Current Opinion in Molecular Therapeutics最新文献_第6页

Near-infrared-emitting semiconductor quantum dots for tumor imaging and targeting. 用于肿瘤成像和靶向的近红外发射半导体量子点。

Current Opinion in Molecular Therapeutics Pub Date : 2010-06-01

Andrey L Rogach, Manfred Ogris

{"title":"Near-infrared-emitting semiconductor quantum dots for tumor imaging and targeting.","authors":"Andrey L Rogach, Manfred Ogris","doi":"","DOIUrl":"","url":null,"abstract":"Visualizing tumors with the help of near-infrared-emitting probes allows not only in vivo imaging, but also online analysis during surgical resection. Near-infrared-emitting semiconductor quantum dots (QDs) are highly fluorescent nanocrystals that can be modified to meet the needs of tumor-selective probes by variations in size, composition and internal structure (core-only, type I and type II core-shell QDs). The passive accumulation of probes in tumors, as a result of leaky vasculature, can be achieved with systemically injected QDs designed to circulate in the bloodstream and avoid clearance via the kidneys or the reticuloendothelial system. With the help of chemical strategies, QDs are decorated with surface ligands, including antibodies or peptides that bind antigens on tumor cells or tumor endothelium, which further improves the specificity of accumulation within tumors. Encapsulation of QDs into macromolecular structures allows the in vivo tracking of gene and drug carriers in real time. Considerable research has been undertaken to avoid acute and chronic toxicities of QDs by reducing the dose or replacing toxic elements with more biocompatible materials. This review discusses the benefits and potential disadvantages of QDs, and highlights recent advances in the application of these probes for tumor imaging and targeting.","PeriodicalId":50605,"journal":{"name":"Current Opinion in Molecular Therapeutics","volume":"12 3","pages":"331-9"},"PeriodicalIF":0.0,"publicationDate":"2010-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29032040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Do pharmacogenetics, genomics and epigenetics hold promise for molecular therapeutics and health? 药物遗传学、基因组学和表观遗传学对分子治疗和健康有希望吗?

Current Opinion in Molecular Therapeutics Pub Date : 2010-06-01

Lukas A Huber

引用次数: 0

Cationic liposome formulations for RNAi-based validation of therapeutic targets in rheumatoid arthritis. 基于rnai的类风湿性关节炎治疗靶点验证的阳离子脂质体制剂。

Current Opinion in Molecular Therapeutics Pub Date : 2010-06-01

Jessy Presumey, Isabelle Duroux-Richard, Gabriel Courties, Florence Apparailly

{"title":"Cationic liposome formulations for RNAi-based validation of therapeutic targets in rheumatoid arthritis.","authors":"Jessy Presumey, Isabelle Duroux-Richard, Gabriel Courties, Florence Apparailly","doi":"","DOIUrl":"","url":null,"abstract":"Several molecules have been identified as critical mediators of chronic inflammation in immune system-mediated disorders such as rheumatoid arthritis (RA), and biological therapies targeting these molecules have been developed during the past two decades. Compared with conventional therapies, anti-TNF biotherapies have greatly improved the treatment of patients with RA, and several biological agents with distinct mechanisms of action are under development. Despite significant advances in this field, unmet medical needs remain. RA is the prototype disease for the evaluation of targeted therapies, and various novel genes have been described as being critically involved in disease pathogenesis. Thus, a novel area of research has recently emerged in the field of RA therapy, involving the genetic screening and validation of novel candidates in vivo using RNAi. Among the vehicles for the efficient targeting of macrophages, which play a critical role in disease chronicity, cationic liposomes represent the most promising option for the safe and specific use of RNAi in vivo. This review discusses the role of cationic liposomes as a mechanism for the systemic administration of siRNAs in the validation of RA therapeutic targets.","PeriodicalId":50605,"journal":{"name":"Current Opinion in Molecular Therapeutics","volume":"12 3","pages":"325-30"},"PeriodicalIF":0.0,"publicationDate":"2010-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29032039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cancer therapy with bispecific antibodies: Clinical experience. 双特异性抗体治疗癌症:临床经验。

Current Opinion in Molecular Therapeutics Pub Date : 2010-06-01

Archana Thakur, Lawrence G Lum

{"title":"Cancer therapy with bispecific antibodies: Clinical experience.","authors":"Archana Thakur, Lawrence G Lum","doi":"","DOIUrl":"","url":null,"abstract":"The binding of at least two molecular targets simultaneously with a single bispecific antibody is an attractive concept. The use of bispecific antibodies as possible therapeutic agents for cancer treatment was proposed in the mid-1980s. The design and production of bispecific antibodies using antibody- and/or receptor-based platform technology has improved significantly with advances in the knowledge of molecular manipulations, protein engineering techniques, and the expression of antigens and receptors on healthy and malignant cells. The common strategy for making bispecific antibodies involves combining the variable domains of the desired mAbs into a single bispecific structure. Many different formats of bispecific antibodies have been generated within the research field of bispecific immunotherapeutics, including the chemical heteroconjugation of two complete molecules or fragments of mAbs, quadromas, F(ab')2, diabodies, tandem diabodies and single-chain antibodies. This review describes key modifications in the development of bispecific antibodies that can improve their efficacy and stability, and provides a clinical perspective on the application of bispecific antibodies for the treatment of solid and liquid tumors, including the promises and research limitations of this approach.","PeriodicalId":50605,"journal":{"name":"Current Opinion in Molecular Therapeutics","volume":"12 3","pages":"340-9"},"PeriodicalIF":0.0,"publicationDate":"2010-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3785321/pdf/nihms-522763.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29032041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

An emerging role for kinase screening in GPCR drug discovery. 激酶筛选在GPCR药物发现中的新作用。

Current Opinion in Molecular Therapeutics Pub Date : 2010-06-01

Ronald I W Osmond, Michael F Crouch, Vincent J Dupriez

{"title":"An emerging role for kinase screening in GPCR drug discovery.","authors":"Ronald I W Osmond, Michael F Crouch, Vincent J Dupriez","doi":"","DOIUrl":"","url":null,"abstract":"GPCRs are a large class of cell-surface receptors that are involved in a diverse array of biological processes, including many that are critical to diseases. As a result, GPCRs are a major focus for drug discovery research, and have been highly amenable to therapeutic intervention. However, the successes to date may represent the 'low-hanging fruit' (ie, outcomes that have been easiest to achieve). The signaling of many GPCRs is now recognized to be substantially more complex than initially thought. Thus, the traditional analysis of single GPCR-mediated secondary messengers for early-stage drug discovery, such as the measurement of Ca2+ or the formation of cAMP, may not provide all of the relevant signaling information on a target receptor or information on all of the effects of potential drugs. Given this complexity, the determination of other signaling events, such as the GPCR-mediated activation of major kinase pathways, including PI3K and MAPK, is likely to become increasingly important in the identification of indicators of GPCR function. Furthermore, the advent of highly efficient assays for detecting the GPCR-mediated activation of protein kinase targets allows this target class to be readily amenable to cell-based high-throughput screening programs.","PeriodicalId":50605,"journal":{"name":"Current Opinion in Molecular Therapeutics","volume":"12 3","pages":"305-15"},"PeriodicalIF":0.0,"publicationDate":"2010-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29032037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Epigenetic signatures in cancer: Implications for the control of cancer in the clinic. 癌症的表观遗传特征:对临床癌症控制的意义。

Current Opinion in Molecular Therapeutics Pub Date : 2010-06-01

Sheila C S Lima, Hector Hernandez-Vargas, Zdenko Herceg

引用次数: 0

Current progress in pharmacogenetics and individualized immunosuppressive drug dosing in organ transplantation. 器官移植中药物遗传学和个体化免疫抑制药物给药的研究进展。

Current Opinion in Molecular Therapeutics Pub Date : 2010-06-01

Nicholas Ware, Iain A M MacPhee

{"title":"Current progress in pharmacogenetics and individualized immunosuppressive drug dosing in organ transplantation.","authors":"Nicholas Ware, Iain A M MacPhee","doi":"","DOIUrl":"","url":null,"abstract":"The immunosuppressive drugs used in organ transplantation typically have a narrow therapeutic index, with wide variation in the blood concentration achieved from a given dose observed between individuals. This issue has been addressed through the use of therapeutic drug monitoring (TDM), but it may take 5 to 7 days to reach target blood concentrations using this approach. This timeline is not conducive to achieving sufficiently high concentrations in all patients to prevent graft rejection without exposing the patient to excessive toxicity over the critical 2- to 3-day period following transplantation. SNPs in drug-metabolizing enzymes and transporter proteins have been associated with the pharmacokinetic and pharmacodynamic characteristics of immunosuppressive drugs. Data suggest that genetic prediction of the optimal initial drug dose leads to earlier attainment of target blood concentrations compared with using the standard initial dose. The pharmacogenetic strategy that is closest to translation into clinical practice is the use of the cytochrome P450 (CYP)3A5 genotype to predict the optimal initial dose for tacrolimus. Genetic prediction of the optimal dose may be particularly useful for drugs with a long half-life, such as sirolimus, which require several days to achieve a steady state following the implementation of a change in drug dosing, resulting in a long response-time for TDM. The influence of genetic factors on intracellular drug concentrations and the consequences for efficacy and toxicity are an emerging area of research. The SNPs described in this process could be added to existing molecular tissue typing methodology at minimal extra financial expense.","PeriodicalId":50605,"journal":{"name":"Current Opinion in Molecular Therapeutics","volume":"12 3","pages":"270-83"},"PeriodicalIF":0.0,"publicationDate":"2010-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29032688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Trastuzumab emtansine, an antibody-drug conjugate for the treatment of HER2+ metastatic breast cancer. 曲妥珠单抗emtansine，一种用于治疗HER2+转移性乳腺癌的抗体-药物偶联物。

Current Opinion in Molecular Therapeutics Pub Date : 2010-06-01

Ion Niculescu-Duvaz

{"title":"Trastuzumab emtansine, an antibody-drug conjugate for the treatment of HER2+ metastatic breast cancer.","authors":"Ion Niculescu-Duvaz","doi":"","DOIUrl":"","url":null,"abstract":"Roche Holding AG, and its subsidiaries Genentech Inc and Chugai Pharmaceutical Co Ltd, are developing trastuzumab emtansine (trastuzumab-DM1) for the treatment of HER2+ metastatic breast cancer. Trastuzumab emtansine is a tumor-activated prodrug resulting from the conjugation of the humanized anti-HER2 mAb trastuzumab, which has been used in the treatment of breast cancer for over 10 years, with ImmunoGen Inc's cytotoxic and antimitotic maytansine derivative DM1. The maytansinoids bind microtubules in a manner similar to the vinca alkaloids; however, maytansinoids have been recognized to be 20- to 100-fold more potent at blocking mitosis. Nevertheless, the use of these compounds as single agents is limited by toxicity. By conjugating DM1 with trastuzumab, the delivery of the cytotoxic agent to target cells is more specific and reduces the safety concerns. In preclinical studies, the conjugation was effective in breast cancer cell lines resistant to trastuzumab, and demonstrated complete tumor regression in SCID mice bearing KPL4 breast cancer xenografts. Clinically, trastuzumab emtansine exhibited efficacy in patients with HER2+ metastatic breast cancer who had progressed on previous chemotherapy regimens or with trastuzumab therapy. Furthermore, preclinical studies have reported that trastuzumab emtansine potentiates the effect of a number of chemotherapeutic agents (including carboplatin, 5-fluorouracil and docetaxel), other antibodies, receptor tyrosine kinase inhibitors and PI3K inhibitors, and many of these combinations are set to be tested in humans. Trastuzumab emtansine offers an exciting new option for the treatment of patients with refractory, metastatic breast cancer.","PeriodicalId":50605,"journal":{"name":"Current Opinion in Molecular Therapeutics","volume":"12 3","pages":"350-60"},"PeriodicalIF":0.0,"publicationDate":"2010-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29032042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Potential microRNA therapies targeting Ras, NFkappaB and p53 signaling. 潜在的靶向Ras, NFkappaB和p53信号的microRNA疗法。

Current Opinion in Molecular Therapeutics Pub Date : 2010-04-01

Andrea L Kasinski, Frank J Slack

引用次数: 0

NFkappaB decoy oligonucleotides. NFkappaB诱饵寡核苷酸。

Current Opinion in Molecular Therapeutics Pub Date : 2010-04-01

Daniela De Stefano, Giuseppe De Rosa, Rosa Carnuccio

引用次数: 0