Journal of Pharmacogenomics and Pharmacoproteomics最新文献

{"title":"At the Origin of a Never-ending Story","authors":"Evgeny Krynetskiy","doi":"10.4172/2153-0645.1000E107","DOIUrl":"https://doi.org/10.4172/2153-0645.1000E107","url":null,"abstract":"Pharmacogenetics, and its recent hypostasis Pharmacogenomics, has been in existence as a separate discipline for about five decades. In spite of multiple cases where the pharmacogenetic approaches successfully resolved complex problems of pharmacotherapy, and proved to be beneficial for the patients, we witness its slow integration into medical practice [1]. The basis for Pharmacogenomics is mounted on a solid scientific pedestal, the Human Genome Project. This project brought us an understanding that genetic variability between individual organisms of the same species is a common biological phenomenon, rather than a rare and pitiful deviation from the original plan. Second, we learned that human genome is not stable. Genomic DNA permanently acquires changes and, under certain biological conditions, passes them to the next generations. Therefore, though all 7 billion people on this planet are made up according to the same general blueprint, every single one of us is really unique by multiple parameters including our capacity to acquire, process, and respond to medications.","PeriodicalId":333396,"journal":{"name":"Journal of Pharmacogenomics and Pharmacoproteomics","volume":"183 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2012-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114386835","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}

{"title":"Pharmacogenomics: A Promising Approach Towards Treatment of Autism","authors":"Hansen Wang","doi":"10.4172/2153-0645.1000E110","DOIUrl":"https://doi.org/10.4172/2153-0645.1000E110","url":null,"abstract":"Pharmacogenomics investigates variations in the human genome and the ways in which genetic diversity might influence individual response to drug treatment. Autism is a complex genetic disorder, which awaits a pharmacogenomic approach to better its treatment. This article describes recent developments of genetics and pharmacogenomics in the field of autism, and highlights the prospective of pharmacogenomics in developing novel and more effective therapies, and personalizing treatment strategies for autism.","PeriodicalId":333396,"journal":{"name":"Journal of Pharmacogenomics and Pharmacoproteomics","volume":"109 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2012-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114831144","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}

{"title":"Toward a Personalized ?Fountain of Youth? in Future","authors":"Juan Ding","doi":"10.4172/2153-0645.1000E108","DOIUrl":"https://doi.org/10.4172/2153-0645.1000E108","url":null,"abstract":"Copyright: © 2012 Ding J. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. For thousands of years, humans have been searching for the fountain of youth. Today, we are living an average lifespan of almost 80 years. As more and more people are becoming old, the studies of aging and agerelated diseases are on the rise. Accumulated evidence indicates that it is no longer impossible to expend lifespan and/or delay aging and the onset of age-related diseases. For example, calorie restriction has been shown to increase lifespan in a wide range of organisms including monkeys [1]. Moreover, genes have been discovered to be associated with the regulation of aging, e.g., sirt1, a gene conserved across species, has been found to be an important regulator of longevity in mammals [2]. There are now even drugs that some people believe to be anti-aging, for example, resveratrol, a natural phenol originally extracted from grape skin and has shown anticancer, anti-inflammation, anti-diabetes and beneficial cardiovascular effects in rodent studies. So far the success is seen only in laboratory animals. The question remains whether these regimes and drugs are able to confer increased longevity and healthier aging in humans. And if so, will every individual benefit from them?It is well known that humans have much larger diversity and individuality in their genetic makeup compared to model organisms used in research laboratories. A miracle drug for C57BL6 mice may very well be useless for humans, or at least to some of us. Even well-developed drugs can be metabolized differently with different cytochrome P450 genes hence affecting their efficacies. The study of pharmacogenomics will help to identify personalized medicine. In this regard, will pharmacogenomics help us to learn more about personalized aging and personalized regime/drug to combat aging?","PeriodicalId":333396,"journal":{"name":"Journal of Pharmacogenomics and Pharmacoproteomics","volume":"22 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2012-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"121357472","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}

{"title":"Progresses and Challenges of Omics Studies and Their Impacts in Personalized Medicine","authors":"S. Bencharit","doi":"10.4172/2153-0645.1000E105","DOIUrl":"https://doi.org/10.4172/2153-0645.1000E105","url":null,"abstract":"In the past decade, we have entered the new era of omics studies that may lead to a true clinical application of personalized medicine [1]. The discovery of DNA structure and more recently the completion of the human genome project allow us to define the relationship between one or more particular genes to a disease. Unfortunately, genetic aberrations of multiple genes and their interactions with complex environmental factors are the major causes of several diseases, including diabetes, hypertension and cancer. More importantly, the expression of these disease-related genes, the stability of mRNA and the final protein product can be modified by a wide-range of physiological processes including single-nucleotide polymorphisms (SNPs), alternate splicings, epigenetic modifications, post-translational modifications, etc. While these processes are a pathophysiological result of host-environment interactions, they present a complex challenge in understanding the disease process. Recent omics studies, for instance whole transcriptome analysis, microbiomics, proteomics and metabolomics, provide a new insight to unlimited possibilities of host-disease interactions. Typically we use omics methods to compare diseased populations to a control by studying multiple gene products, modifications of genes/proteins, as well as metabolites. These types of study together with the progression of bioinformatics allow us to see a global picture of how each disease affects its host. Each omics study provides us separation between disease and non-disease by alterations of genes, proteins or metabolites, in terms of gene modifications and expression, or protein modifications, or differential metabolites, etc. This may potentially and theoretically lead to gene targets or potential biomarkers that can be used in the future for therapeutic applications. Epidemiologically, disease can affect populations in a certain way, and certain drugs or interventions may work in reducing mortality and morbidity of certain diseases. However, the progression of omics system biology knowledge together with the emerging personalized medicine, suggest that each treatment or intervention can affect individuals differently [2]. Drugs that effectively cure a condition in one person may not work at all in another individual. This challenge can in theory be understood using current omics tools. While omics studies give us hope to understand individual host-disease interaction, they still have several serious limitations. Technical difficulties, expensive instruments, rare expertise, and others make the use of omics limited. Beside these limitations, the massive amount of data generated from each omics study with often small sample size complicates the data interpretation and restricts the clinical value of omics studies [3]. The majority of omics results are therefore often questioned and rejected by traditional epidemiologists, other clinicians and scholars [3].","PeriodicalId":333396,"journal":{"name":"Journal of Pharmacogenomics and Pharmacoproteomics","volume":"9 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2012-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125551535","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}

{"title":"The Oxygen Paradox","authors":"M. Butnariu","doi":"10.4172/2153-0645.1000E104","DOIUrl":"https://doi.org/10.4172/2153-0645.1000E104","url":null,"abstract":"One of the life’s paradoxes is the fact that the molecule supporting aerobic life-oxygen-is not just essential for the energetic metabolism and for respiration, but almost equally involved in the ethiopatogenesis of numerous diseases and degenerative states due to oxygen-based reactive species called free radicals (FR). Nature has selected and included, in an evolutionary manner, in the composition of living bodies, reactions generating FR with multiple roles: functional, intercellular communicational or destructive, cytolitic, etc. At molecular level the main target of the free radical is the sulphurhydril free or protein groups, while at cellular level the main target are cellular membranes. FR occurs in the body, as the result of endogenous metabolic activity or of the local assimilation of some chemical pollutants at cellular level or at the level of several tissues, simultaneously or gradually. Due to their high reactivity, FR has been found responsible for many noxious effects on the living body. Oxidative stress is defined as an exaggerated production of oxygenated FR, accompanied by a dislocation of antioxidation agents. We cannot live without oxygen, since it is essential in the functioning of energy-producing cells. A body transforms and eliminates oxygen (CO2) properly almost entirely (98%) [1]. Unfortunately, the rest is at the origin of some “hyper-reactive” species called FR (is oxidated derivatives of the electron deficit, unstable oxygen molecule, that cause dysfunctions of all body cells). The volume of oxygen contained by a single inspiration produces a billion FR.","PeriodicalId":333396,"journal":{"name":"Journal of Pharmacogenomics and Pharmacoproteomics","volume":"75 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2012-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"127288768","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}

{"title":"Toxicogenomics Investigation Under the eTOX Project","authors":"O. Taboureau, A. Hersey, Karine Audouze, L. Gautier, Ulrik Plesner Jacobsen, R. Akhtar, Francis Atkinson, John P. Overington, S. Brunak","doi":"10.4172/2153-0645.S7-001","DOIUrl":"https://doi.org/10.4172/2153-0645.S7-001","url":null,"abstract":"Attrition of drug candidates during pre-clinical development due to toxicity, especially hepatotoxicity and nephrotoxicity, is an important and continuing problem in the pharmaceutical industry. The reasons for this trend may be multifactorial and there is a need to improve toxicity testing paradigms within the industry. Microarray technologies have the ability to generate massive amounts of gene expression information as an initial step to decipher the molecular mechanisms of toxicologic changes, i.e. toxicogenomics. In the context of the eTOX consortium, one of public private partnership within the framework of the European Innovative Medicines Inititative (IMI), we will discuss here how the integration and analysis of toxicogenomics data can help to understanding the mechanism of toxicity of a compound and so reduce the risk of late-stage failure in pharmaceutical development.","PeriodicalId":333396,"journal":{"name":"Journal of Pharmacogenomics and Pharmacoproteomics","volume":"311 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2012-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114353152","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}

{"title":"Artemisia afra and Modern Diseases","authors":"G. V. Patil, S. Dass, R. Ch, ra","doi":"10.4172/2153-0645.1000105","DOIUrl":"https://doi.org/10.4172/2153-0645.1000105","url":null,"abstract":"Herb Artemisia afra has recently attracted worldwide attention of researchers for its possible use in the modern diseases like diabetes, cardiovascular diseases, cancer, respiratory diseases etc. This review is exhaustive and systematic organization of the available literature on Artemisia afra (A. afra) from January 1922 to July 2011. The literature survey presents the number of publications with respect to time. Patents are briefly described; the traditional uses are classified and summarized. Some emphasis is given to the data and projections of modern diseases and the ongoing research in this area in the context of title of this review. The pharmacognostic aspects, chemical constituents and factors affecting it, the activity, analysis & quality control, pharmaceutical dosage form etc. is dealt in this review.","PeriodicalId":333396,"journal":{"name":"Journal of Pharmacogenomics and Pharmacoproteomics","volume":"48 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2011-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133393552","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}

{"title":"New Anticoagulants for Thrombo-embolic Disease: Clinical Implications","authors":"A. R. Campbell, Richard McKnight, H. Dedhia","doi":"10.4172/2153-0645.1000104","DOIUrl":"https://doi.org/10.4172/2153-0645.1000104","url":null,"abstract":"The medical community and patients have long awaited new oral anticoagulants, a substitute for warfarin. Finally, 2 drugs have received limited approval and many more are in various developmental stage. Recently, as a result of the RE-LY study, a phase 3 clinical trial, the FDA approved an oral anticoagulant Dabigatran (Pradaxa), a direct thrombin inhibitor, for prevention of stroke in patients with non-valvular atrial fibrillation. A major advantage is that there is no need for frequent monitoring of coagulation or dose adjustment. Results of the RE-LY study (NEJM) showed that dabigatran 150 mg twice a day has decreased incidence of systemic embolization and stroke but similar rates of major hemorrhage when compared to warfarin. This drug can be used in both outpatient and inpatient settings and has already been approved in 75 countries including many European countries. It is being investigated for many clinical conditions, including prevention and treatment of DVT and pulmonary embolism. The European Medicines Agency approved dabigatran in 2008 for the prevention of thrombo-embolic disease and expanded the indication in 2011. Additional oral Xa inhibitors; apixaban, edoxaban, betrixaban are in different stages of development and likely to get approval for different indications in the near future. Although the market for oral anticoagulants is billions of dollars, safety, clinical, and economic issues will influence the acceptance and use of these drugs. The costs of these drugs is likely to be higher than warfarin, however, elimination of frequent coagulation tests will help reduce overall costs. Important limitations for these new classes of drugs, is the absence of simple, easily available, cost effective reversal agents. This article reviews the clinical trials, pharmacokinetics, side effects and potential clinical applications of these new oral thrombin inhibitors.","PeriodicalId":333396,"journal":{"name":"Journal of Pharmacogenomics and Pharmacoproteomics","volume":"10 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2011-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115304042","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}

{"title":"Cancer Research Strategies and Cancer Care","authors":"T. Abaffy","doi":"10.4172/2153-0645.1000E103","DOIUrl":"https://doi.org/10.4172/2153-0645.1000E103","url":null,"abstract":"Imatinib mesylate (Gleevec) is a tyrosine kinase inhibitor currently used for treatment of BCR-ABL (Breakpoint Cluster Region–vabl ABelson murine Leukemia viral oncogene) Tyrosine Kinase (TK) positive leukemia, as well as GastroIntestinal Stromal Tumors (GIST). Imatinib represents one of the rare successful stories in drug development [1]. Imatinib binds to the catalytic site of the kinase and traps it in an inactive conformation. This success was made possible through decades of intensive and collaborative research which led to discovery of the involvement of this protein kinase in tumor pathology. However, this success though impressive, was not immortal. A resistance to the drug developed. Drug resistance is often associated with chronic treatment with anticancer drugs and is likely due to the general genomic instability well documented in cancer. It has been shown that Activation Induced Cytidine Deaminase, AICD, the enzyme that converts cytidine to uridine, causing DNA breaks and hypermutations, also causes mutations in BCR-ABL TK resulting in Imatinib resistance. The recently revealed complexity of polyclonal resistance in patients with imatinib-resistant GIST, suggests that a single next generation drug is unlikely to inhibit all mutant clones in a given patient.","PeriodicalId":333396,"journal":{"name":"Journal of Pharmacogenomics and Pharmacoproteomics","volume":"24 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2011-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132050997","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}

{"title":"BRAF Mutations and their Implications in Molecular Targeting Therapies for Gastrointestinal Cancers","authors":"S. Shimoyama","doi":"10.4172/2153-0645.1000E102","DOIUrl":"https://doi.org/10.4172/2153-0645.1000E102","url":null,"abstract":"The epidermal growth factor receptor (EGFR) has become an important therapeutic target in gastrointestinal cancers, especially in colorectal cancer. Stimulation of the EGFR activates at least five intracellular signal cascades such as RAS/RAF/MEK(mitogen-activated ERK activating kinase)/ERK(extracellular signal-regulated kinase), PI3K (phosphatidylinositol 3-kinase) /PTEN (phosphatase and tensin homolog)/AKT(v-akt murine thymoma viral oncogene homolog), STAT (signal transducer and activator of transcription), pospholipase C, and SRC/FAK(focal adhesion kinase). These either phosphorylate their target proteins in the cytoplasm or transmit signals from growth factor receptor to the nucleus, thereby initiating subsequent expression of genes that regulate cell proliferation, differentiation, angiogenesis, and survival [1] Recently, monoclonal antibodies have been developed to target EGFR and to inhibit subsequent cellular responses. They include anti-EGFR antibodies such as cetuximab (a chimeric monoclonal immunoglobulin G1 antibody), panitumumab (a fully human monoclonal immunoglobulin G2 antibody), and trastuzumab (a monoclonal antibody against human epidermal growth factor receptor-2 (HER2) as well as inhibitors of tyrosine kinase (TK) domain of EGFR or subsequent molecules such as gefitinib, erlotinib (both inhibitors of EGFR-TK), lapatinib (a dual inhibitor of HER2-TK and EGFR-TK), sunitinib (an inhibitor of the TK of various kinds of proteins), and sorafenib (an inhibitor of RAF, a downstream molecular of RAS). Among these, cetuximab, panitumumab, and trastuzumab have received the most intensive focus of research, and their efficacy has been clearly demonstrated -especially in gastric and colorectal cancer. However, it is also a fact that this efficacy is sometimes modest as objective response rates comprise at best 50% by adding trastuzumab to chemotherapy -even among HER-2 positive gastric cancer patients [2], or between 8 and 11% by cetuximab [3,4] or pamitumumab [5,6] monotherapy in colorectal cancer patients. The efficacy is thus presumed to be restricted to a certain segment of patients. Therefore, identification of predictive markers of response and resistance in performing the EGFR targeting therapies is urgently needed to stratify those patients benefiting most from them. This in turn obviate unnecessary or futile treatment and reduce health care costs, ultimately allowing treatment to be individualized.","PeriodicalId":333396,"journal":{"name":"Journal of Pharmacogenomics and Pharmacoproteomics","volume":"219 0 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2011-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124223604","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}