A novel rat model for chemotherapy-induced alopecia

Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
Clinical and Experimental Dermatology (Impact Factor: 1.23). 04/2012; 37(3):284-9. DOI: 10.1111/j.1365-2230.2011.04239.x
Source: PubMed

ABSTRACT More than half of all people diagnosed with cancer receive chemotherapy, and approximately 65% of these develop chemotherapy-induced alopecia (CIA), a side-effect that can have considerable negative psychological repercussions. Currently, there are very few animal models available to study the mechanism and prevention of CIA.
To develop a clinically relevant adult rat model for CIA.
We first tested whether neonatal pigmented Long-Evans (LE) rats developed alopecia in response to the chemotherapeutic agents etoposide and cyclophosphamide. We then determined whether the rats developed CIA as adults. In the latter experiment, rat dorsal hair was clipped during the early telogen stage to synchronize the hair cycle, and starting 15 days later, the rats were treated with etoposide for 3 days.
Neonatal LE pups developed CIA in response to etoposide and cyclophosphamide, similar to other murine models for CIA. Clipping of the hair shaft during early telogen resulted in synchronized anagen induction and subsequent alopecia after etoposide treatment in the clipped areas only. Hair follicles in the clipped areas had the typical chemotherapy-induced follicular dystrophy (dystrophic catagen). When the hair in the pigmented alopecic areas regrew, it had normal pigmentation.
A novel, pigmented adult rat model has been established for CIA. By hair-shaft clipping during early telogen, synchronized anagen entry was induced, which resulted in alopecia in response to chemotherapy. This is the first clinically relevant adult rat model for CIA, and will be a useful tool to test agents for the prevention and treatment of CIA.


Available from: Tongyu C. Wikramanayake, Apr 03, 2015
  • [Show abstract] [Hide abstract]
    ABSTRACT: In a new strategy, we sought to determine whether topically applied vasoconstrictor, with its accompanying transient skin hypoxia and exclusion of systemic drug, would prevent or suppress radiotherapy or chemotherapy-induced alopecia. Topical vasoconstrictor was applied to 1 cm2 skin patches on the backs of 10 day old rats and minutes later they received either 7.1 Gy whole-body radiation or systemic N-nitroso-N-methylurea (MNU) or Cytoxan. The degree of alopecia was scored 10 days later by visual assessment (% coat retention) and hair follicle histologic analysis. Topical application of epinephrine or norepinephrine in an alcohol:water delivery vehicle induced clear skin blanch, and in a dose-dependent manner, topical epinephrine or norepinephrine (20-1000 mM) applied before 7.1 Gy irradiation conferred 95% coat retention in the treated skin patches versus 0% coat retention in vehicle controls, or in skin outside the treated patches. By histology, small numbers of dystrophic hair follicles were observed in hairless skin versus the normal density of anagen follicles in the immediately adjacent, drug-protected skin patches at day 20; protected coats were retained into adulthood. Topical epinephrine or norepinephrine before systemic MNU (30 µg/gm bw) conferred up to 95% coat retention in treated skin patches versus 0% coat retention elsewhere. Epinephrine-conferred % coat retention dropped to 16% in rats that received systemic Cytoxan, a drug whose plasma half-life is at least 8-10-fold longer than MNU. A general strategy is discussed for the use of topical epinephrine or norepinephrine in the clinic to provide an inexpensive and convenient strategy to prevent cancer therapy-induced alopecia. © 2014 Wiley Periodicals, Inc.
    International Journal of Cancer 01/2015; 136(1). DOI:10.1002/ijc.28961 · 5.01 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Conventional chemotherapy leads to multiple adverse mucocutaneous complications such as oral mucositis, alopecia, ocular toxicity, and onycholysis. Limited pharmacologic interventions are available for preventing these clinical problems. This study aimed to critically review the role of cryotherapy (regional hypothermia) for alleviating these adverse symptoms. A narrative review was performed, with an emphasis on randomized controlled trials. A comprehensive search using PubMed, Ovid, Embase, and MEDLINE(®) was completed. References of all cited articles also were reviewed. Data from the review were composed of articles published between 1970 and May 2013. Available evidence suggests that regional hypothermia decreases the burden of chemotherapy-related oral mucositis, alopecia, ocular toxicity, and onycholysis. The major limitations of studies include the absence of blinded control groups and variable clinical end points. Regional hypothermia decreases the burden of these four chemotherapy-induced complications and is well tolerated. More research is needed to determine what subgroups of cancer patients are most likely to respond to different types of regional hypothermia, the ideal duration of cooling needed, and further improve the ease of use of the cooling devices.
    Journal of pain and symptom management 11/2013; 47(6). DOI:10.1016/j.jpainsymman.2013.07.014 · 2.74 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Introduction: Hair loss or alopecia affects the majority of the population at some time in their life, and increasingly, sufferers are demanding treatment. Three main types of alopecia (androgenic [AGA], areata [AA] and chemotherapy-induced [CIA]) are very different, and have their own laboratory models and separate drug-discovery efforts. Areas covered: In this article, the authors review the biology of hair, hair follicle (HF) cycling, stem cells and signaling pathways. AGA, due to dihydrotesterone, is treated by 5-α reductase inhibitors, androgen receptor blockers and ATP-sensitive potassium channel-openers. AA, which involves attack by CD8(+)NK group 2D-positive (NKG2D(+)) T cells, is treated with immunosuppressives, biologics and JAK inhibitors. Meanwhile, CIA is treated by apoptosis inhibitors, cytokines and topical immunotherapy. Expert opinion: The desire to treat alopecia with an easy topical preparation is expected to grow with time, particularly with an increasing aging population. The discovery of epidermal stem cells in the HF has given new life to the search for a cure for baldness. Drug discovery efforts are being increasingly centered on these stem cells, boosting the hair cycle and reversing miniaturization of HF. Better understanding of the molecular mechanisms underlying the immune attack in AA will yield new drugs. New discoveries in HF neogenesis and low-level light therapy will undoubtedly have a role to play.
    Expert Opinion on Drug Discovery 02/2015; 10(3):1-24. DOI:10.1517/17460441.2015.1009892 · 3.47 Impact Factor