Author
Joel M. Reid
Other affiliations: Oregon Health & Science University, Upjohn, New York University ...read more
Bio: Joel M. Reid is an academic researcher from Mayo Clinic. The author has contributed to research in topics: Pharmacokinetics & Temozolomide. The author has an hindex of 50, co-authored 248 publications receiving 10094 citations. Previous affiliations of Joel M. Reid include Oregon Health & Science University & Upjohn.
Topics: Pharmacokinetics, Temozolomide, Medicine, Neutropenia, Irinotecan
Papers published on a yearly basis
Papers
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TL;DR: The vitreous half-life of 1.25 mg intravitreal bevacizumab (Avastin) is 4.32 days in a rabbit eye, compared with 4.88 days and 6.86 days for the aqueous and serum values, respectively.
673 citations
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TL;DR: It is demonstrated that expression and activity of the NADase CD38 increase with aging and that CD38 is required for the age-related NAD decline and mitochondrial dysfunction via a pathway mediated at least in part by regulation of SIRT3 activity.
512 citations
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TL;DR: Although vitreous concentrations of ranibizumab declined in a monoexponential fashion with a half-life of 2.88 days, concentrations of >0.1 microg/ml ranibzumab were maintained in the Vitreous humor for 29 days, whereas small amounts of intravitreal bevacizumAB have been detected in the serum and fellow uninjected eye.
493 citations
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TL;DR: Both target suppression and antitumor activity were demonstrated in this phase I study of CI-1040, a small-molecule inhibitor of the dual-specificity kinases MEK -1 and MEK2 in patients with advanced malignancy.
Abstract: Purpose This phase I study was undertaken to define the toxicity, pharmacokinetics, pharmacodynamics, maximum tolerated dose (MTD), and clinical activity of CI-1040, a small-molecule inhibitor of the dual-specificity kinases MEK(mitogen-activated protein kinase kinase) -1 and MEK2 , in patients with advanced malignancy. Patients and Methods CI-1040 was tested in multiple daily dosing frequencies administered for 21 days repeated every 28 days leading ultimately to continuous administration, and effect of food on absorption was tested. Single dose and steady-state pharmacokinetics were assessed during cycle 1 and phosphorylated extracellular receptor kinase (pERK) levels were assessed in WBCs and also in tumor tissue from selected patients. Results Seventy-seven patients received CI-1040 at dose levels ranging from 100 mg QD to 800 mg tid. Grade 3 asthenia was dose limiting at the highest dose level tested, 800 mg tid administered with food. Ninety-eight percent of all drug-related adverse events were grad...
382 citations
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TL;DR: In this article, a family of structurally homologous nanoparticles, including neutral (TEGOH), zwitterionic (Tzwit), negative (TCOOH), and positive (TTMA), were injected into mice to investigate how surface properties such as charge played an important role in their in vivo behavior.
Abstract: Background
Inorganic nanoparticles provide promising tools for biomedical applications including detection, diagnosis and therapy. While surface properties such as charge are expected to play an important role in their in vivo behavior, very little is known how the surface chemistry of nanoparticles influences their pharmacokinetics, tumor uptake, and biodistribution.
Method/Principal Findings
Using a family of structurally homologous nanoparticles we have investigated how pharmacological properties including tumor uptake and biodistribution are influenced by surface charge using neutral (TEGOH), zwitterionic (Tzwit), negative (TCOOH) and positive (TTMA) nanoparticles. Nanoparticles were injected into mice (normal and athymic) either in the tail vein or into the peritoneum.
Conclusion
Neutral and zwitterionic nanoparticles demonstrated longer circulation time via both IP and IV administration, whereas negatively and positively charged nanoparticles possessed relatively short half-lives. These pharmacological characteristics were reflected on the tumor uptake and biodistribution of the respective nanoparticles, with enhanced tumor uptake by neutral and zwitterionic nanoparticles via passive targeting.
336 citations
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TL;DR: By successively addressing each of the biological barriers that a particle encounters upon intravenous administration, innovative design features can be rationally incorporated that will create a new generation of nanotherapeutics, realizing a paradigmatic shift in nanoparticle-based drug delivery.
Abstract: Biological barriers to drug transport prevent successful accumulation of nanotherapeutics specifically at diseased sites, limiting efficacious responses in disease processes ranging from cancer to inflammation. Although substantial research efforts have aimed to incorporate multiple functionalities and moieties within the overall nanoparticle design, many of these strategies fail to adequately address these barriers. Obstacles, such as nonspecific distribution and inadequate accumulation of therapeutics, remain formidable challenges to drug developers. A reimagining of conventional nanoparticles is needed to successfully negotiate these impediments to drug delivery. Site-specific delivery of therapeutics will remain a distant reality unless nanocarrier design takes into account the majority, if not all, of the biological barriers that a particle encounters upon intravenous administration. By successively addressing each of these barriers, innovative design features can be rationally incorporated that will create a new generation of nanotherapeutics, realizing a paradigmatic shift in nanoparticle-based drug delivery.
4,457 citations
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TL;DR: Interest in the topic of tumour metabolism has waxed and waned over the past century, but it has become clear that many of the signalling pathways that are affected by genetic mutations and the tumour microenvironment have a profound effect on core metabolism, making this topic once again one of the most intense areas of research in cancer biology.
Abstract: Interest in the topic of tumour metabolism has waxed and waned over the past century of cancer research. The early observations of Warburg and his contemporaries established that there are fundamental differences in the central metabolic pathways operating in malignant tissue. However, the initial hypotheses that were based on these observations proved inadequate to explain tumorigenesis, and the oncogene revolution pushed tumour metabolism to the margins of cancer research. In recent years, interest has been renewed as it has become clear that many of the signalling pathways that are affected by genetic mutations and the tumour microenvironment have a profound effect on core metabolism, making this topic once again one of the most intense areas of research in cancer biology.
4,169 citations
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TL;DR: This Perspective explores and explains the fundamental dogma of nanoparticle delivery to tumours and answers two central questions: ‘ how many nanoparticles accumulate in a tumour?’ and ‘how does this number affect the clinical translation of nanomedicines?'
Abstract: This Perspective explores and explains the fundamental dogma of nanoparticle delivery to tumours and answers two central questions: ‘how many nanoparticles accumulate in a tumour?’ and ‘how does this number affect the clinical translation of nanomedicines?’
3,335 citations
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TL;DR: The Pharmacological Basis of Therapeutics, by Prof. Louis Goodman and Prof. Alfred Gilman, New York: The Macmillan Company, 1941, p.
Abstract: The Pharmacological Basis of Therapeutics A Textbook of Pharmacology, Toxicology and Therapeutics for Physicians and Medical Students. By Prof. Louis Goodman and Prof. Alfred Gilman. Pp. xiii + 1383. (New York: The Macmillan Company, 1941.) 50s. net.
2,686 citations
01 Jan 1999
TL;DR: Caspases, a family of cysteine-dependent aspartate-directed proteases, are prominent among the death proteases as discussed by the authors, and they play critical roles in initiation and execution of this process.
Abstract: ■ Abstract Apoptosis is a genetically programmed, morphologically distinct form of cell death that can be triggered by a variety of physiological and pathological stimuli. Studies performed over the past 10 years have demonstrated that proteases play critical roles in initiation and execution of this process. The caspases, a family of cysteine-dependent aspartate-directed proteases, are prominent among the death proteases. Caspases are synthesized as relatively inactive zymogens that become activated by scaffold-mediated transactivation or by cleavage via upstream proteases in an intracellular cascade. Regulation of caspase activation and activity occurs at several different levels: ( a) Zymogen gene transcription is regulated; ( b) antiapoptotic members of the Bcl-2 family and other cellular polypeptides block proximity-induced activation of certain procaspases; and ( c) certain cellular inhibitor of apoptosis proteins (cIAPs) can bind to and inhibit active caspases. Once activated, caspases cleave a variety of intracellular polypeptides, including major structural elements of the cytoplasm and nucleus, components of the DNA repair machinery, and a number of protein kinases. Collectively, these scissions disrupt survival pathways and disassemble important architectural components of the cell, contributing to the stereotypic morphological and biochemical changes that characterize apoptotic cell death.
2,685 citations