Local excision: some reality testing.
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Adenocarcinoma↗
Biomedical subjects
Joel Goldberg
Publications and source records attributed to Joel Goldberg.
Increasing supervisory effectiveness in a laboratory animal facility.
Management personnel expressed concern that the allocation of work was not properly aligned to permit maximum efficiency in the supervisor job family. Employees at various levels in the supervisor job family also felt that there needed to be greater definition regarding which tasks needed to be done by which level in the organization. Using data collection and interviews, a team of staff employees and consultants successfully evaluated the facility operation and supervision. The information was analyzed and compared with the existing supervisory job descriptions. An action plan was developed and presented to management personnel to increase efficiency and stratify the responsibility of the existing supervisory levels. Supervisory reassignment was proposed.
Animal Experimentation↗
Small-molecule antagonists of Myc/Max dimerization inhibit Myc-induced transformation of chicken embryo fibroblasts.
Myc is a transcriptional regulator of the basic helix-loop-helix leucine zipper protein family. It has strong oncogenic potential, mutated or virally transduced forms of Myc induce lymphoid tumors in animals, and deregulated expression of Myc is associated with numerous types of human cancers. For its oncogenic activity, Myc must dimerize with the ubiquitously expressed basic helix-loop-helix leucine zipper protein Max. This requirement for dimerization may allow control of Myc activity with small molecules that interfere with Myc/Max dimerization. We have measured Myc/Max dimerization with fluorescence resonance energy transfer and have screened combinatorial chemical libraries for inhibitors of dimerization. Candidate inhibitors were isolated from a peptidomimetics library. Inhibition of Myc/Max interaction was validated by ELISA and electrophoretic mobility-shift assay. Two of the candidate inhibitors also interfere with Myc-induced oncogenic transformation in chicken embryo fibroblast cultures. Our work provides proof of principle for the identification of small molecule inhibitors of protein-protein interactions by using high-throughput screens of combinatorial chemical libraries.
Animals↗
Erythropoietin mimetics derived from solution phase combinatorial libraries.
The erythropoietin receptor (EPOr) is activated by ligand-induced homodimerization, which leads to the proliferation and differentiation of erythroid progenitors. Through the screening of combinatorial libraries of dimeric iminodiacetic acid diamides, novel small molecule binders of EPOr were identified in a protein binding assay. Evaluation of a series of analogues led to optimization of binding subunits, and these were utilized in the synthesis of higher order dimer, trimer, and tetramer libraries. Several of the most active EPOr binders were found to be partial agonists and induced concentration-dependent proliferation of an EPO-dependent cell line (UT-7/EPO) while having no effect on a cell line lacking the EPOr (FDC-P1). An additional compound library, based on a symmetrical isoindoline-5,6-dicarboxylic acid template and including the optimized binding subunits, was synthesized and screened leading to the identification of additional EPO mimetics.
Cell Division↗