Abstract:
:Novel biomarkers are often required in the preclinical development of biopharmaceuticals in order to characterize pharmacologic and toxicologic effects and to establish pharmacodynamic and pharmacokinetic relationships. Flow cytometry is uniquely suited for measurement of these biomarkers. Large numbers of single cells in a heterogeneous population can be rapidly identified and characterized with high accuracy and reproducibility. Cells are not damaged by the detection system and can be subsequently sorted for further morphologic or functional analysis. The availability of clinical instruments and a wide range of fluorescent probes have made this technology applicable for use in toxicologic clinical pathology. Flow cytometry has played an integral role in the development of a monoclonal antibody to human CD4 (keliximab, IDEC-CE9.1, SB 210396). Lymphocyte subset analysis and assays for expression, coating, and modulation of human CD4 were used for sequential assessment of the pharmacologic activity of keliximab in transgenic mice expressing human CD4.
journal_name
Toxicol Patholjournal_title
Toxicologic pathologyauthors
Gossett KA,Narayanan PK,Williams DM,Gore ER,Herzyk DJ,Hart TK,Sellers TSdoi
10.1177/019262339902700107subject
Has Abstractpub_date
1999-01-01 00:00:00pages
32-7issue
1eissn
0192-6233issn
1533-1601journal_volume
27pub_type
杂志文章,评审abstract::Pentostatin, an adenosine deaminase inhibitor, has been approved for the treatment of refractory hairy cell leukemia. In a preclinical toxicity study, Wistar rats were administered 0, 1, 10, 25, and 50 mg/kg (0, 6, 60, 150, and 300 mg/m2, respectively) pentostatin intravenously once a week for 26 wk (1.5-75-fold above...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262339402200506
更新日期:1994-09-01 00:00:00
abstract::The common marmoset, Callithrix jacchus, is the smallest nonhuman primate commonly used in biomedical research. Marmoset characteristics and propensities have enabled them to be used in a wide range of research as a model of human disease, physiology, drug metabolism, general toxicology, and reproductive biology. This...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1080/01926230390175002
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abstract::The clinical, laboratory, and pathologic features of a syndrome in dogs characterized by intermittent pain, fever, neutrophilia, and necrotizing arteritis are described to alert others involved in toxicity testing to the existence of this disorder. It is considered that this idiopathic syndrome is a latent condition, ...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262338901700109
更新日期:1989-01-01 00:00:00
abstract::The toxicities of 2'-fluorouridine (2'-FU) and 2'-fluorocytidine-HCl (2'-FC) were separately evaluated in 2 species, male Fischer 344 (F334) rats and woodchucks. Particular attention was focused on the ability of these nucleosides to induce toxicities similar to those induced by the antiviral drug fialuridine (FIAU). ...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262339902700601
更新日期:1999-11-01 00:00:00
abstract::The administration of mesenchymal stromal cells (MSCs) provides an exciting emerging therapeutic modality for the treatment of peripheral arterial disease, a condition that is associated with critical limb ischemia as its end stage. Placental-derived MSCs, termed PLX-PAD cells, are stable adhesive stromal cells isolat...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623309338383
更新日期:2009-08-01 00:00:00
abstract::Oltipraz, developed as an antischistosomal agent, protects against the hepatotoxicity of many xenobiotics and is known to be an effective inhibitor of experimental carcinogenesis in rodents. In the present study, we investigated its effects on the development of lesions in LEC rats, established as a mutant strain char...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1080/019262302753559506
更新日期:2002-03-01 00:00:00
abstract::ISIS 2302 is a phosphorothioate oligodeoxynucleotide with a sequence complementary to the mRNA of human intercellular adhesion molecule 1 (ICAM-1). Hybridization of ISIS 2302 to the mRNA inhibits expression of the ICAM-1 protein in response to inflammatory stimuli. A murine active antisense oligonucleotide, ISIS 3082,...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1177/019262339902700117
更新日期:1999-01-01 00:00:00
abstract::Partial hepatectomy (PH) and neonatal rat short-term liver focus models were used to examine the effects of selected chemicals that had been previously tested in the National Toxicology Program (NTP) 2-yr carcinogenicity studies. C.I. Solvent Yellow 14, monuron, chlorendic acid, and 4-hydroxyacetanilide were tested fo...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623389017004110
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abstract::Cytoplasmic vacuolation of sensory neurons has been reported to occur within the dorsal root ganglia in studies investigating various neuropathic conditions including the effects of neurotoxic chemicals. In this study, we investigated this lesion in adult (98-119 days old) male Long-Evans rats, after multiple exposure...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623310369343
更新日期:2010-06-01 00:00:00
abstract::To investigate pathogenesis of post-bile duct (BD) injury fibrosis, interlobular BD epithelial injury was induced in male F344 rats by a single IP injection of α-naphthylisothiocyanate (75 mg/kg body weight) and rats were observed for 12 days. On days 1 to 2, cholangiocytes were injured and desquamated. On days 3 to 5...
journal_title:Toxicologic pathology
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更新日期:2011-08-01 00:00:00
abstract::Many common inflammatory disorders are characterized by the infiltration of neutrophils across epithelial lined (mucosal) surfaces resulting in disruption of critical barrier function that protects from microbes and noxious agents. In such conditions, disease symptoms are complex but directly related to leukocyte effe...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1177/0192623313511336
更新日期:2014-01-01 00:00:00
abstract::Although arsenic exposure causes liver disease and/or hepatoma, little is known about molecular mechanisms of arsenic-induced liver toxicity or carcinogenesis. We investigated the effects of arsenic on expression of cancer-related genes in a rat liver following subchronic exposure to sodium arsenate (1, 10, 100 ppm in...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1080/01926230490261348
更新日期:2004-01-01 00:00:00
abstract::Interrelationships among induction of cytochrome P-450 (CYP) 1A1/2, decrease in connexin 32 (Cx32), and liver tumor-promoting activity by beta-naphthoflavone (BNF) in the promotion stage were examined in a 2-stage liver carcinogenesis model. A total of 20 male Fischer 344 rats were initiated with a single intraperiton...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262330002800406
更新日期:2000-07-01 00:00:00
abstract::The effects of oral contraceptives have been studied in the beagle bitch for periods up to 7 yr. High doses of these potent estrogen: progestogen (E:P) combinations have been shown to promote tumors in the mammary glands, smooth muscle of the tubular genitalia, and occasionally in the transitional epithelium of the ne...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1177/019262338901700216
更新日期:1989-01-01 00:00:00
abstract::Specific regions in the rodent larynx exhibit cellular changes in response to inhaled xenobiotics. These regions include the base of the epiglottis, ventral pouch, and medial surfaces of the vocal processes of the arytenoid cartilages. There are interspecies differences among laboratory rodents in the microscopic anat...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262339302100604
更新日期:1993-11-01 00:00:00
abstract::Exposure to synthetic fibers with employment in textile mills can be associated with an elevated risk of interstitial lung disease (ILD). A mechanism of injury has not been determined. ILD can follow exposures to inorganic fibers (e.g., asbestos) which are associated with a mobilization of iron and catalysis of an oxi...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1080/01926230600932448
更新日期:2006-01-01 00:00:00
abstract::Determining the carcinogenic potential of materials to which humans have significant exposures is an important, complex, and imperfect exercise. Not only are the methods for such determinations protracted and expensive and use large numbers of animals, extrapolation of data from such studies to human risk is imprecise...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623309351892
更新日期:2010-01-01 00:00:00
abstract::Alternate transgenic mouse models are accepted as replacements for the standard carcinogenicity mouse bioassay by regulatory agencies with a companion 2-year rat bioassay. The slower rate of industry acceptance of these shorter transgenic mouse cancer bioassays has been due to lack of historical data and diagnostic cr...
journal_title:Toxicologic pathology
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更新日期:2012-06-01 00:00:00
abstract::Existing liver perfusion models are largely limited by high degrees of ischemic and reperfusion injury and the lack of standardization. To establish a highly standardized perfusion model and minimize reperfusion injury, a porcine liver perfusion model was developed using an artificial heart pump (Buecherl Artificial H...
journal_title:Toxicologic pathology
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更新日期:2005-01-01 00:00:00
abstract::Enzyme histochemistry was assessed in semi-thin glycolmethacrylate sections after 100 mg/kg 2-bromoethanamine (BEA) hydrobromide had been given ip to male Wistar rats to induce renal papillary necrosis. Changes in the proximal tubular marker enzymes alkaline phosphatase (Alk Phos), gamma-glutamytranspeptidase (GGT) an...
journal_title:Toxicologic pathology
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abstract::Microminipigs have become an attractive animal model for toxicology and pharmacology studies and for human disease models, owing to their manageable size. Although there are numerous reports of spontaneous age-related lesions in mice, rats, dogs, and monkeys, those in minipigs are scarce. In the present study, spontan...
journal_title:Toxicologic pathology
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doi:10.1177/0192623319861350
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abstract::When chemicals that are nongenotoxic in conventional assays produce increases in tumor incidence in rodents in chronic bioassays, the determination of the significance of these data for human safety is a challenging task. An important first step in this process is consideration of available data on the mechanism of ac...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1177/019262339402200206
更新日期:1994-03-01 00:00:00
abstract::Cyclodextrins are oligosaccharides which are used in the pharmaceutical industry and research as vehicles for application of apolar substances such as steroids. The aim of this study was to examine the long-term effects of parenteral administration of 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) on bone. Sham-operated (SH...
journal_title:Toxicologic pathology
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更新日期:2012-07-01 00:00:00
abstract::The microbiome is increasingly recognized as a critical component in human development, health, and disease. Its relevance to toxicology and pharmacology involves challenges to current concepts related to absorption, metabolism, gene:environment, and pathways of response. Framing testable hypotheses for experimental a...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1177/0192623316672073
更新日期:2017-01-01 00:00:00
abstract::This continuing education course presented at the Society of Toxicologic Pathology's 31st Annual Symposium explored and defined the many roles that toxicologic pathologists serve Good Laboratory Practice (GLP)-conducted toxicology and carcinogenicity studies. ...
journal_title:Toxicologic pathology
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doi:10.1177/0192623313506521
更新日期:2014-01-01 00:00:00
abstract::An eosinophilic substance (ES) is usually observed in the mouse nasal septum. In contrast to textbooks and one report describing ES as amyloid, a previous study by the authors revealed that ES is not amyloid but consists of collagen and an amorphous material. Furthermore, it was suggested that the amorphous material w...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623310367805
更新日期:2010-06-01 00:00:00
abstract::Chlorozotocin is a chloroethylnitrosourea antitumor agent that is in clinical trial for a variety of human tumors. Renal failure has been a reported side effect of treatment with several of the chloroethylnitrosoureas, including chlorozotocin. To better understand the pathogenesis of this target organ toxicity, we hav...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262338601400211
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abstract::Cysteamine is the first chemical identified that induces acute and chronic duodenal ulcers in rodents. Structure-activity studies with cysteamine, propionitrile and their derivatives, as well as with analogues of toluene, revealed numerous alkyl and aryl duodenal ulcerogens. Among these, one of the most interesting fr...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
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更新日期:1988-01-01 00:00:00
abstract::Many goitrogenic xenobiotics that increase the incidence of thyroid tumors in rodents exert a direct effect on the thyroid gland to disrupt one of several possible steps in the biosynthesis, secretion, and metabolism of thyroid hormones. This includes (a) inhibition of the iodine trapping mechanism, (b) blockage of or...
journal_title:Toxicologic pathology
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更新日期:1997-01-01 00:00:00
abstract::A factor limiting widespread use of the transgenic rasH2 mouse model for carcinogenicity testing of pharmaceuticals is the paucity of published data on actual drug candidates in rasH2 mice. This report addresses this gap by highlighting rasH2 mouse study data for 10 pharmaceutical candidates. These results were compar...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623313477257
更新日期:2013-01-01 00:00:00