Fas and c-kit are involved in the control of hair follicle melanocyte apoptosis and migration in chemotherapy-induced hair loss.

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J Invest Dermatol 2003 Jan;120(1):27-35

Fas and c-kit are involved in the control of hair follicle melanocyte apoptosis and migration in chemotherapy-induced hair loss.

Chemotherapy alters the structure and function of hair follicle melanocytes. Molecular mechanisms controlling melanocyte responses during chemotherapy-induced hair loss, however, remain largely unknown. Using immunohistology and multicolor confocal microscopy, we show here that cyclophosphamide administration to C57BL/6 mice alters the activity and fate of hair follicle melanocytes. After 24-48 h, hair bulb melanocytes expressing Fas undergo apoptosis. The number of apoptotic follicular melanocytes is significantly reduced (p<0.01) in cyclophosphamide-treated Fas knockout mice compared to wild-type controls, suggesting that Fas signaling contributes to chemotherapy-induced melanocyte death. After 3-5 d, surviving hair bulb melanocytes express c-kit receptor, proliferate, and appear to migrate up the outer root sheath. Tyrosinase-positive and melanogenically active cells then appear in the epidermis. By Western blotting and immunohistochemistry, expression levels of the c-kit ligand, stem cell factor, in skin and epidermis are strongly increased after cyclophosphamide treatment. Cyclophosphamide-induced migration of the hair follicle melanocytes into epidermis is completely abrogated by administration of c-kit neutralizing antibody. These data suggest that chemotherapy induces a complex response in the hair follicle melanocytes, which includes apoptosis, proliferation, and migration. Pharmacologic manipulation of Fas and c-kit signaling pathways might be useful for the correction of skin hyperpigmentation as a side-effect of chemotherapy.

Br J Dermatol 2002 Nov;147(5):982-4

There is no clear association between low serum ferritin and chronic diffuse telogen hair loss.

BACKGROUND: Low iron stores are considered a possible cause of chronic diffuse telogen hair loss in women. Estimation of serum ferritin is recommended as part of the initial assessment when women present with chronic diffuse telogen hair loss, and iron supplementation therapy is commonly recommended for those found to have low iron stores. OBJECTIVES: To evaluate the relationship between low serum ferritin ( 20 micro g L-1. Cessation or reversal of hair loss was not seen in any of these women. CONCLUSIONS: No direct relationship between low serum ferritin and hair loss can be established. The usefulness of serum ferritin in the routine investigation of women with chronic diffuse telogen hair loss is unclear, as is the role of iron supplementation therapy in the management of hair loss.

Gan To Kagaku Ryoho. 2003 May;30(5):653-9.

Weekly paclitaxel administration in the adjuvant therapy of primary breast cancer

PURPOSE: To investigate feasibility and toxicity of weekly paclitaxel administration in the adjuvant therapy of primary breast cancer. PATIENTS AND METHODS: Thirty-one patients with primary breast cancer received sustained weekly infusion of paclitaxel at a dose of 90 mg/body for 6 weeks followed by a 2-week interval. This weekly schedule was repeated twice. Leukocytes were checked immediately before every infusion and the dose was reduced to 80 mg/body when grade 1 neutropenia occurred. All patients were assessable for feasibility and toxicity. RESULTS: A total 349 weekly paclitaxel infusions were administrated to 31 patients (median, 12 infusions/patient). The median delivered dose-intensity was 88.0 mg/body/week (range 80 to 90). Therapy was well tolerated and completed in 27 patients. Four patients refused to continue the therapy because of nausea, fatigue, dizziness and weight gain. Grade 2 neutropenia occurred in 10 patients (32.3%), but grade 3 neutropenia did not occur. Grade 1 peripheral neuropathy occurred in 3 patients (9.7%). Grade 1 nausea occurred in 3 patients (9.7%). CONCLUSION: Weekly paclitaxel administration is well tolerated with a favorable toxicity profile in patients with primary breast cancer in the adjuvant setting. Weekly paclitaxel therapy can be performed safely in the outpatient setting.

Australas J Dermatol. 2003 May;44(2):106-9.

PUVA treatment of alopecia areata totalis and universalis: a retrospective study.

The results of PUVA treatment of alopecia areata (AA) totalis and universalis were reviewed in 26 adult patients. Eight of 15 patients with AA totalis and six of 11 patients with AA universalis achieved a complete response (>90% hair regrowth). Patients with AA totalis had a greater incidence of treatment failure (<25% hair regrowth) than those with AA universalis. Patients with a family history of AA were significantly less likely to have a positive response to PUVA than those with no family history. Sex, age at diagnosis and treatment, interval between diagnosis and treatment, and background of atopy were not significant determinants of outcome. Although unable to show significance for clinical response to treatment, this study demonstrates complete hair regrowth in patients with both AA totalis (53%) and universalis (55%) while reporting a low relapse rate among these patients (21%) within a long period of follow up (mean 5.2 years).

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