aPediatric Endocrinology, Children's Hospital at Montefiore and Albert Einstein College of Medicine, Bronx, New York bDepartment of Chemistry and Biochemistry, University of Arkansas, Fayetteville, Arkansas, USA cDepartment of Bacteriology, Okayama University Graduate School of Medicine, Okayama, Japan.
Anticancer Drugs. 2014 Jan;25(1):30-8. doi: 10.1097/CAD.0b013e3283650bff.
Alopecia is a psychologically devastating complication of chemotherapy for which there is currently no effective therapy. PTH-CBD is a collagen-targeted parathyroid hormone analog that has shown promise as a therapy for alopecia disorders. This study compared the efficacy of prophylactic versus therapeutic administration of PTH-CBD in chemotherapy-induced alopecia using a mouse model that mimics the cyclic chemotherapy dosing used clinically. C57BL/6J mice were treated with a single subcutaneous injection of PTH-CBD (320 mcg/kg) or vehicle control before or after hair loss developing from three courses of cyclophosphamide chemotherapy (50-150 mg/kg/week). Mice receiving chemotherapy alone developed hair loss and depigmentation over 6-12 months. Mice pretreated with PTH-CBD did not develop these changes and maintained a normal-appearing coat. Mice treated with PTH-CBD after development of hair loss showed a partial recovery. Observations of hair loss were confirmed quantitatively by gray scale analysis. Histological examination showed that in mice receiving chemotherapy alone, there were small, dystrophic hair follicles mostly in the catagen phase. Mice receiving PTH-CBD before chemotherapy showed a mix of normal-appearing telogen and anagen hair follicles with no evidence of dystrophy. Mice receiving PTH-CBD therapy after chemotherapy showed intermediate histological features. PTH-CBD was effective in both the prevention and the treatment of chemotherapy-induced alopecia in mice, but pretreatment appears to result in a better cosmetic outcome. PTH-CBD shows promise as an agent in the prevention of this complication of chemotherapy and improving the quality of life for cancer patients.
脱发是化疗引起的一种心理上极具破坏性的并发症，目前尚无有效的治疗方法。PTH-CBD 是一种靶向胶原蛋白的甲状旁腺激素类似物，已被证明是治疗脱发疾病的一种有前途的药物。本研究使用模拟临床中周期性化疗给药的小鼠模型，比较了 PTH-CBD 预防性给药与治疗性给药在化疗诱导性脱发中的疗效。C57BL/6J 小鼠在接受环磷酰胺化疗（50-150mg/kg/周）三疗程后出现脱发和色素减退之前或之后，接受单次皮下注射 PTH-CBD（320mcg/kg）或载体对照。单独接受化疗的小鼠在 6-12 个月内出现脱发和脱色素。用 PTH-CBD 预处理的小鼠未发生这些变化，且保持正常外观的被毛。在出现脱发后用 PTH-CBD 治疗的小鼠显示部分恢复。通过灰度分析定量观察脱发。组织学检查显示，单独接受化疗的小鼠中，大多数处于退行期的小而营养不良的毛囊。接受化疗前 PTH-CBD 的小鼠表现出正常外观的休止期和生长期毛囊的混合，没有营养不良的证据。接受化疗后 PTH-CBD 治疗的小鼠显示出中间组织学特征。PTH-CBD 对预防和治疗化疗诱导的小鼠脱发均有效，但预处理似乎会产生更好的美容效果。PTH-CBD 有望作为预防这种化疗并发症和提高癌症患者生活质量的药物。
