Abstract:
:Cancer affects approximately 1 in 3 individuals. An individual's susceptibility to cancer is partly determined by environmental exposures and by the combination of inherited cancer susceptibility and resistance genes. Initial mapping of these low penetrance cancer susceptibility genes has been done in the mouse because human low penetrance genes are extremely difficult to find using traditional methods due to heterogeneity and interacting factors. Also, the choice of candidate genes for human association studies can miss the unknown or unexpected. Mouse models also have limitations; it can be difficult to identify causal polymorphisms in the mouse because linkage disequilibrium often extends across several genes. To exploit the strengths of both systems, we outline a cross-species strategy to identify human variants associated with increased cancer risk. This approach uses linkage analysis and haplotyping, allelic imbalance in tumors, and gene expression studies in the mouse, combined with association studies and tumor imbalance studies in humans to identify causal cancer susceptibility variants. Allelic variants in both mouse and human can then be used to better understand the mechanisms behind cancer risk and as targets for intervention.
journal_name
Toxicol Patholjournal_title
Toxicologic pathologyauthors
Ewart-Toland A,Balmain Adoi
10.1080/01926230490424716subject
Has Abstractpub_date
2004-03-01 00:00:00pages
26-30eissn
0192-6233issn
1533-1601journal_volume
32 Suppl 1pub_type
杂志文章,评审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
pub_type: 杂志文章
doi:10.1177/0192623313478692
更新日期:2013-01-01 00:00:00
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
更新日期:2003-01-01 00:00:00
abstract::A delay in the exposure of initiated rats to orotic acid (OA) beyond a specific time frame results in a progressive loss of promotional effect in liver carcinogenesis. The current study was designed to ascertain whether the loss of promotional effect could be counteracted by pre-exposing the initiated animals to other...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262338701500212
更新日期:1987-01-01 00:00:00
abstract::This report demonstrates the advantages of using a noninvasive soft tissue imaging technique--magnetic resonance imaging (MRI)--to monitor liver regeneration after 70% partial hepatectomy in the rat in a longitudinal manner. Six animals were scanned prior to and on 6 subsequent occasions up to 9 days after surgical re...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1080/01926230290105811
更新日期:2002-09-01 00:00:00
abstract::Analgesics and nonsteroidal anti-inflammatory drugs (NSAIDs) are well recognized as a major class of therapeutic agent that causes renal papillary necrosis (RPN). Over the last decade a broad spectrum of other therapeutic agents and many chemicals have also been reported that have the potential to cause this lesion in...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1177/019262339802600110
更新日期:1998-01-01 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
pub_type: 杂志文章
doi:10.1177/0192623311432436
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
pub_type: 杂志文章
doi:10.1177/0192623312464122
更新日期:2013-01-01 00:00:00
abstract::One application of genomics in drug safety assessment is the identification of biomarkers to predict compound toxicity before it is detected using traditional approaches, such as histopathology. However, many genomic approaches have failed to demonstrate superiority to traditional methods, have not been appropriately ...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1080/01926230500321213
更新日期:2005-01-01 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
pub_type: 杂志文章
doi:10.1177/0192623310369343
更新日期:2010-06-01 00:00:00
abstract::Weber, K. (2017). Differences in Types and Incidence of Neoplasms in Wistar Han and Sprague-Dawley Rats. J Toxicol Pathol45, 64-75. (Original DOI: 10.1177/0192623316672075) In the January 2017 issue of Toxicologic Pathology, a number of in text Table citations were incorrectly labeled. The following are the sentences ...
journal_title:Toxicologic pathology
pub_type: 杂志文章,已发布勘误
doi:10.1177/0192623317702643
更新日期:2017-04-01 00:00:00
abstract::The carcinogenic potential of chloroform was evaluated in a short-term carcinogenicity testing system using CB6F1 rasH2-Tg (rasH2-Tg) mice. Chloroform was administered to rasH2-Tg males at doses of 28, 90, or 140 mg/kg and rasH2-Tg females at 24, 90, or 240 mg/kg by oral gavage for 26 weeks. Wild-type (non-Tg) male an...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1080/01926230252929909
更新日期:2002-05-01 00:00:00
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::Glucokinase activators (GKAs) are being developed for the treatment of type 2 diabetes. The toxicity of 4 GKAs (PF-04279405, PF-04651887, piragliatin, and PF-04937319) was assessed in mice, rats, dogs, and/or monkeys. GKAs were administered for 2 to 8 weeks. Standard endpoints, glucose, and insulin were assessed. All ...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623314526006
更新日期:2014-06-01 00:00:00
abstract::Groups of C57BL6 mice of each sex were assigned to one of 2 dietary regimens, ad libitum (AL) or dietary restriction (DR), to study effects of food restriction on body weight, survival, and neoplasia. The AL and DR groups were subdivided into a scheduled sacrifice group for examination at 6-mo intervals, and a lifetim...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262339502300503
更新日期:1995-09-01 00:00:00
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::Dichloroacetic acid (DCA) and trichloroacetic acid (TCA) are metabolites of the industrial solvent and environmental contaminant trichloroethylene (TCE), as well as contaminants of chlorinated drinking water. Human exposure to these chemicals is of concern as all three have been shown to increase liver tumor incidence...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262339702500501
更新日期:1997-09-01 00:00:00
abstract::The renal toxicity of harman and norharman, administered for 2 or 4 weeks at dietary levels of 1,000, 500, or 0 parts per million (ppm), was investigated in 6-week-old male F344/DuCrj rats. Although rats fed 1,000 ppm harman or norharman, but not the 500 ppm level, demonstrated marked body weight retardation from 1 we...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262339202000206
更新日期:1992-01-01 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
pub_type: 杂志文章
doi:10.1177/019262339402200407
更新日期:1994-07-01 00:00:00
abstract::Statistical issues related to the design, analysis and interpretation of carcinogenicity studies are considered. A proposed modification of the "standard" National Cancer Institute (NCI) design of carcinogenicity studies in rodents is discussed. The primary objective was to obtain a design that maintained the power of...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262338301100113
更新日期:1983-01-01 00:00:00
abstract::Cardiac troponin (cTn) is a sensitive and specific biomarker for assessing cardiac damage and should be utilized in drug safety assessment. Lactate dehydrogenase and creatine kinase isoenzyme analyses have historically been used in pre-clinical toxicity testing to assess cardiac injury, but since these assays are less...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623310382438
更新日期:2010-12-01 00:00:00
abstract::The usefulness of isolated adult cardiac myocytes, both in suspension and in culture, as a model system for measuring cardiotoxicity is evaluated. It has been suggested that isolated adult myocytes should preferably be cultured for such experimentation, as this restores the cells to a physiological preference for fatt...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:
更新日期:1990-01-01 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
pub_type: 杂志文章
doi:10.1080/01926230490440925
更新日期:2004-07-01 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
pub_type: 杂志文章
doi:10.1177/019262339302100210
更新日期:1993-01-01 00:00:00
abstract::Swine, especially the miniature swine or minipigs, are increasingly being used in preclinical safety assessment of small molecules, biopharmaceutical agents, and medical devices as an alternate nonrodent species. Although swine have been used extensively in biomedical research, there is a paucity of information in the...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623315611762
更新日期:2016-04-01 00:00:00
abstract::To characterize genetic alterations occurring in renal tumorigenesis, EHEN-induced renal cell tumors were examined using restriction landmark genomic scanning (RLGS) analysis, an electrophoretic separation technique that detects gene amplifications and deletions. Comparison of DNAs from tumor against those from corres...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1080/019262301317052503
更新日期:2001-03-01 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::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::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
pub_type: 杂志文章
doi:10.1177/019262339402200106
更新日期:1994-01-01 00:00:00
abstract::Recent clinical evidence suggests that hylan, a modified hyaluronan, and related products potentially elicit foreign body granulomatous inflammation in human soft tissue. We investigated the biocompatibility of hylan G-F 20 (Synvisc) for up to 28 days after intradermal injection in guinea pigs and intramuscular inject...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1080/01926230390204360
更新日期:2003-05-01 00:00:00