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Urinary excretion of 5-S-cysteinyldopa (5-S-CD) was followed in 20 patients receiving PUVA therapy. Large increases were observed after PUVA treatment, more predominant in males and unrelated to skin types. Relative increases rather than absolute values paralleled cutaneous reactions.
This is the first in vivo study of the effects of UV on the epidermal melanocytes in dysplastic nevus syndrome (DNS). Eleven DNS patients and 22 healthy subjects were given total body UVB irradiation 8 times during 17 days and the melanocyte population was estimated in biopsies from shielded and irradiated skin. There was a doubling of the melanocyte counts in irradiated skin and a less pronounced but significant increase in the shielded skin area. The urinary excretion of 5-S-cysteinyldopa (5-S-CD) was measured before, during and after the irradiation period. The 5-S-CD excretion reached a maximum after 2 weeks of irradiation and returned towards the basal value after the irradiation period. We were not able to document any abnormal melanocytic UV response in DNS patients before, during or after the irradiation.
The urinary excretion of the eumelanin metabolite 6-hydroxy-5-methoxyindole-2-carboxylic acid and the pheomelanin metabolite 5-S-cysteinyldopa was followed during PUVA treatment for 6 weeks. They showed similar excretion patterns, with the highest values within 1-2 wk.
The effect of anti-Parkinson therapy on the urinary excretion of 5-S-cysteinyldopa (5SCD), a catechol metabolite of dihydroxyphenylalanine (DOPA) and marker for the melanocyte, was studied by means of high performance liquid chromatography. 5SCD was normal in Parkinson patients treated with anticholinergics. DOPA administration increased 5SCD excretion. Carbidopa and DOPA together elevated 5SCD markedly in a dose-dependent manner to values higher than seen in some patients with metastatic malignant melanoma. The effect of anti-Parkinson therapy should be considered when using 5SCD as a tumor marker or when a Parkinson patient has a melanoma.
27 patients with SSM or NM level IV and V have been submitted to a monthly evaluation of their level of 5-S-cysteinyldopa in the urine and IgG4 subclass in their sera. For 5 patients who entered the stage II of their disease during the follow-up, 3 had elevation of the 5S and 5 had large variations of IgG4. On 21 patients in clinical remission, 10 had conjunctly an increase of 5S and variations of IgG4. The predictional value of these tests is discussed.
A 36-year-old Japanese female, in whom malignant melanoma was detected from symptoms of brain metastasis, died 7 months later. The serum levels of 5-S-Cysteinyldopa (5-S-CD) and intercellular adhesion molecule-1 (ICAM-1) correlated with the disease progression. These values may be useful markers of disease progression for malignant melanoma, because the material is easily, frequently, and non-invasively obtained at regular intervals.
Red cock feathers (Rhode Island) were found to contain dopa and cysteinyldopa, trichochromes B and C, and two unidentified trichochromes. Trichochromes E and F were not found. Previous findings of trichochromes E and F may be explained as artifacts.
Urinary excretion of 5-S-cysteinyldopa was investigated in 12 genetically dark-skinned men living in Sweden. Ten subjects showed excretion values in the same range as persons of Swedish origin, whereas the excretion was higher in 2 subjects.
The melanin metabolite 5-S-cysteinyldopa (5-S-CD) has been reported to be helpful in detecting occult melanoma metastases and as a prognostic marker in B16 melanoma-bearing mice. The goal of our study was to analyze the significance of the serum 5-S-CD level for the biochemical detection of metastases in human malignant melanoma (MM) and for monitoring the progression or the immunochemotherapeutically induced regression of MM. From 11 patients with metastatic MM observed between 1991 and 1995, serum samples were collected before and after each cycle of immunotherapy or immunochemotherapy. Samples were analyzed for 5-S-CD by automated high performance liquid chromatography with electrochemical detection. Cycles of immunochemotherapy consisted of human interleukin 2 and IFN-alpha (four patients) or of human interleukin 2, IFN-alpha, and dacarbazine (seven patients). Serum value of 5-S-CD in our normal controls was 1.9 +/- 0.6 ng/ml. All patients with metastatic MM showed 5-S-CD serum levels above the upper normal limit of 3.2 ng/ml (10 nM) and ranged from 2.3-fold (4.3 +/- 3.9 ng/ml) of the normal control values in early stages of metastases to more than 50-fold (94.3 +/- 220.3 ng/ml) of the normal control values in advanced stages of the disease. In 28 of 41 (68%) immunochemotherapeutical cycles, a decrease of 5-S-CD was seen during therapy, and in 13 cycles (31.7%), an increase was seen. Patients with more than 68% decreasing cycles (defined as responders; n = 5) showed significantly longer survival times (P = 0.008) than patients with less than 68% decreasing cycles (nonresponders; n = 6). High levels of 5-S-CD were also observed in metastasizing amelanotic melanoma. Serum 5-S-CD is a useful marker for monitoring the clinical course of MM patients, for discriminating between responders and nonresponders to immunochemotherapy, and as a prognostic factor concerning survival time and death risk.
The clinical significance of 5-S-cysteinyldopa (5-S-CD), a major intermediate in melanin synthesis, was evaluated as a potential diagnostic tumor marker for uveal melanoma. Serum concentrations of 5-S-CD in 6 out of 7 patients with uveal melanoma in the absence of extraocular metastases were close to those of controls. In contrast, serum concentrations of 5-S-CD were found to be elevated in 3 patients with systemic metastases of melanoma. In addition, 5-S-CD in intraocular fluids, including both aqueous and vitreous humor, was elevated in patients with uveal melanoma regardless of the presence or absence of systemic metastases. These results suggest that 5-S-CD in the intraocular fluid may serve as a useful biochemical marker for the diagnosis of uveal melanoma.
PURPOSE: To evaluate the clinical significance of 5-S-cysteinyldopa (5-S-CD), a major intermediate in melanin synthesis, as a potential diagnostic tumor marker for uveal malignant melanoma. METHODS: The levels of 5-S-CD in the serum were measured by high-performance liquid chromatography in 16 patients with primary uveal melanoma. The levels of 5-S-CD were also measured in both aqueous and vitreous humor in 10 patients with uveal melanoma. The serum of healthy volunteers and patients with skin diseases other than melanoma, and the intraocular fluids of patients with cataract and vitreoretinal diseases were used as controls. RESULTS: Serum concentrations of 5-S-CD in patients with uveal melanoma in the absence of extraocular metastases were close to those of controls; however, serum concentrations of 5-S-CD were significantly elevated in patients with extraocular metastases of melanoma. Concentrations of 5-S-CD in the intraocular fluids, especially vitreous humor, were higher in patients with uveal melanoma than in controls. CONCLUSIONS: 5-S-CD in intraocular fluids may serve as a useful biochemical marker for the diagnosis of uveal melanoma. Serum 5-S-CD may contribute to the assessment of the presence and progression of extraocular metastases in patients with uveal melanoma.
We have previously shown that the urinary excretion of 5-S-cysteinyldopa (5-S-CD) reflects well the progression of B16 mouse melanoma. We examined the usefulness of plasma concentration of 5-S-CD in following the progression of melanoma and evaluating the efficacy of immuno- and chemotherapeutic agents in the B16 mouse model. Murine interferon-beta (MuINF-beta; 3 x 10(5) U) or dacarbazine (DTIC; 50 mg/kg) was administered once a day for 10 or 5 consecutive days starting 8 days after subcutaneous inoculation of B16 melanoma cells in C57BL/6 mice. Blood samples were collected from the tail vein and tumour volumes were measured every other day until day 24. Levels of 5-S-CD in plasma were determined by high-performance liquid chromatography. Tumours became palpable on day 6-8 and grew exponentially thereafter in the control mice. Tumours in INF-beta-treated mice also grew exponentially, although at a reduced rate. However, the growth of tumours in the DTIC-treated mice was almost suppressed between days 12 and 18. Mean values of tumour volume on day 16 were 1.45, 1.05, and 0.83 cm3 in the control, INF-beta-treated, and DTIC-treated groups, respectively. The plasma concentration of 5-S-CD began to increase on day 8, at much slower rates in the experimental groups than those in the control group. Mean values of plasma 5-S-CD on day 16 were 14.3, 5.9, and 5.6 nmol/l in the control, INF-beta-treated, and DTIC-treated groups; 5-S-CD level on day -2 was 1.8 nmol/l.(ABSTRACT TRUNCATED AT 250 WORDS)
The binding of tetra(4-N,N,N,N-trimethylanilinium)porphyrin (TAP) to melanins quenches the porphyrin emission. Time-resolved femtosecond absorption spectroscopy reveals that the mechanism behind this quenching is ultrafast nonradiative energy transfer ((tau)ET < 100 fs) from electronically excited TAP to melanin. Similar dynamics are observed for both dopa and cysteinyldopa melanins. Steady-state emission studies demonstrate that the emission from melanin increases upon excitation of bound TAP, thereby confirming that rapid energy transfer occurs. These results are consistent with previous photoacoustic studies, which revealed that the TAP-melanin complex behaves like a supermolecular system liberating heat as a whole.
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