All-trans retinoic acid (atRA) differentially induces apoptosis in matched primary and metastatic melanoma cells -- a speculation on damage effect of atRA via mitochondrial dysfunction and cell cycle redistribution.

All-trans retinoic acid (atRA) has been suggested to exert its cytotoxicity via apoptosis but the mechanisms behind the damage effects have not been fully understood. In this study, we investigated the cytotoxic effects of atRA in eleven primary and matched metastatic cutaneous melanoma cell lines. All the primary and metastatic melanoma cell lines examined expressed the retinoic acid receptors. The cultured melanoma cells treated with atRA showed dysfunction of mitochondria and altered cell cycle distribution, inhibited cell proliferation and apoptosis. The cytotoxic effects of atRA were dose- and time-dependent. The dysfunction of mitochondria and induction of apoptosis were more pronounced in the primary tumor cells than in the metastatic cell lines from the same patients. The data indicate that the cytotoxic effect of atRA was mediated through dysfunction of mitochondria, alterations in cell cycle and induction of apoptosis. Melanoma in early stage may have better response to atRA adjuvant therapy than the melanoma in late stage, suggesting the early utility of atRA in melanoma chemotherapy.

Assessment of sun-related behaviour in individuals with dysplastic naevus syndrome: a comparison between diary recordings and questionnaire responses.

In Sweden, individuals with dysplastic naevus syndrome (DNS-D2), a high risk group for malignant melanoma, are regularly screened and informed about self-examination and sun protection. During the summer of 1994, 54 out of 65 consecutive patients completed 1 month of daily self-recordings of sun-related behaviour. The diary report was compared with questionnaire responses obtained 6 months later concerning sun-related behaviour, both habitual and during the month of self-recording. The correspondence between the sun-related behaviour recorded in the diary and given in response to the questionnaire was fairly high, but 48% underestimated and 29% overestimated their actual number of sunbathing occasions in the questionnaire. Few patients indicated habitual high frequencies of sunbathing, although some of them recorded six or more occasions during 1 month in the diary. Those who recorded multiple sunburns reported the highest number of sunburns in the questionnaire. Patients who scored high on sunbed use also recorded high numbers of sunbathing occasions. Diaries should be used when detailed information about the magnitude of sun-related behaviour is essential, whereas questionnaires should be sufficient in studies aiming to differentiate between high and low frequencies of such behaviour.

Sun-related behaviour in individuals with dysplastic naevus syndrome.

In Sweden, individuals with dysplastic naevus syndrome are regularly screened and informed about self-examination and sun-protection at special clinics. This study describes sun-related behaviour in this group. A total of 54/65 consecutive patients with dysplastic naevus syndrome (28 women and 26 men) completed diary recordings of sun-related behaviour during 1 month in 1994. A majority (81%) reported sunbathing with the intention to get a tan, mean number of occasions 9.2, range 1-24 occasions, during the month of recordings. Out of these, 61% reported sunburns, some of them repeatedly up to 7 times. Sunbathing occurred mainly in bathing suits during midday in sunny weather, with a mean duration of 2.5 h per occasion. Such a hazardous behaviour in the sun in a melanoma high risk group is alarming. New models for intervention to support a more sun protective life style in this group of patient have to be elaborated.

Epidermal Langerhans' cells in chronic eczematous dermatitis of the palms treated with PUVA and UVB.

Epidermal Langerhans' cells (LC) were studied in patients with chronic eczematous dermatitis of the palms. The monoclonal antibodies anti-Leu 6 and anti-HLA-DR were used, and the cells visualized with an immunoperoxidase technique. Increased numbers of LC were found in allergic contact dermatitis as well as in irritant contact dermatitis and hyperkeratotic dermatitis of the palms. The increased number of epidermal LC in lesional skin may facilitate presentation of exogenous or endogenous antigens to activated T-cells. One hand was treated with PUVA or UVB and the other hand served as a non-exposed control. PUVA treatment cleared the dermatitis and the LC number decreased markedly. With UVB treatment clinical improvement was achieved, and a less pronounced decrease in epidermal LC was noticed. There seems to be a crude relationship between the extent of clinical improvement and the reduction in epidermal LC numbers. The change in LC might be a primary event or secondary to a reduction of the inflammatory process.

Epidermal Langerhans' cells in patients with pustulosis palmoplantaris treated with etretinate or etretinate + methoxsalen photochemotherapy.

Epidermal Langerhans' cells (LC) were studied in patients with pustulosis palmoplantaris (PPP) by utilizing the monoclonal antibodies anti-Leu6 and anti-HLA-DR in combination with an immunoperoxidase technique. In non-pustular areas of the skin lesions in PPP, an increased number of epidermal LC was found compared with control subjects. No change in LC counts was observed following etretinate monotherapy for 2 weeks. Etretinate was then combined with PUVA treatment of one palm/sole with the contralateral side as a non-UVA exposed control. After 6-12 weeks of etretinate + PUVA treatment the PPP had resolved and the number of epidermal dendritic HLA-DR+ and Leu6+ cells had normalized. On the contralateral side, etretinate treatment induced a marked clinical improvement and a reduction of HLA-DR+ cells. The observation of an increased LC population in active PPP and a reduction during clinical improvement indicates a close relationship between LC and the activity of PPP.