Assay assessment

Chromosomal Physical damage to chromosomes (large ordered Chromosomal aberration assay assesses the potential for... 

Carmichael J, DeGraff WG, Gazdar AF et al. (1987) Evaluation of a tetrazolium-based semiauto-mated colorimetric assay assessment of chemosensitivity testing. Cancer Res. 47 936-942. 

Punzel, M., Wissink, S., Miller, J., Moore, K., Lemishka, I. and Verfaillie, C. (1999) The myeloid-lymphoid initiating cell (ML-IC) assay assesses the fate of multipotent human progenitors in vitro, Blood93,3750-3756. 

Subacute or subchronic assays assess the effects of daily exposures of an animal population to a toxicant over approximately 10% of the animal s lifetime. In rats, this corresponds to about 3 months. Careful study of the animals—including examination of all body tissues and fluids—reveals the dose at which toxic effects begin to occur at several endpoints, such as organ dysfunction, behavioral changes, or alterations in levels of normal body fluid components. The highest dose at which none of the animals show toxic effects is called NOAEL (i.e., no observable adverse effect). Other doses include LOEL (lowest observed effect level), the lowest dose for which effects were expressed and LOAEL (lowest observed adverse effect level), a stricter version of LOEL that addresses only adverse effects. In these tests several species are tested and the most sensitive one is selected as a human surrogate. See Figure 9.32. 

Data indicate butyric acid is not genotoxic. Negative results were observed in assays assessing for both mutations (Ames test) and chromosomal aberrations. 

In vivo assays Assess functional or behavioral effects (e.g., blood pressure diuresis pain heart rate respiration pigmentation). 

Behavioral assays Assess changing behaviors (e.g., pain addiction feeding sexual aggression learning etc.). 

Carmichael J, Degraff WG, Gazdar AL, Minna JD, Mitchell JB (1987) Evaluation of Tetrazolium-Based Semiautomated Colorimetric Assay Assessment of Chemosen-sitivity Testing. Cancer Res 47 936... 

Transporters P-gp assay (see Section 6.3.2.2) Other transporter assays Assessing transporter involvement in in vitro absorption experiments Predicting in vivo transporter-related habihties Assay ° Bidirectional permeability assays using Caco-2 or other cell lines ° 3-50 xM compound concentration Analysis ° PPT followed by LC-MS/MS... 

B. Mosadegh, et al., A paper-based invasion assay assessing chemotaxis of cancer cells in gradients of oxygen. Biomaterials 52 (2015) 262-271. 

Carmichael, J. DeGraff, W.G. Gazdar, A.F. Minna, J.D. Mitchell, J.B. (1987). Evaluation of a tetrazolium-based semiautomated colorimetric assay Assessment of radiosensitivity. Cancer. Res., 47,4, 943-946... 

Dr John Lipani s presentation (See Chapter 1) illustrated quite succinctly the potential for long-term effects of a MAb s pharmacodynamic action for example, the occurrence of tumours up to 1 year after the end of treatment with an anti-TNF MAb. Hence, consideration should be given to evaluating the potential for tumour formation after treatment with such compounds the effects of immunosuppression caused by MAbs can be addressed in short-term assays assessing the effects of MAbs with growth factor-like activity is more problematical. 

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