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Broad-Spectrum Protection Against Chemotherapy-Induced Alopecia by Acidic and Basic Fibroblast Growth Factors

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2005, Doctor of Philosophy, Ohio State University, Pharmacy.
Our laboratory reported that acidic and basic fibroblast growth factors (aFGF/bFGF, FGFs) confer broad-spectrum chemoresistance in solid tumors. The four studies in this dissertation tested the hypothesis that the combination of these two growth factors offers broad-spectrum protection against chemotherapy-induced alopecia (CIA). In chapter 2, we established and characterized CIA animal models by different chemotherapeutic agents representing four major classes of anticancer drugs, i.e., alkylators (cyclophosphamide), topoisomerase 2 inhibitors (doxorubicin), antimicrotubules (paclitaxel), and antimetabolites (cytosine arabinoside, or ara-c). In chapter 3, we evaluated the pharmacodynamic endpoints in the two CIA animal models. The data showed that the chemotherapeutic agents induced dermal layer shrinkage, reduced hair bulb diameter, shortened hair follicle length, altered hair bulb matrix cell proliferative activity and induced hair follicular apoptosis. Paclitaxel induced disruptions of hair follicle melanogenesis in the black C57BL-6 mice resulting in relocation of melanin to ectopic hair bulb locations. The collective data indicated that hair bulb matrix and outer root sheath (ORS) were the two major targets of chemotherapy in hair follicles. In chapter 4, we evaluated the protective effect of subcutaneous FGFs against CIA in the two animal models. The results showed that FGFs offered broad-spectrum protection against CIA by all four chemotherapeutic agents. In addition, FGFs accelerated the hair regrowth after CIA by high dose cyclophosphamide. Chapter 5 further investigated the protective effect of topical FGFs dissolved in 75% dimethyl sulfoxide (DMSO) against CIA. The data showed that topical FGFs reversed CIA by all four chemotherapeutic agents in the animal models. The data further showed that no or insignificant exposure of bFGF after subcutaneous or topical delivery of bFGF, suggesting that applying FGFs to the scalp will not compromise the efficacy of chemotherapy in tumor.
Jessie Au (Advisor)
128 p.

Recommended Citations

Citations

  • Wang, J. (2005). Broad-Spectrum Protection Against Chemotherapy-Induced Alopecia by Acidic and Basic Fibroblast Growth Factors [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1111433922

    APA Style (7th edition)

  • Wang, Jie. Broad-Spectrum Protection Against Chemotherapy-Induced Alopecia by Acidic and Basic Fibroblast Growth Factors. 2005. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1111433922.

    MLA Style (8th edition)

  • Wang, Jie. "Broad-Spectrum Protection Against Chemotherapy-Induced Alopecia by Acidic and Basic Fibroblast Growth Factors." Doctoral dissertation, Ohio State University, 2005. http://rave.ohiolink.edu/etdc/view?acc_num=osu1111433922

    Chicago Manual of Style (17th edition)