169 results match your criteria Am J Pharmacogenomics[Journal]


Oncogenes as novel targets for cancer therapy (part IV): regulators of the cell cycle and apoptosis.

Am J Pharmacogenomics 2005 ;5(6):397-407

Division of Clinical Pharmacology, Department of Pharmacology and Toxicology, University of Alabama, Birmingham, Alabama 35294-0019, USA.

This is the final part of a four-part serial review on oncogenes and their potential use as targets for cancer therapy. Previous sections discussed various categories of oncogenes (growth factors, tyrosine kinases, intermediate signaling molecules, and transcription factors) and the advances made in various strategies being used to alter their actions. This part describes four oncogenes, MDM2, BCL2, XIAP, and Survivin, that are involved in regulation of the cell cycle and apoptosis. Read More

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February 2006

Using bioinformatics for drug target identification from the genome.

Am J Pharmacogenomics 2005 ;5(6):387-96

Hubei Bioinformatics and Molecular Imaging Key Laboratory, School of Computer Science, Huazhong University of Science and Technology, Wuhan, China.

Genomics and proteomics technologies have created a paradigm shift in the drug discovery process, with bioinformatics having a key role in the exploitation of genomic, transcriptomic, and proteomic data to gain insights into the molecular mechanisms that underlie disease and to identify potential drug targets. We discuss the current state of the art for some of the bioinformatic approaches to identifying drug targets, including identifying new members of successful target classes and their functions, predicting disease relevant genes, and constructing gene networks and protein interaction networks. In addition, we introduce drug target discovery using the strategy of systems biology, and discuss some of the data resources for the identification of drug targets. Read More

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February 2006
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Antimycotic drug discovery in the age of genomics.

Am J Pharmacogenomics 2005 ;5(6):365-86

Department of Pharmacy Practice & Medicine, University of Mississippi, Jackson, Mississippi 39216, USA.

Genomic-based methodologies are increasingly used at all stages of drug development. The most extensive applications have occurred in early drug discovery stages due to advances in technologies that allow for automated synthesis and characterization of organic compounds, and for high-throughput screening of these molecules against known drug targets. The adaptation of genomic-based methodologies in later stages of drug development presents a more difficult task. Read More

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February 2006
2 Reads

Cancer diagnostics: decision criteria for marker utilization in the clinic.

Am J Pharmacogenomics 2005 ;5(6):357-64

Cancer Diagnosis Program, Division of Cancer Treatment & Diagnosis, National Cancer Institute, Rockville, Maryland 20952, USA.

A new diagnostic tool must pass three major tests before it is adopted for routine clinical use. First, the tool must be robust and reproducible; second, the clinical value of the tool must be proven, i.e. Read More

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February 2006
1 Read

The Personalized Medicine Coalition: goals and strategies.

Am J Pharmacogenomics 2005 ;5(6):345-55

Personalized Medicine Coalition, Washington, DC 20005, USA.

The concept of personalized medicine--that medical care can be tailored to the genomic and molecular profile of the individual--has repercussions that extend far beyond the technology that makes it possible. The adoption of personalized medicine will require changes in healthcare infrastructure, diagnostics and therapeutics business models, reimbursement policy from government and private payers, and a different approach to regulatory oversight. Personalized medicine will shift medical practices upstream from the reactive treatment of disease, to proactive healthcare management including screening, early treatment, and prevention, and will alter the roles of both physician and patient. Read More

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February 2006
8 Reads

Expectations from structural genomics revisited: an analysis of structural genomics targets.

Am J Pharmacogenomics 2005 ;5(5):339-42

Queen Mary's School of Medicine and Dentistry, Institute of Cell and Molecular Sciences, Barts and The London, Queen Mary, University of London, London, England.

Background: Current structural genomics projects are being driven by two main goals; to produce a representative set of protein folds that could be used as templates for comparative modeling purposes, and to provide insight into the function of the currently unannotated protein sequences. Such projects may reveal that a newly determined protein structure shares structural similarity with a previously observed structure or that it is a novel fold. The manner in which structure can be used to suggest the function of a protein will depend on the number and diversity of homologous sequences and the extent to which these sequences are functionally characterized. Read More

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December 2005

Oncogenes as novel targets for cancer therapy (part III): transcription factors.

Am J Pharmacogenomics 2005 ;5(5):327-38

Department of Pharmacology and Toxicology and Division of Clinical Pharmacology, University of Alabama at Birmingham, Birmingham, Alabama 35294-0019, USA.

This is the third paper in a four-part serial review on potential therapeutic targeting of oncogenes. The previous parts described the involvement of oncogenes in different aspects of cancer growth and development, and considered the new technologies responsible for the advancement of oncogene identification, target validation, and drug design. Because of such advances, new specific and more efficient therapeutic agents can be developed for cancer. Read More

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December 2005
1 Read

Clinical trial designs for prospective validation of biomarkers.

Am J Pharmacogenomics 2005 ;5(5):317-25

Division of Biostatistics, Mayo Clinic, Rochester, Minnesota, USA.

Traditionally, anatomic staging systems have been used to determine predictions of individual patient outcome and, to a lesser extent, guide the choice of treatment in patients with cancer. With new targeted therapies, the role of biomarkers is increasingly promising, suggesting an integrated approach using the genetic make-up of the tumor and the genotype of the patient for treatment selection and patient management. Specifically, biomarkers can aid in patient stratification (risk assessment), treatment response identification (surrogate markers), or in differential diagnosis (identifying individuals who are likely to respond to specific drugs). Read More

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December 2005

Pharmacodiagnostic testing in breast cancer: focus on HER2 and trastuzumab therapy.

Am J Pharmacogenomics 2005 ;5(5):303-15

Section of Surgical and Translational Research, Division of Cancer, Department of Surgery, Sciences and Molecular Pathology, Endocrine Cancer Group, Glasgow Royal Infirmary, University of Glasgow, Glasgow, Scotland.

Pharmacogenomics is defined as research into inherited genetic variations that determine an individual's response to therapeutic agents. In oncology, pharmacogenomics based on somatic molecular alterations inherited by subsequent cancer cell generations forms the basis of molecular targeting of novel therapeutic agents. What has emerged from clinical experience with such agents is the need for appropriate pharmacodiagnostic approaches to ensure the drugs are correctly targeted. Read More

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December 2005

Detection of resistance to imatinib by metabolic profiling: clinical and drug development implications.

Am J Pharmacogenomics 2005 ;5(5):293-302

Department of Anesthesiology, Biomedical MRS/MRI Cancer Core, University of Colorado Health Sciences Center, Denver, Colorado, USA.

Acquired resistance to imatinib mesylate is an increasing and continued challenge in the treatment of BCR-ABL tyrosine kinase positive leukemias as well as gastrointestinal stromal tumors. Stable isotope-based dynamic metabolic profiling (SIDMAP) studies conducted in parallel with the development and clinical testing of imatinib revealed that this targeted drug is most effective in controlling glucose transport, direct glucose oxidation for RNA ribose synthesis in the pentose cycle, as well as de novo long-chain fatty acid synthesis. Thus imatinib deprives transformed cells of the key substrate of macromolecule synthesis, malignant cell proliferation, and growth. Read More

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December 2005
3 Reads

Proteomic cancer classification with mass spectrometry data.

Am J Pharmacogenomics 2005 ;5(5):281-92

BioInformatics Research Centre, School of Computer Engineering, Nanyang Technological University, Singapore.

The ultimate goal of cancer proteomics is to adapt proteomic technologies for routine use in clinical laboratories for the purpose of diagnostic and prognostic classification of disease states, as well as in evaluating drug toxicity and efficacy. Analysis of tumor-specific proteomic profiles may also allow better understanding of tumor development and the identification of novel targets for cancer therapy. The biological variability among patient samples as well as the huge dynamic range of biomarker concentrations are currently the main challenges facing efforts to deduce diagnostic patterns that are unique to specific disease states. Read More

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December 2005
1 Read

Inter-gene correlation on oligonucleotide arrays: how much does normalization matter?

Am J Pharmacogenomics 2005 ;5(4):271-9

Department of Biostatistics and Applied Mathematics, M.D. Anderson Cancer Center, The University of Texas, Houston, Texas 77030-4009, USA.

Background And Objective: Normalization is a standard low-level preprocessing procedure in microarray data analysis to minimize the systematic technological variations and produce more reliable results. A variety of normalization approaches have been introduced and are widely applied. Normalization, however, remains controversial. Read More

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October 2005

The proteomics of neurodegeneration.

Am J Pharmacogenomics 2005 ;5(4):259-70

Department of Neurological Surgery, University of Washington School of Medicine, Seattle, Washington 98195-6470, USA.

The continuing improvement and refinement of proteomic and bioinformatic tools has made it possible to obtain increasing amounts of structural and functional information about proteins on a global scale. The emerging field of neuroproteomics promises to provide powerful strategies for further characterizing neuronal dysfunction and cell loss associated with neurodegenerative diseases. Neuroproteomic studies have thus far revealed relatively comprehensive quantitative changes and post-translational modifications (mostly oxidative damage) of high abundance proteins, confirming deficits in energy production, protein degradation, antioxidant protein function, and cytoskeletal regulation associated with neurodegenerative diseases such as Alzheimer and Parkinson disease. Read More

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October 2005
5 Reads

Oncogenes as novel targets for cancer therapy (part II): Intermediate signaling molecules.

Am J Pharmacogenomics 2005 ;5(4):247-57

Department of Pharmacology and Toxicology and Division of Clinical Pharmacology, Birmingham, Alabama 35294-0019, USA.

This is the second part of a four-part review on potential therapeutic targeting of oncogenes. The previous part introduced the new technologies responsible for the advancement of oncogene identification, target validation, and drug design. Because of such advances, new specific and more efficient therapeutic agents can be developed for cancer. Read More

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October 2005
2 Reads

The Autism Genome Project: goals and strategies.

Am J Pharmacogenomics 2005 ;5(4):233-46

Neurogenomics Division, Translational Genomics Research Institute, Phoenix, Arizona 85004, USA.

Autism is a complex neurodevelopmental disorder with a broad spectrum of symptoms and varying severity. Currently, no biological diagnosis exists. Although there has been a significant increase in autism genetics research recently, validated susceptibility genes for the most common, sporadic forms of autistic disorder, as well as familial autism, have yet to be identified. Read More

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October 2005
4 Reads

Identifying DNA methylation biomarkers of cancer drug response.

Am J Pharmacogenomics 2005 ;5(4):223-32

Epigenomics AG, Berlin, Germany.

In the last few years, DNA methylation has become one of the most studied gene regulation mechanisms in carcinogenesis as a result of the cumulative evidence produced by the scientific community. Moreover, advances in the technologies that allow detection of DNA methylation in a variety of analytes have opened the possibility of developing methylation-based tests. A number of studies have provided evidence that specific methylation changes can alter the response to different therapeutic agents in cancer and, therefore, be useful biomarkers. Read More

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October 2005
3 Reads

Genetic testing in Crohn disease: utility in individualizing patient management.

Am J Pharmacogenomics 2005 ;5(4):213-22

Institute for Clinical Molecular Biology, Kiel, Germany.

Inflammatory bowel disease (IBD), with its two subforms of Crohn disease and ulcerative colitis, is a polygenic disease that manifests due to environmental trigger factors on the background of a complex genetic predisposition. The first risk gene underlying susceptibility to Crohn disease has been identified as CARD15 (located on chromosome 16q12, encoding NOD2). Three single nucleotide polymorphisms in the leucine rich region (LRR) of this gene are strongly and independently associated with Crohn disease susceptibility and explain up to 20% of the total genetic predisposition for Crohn disease. Read More

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October 2005

Towards molecular medicine: a case for a biological periodic table.

Authors:
Charles Gawad

Am J Pharmacogenomics 2005 ;5(4):207-11

College of Medicine, University of Arizona, Tucson, Arizona 85724-5017, USA.

The recently amplified pace of development in the technologies to study both normal and aberrant cellular physiology has allowed for a transition from the traditional reductionist approaches to global interrogations of human biology. This transformation has created the anticipation that we will soon more effectively treat or contain most types of diseases through a 'systems-based' approach to understanding and correcting the underlying etiology of these processes. However, to accomplish these goals, we must first have a more comprehensive understanding of all the elements involved in human cellular physiology, as well as why and how they interact. Read More

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October 2005
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Comparison of linear weighting schemes for perfect match and mismatch gene expression levels from microarray data.

Am J Pharmacogenomics 2005 ;5(3):197-205

Section on Statistical Genetics, Department of Biostatistics, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.

Background: Data analytic approaches to Affymetrix microarray data include: (a) a covariate model, in which the observed signal is some estimated linear function of perfect match (PM) and mismatch (MM) signals; (b) a difference model [PM-MM]; and (c) a PM-only model, in which MM data is not utilized.

Methods: By decomposing the correlations among the variables in the statistical model and making certain assumptions, we theoretically derive the statistical model that reflects the actual gene expression level under a variety of conditions expected in microarray data.

Results And Conclusion: When modeling non-systematic variation, the covariate model provides maximum flexibility and often reflects the actual gene expression levels better than the difference model. Read More

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September 2005
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CYP3A5 genotype is associated with diagnosis of hypertension in elderly patients: data from the DEBATE Study.

Am J Pharmacogenomics 2005 ;5(3):191-5

Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany.

Objective: The aim of this study was to address the presently controversial question of whether cytochrome P450 (CYP) 3A5 polymorphism is associated with hypertension.

Method: We studied 373 elderly (age > or =75 years) Finnish (Caucasian) patients from the ongoing DEBATE (Drugs and Evidence Based Medicine in the Elderly) trial. The patients were classified into those with a history of hypertension (n = 229) and those without a history of hypertension (n = 144) on the basis of a detailed questionnaire on each patient's medical history and an interview. Read More

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September 2005
10 Reads

Oncogenes as novel targets for cancer therapy (part I): growth factors and protein tyrosine kinases.

Am J Pharmacogenomics 2005 ;5(3):173-90

Department of Pharmacology and Toxicology, and Division of Clinical Pharmacology, University of Alabama at Birmingham, Birmingham, Alabama 35294-0019, USA.

In the past 10 years, progress made in cancer biology, genetics, and biotechnology has led to a major transition in cancer drug design and development. There has been a change from an emphasis on non-specific, cytotoxic agents to specific, molecular-based therapeutics. Mechanism-based therapy is designed to act on cellular and molecular targets that are causally involved in the formation, growth, and progression of human cancers. Read More

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September 2005
3 Reads

Preclinical drug safety analysis by chemogenomic profiling in the liver.

Am J Pharmacogenomics 2005 ;5(3):161-71

Iconix Pharmaceuticals, Mountain View, California 94043, USA.

The economic hurdles of drug development and the emergence of genomic technologies such as chemogenomics are combining to shift the existing paradigms in preclinical drug development. Today, the information gleaned from high content molecular data has begun to augment traditional approaches to the assessment of drug safety. The optimal approach is a hybrid strategy employing chemogenomic data and gene expression-based biomarkers of drug efficacy and toxicity to supplement low content and insensitive methods for risk assessment and mechanistic evaluation of drug candidates. Read More

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September 2005
3 Reads

Genetics and epigenetics in major psychiatric disorders: dilemmas, achievements, applications, and future scope.

Am J Pharmacogenomics 2005 ;5(3):149-60

Department of Psychiatry, Harvard Medical School at Massachusetts Mental Health Center, Boston, Massachusetts, USA.

No specific gene has been identified for any major psychiatric disorder, including schizophrenia, in spite of strong evidence supporting a genetic basis for these complex and devastating disorders. There are several likely reasons for this failure, ranging from poor study design with low statistical power to genetic mechanisms such as polygenic inheritance, epigenetic interactions, and pleiotropy. Most study designs currently in use are inadequate to uncover these mechanisms. Read More

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September 2005
3 Reads

Applying proteomics in clinical trials: assessing the potential and practical limitations in ovarian cancer.

Am J Pharmacogenomics 2005 ;5(3):141-8

Laboratory of Pathology, Molecular Signaling Section Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892, USA.

Ovarian cancer is the leading cause of death from gynecologic malignancies among American women and the fourth most frequent cause of death from cancer in women in Europe and the US. Despite appropriate surgical and chemotherapeutic intervention, the 5-year survival in patients with metastatic cancer remains poor. Currently available screening methods, including CA125, additional biomarkers, and transvaginal ultrasound lack the necessary sensitivity and specificity to provide accurate and cost-efficient screening for the general population or the ability to assess who will benefit most from each treatment. Read More

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September 2005
3 Reads

EGFR pharmacogenomics: the story continues to mutate and evolve.

Am J Pharmacogenomics 2005 ;5(2):137-9

Section of Hematology and Oncology, University of Chicago, Illinois 60637, USA.

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Spotlight on gefitinib in non-small-cell lung cancer.

Am J Pharmacogenomics 2005 ;5(2):133-6

Adis International Inc., Langhorne, Pennsylvania 19047, USA.

Gefitinib (Iressa), the first commercially available epidermal growth factor receptor-tyrosine kinase (EGFR-TK) inhibitor, is indicated in the management of patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC). However, approved uses differ between countries; in most markets, gefitinib is approved for third-line use only (e.g. Read More

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May 2006
2 Reads

Detection of single nucleotide polymorphisms in the ABCG2 gene in a Dutch population.

Am J Pharmacogenomics 2005 ;5(2):123-31

Department of Pharmacy & Pharmacology, The Netherlands Cancer Institute/Slotervaart Hospital, 1066 EC Amsterdam, The Netherlands.

Background: ABCG2 is a drug transporter involved in the protection of tissues by actively transporting toxic substances and xenobiotics out of cells. Cancer cells overexpressing the ABCG2 gene show multidrug resistance to mitoxantrone-, methotrexate-, doxorubicin-, and camptothecin-based anticancer drugs, such as topotecan and SN-38. Large interindividual differences have been shown in oral availability and clearance of drugs that are substrates for ABCG2. Read More

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May 2006
2 Reads

Pathway proteomics: global and focused approaches.

Am J Pharmacogenomics 2005 ;5(2):113-22

Department Analytical Chemistry, Lund University, SE-221 87 Lund, Sweden.

Biological pathways represent the relationships (reactions and interactions) between biological molecules in the context of normal cellular functions and disease mechanisms. Understanding the roles of proteins and signaling pathways expressed within disease, and their link to drug discovery and drug development are central in today's target-driven pharmaceutical processes. This article gives an overview of proteomics strategies, including global expression analysis as well as focused approaches using multidimensional separation by both gel- and liquid-phase techniques linked to mass spectrometry, as applied to two of the pathways involved in inflammatory diseases. Read More

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Mechanisms of clinical resistance to small molecule tyrosine kinase inhibitors targeting oncogenic tyrosine kinases.

Am J Pharmacogenomics 2005 ;5(2):101-12

Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany.

A number of highly specific small molecule inhibitors of oncogenic tyrosine kinases have been developed and may potentially improve the treatment of different malignant diseases. However, it became rapidly evident that multiple resistance mechanisms compromise the successful clinical application of these inhibitors, particularly in advanced solid tumors. To develop efficient therapeutic strategies with small molecule inhibitors, one must understand the causes for treatment failure. Read More

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May 2006
3 Reads

Platelet glycoprotein IIb/IIIa polymorphism and coronary artery disease: implications for clinical practice.

Am J Pharmacogenomics 2005 ;5(2):93-9

Research Laboratories, Centre for High Technology Research and Education in Biomedical Sciences, Catholic University, 86100 Campobasso, Italy.

Membrane glycoprotein (GP) IIb/IIIa plays a major role in platelet function; indeed it enables stimulated platelets to bind fibrinogen and related adhesive proteins, a process that is considered key in the development of thrombosis. The gene encoding GPIIIa (ITGB3, also known as GP3A) shows a common platelet antigen polymorphism [PL(A1)/PL(A2); expressed by alleles ITGB3*001 and ITGB3*002] that was variably associated with vascular disease. In 1996, the presence of the PL(A2) allele (ITGB3*001) was first reported to increase the risk of coronary heart disease. Read More

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May 2006
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What is known about autism: genes, brain, and behavior.

Am J Pharmacogenomics 2005 ;5(2):71-92

Psychiatric & Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA.

Autism is a neurodevelopmental disorder of genetic origins, with a heritability of about 90%. Autistic disorder is classed within the broad domain of pervasive developmental disorders (PDD) that also includes Rett syndrome, childhood disintegrative disorder, Asperger syndrome, and PDD not otherwise specified (PDD-NOS). Prevalence estimates suggest a rate of 0. Read More

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May 2006
9 Reads

Bayesian decomposition analysis of bacterial phylogenomic profiles.

Am J Pharmacogenomics 2005 ;5(1):63-70

Division of Population Science, Bioinformatics, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.

Background: The past two decades have seen the appearance of new infectious diseases and the reemergence of old diseases previously thought to be under control. At the same time, the effectiveness of the existing antibacterials is rapidly decreasing due to the spread of multidrug-resistant pathogens.

Aim: The aim of this study was to the identify candidate molecular targets (e. Read More

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May 2005
5 Reads

Pharmacogenomics and the drug discovery pipeline: when should it be implemented?

Am J Pharmacogenomics 2005 ;5(1):53-62

Clinical Pharmacogenomics, Pfizer Global Research and Development, Sandwich Laboratories (ipc 746), Sandwich, Kent, Ramsgate Road, CT13 9NJ, UK.

One of the key factors in developing improved medicines lies in understanding the molecular basis of the complex diseases we treat. Investigation of genetic associations with disease utilizing advances in linkage disequilibrium-based whole genome association strategies will provide novel targets for therapy and define relevant pathways contributing to disease pathogenesis. Genetic studies in conjunction with gene expression, proteomic, and metabonomic analyses provide a powerful tool to identify molecular subtypes of disease. Read More

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May 2005
11 Reads

Monoamine oxidase a and tryptophan hydroxylase gene polymorphisms: are they associated with bipolar disorder?

Am J Pharmacogenomics 2005 ;5(1):45-52

University Department of Adult Psychiatry, Site de Cery, CH-1008 Prilly-Lausanne, Switzerland.

Most of the candidate gene studies in bipolar disorder have focused on the major neurotransmitter systems that are influenced by drugs used in the treatment of this disorder. The monoamine oxidase A (MAOA) and the tryptophan hydroxylase (TPH1, TPH2) genes are two of the candidates that have been tested in a series of association studies using unrelated or family-based controls. This review summarizes the existing association studies regarding these genes. Read More

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May 2005
2 Reads

Advances in myeloma genetics and prospects for pharmacogenomic testing in multiple myeloma.

Am J Pharmacogenomics 2005 ;5(1):35-43

Department of Medical Oncology, Princess Margaret Hospital, Toronto, Ontario, Canada

Pharmacogenomic studies in multiple myeloma, a neoplasia of clonally expanded malignant bone marrow plasma cells, are helping to set the stage for individualized therapy. Although relatively few in numbers, these studies are already providing new therapeutic targets and avenues for drug discoveries as well as contributing to novel prognostic markers in multiple myeloma. High-throughput mutation screening of the kinome promises to identify further novel targets for therapy. Read More

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May 2005
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Pharmacogenomics of fluorouracil, irinotecan, and oxaliplatin in hepatic metastases of colorectal cancer: clinical implications.

Am J Pharmacogenomics 2005 ;5(1):21-33

Service de Pharmacologie, Hôpital Saint Vincent de Paul, avenue Denfert-Rochereau, Paris, 75014, France.

Hepatic metastases occur in about half of patients with colorectal cancer. Since hepatic metastases are often not accessible for surgery, chemotherapy of metastases is important. The most commonly used chemotherapy drugs for hepatic metastases are fluorouracil, irinotecan, and oxaliplatin. Read More

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May 2005
10 Reads

The epidemiologic approach to pharmacogenomics.

Am J Pharmacogenomics 2005 ;5(1):1-20

Department of Epidemiology and Community Medicine, University of Ottawa, 451 Smyth Rd, Ottawa, Ontario K1H 8M5, Canada.

The epidemiologic approach enables the systematic evaluation of potential improvements in the safety and efficacy of drug treatment which might result from targeting treatment on the basis of genomic information. The main epidemiologic designs are the randomized control trial, the cohort study, and the case-control study, and derivatives of these proposed for investigating gene-environment interactions. However, no one design is ideal for every situation, and methodological issues, notably selection bias, information bias, confounding and chance, all play a part in determining which study design is best for a given situation. Read More

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Polymorphisms of CYP2C19 and CYP2D6 in Israeli ethnic groups.

Am J Pharmacogenomics 2004 ;4(6):395-401

Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, Kansas 66160-7417, USA.

Background: The cytochrome P450 isoenzymes CYP2C19 and CYP2D6 catalyze reactions involved in the metabolism of many widely used drugs. Their polymorphisms give rise to important interindividual and interethnic variability in the metabolism and disposition of several therapeutic agents and may cause differences in clinical response to some drugs. Individuals who carry two null alleles of either gene are known as poor metabolizers (PMs), while those who carry more than two copies of the functional CYP2D6 gene are ultrarapid metabolizers (UMs). Read More

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February 2005
14 Reads

Biomedical literature mining: challenges and solutions in the 'omics' era.

Am J Pharmacogenomics 2004 ;4(6):383-93

Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.

It is now obvious that the rate-limiting step in high throughput experimentation is neither data acquisition nor analysis, but rather our ability to interpret data on a genome-wide scale. Indeed, the explosion of data sampling capacity combined with increasing publication rates greatly impairs our ability to find meaning in vast collections of data. In order to support data interpretation, bioinformatic tools are needed to identify critical information contained in large bodies of literature. Read More

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February 2005

Activity-based protein profiling: applications to biomarker discovery, in vivo imaging and drug discovery.

Am J Pharmacogenomics 2004 ;4(6):371-81

Department of Pathology, Stanford University School of Medicine, Stanford, California 94305-5324, USA.

The genomic revolution has created a wealth of information regarding the fundamental genetic code that defines the inner workings of a cell. However, it has become clear that analyzing genome sequences alone will not lead to new therapies to fight human disease. Rather, an understanding of protein function within the context of complex cellular networks will be required to facilitate the discovery of novel drug targets and, subsequently, new therapies directed against them. Read More

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February 2005
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Sequence tag catalogs of dust mite-expressed genomes: utility in allergen and acarologic studies.

Am J Pharmacogenomics 2004 ;4(6):357-69

Department of Biological Sciences, National University of Singapore, Singapore.

Dust mites are a major source of indoor allergens. They contain a large number of components that react with immunoglobulin (Ig) E in individuals with allergies and are capable of inducing sensitization, and allergic respiratory and cutaneous diseases. With a significant proportion of the population affected in some way by mite allergies, it is essential that we improve our understanding of these organisms so that control strategies could be defined and its allergens better understood. Read More

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February 2005
3 Reads

Use of DNA microarrays to monitor host response to virus and virus-derived gene therapy vectors.

Am J Pharmacogenomics 2004 ;4(6):345-56

Department of Genetics and Molecular Biology, University of Rome La Sapienza, Rome, Italy.

Given the biological complexity of viral infections, the variability of the host response, and the safety concerns related to viral-mediated gene transfer, recent studies have made use of DNA mircoarrays to integrate multi-layered experimental approaches aimed at completely clarifying virus-host interactions. Particular attention has been given to those viruses that are implicated in clinical use and/or in life-threatening diseases. Examples of such use can be divided into three main categories, including: (i) the use of microarrays to study viral expression; (ii) the use of microarrays to analyze the host response to viral infection; and (iii) the use of microarrays to characterize the host response to viral vector-mediated transduction. Read More

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February 2005
2 Reads

Polymorphisms in genes involved in the corticosteroid response and the outcome of childhood acute lymphoblastic leukemia.

Am J Pharmacogenomics 2004 ;4(5):331-41

Research Center, Sainte-Justine Hospital, Centre Hospitalier Universitaire Mère-Enfant, Montreal, Quebec, Canada.

Background: Considerable variability in sensitivity to corticosteroids (CS) has been observed among individuals with regard to both the natural and synthetic compounds. The role of genetic polymorphisms in modulating CS function, and hence in disease susceptibility, has been extensively analyzed. Their impact on therapeutic response still remains to be explored. Read More

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December 2004
5 Reads

Analysis of microglial gene expression: identifying targets for CNS neurodegenerative and autoimmune disease.

Am J Pharmacogenomics 2004 ;4(5):321-30

Department of Molecular Biology, The Scripps Research Institute, La Jolla, California, USA.

Microglia are the tissue macrophage of the central nervous system (CNS) and their activation is among the earliest signs of CNS dysfunction and disease. Because microglia express many macrophage markers, they are presumed to act primarily as effectors of CNS inflammation and destruction. While such responses are beneficial to the extent that they destroy CNS pathogens, these responses do have the potential to have neurotoxic outcomes. Read More

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December 2004
9 Reads

Chemical genomics: probing protein function using small molecules.

Am J Pharmacogenomics 2004 ;4(5):313-20

The Eli and Edythe L. Broad Institute, Massachusetts Institute of Technology & Harvard University, Institute of Chemistry & Cell Biology (ICCB), Initiative for Chemical Genetics, Cambridge, Massachusetts, USA.

Chemical genomics is concerned with the effects of both genetic variation and chemical perturbation on the cellular effects of small molecules. Chemical genomics relies on selecting biological networks for study, such as those represented by different cell types or disease models, in order to build the desired specificity into the experimental design. The most relevant network property for such experiments is the global connectivity of all cellular proteins comprising the functional ensemble, as illustrated by case studies of the evolution of cyclooxygenase inhibitors and heat-shock protein modulators. Read More

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December 2004
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Microarray expression profiling reveals candidate genes for human uterine receptivity.

Authors:
Linda C Giudice

Am J Pharmacogenomics 2004 ;4(5):299-312

Department of Gynecology & Obstetrics, Center for Research on Women's Health and Reproduction, Stanford University School of Medicine, Stanford, California, USA.

The endometrium undergoes cyclic changes in response to circulating ovarian steroid hormones as it prepares for implantation. This dynamic tissue is well suited to microarray expression profiling for elucidation of molecular players participating in the maturation of the endometrium and during the process of implantation. Recent advances in sequencing the human and mouse genomes and the availability of microarray technology and bioinformatic analyses have made elucidating these molecular participants and dialogs a reality. Read More

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December 2004
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Human genetics and responses to influenza vaccination: clinical implications.

Am J Pharmacogenomics 2004 ;4(5):293-8

Department of Medical Microbiology and Retroscreen Virology, Queen Mary's School of Medicine and Dentistry, London, England.

Influenza A and B viruses are negative-strand RNA viruses that cause regular outbreaks of respiratory disease and substantially impact on morbidity and mortality. Our primary defense against the influenza virus infection is provided by neutralizing antibodies that inhibit the function of the virus surface coat proteins hemagglutinin and neuraminidase. Production of these antibodies by B lymphocytes requires help from CD4+ T cells. Read More

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December 2004
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Costs and benefits of genomics patents.

Am J Pharmacogenomics 2004 ;4(5):277-92

Centre for Innovation Law and Policy, University of Toronto, Toronto, Ontario, Canada.

Genomics patents are controversial on religious, ethical, legal, and economic grounds. An economic approach is desirable for valuing the patent system generally, and genomics patents in particular, in terms of its stated constitutional objective, which is to 'promote progress'. Several types of criticisms and warnings have been issued regarding the suitability of genomics inventions for patent protection; here these are evaluated in the context of more general concerns about the efficacy of the patent system. Read More

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December 2004

Technological advances in high-throughput screening.

Am J Pharmacogenomics 2004 ;4(4):263-76

Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu, Peoples Republic of China.

High-throughput screening (HTS) is the process of testing a large number of diverse chemical structures against disease targets to identify 'hits'. Compared to traditional drug screening methods, HTS is characterized by its simplicity, rapidness, low cost, and high efficiency, taking the ligand-target interactions as the principle, as well as leading to a higher information harvest. As a multidisciplinary field, HTS involves an automated operation-platform, highly sensitive testing system, specific screening model (in vitro), an abundant components library, and a data acquisition and processing system. Read More

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November 2004
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Genome-wide linkage disequilibrium and haplotype maps.

Am J Pharmacogenomics 2004 ;4(4):253-62

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.

There is currently a broad effort to produce genome-wide high-density linkage disequilibrium (LD) maps with single nucleotide polymorphisms. The hope is that the resulting maps can be exploited to find genes that affect the onset and severity of at least some common human diseases. These maps may also be useful for identifying genes that affect drug response or the likelihood of drug toxicities. Read More

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November 2004