Approach to Targeting

Pharmacologic or biologic methods are usually employed in preclinical studies to establish the effect of altering the expression of the target gene or of interfering with the function of the target protein. Most approaches have utilized either small molecule inhibitors (often detected in screening assays) or monoclonal antibodies (MAbs) to interfere with the function of the target protein. In general, small molecule inhibitors have a short half-life and are orally delivered on a continuous long-term basis. However, side effects can be common and potentially troublesome, especially if there is a broader substrate for related cellular proteins/kinases. By contrast, MAbs have a longer half-life with a more acceptable toxicity profile, although they require regular intravenous administration. Monoclonal antibodies usually target surface receptors and may also lead to receptor downregulation, although there is the additional theoretical potential for direct tumor cell cytotoxicity via complement and antibody (antibody-mediated cellular cytotoxicity, ADCC). Side effects may relate to hypersensitivity reactions, with the potential also to develop human antimonoclonal antibodies (HAMAs) that may limit effectiveness. Other approaches to targeting include the use of antisense technology to inhibit target messenger RNA that is transcribed from a given gene, although a key limiting factor is appropriate delivery of nucleic acids to the tumor cell. The use of viral vectors in targeted therapy approaches to modify/replace or inhibit target genes has therefore attracted much attention, and this method has been used to replace or stabilize key tumor suppressor proteins that may regulate cell survival and apoptosis.

A Disquistion On The Evils Of Using Tobacco

A Disquistion On The Evils Of Using Tobacco

Among the evils which a vitiated appetite has fastened upon mankind, those that arise from the use of Tobacco hold a prominent place, and call loudly for reform. We pity the poor Chinese, who stupifies body and mind with opium, and the wretched Hindoo, who is under a similar slavery to his favorite plant, the Betel but we present the humiliating spectacle of an enlightened and christian nation, wasting annually more than twenty-five millions of dollars, and destroying the health and the lives of thousands, by a practice not at all less degrading than that of the Chinese or Hindoo.

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