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Current Opinion in Molecular Therapeutics最新文献

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Cytochrome P450 enzymes and genotype-guided drug therapy. 细胞色素P450酶与基因型引导药物治疗。
Current Opinion in Molecular Therapeutics Pub Date : 2009-12-01
Mary W Roederer
{"title":"Cytochrome P450 enzymes and genotype-guided drug therapy.","authors":"Mary W Roederer","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The cytochome P450 enzyme system is responsible for the metabolism of xenobiotics, including > 75% of commonly prescribed medications. Many of the cytochrome enzymes exhibit polymorphic genotypes, partly accounting for the variations observed in individual drug responses. Recent advances in the understanding of functional alleles of cytochrome P450 enzymes have changed the use of medications. Improvements in drug efficacy and the prevention of toxicity, as well as improvements in clinical drug dosing, have enhanced pharmacotherapy decisions in medical practice. In addition to personalizing medicine, the identification and quantification of genotypic differences in cytochrome P450 metabolism has the potential to facilitate population-based personalized medicine in countries without the resources to perform genotypic tests at the point of care. This review provides an update on the utility of genotype-guided therapy when treating breast cancer, malaria and coagulation disorders. Also discussed are advancements made in diagnostic tests for cytochrome genotypes and the need for future research in the area of diagnostic tests.</p>","PeriodicalId":50605,"journal":{"name":"Current Opinion in Molecular Therapeutics","volume":"11 6","pages":"632-40"},"PeriodicalIF":0.0,"publicationDate":"2009-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28645776","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
Building the 'practical' human proteome project - the next big thing in basic and clinical proteomics. 建立“实用的”人类蛋白质组计划——基础和临床蛋白质组学的下一个重大事件。
Current Opinion in Molecular Therapeutics Pub Date : 2009-12-01
Mark S Baker
{"title":"Building the 'practical' human proteome project - the next big thing in basic and clinical proteomics.","authors":"Mark S Baker","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":50605,"journal":{"name":"Current Opinion in Molecular Therapeutics","volume":"11 6","pages":"600-2"},"PeriodicalIF":0.0,"publicationDate":"2009-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28649901","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
Novel functions for small RNA molecules. 小RNA分子的新功能。
Current Opinion in Molecular Therapeutics Pub Date : 2009-12-01
Chunxiang Zhang
{"title":"Novel functions for small RNA molecules.","authors":"Chunxiang Zhang","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Small RNAs are short (approximately 18 to 30 nucleotides), non-coding RNA molecules that can regulate gene expression in both the cytoplasm and the nucleus via post-transcriptional gene silencing (PTGS), chromatin-dependent gene silencing (CDGS) or RNA activation (RNAa). Three classes of small RNAs have been defined: microRNAs (miRNAs), siRNAs and Piwi-interacting RNAs (piRNAs). Research has indicated that small RNAs play important roles in cellular processes such as cell differentiation, growth/proliferation, migration, apoptosis/death, metabolism and defense. Accordingly, small RNAs are critical regulators of normal development and physiology. More interestingly, increasing evidence indicates that small RNAs are involved in the pathogenesis of diverse diseases including cancer, cardiovascular disease, stroke, neurodegenerative disease, diabetes, liver disease, kidney disease and infectious disease. More than 20 clinical trials are ongoing to evaluate therapies based on small RNA. Additionally, small RNAs may serve as novel biomarkers and therapeutic targets for the majority of diseases.</p>","PeriodicalId":50605,"journal":{"name":"Current Opinion in Molecular Therapeutics","volume":"11 6","pages":"641-51"},"PeriodicalIF":0.0,"publicationDate":"2009-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3593927/pdf/nihms203150.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28645779","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
Membrane proteomics for leukemia classification and drug target identification. 膜蛋白质组学用于白血病分类和药物靶点鉴定。
Current Opinion in Molecular Therapeutics Pub Date : 2009-12-01
Philippa L Kohnke, Stephen P Mulligan, Richard I Christopherson
{"title":"Membrane proteomics for leukemia classification and drug target identification.","authors":"Philippa L Kohnke,&nbsp;Stephen P Mulligan,&nbsp;Richard I Christopherson","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Knowledge of protein expression in the plasma membrane of leukemia cells has contributed to improvements in the detection and treatment of hematological malignancies. Recently engineered antibodies against leukemia surface molecules have improved therapeutic efficacy compared with earlier agents, but there are still side effects. An increased understanding of the surface expression profiles and interactions of membrane proteins on leukemia cells will facilitate the expansion of the role of antibodies in therapy and enable the identification of novel biomarkers for the various stages of leukemogenesis and leukemia progression. Proteomic analysis enables the identification of thousands of proteins in a membrane extract and provides information on their relative abundance, interactions and post-translational modifications. Plasma membrane proteome analysis of leukemia cells can be used to define biomarkers for diagnosis, classification, prognosis and progression monitoring, as well as to predict therapeutic response or resistance. The effects of chemotherapy on the surface proteome and the functional consequences of perturbations to membrane protein networks can provide insights into leukemia cell signaling and survival mechanisms. Surface proteins that are differentially expressed on leukemia cells are prospective targets for the development of engineered antibodies or small-molecule therapeutics. This review focuses on recent discoveries in leukemia membrane proteomics and the potential for future research into leukemia classification and drug target identification.</p>","PeriodicalId":50605,"journal":{"name":"Current Opinion in Molecular Therapeutics","volume":"11 6","pages":"603-10"},"PeriodicalIF":0.0,"publicationDate":"2009-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28645870","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
MenACWY-CRM, a novel quadrivalent glycoconjugate vaccine against Neisseria meningitidis for the prevention of meningococcal infection. MenACWY-CRM，一种预防脑膜炎球菌感染的新型四价糖结合疫苗。
Current Opinion in Molecular Therapeutics Pub Date : 2009-12-01
David Pace
{"title":"MenACWY-CRM, a novel quadrivalent glycoconjugate vaccine against Neisseria meningitidis for the prevention of meningococcal infection.","authors":"David Pace","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Invasive meningococcal disease remains a major public health concern, with infants, children younger than 4 years and adolescents bearing the majority of the global disease burden. Protecting the vulnerable individuals in these age groups through vaccination remains the most rational strategy for the prevention of meningococcal disease. The formulation of polysaccharide-protein conjugate vaccines has been a major breakthrough in vaccinology, and has extended protection against pathogenic encapsulated bacteria to younger age groups. The dramatic decline in the incidence of Neisseria meningitidis serogroup C disease, observed following the introduction of glycoconjugate meningococcal C vaccines, demonstrates that vaccination can control disease at a population level. The development of quadrivalent glycoconjugate meningococcal ACWY vaccines has broadened protection against meningococcal disease. A novel meningococcal MenACWY-CRM (Menveo) glycoconjugate vaccine, formulated by selective conjugation chemistry of intermediate-chain-length meningococcal saccharides, was immunogenic in individuals aged 2 months to 65 years. The reactogenicity of MenACWY-CRM was similar to that of other licensed meningococcal glycoconjugates, yet the vaccine has the potential to extend protection against meningococcal serogroups A, Y and W-135 to children younger than 2 years of age - a need that remains unmet.</p>","PeriodicalId":50605,"journal":{"name":"Current Opinion in Molecular Therapeutics","volume":"11 6","pages":"692-706"},"PeriodicalIF":0.0,"publicationDate":"2009-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28646270","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
REG-1, a regimen comprising RB-006, a Factor IXa antagonist, and its oligonucleotide active control agent RB-007 for the potential treatment of arterial thrombosis. REG-1，一种包含RB-006(一种因子IXa拮抗剂)及其寡核苷酸活性控制剂RB-007的方案，用于动脉血栓形成的潜在治疗。
Current Opinion in Molecular Therapeutics Pub Date : 2009-12-01
Richard C Becker, Mark Y Chan
{"title":"REG-1, a regimen comprising RB-006, a Factor IXa antagonist, and its oligonucleotide active control agent RB-007 for the potential treatment of arterial thrombosis.","authors":"Richard C Becker,&nbsp;Mark Y Chan","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>REG-1, under development by Regado Biosciences Inc, is an intravenously administered anticoagulant system comprising the Factor IXa-inhibiting aptamer RB-006 and its complementary active control oligonucleotide, RB-007, for the potential treatment of arterial thrombosis. The evolution of anticoagulant therapy for the prevention and acute treatment of thrombotic disorders has progressed at a relatively modest pace considering the scope of the problem and the current understanding of platelet biology, coagulation proteases and vascular science, and their role in protective hemostasis and pathological thrombosis. This drug profile highlights a novel field of anticoagulant therapy referred to as aptamers (derived from the Latin aptus - to fit) and, in particular, the aptamer/active control agent system REG-1, which demonstrated efficacy as an anticoagulant in preclinical studies. In phase I clinical trials in healthy volunteers and patients with stable coronary artery disease, RB-006 inhibited Factor IXa activity, an effect that was titratibly reversible by the application of RB-007. In a phase IIa trial, REG-1 was well tolerated in patients undergoing elective percutaneous coronary intervention, and the treatment was successful with no procedural complications. At the time of publication, an extensive phase IIb trial in patients with acute coronary syndrome undergoing cardiac catheterization was ongoing.</p>","PeriodicalId":50605,"journal":{"name":"Current Opinion in Molecular Therapeutics","volume":"11 6","pages":"707-15"},"PeriodicalIF":0.0,"publicationDate":"2009-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28646271","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
VCL-CB01, an injectable bivalent plasmid DNA vaccine for potential protection against CMV disease and infection. VCL-CB01，一种可注射的二价质粒DNA疫苗，对巨细胞病毒疾病和感染具有潜在的保护作用。
Current Opinion in Molecular Therapeutics Pub Date : 2009-10-01
Mark R Schleiss
{"title":"VCL-CB01, an injectable bivalent plasmid DNA vaccine for potential protection against CMV disease and infection.","authors":"Mark R Schleiss","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Vaccines for the prevention of human CMV (hCMV) infection and disease are a major public health priority. Immunization with DNA vaccines encoding key proteins involved in the immune response to hCMV has emerged as a major focus of hcmv vaccine research. Validation of the protective effect of DNA vaccination in animal models has provided support for clinical trials. VCL-CB01, under development by Vical Inc for the prevention of hCMV infection and disease, is a poloxamer-formulated, bivalent DNA vaccine that contains plasmids encoding hCMV tegument phosphoprotein 65 and the major hCMV surface glycoprotein B. In a phase I trial in healthy adults, VCL-CB01 was well tolerated. In interim results from a phase II trial in hCMV-seropositive hematopoietic cell transplant recipients, VCL-CB01 increased T-cell responses compared with placebo. The final results from the phase II trial will be of value for developing strategies to prevent hCMV disease in hCMV-seropositive transplant recipients, and may lead to other trials of VCL-CB01 or related vaccines for the prevention of congenital hCMV infection.</p>","PeriodicalId":50605,"journal":{"name":"Current Opinion in Molecular Therapeutics","volume":"11 5","pages":"572-8"},"PeriodicalIF":0.0,"publicationDate":"2009-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3539801/pdf/nihms185333.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28417937","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
Adenovirus de-targeting from the liver. 腺病毒从肝脏脱靶。
Current Opinion in Molecular Therapeutics Pub Date : 2009-10-01
Nelson C Di Paolo, Dmitry M Shayakhmetov
{"title":"Adenovirus de-targeting from the liver.","authors":"Nelson C Di Paolo,&nbsp;Dmitry M Shayakhmetov","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Adenovirus (Ad) vectors have substantial potential as biological therapeutics for the treatment of human diseases. Evidence from preclinical studies and clinical trials indicated that several acquired and inherited diseases could be corrected or ameliorated with cell type-specific Ad targeting. One of the major barriers for in vivo Ad targeting is the sequestration of the blood-borne virus in the liver. Significant recent advances have been made in understanding the molecular mechanisms involved in mediating Ad sequestration in the liver. Recognizing the redundancy and synergism between the mechanisms that mediate Ad liver cell transduction and those that mediate the sequestration of blood-borne Ads in the liver creates an opportunity for the development of safe and targeted Ads for gene therapy applications.</p>","PeriodicalId":50605,"journal":{"name":"Current Opinion in Molecular Therapeutics","volume":"11 5","pages":"523-31"},"PeriodicalIF":0.0,"publicationDate":"2009-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28420219","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
M-01ZH09, an oral live attenuated Salmonella enterica serovar Typhi vaccine for the prevention of typhoid fever. M-01ZH09，口服伤寒减毒沙门氏菌血清型伤寒活疫苗，用于预防伤寒。
Current Opinion in Molecular Therapeutics Pub Date : 2009-10-01
S K Jain
{"title":"M-01ZH09, an oral live attenuated Salmonella enterica serovar Typhi vaccine for the prevention of typhoid fever.","authors":"S K Jain","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Typhoid fever remains a major health problem globally, particularly in the developing world. The increased emergence of several multidrug-resistant strains of Salmonella enterica serovar Typhi has made the management of the disease increasingly difficult. Although vaccines against typhoid fever are available, improvements are desired in dosage, immunogenicity and tolerability. Emergent BioSolutions Inc is developing M-01ZH09, a single-dose oral vaccine against typhoid fever based on an attenuated strain of S enterica serovar Typhi. Several clinical trials have been completed for the vaccine, including large phase II trials in the US and Vietnam. Additionally, a phase IIc clinical trial was ongoing in India at the time of publication. The available data suggest that M-01ZH09 is well tolerated in clinical trials, and is highly immunogenic, provoking broad immune responses. Because M-01ZH09 involves administration as a single oral dose, the vaccine has the potential to be used in a mass immunization program.</p>","PeriodicalId":50605,"journal":{"name":"Current Opinion in Molecular Therapeutics","volume":"11 5","pages":"565-71"},"PeriodicalIF":0.0,"publicationDate":"2009-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28420224","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
Albiglutide, an albumin-based fusion of glucagon-like peptide 1 for the potential treatment of type 2 diabetes. Albiglutide，一种以白蛋白为基础的胰高血糖素样肽1融合物，有望治疗2型糖尿病。
Current Opinion in Molecular Therapeutics Pub Date : 2009-10-01
Gerald H Tomkin
{"title":"Albiglutide, an albumin-based fusion of glucagon-like peptide 1 for the potential treatment of type 2 diabetes.","authors":"Gerald H Tomkin","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Albiglutide, under development by GlaxoSmithKline plc for the treatment of type 2 diabetes mellitus (T2DM), is an albumin-fusion peptide. The compound is a mimetic of glucagon-like peptide 1 (GLP-1), a hormone that decreases glucose levels, but has a short half-life because of degradation by dipeptidyl peptidase (DPP)-4. Albiglutide has a longer half-life as a result of its fusion with albumin and its resistance to degradation by DPP-4, caused by an amino acid substitution (Ala to Glu) at the DPP-4-sensitive hydrolysis site. Data from phase II clinical trials in patients with T2DM revealed that albiglutide was well tolerated and that the drug significantly reduced HbA1c levels compared with placebo. At the time of publication, phase III trials assessing albiglutide alone and in combination with other antidiabetic drugs were recruiting patients with T2DM. Albiglutide represents a promising new drug for the treatment of patients with T2DM; the results of long-term trials are awaited with interest.</p>","PeriodicalId":50605,"journal":{"name":"Current Opinion in Molecular Therapeutics","volume":"11 5","pages":"579-88"},"PeriodicalIF":0.0,"publicationDate":"2009-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28417938","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
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