Prevention of chemotherapy-induced alopecia in rodent models

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

doi:10.1007/s12192-007-0005-1

Cited by 33 publications

(37 citation statements)

References 35 publications

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“…3a and b). This is consistent with our previous observation that increased HSPA1A/B expression was detected by immunohistochemistry throughout the hair follicles after heat treatment of skin at 48.5°C for 20 min compared with control (Jimenez et al 2008). These results suggest that increased HSPA1A/B expression may predispose genetically susceptible mice to AA development.…”

Section: Hspa1a/b Expression In C3h/hej Micesupporting

confidence: 93%

“…The increase in the incidence of AA in the heat-treated group was statistically significant (p<0.0001). We also heat-or sham-treated 18-month-old mice once a week for 6 weeks (Jimenez et al 2008). Similar hair loss pattern was observed in heat-treated mice and mice that developed AA spontaneously ( Fig.…”

Section: Resultssupporting

confidence: 69%

“…In the first experiment, we investigated whether heat treatment, as an external stressor, increased the incidence of AA. Eight-month-old mice were heated on the trunk with 48.5°C circulating water for 20 min daily for 12 consecutive days (Jimenez et al 2008). Control mice were sham-treated with room temperature water.…”

Section: Resultsmentioning

confidence: 99%

“…The copper cylinder and tubing are wrapped with insulation material so that the actual temperature of the bottom of the copper cylinder is less than 0.1°C lower than the set temperature of the water bath. Eight-month-old mice were heated on the entire trunk, including dorsal and ventral areas, with 48.5°C circulating water for 20 min daily for 12 consecutive days, and 18-month-old mice were heated at the same temperature and duration once a week for 6 weeks as previously described (Jimenez et al 2008). Control mice were shamtreated with room temperature water.…”

Section: Mice and Treatmentmentioning

confidence: 99%

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Heat treatment increases the incidence of alopecia areata in the C3H/HeJ mouse model

Wikramanayake¹,

Alvarez‐Connelly²,

Simon³

et al. 2010

Cell Stress and Chaperones

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Alopecia areata (AA) is a common autoimmune disease characterized by non-scarring hair loss. Previous studies have demonstrated an association between AA and physiological/psychological stress. In this study, we investigated the effects of heat treatment, a physiological stress, on AA development in C3H/HeJ mice. Whereas this strain of mice are predisposed to AA at low incidence by 18 months of age, we observed a significant increase in the incidence of hair loss in heat-treated 8-month-old C3H/HeJ mice compared with sham-treated mice. Histological analysis detected mononuclear cell infiltration in anagen hair follicles, a characteristic of AA, in heat-treated mouse skin. As expected, increased expression of induced HSPA1A/B (formerly called HSP70i) was detected in skin samples from heat-treated mice. Importantly, increased HSPA1A/B expression was also detected in skin samples from C3H/HeJ mice that developed AA spontaneously. Our results suggest that induction of HSPA1A/B may precipitate the development of AA in C3H/HeJ mice. For future studies, the C3H/HeJ mice with heat treatment may prove a useful model to investigate stress response in AA.

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Section: Hspa1a/b Expression In C3h/hej Micesupporting

confidence: 93%

Section: Resultssupporting

confidence: 69%

Section: Resultsmentioning

confidence: 99%

Section: Mice and Treatmentmentioning

confidence: 99%

See 2 more Smart Citations

Heat treatment increases the incidence of alopecia areata in the C3H/HeJ mouse model

Wikramanayake¹,

Alvarez‐Connelly²,

Simon³

et al. 2010

Cell Stress and Chaperones

Self Cite

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show abstract

“…Heat was then applied with a copper cylinder connected to a precision water bath (48.5°C) for 20 min. The heat-treated area was immediately cooled with a small icepack for 5 min (Jimenez et al 2008). Mice were monitored for 6 weeks for hair loss.…”

Section: Mice and Treatmentmentioning

confidence: 99%

Prevention and treatment of alopecia areata with quercetin in the C3H/HeJ mouse model

Wikramanayake

Villasante

Mauro

et al. 2012

Cell Stress and Chaperones

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Alopecia areata (AA) is an autoimmune nonscarring hair loss disorder. AA can be acute, recurrent, or chronic. Current therapeutic options for AA are limited, and there is no effective prevention for recurrent AA. We have previously shown a correlation between the expression of HSP70 (HSPA1A/B), a heat shock protein involved in the inflammatory response, and the onset of AA in the C3H/ HeJ mouse model. In this study, we tested the effects of quercetin, a bioflavonoid with anti-inflammatory properties, on AA development and HSP70 expression in the C3H/HeJ model. Mice with spontaneous AA were treated with subcutaneous quercetin or sham injections. Hair regrowth was observed in lesional areas in all the quercetin-treated mice, but in none of the sham-treated mice. In addition, non-alopecic C3H/HeJ mice were heat-treated to induce alopecia, along with quercetin or sham injections. Whereas 24% of the heat-treated mice with sham injections developed alopecia, none of the mice receiving quercetin injections did. As expected, the level of HSP70 expression in quercetin-treated areas was comparable to control. Furthermore, we showed that systemic delivery of quercetin by intraperitoneal injections prevented/reduced spontaneous onset of AA. Our results demonstrated that quercetin provided effective treatment for AA as well as prevention of onset of AA in the C3H/HeJ model, and warrant further clinical studies to determine whether quercetin may provide both treatment for preexisting AA and prevention of recurrent AA. The ready availability of quercetin as a dietary supplement may lead to increased patient compliance and positive outcomes for AA.

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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 33 publications

References 35 publications

Heat treatment increases the incidence of alopecia areata in the C3H/HeJ mouse model

Heat treatment increases the incidence of alopecia areata in the C3H/HeJ mouse model

Prevention and treatment of alopecia areata with quercetin in the C3H/HeJ mouse model

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

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