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Antibody-platinum(IV)prodrugs conjugates for targeted treatment of cutaneous squamous cell carcinoma
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作者 Xiangye Yin Yingjie Zhuang +9 位作者 Haiqin Song Yujian Xu Fan Zhang Jianxin Cui Lei Zhao Yingjie Yu Qixu Zhang Jun Ye Youbai Chen Yan Han 《Journal of Pharmaceutical Analysis》 SCIE CAS CSCD 2024年第3期389-400,共12页
Antibody-drug conjugates(ADCs)are a new type of targeting antibodies that conjugate with highly toxic anticancer drugs via chemical linkers to exert high specificity and efficient killing of tumor cells,thereby attrac... Antibody-drug conjugates(ADCs)are a new type of targeting antibodies that conjugate with highly toxic anticancer drugs via chemical linkers to exert high specificity and efficient killing of tumor cells,thereby attracting considerable attention in precise oncology therapy.Cetuximab(Cet)is a typical antibody that offers the benefits of good targeting and safety for individuals with advanced and inoperable cutaneous squamous cell carcinoma(cSCC);however,its anti-tumor activity is limited to a single use.Cisplatin(CisPt)shows good curative effects;however,its adverse effects and non-tumor-targeting ability are major drawbacks.In this study,we designed and developed a new ADC based on a new cytotoxic platinum(IV)prodrug(C8Pt(IV))and Cet.The so-called antibody-platinum(IV)prodrugs conjugates,named Cet-C8Pt(IV),showed excellent tumor targeting in cSCC.Specifically,it accurately delivered C8Pt(IV)into tumor cells to exert the combined anti-tumor effect of Cet and CisPt.Herein,metabolomic analysis showed that Cet-C8Pt(IV)promoted cellular apoptosis and increased DNA damage in cSCC cells by affecting the vitamin B6 metabolic pathway in tumor cells,thereby further enhancing the tumor-killing ability and providing a new strategy for clinical cancer treatment using antibody-platinum(IV)prodrugs conjugates. 展开更多
关键词 antibody drug conjugate Cutaneous squamous cell carcinoma DNA damage Platinum drug Targeted therapy
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Association between glucose-lowering drugs and circulating insulin antibodies induced by insulin therapy in patients with type 2 diabetes
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作者 Peng Zhang Qing Jiang +3 位作者 Bo Ding Reng-Na Yan Yun Hu Jian-Hua Ma 《World Journal of Diabetes》 SCIE 2024年第7期1489-1498,共10页
BACKGROUND Insulin antibodies(IAs)affect blood glucose control in patients receiving insulin therapy.AIM To investigate the relationship between different hypoglycemic treatments and IAs in patients with type 2 diabet... BACKGROUND Insulin antibodies(IAs)affect blood glucose control in patients receiving insulin therapy.AIM To investigate the relationship between different hypoglycemic treatments and IAs in patients with type 2 diabetes mellitus(T2DM).METHODS This cross-sectional,retrospective study included 1863 patients with T2DM who were receiving exogenous insulin therapy.All patients received stable antidiabetic therapy in the last 3 months and IA levels were measured using an iodine-125 array.RESULTS A total of 1863 patients were enrolled.There were 902(48.4%)patients who had positive IAs(IA level>5%),with a mean IA level of 11.06%(10.39%-11.72%).IA levels were positively correlated with high fasting blood glucose(odds ratio=1.069,P<0.001).The proportion of positive IAs was lowest in patients using glargine only(31.9%)and highest in patients using human insulin only(70.3%),P<0.001.The IA levels in patients using sulfonylureas/glinides(8.3%),metformin(9.6%),and dipeptidyl peptidase-4 inhibitors(8.2%)were all lower than in patients without these drugs(all P<0.05).CONCLUSION Nearly half of patients on insulin therapy have positive IA antibodies,and IA antibody levels are associated with blood glucose control.Insulin glargine and a combination of oral glucose-lowering drugs were correlated with lower IA levels. 展开更多
关键词 Insulin antibodies Insulin therapy Glucose-lowering drugs GLARGINE Type 2 diabetes
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Research on Incentive Policies for Chinese Innovative Drug R&D - Taking Innovative Anti-tumor Drugs as an Example
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作者 Wang Yuejun Yang Yue Huang Zhe 《Asian Journal of Social Pharmacy》 2023年第4期303-314,共12页
Objective To provide reference for improving Chinese innovative drug research and development incentive policies.Methods Based on investigating the incentive policies for innovative drug research and development in cl... Objective To provide reference for improving Chinese innovative drug research and development incentive policies.Methods Based on investigating the incentive policies for innovative drug research and development in clinical research,evaluation and approval in China,anti-tumor drugs were taken as the research object to discuss relevant policies from the perspective of clinical trials and registration approval based on data statistics and current situation analysis.Results and Conclusion Driven by a series of incentive policies for innovative drug R&D,great achievements have been made on anti-tumor drugs.However,there are problems such as concentration of drug targets,homogenization of clinical trials,and gaps in some drugs with large clinical needs.To improve incentive policies for innovative drug R&D,China should adhere to the orientation of clinical value,focusing on basic research and translational research,improving evaluation and approval capabilities,and establishing a sound ecosystem for innovative drugs. 展开更多
关键词 innovative drug innovative anti-tumor drug incentive policy policy analysis
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Antibody-Coupled Drugs in HER2-Positive Gastric Cancer
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作者 Baofeng Liu Yuanmei Dai +1 位作者 Xiaohui Shen Xiangyang Tian 《Journal of Biosciences and Medicines》 2023年第7期9-17,共9页
Antibody drug conjugates (ADCs) are a new class of drugs that combine chemosynthetic drugs with antibody drugs through a linker. Antibody drug conjugates combine the targeting characteristics of traditional antibody d... Antibody drug conjugates (ADCs) are a new class of drugs that combine chemosynthetic drugs with antibody drugs through a linker. Antibody drug conjugates combine the targeting characteristics of traditional antibody drugs with the cytotoxic characteristics of small molecule drugs, while reducing the side effects of both drugs, making them a kind of “biological missile” and representing a relatively new and evolving class of anti-cancer drugs. Antibody-coupled drugs are currently used in many solid tumors, and this article reviews the clinical application of antibody-coupled drugs in HER2-positive gastric cancer. 展开更多
关键词 antibody-Coupled drugs HER2-Positive Gastric Cancer REVIEW
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An investigation into the occupational protection status of clinical nursing staff exposed to anti-tumor drugs 被引量:3
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作者 Yuan Yanqin Xu Dezhong 《Journal of Medical Colleges of PLA(China)》 CAS 2012年第2期113-119,共7页
Objective:To investigate the occupational protection status of clinical nursing staff vocationally exposed to anti-tumor drugs.Methods:A self-designed questionnaire was used to survey 180 clinical nursing staff vocati... Objective:To investigate the occupational protection status of clinical nursing staff vocationally exposed to anti-tumor drugs.Methods:A self-designed questionnaire was used to survey 180 clinical nursing staff vocationally exposed to anti-tumor drugs.Results:Recognition of the need for protection and dependent occupational protection behaviors were very poor in clinical nursing staff vocationally exposed to anti-tumor drugs.The management of the occupational protection of clinical nursing staff vocationally exposed to anti-tumor drugs was also seriously underdeveloped.Conclusion:There is deficiency in the understanding and related protection practices of clinical nursing staff vocationally exposed to anti-tumor drugs in our hospital.The protection measures currently employed in medical practice are inadequate in virtually every aspect considered.It is recommended that all clinical nursing staff should receive full occupational protection training in these matters.The training must raise nursing staff's awareness of the need for occupational protection and standardize their occupational protection behaviors to conform to "best practice" models.These "best practice" models should be quickly established and all staff made cognizant of them forthwith.In addition,where occupational protection systems are already in place,they should be improved to come into line with the new "best practice" models instigated. 展开更多
关键词 Nursing staff anti-tumor drug Occupational protection
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Antibody-Drug Conjugates (ADCs): Navigating Four Pillars of Safety, Development, Supply Chain and Manufacturing Excellence
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作者 Kishore Kumar Hotha 《Advances in Chemical Engineering and Science》 2023年第4期351-362,共12页
Antibody-drug conjugates (ADCs) are pioneering biologics that merge antibodies’ specificity with small molecules’ potency. With a handful of FDA-approved ADCs in the market and many under development, ADCs are poise... Antibody-drug conjugates (ADCs) are pioneering biologics that merge antibodies’ specificity with small molecules’ potency. With a handful of FDA-approved ADCs in the market and many under development, ADCs are poised to revolutionize therapeutics. This paper examines the complexities of ADC production, emphasizing the importance of process characterization and the pivotal role of supply chain characteristics, safety requirements, and Contract Manufacturing Organizations (CMOs) with proficiency. The swift transition of antibody-drug conjugate (ADC) programs from early to advanced clinical stages underscores the urgency for quick and efficient commercial launch preparation. This article delves into strategies to hasten commercial readiness, supply chain strategy, the significance of partnering with adept contract development and manufacturing organizations (CDMOs), and the challenges of ADC production. 展开更多
关键词 antibody drug Conjugates ADC’s Payload LINKER antibody HPAPI SAFETY Technology Transfer CDMO CMO
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Anti-PD1 antibody and not anti-LAG-3 antibody improves the antitumor effect of photodynamic therapy for treating metastatic breast cancer
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作者 Shan Long Yibing Zhao +9 位作者 Yuanyuan Xu Bo Wang Haixia Qiu Hongyou Zhao Jing Zeng Defu Chen Hui Li Jiakang Shao Xiaosong Li Ying Gu 《Journal of Innovative Optical Health Sciences》 SCIE EI CSCD 2024年第1期87-103,共17页
Photodynamic therapy(PDT)has limited effects in treating metastatic breast cancer.Immune checkpoints can deplete the function of immune cells;however,the expression of immune checkpoints after PDT is unclear.This stud... Photodynamic therapy(PDT)has limited effects in treating metastatic breast cancer.Immune checkpoints can deplete the function of immune cells;however,the expression of immune checkpoints after PDT is unclear.This study investigates whether the limited e±cacy of PDT is due to upregulated immune checkpoints and tries to combine the PDT and immune checkpoint inhibitor to observe the e±cacy.A metastatic breast cancer model was treated by PDT mediated by hematoporphyrin derivatives(HpD-PDT).The anti-tumor effect of HpD-PDT was observed,as well as CD4þT,CD8þT and calreticulin(CRT)by immunohistochemistry and immunofluorescence.Immune checkpoints on T cells were analyzed byflow cytometry after HpD-PDT.When combining PDT with immune checkpoint inhibitors,the antitumor effect and immune effect were assessed.For HpD-PDT at 100 mW/cm2 and 40,60 and 80 J/cm2,primary tumors were suppressed and CD4þT,CD8þT and CRT were elevated;however,distant tumors couldn't be inhibited and survival could not be prolonged.Immune checkpoints on T cells,especially PD1 and LAG-3 after HpD-PDT,were upregulated,which may explain the reason for the limited HpD-PDT effect.After PDT combined with anti-PD1 antibody,but not with anti-LAG-3 antibody,both the primary and distant tumors were signi-cantly inhibited and the survival time was prolonged,additionally,CD4þT,CD8þT,IFN-þCD4þT and TNF-þCD4þT cells were signi-cantly increased compared with HpD-PDT.HpD-PDT could not combat metastatic breast cancer.PD1 and LAG-3 were upregulated after HpD-PDT.Anti-PD1 antibody,but not anti-LAG-3 antibody,could augment the antitumor effect of HpD-PDT for treating metastatic breast cancer. 展开更多
关键词 Photodynamic therapy anti-PD1 antibody anti-LAG-3 antibody anti-tumor im-mune effects metastatic breast cancer
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Strategies for overcoming anti-tumor necrosis factor drug antibodies in inflammatory bowel disease:Case series and review of literature
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作者 Mansi M Kothari Douglas L Nguyen Nimisha K Parekh 《World Journal of Gastrointestinal Pharmacology and Therapeutics》 CAS 2017年第3期155-161,共7页
Anti-tumor necrosis factor(TNF) biologics are currentlyamongst the most widely used and efficacious therapies for inflammatory bowel disease(IBD). The development of therapeutic drug monitoring for infliximab and ada-... Anti-tumor necrosis factor(TNF) biologics are currentlyamongst the most widely used and efficacious therapies for inflammatory bowel disease(IBD). The development of therapeutic drug monitoring for infliximab and ada-limumab has allowed for measurement of drug levels and antidrug antibodies. This information can allow for manipulation of drug therapy and prediction of response. It has been shown that therapeutic anti-TNF drug levels are associated with maintenance of remission, and development of antidrug antibodies is predictive of loss of response. Studies suggest that a low level of drug antibodies, however, can at times be overcome by dose escalation of anti-TNF therapy or addition of an immunomodulator. We describe a retrospective case series of twelve IBD patients treated at the University of California-Irvine, who were on infliximab or adalimumab therapy and were found to have detectable but low-level antidrug antibodies. These patients underwent dose escalation of the drug or addition of an immunomodulator, with subsequent follow-up drug levels obtained. Eight of the twelve patients(75%) demonstrated resolution of antidrug antibodies, and were noted to have improvement in disease activity. Though data regarding overcoming low-level anti-TNF drug antibodies remains somewhat limited, cases described in the literature as well as our own experience suggest that this may be a viable strategy for preserving the use of an anti-TNF drug. Low-level anti-TNF drug antibodies may be overcome by dose escalation and/or addition of an immunomodulator, and can allow for clinical improvement in disease status. Therapeutic drug monitoring is an important tool to guide this strategy. 展开更多
关键词 Inflammatory bowel disease ADALIMUMAB anti-tumor necrosis factor INFLIXIMAB Therapeutic drug monitoring drug antibody Antidrug antibodies Dose escalation
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The ABC of ADCs (Antibody-Drug Conjugates): A Comprehensive Review of Technical, Regulatory, and Clinical Challenges
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作者 Kishore Kumar Hotha 《Advances in Chemical Engineering and Science》 2023年第4期363-381,共19页
Over the past several decades, there has been a significant surge in the development of Antibody-Drug Conjugates (ADCs). Designing an ideal ADC presents a multifaceted challenge, requiring the precise orchestration of... Over the past several decades, there has been a significant surge in the development of Antibody-Drug Conjugates (ADCs). Designing an ideal ADC presents a multifaceted challenge, requiring the precise orchestration of various elements such as antigens, antibodies, linkers, and payloads. While ADCs aim to target tumor cells specifically, several antigens can also be found in regular tissues, potentially compromising the specificity of ADCs in therapeutic applications. The complexity extends to antibody selection, necessitating effective targeting of the desired antigen and ensuring compatibility with linkers for effective payload delivery. Additionally, the linker and payload combination are critical for the ADC’s therapeutic efficiency, balancing stability in circulation and timely payload release upon target binding. ADC doses must be safe for normal tissues while ensuring the released payloads are effective. The success of ADCs is attributed to their unmatched efficacy compared to traditional chemotherapy agents. The current research article aims to provide a technical review of Antibody-Drug Conjugates (ADCs) for cancer therapies. A brief discussion on the basics of ADCs, regulatory approach, overview, and technical complexities for quantification is presented. This review also summarizes recently approved ADCs and introduces the concepts of antibodies, linkers, and payloads. The article also outlines cancer-specific ADCs currently in late-stage clinical trials for cancer treatment. 展开更多
关键词 antibody-drug Conjugates Cancer Therapy PAYLOAD LINKER Conjugation Chemistry antibody Analytical Development Manufacturing of ADCs
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A living cell-based fluorescent reporter for high-throughput screening of anti-tumor drugs
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作者 Ningning Tang Ling Li +5 位作者 Fei Xie Ying Lu Zifan Zuo Hao Shan Quan Zhang Lianwen Zhang 《Journal of Pharmaceutical Analysis》 SCIE CAS CSCD 2021年第6期808-814,共7页
Suppression of cellular O-linkedβ-N-acetylglucosaminylation(O-Glc NAcylation)can repress proliferation and migration of various cancer cells,which opens a new avenue for cancer therapy.Based on the regulation of insu... Suppression of cellular O-linkedβ-N-acetylglucosaminylation(O-Glc NAcylation)can repress proliferation and migration of various cancer cells,which opens a new avenue for cancer therapy.Based on the regulation of insulin gene transcription,we designed a cell-based fluorescent reporter capable of sensing cellular O-Glc NAcylation in HEK293 T cells.The fluorescent reporter mainly consists of a reporter(green fluorescent protein(GFP)),an internal reference(red fluorescent protein),and an operator(neuronal differentiation 1),which serves as a"sweet switch"to control GFP expression in response to cellular OGlc NAcylation changes.The fluorescent reporter can efficiently sense reduced levels of cellular OGlc NAcylation in several cell lines.Using the fluorescent reporter,we screened 120 natural products and obtained one compound,sesamin,which could markedly inhibit protein O-Glc NAcylation in He La and human colorectal carcinoma-116 cells and repress their migration in vitro.Altogether,the present study demonstrated the development of a novel strategy for anti-tumor drug screening,as well as for conducting gene transcription studies. 展开更多
关键词 Fluorescent reporter High-throughput screening O-linkedβ-N-acetylglucosaminylation anti-tumor drug Gene transcriptional regulation
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Research Progress on Dimension and Indicators of Comprehensive Value Assessment of Anti-Tumor Drugs
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作者 Jia Hanxue Zhang Fang 《Asian Journal of Social Pharmacy》 2021年第4期343-351,共9页
Objective To sort out the dimension and indicators of comprehensive value assessment of anti-tumor drugs abroad,and provide a reference for constructing a similar system in China.Methods The keywords such as anti-tumo... Objective To sort out the dimension and indicators of comprehensive value assessment of anti-tumor drugs abroad,and provide a reference for constructing a similar system in China.Methods The keywords such as anti-tumor drugs,value,assessment,method,and framework were used to search CNKI,WanFang database,VIP database,Embase,PubMed and Web of Science.Results and Conclusion According to the research on the value framework of anti-tumor drugs,6 first-level dimensions and 8 second-level indicators with common characteristics were summarized.In view of China’s national conditions,this study summarizes the available value judgment dimensions of anti-tumor drugs at home and abroad,so as to learn from international experience and their mature methodologies,and provide ideas for constructing a multi-dimensional value system of anti-tumor drugs in China. 展开更多
关键词 value anti-tumor drug multi-criteria decision analysis evidence-based decision making DIMENSION index
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Current status of novel biologics and small molecule drugs in the individualized treatment of inflammatory bowel disease 被引量:2
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作者 Yi-Han Xu Wei-Ming Zhu Zhen Guo 《World Journal of Gastroenterology》 SCIE CAS 2022年第48期6888-6899,共12页
Treatment strategies for inflammatory bowel disease(IBD)are rapidly evolving with the development of biologics and small molecule drugs(SMDs).However,these drugs are not guaranteed to be effective in all patients,and ... Treatment strategies for inflammatory bowel disease(IBD)are rapidly evolving with the development of biologics and small molecule drugs(SMDs).However,these drugs are not guaranteed to be effective in all patients,and a“ceiling effect”of biologic monotherapy may occur.This issue highlights an unmet need for optimizing the use of biologics and predicting therapeutic responses.Thus,the development of new drugs with novel mechanisms of action is urgently needed for patients with primary nonresponse and secondary loss of response to conventional biologics and SMDs.In addition,combining different biologics or SMDs has been proposed as a novel strategy to enhance treatment efficacy in IBD,which theoretically has multidimensional anti-inflammatory potential.Based on the current evidence available for IBD,dual targeted therapy may be a promising strategy for refractory IBD patients who have failed in multiple biologic treatments or who have extraintestinal manifestation.Additionally,identifying the subgroup of IBD patients who are responding to biological combination therapies is also equally important in stable disease remission.In this review,we summarize the newly developed biologics and SMDs and the current status of biologics/SMDs to highlight the development of individualized treatment in IBD. 展开更多
关键词 Inflammatory bowel diseases BIOLOGIC Dual targeted therapy Therapeutic drug monitoring Bispecific antibodies
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Excellent effects and possible mechanisms of action of a new antibody–drug conjugate against EGFR-positive triple-negative breast cancer 被引量:2
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作者 Dan-Dan Zhou Wei-Qi Bai +4 位作者 Xiao-Tian Zhai Li-Ping Sun Yong-Su Zhen Zhuo-Rong Li Qing-Fang Miao 《Military Medical Research》 SCIE CAS CSCD 2022年第4期419-431,共13页
Background:Triple-negative breast cancer(TNBC)is the most aggressive subtype and occurs in approximately 15%–20%of diagnosed breast cancers.TNBC is characterized by its highly metastatic and recurrent features,as wel... Background:Triple-negative breast cancer(TNBC)is the most aggressive subtype and occurs in approximately 15%–20%of diagnosed breast cancers.TNBC is characterized by its highly metastatic and recurrent features,as well as a lack of specific targets and targeted therapeutics.Epidermal growth factor receptor(EGFR)is highly expressed in a variety of tumors,especially in TNBC.LR004-VC-MMAE is a new EGFR-targeting antibody–drug conjugate produced by our laboratory.This study aimed to evaluate its antitumor activities against EGFR-positive TNBC and further studied its possible mechanism of antitumor action.Methods:LR004-VC-MMAE was prepared by coupling a cytotoxic payload(MMAE)to an anti-EGFR antibody(LR004)via a linker,and the drug-to-antibody ratio(DAR)was analyzed by HIC-HPLC.The gene expression of EGFR in a series of breast cancer cell lines was assessed using a publicly available microarray dataset(GSE41313)and Western blotting.MDA-MB-468 and MDA-MB-231 cells were treated with LR004-VC-MMAE(0,0.0066,0.066,0.66,6.6 nmol/L),and the inhibitory effects of LR004-VC-MMAE on cell proliferation were examined by CCK-8 and colony formation.The migration and invasion capacity of MDA-MB-468 and MDA-MB-231 cells were tested at different LR004-VCMMAE concentrations(2.5 and 5 nmol/L)with wound healing and Transwell invasion assays.Flow cytometric analysis and tumorsphere-forming assays were used to detect the killing effects of LR004-VC-MMAE on cancer stem cells(MDA-MB-468 and MDA-MB-231 cells).The mouse xenograft models were also used to evaluate the antitumor efficacy of LR004-VC-MMAE in vivo.Briefly,BALB/c nude mice were subcutaneously inoculated with MDA-MB-468 or MDAMB-231 cells.Then they were randomly divided into 4 groups(n=6 per group)and treated with PBS,naked LR004(10 mg/kg),LR004-VC-MMAE(10 mg/kg),or doxorubicin,respectively.Tumor sizes and the body weights of mice were measured every 4 d.The effects of LR004-VC-MMAE on apoptosis and cell cycle distribution were analyzed by flow cytometry.Western blotting was used to detect the effects of LR004-VC-MMAE on EGFR,ERK,MEK phosphorylation and tumor stemness marker gene expression.Results:LR004-VC-MMAE with a DAR of 4.02 were obtained.The expression of EGFR was found to be significantly higher in TNBC cells compared with non-TNBC cells(P<0.01).LR004-VC-MMAE inhibited the proliferation of EGFRpositive TNBC cells,and the ICvalues of MDA-MB-468 and MDA-MB-231 cells treated with LR004-VC-MMAE for 72 h were(0.13±0.02)nmol/L and(0.66±0.06)nmol/L,respectively,which were significantly lower than that of cells treated with MMAE[(3.20±0.60)nmol/L,P<0.01,and(6.60±0.50)nmol/L,P<0.001].LR004-VC-MMAE effectively inhibited migration and invasion of MDA-MB-468 and MDA-MB-231 cells.Moreover,LR004-VC-MMAE also killed tumor stem cells in EGFR-positive TNBC cells and impaired their tumorsphere-forming ability.In TNBC xenograft models,LR004-VC-MMAE at 10 mg/kg significantly suppressed tumor growth and achieved complete tumor regression on day 36.Surprisingly,tumor recurrence was not observed until the end of the experiment on day 52.In a mechanistic study,we found that LR004-VC-MMAE significantly induced cell apoptosis and cell cycle arrest at G/M phase in MDAMB-468[(34±5)%vs.(12±2)%,P<0.001]and MDA-MB-231[(27±4)%vs.(18±3)%,P<0.01]cells.LR004-VC-MMAE also inhibited the activation of EGFR signaling and the expression of cancer stemness marker genes such as Oct4,Sox2,KLF4 and EpCAM.Conclusions:LR004-VC-MMAE showed effective antitumor activity by inhibiting the activation of EGFR signaling and the expression of cancer stemness marker genes.It might be a promising therapeutic candidate and provides a potential therapeutic avenue for the treatment of EGFR-positive TNBC. 展开更多
关键词 Triple-negative breast cancer Epidermal growth factor receptor antibodydrug conjugate Targeted therapy Antitumor effect
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Overview of Research and Development for Anticancer Drugs 被引量:1
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作者 Junjie Xu Wenwei Mao 《Journal of Cancer Therapy》 2016年第10期762-772,共12页
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
关键词 Anticancer drugs Research and Development Target Therapy Phenotype Targeting anti-tumor Immunity
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Chronic hepatitis B:New potential therapeutic drugs target 被引量:5
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作者 Wattana Leowattana Tawithep Leowattana 《World Journal of Virology》 2022年第1期57-72,共16页
liverrelated morbidity and mortality worldwide.It impacts nearly 300 million people.The current treatment for chronic infection with the hepatitis B virus(HBV)is complex and lacks a durable treatment response,especial... liverrelated morbidity and mortality worldwide.It impacts nearly 300 million people.The current treatment for chronic infection with the hepatitis B virus(HBV)is complex and lacks a durable treatment response,especially hepatitis B surface antigen(HBsAg)loss,necessitating indefinite treatment in most CHB patients due to the persistence of HBV covalently closed circular DNA(cccDNA).New drugs that target distinct steps of the HBV life cycle have been investigated,which comprise inhibiting the entry of HBV into hepatocytes,disrupting or silencing HBV cccDNA,modulating nucleocapsid assembly,interfering HBV transcription,and inhibiting HBsAg release.The achievement of a functional cure or sustained HBsAg loss in CHB patients represents the following approach towards HBV eradication.This review will explore the up-to-date advances in the development of new direct-acting anti-HBV drugs.Hopefully,with the combination of the current antiviral drugs and the newly developed direct-acting antiviral drugs targeting the different steps of the HBV life cycle,the ultimate eradication of CHB infection will soon be achieved. 展开更多
关键词 Chronic hepatitis B Hepatitis B surface antigen Hepatitis B surface antibody Covalently closed circular DNA Direct acting antiviral drugs Functional cure Entry block Nucleocapsid assembly modulator Interfering hepatitis B virus transcription Inhibiting hepatitis B surface antigen release
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Cell Surface Transmembrane Protein Database for Detecting Potential Targets of Antibody Drug in Application of Cancer Therapies
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作者 Po-Yuan Chen Cheng-Shang Kao +5 位作者 Mien-De Jhuo Tzu-Hurng Cheng Wei-Tse Hsu Che-Yen Ou Tzu-Ching Shih Chieh-Hsi Wu 《Journal of Life Sciences》 2010年第7期46-52,共7页
Background: Antibody drug conjugated (ADC) is one kind of very important method of therapy to cancer diseases. In this research, the authors introduce BLAST and some other important algorithms to create transmembra... Background: Antibody drug conjugated (ADC) is one kind of very important method of therapy to cancer diseases. In this research, the authors introduce BLAST and some other important algorithms to create transmembrane protein databases. These databases are acquired from well-known databases such as NCBI or Swiss-Prot as template, and then collect all possible transmembrane protein by using BLAST or physical character. After collect these databases, the authors will aim at each nucleotide sequences to design the probes of oligonucleotide microarray, which can detect the high express transmembrane proteins very efficiently. Finally, the authors can accelerate the anti-cancer drug discovery by using these databases. Result: This study constructed a web service, the Transmembrane Protein Database, to researchers that are interested in or need to oligonucleotide microarray probe design for detecting potential targets of antibody drug. With user friendly web based windows containing each necessary selections, users can easily choose the parameters and get the suitable probe design suggestions. Conclusion: Transmembrane protein database is very important and powerful in detecting cancers or other human disease. By using this database, the authors offer a good strategy in transmembrane protein research as well. 展开更多
关键词 antibody drug transmembrane protein databases.
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Internalization of immunotargeting drugs against hepatoma
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作者 隋延枋 孙志伟 +1 位作者 陈志南 刘彦仿 《Journal of Medical Colleges of PLA(China)》 CAS 1997年第3期177-180,共4页
To study the internalization of immunotargeting drugs for hepatocellular carcinoma. Methods: By using colloidal gold technique, the processes of internalization of the immunotargeting drugs, HAb18 and HAb25, against h... To study the internalization of immunotargeting drugs for hepatocellular carcinoma. Methods: By using colloidal gold technique, the processes of internalization of the immunotargeting drugs, HAb18 and HAb25, against hepatoma in the targeting cells of human hepatoma cell line SMMC-7721 were observed separatelly ctively under an electron microscope. Results: 80% of the target cells were conjugated with gold-labeled particles on the cellular surfaces. The internalization of gold-labeled particles were present in all of the target cells conjugated with gold-labeled particles, while no internalization of gold-labeled particles could be seen in the target cells not conjugated with gold-labeled particles. The chief way of internalization was invariably through a non-coated microinvagination. After entering the cells. all of the gold-labled particles were first localized in the primary endocytic vacuoles, and then transferred intracellularly. Simultaneously, the vacuole-vacuole fusion occurred forming the larger multi-vesicular bodies, the endosome. In the Golgi region, the endosome fused with the Golgic vacuoles, and finally located in the secondary lysosomes. 18h after the intercellular internalization of the immunotargeting drugs, the cytoplasmic vacuolization, and sometimes even cellular necrosis, could be noticed. The control cells grew well. Conclusion: After entering the targeting cells, the immunotargeting drugs would degrade within the lysosomes. And when ADM arrives at its function site it would play the role of cell toxicity intranuclearly.Therefore, internalization of HAb18-ADM and HAb25-ADM might have a good prospect in clinical application. 展开更多
关键词 HEPATOMA drug-antibody CONJUGATE microscopy electron
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Analysis of Detecting HIV-1 Antibody in Paired Urine and Serum Specimens from Drug Users by ELISA
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作者 刘中夫 李志军 +3 位作者 刘世亮 李莉 梁富雄 郑锡文 《Chinese Journal of Sexually Transmitted Infections》 2001年第2期27-28,共2页
Objective- To compare the consistency of the results from detecting HIV-1 antibody in the paired urine and serum specimens from drug users by ELISA. Methods: The paired urine and serum specimens from 273 drug users de... Objective- To compare the consistency of the results from detecting HIV-1 antibody in the paired urine and serum specimens from drug users by ELISA. Methods: The paired urine and serum specimens from 273 drug users detained at a detoxification unit were collected, and the HIV-1 antibodies in the specimens of them were screened by urine and serum ELISA kits, respectively. Results: Of 273 serum specimens, 94 ones showed positive reaction and among 94 counterpart urine specimens, 93 ones also appeared positive reaction. Taking the results together,the consistent rate of HIV-1 antibody screened by urine and serum ELISA kits was 99.6%. Conclusion: The urine ELISA kit, which screened HIV-1 antibody of urine showing almost the same results tested by serum ELISA kit, is reliable. It is proposed that urine ELISA be introduced in many fields. 展开更多
关键词 AIDS drug user Urine specimens Serum specimens HIV-1 antibody
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药源性血小板减少症的发生机制及诊断 被引量:1
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作者 聂晓璐 马静瑶 +1 位作者 孙凤 詹思延 《中国药物警戒》 2024年第7期829-835,共7页
药源性血小板减少症(drug-induced thrombocytopenia,DITP)是临床最常见的一种继发性血小板减少症。根据血小板减少症的发病机制可分为2大类:非免疫介导和药源性免疫性血小板减少症(drug-induced immune thrombocytopenia,DIIT)。后者... 药源性血小板减少症(drug-induced thrombocytopenia,DITP)是临床最常见的一种继发性血小板减少症。根据血小板减少症的发病机制可分为2大类:非免疫介导和药源性免疫性血小板减少症(drug-induced immune thrombocytopenia,DIIT)。后者进一步根据不同的免疫介导作用机制划分为4类。除经典途径由药物依赖性血小板抗体(drug-dependent platelet-reactive antibodies,DDAbs)与血小板结合引起的DIIT、肝素诱导的血小板减少(heparin-induced thrombocytopenia,HIT)、免疫抑制剂诱导的血小板减少(immune checkpoint inhibitors-induced thrombocytopenia,ICI-ITP)以外,随着新型冠状病毒感染(COVID-19)后开展广泛疫苗研发及接种,新近出现的疫苗诱导的血栓性血小板减少(vaccine-induced thrombotic thrombocytopenia,VITT)也属于DITP范畴。本研究结合近年发表的相关文献,全面综述上述各类型DITP的发生机制特点及诊断,梳理DITP相关数据库,并提出未来研究展望。 展开更多
关键词 药源性血小板减少症 免疫性 半抗原 药物依赖性 肝素 疫苗 诱导 药品不良反应
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2024年欧洲肿瘤内科学会乳腺癌年会研究进展
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作者 吕文杰 吴萍 《中国肿瘤临床》 CAS CSCD 北大核心 2024年第11期572-579,共8页
2024年5月举行的欧洲肿瘤内科学会乳腺癌年会(European Society for Medical Oncology Breast Cance,ESMO BC)在德国柏林召开。本次年会展示了一系列针对乳腺癌治疗的最新进展,包括创新疗法和诊治策略。特别值得关注的是,细胞周期蛋白... 2024年5月举行的欧洲肿瘤内科学会乳腺癌年会(European Society for Medical Oncology Breast Cance,ESMO BC)在德国柏林召开。本次年会展示了一系列针对乳腺癌治疗的最新进展,包括创新疗法和诊治策略。特别值得关注的是,细胞周期蛋白依赖性激酶4和6(cyclin-dependent kinases 4 and 6,CDK4/6)抑制剂联合内分泌治疗(endocrine therapy,ET)在早期乳腺癌新辅助治疗中的研究尚未达到主要终点,而探索性分析结果表明,该领域仍有待进一步研究。CDK4/6抑制剂联合ET继续作为高危患者辅助治疗的标准。同时,阿贝西利在携带BRCA1/2突变的患者亚组中显示出初步的一致性获益。瑞波西利虽然不良反应可控,但仍需进行密切监测。新型CDK4选择性抑制剂、AKT抑制剂、抗体药物偶联物(antibody-drug conjugates,ADC)以及免疫治疗为晚期乳腺癌患者提供了新的治疗选项。本次年会所展现的研究成果,不仅代表了乳腺癌治疗领域的进步,也为未来的研究方向和患者治疗策略提供了新的视野。本文就此次年会上重点的研究进展进行综述。 展开更多
关键词 乳腺癌 研究进展 免疫治疗 CDK4/6抑制剂 抗体药物偶联物
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