PREVENTION OF CHEMOTHERAPY-INDUCED HAIR LOSS

描述(由申请人提供)：目前的癌症化疗通常使用强大的抗肿瘤药物的组合。大多数治疗组合包括导致头皮脱发的抗肿瘤药物(化疗导致的脱发)。尤其是常用的脱发抗肿瘤药物有环磷酰胺、阿霉素、依托泊苷、紫杉醇和长春新碱。脱发显然是化疗最令人畏惧的副作用。众所周知，患者会因此而拒绝化疗，而怀疑这种与治疗相关的脱发造成的心理创伤可能会影响治疗的成功，似乎并不是没有道理的。到目前为止，患者还没有可供选择的预防性治疗。许多实验室证明，诱导一种保守的保护性反应，即所谓的应激蛋白反应，可以保护各种类型的培养细胞免受目前临床上使用的几乎所有类别的抗肿瘤药物的杀伤。本提案将在动物模型中检验这样一种假设，即预先在(头皮)毛囊有丝分裂活性细胞中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。应激蛋白反应诱导的局部化将确保预防性治疗不会干扰抗肿瘤药物在毛囊以外的细胞中的细胞毒活性，即脱发的预防性治疗不会降低化疗效果。

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.