The schweinfurthins: issues in the development of a plant-derived anticancer lead

The development of a natural product into a pharmaceutical drug product can follow a long and tortuous path in the best of cases. This chapter highlights issues that have arisen in the development of the schweinfurthins, a compound class discovered from an African plant, Macaranga schweinfurthii, as a potential cancer drug lead. Resupply of the plant from Cameroon, synthetic access to this series of compounds, and investigation of its mechanism of action, have all played major roles in the story to date. An interdisciplinary network of scientific collaboration has been assembled to make advancement possibl

Analysis of Visitor Decision Making System When Visiting Natural Recreation Sites by Multinomial Logit Model

ecological economy, ecological tourism, multinomial logit model, natural resources, recreational site,

Characterization of new human CD20 monoclonal antibodies with potent cytolytic activity against non-Hodgkin lymphomas

Despite the rapid and widespread integration of chimeric CD20 monoclonal antibody (mAb), rituximab, into the management of non-Hodgkin lymphoma, its efficacy remains variable and often modest when used as a single agent. To develop more potent reagents, human immunoglobulin transgenic mice were used to generate a panel of immunoglobulin G1kappa (IgG1kappa) CD20 mAbs. All reagents bound strongly to CD20(+) cells and recruited mononuclear cells for the lysis of malignant B cells. However, 2 mAbs, 2F2 and 7D8, were exceptionally active in complement-dependent cytotoxicity (CDC), being able to lyse a range of rituximab-resistant targets, such as CD20-low chronic lymphocytic leukemia (CLL), in the presence of human plasma or unfractionated blood. Further analysis showed that 2F2 and 7D8, like rituximab, redistributed CD20 into Triton X-100-insoluble regions of the plasma membrane, but that they had markedly slower off-rates. To determine whether off-rate influenced CDC, a non-complement activating F(ab')(2) antihuman kappa reagent was used. This reagent markedly slowed the off-rate of rituximab and increased its CDC activity to that of 2F2 and 7D8. Thus, with increasing evidence that mAb therapeutic activity in vivo depends on complement activation, these new CD20 reagents with their slow off-rates and increased potency in CDC hold considerable promise for improved clinical activity