Preclinical evaluation

Figure 11 Antiinflammatory or anti-cancer marine natural products and synthetic analogs that are in commercial use or in clinical and preclinical evaluation...

Halomon in preclinical evaluation as a cytotoxic agent against certain tumor cell types. 

Toxicity and effectivity studies have often been performed in rodent fibroblast cells containing oncogenic H-Ras. However, prenylation of K-Ras B and N-Ras are not as effectively blocked by the farnesyltransferase inhibitors as H-Ras [48] (see below). Thus normal cells may be less sensitive to these drugs because they express K-Ras 4B and N-Ras. In this context it should be noted that H-Ras mutations are relatively uncommon in human tumors [49]. Rather, the K-Ras gene is the most frequently mutated in solid human cancers, whereas N-Ras is prevalent in leukemias. Thus the preclinical evaluation of the farnesylation inhibitors has yet to be critically re-evaluated for trials in humans. 

House, R.V., An overview of in vitro/ex vivo assays for preclinical evaluation of immu-nomodulation, Hum. Exp. Toxicol., 19, 246, 2000. 

SPECIAL CONCERNS FOR THE PRECLINICAL EVALUATION OF BIOTECHNOLOGY PRODUCTS... 

Development Focus on preclinical evaluation Focus on occupational and general environment... 

Dean, J.H., Comacoff, J.B., Labrie, T. and Barbolt, T.A. (1990). Assessment of immune responses in rodents and non-human primates—Implications in preclinical evaluation of proteins. In Preclinical Evaluation of Peptides and Recombinant Proteins, (Sundwall, A. et al., Eds.) Malmo. Skogs Grafiska AB, Stockholm, Sweden, pp. 23-34. 

Doncel, G. F. Chemical vaginal contraceptives Preclinical evaluation, in Barrier Contraceptives Current Status and Future Prospects, Mauck, C., Cordero, M., Gabelnick, J. L., Spieler, J. M., and Rivera, R. (Eds), pp. 147-162, WUey-Liss, New York, 1994. 

Some of these compounds are currently undergoing pharmacological studies on models of attention, learning and memory, as well as extensive preclinical evaluation [77]. 

Currently available devices are able to provide left ventricular support for a short duration only. Development of percutaneously or minimally invasive long-term support devices is also underway. At least three such devices are undergoing preclinical evaluation. The Synergy device (CircuLite, Inc., Hackensack, NJ) is being developed as a pocket circulatory assist (PAC) device that would sit in a subcuatenous pocket over the chest wall and use a micro-pump with cannulas in the subclavian artery and vein to withdraw blood from the left atrium through a transseptal approach and deliver it to the subclavian artery. The device is connected to a power... 

Cord blood has long been used as a source of MSCs for bone marrow transplantation. The stem cell compartment is more abundant and less mature in cord blood than in bone marrow. Moreover, MSCs in cord blood have a higher proliferative potential because of their extended lifespan and longer telomeres [91-94]. Not only can cord-blood MSCs be harvested without morbidity to the donor, but they also display a robust in vitro capacity for directable or spontaneous differentiation into mesodermal, endodermal, and ectodermal cell fates. Cord-blood MSCs are CD45 and HLA-II and can be expanded without losing their pluripotency. Therefore, cord blood is also undergoing preclinical evaluation as a possible easily accessible source of multipotent cells. 

G. L. Hammond, J.E. van Lier, F-18-labeled difluoroestradiols Preparation and preclinical evaluation as estrogen receptor-binding radiopharmaceuticals. Steroids 67 (2002) 765-775. 

The jS-AR binding potency of 10 /n vitro was achieved using the corresponding nonradioactive fluorinated compound and ventricular membrane preparations from dilute brown agouti (DBA) mouse hearts. First preclinical evaluation studies in vivo using compound 10 that aim at the visualization of cardiac jS -AR receptors in small animals are planned. 

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