Prevention of chemotherapy-induced alopecia in rodent models

Jiménez, Joaquín J.; Roberts, Stephen; Mejia, Jessica; Mauro, Lucía Mercedes; Munson, John C.; Elgart, George W.; Connelly, Elizabeth Alvarez; Chen, Qingbin; Zou, Jiangying; Goldenberg, Carlos; Voellmy, Richard

doi:10.1379/csc-287

Cited by 5 publications

(9 citation statements)

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“…Therefore, a clinically relevant animal model for CIA needs to show synchronized anagen, hair loss and HF histopathology similar to CIA in patients. Two young rat models and a young mouse model for CIA take advantage of the fact that rat and mouse HFs are synchronized during the perinatal HF morphogenesis 5,10,11 . However, because human scalp hair is pigmented, it is preferable to have animal models with mature, pigmented terminal HFs.…”

Section: Discussionmentioning

confidence: 99%

“…There have been two neonatal rat models developed, a Sprague–Dawley (SD) model 5 and a Wistar model, 10 in which alopecia can be induced by chemotherapeutic agents during perinatal follicular morphogenesis. Similarly, a young (12 days old) mouse model has also been developed, 11 as well as an adult (6–8 weeks old) mouse model using the C57BL/6 strain, in which synchronized anagen is induced by depilation during telogen before administration of the chemotherapeutic agent 7 . To date, however, there has been no pigmented, adult rat mode developed for CIA.…”

Section: Introductionmentioning

confidence: 99%

“…In this study, we tested whether LE rats developed alopecia in response to chemotherapeutic agents, as seen in young albino rats 5,10,11 and adult mice 7 . We chose etoposide (a topoisomerase inhibitor) and cyclophosphamide (an alkylating compound) for our experiments because they are common chemotherapeutic agents that are known to cause severe alopecia in patients, and have been shown to induce complete loss of body hair in young albino rats 11 . We then investigated whether clipping (not plucking) of the hair shaft affected the hair cycle, and whether clipping influenced the HF response to subsequent chemotherapy.…”

Section: Introductionmentioning

confidence: 99%

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A novel rat model for chemotherapy-induced alopecia

Wikramanayake¹,

Amini²,

Simon³

et al. 2012

Clinical and Experimental Dermatology

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Summary Background 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. Aim To develop a clinically relevant adult rat model for CIA. Methods 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. Results 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. Conclusions A novel, pigmented adult rat model has been established for CIA. By hair shaft clipping during early telogen, synchronized anagen entry was induced that 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.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A novel rat model for chemotherapy-induced alopecia

Wikramanayake¹,

Amini²,

Simon³

et al. 2012

Clinical and Experimental Dermatology

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“…Depending on preference, using a wig or any other type of head covering until the hair regrows is an effective way of dealing with this condition, while at the same time it can protect the scalp from sun and cold exposure. [76][77][78] …”

Section: Investigations Investigationsmentioning

confidence: 99%

Anagen effluvium

Kanwar¹,

Narang²

2013

Indian J Dermatol Venereol Leprol

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Disturbances of hair follicle cycling lie at the heart of most hair growth disorders, and have dramatic effects on visible hair growth and shedding. The two common disorders due to aberration in hair follicle cycling are telogen and anagen effluvium. Though a lot of literature addresses the problem of telogen effluvium, there are not many reviews on anagen effluvium or anagen hair loss. Anagen effluvium is considered synonymous with chemotherapy-induced alopecia and other causes are rarely considered. In this review, we try to discuss the etiopathogenesis, clinical presentation, differentials, and management issues in anagen effluvium. Anagen effluvium is the abrupt loss of hairs that are in their growing phase (anagen) due to an event that impairs the mitotic or metabolic activity of hair follicle. Chemotherapy, radiation and toxic chemicals, and sometimes inflammatory diseases like alopecia areata and pemphigus are also capable of diminishing the metabolic activity of hair follicles resulting in anagen hair loss. Although it is reversible, and hair regrowth occurs after a delay of 1-3 months; sometimes it can lead to permanent alopecia and can be psychologically devastating with negative impact on individual perceptions of appearance, body image, sexuality, and self-esteem. For some patients, the emotional trauma may be so severe that it may lead to discontinuing or refusing therapy that might otherwise be beneficial. In such cases, a psychosomatic approach as well as empathic consideration of the patients concerns and fears as well as the provision of practical medical-aesthetic and styling tips are equally important and can be integrated in management.

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“…However, scalp cooling is not recommended in patients with extensive hematological malignancies, as cooling might reduce the effect of chemotherapy on tumor cells in the scalp skin 6. Thus far, no satisfactory preventative strategy is available for CIA, and no treatment modality has been shown to be clearly effective 7–9…”

mentioning

confidence: 99%

Treatment for chemotherapy‐induced alopecia in mice using parathyroid hormone agonists and antagonists linked to a collagen binding domain

Katikaneni

Ponnapakkam

Suda

et al. 2012

Intl Journal of Cancer

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Parathyroid hormone (PTH) agonists and antagonists have been shown to improve hair growth after chemotherapy; however, rapid clearance and systemic side-effects complicate their usage. To facilitate delivery and retention to skin, we fused PTH agonists and antagonists to the collagen binding domain (CBD) of Clostridium histolyticum collagenase. in-vitro studies showed that the agonist fusion protein, PTH-CBD, bound collagen and activated the PTH/parathyroid hormone-related peptide receptor in SaOS-2 cells. The antagonist fusion proteins, PTH(7–33)-CBD and PTH([−1]–33)-CBD, also bound collagen and antagonized PTH(1–34) effect in SaOS-2 cells; however, PTH(7–33)-CBD had lower intrinsic activity. Distribution studies confirmed uptake of PTH-CBD to the skin at 1 and 12 hr after subcutaneous injection. We assessed in vivo efficacy of PTH-CBD and PTH(7–33)-CBD in C57BL/6J mice. Animals were depilated to synchronize the hair follicles; treated on Day 7 with agonist, antagonist, or vehicle; treated on Day 9 with cyclophosphamide (150 mg/kg i.p.) or vehicle; and sacrificed on Day 39. Normal mice (no chemo and no treatment) showed rapid regrowth of hair and normal histology. Chemo + Vehicle mice showed reduced hair regrowth and decreased pigmentation; histology revealed reduced number and dystrophic anagen/catagen follicles. Chemo + Antagonist mice were grossly and histologically indistinguishable from Chemo + Vehicle mice. Chemo + Agonist mice showed more rapid regrowth and repigmentation of hair; histologically, there was a normal number of hair follicles, most of which were in the anagen phase. Overall, the agonist PTH-CBD had prominent effects in reducing chemotherapy-induced damage of hair follicles and may show promise as a therapy for chemotherapy-induced alopecia.

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Prevention of chemotherapy-induced alopecia in rodent models

Cited by 5 publications

References 0 publications

A novel rat model for chemotherapy-induced alopecia

A novel rat model for chemotherapy-induced alopecia

Anagen effluvium

Treatment for chemotherapy‐induced alopecia in mice using parathyroid hormone agonists and antagonists linked to a collagen binding domain

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