Cancer risk assessment approaches at the FDA/CDER: Is the era of the 2-year bioassay drawing to a close?

abstract：:Alanine aminotransferase (ALT) is used as an indicator of hepatocellular injury. Since ALT consists of two isoenzymes, a better understanding of ALT isoenzyme biology in response to compounds that cause metabolic adaptive versus hepatotoxic responses will allow for a more accurate assessment of the significance of an ...

journal_title：Toxicologic pathology

authors： Reagan WJ,Yang RZ,Park S,Goldstein R,Brees D,Gong DW

更新日期：2012-12-01 00:00:00

abstract：:Mouse renal cell tumors (RCTs) were induced in male CBA mice by 5 subcutaneous injections of 8 mg 1,2-dimethylhydrazine (DMH)/kg body weight once a week. After a lag period of 2 yr kidneys were removed, and serial cryostat sections of the kidneys were histochemically analyzed for the following parameters: glycogen con...

journal_title：Toxicologic pathology

authors： Ahn YS,Chemeris GY,Turusov VS,Bannasch P

更新日期：1994-07-01 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

authors： Silbergeld EK

更新日期：2017-01-01 00:00:00

abstract：:Lung cancer is the most common cause of cancer-related deaths in humans worldwide. There is strong evidence that the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and its metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) play an important role in carcinogenesis caused ...

journal_title：Toxicologic pathology

authors： Kovi RC,Johnson CS,Balbo S,Hecht SS,O'Sullivan MG

更新日期：2018-02-01 00:00:00

abstract：:Osteogenic Protein-1 (OP-1) is a bone morphogen involved in tissue repair and development. We have shown that OP-1 is downregulated during acute ischemic renal injury. Here we report the use of the rat remnant kidney model (RRKM) to evaluate changes in kidney OP-1 expression during chronic injury, and determine if tre...

journal_title：Toxicologic pathology

authors： Dube PH,Almanzar MM,Frazier KS,Jones WK,Charette MF,Paredes A

更新日期：2004-07-01 00:00:00

abstract：:This experiment evaluated effects following chronic toxicity with 20 ppm fenvalerate (synthetic pyrethroid), 2 ppm monocrotophos (organophosphate) and 2 ppm endosulfan (chlorinated hydrocarbon) on bone health of broiler chicks. A total of 120 chicks were divided equally into 4 groups and were fed poultry mash without ...

journal_title：Toxicologic pathology

authors： Garg UK,Pal AK,Jha GJ,Jadhao SB

更新日期：2004-05-01 00:00:00

abstract：:BMS-645737, an inhibitor of vascular endothelial growth factor (VEGF) receptor-2 and fibroblast growth factor (FGF) receptor-1, has anti-angiogenic activity and was evaluated in nonclinical studies as a treatment for cancer. This article characterizes the BMS-645737-induced clinical, gross, and histologic lesions of i...

journal_title：Toxicologic pathology

authors： Fletcher AM,Bregman CL,Woicke J,Salcedo TW,Zidell RH,Janke HE,Fang H,Janusz WJ,Schulze GE,Mense MG

更新日期：2010-02-01 00:00:00

abstract：:Quinolone antibacterial agents have adverse effects on the musculoskeletal system in humans, consisting mainly of myalgia and arthralgia, and additionally of tendon disorders and rhabdomyolysis. The present study was conducted to examine the toxic effects of quinolones on the musculoskeletal system in juvenile rats us...

journal_title：Toxicologic pathology

authors： Kashida Y,Kato M

更新日期：1997-11-01 00:00:00

abstract：:Furan is a potent cholangiocarcinogen in rat by an as yet undefined mechanism. The risk to man remains unclear. Using a time-course stop study design, we have investigated the potential of furan to induce oxidative stress and DNA damage associated with inflammatory and regenerative responses in rat liver. Furan was ad...

journal_title：Toxicologic pathology

authors： Hickling KC,Hitchcock JM,Oreffo V,Mally A,Hammond TG,Evans JG,Chipman JK

更新日期：2010-02-01 00:00:00

abstract：:High doses of insulin and the insulin analog AspB10 have been reported to increase mammary tumor incidence in female rats likely via receptor-mediated mechanisms, possibly involving enhanced IGF-1 receptor activation. However, insulin and IGF-1 receptor functionality and intracellular signaling in the rat mammary glan...

journal_title：Toxicologic pathology

authors： Hvid H,Fels JJ,Kirk RK,Thorup I,Jensen HE,Hansen BF,Oleksiewicz MB

更新日期：2011-06-01 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：:Toxicokinetic (TK) studies are the basis for demonstrating dose-related drug exposure in animals and for ensuring that drug exposure is substantially greater in animals than that expected in humans at therapeutic doses. The usefulness of TK studies can be further enhanced by correlating TK parameters with relevant tox...

journal_title：Toxicologic pathology

authors： Batra VK

更新日期：1995-03-01 00:00:00

abstract：:The cancer stem cell concept assumes that cancers are mainly sustained by a small pool of neoplastic cells, known as cancer stem cells or tumor initiating cells, which are able to reproduce themselves and produce phenotypically heterogeneous cells with lesser tumorigenic potential. Cancer stem cells represent an appea...

journal_title：Toxicologic pathology

authors： Cheng L,Ramesh AV,Flesken-Nikitin A,Choi J,Nikitin AY

更新日期：2010-01-01 00:00:00

abstract：:Single doses of aspirin induce scattered foci of necrosis of proximal tubules in some strains of rats, whereas acute or sub-acute administration of phenylbutazone causes renal papillary necrosis. Initially, using Sprague-Dawley rats of CFY and CD strains, it became clear that these rats were not as susceptible to thes...

journal_title：Toxicologic pathology

authors： Owen RA,Heywood R

更新日期：1986-01-01 00:00:00

abstract：:Changes in the mRNA and protein expression of renin-secreting cells in the juxtaglomerular apparatus (JGA) were examined in the rat following administration of ZENECA ZD8731, an angiotensin II receptor antagonist. Doses of 0 or 90 mg/kg were administered daily by gavage for 26 wk. JGA hypertrophy was apparent in histo...

journal_title：Toxicologic pathology

authors： Doughty SE,Ferrier RK,Hillan KJ,Jackson DG

更新日期：1995-05-01 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

authors： Richardson FC,Tennant BC,Meyer DJ,Richardson KA,Mann PC,McGinty GR,Wolf JL,Zack PM,Bendele RA

更新日期：1999-11-01 00:00:00

abstract：:In vitro techniques for the culture of hemopoietic stem cells and committed hemopoietic progenitor cells in rat bone marrow have not been adequately described in the literature. In the present investigations, and using commercially available hemopoietic cytokines and growth factors, the conditions required to perform ...

journal_title：Toxicologic pathology

authors： Molyneux G,Rizzo S,Turton J,Phul P,Gibson F

更新日期：2009-02-01 00:00:00

abstract：:A significant correlation exists between average daily food consumption and 2-yr survival in control ad libitum (AL)-fed Sprague-Dawley (SD) rats. SD rats were fed Purina Rodent Chow 5002 or a modified chow, 5002-9, with lower protein, fat, metabolizable energy and increased fiber AL or by dietary restriction (DR) to ...

journal_title：Toxicologic pathology

authors： Keenan KP,Smith PF,Hertzog P,Soper K,Ballam GC,Clark RL

更新日期：1994-05-01 00:00:00

abstract：:Colorectal cancer, responsible for 50,000 deaths per year, is a contributing factor for considerable mortalities in the United States. Consumption of well-done red meat and saturated fats rich in polycyclic aromatic hydrocarbons may be one of the causative factors for sporadic colon cancer. The objective of this study...

journal_title：Toxicologic pathology

authors： Harris DL,Washington MK,Hood DB,Roberts LJ 2nd,Ramesh A

更新日期：2009-12-01 00:00:00

abstract：:Many antisense oligonucleotides (ASOs) from several classes of molecules are currently in drug development. Despite over 20 years of pharmaceutical research, few ASOs have been marketed due to problems with clinical efficacy or preclinical toxicologic challenges. However, a number of recent developments have renewed i...

journal_title：Toxicologic pathology

authors： Frazier KS

更新日期：2015-01-01 00:00:00

abstract：:Conazoles are a class of azole based fungicides used in agriculture and as pharmaceutical products. They have a common mode of antifungal action through inhibition of ergosterol biosynthesis. Some members of this class have been shown to be hepatotoxic and will induce mouse hepatocellular tumors and/or rat thyroid fol...

journal_title：Toxicologic pathology

authors： Wolf DC,Allen JW,George MH,Hester SD,Sun G,Moore T,Thai SF,Delker D,Winkfield E,Leavitt S,Nelson G,Roop BC,Jones C,Thibodeaux J,Nesnow S

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

authors： Tansy MF,Kendall FM

更新日期：1988-01-01 00:00:00

abstract：:A spontaneous multicystic peritoneal mesothelioma was detected in a 108-wk-old male Fischer-344/DuCrj rat. Grossly, a tumor containing numerous, semi-transparent, variously sized, thin-walled cysts was found on the splenic serosal surface. Microscopically, each cyst was surrounded by variable amounts of loose connecti...

journal_title：Toxicologic pathology

authors： Shibuya K,Tajima M,Yamate J

更新日期：1993-01-01 00:00:00

abstract：:Ribonucleic acid (RNA) interference (RNAi) is a recently discovered phenomenon whereby the introduction of double stranded (ds) RNA into the cytoplasm of the cell results in the specific and efficient degradation of complementary messenger (m) RNA and, therefore, reduced protein production. It was discovered by chance...

journal_title：Toxicologic pathology

authors： Martineau HM,Pyrah IT

更新日期：2007-04-01 00:00:00

abstract：:Sprague-Dawley CD rats received daily oral doses (45 mg/kg) of the cationic amphiphilic tricyclic antidepressant imipramine HCl (Tofranil) for up to two years. Representative specimens of liver, lung, spleen, mesenteric lymph node, retina and dorsal root ganglion were examined for myeloid bodies (MB). The extent that ...

journal_title：Toxicologic pathology

authors： Spaet RH,Sullivan DJ,Diener RM

更新日期：1983-01-01 00:00:00

abstract：:A number of novel urinary biomarkers have been identified and partially qualified for use as markers for renal injury in rats. We used two multiplex assays for these novel biomarkers to quantify biomarker concentration in serial urine collections from rats of both sexes administered varying concentrations of cisplatin...

journal_title：Toxicologic pathology

authors： Pinches MD,Betts CJ,Bickerton SJ,Beattie L,Burdett LD,Thomas HT,Derbyshire NA,Moores M,Price SA

更新日期：2012-04-01 00:00:00

abstract：:Contrast-induced nephropathy (CIN) refers to a decline in renal function following exposure to iodinated contrast media (CM). The present study was initiated to explore the role of known human risk factors (spontaneous hypertension, diabetes, protein-losing nephropathy) on CIN development in rodent models and to deter...

journal_title：Toxicologic pathology

authors： Rouse RL,Stewart SR,Thompson KL,Zhang J

更新日期：2013-01-01 00:00:00

abstract：:A nondopaminergic antipsychotic agent, 5-ethyl-1,3,8-trimethyl-1H-imidazo]1,2-c]pyrazolo[3,4-e]pyrimidine (TIPP; PD 112488), has been tested for potential toxicity in rats. As part of a preclinical safety evaluation, 10 Wistar rats per sex were administered TIPP as a dietary admixture, receiving doses of 0, 5, 10, 20,...

journal_title：Toxicologic pathology

authors： Macallum GE,Albassam MA

更新日期：1994-01-01 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

authors： Nakamura H,Nishikawa A,Furukawa F,Kasahara K,Miyauchi M,Okazaki K,Imazawa T,Uchida K,Hirose M

更新日期：2002-03-01 00:00:00

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

authors： Rogers-Cotrone T,Burgess MP,Hancock SH,Hinckley J,Lowe K,Ehrich MF,Jortner BS

更新日期：2010-06-01 00:00:00