairing DNA damage and tumor cell apoptosis inactivation. This article reviews the drug resistance mechanism and coping strategy of platinum anti-tumor drugs, providing ideas for the development of platinum anti-tumor drugs and references for overcoming clinical platinum drug resistance.

Overview and changes of Guiding Principles of Clinical Application of Novel Anti -tumor Drugs over the years / 中国药房

OBJECTIVE To provide the suggestions and reference for the follow-up update of Guiding Principles of Clinical Application of Novel Anti -tumor Drugs （hereinafter referred to as “Guiding Principles ”）. METHODS The update of 2018-2021 editions of Guiding Principles were compared ；the changes of its style ，the variety and quantity of novel anti-tumor drugs ，the classification of indications ，the target ，the inclusion of medical insurance and other aspects were analyzed. Its change trend and possible problems were summarized. RESULTS There was a great change in the style of Guiding Principles in 2020 edition，i.e. deleting the item of “clinical application management ”and adding the item of “attached table ”. Totally 33 novel anti-tumor drugs were included in the 2018 edition of Guiding Principles ，and the number of novel anti-tumor varieties increased to 46，60 and 77 in 2019，2020 and 2021 editions，respectively. The time when the new varieties were included in Guiding Principles was the same year or one year after the domestic market time. Totally 26 varieties of national medical insurance negotiation were included in the 2018 edition of Guiding Principles ，and 8，10 and 12 varieties were added respectively in 2019，2020 and 2021 editions on the basis of the previous edition . Novel anti-tumor drug in the 2018 edition of Guiding Principles mainly focused on traditional targets such as EGFR，HRE2 and VEGFR. However ，since 2019，the number of new targets such as PD-1，PARP，ALK and CDK had been increasing，among which domestic original drugs accounted for a large proportion. CONCLUSIONS The revision of Guiding Principles aims to further guide the clinical application of novel anti-tumor drugs from the professional level of health technology. The new varieties and indications conform to the principles of scientificity and dynamics ；domestic original varieties have developed rapidly ，and innovative varieties to novel target have emerged. The follow-up update of Guiding Principles should refer to authoritative medical guidelines and high-quality evidence- based evidence. Attention should be paid to the types of tumors lacking therapeutic drugs and the clinical value of oushun- novel anti-tumor drugs.

Ultra-performance liquid chromatography-tandem mass spectrometry for simultaneous determination of 12 anti-tumor drugs in human plasma and its application in therapeutic drug monitoring.

The effectiveness and safety of anti-tumor drugs are clinically important issues, and their therapeutic drug monitoring (TDM) is recommended. This study aimed to develop an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for simultaneous TDM and exploration of clinical pharmacokinetics of anti-tumor drugs, including cyclophosphamide, ifosfamide, cisplatin, methotrexate, pemetrexed disodium, capecitabine, 5-fluorouracil, gemcitabine, doxorubicin, fulvestrant, tamoxifen, and irinotecan. After magnetic solid-phase extraction of plasma samples, the isotope internal standards and 12 anti-tumor drugs were separated using a ZORBAX Eclipse Plus C18 column (50.0 × 2.1 mm, 1.7 µm) with water containing 0.1% formic acid and acetonitrile as the mobile phase in a total run time of 5.0 min. The developed UPLC-MS/MS method was validated based on the Chinese Pharmacopoeia and the US Food and Drug Administration guidelines for bioanalytical method validation, including assessment of specificity, calibration curves, carryover, accuracy, crosstalk, precision, stability, recovery, dilution integrity, incurred sample reanalysis, and matrix effect. The results showed that a simple, fast, reliable, and specific UPLC-MS/MS method was developed and validated, and all the performance characteristics of the method met the requirements. The response function was established for concentration range of 0.10-25.00 µg/mL for gemcitabine, cyclophosphamide, ifosfamide, methotrexate, pemetrexed disodium, capecitabine, 5-fluorouracil, and cisplatin, and 0.05-12.50 µg/mL for doxorubicin, fulvestrant, tamoxifen, and irinotecan, with a coefficient of correlation of>0.9984 for all the compounds. The precision and accuracy of all the analytes were<6.5% and 5.9%, respectively. Hence, it could be used for TDM and exploration of pharmacokinetics of the aforementioned 12 anti-tumor drugs.

Dihydroartemisinin as a Sensitizing Agent in Cancer Therapies.

Cancer is one of the major threats to human health. Although humans have struggled with cancer for decades, the efficacy of treatments for most tumors is still very limited. Dihydroartemisinin (DHA) is a derivative of artemisinin, a first-line antimalarial drug originally developed in China. Beyond the anti-malarial effect, DHA has also been reported to show anti-inflammatory, anti-parasitosis, and immune-modulating properties in vitro and in vivo. Furthermore, an increasing number of studies report that DHA possesses anticancer activities on a wide range of cancer types both in vitro and in vivo, as well as enhances the efficacy of chemotherapy, targeted therapy, and even radiotherapy. However, the mechanisms of DHA on different tumors differ in various ways. In this review, we intend to summarize how DHA sensitizes cancer cells to anti-cancer therapies, highlight its molecular mechanisms and pharmacological effects in vitro and in vivo as well as in current clinical trials, and discuss potential issues concerning DHA. Hopefully, more attention will be paid to DHA as a sensitizer for cancer therapy in the future.

Pharmacokinetic Research Progress of Anti-tumor Drugs Targeting for Pulmonary Administration.

BACKGROUND: Cancer is a major problem that threatens human survival and has a high mortality rate. The traditional chemotherapy methods are mainly intravenous injection and oral administration, but have obvious toxic and side effects. Anti-tumor drugs for pulmonary administration can enhance drug targeting, increase local drug concentration, and reduce the damage to systemic organs, especially for the treatment of lung cancer. METHODS: The articles on the pharmacokinetics of anti-tumor drugs targeting pulmonary administration were retrieved from the Pub Med database. This article mainly took lung cancer as an example and summarized the pharmacokinetic characteristics of anti-tumor drugs targeting for pulmonary administration contained in nanoparticles, dendrimers, liposomes and micelles. RESULTS: The review shows that the pharmacokinetics process of pulmonary administration is associated with a drug carrier by increasing the deposition and release of drugs in the lung, and retarding the lung clearance rate. Among them, the surface of dendrimers could be readily modified, and polymer micelles have favorable loading efficiency. In the case of inhalation administration, liposomes exhibit more excellent lung retention properties compared to other non-lipid carriers. Therefore, the appropriate drug carrier is instrumental to increase the curative effect of anti-tumor drugs and reduce the toxic effect on surrounding healthy tissues or organs. CONCLUSION: In the process of pulmonary administration, the carrier-embedded antitumor drugs have the characteristics of targeted and sustained release compared with non-packaging drugs, which provides a theoretical basis for the clinical rational formulation of chemotherapy regimens. However, there is currently a lack of comparative research between drug packaging materials, and more importantly, the development of safe and effective anti-tumor drugs targeting for pulmonary administration requires more data.

Developing protein arginine methyltransferase 1 (PRMT1) inhibitor TC-E-5003 as an antitumor drug using INEI drug delivery systems.

Injectable implants with the ability to form in situ are one of the most promising carriers for the delivery of chemotherapeutic drugs to tumor sites. We have reported a novel injectable in situ-forming implant system composed of n-butyl-2-cyanoacrylate (NBCA), ethyl oleate, along with the sol-gel phase transition. The chemotherapeutic drug-loaded injectable NBCA ethyl oleate implant (INEI) exhibited excellent therapeutic efficacy for local chemotherapy. Herein, we utilize this INEI to carry N, N'-(Sulfonyldi-4,1-phenylene)bis(2-chloroacetamide) (TE-C-5003), which is a selective protein arginine methyltransferase 1 (PRMT1) inhibitor, to treat the lung cancer mice model. The in vitro experiment shows that TE-C-5003 has a good anti-tumor effect on lung cancer (IC50 = 0.7022 µM for A549; IC50 = 0.6844 µM for NCL-H1299) and breast cancer (IC50 = 0.4128 µM for MCF-7; IC50 = 0.5965 µM for MDA-MB-231). Anti-tumor experiments in animal models showed that the average growth inhibition rate of xenografted human lung cancer cells by the TE-C-5003-loaded INEI (40% NBCA) was 68.23%, which is far more than TC-E-5003 alone (31.76%). Our study further confirms that INEI is an effective technique to improve the anti-tumor effect. The druggability of small molecule compounds can be improved with the help of the mentioned technology. Also, TC-E-5003 may be developed as a broad spectrum anti-tumor drug.

Reversine: A Synthetic Purine with a Dual Activity as a Cell Dedifferentiating Agent and a Selective Anticancer Drug.

The development of new therapeutic applications for adult and embryonic stem cells has dominated regenerative medicine and tissue engineering for several decades. However, since 2006, induced Pluripotent Stem Cells (iPSCs) have taken center stage in the field, as they promised to overcome several limitations of the other stem cell types. Nonetheless, other promising approaches for adult cell reprogramming have been attempted over the years, even before the generation of iPSCs. In particular, two years before the discovery of iPSCs, the possibility of synthesizing libraries of large organic compounds, as well as the development of high-throughput screenings to quickly test their biological activity, enabled the identification of a 2,6-disubstituted purine, named reversine, which was shown to be able to reprogram adult cells to a progenitor-like state. Since its discovery, the effect of reversine has been confirmed on different cell types, and several studies on its mechanism of action have revealed its central role in inhibitory activity on several kinases implicated in cell cycle regulation and cytokinesis. These key features, together with its chemical nature, suggested a possible use of the molecule as an anti-cancer drug. Remarkably, reversine exhibited potent cytotoxic activity against several tumor cell lines in vitro and a significant effect in decreasing tumor progression and metastatization in vivo. Thus, 15 years since its discovery, this review aims at critically summarizing the current knowledge to clarify the dual role of reversine as a dedifferentiating agent and anti-cancer drug.

Use of Anticancer Platinum Compounds in Combination Therapies and Challenges in Drug Delivery.

As one of the leading and most important metal-based drugs, platinum-based pharmaceuticals are widely used in the treatment of solid malignancies. Despite significant side effects and acquired drug resistance have limited their clinical applications, platinum has shown strong inhibitory effects for a wide assortment of tumors. Drug delivery systems using emerging technologies such as liposomes, dendrimers, polymers, nanotubes and other nanocompositions, all show promise for the safe delivery of platinum-based compounds. Due to the specificity of nano-formulations; unwanted side-effects and drug resistance can be largely averted. In addition, combinational therapy has been shown to be an effective way to improve the efficacy of platinum based anti-tumor drugs. This review first introduces drug delivery systems used for platinum and combinational therapeutic delivery. Then we highlight some of the recent advances in the field of drug delivery for combinational therapy; specifically progress in leveraging the cytotoxic nature of platinum-based drugs, the combinational effect of other drugs with platinum, while evaluating the drug targeting, side effect reducing and sitespecific nature of nanotechnology-based delivery platforms.

Analysis of Abnormal Use of Anti-tumor Drugs in the Clinic / 中国药房

OBJECTIVE：To study the abnormal use of anti-tumor dr ugs i n the clinic in order to provide reference for rational use of drugs in the clinic. METHODS ：Referring to foreign and domestic anti-tumor drug use guidelines and literatures ，Guidelines for Clinical Use of New Anti-tumor Drugs （2018 edition），Off-label Drug Use List （2019 edition），Practical Oncology （secondary edition），anti-tumor drug package inserts approved by FDA and package inserts of anti-tumor drug listed in China ，abnormal use of antitumor drugs （including instructions ，special indications ，and the order of administration of new anti-tumor drugs ） was summarized and analyzed. RESULTS & CONCLUSIONS ：The off-label use of anti-tumor drugs were summarized in this paper ， including 11 drug varieties and 4 kinds of off-label drug items ，such as off-label drug use plan （recombinant human endostatin ， rituximab），off-label administration route （pemetrexed disodium ，bortezomib，bevacizumab），off-label administration lines （erlotinib，gefitinib），off-label drug dosage （actinomycin D ，gemcitabine，ifosfamide，etoposide）. They should be carefully selected and strictly monitored in clinical use ，and treatment plan should be adjusted according to needs. Among the special indications，cyclophosphamide，cytarabine，methotrexate and cisplatin were used in large doses ，which were 2 000-2 400 mg/m2， 2 000 mg/m2，12 g/m2 and 80-120 mg/m2，respectively；individual differences should be paid attention to and therapeutic drug monitoring should be carried out if necessary. In the scheme of combination of new anti-tumor drugs or traditional chemotherapy drugs，there were 5 categories and 11 items in total ，such as combination of molecular targeted anti-tumor drugs with traditional chemotherapy drugs （such as docetaxel at first ，gefitinib at the same time or later ），combination of target immunocheckpoint drugs with traditional chemotherapy drugs （such as platinum at first ，then nivolumab ），and molecular targeted anti-tumor drugs combination（such as pertuzumab and trastuzumab should be given in sequence ，in either order ）. In clinical use ，histopathological diagnosis should be made clear ， and drugs with specific targets should be used after gene detection and strictly follow the indications.

[Prevention and Treatment of Cancer Therapeutics-related Cardiac Dysfunction].

Cancer therapeutics-related cardiac dysfunction(CTRCD)is receiving more attention.Risk factors assessment before cancer therapy,cardiac function monitoring during and after cancer therapy,and early detection and treatment of myocardial injury are key to preventing clinical heart failure.The incidence and severity of cardiotoxicity can be reduced by measures such as reducing drug dose,adjusting administration route,and using low toxic drugs.Cardioprotective agents including anti-heart failure drugs and dexrazoxane are important for the prevention and treatment of CTRCD.Patients with advanced heart failure may also benefit from mechanical treatments including cardiac resynchronization therapy and mechanically-assisted ventricular devices.This article reviews the recent advances in the prevention and treatment of CTRCD.

Anti-leukemia activity of 4-amino-2-aryl-6,9-dichlorobenzo[g]pteridines.

Pteridines are bicyclic heterocyclic compounds with a pyrazino[2,3-d]pyrimidine nucleus that have shown a wide range of therapeutic utilities. Concretely, 4-aminopteridine derivatives have demonstrated both anti-inflammatory and anti-cancer properties, and some of them, such as methotrexate, are profusely used in medical practice. We have recently synthesized and tested the biological activity of a novel series of 4-amino-2-aryl-6,9-dichlorobenzo[g]pteridines, finding that they present anti-inflammatory properties, as they were able to inhibit in vitro the production of pro-inflammatory cytokines TNF-α and IL-6. Now, we have evaluated the anti-tumor potential of these compounds on HL-60 and K562 leukemia cell lines. Cells growing at exponential rate were exposed to decreasing doses of each compound, from 50 to 0.39 µM, for 24, 48, and 72 h. Cell viability was tested by MTT assay and cell death fashion determined by annexin V/propidium iodide assay. The cytotoxicity of the compounds was determined in differentiated macrophage-like HL-60 cells and in human peripheral blood mononuclear cells to evaluate the potential side effects on quiescent tumor cells and normal cells, respectively. Among the series, compounds 1a, 1b, 1g, 1j, and 1k showed anti-proliferative activity. Compounds 1j and 1k were active against both HL-60 and K562 cells, with a lower IC50 against HL-60 cells. Compounds 1a, 1b, and 1g had a great cytotoxic activity against HL-60, but they were far less potent against K562 cells. None had side effects in differentiated tumor cells or in human peripheral blood mononuclear cells. In conclusion, our results demonstrate that some compounds of this series of 4-amino-2-aryl-6,9-dichlorobenzo[g]pteridines have anti-cancer properties in vitro.

Exosomes: An endogenous natural nano-drug delivery system / 中国药理学通报

Exosomes are naturally nanometer-sized (40-100 nm) vesicles that contribute to the communication among the cells through the proteins, lipids and RNA which they carried. Exosomes derived at different physiological conditions play different role, which therefore can be widely used in the diagnosis and treatment of cancer. Besides, exosomes as the natural nanomaterials have the unique advantage in drug delivery system. Although the intrinsic advantages of exosomes have evoked a surge of interest, improvements in standardized isolation techniques with high efficiency and robust yield are still a huge challenge. Here, we provide an overview of the isolation and the application of exosomes in drug delivery system.