Abstract:
:Animal models have provided an important tool to help make the decision to take potential therapies from preclinical studies to humans. In the past several years, the strong reliance of the pharmaceutical discovery and development process on the use of animal models has come under increasing scrutiny for ethical and scientific reasons. Several prominent and widely publicized articles have reported limited concordance of animal experiments with subsequent human clinical trials. Recent assessments of the quality of animal studies have suggested that this translational failure may be due in part to shortcomings in the planning, conduct, and reporting of in vivo studies. This article will emphasize methods to assure best practice rigor in animal study methods and reporting. It will introduce the so-called scientific 3Rs of relevance, robustness, and reproducibility to the in vivo study approach and will review important new trends in the animal research and pharmaceutical discovery and development communities.
journal_name
Toxicol Patholjournal_title
Toxicologic pathologyauthors
Everitt JIdoi
10.1177/0192623314555162subject
Has Abstractpub_date
2015-01-01 00:00:00pages
70-7issue
1eissn
0192-6233issn
1533-1601pii
0192623314555162journal_volume
43pub_type
杂志文章abstract::Necropsies conducted to support medical device development may be conducted in facilities that do not have the infrastructure in place to support Good Laboratory Practice for Nonclinical Laboratory Studies (GLP) studies and for a variety of reasons they may be conducted without a pathologist present at necropsy. Howev...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623315617035
更新日期:2016-01-01 00:00:00
abstract::Toxicogenomics using a reference database can provide a better understanding and prediction of toxicity, largely by creating biomarkers that tie gene expression to actual pathology events. During the course of building a toxicogenomic database, an observation was made that a number of non-steroidal anti-inflammatory c...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1080/01926230600611752
更新日期:2006-01-01 00:00:00
abstract::A comparative study of histochemical detection of eosinophils in fixed murine tissue is lacking. Five histochemical methods previously reported for eosinophil detection were quantitatively and qualitatively compared in an established murine RSV vaccine-enhanced inflammation model. Nonspecific neutrophil staining was e...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623308329342
更新日期:2009-02-01 00:00:00
abstract::Clinical, pathologic, and analytical records from 200 cattle were reviewed to determine if long-term exposures to elevated fluorides resulted in previously unrecognized or unreported pathologic changes, especially skeletal neoplasia. Animals were part of comprehensive field and laboratory investigations of bovine fluo...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262339202000216
更新日期:1992-01-01 00:00:00
abstract::We believe the development and validation of in vitro alternatives to eliminate the need to use animals in ocular irritation testing must be based on a thorough understanding of the mechanisms of ocular irritation. We have recently undertaken the task of developing such an understanding for a panel of surfactants. The...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262339802600206
更新日期:1998-03-01 00:00:00
abstract::Hyaline droplet formation in the proximal tubular cells of the kidney commonly occurs under different pathological conditions in experimental animals. In rats, intracytoplasmic hyaline droplet formation is predominantly associated with accumulation of the male rat-specific alpha(2u)-globulin, whereas under other (path...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1080/01926230390213775
更新日期:2003-07-01 00:00:00
abstract::In order to investigate the role of the stimulation of cell division for the initiation (and possibly promotion) of liver tumors by chemical carcinogens, the incorporation of radiolabelled thymidine into liver DNA was determined in male rats. Single doses of various levels of aflatoxin B1, benzidine and carbon tetrach...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262338401200118
更新日期:1984-01-01 00:00:00
abstract::Some developmental dual-acting PPARalpha/gamma agonists, such as ragaglitazar, have shown carcinogenic effects in the rodent urinary bladder urothelium after months-years of dosing. We examined early (precancerous) changes in the bladder urothelium of rats orally dosed with ragaglitazar, using a newly developed flow c...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1080/01926230500214657
更新日期:2005-01-01 00:00:00
abstract::Excitatory amino acids (EAAs) mediate their effects through the glutamate receptors (GluRs) in the brain. GluRs play an important role in the treatment of a variety of neuropsychiatric conditions and are central to the neurotoxicity of EAAs such as domoic and kainic acid. Unstained histological preparations of human h...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1080/01926230701230361
更新日期:2007-04-01 00:00:00
abstract::Peroxisome proliferator-activated receptor gamma (PPARγ) agonists and PPARγ/α dual agonists are used in the treatment of type 2 diabetes mellitus and hyperlipidemias. In carcinogenicity studies, some of these agonists induced hemangiomas/hemangiosarcomas in mice, but not in rats. We hypothesized that increased endothe...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623311422080
更新日期:2011-12-01 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
更新日期:1986-01-01 00:00:00
abstract::Zibotentan, an endothelin-A receptor antagonist, has been used in the treatment of various cardiovascular disorders and neoplasia. Castrated athymic nude mice receiving zibotentan for a preclinical xenograft efficacy study experienced weight loss, gastrointestinal bloat, and the presence of an audible respiratory clic...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623318816295
更新日期:2019-02-01 00:00:00
abstract::Repeated intraperitoneal injections of crocidolite asbestos fibers induced diffuse malignant mesotheliomas in mice. A series of mesothelial cell lines was isolated from mice at different stages in the development of these tumors. The cell lines isolated from mice with mesotheliomas recapitulated their growth pattern i...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262339702500605
更新日期:1997-11-01 00:00:00
abstract::Previous work in our laboratory revealed that the pubertal period of reproductive development in the male rat was particularly vulnerable to gossypol exposure, with a higher frequency of round structures in the lumen of the cauda epididymidis in the treated rats. Herein, we utilized hemicastration and electron microsc...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1080/01926230600932455
更新日期:2006-01-01 00:00:00
abstract::Transgenic Tg.AC mice carry a v-Ha-ras coding region flanked by a zeta-globin promoter and an SV40 polyadenylation signal sequence. These mice respond to carcinogens by developing epidermal papillomas. In some cases, malignancies develop at the sites of these papillomas. Various patterns of squamous cell differentiati...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262339802600407
更新日期:1998-07-01 00:00:00
abstract::Astrocytes assume multiple roles in maintaining an optimally suited milieu for neuronal function. Select astrocytic functions include the maintenance of redox potential, the production of trophic factors, the regulation of neurotransmitter and ion concentrations, and the removal of toxins and debris from the cerebrosp...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1177/0192623310385254
更新日期:2011-01-01 00:00:00
abstract::The role of articular chondrocytes and matrix degrading enzymes such as collagenase and neutral protease in the pathogenesis of quinolone-induced cartilage degeneration was investigated in immature guinea pigs. Articular cartilage from nalidixic acid (NA) treated guinea pigs was examined for the presence of protease a...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262339001800209
更新日期:1990-01-01 00:00:00
abstract::Pepsinogens are acid protease enzymes of pepsin usually found in gastric mucosa. In the present study, we demonstrated the presence of pepsinogen isozymes in male Syrian golden hamster lung tissues by a combined immunohistochemical and biochemical approach. Immunohistochemically, using rat pepsinogen 1 antibody, pepsi...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262339101900305
更新日期:1991-01-01 00:00:00
abstract::At present (putative) human carcinogens are identified via epidemiological studies and testing using the chronic 2-yr rodent bioassay. Both methods have severe limitations in that they are slow, insensitive, expensive, and are also hampered by many uncertainties. The development of methods to modify specific genes in ...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1177/019262339802600605
更新日期:1998-11-01 00:00:00
abstract::ZD7114, [(S)-4-[2-(2-hydroxy-3 phenoxypropylamine)ethoxy]-N-(2-methoxyethyl) phenoxyacetamide], and ZD2079, [(R)-N-(2-[4- (carboxymethyl)phenoxy]ethyl)-N-(beta-hydroxyphenethyl)ammonium chloride], are beta 3-adrenoceptor stimulants with selectivity for brown adipose tissue. ZD7144 is the hydrochloride salt of the S-en...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262339902700203
更新日期:1999-03-01 00:00:00
abstract::Female mammals are born with a finite number of ovarian primordial follicles that cannot be regenerated; thus, chemicals that destroy oocytes contained in these follicles can produce premature ovarian failure (early menopuase in women). Exposure of women to known ovotoxicants, such as contaminants in cigarette smoke, ...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1080/019262301301418892
更新日期:2001-01-01 00:00:00
abstract::The spleen contains hematopoietic and lymphoid elements, is a primary site of extramedullary hematopoiesis, and removes degenerate and aged red blood cells as well as particulate materials and circulating bacteria from the blood supply. Lesions of this important component of the immune system may center on the red pul...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1080/01926230600867750
更新日期:2006-01-01 00:00:00
abstract::This is a survey of the results of recent investigations on gastrointestinal (GI) peptide hormones. In addition to the classical GI hormones (secretin, gastrin, and cholecystokinin-pancreozymin (CCK-PZ], there are at least nine other peptides whose structures and GI effects are known. These include vasoactive intestin...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1177/019262338801600203
更新日期:1988-01-01 00:00:00
abstract::Standard histology trimming practices for toxicity studies in dogs include preparation of a section of the papillary muscle associated with the left ventricular free wall-the anteriolateral or anterior muscle. In contrast, the posteromedial or posterior papillary muscle, associated with the interventricular septum, is...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623320963020
更新日期:2020-10-01 00:00:00
abstract::In the present study, beta-catenin localization in hepatocellular neoplasms and hepatoblastomas, induced by oral administration of p-Nitroanisole (pNA) in Crj:BDF1 for 2 years, was evaluated by immunohistochemistry along with genetic alterations in exon 2 of beta-catenin by the polymerase chain reaction-single strand ...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1080/01926230600695474
更新日期:2006-01-01 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::A variety of phenotypic cellular changes emerge in the liver of different species prior to the appearance of hepatocellular adenomas and carcinomas induced by carcinogenic agents (chemicals, radiation, hepadna viruses) or develop "spontaneously." Foci of altered hepatocytes have been studied most extensively in rats t...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1177/0192623389017004107
更新日期:1989-01-01 00:00:00
abstract::Expression of antigens in cells and tissues can be readily studied immunohistochemically with the use of antibodies. A panel of antibodies to cell-specific markers can be used to diagnose lesions, including tumors, in the hematopoietic and lymphoid systems. This review discusses the use of readily available antibodies...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1177/0192623311430695
更新日期:2012-01-01 00:00:00
abstract::Most available data on the involvement of p53 in rodent carcinogenesis are based on results of the end point of chemically or virally induced carcinogenesis, i.e., tumors. To investigate the role of altered p53 expression in early stages of rodent hepatocarcinogenesis in a systematic way, we treated male Wistar rats f...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262339802600507
更新日期:1998-09-01 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