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Personalized Medicine (personalized + medicine)
Selected AbstractsRedefining Personalized Medicine in the Postgenomic EraBJU INTERNATIONAL, Issue 2 2010Developing bladder cancer therapeutics with proteomics First page of article [source] Foundations, promises and uncertainties of personalized medicineMOUNT SINAI JOURNAL OF MEDICINE: A JOURNAL OF PERSONALIZED AND TRANSLATIONAL MEDICINE, Issue 1 2007Erwin P. Bottinger Abstract Personalized medicine introduces the promise to use molecular markers that signal the risk of disease or its presence before clinical signs and symptoms appear. This information underlies a new healthcare strategy focused on prevention and early intervention, rather than reaction to advanced stages of disease. Such a strategy can delay disease onset or minimize symptom severity. The molecular foundations that enable personalized medicine include detection of variation in nucleotide sequence of genes and in characteristic patterns of gene expression, proteins and metabolites. Genetic and molecular patterns are correlated with disease manifestations, drug responses, treatment prognosis, or prediction of predisposition to future disease states. However, the uncertainties for personalized medicine are considerable, including economic, ethical, legal, and societal questions. Although much of its promise remains unproven to date, the foundations of personalized medicine appear solid and evidence is accumulating rapidly pointing to its growing importance in healthcare (Fig. 1). Mt Sinai J Med 74:15,21, 2007. © 2007 Mount Sinai School of Medicine [source] An "Omics" view of drug developmentDRUG DEVELOPMENT RESEARCH, Issue 2 2004Russ B. Altman Abstract The pharmaceutical industry cannot be blamed for having a love/hate relationship with the fields of pharmacogenetics and pharmacogenomics. At the same time that pharmacogenetics and pharmacogenomics promise to save pipeline drugs by identifying subsets of the population for which they work best, they also threaten to increase the complexity of new drug applications, fragment markets, and create uncertainty for prescribers who simply do not understand or have time to master "personalized medicine." Most importantly, the logical case for genetics-specific drug selection and dosing is much more mature than the practical list of drugs for which outcomes are demonstrably improved. Understandably, pharmaceutical developers and regulators have been careful in creating strategies for using genetics in drug development, and only recently has the FDA begun to establish preliminary rules for pharmacogenetic testing. A growing public academic effort in pharmacogenetics and pharmacogenomics is helping flesh out the basic science underpinnings of the field, and this should combine with extensive efforts of industry to create a solid foundation for future use of genetics in drug development. Two grand challenges to accelerate our capabilities include the characterization of all human genes involved in the basic pharmacokinetics of drugs, and the detailed study of the genes and pathways associated with G-protein-coupled receptors and how they are affected by genetic variation. Drug Dev. Res. 62:81,85, 2004. © 2004 Wiley-Liss, Inc. [source] Pharmacogenetics and personalised medicineFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 5 2002Werner Kalow ABSTRACT The traditional concern of pharmacogenetics was Mendelian (monogenic) variation, which visibly affected some drug responses. Pharmacogenetics was broadened by the observation that multifactorial genetic influences, in conjunction with environmental factors, usually determine drug responses. Variability of gene expression, a new theme of the science of genetics, also affects pharmacogenetics; for example, enhanced enzyme activity does not necessarily indicate a mutation, but may be the consequence of a drug-induced enhancement of gene expression. Methodological advances permit the conversion of pharmacogenetics into the broad practice of pharmacogenomics; this improves the possibility of identifying genetic causes of common diseases, which means establishing new drug targets, thereby stimulating the search for new drugs. While the main medical effect of pharmacogenetics was an improvement of drug safety, pharmacogenomics is hoped to improve drug efficacy. On the way to personalized medicine, we may stepwise improve the chances of choosing the right drug for a patient by categorizing patients into genetically definable classes that have similar drug effects (as, for example, human races, or any population group carrying a particular set of genes). It is wise to expect that, even after we have reached the goal to establish personalized medicine, we will not have eliminated all uncertainties. [source] New Generation of Multifunctional Nanoparticles for Cancer Imaging and TherapyADVANCED FUNCTIONAL MATERIALS, Issue 10 2009Kyeongsoon Park Abstract Advances in nanotechnology have contributed to the development of novel nanoparticles that enable the tumor-specific delivery of imaging probes and therapeutic agents in cancer imaging and therapy. Nanobiotechnology combines nanotechnology with molecular imaging, which has led to the generation of new multifunctional nanoparticles for cancer imaging and therapy. Multifunctional nanoparticles hold great promise for the future of cancer treatment because they can detect the early onset of cancer in each individual patient and deliver suitable therapeutic agents to enhance therapeutic efficacy. The combination of tumor-targeted imaging and therapy in an all-in-one system provides a useful multimodal approach in the battle against cancer. Novel multifunctional nanoparticles thus offer a new avenue in the application of personalized medicine in the near future. Herein, new trends and the significance of novel multifunctional nanoparticles in cancer imaging and therapy are reviewed. [source] New drugs for the treatment of hepatocellular carcinomaLIVER INTERNATIONAL, Issue 2009Eveline Boucher Abstract Treatment of hepatocellular carcinoma has dramatically changed in the last years. The better knowledge of the molecular mechanisms responsible of tumor initiation and progression has allowed the development of molecular targeted therapies that specifically block the disrupted pathways. Among all these new agents, Sorafenib is the only one that has shown efficacy in terms of survival in advanced stage in two randomized, double-blind, controlled trials. The positive result of these two trials are the proof of the efficacy of molecular targeted therapies in hepatocellular carcinoma and opens the door to multipathway blockade and the use of these targeted therapies in the adjuvant setting. Other agents have shown promising results in phase 1-2 trials but further studies are needed to demonstrate their efficacy. In the next years, efforts should be directed to identifying genomic and proteomic profiling that will help us to assess the prognosis and to define what treatment benefits whom, ultimately giving way to personalized medicine. [source] Foundations, promises and uncertainties of personalized medicineMOUNT SINAI JOURNAL OF MEDICINE: A JOURNAL OF PERSONALIZED AND TRANSLATIONAL MEDICINE, Issue 1 2007Erwin P. Bottinger Abstract Personalized medicine introduces the promise to use molecular markers that signal the risk of disease or its presence before clinical signs and symptoms appear. This information underlies a new healthcare strategy focused on prevention and early intervention, rather than reaction to advanced stages of disease. Such a strategy can delay disease onset or minimize symptom severity. The molecular foundations that enable personalized medicine include detection of variation in nucleotide sequence of genes and in characteristic patterns of gene expression, proteins and metabolites. Genetic and molecular patterns are correlated with disease manifestations, drug responses, treatment prognosis, or prediction of predisposition to future disease states. However, the uncertainties for personalized medicine are considerable, including economic, ethical, legal, and societal questions. Although much of its promise remains unproven to date, the foundations of personalized medicine appear solid and evidence is accumulating rapidly pointing to its growing importance in healthcare (Fig. 1). Mt Sinai J Med 74:15,21, 2007. © 2007 Mount Sinai School of Medicine [source] The role of the pathologist in translational and personalized medicineMOUNT SINAI JOURNAL OF MEDICINE: A JOURNAL OF PERSONALIZED AND TRANSLATIONAL MEDICINE, Issue 1 2007Daniel P. Perl MD Abstract Over the years, pathologists have served to make morphologic diagnoses for clinicians when provided with a biopsy or surgically resected tissue specimen. Traditionally, pathologists have used a series of morphologic techniques and relied on the microscopic appearance of resected tissues to determine a pathologic diagnosis and, with respect to neoplastic lesions, provide predictions of the potential growth pattern that might be anticipated. With the introduction of the techniques of molecular biology in medicine, the role of the pathologist has changed as have the tools available for characterizing pathologic specimens. With the pathologist's unique perspective on disease processes and access to tissue specimens from the operating room, he has become a key player in the area of translational and personalized medicine and the development of new approaches to diagnosis and translational research. Mt Sinai J Med 74:22,26, 2007. © 2007 Mount Sinai School of Medicine [source] Subjects of Speculation: Emergent Life Sciences and Market Logics in the United States and IndiaAMERICAN ANTHROPOLOGIST, Issue 1 2005KAUSHIK SUNDER RAJAN This article traces systems of exchange concerning the life sciences and capital and how they configure subjectivity in the United States and India. This is done through case studies concerning the emergence of personalized medicine in the two locales. In the U.S. case, I argue for the configuration of the subjects of personalized medicine as sovereign consumers; in the Indian case, I argue for their configuration as experimental subjects. I situate these arguments in the context of epistemologies of genomics and the consolidation of systems of speculative capitalism. [source] High-resolution biomarker discovery: Moving from large-scale proteome profiling to quantitative validation of lead candidatesPROTEOMICS - CLINICAL APPLICATIONS, Issue 10-11 2008Johannes A. Hewel Abstract Diverse proteomic techniques based on protein MS have been introduced to systematically characterize protein perturbations associated with disease. Progress in clinical proteomics is essential for personalized medicine, wherein treatments will be tailored to individual needs based on patient stratification using noninvasive disease monitoring procedures to reveal the most appropriate therapeutic targets. However, breakthroughs await the successful development and application of a robust proteomic pipeline capable of identifying and rigorously assessing the relevance of multiple candidate proteins as informative diagnostic and prognostic indicators or suitable drug targets involved in a pathological process. While steady progress has been made toward more comprehensive proteome profiling, the emphasis must now shift from in depth screening of reference samples to stringent quantitative validation of selected lead candidates in a broader clinical context. Here, we present an overview of the emerging proteomic strategies for high-throughput protein detection focused primarily on targeted MS/MS as the basis for biomarker verification in large clinical cohorts. We discuss the conceptual promise and practical pitfalls of these methods in terms of achieving higher dynamic range, higher throughput, and more reliable quantification, highlighting research avenues that merit additional inquiry. [source] Body fluid proteomics: Prospects for biomarker discoveryPROTEOMICS - CLINICAL APPLICATIONS, Issue 9 2007Sung-Min Ahn Abstract Many diseases are caused by perturbations of cellular signaling pathways and related pathway networks as a result of genetic aberrations. These perturbations are manifested by altered cellular protein profiles in the fluids bathing tissue/organs (i.e., the tissue interstitial fluid, TIF). A major challenge of clinical chemistry is to quantitatively map these perturbed protein profiles , the so-called "signatures of disease" , using modern proteomic technologies. This information can be utilized to design protein biomarkers for the early detection of disease, monitoring disease progression and efficacy of drug action. Here, we discuss the use of body fluids in the context of prospective biomarker discovery, and the marked 1000,1500-fold dilution of body fluid proteins, during their passage from TIF to the circulatory system. Further, we discuss proteomics strategies aimed at depleting major serum proteins, especially albumin, in order to focus on low-abundance protein/peptides in plasma. A major limitation of depletion strategies is the removal of low-molecular weight protein/peptides which specifically bind major plasma proteins. We present a prototype model, using albumin, for understanding the multifaceted nature of biomarker research, highlighting the involvement of albumin in Alzheimer's disease. This model underscores the need for a system-level understanding for biomarker research and personalized medicine. [source] Systems biology and its application to the understanding of neurological diseases,ANNALS OF NEUROLOGY, Issue 2 2009Pablo Villoslada MD Recent advances in molecular biology, neurobiology, genetics, and imaging have demonstrated important insights about the nature of neurological diseases. However, a comprehensive understanding of their pathogenesis is still lacking. Although reductionism has been successful in enumerating and characterizing the components of most living organisms, it has failed to generate knowledge on how these components interact in complex arrangements to allow and sustain two of the most fundamental properties of the organism as a whole: its fitness, also termed its robustness, and its capacity to evolve. Systems biology complements the classic reductionist approaches in the biomedical sciences by enabling integration of available molecular, physiological, and clinical information in the context of a quantitative framework typically used by engineers. Systems biology employs tools developed in physics and mathematics such as nonlinear dynamics, control theory, and modeling of dynamic systems. The main goal of a systems approach to biology is to solve questions related to the complexity of living systems such as the brain, which cannot be reconciled solely with the currently available tools of molecular biology and genomics. As an example of the utility of this systems biological approach, network-based analyses of genes involved in hereditary ataxias have demonstrated a set of pathways related to RNA splicing, a novel pathogenic mechanism for these diseases. Network-based analysis is also challenging the current nosology of neurological diseases. This new knowledge will contribute to the development of patient-specific therapeutic approaches, bringing the paradigm of personalized medicine one step closer to reality. Ann Neurol 2009;65:124,139 [source] Biotec Visions 2010, May,JuneBIOTECHNOLOGY JOURNAL, Issue 5 2010Article first published online: 3 MAY 2010 News:Ethanol biofuels from orange peels , Targeting leukaemia's gene addiction , Pea-derived solar cells , HIV is a kick in the head , Nano-scale DNA reader , Membrane in black , Cheese improves the immune response of elderly , Synthetic proteins built from standard parts , Therapeutic proteins produced in algae , Biosensor detects 100 mycoplasma cells , Protecting maggots against bacteria , Advanced biofuels from microbes , Fluorescent bacterial uptake , Two disparate stem cell states , Brachypodium genome sequenced Encyclopedia of Life Sciences: Nuclear transfer for cell lines WIREs Nanomedicine and Nanobiotechnology: Nanoparticle detection of respiratory infection Journal Highlights: Biocatalysis , Synthetic Biology In the news: Nanobiotech to detect cancer Most Read Industry News: Biomarker assays for personalized medicine , Bioplastic industry defies economic crisis , SDS-PAGE monitoring of mAB Awards: BTJ Editors elected members of the US National Academy of Engineering (NAE) Meeting highlight Writing tips: Figure preparation made simple , Some useful tutorials on the web Book Highlights:Molecular Biotechnology , Bacterial Signaling , Yeast Test your knowledge:Do you recognize this? WIREs Authors Spotlight:Nanotechnology and orthopedics [source] Search for new biomarkers of gastric cancer through serial analysis of gene expression and its clinical implicationsCANCER SCIENCE, Issue 5 2004Wataru Yasui Gastric cancer is one of the most common human cancers and is the second most frequent cause of cancer-related death in the world. Serial analysis of gene expression (SAGE) is a powerful technique to allow genome-wide analysis of gene expression in a quantitative manner without prior knowledge of the gene sequences. SAGE on 5 samples of gastric cancer with different histology and clinical stages have created large SAGE libraries of gastric cancer that enable us to identify new cancer biomarkers. Commonly up-regulated genes in gastric cancer in comparison with normal gastric epithelia included CEACAM6, APOC1 and YF13H12. By comparing gene expression profiles of gastric cancers at early and advanced stages, several genes differentially expressed by tumor stage were also identified, including FUS, CDH17, COL1A1 and COL1A2, which should be novel genetic markers for high-grade malignancy. Regenerating gene type IV (REGIV) is one of the most up-regulated genes in a SAGE library of a scirrhous-type gastric cancer. In vitro studies using RegIV-transfected cells revealed that RegIV is secreted by cancer cells and inhibits apoptosis, suggesting that RegIV may serve as a novel biomarker and therapeutic target for gastric cancer. Production of RNA aptamers could be a useful approach to establish a detection system in blood. A custom-made array, named Ex-STO-MACHIP, consisting of 395 genes, including highly differentially expressed genes identified by our SAGE and other known genes related to carcinogenesis and chemosensitivity, is useful to study the molecular pathogenesis of gastric cancer and to obtain information about biological behavior and sensitivity to therapy in the clinical setting. Combined analyses of gene expression profile, genetic polymorphism and genetic instability will aid not only cancer detection, but also characterization of individual cancers and patients, leading to personalized medicine and cancer prevention. [source] DNA Labeling by Ligand Inducible Secondary StructureCHEMBIOCHEM, Issue 12 2008Tao Peng Dr. Personalized medical solutions: Simple, accurate, and cost effective methods of single nucleotide polymorphism typing would be necessary for personalized medicine. Towards this end, a number of SNP typing methods have been investigated and reported. We report herein, our chemical approach to practical SNP typing based on allele-specific PCR integrated with a new concept of DNA-labeling by ligand-inducible secondary structure. [source] The promise and challenges of personalized medicine for eye diseasesCLINICAL & EXPERIMENTAL OPHTHALMOLOGY, Issue 3 2004Catherine A McCarty PhD MPH No abstract is available for this article. [source] Sex-Specific Impact of Aldosterone Receptor Antagonism on Ventricular Remodeling and Gene Expression after Myocardial InfarctionCLINICAL AND TRANSLATIONAL SCIENCE, Issue 2 2009Ph.D., Rosemeire M. Kanashiro-Takeuchi D.V.M. Abstract Aldosterone receptor antagonism reduces mortality and improves post-myocardial infarction (Ml) remodeling. Because aldosterone and estrogen signaling pathways interact, we hypothesized that aldosterone blockade is sex-specific. Therefore, we investigated the mpact of eplerenone on left ventricular (LV) remodeling and gene expression of male infarcted rats versus female infarcted rats. Ml and Sham animals were randomized to receive eplerenone (100 mg/kg/day) or placebo 3 days post-surgery for 4 weeks and assessed by echocardiography. In the Ml placebo group, left ventricular end-diastolic dimension (LVEDD) increased from 7.3 ± 0.4 mm to 10.2 ± 1.0 mm (p < 0.05) and ejection fraction (EF) decreased from 82.3 + 4% to 45.5 + 11% (p < 0.05) in both sexes (p= NS between groups). Eplerenone attenuated LVEDD enlargement more effectively in females (8.8 ± 0.2 mm, p < 0.05 vs. placebo) than in males (9.7 ± 0.2 mm, p= NS vs. placebo) and improved EF in females (56.7 ± 3%, p < 0.05 vs. placebo) but not in males (50.6 + 3%, p= NS vs. placebo). Transcriptomic analysis using Rat_230,2.0 microarrays (Affymetrix) revealed that in females 19% of downregu-lated genes and 44% of upregulated genes post-MI were restored to normal by eplerenone. In contrast, eplerenone only restored 4% of overexpressed genes in males. Together, these data suggest that aldosterone blockade reduces Ml-induced cardiac remodeling and phenotypic alterations of gene expression preferentially in females than in males. The use of transcriptomic signatures to detect greater benefit of eplerenone in females has potential implications for personalized medicine. [source] On the bumpy road towards ,personalized medicine'EMBO MOLECULAR MEDICINE, Issue 1 2010Uta Francke No abstract is available for this article. [source] Validation study of the prediction system for clinical response of M-VAC neoadjuvant chemotherapyCANCER SCIENCE, Issue 1 2007Ryo Takata To predict the efficacy of the M-VAC neoadjuvant chemotherapy for invasive bladder cancers, we previously established the method to calculate the prediction score on the basis of expression profiles of 14 predictive genes. This scoring system had clearly distinguished the responder group from the non-responder group. To further validate the clinical significance of the system, we applied it to 22 additional cases of bladder cancer patients and found that the scoring system correctly predicted clinical response for 19 of the 22 test cases. The group of patients with positive predictive scores had significantly longer survival than that with negative scores. When we compared our results with a previous report describing the prognosis of the patients with cystectomy alone, the results imply that patients with positive scores are likely to benefit from M-VAC neoadjuvant chemotherapy, but that the chemotherapy would shorten the lives of patients with negative scores. We are confident that our prediction system to M-VAC therapy should provide opportunities for achieving better prognosis and improving the quality of life of patients. Taken together, our data suggest that the goal of ,personalized medicine', prescribing the appropriate treatment regimen for each patient, may be achievable by selecting specific sets of genes for their predictive values according to the approach shown here. (Cancer Sci 2007; 98: 113,117) [source] Manufacturing antibodies in the plant cellBIOTECHNOLOGY JOURNAL, Issue 12 2009Diego Orzáez Dr. Abstract Plants have long been considered advantageous platforms for large-scale production of antibodies due to their low cost, scalability, and the low chances of pathogen contamination. Much effort has therefore been devoted to efficiently producing mAbs (from nanobodies to secretory antibodies) in plant cells. Several technical difficulties have been encountered and are being overcome. Improvements in production levels have been achieved by manipulation of gene expression and, more efficiently, of cell targeting and protein folding and assembly. Differences in mAb glycosylation patterns between animal and plant cells are being successfully addressed by the elimination and introduction of the appropriate enzyme activities in plant cells. Another relevant battlefield is the dichotomy between production capacity and speed. Classically, stably transformed plant lines have been proposed for large scale mAb production, whereas the use of transient expression systems has always provided production speed at the cost of scalability. However, recent advances in transient expression techniques have brought impressive yield improvements, turning speed and scalability into highly compatible assets. In the era of personalized medicines, the combination of yield and speed, and the advances in glyco-engineering have made the plant cell a serious contender in the field of recombinant antibody production. [source] | ||||||||||||||||