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Practical Aspects of Discovery Pathology
John E. Burkhardt
Department of Drug Safety Evaluation, Pfizer Global Research and Development, Groton, CT, USA, John_E_Burkhardt{at}groton.pfizer.com.
Anne M. Ryan
Department of Drug Safety Evaluation, Pfizer Global Research and Development, Groton, CT, USA
Paul-Georg Germann
Preclinical Safety, Novartis Pharma AG, Basel, Switzerland
Pathologists are uniquely qualified to play a central role in driving drug discovery and development programs by: 1) establishing disease models to assess potential therapies, 2) characterizing modifications in the disease state in response to therapies, 3) characterizing toxicologic mechanisms and responses to drug candidates, and 4) facilitating multidisciplinary efforts to monitor for the clinical occurrence, progression, and reversibility of adverse events. Such nontraditional deployment of resources must, to be viable, produce benefits to the pharmaceutical industry comparable to those of more conventional activities such as delivery of data in nonclinical safety studies. Additionally, benefits must be tangible from standpoints such as timesavings or improved quality of research decisions, manifesting as either program acceleration or improved candidate survival.
Key Words: Animal models • confidence in mechanism • confidence in safety • toxicology • rats • mouse phenotyping • monoclonal antibodies • VEGF • AMD.
References
- Ahlijanian MK, Barrezueta NX, Williams RD, Jakowski A., Kowsz K., McCarthy S., Coskran T., Carlo A., Seymour P., Burkhardt JE, Nelson RB, McNeish JD (200 ). Hyperphosphorylated tau and neurofi lament and cytoskeletal disruptions in mice overexpressing human p25, an activator of cdk5. Proc Natl Acad Sci USA 97: 2910—2915.
- Burkhardt JE, Eskra JD, Clemo Fas, Otterness IG (1999). Effects of nalidixic acid on hamster knee cartilage morphology and synovial fluid composition. Toxicol Pathol 27: 421—426.[Abstract/Free Full Text]
- Germann P-G., Häfner D., Hanauer G., Drommer W. (1998). J Exp Anim Sci 39: 22—33.[Web of Science]
- Haczku A., Moqbel R., Elwood W., Sun J., Kay AB, Barnes PJ, Chung KF, (1994). Effects of prolonged repeated exposure to ovalbumin in sensitized Brown Norway rats. Am J Respir Care Med 150: 23—27.[Abstract]
- van Hillegersberg R., Hekking-Weijma JM, Wilson JH, Edixhoven-Bosdij k A., Kort WJ ( 1995). Adjuvant intraoperative photodynamic therapy diminishes the rate of local recurrence in a rat mammary tumour model. Br J Cancer 71: 733—737.[Web of Science][Medline]
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- Karol MH (1994). Animal models of occupational asthma. Eur Respir J 7: 555—568.[Abstract]
- Mordenti J., Cuthbertson RA, Ferrara N., Thomsen K., Berleau L., Licko V., Allen PC, Valverde CR, Meng YG, Fei DTW, Fourre KM, Ryan AM ( 1999). Comparisons of the intraocular tissue distribution, pharmacokinetics, and safety of 125 I-labeled full-length and Fab antibodies in Rhesus monkeys following intravitreal administration. Toxicol Pathol 27: 536—544.[Abstract/Free Full Text]
- Ryan AM, Eppler DB, Hagler KE, Bruner, RH, Thomford PJ, Hall RL, Shopp GM, O'Neill CA (1999). Preclinical safety evaluation of rhuMabVEGF, an antiangiogenic humanized monoclonal antibody. Toxicol Pathol 27: 78—86.[Abstract/Free Full Text]
- Schaffner J-C., Wood J., Germann P-G. (2000). Effectiveness of a VEGFinhibitor on tumor growth and histopathology in a human prostatic carcinoma model in nude mice. Pathol Res Pract 196: 398.
Toxicologic Pathology, Vol. 30, No. 1,
8-10 (2002)
DOI: 10.1080/01926230252824653
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