Characterizing "Adversity" of Pathology Findings in Nonclinical Toxicity Studies: Results from the 4th ESTP International Expert Workshop.

abstract：:Focal spontaneously occurring eosinophilic hypertrophic cells, histomorphologically resembling oncocytes and hepatocytes, were observed in the pancreas from 11 (0.3%) of 4,177 Sprague-Dawley rats, 3 to 26 months old. The age of these eleven rats ranged from 13 to 25 months. The incidence was not different between sexe...

journal_title：Toxicologic pathology

authors： Chiu T

更新日期：1987-01-01 00:00:00

abstract：:Fusion of biologic therapeutics to hyaluronic acid binding proteins, such as the link domain (LD) of Tumor necrosis factor (TNF)-Stimulated Gene-6 (TSG-6), is expected to increase vitreous residence time following intravitreal injection and provide for long-acting delivery. The toxicity of a single intravitreal dose o...

journal_title：Toxicologic pathology

authors： Laing ST,Tassew N,Tesar D,Wang Y,Crowell SR,Gray J,Kwong M,Loyet KM,Andaya R,Kusi A,Kelley RF

更新日期：2020-12-21 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

authors： Nambiar PR,Morton D

更新日期：2013-01-01 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

authors： Henry SP,Templin MV,Gillett N,Rojko J,Levin AA

更新日期：1999-01-01 00:00:00

abstract：:An annular, reddened lesion with mild serosal hemorrhage and no tumorous mass formation was detected in the right uterine horn of a 37-week-old female Sprague-Dawley rat that had postpubertal vaginal bleeding. Histological examination revealed prominent proliferation of the endometrium, which occupied the uterine lume...

journal_title：Toxicologic pathology

authors： Shirota M,Kawashima J,Nakamura T,Ogawa Y,Kamiie J,Shirota K

更新日期：2013-01-01 00:00:00

abstract：:This report documents the histological changes in nude mouse skin and in human skin xenografts on nude mice following exposure to phenyldichloroarsine (PDA), a vesicant arsenical. Under light microscopy, we observed in PDA-treated human skin grafts: 1) degeneration of epidermal cell nuclei (apparent by 2 hr after expo...

journal_title：Toxicologic pathology

authors： McGown EL,van Ravenswaay T,Dumlao CR

更新日期：1987-01-01 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

authors： Golbar HM,Izawa T,Yano R,Ichikawa C,Sawamoto O,Kuwamura M,Lamarre J,Yamate J

更新日期：2011-08-01 00:00:00

abstract：:The literature evidencing the role of iron in promoting a range of neoplasms in humans and animals prompted us to search for a possible association between chemically induced hemosiderosis and hemangiosarcomas in the liver of mice in selected studies conducted by the National Toxicology Program (NTP). Its historical c...

journal_title：Toxicologic pathology

authors： Nyska A,Haseman JK,Kohen R,Maronpot RR

更新日期：2004-03-01 00:00:00

abstract：:Sensitive kidney safety assessment is important for successful drug development in both preclinical and clinical stages. The Food and Drug Administration recently qualified a composite measure of 6 urine creatinine-normalized biomarkers, such as clusterin, cystatin C, kidney injury molecule 1 (KIM-1), N-acetyl-β-d-glu...

journal_title：Toxicologic pathology

authors： Sandelius Å,Basak J,Hölttä M,Sultana S,Hyberg G,Wilson A,Andersson P,Söderberg M

更新日期：2020-12-01 00:00:00

abstract：:The nonnucleoside inhibitor (NNI) of HIV-1 reverse transcriptase, PHI-346 (N-[2-(1-cyclohexenyl)ethyl]-N'-[2-(5-bromopyridyl)]-thiourea), is a dual-function spermicidal agent with potent anti-HIV activity against drug-sensitive as well as drug-resistant HIV-1 strains with genotypic and phenotypic NNI resistance. PHI-3...

journal_title：Toxicologic pathology

authors： D'Cruz OJ,Waurzyniak B,Uckun FM

更新日期：2002-11-01 00:00:00

abstract：:Cardiovascular safety signals in nonclinical studies remain among the main reasons for drug attrition during pharmaceutical research and development. Drug-induced changes can be functional and/or associated with morphological alterations in the normal heart histology. It is therefore crucial to understand the normal v...

journal_title：Toxicologic pathology

authors： Chanut F,Kimbrough C,Hailey R,Berridge B,Hughes-Earle A,Davies R,Roland K,Stokes A,Casartelli A,York M,Jordan H,Crivellente F,Cristofori P,Thomas H,Klapwijk J,Adler R

更新日期：2013-01-01 00:00:00

abstract：:Tubular injury sensitizes glomeruli to injury. We review potential mechanisms of this tubuloglomerular cross talk. In the same nephron, tubular injury can cause stenosis of the glomerulotubular junction and finally result in atubular glomeruli. Tubular injury also affects glomerular filtration function through tubulog...

journal_title：Toxicologic pathology

authors： Wang J,Zhong J,Yang HC,Fogo AB

更新日期：2018-12-01 00:00:00

abstract：:Morphologic lesions have received only limited attention as in vitro endpoints of toxicity. In the present work, "tissue" and cell morphology of control and toxicant-treated primary dissociated cerebrocortical cell cultures from fetal mice were examined using phase-contrast and bright-field microscopy. In untreated co...

journal_title：Toxicologic pathology

authors： Bolon B,Dorman DC,Bonnefoi MS,Randall HW,Morgan KT

更新日期：1993-09-01 00:00:00

abstract：:Overexpression of c-myc and transforming growth factor-alpha (TGF-alpha) has been frequently observed in human hepatocellular carcinoma (HCC),suggesting a pivotal role played by these protooncogenes in liver oncogenesis. In order to investigate the molecular events underlying human hepatic malignant transformation, we...

journal_title：Toxicologic pathology

authors： Calvisi DF,Thorgeirsson SS

更新日期：2005-01-01 00:00:00

abstract：:A rat liver foci bioassay (RLFB) based on an initiation-promotion protocol employing preneoplastic foci of altered hepatocytes (FAH) as an endpoint, was prevalidated in 5 different laboratories. FAH were identified by immunohistochemical demonstration of glutathione-S-transferase (placental form, GSTP) and by staining...

journal_title：Toxicologic pathology

authors： Ittrich C,Deml E,Oesterle D,Küttler K,Mellert W,Brendler-Schwaab S,Enzmann H,Schladt L,Bannasch P,Haertel T,Mönnikes O,Schwarz M,Kopp-Schneider A

更新日期：2003-01-01 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

authors： Silbergeld EK

更新日期：2017-01-01 00:00:00

abstract：:Livers of male Sprague-Dawley rats were evaluated for foci and nodules 90 days and 16 months after one or two oral doses of 1,2-dibromoethane (DBE). Rats (190 g) were given the following oral treatments. Controls received corn oil (2.5 ml/kg) at 0 and 24 hr. DBE X 1 received corn oil at 0 hr and 75 mg DBE/kg at 24 hr....

journal_title：Toxicologic pathology

authors： Moslen MT

更新日期：1984-01-01 00:00:00

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

authors： Hayes TJ,Roberts GK,Halliwell WH

更新日期：1989-01-01 00:00:00

abstract：:The histologic effect of 400 mg/M2/day of hydrocortisone, given alternatively from day 7 to day 19 after birth, was studied on the spleen of the immunologically immature rat. Two days after the cessation of treatment, the periarteriolar lymphatic sheaths were found to be largely depleted of small lymphocytes. Immunope...

journal_title：Toxicologic pathology

authors： el Fouhil AF,Iskander FA,Turkall RM

更新日期：1993-01-01 00:00:00

abstract：:Two-year toxicity studies were conducted on the widely used herbal products, goldenseal and milk thistle, in male and female F344/N rats and B6C3F1 mice. With goldenseal root powder, the primary finding was an increase in liver tumors in rats and mice, and with milk thistle extract, a decrease in spontaneous backgroun...

journal_title：Toxicologic pathology

authors： Dunnick JK,Singh B,Nyska A,Peckham J,Kissling GE,Sanders JM

更新日期：2011-02-01 00:00:00

abstract：:Peroxisome proliferator-activated receptor-alpha (PPARalpha) agonists such as fenofibrate are used to treat dyslipidemia. Although fenofibrate is considered safe in humans, it is known to cause hepatocarcinogenesis in rodents. To evaluate untargeted metabolic profiling as a tool for gaining insight into the underlying...

journal_title：Toxicologic pathology

authors： Ohta T,Masutomi N,Tsutsui N,Sakairi T,Mitchell M,Milburn MV,Ryals JA,Beebe KD,Guo L

更新日期：2009-06-01 00:00:00

abstract：:Systemic hypoxemia, occurring in space-occupying lung pathologies such as inflammation and neoplasms. reduces the gas exchange area and stimulates catecholamine secretion from the adrenal medulla where chronic endocrine hyperactivity may lead to hyperplasia and neoplasia. We investigated the possible correlation betwe...

journal_title：Toxicologic pathology

authors： Ozaki K,Haseman JK,Hailey JR,Maronpot RR,Nyska A

更新日期：2002-03-01 00:00:00

abstract：:Blood platelets play a fundamental role in hemostasis and thrombosis. The physiological role of platelets is to preserve the integrity of the cardiovascular system such that upon injury platelets are activated and serve to interrupt a potentially deleterious situation (i.e., hemorrhage). However, platelets are also in...

journal_title：Toxicologic pathology

authors： Shebuski RJ

更新日期：1993-01-01 00:00:00

abstract：:Direct tissue profiling and imaging mass spectrometry (MS) allow for detailed mapping of the complex protein pattern across a tissue sample. Utilization of these tools provides spatial information across a tissue section for target protein expression and can be used to correlate changes in expression levels with speci...

journal_title：Toxicologic pathology

authors： Chaurand P,Schwartz SA,Reyzer ML,Caprioli RM

更新日期：2005-01-01 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

authors： Suttie AW

更新日期：2006-01-01 00:00:00

abstract：:Successful development and use of biomarkers will improve the productivity of oncology drug development. Recognition of the importance of biomarkers for speeding drug development is reflected in the precise definitions and concepts proposed by an NIH Working Group to standardize terminology and promote a more coherent...

journal_title：Toxicologic pathology

authors： Floyd E,McShane TM

更新日期：2004-03-01 00:00:00

abstract：:The outcome of cardiac ischemic events depends not only on the extent and duration of the ischemic stimulus but also on the myocardial intrinsic tolerance to ischemic injury. Cardiac ischemic tolerance reflects myocardial functional reserves that are not always used when the tissue is appropriately oxygenated. Ischemi...

journal_title：Toxicologic pathology

authors： Golomb E,Nyska A,Schwalb H

更新日期：2009-08-01 00:00:00

abstract：:Oxymetholone has been identified as a suspected nongenotoxic carcinogen and has recently completed testing in a conventional National Toxicology Program (NTP) 2-yr rodent bioassay program. As a synthetic androgen with a limited historical database in toxicology, oxymetholone is an ideal candidate for prospective exami...

journal_title：Toxicologic pathology

authors： Stoll RE,Holden HE,Barthel CH,Blanchard KT

更新日期：1999-09-01 00:00:00

abstract：:Clinically, girls appear to be more sensitive than boys to the cardiotoxic effects of doxorubicin, whereas the opposite may be true for adults. To identify and characterize potential sex-related differences, adult male and female spontaneously hypertensive rats (SHR; some ovariectomized [OVX]) received 1 mg/kg of doxo...

journal_title：Toxicologic pathology

authors： Zhang J,Knapton A,Lipshultz SE,Cochran TR,Hiraragi H,Herman EH

更新日期：2014-01-01 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

authors： Wirnitzer U,Töpfer R,Rosenbruch M

更新日期：1998-09-01 00:00:00