Katikaneni Ranjitha, Ponnapakkam Tulasi, Seymour Andrew, Sakon Joshua, Gensure Robert
aPediatric Endocrinology bDepartment of Pathology, Children's Hospital at Montefiore and Albert Einstein College of Medicine, Bronx, New York cDepartment of Chemistry and Biochemistry, University of Arkansas, Fayetteville, Arkansas, USA.
Anticancer Drugs. 2014 Aug;25(7):819-25. doi: 10.1097/CAD.0000000000000110.
Chemotherapy-induced alopecia is a major source of psychological stress in patients undergoing cancer chemotherapy, and it can influence treatment decisions. Although there is currently no therapy for alopecia, a fusion protein of parathyroid hormone and collagen binding domain (PTH-CBD) has shown promise in animal models. The aim of this study was to determine whether there are dose-dependent effects of PTH-CBD on chemotherapy-induced alopecia in a mouse model. C57BL/6J mice were waxed to synchronize hair follicles; treated on day 7 with vehicle or PTH-CBD (100, 320, and 1000 mcg/kg subcutaneous injection); and treated on day 9 with vehicle or cyclophosphamide (150 mg/kg intraperitoneally). Mice were photographed every 3-4 days and killed on day 63 for histological analysis. Photographs were quantified by gray scale analysis to assess hair content. Mice not receiving chemotherapy showed regrowth of hair 2 weeks after waxing and normal histology after 2 months. Mice receiving chemotherapy alone showed marked hair loss after chemotherapy, which was sustained for 10 days and was followed by rapid regrowth of a normal coat. Histological analysis revealed rapid cycling dystrophic anagen/catagen follicles. Animals receiving chemotherapy and PTH-CBD showed decreased hair loss and more rapid regrowth of hair than that seen with chemotherapy alone (increased hair growth by gray scale analysis, P<0.05), and the effects were dose dependent. Histologically, hair follicles in animals receiving the highest dose of PTH-CBD were in a quiescent phase, similar to that in mice that did not receive chemotherapy. Single-dose subcutaneous administration of PTH-CBD showed dose-dependent effects in minimizing hair loss and speeding up recovery from chemotherapy-induced alopecia.
化疗引起的脱发是癌症化疗患者心理压力的主要来源，并且会影响治疗决策。虽然目前尚无治疗脱发的方法，但甲状旁腺激素与胶原蛋白结合域的融合蛋白（PTH-CBD）在动物模型中已显示出前景。本研究的目的是确定PTH-CBD在小鼠模型中对化疗引起的脱发是否存在剂量依赖性效应。将C57BL/6J小鼠进行脱毛处理以使毛囊同步化；在第7天用赋形剂或PTH-CBD（100、320和1000 mcg/kg皮下注射）进行处理；并在第9天用赋形剂或环磷酰胺（150 mg/kg腹腔注射）进行处理。每3-4天对小鼠拍照一次，并在第63天处死以进行组织学分析。通过灰度分析对照片进行量化以评估毛发含量。未接受化疗的小鼠在脱毛后2周毛发开始再生，2个月后组织学正常。单独接受化疗的小鼠在化疗后出现明显脱发，持续10天，随后迅速重新长出正常毛发。组织学分析显示毛囊快速循环营养不良性生长期/退行期。接受化疗和PTH-CBD的动物与单独接受化疗相比，脱发减少且毛发再生更快（通过灰度分析毛发增长增加，P<0.05），并且这些效应具有剂量依赖性。组织学上，接受最高剂量PTH-CBD的动物的毛囊处于静止期，类似于未接受化疗的小鼠。单剂量皮下注射PTH-CBD在最小化脱发和加速化疗引起的脱发恢复方面显示出剂量依赖性效应。
