Local knowledge, environmental politics, and the founding of ecology in the United States. Stephen Forbes and "The Lake as a Microcosm" (1887).

Stephen Forbes's "The Lake as a Microcosm" is one of the founding documents of the science of ecology in the United States. By tracing the connections between scientists and local fishermen underlying the research on floodplain lakes presented in "The Lake as a Microcosm," this essay shows how the birth of ecology was tied to local knowledge and the local politics of environmental transformation. Forbes and the other scientists of the Illinois Natural History Survey relied on fishermen for manual labor, expertise in catching fish, and knowledge of the natural history of the fishes. As Forbes and his colleagues worked in close contact with fishermen, they also adopted many of their political concerns over the privatization of the floodplain and became politically active in supporting their interests. The close connection between scientists and local knowledge forced the ecologists to reframe the boundaries of ecology as objective or political, pure or applied, local or scientific.

Prevention of EGF-modulated adhesion of tumor cells to matrix proteins by specific EGF receptor inhibition.

The adhesion of tumor cells to various extracellular matrix (ECM) proteins is influenced by epidermal growth factor (EGF). Maximal effects are obtained at low EGF concentrations, at which mostly the cytoskeleton-associated high-affinity EGF receptors (EGFRs) are saturated. Tumor cells expressing EGFR either endogenously (MDA MB 231, MTLn3) or, for the human EGFR, ectopically (MTC HER1/1) in intermediate amounts exhibited, upon EGF addition, increased cellular adhesion to various ECM proteins, such as fibronectin, collagens and vitronectin. In contrast, human A431 and MDA MB 468 cells, over-expressing EGFR, demonstrated reduced attachment in similar experimental conditions. Both increased as well as reduced EGF-dependent adhesion could be blocked using either ligand-blocking monoclonal antibody 14E1 or the potent EGFR tyrosine kinase inhibitor PD 153035. Our data indicate that signals downstream of EGFR activation are responsible for the opposing effects of EGF on cellular adhesion since both can be prevented by EGFR inhibition. Thus, the integration of EGFR- and integrin-dependent signals can be different in carcinoma cell lines and might be influenced by EGFR numbers.

Construction and functional characterization of scFv(14E1)-ETA - a novel, highly potent antibody-toxin specific for the EGF receptor.

Epidermal growth factor (EGF) receptor-overexpression is characteristic of many human tumours of epithelial origin and has been correlated with unfavourable patient prognosis. Its involvement in the malignant process, its elevated expression in tumours and its accessibility on the tumour cell surface make the EGF receptor a potential target for directed tumour therapy. We have previously characterized a recombinant antibody - Pseudomonas exotoxin A fusion protein, scFv(225)-ETA, which displayes antitumoral activity towards EGF receptor-overexpressing tumour cells but is less potent in tumour cell killing than TGF-alpha-ETA, a recombinant toxin using the natural EGF receptor ligand transforming growth factor alpha (TGF-alpha) as a targeting domain. Here, we describe the construction and functional characterization in vitro of a novel single-chain antibody-toxin, scFv(14E1)-ETA, based on the independently isolated EGF receptor-specific monoclonal antibody 14E1. ScFv(14E1)-ETA binds to an EGF receptor epitope that is very similar or identical to that of scFv(225)-ETA with nine times higher affinity than the latter and displays more than tenfold higher cytotoxic activity on EGF receptor-overexpressing tumour cells. ScFv(14E1)-ETA cell killing activity was very similar to that of TGF-alpha-ETA on receptor-overexpressing cells but, in contrast to the latter, scFv(14E1)-ETA was much more selective and did not display significant cytotoxic activity on cells expressing moderate EGF receptor levels.