PREVENTION OF CHEMOTHERAPY-INDUCED HAIR LOSS

描述（由申请人提供）：目前的癌症化疗通常采用强效抗肿瘤剂的组合。大多数治疗组合包括抗肿瘤剂，导致头皮毛发脱落（化疗诱导的脱发）。特别地，经常使用的诱导脱发的抗肿瘤剂是环磷酰胺、阿霉素、依托泊苷、紫杉醇和长春新碱。脱发显然是化疗最可怕的副作用。众所周知，患者会因此拒绝化疗，怀疑这种治疗相关脱发造成的心理破坏可能会影响治疗的成功，这似乎是不合理的。到目前为止，没有选择性的预防性治疗提供给病人。许多实验室显示，诱导保守的保护性反应，即所谓的应激蛋白反应，可保护各种类型的培养细胞免受目前临床使用的基本上所有类别的抗肿瘤剂的杀伤。本建议将在动物模型中测试以下假设：在（头皮）毛囊的有丝分裂活性细胞中预先局部诱导应激蛋白反应将保护这些细胞免受环磷酰胺、阿霉素、依托泊苷、紫杉醇和长春新碱的杀伤，从而预防脱发。应激蛋白应答诱导的定位将确保预防性治疗不会干扰抗肿瘤剂在除毛囊细胞以外的细胞中的细胞毒性活性，即，脱发的预防性治疗不会降低化疗的疗效。

DESCRIPTION (provided by applicant): Current chemotherapy of cancer typically employs combinations of powerful anti-neoplastic agents. Most therapeutic combinations include anti-neoplastic agents that cause loss of scalp hair (chemotherapy-induced alopecia). Particularly, frequently used alopecia-inducing anti-neoplastic agents are cyclophosphamide, adriamycin, etoposide, taxol and vincristine. Alopecia is clearly the most feared side effect of chemotherapy. Patients have been known to refuse chemotherapy treatment because of it, and it seems not unreasonable to suspect that the psychological devastation resulting from this treatment-related hair loss may impact therapy success. To date, no elective preventive treatment is available to patients. Induction of a conserved protective response, the so-called stress protein response, was shown by many laboratories to protect various types of cultured cells against killing by essentially all classes of anti-neoplastic agents currently in clinical use. The present proposal will test in animal models the hypothesis that prior localized induction of the stress protein response in mitotically active cells of (scalp) hair follicles will protect these cells against killing by cyclophosphamide, adriamycin, etoposide, taxol and vincristine, resulting in the prevention of alopecia. Localization of the induction of the stress protein response will ensure that the preventive treatment will not interfere with the cytotoxic activity of the anti-neoplastic agents in cells other than those of hair follicles, i.e., that the preventive treatment of alopecia will not diminish chemotherapy efficacy.