bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunomodulatory Biopharmaceuticals and Risk of Neoplasia
Authors: Bugelski Peter J. , Sachs Clifford , Cornacoff Joel , Martin Pauline , Treacy George 
Published: March 2010

AbstractA number of immunomodulatory biopharmaceuticals (IMBPs), such as peptides, recombinant proteins, and monoclonal antibodies, have been approved or are currently in development to treat chronic inflamatory diseases. IMBPs by virtue of their intended pharmacologic activity may act as atypical tumor promoters and thus pose a hazard for developing certain tumor types, especially lymphomas and skin cancer. This article focuses on focus on well‐characterized, high‐purity protein biopharmaceuticals derived from conventional recombinant expression systems that modulate immune function.
Practical Considerations in the Design of Preclinical Safety Assessments for Biopharmaceuticals
Authors: Demady Damon R. 
Published: March 2010

Abstract
The primary goals of preclinical safety evaluation articulated in ICH S6 are to identify an initial safe dose and subsequent dose escalation schemes in humans. It also involves the identification of potential target organs for toxicity and for the study of whether such toxicity is reversible, and to identify safety parameters for clinical monitoring. These goals are generally accepted across all product classes.
Predicting Human Adverse Drug Reactions from Nonclinical Safety Studies
Authors: Valentin Jean‐Pierre , Keisu Marianne , Hammond Tim G. 
Published: March 2010

AbstractAn adverse drug reaction (ADR) is an adverse event where a causal relationship between the adverse event (AE) and the medicinal product is at least a reasonable possibility. Lack of safety remains the major cause of attrition during clinical development, accounting for approximately 35–40 percent of all drug discontinuation. This article focuses on the nature, frequency, and consequences of ADRs in two different clinical situations.
History of Clinical Trial Development and the Pharmaceutical Industry
Authors: Peppercorn Jeffrey , Roberts Thomas G. , Hammond Tim G. 
Published: March 2010

AbstractThe history of clinical trials and the pharmaceutical industry is closely tied to the history of bioethics, which shape the regulation of clinical research and pharmaceutical development.The history of clinical trials begins with the recognition of disease as a discrete condition that is similar enough from patient to patient to allow the rational application of the experimental method to determine which therapies work and which do not. This article presents an overview of some of the key developments and ongoing issues that should serve as an introduction to the rich history of clinical trials and the rise of the pharmaceutical industry.
Phase
I
Clinical Trials
Authors: Norfleet Elizabeth , Cox Gad Shayne 
Published: March 2010

Abstract
Phase I trials are the earliest stage clinical trials of a new drug or device typically performed with just a few persons to determine the safety and pharmacokinetics of a new drug. The main objectives of phase I trials are to assess tolerability, monitoring the side effects in relation to increase of the doses, and confirm the maximum tolerated dose. This article discusses design characteristics of different kind of Phase I trials.
Phase
II
Clinical Trials
Authors: Tan Say‐Beng , Machin David 
Published: March 2010

Abstract
Phase II trials are conducted to evaluate the drug's activity for patients with a particular disease or condition and to determine the level of short‐term side effects and possible risks associated with the use of the drug. The drug is further evaluated in randomized phase III trials where it is compared with the current standard treatment in a larger number of patients when preliminary evidence of effectiveness is found in these phase II trials. Phase II trials are single‐armed studies that investigate the antidisease activity of the new therapeutic regimen.
Oncology
Authors: Zwitter Matjaz 
Published: March 2010

AbstractVarious issues associated with the design and conduct of clinical research in oncology are discussed. It is estimated that only between 3 and 10% of cancer patients participate in clinical trials, with even lower representation of elderly patients and minorities. There is a critical need for infrastructure to support trials, especially additional support staff and research nurses. Other obstacles to clinical research include legal restrictions, as seen in the European Union Clinical Trials Directive or in the Declaration of Helsinki.
Clinical Trials on Cognitive Drugs
Authors: Farina Elisabetta , Baglio Francesca 
Published: March 2010

AbstractCognitive disabilities, especially memory disturbances and cognitive deficits, posttraumatic brain injury (TBI), and poststroke are important targets for clinical pharmacological trials due to their important epidemiological and social impact. Brain changes leading to cognitive decline and dementia, and their relation to disability, are key topics requiring investigation at the population level. It is expected that pharmacological approaches will become increasingly integrated with behavioral, genetic, and neuroimaging methods to investigate disease processes and the normal and preclinical individual differences that underlie successful— or unsuccessful—aging.
Ethical Issues in Clinical Research
Authors: Tremellen Kelton , Belford David 
Published: March 2010

AbstractMedical research has the potential to create huge benefits to society and enhance the professional reputation of the researchers responsible for the discoveries. However, a researcher must never knowingly compromise the welfare of a research participant, irrespective of how important the research outcomes are to society in general. This article aims to educate clinical researchers in the common pitfalls of human experimentation and ways to avoid these ethical problems in pharmaceutical trials.
Imaging as a Localized Biomarker: Opportunities and Challenges
Authors: Moody Jonathan B. , Murphy Philip S. , Ficaro Edward P. 
Published: March 2010

AbstractIn recent years, the concept of imaging biomarkers is increasingly being utilized in drug development and for producing images of physiological and physicochemical processes in a living subject. Continuous research and development for more than 30 years has produced a steady stream of new imaging technologies as well as incremental improvements that address the limitations of existing technologies. This article focuses on understanding the opportunities for using imaging biomarkers as tools in drug development while recognizing the current challenges and how efforts to overcome these challenges are evolving.
Qualification of Safety Biomarkers for Application to Early Drug Development
Authors: Mattes William B. , Sistare Frank D. 
Published: March 2010

Abstract
Biomarkers are judged on the basis of whether they have been subjected to a process of validation. There are a number of preclinical and clinical studies and resources available to qualify a biomarker as a characterization biomarker appropriate for regulatory decision making. This article focuses on the qualification of safety biomarkers for application to early drug development.
Development of Serum Calcium and Phosphorus as Clinical Biomarkers for Drug‐Induced Systemic Mineralization: Case Study with aMEKInhibitor
Authors: Brown Alan P. 
Published: March 2010

AbstractThe nonclinical safety of PD0325901 was evaluated in Sprague‐Dawley rats given single oral or intravenous (IV) doses, in beagle dogs given oral and IV escalating doses, and in cynomolgus monkeys given escalating oral doses to assess acute toxicity and assist in dose selection for subsequent studies. A significant toxicity was observed that involved mineralization of vasculature and various soft tissues. This article focuses on the development of serum calcium and phosphorus as clinical biomarkers for drug‐induced systemic mineralization.
Opportunities and Pitfalls Associated with Early Utilization of Biomarkers: Case Study in Anticoagulant Development
Authors: Criswell Kay A. 
Published: March 2010

AbstractAll pharmaceutical companies are focusing on ways, such as improving target validation, selecting candidates with a greater chance of success, and identifying those compounds that will fail earlier in their development, to reduce the cost of discovering and developing new drugs. Therefore, developing a strategy for development of safety and efficacy biomarkers is key to early prediction of compound success or failure. This article focuses on opportunities and pitfalls associated with early utilization of biomarkers in drug development process.
Funding Biomarker Research and Development through the Small Business Innovative Research Program
Authors: Varani James 
Published: March 2010

Abstract
Obtaining funds through the Small Business Innovative Research (SBIR) program is every bit as challenging as being successful through the traditional mechanisms. One can increase the chances of being successful by understanding the process and by carefully studying past successes as well as past failures. This article discusses some of the key features of the SBIR program and things that may increase the likelihood of success in funding a biomarker‐development project through the SBIR program.
Novel and Traditional Nonclinical Biomarker Utilization in the Estimation of Pharmaceutical Therapeutic Indices
Authors: Car Bruce D. , Gemzik Brian , Foster William R. 
Published: March 2010

Abstract
Accurate determination of therapeutic indices from nonclinical studies across multiple species provides an invaluable tool for advancing compounds with reduced potential for harm and reduced likelihood of attrition for safety concerns. The robustness of those estimates over time is also central to the ability to conduct proof‐of‐concept studies in humans in phases IIa and IIb. This article focuses on novel and traditional nonclinical biomarker utilization in the estimation of pharmaceutical therapeutic indices.
Optimizing the Use of Biomarkers for Drug Development: A Clinician's Perspective
Authors: Gimona Alberto 
Published: March 2010

Abstract
The need for the pharmaceutical industry to increase its productivity and, in particular, the need to concentrate the available limited resources to the most promising drug candidates lead to the current emphasis on development and use of biomarkers. Biomarkers predict the efficacy of a compound at the early stage of development, increasing the efficiency of the development process. This article provides clinician's perspective on optimizing the use of biomarkers for drug development.
Strategies for the Cytosolic Delivery of Macromolecules: An Overview
Authors: Asokan Aravind , Cheung Roland , Cho Moo J. 
Published: March 2010

AbstractThe advent of molecular biology and genetics has identified numerous biotechnology‐derived macromolecular drugs as potential targets for development. The delivery of small molecules requires compromise between aqueous solubility and membrane partition properties while that of proteins and genes requires protection from enzymatic degradation and denaturation. This article focuses on strategies to promote the cytosolic delivery of macromolecular therapeutics.
Pharmaceutical Bioassay
Authors: Li Jun , Zhao Ming , Peng Shiqi 
Published: March 2010

AbstractThis article focuses on various types of biopharmaceutical bioassays, such as toxicity bioassay, antiviral assay, anticancer assay, hepatoxicity assay, hepatoprotective assay, anti‐inflammatory assay, thrombus‐related assay, immunomodulating assay, estrogen assay, antimalarial assay, and blood pressure‐related assay. The elucidation of the mechanisms of special enzymes provides the bases for highly specific and sensitive bioassays focused on the target enzymes and cells. Lux‐Fluoro assay is developed on specific lesions for cells induced by DNA damaging chemicals may lead to cell death or induce an error‐prone repair pathway leading to mutagenesis and cancer induction.
Genetic Markers and Genotyping Analyses for Genetic Disease Studies
Authors: Kwitek Anne E. , Olivier Michael 
Published: March 2010

AbstractMajor research efforts have resulted in a sequence of information for many genomes, providing a tremendous resource for biomedical researchers to examine gene sequences, their regulation, and their role in health and disease. The discovery of the microsatellite as a highly polymorphic genetic marker, and its ability to generate genotypes in a high‐throughput manner, revolutionized genetic analyses of disease and greatly facilitated the mapping and sequencing of not only the human genome. This article focuses on different genotyping approaches commonly used in genetic laboratories.
Pharmacokinetics
Authors: Shibata Nobuhito , Ito Yukako , Takada Kanji 
Published: March 2010

AbstractRecombinant DNA technology has produced many proteins and peptides drugs in large scale, and they are becoming increasingly important as therapeutic agents. The successful development of recombinant proteins depends on the proper characterization of their pharmacokinetics and an understanding of the relationship between drug exposure or dose and the pharmacological response. This article describes the pharmacokinetics of clinically important peptide/protein drugs, such as insulin, erythropoietin (EPO), granulocyte‐colony stimulating factor (G‐CSF), interferon, growth hormone, leuprolide, desmopressin, and antibodies in relation to their administration routes and formulations.
Pharmacokinetics Of Nucleic‐Acid‐Based Therapeutics
Authors: Schmitz John C. , Pandyra Aleksandra , Koropatnick James , Berg Randal W. 
Published: March 2010

AbstractNucleic‐acid‐based therapies consist of various forms of gene and antisense therapeutics. Gene and antisense therapeutics have unique applications based on local delivery, which limits the distribution of the therapeutic in the body and precludes considerations of their pharmacokinetics (PK). This article presents chemical structures of antisense oligonucleotides (ASOs) being developed as therapeutics and the published animal and human PK data regarding ASOs of two chemistries, exemplified by Genasense and OGX‐011.
Growth Factors and Cytokines
Authors: Mann Mandeep K. , Cairns Brian E. 
Published: March 2010

AbstractNeurotrophic factors, such as nerve growth factor (NGF) and cytokines, are involved in nociceptive and neuropathic pain conditions, such as diabetic peripheral neuropathies. It is also observed that intramuscular injection of human NGF at a concentration equivalent to that which resulted in mechanical sensitization in humans caused a significant decrease in the mechanical threshold of rat masseter muscle afferent fibers. This article focuses on NGF and tumor necrosis factor alpha and their role in the mechanisms of neuropathic and nociceptive pain.
Protein Engineering with Noncoded Amino Acids: Applications to Hirudin
Authors: De Filippis Vincenzo 
Published: March 2010

Abstract

The incorporation of noncoded amino acids into proteins has emerged as a novel and promising approach in protein science. Several different strategies are being pursued to incorporate noncoded amino acids, including peptide synthesis native chemical ligation, enzyme‐catalyzed semisynthesis, biosynthetic incorporation
via
auxotrophic bacterial strain expression, and nonsense suppression methodologies in cell‐free or whole‐cell expression systems. This article discusses the use of noncoded amino acids in structure‐activity relationship (SAR) studies of hirudin binding to thrombin, as well as the incorporation of noncoded analogs of tryptophan and tyrosine as spectroscopic probes for studying the hirudin‐thrombin interaction.
Manufacturing Specialties
Authors: Carl Stephen M. , Lindley David J. , Knipp Gregory T. , Morris Kenneth R. , Oliver Erin , Becker Gerald W. , Arnold Robert D. 
Published: March 2010

AbstractRecent advances in molecular and cellular biological techniques and the potential clinical benefits of biotechnology drug products have led to a substantial increase in their development by biotechnology and traditional pharmaceutical companies. As the clinical importance and commercial potential for biological products grows, new challenges are arising based on the many technological limitations related to the development and marketing of these complex agents. This article focuses on some of the fundamental issues associated with successful biopharmaceutical drug product development and aims to provide an understanding of the subtleties associated with their characterization, processing, and manufacturing.
Oil‐in‐Water Nanosized Emulsions: Medical Applications
Authors: Tamilvanan Shunmugaperumal 
Published: March 2010

AbstractOil‐in‐water (o/w) nanosized emulsions have been used for enhancing lipophilic drug absorption and clinical efficacy of lipophilic drugs. Due to their subcellular and submicrometer size, emulsions allow for efficient delivery of therapeutic agents to target sites in the body. This chapter focuses on the classification, preparation, and medical applications of o/w nanosized emulsions.
Chemical Imaging and Chemometrics: Useful Tools for Process Analytical Technology
Authors: Roggo Yves , Ulmschneider Michel 
Published: March 2010

AbstractChemical imaging or vibrational hyperspectral imaging is a form of imaging in which chemical information from spectroscopy is combined with spatial information. Hyperspectral images can be collected with a single‐point detector, however array detectors measure all pixels simultaneously, reduce recording time, provide uniform background, and improve the signal‐to‐noise ratio. This article defines chemical imaging and describes image formation and instrumentation in chemical imaging.
Analytical Method Validation and Quality Assurance
Authors: Taverniers Isabel , Van Bockstaele Erik , De Loose Marc 
Published: March 2010

AbstractDue to fast development of analytical methodologies, great importance is nowadays attached to the quality and reliability of the measurement data. This is influenced by a higher demand for regulatory compliance and under more exigent European and international standards such as the International Organization of Standardization/International Electrotechnical Commission 17025 norm for laboratory accreditation. This article focuses on method validation, traceability, measurement uncertainty (MU) of results, standardization, internal quality control (IQC), external quality control (EQC), and the role of method validation within quality assurance (QA).
Modeling transdermal permeation. Part 2. Predicting the dermatopharmacokinetics of percutaneous solute
Authors: Lian Guoping , Chen Longjian , Pudney Paul D. A. , Mélot Mickaël , Han Lujia 
Published: March 2010

AbstractThe prediction of percutaneous absorption and bioavailability in vivo, using the recently reported “bricks‐and‐mortar” model is discussed. Two sets of in vivo data have been simulated: the tape‐striping data of 4‐cyanophenol and Raman spectrometry data of transretinol. The predicted transdermal permeation using theoretically derived properties agreed well with the experimental data. The prediction shows that about 2/3 of the 4‐cynophenol in the SC partitioned into the corneocytes, indicating diffusion of moderately hydrophobic solutes across the corneocytes is also important. Only for highly hydrophobic solute like transretinol, diffusion across the corneocytes is negligibly small. The study demonstrates that with the mechanism‐based computer model, many dermatopharmacokinetic parameters can be derived, providing much insight into how vehicle formulation and topical administration affects the absorption and distribution of solute in the SC, as well as its bioavailability in epidermis/dermis. © 2010 American Institute of Chemical Engineers AIChE J, 2010
Serum immunoglobulin free light chain measurements and heavy chain isotype usage provide insight into disease biology in patients with POEMS syndrome
Authors: Stankowski‐Drengler Trista , Gertz Morie A. , Katzmann Jerry A , Lacy Martha Q. , Kumar Shaji , Leung Nelson , Hayman Suzanne R. , Buadi Francis , Kyle Robert A. , Rajkumar S. Vincent , Dispenzieri Angela 
Published: March 2010

AbstractPOEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin changes) syndrome is a rare paraneoplastic syndrome in which nearly all patients have a monoclonal lambda restricted plasma cell disorder. We investigated whether patients with POEMS have abnormal serum immunoglobulin free light chain (FLC) ratios. Fifty patients with newly diagnosed POEMS syndrome were assessed. Cystatin C levels were measured to discern whether subclinical renal insufficiency could account for FLC elevations in the presence of a normal FLC ratio. Forty‐five patients (90%) had elevated lambda FLC; however, only nine (18%) had abnormal FLC ratios. The rise in serum FLC of POEMS patients appeared to be multifactorial—both a function of subclinical renal insufficiency and polyclonal activation of medullary and extramedullary plasma cells. Those patients expressing a clonal IgA were more likely to have clonal plasmacytosis observed on iliac crest biopsy than those with IgG. In summary, serum immunoglobulin profiles are unique in POEMS syndrome as compared with other plasma cell disorders. Am. J. Hematol. 2010. © 2010 Wiley‐Liss, Inc.
Novel Conjugates of Aspirin with Phenolic Acid as Anti‐inflammatory Agents Having Significantly Reduced Gastrointestinal Toxicity
Authors: Jiang Shan , Ding Ning , Zhang Wei , Zhang Yichun , Geng Meiyu , Li Yingxia 
Published: March 2010

AbstractA series of novel conjugates of aspirin with natural phenolic acid antioxidants connected through a diol linker were designed and synthesized as potential bifunctional agents combining antioxidant and anti‐inflammatory activity for reducing gastrointestinal toxicity. In general, the conjugates were found to be efficient antioxidants and many of them demonstrated much more potent anti‐inflammatory activity than aspirin. Among them, 5a and 5b which bear the best anti‐inflammatory activity exhibited significantly reduced ulcerogenic potency and toxicity compared to aspirin. However, it is evident that the anti‐inflammatory activity of these dual‐acting molecules in vivo, was not simply consistent with their antioxidant ability in vitro.
Synthesis and in‐vitro Cytotoxic Evaluation of Novel Pyridazin‐4‐one Derivatives
Authors: Mojahidi Souad , Rakib El Mostapha , Sekkak Hanan , Abouricha Said , Benchat Nouredine , Mousse Hassan Ait , Zyad Abdelmajid 
Published: March 2010

AbstractA new series of N‐aryl‐4‐oxo‐1,4‐dihydro‐pyridazine‐3‐carboxylic acids has been synthesized by condensation of aryldiazonium with 4‐hydroxy‐6‐methyl‐2‐pyrone. Some of these compounds exhibited in‐vitro cytotoxic activity with moderate to excellent growth inhibition against the murine P815 mastocytoma cell line. Compound 5b showed an important cytotoxic activity against cell line P815 (IC50 = 0.40 μg/mL).