[Multidisciplinary management of voluntary pink oleander poisoning: How to estimate the quantities ingested?] / Prise en charge multidisciplinaire d'une intoxication volontaire au laurier rose : comment estimer les quantités ingérées ?

This is a case of voluntary ingestion of Nerium oleander leaves in an adolescent requiring the use of atropine and emergency chartering of antidigoxin antibodies (Digifab®) due to the difficulty of assessing oleandrin level and associated toxicity. Upon hospital admission, a digoxinemia was performed (0.44µg/mL) and the presence of oleandrine was detected. Oleandrin levels at toxic levels may be suspected by a measure of blood digoxin and explain the patient's clinical signs, which could adapt the therapeutic management.

Quantification of urinary allantoin by capillary zone electrophoresis during recombinant urate oxydase (rasburicase) therapy.

OBJECTIVES: Rasburicase (Fasturtec) is used to prevent or treat hyperuricemia associated with chemotherapy. We developed a capillary zone electrophoresis method to measure urinary allantoin, the degradation product of uric acid by rasburicase. DESIGN AND METHODS: Electrophoresis was performed using a P/ACE 5500 system (Beckman) with a fused silica capillary tube and a UV-visible detector set at 214 nm. Urine samples from 10 patients with non-Hodgkin's lymphoma were analyzed to validate the technique. RESULTS: Using a sodium tetraborate running buffer, urinary allantoin was separated from related compounds and internal standard in less than 30 min. The method was linear up to 1.25 g/L (quantification limit: 30 mg/L); precision was below 10%. The total amount of allantoin excreted in patients treated by rasburicase ranged from 1.5 g to 7.9 g/4 days. CONCLUSION: This CZE assay is a simple, rapid and reproducible method to measure allantoin in urine. Different elimination profiles have been found in patients treated with rasburicase.

Parallel insulin-like growth factor I and insulin resistance in muscles of rats fed a high fat diet.

The possibility of a similarity between insulin-like growth factor-I (IGF-I) and insulin resistance in epitrochlearis muscles of rats fed a high fat diet [20% (wt/wt) fat] vs. a low fat diet [5% (wt/wt) fat] was investigated. Half-maximally and maximally effective concentrations of IGF-I- and insulin-stimulated 3-O-methyl-glucose transport were 2.32 and 25 nM, respectively, for IGF-I, compared with 0.79 and 20 nM for insulin. The high fat diet reduced both responsiveness and sensitivity of IGF-I-stimulated 3-O-methyl-glucose transport in parallel with the impaired insulin-stimulated 3-O-methyl-glucose transport. IGF-I binding at 2.5 nM to incubated epitrochlearis muscle was also decreased by the high fat diet (P < 0.05). Thus, the high fat diet caused simultaneous IGF-I and insulin resistance in rat skeletal muscle. The IGF-I resistance induced by feeding the high fat diet seems at least partially due to a reduction in IGF-I binding.

Ornithine alpha-ketoglutarate metabolism after enteral administration in burn patients: bolus compared with continuous infusion.

Ornithine alpha-ketoglutarate (OKG) has been successfully used as an enteral supplement in the treatment of catabolic states, including burn injury. However, specific questions remain unanswered concerning burn patients, including OKG metabolism and metabolite production, appropriate mode of administration, and dose. We thus performed a kinetic study and followed plasma ornithine and OKG metabolite concentrations on day 7 postburn in 42 (35 men, 7 women) consecutive burn patients aged 33 +/- 2 y with a mean (+/-SEM) total burn surface area (TBSA) of 31 +/- 1%. Patients were randomly assigned to receive OKG as a single bolus (10 g; n = 13) or in the form of a continuous gastric infusion (10, 20, or 30 g/d over 21 h; n = 13) or an isonitrogenous control (n = 16). Plasma pharmacokinetics of ornithine followed a one-compartment model with first-order input (r = 0.993, P < 0.005). OKG was extensively metabolized in these patients (absorption constant = 0.028 min-1, elimination half-life = 89 min), with the production of glutamine, arginine, and proline; proline was quantitatively the main metabolite [in OKG bolus, area under the curve (AUC)0-7h: proline, 41.4 +/- 5.6 mmol.min/L; glutamine, 20.4 +/- 5.7 mmol.min/L; and arginine, 7.3 +/- 1.9 mmol.min/L]. Proline production was dose-dependent and quantitatively similar between modes of OKG administration. Glutamine and arginine production were not dose-dependent and were higher in the bolus group than in the infusion group. Overall, the bolus mode of OKG administration appeared to be associated with higher metabolite production compared with continuous infusion in burn patients, especially for glutamine and arginine.

Ornithine alpha-ketoglutarate limits muscle protein breakdown without stimulating tumor growth in rats bearing Yoshida ascites hepatoma.

The growth of the Yoshida ascites hepatoma AH130 (YAH) is associated with early wasting, depletion of intracellular amino acid pools, and a pronounced activation of protein degradation in skeletal muscle of the host animal. Ornithine alpha-ketoglutarate (OKG) is used in the treatment of hypercatabolic states, and it has been suggested that it may improve nitrogen balance through repletion of free amino acid pools and suppression of protein catabolism. In cancer, OKG might similarly improve host nutritional status or stimulate tumor growth if its metabolites are limiting for tumor growth. Enteral supplementation with OKG was investigated in Sprague-Dawley rats bearing YAH. Tumor-bearing rats were compared with ad libitum- and pair-fed controls. Rats received OKG (3.4 to 4.0 g/kg body weight/d) or an equal amount of nitrogen as glycine (n = 8 in each group) for 5 days. Tumor implantation decreased cumulative food intake (-40%), host weight (-6%), skeletal muscle weight, and free amino acid levels in muscle and plasma. Muscle protein balance was estimated in vitro; decreased protein synthesis (-30%) and increased proteolysis (+113%) were observed in epitrochlearis muscles (EPI) of YAH-bearing rats compared with control groups. OKG had no effect on the wet weight (10 +/- 1 g) and nitrogen content of the tumor, or on free amino acid levels in the tumor. In tumor-bearing rats, OKG improved muscle protein balance by reducing breakdown by 33% and overall amino acid release of incubated EPI by 46%.

Negative impact of cancer chemotherapy on protein metabolism in healthy and tumor-bearing rats.

Although chemotherapeutic agents are widely used in the treatment of cancer, few experimental data are available on their effects on host N metabolism. We studied the effects of a single intraperitoneal (IP) injection of cyclophosphamide ([CYP] 120 mg/kg), 5-fluorouracil ([5-FU], 50 mg/kg), cisplatinum ([CDDP], 5 mg/kg), or methotrexate ([MTX], 30 mg/kg). N balance was studied for 6 days following chemotherapy in healthy rats (n = 40) and in rats bearing Morris Hepatoma 7777 ([MH7777] n = 40) in a situation comparable to that of human cancer (tumor burden < 0.2% of body weight, moderate anorexia, and weight loss). In healthy rats, all drugs induced transient body weight loss, anorexia, and poor N balance. At day 6 posttreatment, all animals had resumed normal feed intake and positive N balance except CDDP-treated rats, which showed continued weight loss and poor N balance. CDDP and MTX exhibited antitumor activity; however, CDDP induced diarrhea in six of eight tumor-bearing rats. Drug-induced anorexia was more severe in tumor-bearing than in healthy treated rats. N balance was more severely decreased in MH7777-bearing rats than in healthy treated animals in response to 5-FU (159 +/- 36 v 273 +/- 27 mg N/2 d) and MTX (-66 +/- 36 v 153 +/- 37 mg N/2 d) at days 3 to 4 postinjection. These results establish the presence of drug-specific effects on host N balance and the existence of a drug-tumor interaction for N metabolism in the tumor-bearing host.

Simultaneous analysis of tyrosinase mRNA and markers of tyrosinase activity in the blood of patients with metastatic melanoma.

Determination of blood tyrosinase mRNA by RT-PCR and markers of tyrosinase activity (L-DOPA/L-tyrosine ratio) by HPLC have been proposed as biological tools for the detection of metastases in melanoma patients. We prospectively evaluated their significance and clinical value in a group of 30 stage III (n = 10) and IV (n = 20) melanoma patients and one with melanosis of Dubreuilh. L-DOPA/L-tyrosine ratio was elevated in 30% of stage III, 41% of stage IV patients (range: 7.5-261.0 x 10(5)) and in melanosis of Dubreuilh (184.8) (reference values: 6-16 X 10(5)). One stage III and four stage IV melanoma patients were positive for tyrosinase mRNA. In stage IV patients, tyrosinase mRNA positivity was associated with disease progression (P<0.01). The presence of tyrosinase mRNA in blood is more related to clinical status than level of melanin precursors, which probably reflects tumor burden.

Evaluation of standard tyrosinase RT-PCR in melanoma patients by the use of the LightCycler system.

BACKGROUND: Haematogenous spread influences outcome in melanoma patients. The clinical relevance of detecting circulating melanoma cells in peripheral blood by tyrosinase mRNA RT-PCR is, however, questioned as rates of positivity considerably vary between studies. Standard tyrosinase-nested RT-PCR was here compared with a real-time PCR technique. METHODS: Forty-three blood samples from 20 stage III--IV melanoma patients were analyzed. Mononuclear cells were isolated using a Ficoll Hypaque gradient technique. Total RNA extracted by the acid guanidinum thiocyanate-phenol-chloroform method was reverse transcribed using random hexamers or specific primers. Standard tyrosinase-nested PCR was performed on Touchdown machine (Hybaid) and real-time PCR on a LightCycler instrument (Roche). RESULTS: Only two samples from stage IV patients (one from random hexamers, one from antisense primers) were found tyrosinase positive with a 100% agreement between the two PCR techniques. A 10-fold dilution of the first-round products improved the PCR kinetic and the final amount of amplified product of positive samples, but not the rate of positivity. CONCLUSIONS: Efficiency of the PCR reaction can be monitored in an online fashion by the LightCycler instrument allowing technical improvements. However, tyrosinase mRNA RT-PCR cannot be yet considered as a useful technique in the monitoring of melanoma patients.

Tumor and host tissue responses to branched-chain amino acid supplementation of patients with cancer M A McNurlan, S D Heys, K G M Park et al Clinical Science 1994; 86: 339-345.

The metabolic effects of intravenous nutrition (IVN) with branched chain amino acid (BCAA) enriched solutions on skeletal muscle and tumor were investigated in patients with colorectal cancer. Patients (n = 26) undergoing surgical removal of clinically localized tumors were allocated to 3 treatment groups: fasted, conventional IVN or BCAA supplemented (30% of nitrogen as BCAA). Nutritional treatments started 20 h before surgery and protein synthesis was assessed in vivo using a flooding dose technique with L-[1-13C]leucine. The plasma level of most amino acids was higher in the fed groups than in the fasted group; the level of BCAA was increased in the BCAA fed group. Conventional IVN stimulated protein synthesis in tumor (+94%) and in skeletal muscle (+48%) compared to the fasted group; this effect was less pronounced in the BCAA group (+49% and +19% respectively). Anti-proliferative cell nuclear antigen (PCNA) expression in the tumors was increased in both fed groups compared to the fasted state, and correlated with the rate of protein synthesis. It is concluded that the rate of tumor growth can be influenced by the composition of nutrient infused. However, BCAA seems to provide no clear advantage over a conventional IVN, since lower stimulation of tumor protein synthesis was associated with a lower stimulation of muscle protein synthesis.

Fish oil enhances macrophage tumour necrosis factor-alpha mRNA expression at the transcriptional level.

The impact of fish oil on tumour necrosis-alpha (TNF-alpha) production by macrophages stimulated by lipopolysaccharide (LPS) was examined in mice. Animals were fed high fat diets (20% fat wt/wt) rich in fish oil, corn oil or coconut oil for 4 weeks; a group of mice fed a low fat diet (5%) was included. Peritoneal macrophages were incubated with or without LPS for 24 h and the level of TNF-alpha measured in the culture medium. TNF-alpha mRNA was measured every 30 min for 2 h after addition of LPS by dot blot hybridization. Post-transcriptional studies were performed using actinomycin D and/or cycloheximide in the fish oil and corn oil groups. Production of TNF-a by macrophages was increased by more than 10-fold in the fish oil group compared to other groups; no difference was seen between low fat, corn oil and coconut oil groups. Compared to the low fat diet, higher levels of TNF-alpha mRNA were detected in the fish oil group (2.3-fold), and to a lesser extent in the coconut oil and corn oil groups (1.5- 1.2 fold, respectively). TNF-alpha mRNA accumulation in the fish oil group was not due to increased stability of mRNA and protein synthesis was not involved in this phenomenon. The authors discussed the mechanisms by which fish oil could increase TNF-alpha production by LPS stimulated macrophages.

Involvement of human interleukin 6 in experimental cachexia induced by a human uterine cervical carcinoma xenograft.

In this experimental study, the authors examined the role of various cytokines in the development of cancer cachexia. After in vitro culture and selection of a single clone of tumor cells, a growing uterine cervical carcinoma from human origin was implanted subcutaneously in nude mice. Body weight and tumor volume were measured throughout the study period; tissue wasting was assessed by weighing the gastrocnemius muscle and the peri-ovarian white adipose tissue. Serum and tumor cytokine concentrations, including human G-CSF, murine and human tumor necrosis factor (TNF)- proportional, variant, IFN-gamma, interleukin (IL)-1 proportional, variant and IL-6, were determined by ELISA at the end of the study. Two months after implantation, the tumor (4% of carcass weight) induced severe loss of adipose tissue (-95%) and muscle mass (-49%). Human IL-6 (0.38 +/- 0.19 ng/ml) and human G-CSF were detected in the serum and the tumor tissue of these animals; none of the cytokines of murine origin was detected in the serum, except IL-6 (0.14 +/- 0.05 ng/ml). Treatment with neutralizing anti-human IL-6 antibodies reduced plasma IL-6 and G-CSF levels and significantly increased host carcass weight (16%) and fat mass (353%). The authors conclude that human IL-6 produced by tumor cells is an essential mediator of cachexia in this model.

Effect of glutamine supplementation on protein metabolism and glutathione in tumor-bearing rats.

The effect of glutamine (GLN)-supplemented total parenteral nutrition (TPN) on tumor growth and protein metabolism was investigated in tumor-bearing rats. Six days after implantation of AH109A hepatoma, rats received isonitrogenous TPN without or with alanyl-glutamine (25% of total N) for a period of 6 days. Protein turnover was assessed by continuous infusion of l4C-leucine and levels of GLN and glutathione were determined in muscle, jejunum and liver. Diet had no effect on tumor parameters: weight (mean = 4.4 g), GLN and glutathione concentrations, protein synthesis rate and bromodeoxyuridine-labeling index. Body weight loss was less pronounced in the GLN group (-5.5 +/- 1.2 vs. -9.4 +/- 1.4 g/5d). Decrease in plasma and muscle GLN concentrations (-30% and -17% vs. healthy controls, respectively) was limited in tumor-bearing rats receiving GLN-enriched TPN (-15% and +3%). GLN-supplemented TPN increased muscle and jejunum fractional synthesis rates (36% and 25% vs. standard TPN, respectively) and reduced body protein breakdown in tumor-bearing animals (303 +/- 33 vs. 421 +/- 66 mumol Leu/Kg/h). Decrease in jejunum glutathione levels was partially abolished in the GLN group: -50% vs. -64% in the standard TPN group; no effect was noticed in other tissues. The authors conclude that GLN-supplemented TPN improves protein metabolism at both the whole body and the tissue level, and prevents GLN and glutathione deficiencies associated with tumor implantation.

Effects of administration of oral branched-chain amino acids on anorexia and caloric intake in cancer patients.

In this double-blind prospective study, the authors examined the effect of an oral supplement consisting of a branched-chain amino acid (BCAA) mixture or an isonitrogenous placebo on food intake in anorexic cancer patients (n = 28). For all patients, biochemical indices of nutritional status were within the normal range before and after the study. BCAA supplement (3 times 4.8 g/d for 7 consecutive days) increased BCAA concentrations in plasma (+121% on day 7 vs day 0) and decreased the tryptophan/large neutral amino acids (LNAA) ratio by 40%. Meanwhile, incidence of anorexia decreased in the BCAA-treated group (100% prior vs. 45% at the end of the study) but not in the placebo group (84% at the end of the study). The authors conclude that oral BCAA supplement can be safely used in the treatment of cancer-induced anorexia.

Melanoma progression and serum L-dopa/L-tyrosine ratio: a comparison with S100B.

The challenge to find a reliable tumour marker for the management of melanoma patients still remains. In this study, the serum L-dopa/L-tyrosine ratio was compared with serum S100B as a reference marker. A total of 89 melanoma patients were sampled and staged according to the American Joint Committee on Cancer (AJCC) classification. Of these, 19 stage III and 28 stage IV patients were evaluated for disease progression at 1.5 years and 6 months post-sampling, respectively. Serum L-dopa and L-tyrosine were measured by high performance liquid chromatography (HPLC) (normal value for ratio < 16 x 10(-5)) and S100B using the LIA-mat Sangtec 100 assay (normal value < 0.10 microg/l). Non-parametric tests (Kruskal-Wallis analysis of variance, Dunn's and Spearman) were used for the statistical analysis. The median serum L-dopa/L-tyrosine ratio was 16.0 x 10(-5) (range 2.7-545.1 x 10-5 and the median S100B level was 0.15 microg/l (range < 0.10-13.8 microg/l), with a sensitivity of 51% for the ratio and 66% for S100B. There was a 47% discordance and no correlation between the two markers (r = 0.149). The ratio was higher in stage IV than in other stages (P < 0.05), as was the S100B level (P < 0.0001). Both markers were higher in patients with evolutive disease (n = 23) than in stable patients (n = 24), with values of 20.8 x 10(-5) versus 13.1 x 10(-5) for the ratio (P < 0.05) and 0.89 microg/l versus 0.16 microg/l for S100B (P < 0.001); for the ratio, this difference was more pronounced in stage III than in stage IV patients. The overall sensitivity and specificity of the markers to predict disease progression were 78% and 67%, respectively, for the ratio, and 74% and 83%, respectively, for S100B (using an ROC cut-off of 0.38 microg/l). In conclusion, the serum L-dopa/L-tyrosine ratio correlates with melanoma progression and has predictive value, especially in stage III patients. This tumour marker, like S100B, could serve as an additional tool in the management of melanoma.

Development of metastases in malignant melanoma is associated with an increase in the plasma L-dopa/L-tyrosine ratio.

In this prospective study we evaluated a new biochemical approach in which the plasma ratio of the melanin precursors L-dopa and L-tyrosine serves as a marker of metastatic dissemination in malignant melanoma. Control values (11.20 x 10(-5) +/- 2.92 x 10(-5)) were determined. The L-dopa/L-tyrosine ratio was evaluated in the plasma of 90 patients with malignant melanoma (stage I/II, n = 33; stage III, n = 33; stage IV, n = 24) classified according to the tumour/node/metastasis (pTNM) classification. A total of 106 samples were studied. Serial measurements were performed in eight stage III-IV patients. The L-dopa/L-tyrosine ratio was significantly elevated in melanoma patients with clinical stage III (15.23 x 10(-5) +/- 3.34 x 10(-5)) compared with stage I (10.88 x 10(-5) +/- 2.52 x 10(-5)). Stage IV patients showed a significant increase in the plasma L-dopa/L-tyrosine ratio (45.73 x 10(-5) +/- 61.75 x 10(-5)) compared with the other groups. The ratio was higher for those with two rather than one metastatic site and markedly higher for those with widespread metastases. The development of metastases was associated with an increase in plasma L-dopa, a decrease in plasma L-tyrosine and a significant increase in the plasma L-dopa/L-tyrosine ratio. These data suggest that the plasma L-dopa/L-tyrosine ratio reflects the tumour burden and correlates with the progression of malignant melanoma.

Biochemical assessment of nutritional status in patients with chronic obstructive pulmonary disease and acute respiratory failure on admission to an intensive care unit.

Although chronic obstructive pulmonary disease (COPD) is associated with weight loss and malnutrition, there is a paucity of relevant data on COPD patients with acute respiratory failure (ARF). We studied 30 consecutive patients on the day of admission to our intensive care unit for ARF. In addition to a clinical work-up, the following biochemical parameters were determined: markers of nutritional status (albumin - ALB, transferrin - TRF, transthyretin - TTR, retinol binding protein - RBP, fibronectin), inflammation (C-reactive protein - CRP, alpha(1) glycoprotein acid - alpha(1)GPA) and catabolism (plasma phenylalanine - PHE, urinary 3-methylhistidine - 3-MH). Values were expressed as mean +/- SD and compared to those of 10 healthy subjects matched for age. COPD-ARF patients had a poor protein status (ALB = 30 +/- 5 vs 42 +/- 3 g.l(-1); TTR = 118 +/- 75 vs 251 +/- 43 mg.l(-1); RBP = 23 +/- 12 vs 46 +/- 8 mg.l(-1); p < 0.001), were hypercatabolic (3-MH Cr = 31 +/- 12 vs 22 +/- 7 mumol.mmol Cr (-1); PHE = 62 +/- 27 vs 46 +/- 10 mumol.l(-1); p < 0.001) and inflamed (CRP = 68 +/- 50 vs 12 +/- 5 mg.l(-1); alpha(1)GPA = 1.2 +/- 0.4 vs 0.5 +/- 0.1 g.l(-1); p < 0.001). Severity of the disease correlated with short half-life proteins and protein catabolism markers but not with inflammation markers. Considering ALB, TTR, RBP, the 3- MH Cr ratio and PHE values, the 30 COPD patients fell into 3 groups: chronic malnutrition (n = 7), acute malnutrition (n = 2), and acute + chronic malnutrition (n = 18). 3 patients had normal nutritional status. We conclude that an assessment of nutritional status at admission to intensive care units could contribute towards a rapid formulation of specific nutritional therapy.

[Laboratory identification and measurement of urinary proteins]. / Identification et dosage des protéines urinaires au laboratoire d'analyses.

A permanent and quantitatively abnormal proteinuria (> 150 mg/ 24 h) found at the laboratory should be followed by an identification and quantification of all proteins present. Specific immunochemistry techniques (immunoturbidimetric or immuno-nephelometric) are almost exclusively used for measuring albumin (or microalbuminuria) in nephropathic diabetic patients. Measurement of monoclonal free light chains is not recommended due to poor accuracy. Determination of other small proteins (molecular mass, MM < 40 kDa), transferrine, immunoglobulins G (assessment of selectivity) is far less frequent and Tamm-Horsfall protein is measured in specialized laboratories. Global electrophoresis techniques are the reference methods for the study of urinary proteins. Significant progress have been made during the past ten years in terms of sensitivity (analysis down to 50 mg/L total protein with no need to concentrate urinary specimens) and separation (high resolution or according to MM). Improvement in sensitivity is a key point for the diagnostic and follow-up of low grade or treated gammapathies. Electrophoretic separation according to MM is perfectly adapted to visual typing of renal proteinuria (glomerular, tubular or mixed) and overload proteinuria, particularly by monoclonal free light chains (MM: 25 kDa, Bence Jones proteinuria) allowing their quantification by densitometry. Immunofixation combining electrophoresis and immunoprecipitation in gel has emerged as the reference technique to identify monoclonal proteins. Data obtained by urinary protein analysis need to be compared with serum results for interpretation.

[Biological analysis of proteinuria in the laboratory: quantitative features]. / Exploration biologique de la protèinurie au laboratoire d'analyses: aspects quantitatifs.

Total protein analysis is one of the most frequent laboratory analyses in urine. A proteinuria above 150 mg/L is often observed in a random way in preventive or school medicine (dipsticks) or during laboratory analysis (quantitative determination). Complete (quantitative, then qualitative) and repeated evaluation of proteinuria is of major interest for the clinician to establish a diagnosis of abnormality and for therapeutic follow-up of a nephropathy, uropathy or a non-renal disease (diabetes, multiple myeloma). Most frequent (90% of cases) and severe forms of proteinuria are of glomerular type, associated to the nephrotic syndrome, hypertension, and progressive renal failure. Attention should be paid by the biologist to the pre-analytical phase (specimen collection, treatment, and storage), to clinical data, and to prescription of drugs that could interfere with protein analysis. During the last past 10 years, significant analytical advances have been made: dipstick analysis has been dropped (false positives and most importantly false negatives) as manual precipitation techniques with turbidimetric detection (poor inter-laboratory coefficients of variation, CV), replacement of Coomassie blue by pyrogallol red (improved practicability). Urinary quality control data reflect these positive changes, as demonstrated by a dramatic reduction in reported CVs. There is, however, still no reference method for total urinary protein determination and limits of existing pyrogallol red methods should be emphasized: variable reagent composition between manufacturers (such as the presence of SDS additive), limited sensitivity, difficulty in the choice of a calibration material, underestimation of free light chains, and interference with gelatin based vascular replacement fluids.

[Current biological markers of cutaneous melanoma progression]. / Marqueurs biologiques actuels de progression du mélanome cutané.

Melanoma is the most agressive skin cancer in humans. The most important prognostic factors are the histological features of the tumor, while the clinical ones play a secondary role. Melanoma progression is characterized by the metastatic process which directly threatens the patients life. Unfortunately, routine imaging methods cannot estimate early enough this metastatic risk. Are biologic markers of cancer progression more efficient than those applied in everyday practice? Are they able to evaluate the metastatic risk and thus help the therapeutic strategy? In this review, we analysed the analytical and the clinical aspects of biologic markers of cutaneous melanoma currently available or in development. At the present time it is very difficult to distinguish one single marker of melanoma progression in the blood which correlates with the stage and the prognosis of melanoma. The most specific and sensitive enough are the melanoma associated antigens protein S-100, MIA (melanoma inhibiting activity) and the melanin precursors 5-S-cysteinyldopa and the ratio L-dopa/L-tyrosine. Tyrosinase mRNA remains the best target for the detection of circulating metastatic melanoma cells by RT-PCR. Simultaneous detection of several markers might be useful if they are carefully selected. Despite the progress in the field, more clinical studies should be performed for the development of new techniques or improvements of the existing ones for the follow-up of cutaneous melanoma.