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 a...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.展开更多
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 pharmacist...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.展开更多
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.Nanotec...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.展开更多
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 ...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.展开更多
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...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.展开更多
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 ...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.展开更多
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 cytos...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.展开更多
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 innovat...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.展开更多
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 po...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).展开更多
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 age...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展开更多
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 promisin...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.展开更多
In the last few decades numbers of review and research articles have been published on niosomes. This shows the relevant interest of academias & researchers in niosomes because of the advantages sponsored by them ...In the last few decades numbers of review and research articles have been published on niosomes. This shows the relevant interest of academias & researchers in niosomes because of the advantages sponsored by them over other colloidal drug delivery systems. Niosomes formation occurs when non-ionic surfactant vesicles assemble themselves. Various antineoplastic agents are used in chemotherapy, but they have some drawbacks that these agents cause cell death in normal tissues as well. There are two approaches to overcome this limitation. First, to modify the structure of existing drugs, but this will not possible because it changes the properties of drugs. Second, the development of nano-carriers like liposomes, dendrimers, nanoparticles, niosomes et al. Among all, niosomes (non-ionic surfactant vesicles) have more advantages besides all nano-carriers. Drugs either hydrophilic in nature or hydrophobic in nature, both can be incorporated in niosomes. And by embedding specific ligands over vesicular surface enables us to target the drug to specific cancer cells.展开更多
Currently,cancer is the most rapidly growing life-threatening disease after cardiovascular in the world,posing a major threat to human life.Telomerase promotes tumorigenesis and development in most cancers and dyskeri...Currently,cancer is the most rapidly growing life-threatening disease after cardiovascular in the world,posing a major threat to human life.Telomerase promotes tumorigenesis and development in most cancers and dyskerin plays a crucial role in telomere maintenance.Cancer molecules are being developed continuously as a result of continuous research.A series of novel anticancer agents have been developed using telomerase inhibitors with improved specificity and pharmacokinetics.As medicinal chemistry advances,heterocyclic-based drugs find increasing applications,including anticancer agents.These properties have led to the development of five-membered aromatic rings of oxadiazoles.In order to enhance their anticancer activity,oxadiazole scaffolds can be modified.In this review,we discuss the functions and mechanism of action of the telomerase enzyme.The paper also summarizes the interaction between 1,3,4-oxadiazole inhibitors and telomerase enzymes.展开更多
Cancer stem cells(CSCs)are tumor cells that share functional characteristics with normal and embryonic stem cells.CSCs have increased tumor-initiating capacity and metastatic potential and lower sensitivity to chemo-a...Cancer stem cells(CSCs)are tumor cells that share functional characteristics with normal and embryonic stem cells.CSCs have increased tumor-initiating capacity and metastatic potential and lower sensitivity to chemo-and radiotherapy,with important roles in tumor progression and the response to therapy.Thus,a current goal of cancer research is to eliminate CSCs,necessitating an adequate phenotypic and functional characterization of CSCs.Strategies have been developed to identify,enrich,and track CSCs,many of which distinguish CSCs by evaluating the expression of surface markers,the initiation of specific signaling pathways,and the activation of master transcription factors that control stemness in normal cells.We review and discuss the use of reporter gene systems for identifying CSCs.Reporters that are under the control of aldehyde dehydrogenase 1A1,CD133,Notch,Nanog homeobox,Sex-determining region Y-box 2,and POU class 5 homeobox can be used to identify CSCs in many tumor types,track cells in real time,and screen for drugs.Thus,reporter gene systems,in combination with in vitro and in vivo functional assays,can assess changes in the CSCs pool.We present relevant examples of these systems in the evaluation of experimental CSCs-targeting therapeutics,demonstrating their value in CSCs research.展开更多
Objective:To examine the effects of paclitaxel and resveratrol on rabbit semen.Methods:This study consisted of four groups: control group (40 mL saline), paclitaxel group (5 mg/kg paclitaxel), resveratrol group (4 mg/...Objective:To examine the effects of paclitaxel and resveratrol on rabbit semen.Methods:This study consisted of four groups: control group (40 mL saline), paclitaxel group (5 mg/kg paclitaxel), resveratrol group (4 mg/kg resveratrol) and paclitaxel+resveratrol group (5 mg/kg paclitaxel+4 mg/kg resveratrol). Administrations werei.v.(in 40 mL saline) and continued 8 weeks. Sperm motility was evaluated using phase-contrast microscopy. Mitochondrial activity, membrane and acrosome integrity were performed by fluorescence staining. Lipid peroxidation, total glutathione and antioxidant potential levels were determined by spectrophotometry.Results: Paclitaxel decreased the sperm motility and fluorescence staining results compared to the control (P<0.05). The paclitaxel and resveratrol group showed better results of the same parameters compared to the paclitaxel group (P<0.05). No significant difference was observed in lipid peroxidation, total glutathione, antioxidant potential and fertility results (P>0.05). Results of this study showed that paclitaxel decreased semen parameters and resveratrol had a protective effect on these parameters.Conclusions:Paclitaxel has negative effects on spermatological indicators and biochemical assays, while resveratrol prevents these negative effects of paclitaxel.展开更多
Cancer is a group of diseases with significant morbidity and mortality.In cancer cells,where energy requirements are exceptionally high,angiogenesis,which is the sprouting of new blood vessels from pre-existing ones,i...Cancer is a group of diseases with significant morbidity and mortality.In cancer cells,where energy requirements are exceptionally high,angiogenesis,which is the sprouting of new blood vessels from pre-existing ones,is an important process for tumour survival and progression.Hence,extensive research in recent years focuses on the discovery of new anticancer drugs that target angiogenesis.Several methodologies have been developed preclinically,including the inhibition of pro-angiogenic factors and their receptors via micromolecular agents or monoclonal antibodies and the inhibition of other compensatory pathways beyond the traditional angiogenic ones.The purpose of the literature review is to present new anticancer drugs that target the process of angiogenesis and have been under preclinical or clinical investigation during the last five years.Many new anticancer drugs targeting angiogenesis are identified in the literature.The results of the in vitro and in vivo evaluation of these drugs show that,apart from inhibiting angiogenesis,they also affect cancer cell proliferation and tumour growth.Recent clinical studies show that these drugs increase the overall or disease-free survival of patients,even those with persistent,chemotherapy-resistant and metastatic types of cancer,although treatment-related side effects are not uncommon.Drugs that target the process of angiogenesis are likely to be the future of anticancer therapy,especially in cases where more traditional treatments do not produce the desired results and where combination regimens of anti-angiogenic agents with standard chemotherapeutics increase patient survival.展开更多
A library of new 1,4-benzodioxane-6-carboxylic acid amide analogs was designed and synthesized. These analogs were obtained in six steps from gallic acid. Firstly, esterification of the commercially available gallic a...A library of new 1,4-benzodioxane-6-carboxylic acid amide analogs was designed and synthesized. These analogs were obtained in six steps from gallic acid. Firstly, esterification of the commercially available gallic acid in methanol in the presence of sulfuric acid afforded methyl 3,4,5-trihydroxybenzoate (9) in satisfactory yield. The ester 9 was then reacted with an excess of 1,2-dibromoethane in the presence of K<sub>2</sub>CO<sub>3</sub> in acetone to furnish the 6,8-disubstituted-1,4-benzodioxane (10) in 45% yield. The reaction of 10 with various mercaptans gave the sulfide derivative 11, 12, and 13 in moderate yield. Subsequent hydrolysis of the methyl ester in 13 followed by conversion to the acid chloride and reaction of the acid chloride intermediate with different commercially available primary and secondary amines gave the amide analogs 18 - 32 with an average yield of 43%. Conversion of the sulfide group in Compound 23 to Sulfoxide 33 or Sulfone 34 was accomplished by reaction with either 30% H<sub>2</sub>O<sub>2</sub>/TeO<sub>2</sub> or 30% H<sub>2</sub>O<sub>2</sub>, respectively. The structures of the synthesized compounds were characterized using FTIR, <sup>1</sup>H-NMR, <sup>13</sup>C-NMR, and high-resolution ESI-MS.展开更多
Molecular hydrogen is an effective antioxidant.Numerous studies have demonstrated the therapeutic effects of hydrogen in the treatment of various human diseases.The possibility of using hydrogen in the treatment of ca...Molecular hydrogen is an effective antioxidant.Numerous studies have demonstrated the therapeutic effects of hydrogen in the treatment of various human diseases.The possibility of using hydrogen in the treatment of cancer was first discovered in 1975,and in recent studies,researchers have reported numerous positive effects of hydrogen in cancer therapy,including:1)the alleviation of complications caused by chemotherapy;2)a reduction of complications caused by radiotherapy;3)delays in the progression of cancer;and 4)enhanced efficacy of conventional therapy when used in combination with hydrogen.This article reviews the research progress in the use of hydrogen in the treatment of cancer,and proposes future directions for research in this field.展开更多
Off-label use is defined by the prescription of a marketed drug outside the conditions described in the summary of product characteristics.In oncology,off-label prescribing of targeted therapies may occur in patients ...Off-label use is defined by the prescription of a marketed drug outside the conditions described in the summary of product characteristics.In oncology,off-label prescribing of targeted therapies may occur in patients with other tumor types expressing the same target.Agents associated to phenotypic approaches such as therapies against the tumoral vasculature(anti-angiogenic drugs) and new immunotherapies(checkpoint inhibitors) also carry the potential of alternative indications or combinations.Off-label use of targeted therapies is little documented and appears to be in the same range than that regarding older drugs with wide variations among agents.When compared with older agents,off-label use of targeted therapies is probably more rational through tumoral genotyping but is faced with a limited clinical support,reimbursement challenges related to the very high pricing and the cost of genotyping or molecular profiling,when applicable.展开更多
Even today,lung cancer remains one of the most frequently diagnosed cancers and the leading cause of cancer-related deaths worldwide.Throughout the past decades,remarkable advances have been made in the research and d...Even today,lung cancer remains one of the most frequently diagnosed cancers and the leading cause of cancer-related deaths worldwide.Throughout the past decades,remarkable advances have been made in the research and development of anti-lung cancer drugs in China.Since the first registered Chinese clinical trial on May 2,2006,many potent anti-lung cancer drugs have been developed and approved by the China Food and Drug Administration and the National Medical Product Administration of China.Among them,the most advance were observed in the development of targeted agents and immunotherapeutic agents such as epidermal growth factor receptor(EGFR)-tyrosine kinase inhibitors(TKIs)icotinib,aumolertinib,and furmonertinib,anaplastic lymphoma kinase(ALK)-TKI ensartinib,programmed cell death-1(PD-1)monoclonal antibodies(mAbs)camrelizumab,sintilimab,and tislelizumab,and programmed cell death-ligand 1(PD-L1)mAb sugemalimab,which have made huge breakthrough in recent years.Some other investigational innovative drug also demonstrated promising efficacy and acceptable safety profiles.Results from clinical studies on these China innovative drugs have led to changes in clinical practice guidelines and considerably improved the outcomes for patients with lung cancer.Thus,in this review,we aim to provide further insight into the clinical development and achievement of China innovative anti-lung cancer drugs.展开更多
基金supported by grants from CAMS Innovation Fund for Medical Sciences(CIFMS)(No.2021-I2M-1-014)and National Key R&D Program of China(No.2021YFC2500700).
文摘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.
文摘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.
基金Science and Technology Development Fund,Macao SAR(0168/2019/A3)。
文摘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.
文摘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.
基金The authors are grateful to the Gazi University Scientific Research Foundation for support of this study.
文摘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.
文摘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.
基金funded by"Beijing Natural Science Foundation,grant number 6224060","Young Elite Scientists Sponsorship Program by BAST,grant number",BYESS2023192"Program of Beijing Municipal Education Commission,grant number KM202310020006"+1 种基金"Bejing University of Agriculture science and Technology innovation Sparkling support plan,grant number,BUA-HHXD2022007""2022 Research and Innovation ability improvement plan for young teachers of Beijing University of Agriculture,grant number QJKC2022028".
文摘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.
文摘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.
文摘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).
文摘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
文摘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.
文摘In the last few decades numbers of review and research articles have been published on niosomes. This shows the relevant interest of academias & researchers in niosomes because of the advantages sponsored by them over other colloidal drug delivery systems. Niosomes formation occurs when non-ionic surfactant vesicles assemble themselves. Various antineoplastic agents are used in chemotherapy, but they have some drawbacks that these agents cause cell death in normal tissues as well. There are two approaches to overcome this limitation. First, to modify the structure of existing drugs, but this will not possible because it changes the properties of drugs. Second, the development of nano-carriers like liposomes, dendrimers, nanoparticles, niosomes et al. Among all, niosomes (non-ionic surfactant vesicles) have more advantages besides all nano-carriers. Drugs either hydrophilic in nature or hydrophobic in nature, both can be incorporated in niosomes. And by embedding specific ligands over vesicular surface enables us to target the drug to specific cancer cells.
文摘Currently,cancer is the most rapidly growing life-threatening disease after cardiovascular in the world,posing a major threat to human life.Telomerase promotes tumorigenesis and development in most cancers and dyskerin plays a crucial role in telomere maintenance.Cancer molecules are being developed continuously as a result of continuous research.A series of novel anticancer agents have been developed using telomerase inhibitors with improved specificity and pharmacokinetics.As medicinal chemistry advances,heterocyclic-based drugs find increasing applications,including anticancer agents.These properties have led to the development of five-membered aromatic rings of oxadiazoles.In order to enhance their anticancer activity,oxadiazole scaffolds can be modified.In this review,we discuss the functions and mechanism of action of the telomerase enzyme.The paper also summarizes the interaction between 1,3,4-oxadiazole inhibitors and telomerase enzymes.
基金Supported by UNAM-PAPIIT,No.IN219719 and No.IA205421CONACYT,No.A1-S-18285.
文摘Cancer stem cells(CSCs)are tumor cells that share functional characteristics with normal and embryonic stem cells.CSCs have increased tumor-initiating capacity and metastatic potential and lower sensitivity to chemo-and radiotherapy,with important roles in tumor progression and the response to therapy.Thus,a current goal of cancer research is to eliminate CSCs,necessitating an adequate phenotypic and functional characterization of CSCs.Strategies have been developed to identify,enrich,and track CSCs,many of which distinguish CSCs by evaluating the expression of surface markers,the initiation of specific signaling pathways,and the activation of master transcription factors that control stemness in normal cells.We review and discuss the use of reporter gene systems for identifying CSCs.Reporters that are under the control of aldehyde dehydrogenase 1A1,CD133,Notch,Nanog homeobox,Sex-determining region Y-box 2,and POU class 5 homeobox can be used to identify CSCs in many tumor types,track cells in real time,and screen for drugs.Thus,reporter gene systems,in combination with in vitro and in vivo functional assays,can assess changes in the CSCs pool.We present relevant examples of these systems in the evaluation of experimental CSCs-targeting therapeutics,demonstrating their value in CSCs research.
基金financially supported from Selecuk University Scientific Research Projects(BAP)(project No:12102013)
文摘Objective:To examine the effects of paclitaxel and resveratrol on rabbit semen.Methods:This study consisted of four groups: control group (40 mL saline), paclitaxel group (5 mg/kg paclitaxel), resveratrol group (4 mg/kg resveratrol) and paclitaxel+resveratrol group (5 mg/kg paclitaxel+4 mg/kg resveratrol). Administrations werei.v.(in 40 mL saline) and continued 8 weeks. Sperm motility was evaluated using phase-contrast microscopy. Mitochondrial activity, membrane and acrosome integrity were performed by fluorescence staining. Lipid peroxidation, total glutathione and antioxidant potential levels were determined by spectrophotometry.Results: Paclitaxel decreased the sperm motility and fluorescence staining results compared to the control (P<0.05). The paclitaxel and resveratrol group showed better results of the same parameters compared to the paclitaxel group (P<0.05). No significant difference was observed in lipid peroxidation, total glutathione, antioxidant potential and fertility results (P>0.05). Results of this study showed that paclitaxel decreased semen parameters and resveratrol had a protective effect on these parameters.Conclusions:Paclitaxel has negative effects on spermatological indicators and biochemical assays, while resveratrol prevents these negative effects of paclitaxel.
文摘Cancer is a group of diseases with significant morbidity and mortality.In cancer cells,where energy requirements are exceptionally high,angiogenesis,which is the sprouting of new blood vessels from pre-existing ones,is an important process for tumour survival and progression.Hence,extensive research in recent years focuses on the discovery of new anticancer drugs that target angiogenesis.Several methodologies have been developed preclinically,including the inhibition of pro-angiogenic factors and their receptors via micromolecular agents or monoclonal antibodies and the inhibition of other compensatory pathways beyond the traditional angiogenic ones.The purpose of the literature review is to present new anticancer drugs that target the process of angiogenesis and have been under preclinical or clinical investigation during the last five years.Many new anticancer drugs targeting angiogenesis are identified in the literature.The results of the in vitro and in vivo evaluation of these drugs show that,apart from inhibiting angiogenesis,they also affect cancer cell proliferation and tumour growth.Recent clinical studies show that these drugs increase the overall or disease-free survival of patients,even those with persistent,chemotherapy-resistant and metastatic types of cancer,although treatment-related side effects are not uncommon.Drugs that target the process of angiogenesis are likely to be the future of anticancer therapy,especially in cases where more traditional treatments do not produce the desired results and where combination regimens of anti-angiogenic agents with standard chemotherapeutics increase patient survival.
文摘A library of new 1,4-benzodioxane-6-carboxylic acid amide analogs was designed and synthesized. These analogs were obtained in six steps from gallic acid. Firstly, esterification of the commercially available gallic acid in methanol in the presence of sulfuric acid afforded methyl 3,4,5-trihydroxybenzoate (9) in satisfactory yield. The ester 9 was then reacted with an excess of 1,2-dibromoethane in the presence of K<sub>2</sub>CO<sub>3</sub> in acetone to furnish the 6,8-disubstituted-1,4-benzodioxane (10) in 45% yield. The reaction of 10 with various mercaptans gave the sulfide derivative 11, 12, and 13 in moderate yield. Subsequent hydrolysis of the methyl ester in 13 followed by conversion to the acid chloride and reaction of the acid chloride intermediate with different commercially available primary and secondary amines gave the amide analogs 18 - 32 with an average yield of 43%. Conversion of the sulfide group in Compound 23 to Sulfoxide 33 or Sulfone 34 was accomplished by reaction with either 30% H<sub>2</sub>O<sub>2</sub>/TeO<sub>2</sub> or 30% H<sub>2</sub>O<sub>2</sub>, respectively. The structures of the synthesized compounds were characterized using FTIR, <sup>1</sup>H-NMR, <sup>13</sup>C-NMR, and high-resolution ESI-MS.
基金supported by the Major State Basic Research Development Program(2015CB856302,2015CB553602)the National Natural Science Foundation of China(31870848,81741110,81802787)the Natural Science Foundation of Shaanxi(2018JZ3005).
文摘Molecular hydrogen is an effective antioxidant.Numerous studies have demonstrated the therapeutic effects of hydrogen in the treatment of various human diseases.The possibility of using hydrogen in the treatment of cancer was first discovered in 1975,and in recent studies,researchers have reported numerous positive effects of hydrogen in cancer therapy,including:1)the alleviation of complications caused by chemotherapy;2)a reduction of complications caused by radiotherapy;3)delays in the progression of cancer;and 4)enhanced efficacy of conventional therapy when used in combination with hydrogen.This article reviews the research progress in the use of hydrogen in the treatment of cancer,and proposes future directions for research in this field.
文摘Off-label use is defined by the prescription of a marketed drug outside the conditions described in the summary of product characteristics.In oncology,off-label prescribing of targeted therapies may occur in patients with other tumor types expressing the same target.Agents associated to phenotypic approaches such as therapies against the tumoral vasculature(anti-angiogenic drugs) and new immunotherapies(checkpoint inhibitors) also carry the potential of alternative indications or combinations.Off-label use of targeted therapies is little documented and appears to be in the same range than that regarding older drugs with wide variations among agents.When compared with older agents,off-label use of targeted therapies is probably more rational through tumoral genotyping but is faced with a limited clinical support,reimbursement challenges related to the very high pricing and the cost of genotyping or molecular profiling,when applicable.
基金This work was supported by the China National Major Project for New Drug Innovation(No.2017ZX09304015).
文摘Even today,lung cancer remains one of the most frequently diagnosed cancers and the leading cause of cancer-related deaths worldwide.Throughout the past decades,remarkable advances have been made in the research and development of anti-lung cancer drugs in China.Since the first registered Chinese clinical trial on May 2,2006,many potent anti-lung cancer drugs have been developed and approved by the China Food and Drug Administration and the National Medical Product Administration of China.Among them,the most advance were observed in the development of targeted agents and immunotherapeutic agents such as epidermal growth factor receptor(EGFR)-tyrosine kinase inhibitors(TKIs)icotinib,aumolertinib,and furmonertinib,anaplastic lymphoma kinase(ALK)-TKI ensartinib,programmed cell death-1(PD-1)monoclonal antibodies(mAbs)camrelizumab,sintilimab,and tislelizumab,and programmed cell death-ligand 1(PD-L1)mAb sugemalimab,which have made huge breakthrough in recent years.Some other investigational innovative drug also demonstrated promising efficacy and acceptable safety profiles.Results from clinical studies on these China innovative drugs have led to changes in clinical practice guidelines and considerably improved the outcomes for patients with lung cancer.Thus,in this review,we aim to provide further insight into the clinical development and achievement of China innovative anti-lung cancer drugs.
