An expression vector for the epidermal growth factor (EGF) receptor was introduced into the 32D myeloid cell line, which is devoid of EGF receptors and absolutely dependent on interleukin-3 (IL-3) for its proliferation and survival. Expression of the EGF receptor conferred the ability to utilize EGF for transduction of a mitogenic signal. When the transfected cells were propagated in EGF, they exhibited a more mature myeloid phenotype than was observed under conditions of IL-3-directed growth. Moreover, exposure to EGF led to a rapid stimulation of phosphoinositide metabolism, while IL-3 had no detectable effect on phosphoinositide turnover either in control or EGF receptor-transfected 32D cells. Although the transfected cells exhibited high levels of functional EGF receptors, they remained nontumorigenic. In contrast, transfection of v-erbB, an amino-terminal truncated form of the EGF receptor with constitutive tyrosine kinase activity, not only abrogated the IL-3 growth factor requirement of 32D cells, but caused them to become tumorigenic in nude mice. These results show that a naïve hematopoietic cell expresses all of the intracellular components of the EGF-signaling pathway necessary to evoke a mitogenic response and sustain continuous proliferation.

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ventricle and overlapping with the interventricular septum and the right ventricle. Conclusion: The VBA highlighted subregions with dose differences associated with RILD in both heart and lungs. The S .05 lung cluster shares a similar parenchymal position with analogous statistical structure found by Palma et al. 2016 on a different patient cohort (Hodgkin lymphoma) treated with different RT beam arrangement, thus supporting preliminarily reported patterns of the VBA findings on lung toxicity. Furthermore, the first inclusion of covariates within a dosimetric statistical model that faces the multiple comparison problem expands the potential of VBA, thus paving the way to a reliable VBA of radiation-induced toxicity in datasets with strong correlation of the outcome with non-dosimetric variables.

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