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Experimental approaches for enhancing wound healing and inhibiting tumor growth

Andreatta-Van Leyen, Sheila

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1994, Doctor of Philosophy, Case Western Reserve University, Physiology and Biophysics.
Growth factors are regulatory peptides involved in many processes of cell physiology and pathology, including tissue repair and tumor growth. Part of this work concerned the development of a genetically engineered biological bandage (GEBB) designed to improve wound healing. Human epidermal keratinocytes (SCC-13) were genetically engineered to produce bovine growth hormone (bGH), giving raise to higher producer bGH cell lines (1 ug/ 1 × 106 cells/24hs). Selection of biocompatible polymers for bandage composition and appropriate conditions for cell maintenance was also established. The GEBB consists of a hydrophylic and gas permeable top and bottom membranes (Z-bind) united by a gasket. The bottom membrane allows cell attachment and growth, and diffusion of macromolecules. This system was functional under ambient conditions; when placed onto a full-thickness, surgically generated wound on rats, the cells within the bandage released bGH for three days. The GEBB represents a versatile system for delivering a variety of biological agents to wounds. In the second part of these studies, the role of retinoic acid (RA) and epidermal growth factor (EGF) in the regulation of insulin-like growth factor binding protein-3 (IGFBP-3) was addressed. IGFBP-3 regulates insulin-like gr owth factors (IGFs) which in turn are important modulators of epithelium proliferation. Treatment of the ectocervical epithelial cell line ECE16-1 with EGF caused a marked reduction in IGFBP-3 levels. In contrast, RA increased mRNA and protein levels in the presence or absence of EGF. This response was concentration-dependent with a half-maximal increase observed at 1 nM RA. RA was able to reverse the EGF supression in IGFBP-3 when added simultaneously or three days after EGF treatment. Conversely, when ECE16-1 were treated with RA, IGFBP-3 levels increased within 24 h and subsequent addition of EGF was without effect. Thus, the RA-dependent increase in IGFBP-3 is dominant over the EGF supression. Increased IGFBP-3 levels correlated with supressed growth. RA also increased IGFBP-3 mRNA in other ectocervical cell lines. These results suggest that RA may act to inhibit ectocervical proliferation by increasing IGFBP-3 levels and/or reducing the extracellular concentration of free IGFs
Richard Eckert (Advisor)
188 p.

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Citations

  • Andreatta-Van Leyen, S. (1994). Experimental approaches for enhancing wound healing and inhibiting tumor growth [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1061557930

    APA Style (7th edition)

  • Andreatta-Van Leyen, Sheila. Experimental approaches for enhancing wound healing and inhibiting tumor growth. 1994. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1061557930.

    MLA Style (8th edition)

  • Andreatta-Van Leyen, Sheila. "Experimental approaches for enhancing wound healing and inhibiting tumor growth." Doctoral dissertation, Case Western Reserve University, 1994. http://rave.ohiolink.edu/etdc/view?acc_num=case1061557930

    Chicago Manual of Style (17th edition)