Antisense oligonucleotide therapies: the promise and the challenges from a toxicologic pathologist's perspective.

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

authors： Konishi N,Nakamura M,Ishida E,Kawada Y,Nishimine M,Nagai H,Emi M

更新日期：2001-03-01 00:00:00

abstract：:We describe 2 cases of a relatively rare tumor diagnosed as pituicytoma in the pars nervosa of rat pituitary. This tumor was spontaneously noted in one 110-week-old female and one 109-week-old male Fischer 344 (F344)/DuCrj rats during 2-year carcinogenicity studies. Although no gross abnormality of the pituitary was d...

journal_title：Toxicologic pathology

authors： Satoh H,Iwata H,Furuhama K,Enomoto M

更新日期：2000-11-01 00:00:00

abstract：:Residency in cities with high air pollution is associated with neuroinflammation and neurodegeneration in healthy children, young adults, and dogs. Nonsteroidal anti-inflammatory drugs may offer neuroprotection. The authors measured the plasma concentrations of 3-nitrotyrosine and the cerebro-spinal-fluid concentratio...

journal_title：Toxicologic pathology

authors： Calderón-Garcidueñas L,Mora-Tiscareño A,Gómez-Garza G,Carrasco-Portugal Mdel C,Pérez-Guillé B,Flores-Murrieta FJ,Pérez-Guillé G,Osnaya N,Juárez-Olguín H,Monroy ME,Monroy S,González-Maciel A,Reynoso-Robles R,Villarreal-Calderon

更新日期：2009-08-01 00:00:00

abstract：:The new Appendix A of the European Convention for the Protection of Vertebrate Animals Used for Experimental and Other Scientific Purposes, which gives guidelines for accommodation and care of animals and was approved on June 15, 2006, was the main reason the authors decided to investigate the origins of the regulatio...

journal_title：Toxicologic pathology

authors： Atalić B,Fatović-Ferencić S

更新日期：2009-10-01 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：: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：: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 becaus...

journal_title：Toxicologic pathology

authors： Ewart-Toland A,Balmain A

更新日期：2004-03-01 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：:Seventeen mesotheliomas from 395 untreated male Fischer 344/DuCrj rats were studied by light and electron microscopy to define the morphological characteristics of the tumors. In 16 out of 17 rats, mesotheliomas were observed in the abdominal and/or scrotal sac, and the other one was localized on the pleura. Grossly, ...

journal_title：Toxicologic pathology

authors： Tanigawa H,Onodera H,Maekawa A

更新日期：1987-01-01 00:00:00

abstract：:To determine if additive or synergistic toxic effects would occur, adult male rats were exposed orally to lead carbonate (2,000 mg/kg) for 9 days before trichloroethylene (TCE), 2,000 mg/kg, was given concurrently for an additional 7 days. Comparisons were made with groups of vehicle-treated rats and rats given only l...

journal_title：Toxicologic pathology

authors： Nunes J,Ehrich M,Robertson J

更新日期：2001-07-01 00:00:00

abstract：:Alloxan-induced diabetic rats frequently exhibit proliferative lesions of squamous hyperplasia accompanied by chronic inflammation and Candida albicans infection in the forestomach, and some lesions progress to squamous cell carcinoma (SCC). Candida infection causes not only hyperplastic changes with inflammation but ...

journal_title：Toxicologic pathology

authors： Sano T,Ozaki K,Kodama Y,Matsuura T,Narama I

更新日期：2009-10-01 00:00:00

abstract：:Toxicology of the male reproductive system has received increased interest in recent years partly fuelled by the growing reports of falling sperm counts and rising reproductive disorders in the human population. Recently revised regulatory guidelines for the safety assessment of pharmaceuticals and chemicals on reprod...

journal_title：Toxicologic pathology

authors： Creasy DM

更新日期：1997-03-01 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

abstract：:Historical control tumor data are useful in the interpretation of long-term rodent carcinogenicity bioassays, especially to assess the occurrence of rare tumors and marginally increased tumor incidences. The major prerequisites to compare historical control data with studies under evaluation are the validity and consi...

journal_title：Toxicologic pathology

authors： Deschl U,Kittel B,Rittinghausen S,Morawietz G,Kohler M,Mohr U,Keenan C

更新日期：2002-01-01 00:00:00

abstract：:Hepatic changes induced by phenethyl isothiocyanate (PEITC) in the liver of rats were determined by quantitative microscopy. Groups of male Fischer-344 rats were fed either a standard, cereal-based diet (Wayne rodent meal) or a purified diet (AIN-76A) containing PEITC at concentrations of 0.75 and 6.0 mmol/kg for 13 w...

journal_title：Toxicologic pathology

authors： Gray RH,Adam-Rodwell GA,Maris D,Haskins JR,Stoner GD

更新日期：1995-11-01 00:00:00

abstract：:In preclinical safety studies, drug-induced vascular injury can negatively impact candidate-drug selection because there are no obvious diagnostic markers for monitoring this pathology preclinically or clinically. Furthermore, our current understanding of the pathogenesis of this lesion is limited. While vasodilatatio...

journal_title：Toxicologic pathology

authors： Louden C,Brott D,Katein A,Kelly T,Gould S,Jones H,Betton G,Valetin JP,Richardson RJ

更新日期：2006-01-01 00:00:00

abstract：:More than 40% of compounds identified through combinatorial screening programs are poorly soluble in water. These molecules are difficult to formulate using conventional approaches and are associated with innumerable formulation-related performance issues. Formulating these compounds as pure drug nanoparticles is one ...

journal_title：Toxicologic pathology

authors： Merisko-Liversidge EM,Liversidge GG

更新日期：2008-01-01 00:00:00

abstract：:We examined the effects of the quinolone antibacterial agents pefloxacin (PFLX) and ofloxacin (OFLX) on the Achilles tendon of Sprague-Dawley rats. A single oral administration of PFLX 300 and 900 mg/kg or OFLX 900 mg/kg induced edema with mononuclear cell infiltration mainly in the inner sheath of the inner Achilles ...

journal_title：Toxicologic pathology

authors： Kato M,Takada S,Kashida Y,Nomura M

更新日期：1995-05-01 00:00:00

abstract：:In a simulated fire-related smoke exposure protocol, New Zealand white rabbits were utilized to investigate the potential effects of the 21-aminosteroid (lazaroid) analog U75412E on the early events of acute lung injury. Inhalation of a total of 1.6 mg/kg U75412E aerosolized at a rate of 1.53 mg/min at 0.5 hr after sm...

journal_title：Toxicologic pathology

authors： Wang S,Lantz RC,Robledo RF,Breceda V,Hays AM,Witten ML

更新日期：1999-05-01 00:00:00

abstract：:Perfluorooctanoic acid (PFOA) is a chemical used in the production of fluoropolymers. Its persistence in the environment and presence in humans and wildlife has raised health concerns. Liver tumor induction by PFOA is thought to be mediated in rodents by PPAR-alpha. A recent US EPA scientific advisory board questioned...

journal_title：Toxicologic pathology

authors： Wolf DC,Moore T,Abbott BD,Rosen MB,Das KP,Zehr RD,Lindstrom AB,Strynar MJ,Lau C

更新日期：2008-06-01 00:00:00

abstract：:The development process of myelination varies between region and species. Fully myelinated fibers are required if mammalian neural circuits are to function normally. Histology samples at staggered time points throughout the study were examined at days 4, 5, 7, 8, 10, 14, 17, 24, 37, and 44. We suggest that the develop...

journal_title：Toxicologic pathology

authors： Downes N,Mullins P

更新日期：2014-07-01 00:00:00

abstract：:Our previous studies showed that protein kinase Cepsilon (PKCepsilon) verexpression in mouse skin resulted in metastatic squamous cell carcinoma (SCC) elicited by single 7,12-dimethylbenz(a)anthracene (DMBA)-initiation and 12-O-tetradecanoylphorbol-13-acetate (TPA)-promotion in the absence of preceding papilloma forma...

journal_title：Toxicologic pathology

authors： Li Y,Wheeler DL,Ananthaswamy HN,Verma AK,Oberley TD

更新日期：2007-12-01 00:00:00

abstract：:Histopathology of the reproductive system of 76 young adult Dutch Belted and 22 young adult or adult male New Zealand White rabbits was conducted as part of fertility studies. Thirty-five (46%) of the Dutch Belted and 11 (50%) of the New Zealand White males had multifocal vesicular gland basal epithelial cell atypia a...

journal_title：Toxicologic pathology

authors： Zwicker GM,Killinger JM,McConnel RF

更新日期：1985-01-01 00:00:00

abstract：:We have previously indicated that the ideal animal tumor model should mimic the human disease. This means that the investigator should be able to ascertain the influence of host factors on the initiation of tumorigenesis, mimic the susceptibility of tumor response based on age and reproductive history, and determine t...

journal_title：Toxicologic pathology

authors： Russo J

更新日期：2015-02-01 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：: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

authors： Esvelt MA,Freeman ZT,Pearson AT,Harkema JR,Clines GT,Clines KL,Dyson MC,Hoenerhoff MJ

更新日期：2019-02-01 00:00:00

abstract：:The use of biodegradable materials is gaining popularity in medicine, especially in orthopedic applications. However, preclinical evaluation of biodegradable materials can be challenging, since they are located in close contact with host tissues and might be implanted for a long period of time. Evaluation of these com...

journal_title：Toxicologic pathology

authors： Ramot Y,Nyska A,Markovitz E,Dekel A,Klaiman G,Zada MH,Domb AJ,Maronpot RR

更新日期：2015-12-01 00:00:00

abstract：:In standard toxicity studies, the cardiac conduction tissue is not systematically sampled and examined for histopathological changes. Most methods described use serial sectioning perpendicular to the long axis of the sinoauricular node (SAN) and atrioventricular node (AVN). Dozens of slides are needed to allow examina...

journal_title：Toxicologic pathology

authors： Palate BM,Denoël SR,Roba JL

更新日期：1995-01-01 00:00:00

abstract：:We conducted a retrospective analysis of publicly available preclinical toxicology studies with erythropoiesis-stimulating agents (ESAs) to examine common adverse events in rats, Beagle dogs, and cynomolgus monkeys. Mortality and/or thrombotic events were reported sporadically in a subset of studies and attributed to ...

journal_title：Toxicologic pathology

authors： Andrews DA,Pyrah IT,Boren BM,Tannehill-Gregg SH,Lightfoot-Dunn RM

更新日期：2014-01-01 00:00:00

abstract：:A critical event in embryo development is the proper formation of the vascular system, of which the hepatobiliary system plays a pivotal role. This has led researchers to use transgenic mice to identify the critical steps involved in developmental disorders associated with the hepatobiliary vascular system. Vascular d...

journal_title：Toxicologic pathology

authors： Swartley OM,Foley JF,Livingston DP 3rd,Cullen JM,Elmore SA

更新日期：2016-07-01 00:00:00