Expert Consensus on the Diagnosis and Treatment of Anticancer Drug-Induced Interstitial Lung Disease

Drug-induced interstitial lung disease(DILD)is the most common pulmonary adverse event of anticancer drugs.In recent years,the incidence of anticancer DILD has gradually increased with the rapid development of novel anticancer agents.Due to the diverse clinical manifestations and the lack of specific diagnostic criteria,DILD is difficult to diagnose and may even become fatal if not treated properly.Herein,a multidisciplinary group of experts from oncology,respiratory,imaging,pharmacology,pathology,and radiology departments in China has reached the“expert consensus on the diagnosis and treatment of anticancer DILD”after several rounds of a comprehensive investigation.This consensus aims to improve the awareness of clinicians and provide recommendations for the early screening,diagnosis,and treatment of anticancer DILD.This consensus also emphasizes the importance of multidisciplinary collaboration while managing DILD.

Comparison of Anticancer Drug Preparation Techniques between Chemotherapy Specialist Pharmacists and Non-Chemotherapy Pharmacists Using Eye-Tracking Techniques

Anticancer drug preparation by pharmacists is a critical task directly related to medical incidents. This study examined the factors influencing medical errors in chemotherapy, that is, errors by specialist pharmacists (CPh) and pharmacists in other departments (NCPh), by measuring their gaze during the preparation of anticancer drugs. The eye-tracking results showed that the gazing time of NCPh was significantly longer than that of CPh for items such as “preparation of a closed-system device” and “preparation of the syringe” and all preparation times (P < 0.05). The NCPh were not assigned to prepare drugs on a regular basis, indicating their lack of familiarity with the process. There was no significant difference in gaze ratio between CPh and NCPh. This outcome was suggested to be a result of the use of an anticancer drug preparation support system. The results for the pupil diameter variation rate showed that NCPh were significantly more mydriatic in the “mixing injections” category than CPh. However, CPh tended to be more mydriatic in the “checking” category. CPh exhibited a smooth workflow and focused on the important items to be checked. This study showed that the differences in procedure flow and concentration points may lead to errors. Furthermore, the results are of interest from the perspective of medical incident prevention. They will be useful in identifying potential human factors, such as where the pharmacist focuses their attention by measuring eye movements.

Anticancer Drugs ( Ⅳ )——New Derivatives of Podophyllotoxin

Four new derivatives of podophyllotoxin, N'-podophyllic acid-N-[3-(2, 2, 5, 5-te-tramethyl-pyrrolinenyloxy)] semicarbazide(GP-11, 6), podophyllic acid [3-(2,2,5,5-te-tramethyl-pyrrolinenyloxy)]hydrazone (GP-12, 7), podophyllic acid-[4-(2, 2, 6, 6-tetramethyl-1-hydroxy piperidine)]hydrazone(GP-1-OH, 8) and podophyllic acid[4-(2,2, 6, 6-tetramethyl piperidine)]hydrazone(GP-1-H, 9) were synthesized. The inhibition effect of the four new compounds on L-1210 cells were determined. The antitumor activity and toxicity of GP-1(2), GP-1-OH(8), GP-1-H(9) and VP-16-213(1) were discussed.

Anticancer Drugs (V)─—Synthesis of Etoposide Derivatives

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Research progress in nanoparticles as anticancer drug carrier

Nanoparticles drug delivery system has sustained and controlled release features as well as targeted drug delivery, which can change the characteristics of drug distribution in vivo. It can increase the stability of the drug and enhance drug bioavailability. The selective targeting of nanoparticles can be achieved through enhanced permeability and retention effect and a conjugated specific ligand or through the effects of physiological conditions, such as pH and temperature. Nanoparticles can be prepared by using a wide range of materials and can be used to encapsulate chemotherapeutic agents to reduce toxicity, which can be used for imaging, therapy, and diagnosis. In this research, recent progress on nanoparticles as a targeted drug delivery system will be reviewed, including positive-targeting, negative-targeting, and physicochemical-targeting used as anticancer drug carriers.

Overview of Research and Development for Anticancer Drugs

Anticancer drugs research and development have been the largest market area in the pharmaceutical industry in terms of the number of project, clinical trials and spending. In the last 10 - 30 years, targeting therapy for cancers has been developed and achieved enormous clinical effectiveness by transforming some previously deadly malignancies into chronically manageable conditions, but cure problem still remains. This mini review outlined the current status of anticancer drugs development and hinted the opinions of how to further increase the accuracy and efficacy of discovery for cancer treatment.

Hollow-structured nanoparticles as an anticancer drug carrier

Many drug candidates identified from natural products are poorly water-soluble.The surfactants used to disperse the hydrophobic anticancer drugs in water may cause a serious of acute hypersensitivity reactions.Nanotechnology provides an alternative strategy for delivery of anticancer drugs.Drugs can be encapsulated or attached to the nanomaterials such as lipids,polymers and solid-core nanoparticles.In the present study,porous inorganic nanoparticles have been utilized for delivery of water-insoluble anticancer drugs.The synthesized nanoparticles were functionalized with different organic polymers.The porous nanoparticles were readily internalized by human glioblastoma U-87 MG cells,and didn′t display cytotoxicity.The internalized nanoparticles were mainly localized in endosomes/lysosomes in cells.With the hydrophobic curcumin and carfilzomib as model drugs,intracellular delivery of hydrophobic anticancer drugs by the porous inorganic nanoparticles was studied.The porous nanoparticle-based encapsulation of hydrophobic drug provides the aqueous dispersion of the drugs.In endosomes/lysosomes mimicking buffers with a pH of 4.5-5.5,pH-dependent drug release was observed from drug loaded nanoparticles.The intracellular drug content and cytotoxicity were significantly higher for drug loaded nanoparticles than free drug.These results suggested porous inorganic nanoparticles might be a promising intracellular carrier for hydrophobic anticancer drugs.

Determination of Impurity Silicon in Anticancer Drug (Ge-132) by Electrothermally Atomised Atomic Absorption Spectrometry with Optical Temperature Control Accessory

The present paper describes the ashing and atomization processes in silicon analysis by electrothermally atomised atomic absorption spectrometry(EAAAS) with an uncoat-ed graphite tube, a pyrolytically coated graphite tube and a tungsten-coated graphitetube. The sensitivity and linear range of three graphite tubes were compared. By using optical temperature control accessory, the signals are enhanced by a factor of 2 and the germanium interferences in the determination of silicon are eliminated. The effects of time constant and carrier gas flow-rate on the determination of silicon were also tested. The sample can be directly analyzed in its aqueous solution without any pretreatment. The measurements of samples containing 0. 2 μg/mL and 0. 4 μg/mL silicon were run ten times and the variation coefficient is 4. 9% and 2.6%, respectively. The recovery tests for carboxyethyl germanium sesquioxide(Ge-132) synthesized and imported were performed, and the recoveries are 97. 0% and 110%, respectively. Keywords Carboxyethyl germanium sesquioxide, Electrothermally atomised atomic absorption spectrometry, Silicon

Release of Anticancer Drug 5-Fluorouracil from Different Ionically Crosslinked Alginate Beads

In this research;the release of 5-Fluorouracil (5-FU) from different ionically crosslinked alginate (Alg) beads was investigated by using Fe3+, Al3+, Zn2+, and Ca2+, ions as crosslinking agent. The prepared beads were characterized by Fourier Transform Infrared Spectroscopy (FTIR) Differential Scanning Calorimetry (DSC) and Scanning Electron Micros-copy (SEM). The drug release studies were carried out at three pH values 1.2, 6.8 and 7.4 respectively each for two hours. The effects of the preparation conditions as crosslinker type, drug/polymer (w/w) ratio, crosslinker concentration and time of exposure to crosslinker on the release of 5-FU were investigated for 6 hours at 37℃. It was observed that 5-FU release from the beads followed the order of Fe > Zn > Al > Ca-Alg and increased with increasing drug/polymer ratio. At the end of 6 hours, the highest 5-FU release was found to be 90% (w/w) for Fe-Alg beads at the drug/polymer ratio of 1/8 (w/w), crosslinker concentration of 0.05 M, exposure time of 10 minutes respectively. The swelling measurements of the beads supported the release results. Release kinetics was described by Fickian and non-Fickian approaches.

A New Anticancer Drug

After some six years of hard work, a research team headed by Prof. Liu Zhivu (Z.Y. Liu) at the Shanghai Institute of Organic Chemistry, CAS, has scored major progress in independently generating a novel cancer killer called epothilone. Their findings have been granted three patents, and their research paper Total Synthesis of Epothilone: A Thorough Stereospecific Expoxidation of the 3-0-(4-methoxy) Benzyl Ether of Epothilone C has been accepted for publication in the Chemistry - European Journal.

Targeting cancer cytoskeleton: the mechanical properties of natural anticancerdrugs

Anticancer drugs are one of the most direct means of cancer therapy.However,the various cancer progressions hamper the development and discovery of anticancer drugs.In fact,the mechanical properties of the tumor cytoskeleton are extremely vital for any phase of cancer,especially in tumor invasion and metastasis.However,in the current category of anticancer drugs,the cytoskeleton-targeting drugs are limited and their role in tumor progression is unclear.Here,we present the mechanical characteristics of tumor stiffness that are tightly regulated by the cancer cytoskeleton,including actin filaments and microtubules during tumor initiation,growth and metastasis,and review the natural drugs that target the cancer cytoskeleton.We define cytoskeleton dynamics as target mechanisms for anticancer drugs and summarize the plant,microbial and marine sources of natural products.Furthermore,this paper also provides a material pathway to study active tumor mechanics,and introduces the unique advantages and future application potential of tumor cytoskeleton-targeting drugs in clinical use.The material approaches to active cancer mechanics are supplied in this review.We aim to promote the development of anticancer drugs that target tumor mechanics by using those material approaches and finding their pharmacological application.

Investigation of the redox status in H22 hepatocellular carcinoma xenografts treated by a novel anticancer drug-ethaselen

We investigated the redox status of H22 hepatocellular carcinoma xenografts treated with various doses of ethaselen, a novel anticancer drug targeting thioredoxin reductase （TrxR）. The concentrations of low molecular weight antioxidant g!utathione （GSH） and malondialdehyde （MDA）, a product of lipid peroxidation, as well as the activities of important antioxidant enzymes were measured for elucidating the redox status of H22 tumor tissues. We found that the decreased GSH level, decreased thioredoxin reductase and superoxide dismutase （SOD） activities as well as increased MDA content were closely related to the tumor growth inhibition and ethaselen doses. Glutathione peroxidase （GPx） and glutathinne reductase （GR） activities are also affected by ethaselen treatment. However, the catalase （CAT） activity remains unchanged. Finally, we studied the relationship of tumor growth inhibition caused by ethaselen with these redox factors. This study showed that ethaselen could elevate the oxidative stress to suppress the H22 tumor growth in mice model.

Neutrophil-mediated anticancer drug delivery for suppression of postoperative malignant glioma recurrence

Subject Code:H30With the support by the National Natural Science Foundation of China,the research group led by Prof.Zhang Can(张灿)from China Pharmaceutical University made important progress in the chemotherapy of post-operative malignant glioma,which was published in Nature Nanotechnology(2017,12(7):692—700).

DNA G-quadruplex and its potential as anticancer drug target

G-quadruplex secondary structures are four-stranded globular nucleic acid structures form in the specific DNA and RNA G-rich sequences with biological significance such as human telomeres,oncogene-promoter regions,replication initiation sites,and 5′and 3′-untranslated(UTR)regions.The non-canonical G-quadruplex secondary structures can readily form under physiologically relevant ionic conditions and are considered to be new molecular target for cancer therapeutics.This review discusses the essential progress in our lab related to the structures and functions of biologically relevant DNA G-quadruplexes in human gene promoters and telomeres,and the opportunities presented for the development of G-quadruplex-targeted smallmolecule drugs.

Evolution of drug regulations and regulatory innovation for anticancer drugs in China

Over the past two decades,China has introduced significant changes to drug regulations through regulatory innovations to accelerate drug review and approvals,keeping in line with the rapidly growing scientific innovation in drug research and development(R&D).In this study,we outlined the revolution of drug regulation in China since the establishment of the State Drug Administration in 1998.More particularly,we performed a comprehensive analysis of newly approved anticancer drugs in China from the year 2005 to May 2021,as a powerful illustration of how the revolution has changed the drug R&D landscape.Innovative drug development in China has boomed,benefiting in particular from pro-innovation policies as well as expedited program designations by the authority.We found a significant increase in the number of both imported and domestic new anticancer drugs from 2005 to 2021,with the emergence of drugs with novel mechanisms of action,including immune checkpoint inhibitors and cell therapy products.Drug lag has also been dramatically shortened by more than 70%for imported drugs in years 2016-2020 compared to years 2006-2010.Furthermore,we provide an insight into the potential approaches to further optimize the science-based and clinical value-based regulatory and R&D drug ecosystem in China.This review provides evidence of significant impacts of regulations and policies on drug R&D and suggests that the constantly adapting regulatory ecosystem will speed up drug development in China and worldwide.

Real-time detection of the interaction between anticancer drug daunorubicin and cancer cells by Au-MCNT nanocomposites modified electrodes

In this study,we have prepared the blending of gold nanoparticles-multiwalled nanotubes (Au-MCNTs) and then applied the new nanocomposites to modify the glassy carbon electrode (GCE) for highly sensitive detection of the interaction between anticancer drug daunorubicin (DNR) and cancer cells. Electrochemical analysis indicates that the Au-MCNT modified GCE shows high sensitivity and could track the real time response of cancer cells under DNR treatments. Therefore,this new nano-interface and Au-MCNT modified electrode could be explored as a rapid,highly sensitive,and convenient real-time detection strategy in cancer related research and would have prospect in other biomedical applications.

Editorial for targets and anticancer drug research

The research for antitumor therapeutics is a timeless topic and keeps pace with times,especially chemotherapy and target therapy.Drug target identification is a key step in the development of effective therapeutic agents.In this issue,we present the current status of some validated and potential targets in drug discovery for developing therapeutic agents as well as

RECENT PROGRESS IN THE STUDY OF ANTICANCER DRUGS ORIGINATING FROM PLANTS AND TRADITIONAL MEDICINE IN CHINA

Recent progress in the studies of anticancer drugs originating from plants in China is reviewed in this paper. Guided by the experience of traditional Chinese medicine (TCM), several new anticancer drugs have been found. Indirubin from indigofera tinctoria (青黛) is useful for the treatment of chronic myelocytic leukemia. On the basis of structure-activity relationship studies of these compounds, a second generation drug (N-methyl isoindigotin) has been developed. Clinical studies demonstrated that it is more effective than indirubin, 1O-hydroxy campothecin derived from Camptotheca acuminata (喜树) have exhibited definite activity on rodent tumors and it is used for phase Ⅱ studies. Iris latea pallasi Fischer var. Chinensis (马蔺子) may serve as

PROGRESS OF RESEARCH IN THE PREPARATION OF CHINESE TRADITIONAL AND HERBAL DRUGS WITH ANTICANCER ACTIVITY

Research into anticancer substances madefrom Chinese herbal drugs and their clinicalapplication is gaining international attention bythe medical profession of the more than 20analogues of camptothecine isolated from Camp-totheca tree in China, most exhibited anticanceractivity. Among them, 10-hydroxycamptothe-cine has a wide anticancer spectrum and is lesstoxic. In suspension, it exhibits some therapeu-tic effects on primary hepatic cancer, gastriccarcinoma, cancer of the urinary bladder andleukemia.

Plant-derived anticancer agents: A green anticancer approach

Cancer is a frightful disease and represents one of the biggest health-care issues for the human race and demands a proactive strategy for cure. Plants are reservoirs for novel chemical entities and provide a promising line for research on cancer. Hitherto, being effective, chemotherapy is accompanied by certain unbearable side effects. Nevertheless,plants and plant derived products is a revolutionizing field as these are Simple, safer, ecofriendly, low-cost, fast, and less toxic as compared with conventional treatment methods.Phytochemicals are selective in their functions and acts specifically on tumor cells without affecting normal cells. Carcinogenesis is complex phenomena that involves many signaling cascades. Phytochemicals are considered suitable candidates for anticancer drug development due to their pleiotropic actions on target events with multiple manners. The research is in progress for developing potential candidates(those can block or slow down the growth of cancer cells without any side effects) from these phytochemicals. Many phytochemicals and their derived analogs have been identified as potential candidates for anticancer therapy. Effort has been made through this comprehensive review to highlight the recent developments and milestones achieved in cancer therapies using phytomolecules with their mechanism of action on nuclear and cellular factors. Furthermore, drugs for cancer treatment and their limitations have also been discussed.