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1.
J Am Soc Cytopathol ; 9(1): 9-19, 2020.
Article in English | MEDLINE | ID: mdl-31551159

ABSTRACT

The color of urine, once considered by uroscopists to give the most important clues to the diagnosis, still can provide some diagnostic clues in modern medicine. Pigmented cells are an uncommon and surprising find in urine cytology and can at the same time provide important diagnostic clues or represent a dangerous pitfall. We present a review of the significance of pigmented cells in urine cytology. The presence of intracellular pigment granules; their color, size, shape, and variation in size and shape; as well as their staining reactions with special stains can provide useful diagnostic insight, especially when interpreted in the cytologic context (type of pigmented cell and its degree of atypicality) and patient's clinical context. The main differential diagnosis of cytoplasmic pigmented granules includes hemosiderin, lipofuscin, and melanin, each having a different pathogenesis and significance. The goal of this paper is to describe the morphological, histochemical, and ultrastructural characteristics of the pigments seen in urinary cytology, and to review the benign and malignant conditions associated with them.


Subject(s)
Cytodiagnosis/methods , Cytoplasm/chemistry , Lipofuscin/urine , Pigments, Biological/urine , Urine/cytology , Adult , Aged , Aged, 80 and over , Color , Diagnosis, Differential , Female , Hemosiderin/urine , Humans , Male , Melanins/urine , Melanoma/diagnosis , Melanoma/urine , Melanosis/diagnosis , Melanosis/urine , Middle Aged , Pigmentation , Skin Neoplasms/diagnosis , Skin Neoplasms/urine
3.
Plast Reconstr Surg ; 139(6): 1277e-1284e, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28538565

ABSTRACT

BACKGROUND: Hemangiomas are unique endothelial cell tumors that involute spontaneously, which makes interpreting their response to therapies difficult. The objective of this work was to identify a potential biomarker in the urine of children with infantile hemangiomas that would facilitate testing new therapies. METHODS: A prospective longitudinal study in children with hemangiomas and age-matched healthy controls was performed to determine whether microRNA-126, which is highly abundant in fetal endothelial cells, was more abundant in the urine of affected children. Prospective ultrasound measurements of hemangioma size and blood flow velocity were obtained as secondary endpoints to document longitudinal changes in untreated hemangiomas. RESULTS: Urinary microRNA-126 levels were significantly elevated in children with proliferating hemangiomas, and relative levels of urinary microRNA abundance correlated with hemangioma size. Hemangiomas had elevated levels of microRNA abundance compared with healthy controls. Ultrasound data revealed that hemangioma proliferation typically stopped between 6 and 9 months of age. When hemangioma proliferation stopped, urinary microRNA-126 levels in children with hemangiomas dropped to levels observed in healthy age-matched controls. CONCLUSIONS: These are the first reported results to identify a potential microRNA biomarker in the urine of children with hemangiomas. Measurement of urinary levels of microRNA-126 could potentially be used to monitor hemangioma response to therapies. CLINICAL QUESTION/LEVEL OF EVIDENCE: Diagnostic, II.


Subject(s)
Biomarkers, Tumor/urine , Hemangioma, Capillary/urine , MicroRNAs/urine , Skin Neoplasms/urine , Age Factors , Case-Control Studies , Child , Child, Preschool , Disease Progression , Female , Hemangioma, Capillary/diagnostic imaging , Humans , Infant , Longitudinal Studies , Male , Prospective Studies , Reference Values , Sensitivity and Specificity , Sex Factors , Skin Neoplasms/diagnostic imaging , Ultrasonography, Doppler/methods
4.
Br J Dermatol ; 175(6): 1320-1328, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27411377

ABSTRACT

BACKGROUND: The concurrent impact of repeated low-level summer sunlight exposures on vitamin D production and cutaneous DNA damage, potentially leading to mutagenesis and skin cancer, is unknown. OBJECTIVES: This is an experimental study (i) to determine the dual impact of repeated low-level sunlight exposures on vitamin D status and DNA damage/repair (via both skin and urinary biomarkers) in light-skinned adults; and (ii) to compare outcomes following the same exposures in brown-skinned adults. METHODS: Ten white (phototype II) and six South Asian volunteers (phototype V), aged 23-59 years, received 6 weeks' simulated summer sunlight exposures (95% ultraviolet A/5% ultraviolet B, 1·3 standard erythemal doses three times weekly) wearing summer clothing exposing ~35% body surface area. Assessments made were circulating 25-hydroxyvitamin D [25(OH)D], immunohistochemistry for cyclobutane pyrimidine dimer (CPD)-positive nuclei and urinary biomarkers of direct and oxidative (8-oxo-deoxyguanosine) DNA damage. RESULTS: Serum 25(OH)D rose from mean 36·5 ± 13·0 to 54·3 ± 10·5 nmol L-1 (14·6 ± 5·2 to 21·7 ± 4·2 ng mL-1 ) in phototype II vs. 17·2 ± 6·3 to 25·5 ± 9·5 nmol L-1 (6·9 ± 2·5 to 10·2 ± 3·8 ng mL-1 ) in phototype V (P < 0·05). Phototype II skin showed CPD-positive nuclei immediately postcourse, mean 44% (range 27-84) cleared after 24 h, contrasting with minimal DNA damage and full clearance in phototype V (P < 0·001). The findings did not differ from those following single ultraviolet radiation (UVR) exposure. Urinary CPDs remained below the detection threshold in both groups; 8-oxo-deoxyguanosine was higher in phototype II than V (P = 0·002), but was unaffected by UVR. CONCLUSIONS: Low-dose summer sunlight exposures confer vitamin D sufficiency in light-skinned people concurrently with low-level, nonaccumulating DNA damage. The same exposures produce minimal DNA damage but less vitamin D in brown-skinned people. This informs tailoring of sun-exposure policies.


Subject(s)
DNA Damage/radiation effects , Seasons , Sunlight , Vitamin D/biosynthesis , 8-Hydroxy-2'-Deoxyguanosine , Adolescent , Adult , Asia, Southeastern/ethnology , Biomarkers/blood , Biomarkers/urine , DNA Repair/physiology , DNA Repair/radiation effects , Deoxyguanosine/analogs & derivatives , Deoxyguanosine/urine , Diet , Environmental Exposure , Female , Humans , Male , Middle Aged , Pyrimidine Dimers/urine , Skin/metabolism , Skin Neoplasms/blood , Skin Neoplasms/etiology , Skin Neoplasms/urine , Skin Pigmentation/radiation effects , Vitamin D/administration & dosage , Vitamin D/analogs & derivatives , Vitamin D/metabolism , Vitamin D Deficiency/blood , Vitamin D Deficiency/ethnology , Vitamin D Deficiency/urine , Young Adult
5.
JAMA Otolaryngol Head Neck Surg ; 139(10): 1026-31, 2013 Oct.
Article in English | MEDLINE | ID: mdl-24135743

ABSTRACT

IMPORTANCE: Infantile hemangiomas (IHs) vary substantially in localization and extent of tissue involvement, but IH biological progression is remarkably unique and predictable. Propranolol is an effective treatment for symptomatic IH, but its mechanism of action remains unknown and understudied. OBJECTIVE: To compare excreted proteins in infants with IH being treated with propranolol vs prednisolone. DESIGN, SETTING, AND PARTICIPANTS: Exploratory urine proteomics profiling of patients with IH from July 2010 to September 2012 at a tertiary pediatric hospital. Participants were infants with IH treated at our institution who were participating in a blinded, randomized trial comparing prednisolone vs propranolol. They ranged in age from 14 days to 15 months at enrollment. Exclusion criteria included a history of diabetes mellitus, asthma, and/or cardiovascular disease including hypertension or hypotension. Urine samples were longitudinally collected from all participants. Specimens were desalted, concentrated, and gel fractionated, and the protein content was identified using liquid chromatography tandem mass spectrometry. Western blot analyses and enzyme-linked immunosorbent assays (ELISAs) were performed to validate mass spectrometry findings. INTERVENTION: Treatment with propranolol or prednisolone administered starting before the age of 6 months. MAIN OUTCOMES AND MEASURES: Proteins present in urine samples and change in urinary levels of proteins over time. RESULTS: Samples were obtained from 3 patients treated with prednisolone, 3 patients treated with propranolol, and 5 untreated controls with IH. More than 1000 urinary proteins were identified by proteomics. Patients treated with propranolol demonstrated attenuation of excreted matrix metalloproteinase 9 (MMP-9) in urine over the proliferative phase of the condition compared with prednisolone-treated patients. These findings were validated with Western blot analysis and quantified with ELISA, which confirmed mean urinary MMP-9 levels in the first year of life to be significantly lower in propranolol-treated patients with IH compared with prednisolone-treated patients with IH (0.118 vs 0.501 ng/mL; P = .03) or with nontreated patients with IH (0.118 vs 3.69 ng/mL; P = .02). CONCLUSIONS AND RELEVANCE: Propranolol treatment decreases urinary excretion of MMP-9 in patients with IH. Matrix metalloproteinase 9 may be a biomarker for IH propranolol responsiveness, and its signaling pathways may represent the molecular target of this drug.


Subject(s)
Adrenergic beta-Antagonists/therapeutic use , Hemangioma/urine , Matrix Metalloproteinase 9/urine , Propranolol/therapeutic use , Skin Neoplasms/urine , Age Factors , Antineoplastic Agents, Hormonal/therapeutic use , Cohort Studies , Female , Hemangioma/drug therapy , Humans , Infant , Infant, Newborn , Male , Prednisolone/therapeutic use , Single-Blind Method , Skin Neoplasms/drug therapy
6.
Diagn Cytopathol ; 41(11): 997-9, 2013 Nov.
Article in English | MEDLINE | ID: mdl-22730159

ABSTRACT

Malignant melanoma has an unusual predilection for metastasis to the small bowel, sometimes several years after the original diagnosis. In patients who have had a cystoprostatectomy followed by an ileal conduit, metastatic melanoma to the ileal conduit can present in urine cytology. We present a rare case of metastatic malignant melanoma in neo-bladder urine in a patient who had undergone a cystoprostatectomy for high grade urothelial carcinoma of the bladder and prostatic adenocarcinoma of Gleason grade 3+3 and two excisional procedures for cutaneous malignant melanoma. He presented with persistent hematuria and urinary tract infections unresponsive to treatment. Urine cytology revealed single large atypical cells, with large nuclei, prominent nucleoli, and cytoplasmic melanin pigment. Subsequent surgical resection revealed two areas of metastatic melanoma in the ileum, one of them being in the ileal conduit. The tumor cells were immunoreactive for S-100 protein, Melan-A, and HMB-45 and were negative for CAM5.2 and cytokeratins 7 and 20.


Subject(s)
Ileal Neoplasms/diagnosis , Melanoma/diagnosis , Skin Neoplasms/diagnosis , Aged, 80 and over , Fatal Outcome , Humans , Ileal Neoplasms/secondary , Ileal Neoplasms/urine , Male , Melanoma/secondary , Melanoma/urine , Skin Neoplasms/pathology , Skin Neoplasms/urine
7.
J Cutan Pathol ; 37(4): 486-90, 2010 Apr.
Article in English | MEDLINE | ID: mdl-19469863

ABSTRACT

Two cases of males with subcutaneous masses as the first clinical sign of testicular choriocarcinoma are reported. The urine and serum human chorionic gonadotropin (hCG) test confirmed high level hCG from male choriocarcinoma. These cases, although very rare, can be a great diagnostic and therapeutic challenge and should be considered in the differential diagnosis of subcutaneous masses occurring in young males.


Subject(s)
Choriocarcinoma/secondary , Skin Neoplasms/secondary , Testicular Neoplasms/pathology , Adult , Choriocarcinoma/blood , Choriocarcinoma/urine , Chorionic Gonadotropin/blood , Chorionic Gonadotropin/urine , Diagnosis, Differential , Fatal Outcome , Humans , Male , Skin Neoplasms/blood , Skin Neoplasms/urine , Testicular Neoplasms/blood , Testicular Neoplasms/urine
8.
Toxicol Lett ; 169(2): 162-76, 2007 Mar 08.
Article in English | MEDLINE | ID: mdl-17293063

ABSTRACT

The molecular basis and downstream targets of oral selenium supplementation in individuals with elevated risk of cancer due to chronic exposure from environmental carcinogens has been largely unexplored. In this study, we investigated genome-wide differential gene expression in peripheral blood mononuclear cells (PBMC) from individuals with pre-malignant arsenic (As)-induced skin lesions before and after 6 months daily oral supplementation of 200 microg L-selenomethionine. The Affymetrix GeneChip Human 133A 2.0 array, containing probes for 22,277 gene transcripts, was used to assess gene expression. Three different normalization methods, RMA (robust multi-chip analysis), GC-RMA and PLIER (Probe logarithmic intensity error), were applied to explore differentially expressed genes. We identified a list of 28 biologically meaningful, significantly differentially expressed genes. Genes up-regulated by selenium supplementation included TNF, IL1B, IL8, SOD2, CXCL2 and several other immunological and oxidative stress-related genes. When mapped to a biological association network, many of the differentially expressed genes were found to regulate functional classes such as fibroblast growth factor, collagenase, matrix metalloproteinase and stromelysin-1, and thus, considered to affect cellular processes like apoptosis, proliferation and others. Many of the significantly up-regulated genes following selenium-supplementation were previously found by us to be down-regulated in a different set of individuals with As-induced skin lesions compared to those without. In conclusion, findings from this study may elucidate the biological effect of selenium supplementation in humans. Additionally, this study suggests that long-term selenium supplementation may revert some of the gene expression changes presumably induced by chronic As exposure in individuals with pre-malignant skin lesions.


Subject(s)
Antioxidants/administration & dosage , Arsenic Poisoning/genetics , Gene Expression Regulation, Neoplastic/drug effects , Precancerous Conditions/genetics , Selenomethionine/administration & dosage , Skin Neoplasms/genetics , Water Pollutants, Chemical/poisoning , Arsenic/urine , Arsenic Poisoning/metabolism , Arsenic Poisoning/urine , Bangladesh , Gene Expression Profiling , Humans , Leukocytes, Mononuclear/drug effects , Leukocytes, Mononuclear/physiology , Male , Middle Aged , Oligonucleotide Array Sequence Analysis , Precancerous Conditions/chemically induced , Precancerous Conditions/metabolism , Precancerous Conditions/urine , RNA/chemistry , RNA/genetics , Skin Neoplasms/chemically induced , Skin Neoplasms/metabolism , Skin Neoplasms/urine
9.
J Clin Pharmacol ; 46(7): 727-37, 2006 Jul.
Article in English | MEDLINE | ID: mdl-16809798

ABSTRACT

Vincristine sulfate liposomes injection (VSLI) is a liposomal formulation of vincristine encapsulated in sphingosomes composed of sphinogomyelin and cholesterol (58/42; mol/mol). The pharmacokinetics and urinary excretion of VSLI were evaluated in 12 patients with metastatic melanoma after single-dose (2.0 mg/m2 every 2 weeks = 1 cycle) and multiple-dose (cycle 3, pharmacokinetics only) administrations (intravenous infusion over 1 hour). After VSLI infusion, total (released and encapsulated) vincristine concentrations in plasma remained relatively constant for 3 to 12 hours and thereafter declined, with interpatient variability seen in the rate of decline resulting in monoexponential or biexponential profiles. The area under the plasma concentration-time curve from time zero to infinity of total vincristine in plasma ranged from 4933 to 40495 h.ng/mL and total clearance ranged from 131 to 445 mL/h. The volume of distribution at steady state was 2650 +/- 731 mL, indicating VSLI was mainly confined within the plasma. The released vincristine concentrations in plasma were below the level of quantitation in 95% of samples. The pharmacokinetic parameters were similar between cycles 1 and 3, and trough plasma levels of total vincristine were below the level of quantitation of 1 ng/mL. Approximately 8% of the injected dose was excreted in the urine as unchanged vincristine (7%) or N-desformylvincristine (0.8%). Overall, VSLI exhibited a longer circulation half-life and higher area under the plasma concentration-time curve compared to conventional vincristine, whereas its route of elimination remained unchanged.


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacokinetics , Melanoma/urine , Vincristine/pharmacokinetics , Adult , Aged , Antineoplastic Agents, Phytogenic/administration & dosage , Antineoplastic Agents, Phytogenic/blood , Antineoplastic Agents, Phytogenic/urine , Delayed-Action Preparations , Drug Administration Schedule , Female , Humans , Infusions, Intravenous , Liposomes , Male , Melanoma/blood , Melanoma/drug therapy , Melanoma/pathology , Middle Aged , Skin Neoplasms/urine , Vincristine/administration & dosage , Vincristine/blood , Vincristine/urine
10.
Pigment Cell Res ; 19(2): 163-9, 2006 Apr.
Article in English | MEDLINE | ID: mdl-16524432

ABSTRACT

Normal and malignant melanocytes produce melanins and melanin-related metabolites, most of which are retained in the cells but some are secreted into the blood and then excreted in the urine. In this study, we developed a method to measure levels of eumelanin in urine samples and evaluated its clinical significance in comparison with the melanin-related metabolites 6-hydroxy-5-methoxyindole-2-carboxylic acid (6H5MI2C) and 5-S-cysteinyldopa (5-S-CD), and with pheomelanin, measured after degradation as 4-amino-3-hydroxyphenylalanine (4-AHP). The method is based on the production of pyrrole-2,3,5-tricarboxylic acid (PTCA) on permanganate oxidation of eumelanin, followed by quantification by liquid chromatography. For 118 urine samples from 10 control subjects, mean urinary excretions of PTCA, 6H5MI2C, 5-S-CD and 4-AHP were 19, 67, 37 and 59 micromol/mol creatinine respectively. In melanoma patients (n = 45), the mean urinary excretions of PTCA, 6H5MI2C, 5-S-CD, and 4-AHP were 91, 926, 4070 and 3530 micromol/mol creatinine respectively. Median level of PTCA in melanoma patients was elevated 2.1-fold compared with control subjects. The degrees of elevation for 6H5MI2C, 5-S-CD, and 4-AHP were 1.8-, 22- and 6.2-fold respectively. Thus, although urinary PTCA is of little clinical value in following the progression of melanoma, urinary 4-AHP appears to be of considerable value in this respect.


Subject(s)
Melanins/urine , Melanoma/urine , Skin Neoplasms/urine , Adult , Chromatography, High Pressure Liquid , Female , Humans , Male , Melanoma/pathology , Middle Aged , Predictive Value of Tests , Skin Neoplasms/pathology
11.
Cell Immunol ; 230(2): 109-18, 2004 Aug.
Article in English | MEDLINE | ID: mdl-15598426

ABSTRACT

The role of nitric oxide (NO) in graft-versus-tumor-effect (GVT) was evaluated in the present study. GVT was induced by intravenous injection of C57BL/6J (H-2b) mouse splenocytes to {C57BL/6J (H-2b) x BALB/c (H-2d)} F1 mice bearing Meth A (H-2d) ascites tumors. Induction of GVT increased nitrite production and expression of inducible NO synthase by ascites cells. The increased nitrite production was inhibited by NG-monomethyl-L-arginine (MLA). Experiments employing immunomagnetic depletion of Mac-1+ cells from ascites indicated that macrophages were a major cellular source of the nitrite production. Interferon-gamma levels were increased in both serum and ascites fluid during GVT. Induction of GVT prolonged survival of ascites-bearing mice, and increased urinary nitrate excretion. MLA administration inhibited GVT-induced increase in urinary nitrate excretion, and further prolonged GVT-induced increase in survival. These results indicate that NO synthesis is induced in tumors during GVT, and the NO acts as an inhibitor of GVT.


Subject(s)
Graft vs Tumor Effect/immunology , Nitric Oxide/immunology , Skin Neoplasms/immunology , Animals , Ascites/immunology , Blotting, Western , Crosses, Genetic , Enzyme Inhibitors/pharmacology , Female , Interferon-gamma/immunology , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Nitric Oxide Synthase/antagonists & inhibitors , Nitric Oxide Synthase/genetics , Nitric Oxide Synthase/immunology , Nitric Oxide Synthase Type II , Nitrites/urine , RNA/chemistry , RNA/genetics , Reverse Transcriptase Polymerase Chain Reaction , Skin Neoplasms/metabolism , Skin Neoplasms/urine , omega-N-Methylarginine/pharmacology
12.
Melanoma Res ; 12(6): 627-31, 2002 Dec.
Article in English | MEDLINE | ID: mdl-12459653

ABSTRACT

Epidermal-type fatty acid-binding protein (E-FABP), a protein related to the intracellular trafficking of fatty acids, is expressed in melanocytic tumours but not in normal human melanocytes. E-FABP interacts with S100A7. The presence of these two proteins was investigated in the urine of patients with cutaneous melanoma or other types of cancer, and healthy controls. The first voided morning urine samples of 31 patients with melanoma, 73 patients with other types of cancer and 17 healthy controls were concentrated and submitted to sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) immunoblotting for protein detection. In the healthy controls, the incidences of urinary detection of these proteins were higher in females than in males, being 50% (five out of 10) versus 0% (zero out of seven) for E-FABP ( < 0.05), and 70% (seven out of 10) versus 0% (zero out of seven) for S100A7 ( < 0.05). Both proteins were detected in the urine of patients with melanoma. The incidence of S100A7 was higher in the urine of patients with melanoma (77%, 24 out of 31) compared with healthy controls (41%, seven out of 17) and patients with other types of cancer (53%, 39 out of 73) ( < 0.03). In contrast, the incidence of E-FABP was the same among the melanoma group (39%, 12 out of 31), healthy controls (29%, five out of 17) and patients with other types of cancer (23%, 17 out of 73). Surprisingly, E-FABP was always detected in the urine of females with stage I/II or III melanoma, but was no longer detectable in the urine of patients with stage IV melanoma. Urinary S100A7 may have some specificity to the host response to melanoma since its incidence was not increased in other cancers. The lack of E-FABP detection in the urine of patients with distant metastases suggests an inverse relationship between E-FABP release and the spread of melanoma.


Subject(s)
Biomarkers, Tumor/urine , Calcium-Binding Proteins/urine , Carrier Proteins/urine , Melanoma/urine , Neoplasm Proteins , Skin Neoplasms/urine , Tumor Suppressor Proteins , Adult , Aged , Fatty Acid-Binding Protein 7 , Fatty Acid-Binding Proteins , Female , Humans , Male , Middle Aged , Reference Values , S100 Calcium Binding Protein A7 , S100 Proteins , Sex Factors
13.
Br J Haematol ; 113(2): 422-4, 2001 May.
Article in English | MEDLINE | ID: mdl-11380408

ABSTRACT

Thalidomide is active in patients with refractory myeloma. Seventeen patients (nine men/eight women, median age 73 years) with multiple myeloma (MM) were treated with thalidomide. Fifteen patients had refractory disease and two untested relapse. The median dose of thalidomide was 500 mg (range, 200-800 mg). Nine of the 17 patients (53%) responded. The response rate was significantly higher in patients with no extramedullary disease than in those with soft tissue masses (75% CI: 43-95% versus 0%; P = 0.01)). Of note, no decrease in the size of soft tissue plasmacytomas was observed in all the five patients who had extramedullary involvement. This data suggests that the mechanism of action and effectiveness of thalidomide might depend on the site of the tumour cells.


Subject(s)
Immunosuppressive Agents/therapeutic use , Multiple Myeloma/drug therapy , Muscle Proteins , Plasmacytoma/drug therapy , Skin Neoplasms/drug therapy , Thalidomide/therapeutic use , Aged , Bone Marrow Cells/pathology , Connectin , Drug Administration Schedule , Female , Humans , Male , Multiple Myeloma/pathology , Multiple Myeloma/urine , Myeloma Proteins/urine , Plasma Cells/pathology , Plasmacytoma/pathology , Plasmacytoma/urine , Skin Neoplasms/pathology , Skin Neoplasms/urine , Treatment Failure
14.
Melanoma Res ; 10(4): 363-9, 2000 Aug.
Article in English | MEDLINE | ID: mdl-10985671

ABSTRACT

In a series of 92 patients with malignant melanoma, clinical stage III or IV, both 5-S-cysteinyldopa (5SCD) and 6-hydroxy-5-methoxyindole-2-carboxylic acid (6H5MI2C) were measured in urine during chemotherapy. A total of 434 urine specimens were analysed. The sensitivity of 5SCD for the detection of stage III-IV melanoma was 83%, while the corresponding sensitivity of 6H5MI2C was 52%. Fifty per cent of patients with one metastatic site had increased 5SCD excretion, while all patients with four or more metastatic sites had increased excretion. A significant correlation was found between 5SCD decrease and clinical regression (P<0.001) and between 5SCD increase and clinical progression (P<0.001). Corresponding correlations were not found for 6H5MI2C. Increments in 5SCD excretion (median 269 micromol/mol creatinine) were seen for 83% of the occasions when clinical progression was recorded, and decrements in 5SCD excretion (median 145 micromol/mol creatinine) were seen for 85% of the occasions when clinical regression was seen. During clinical 'stable disease' increases in 5SCD excretion were seen in 59% and decreases in 41%. The median value of 5SCD changes for stable disease was 7.0 micromol/mol creatinine, indicating a chemical marker stability in many cases. We recommend the use of 5SCD in urine as a valuable, reliable and simple biochemical marker to use in the clinical follow-up of melanoma patients with advanced disease.


Subject(s)
Biomarkers, Tumor/urine , Cysteinyldopa/urine , Melanoma/urine , Skin Neoplasms/urine , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Disease Progression , Female , Follow-Up Studies , Humans , Indoles/urine , Male , Melanoma/drug therapy , Melanoma/secondary , Middle Aged , Skin Neoplasms/drug therapy , Skin Neoplasms/pathology
15.
J Chromatogr B Biomed Sci Appl ; 727(1-2): 31-42, 1999 Apr 30.
Article in English | MEDLINE | ID: mdl-10360420

ABSTRACT

5-S-Cysteinyldopa (5-SCD) in plasma and urine was determined by means of a newly developed method. This method incorporates optimized conditions for blood collection and storage, as well as a new extraction and separation technique, required for the strong oxidation and light sensitive 5-SCD. The new aspects of the method are the following: immediate centrifugation and freezing of the samples after blood collection, fully automatical solid-phase extraction (SPE) with phenylboronic acid (PBA) cartridges and immediate HPLC injection of the eluate, nearly complete exclusion of light and air-oxygen during extraction, constant sample cooling, use of the more suitable internal standard 5-S-D-cysteinyldopa and easy, sensitive and selective HPLC conditions (RP18-column with isocratic separation and electrochemical detection). The method has a linear range from 0.25 to 50 microg l(-1) and 25 to 5000 microg l(-1) for plasma and urine samples, respectively, a limit of detection of 0.17 microg l(-1), intra-assay variabilities from 1.7 to 3.6%, inter-assay variabilities from 4.0 to 18.3% and an average relative recovery of 103.5% for plasma and 105.4% for urine samples. In our study the measured 5-SCD concentrations of patients with melanomas at various stages correlated better with their clinical pictures than described in literature up to date. The results were obtained in comparison to patients with other skin tumors and in comparison to healthy control persons.


Subject(s)
Biomarkers, Tumor/metabolism , Chromatography, High Pressure Liquid/methods , Cysteinyldopa/metabolism , Melanoma/physiopathology , Skin Neoplasms/metabolism , Automation , Biomarkers, Tumor/blood , Biomarkers, Tumor/urine , Calibration , Case-Control Studies , Cysteinyldopa/blood , Cysteinyldopa/urine , Humans , Melanoma/blood , Melanoma/urine , Prognosis , Reference Standards , Reproducibility of Results , Sensitivity and Specificity , Skin Neoplasms/blood , Skin Neoplasms/urine
17.
Ann Dermatol Venereol ; 125(5): 313-6, 1998 May.
Article in French | MEDLINE | ID: mdl-9747277

ABSTRACT

OBJECTIVES: Hemangiomas of infancy follow a characteristic three-phases course: proliferation, involution, regressed Proliferative endothelial cells predominate during the proliferative phase. Moreover it has been shown that patients with active angiogenesis have elevated levels of urinary bFGF (basic Fibroblast Growth Factor). PATIENTS AND METHODS: Here we report our preliminary results of urinary bFGF assay (ELISA) for the diagnosis and follow up of severe hemangioma. We also assayed bFGF in normal infants, in patients with large vascular malformations and in infants with Kasabach-Merritt syndrome. RESULTS: In the control group, urinary bFGF was elevated in new borns but nul or very low in infants. Urinary bFGF levels were normal, i.e. very low in 4 patients with a vascular malformation. In infants with a clinically proliferative hemangioma, urinary bFGF was elevated in 8 among the 10 studied. bFGF levels guided treatment in 9 patients. Urinary bFGF was elevated in 4 patients with Kasabach-Merritt syndrome. DISCUSSION: Angiogenesis is regulated by angiogenic and inhibitory factors. The angiogenic factor bFGF is an autocrine growth factor for endothelial cells and hemangioma endothelial cells expressing bFGF in their cytosol during the proliferative phase. As suggested by J. Folkman and his group, assay of urinary bFGF appears useful in differentiating between hemangioma and vascular malformation and for follow up of treated patients.


Subject(s)
Fibroblast Growth Factor 2/urine , Hemangioma/diagnosis , Skin Neoplasms/diagnosis , Adrenal Cortex Hormones/therapeutic use , Arteriovenous Malformations/diagnosis , Arteriovenous Malformations/therapy , Arteriovenous Malformations/urine , Child , Child, Preschool , Enzyme-Linked Immunosorbent Assay , Follow-Up Studies , Hemangioma/therapy , Hemangioma/urine , Humans , Infant , Infant, Newborn , Interferon alpha-2 , Interferon-alpha/therapeutic use , Male , Recombinant Proteins , Skin Neoplasms/therapy , Skin Neoplasms/urine , Syndrome , Treatment Outcome
19.
Acta Derm Venereol ; 77(5): 379-81, 1997 Sep.
Article in English | MEDLINE | ID: mdl-9298132

ABSTRACT

The urinary excretion of 5-S-cysteinyldopa (5-S-CD) is known to be increased in certain patients with melanoma. To evaluate its diagnostic and prognostic utility, we measured the urinary excretion of 5-S-CD on at least three different occasions in 50 patients with melanoma. No significant increase was found in 26 patients without metastases, in 10 patients with regional lymph node metastasis and 2 patients with amelanotic melanoma. However, all the 12 patients with distant metastases demonstrated a significant increase. The patients with 5-S-CD > 1,000 micrograms/day survived for a mean of 8.1 +/- 5.6 months, while those with 5-S-CD > 10,000 micrograms/day survived for 3.5 +/- 3.7 months. All the 4 patients with a maximum excretion of 5-S-CD > 40,000 micrograms/day had multiple liver metastases. In conclusion, while data on the urinary excretion of 5-S-CD was not useful in the detection of early regional lymph node metastases, its increase indicated the presence of distant metastases and also provided prognostic information.


Subject(s)
Biomarkers, Tumor/urine , Cysteinyldopa/urine , Melanoma/urine , Skin Neoplasms/urine , Adult , Aged , Cysteinyldopa/metabolism , Female , Follow-Up Studies , Humans , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/secondary , Lymphatic Metastasis , Male , Melanoma/diagnosis , Melanoma/mortality , Melanoma/secondary , Middle Aged , Physical Examination , Prognosis , Radiography , Sensitivity and Specificity , Skin Neoplasms/diagnosis , Skin Neoplasms/mortality , Skin Neoplasms/pathology , Survival Rate
20.
J Pediatr Hematol Oncol ; 19(3): 237-44, 1997.
Article in English | MEDLINE | ID: mdl-9201147

ABSTRACT

PURPOSE: Hemangiomas are benign tumors occurring in 10% of infants. A small percentage are complicated by blockage of vital structures, consumptive coagulopathy, or heart failure, resulting in a mortality of -20% of patients with complications. Here, we describe four infants with complicated hemangiomas responding to interferon-alpha-2b therapy. PATIENTS AND METHODS: Four children with hemangiomas were treated with interferon-alpha-2b for complicating heart failure (1), visual impairment (2), or coagulopathy (1). Patients received interferon-alpha-2b alone or in conjunction with corticosteroid therapy over 2 to 9 months. Imaging studies and urinary basic fibroblast growth factor (bFGF) levels were used to monitor treatment response. RESULTS: Three of four patients demonstrated involution of the hemangiomas with improvement in their coagulopathy or visual impairment. The fourth patient expired due to cardiac complications despite radiologic evidence of hemangioma involution. Side effects associated with interferon-alpha-2b treatment included elevated transaminases (2) and leukocytosis (2), which resolved upon completion of therapy. One patient developed mild gross motor delay (1), which improved after cessation of therapy. Decreased urinary bFGF levels correlated with hemangioma involution. CONCLUSION: Interferon-alpha-2b therapy is an effective, well-tolerated treatment for complicated hemangiomas. Measurement of urinary bFGF levels may provide an objective method for monitoring treatment response.


Subject(s)
Hemangioma/therapy , Interferon-alpha/therapeutic use , Orbital Neoplasms/therapy , Skin Neoplasms/therapy , Exophthalmos/etiology , Female , Fibroblast Growth Factor 2/urine , Hemangioma/complications , Hemangioma/diagnosis , Hemangioma/urine , Humans , Infant , Interferon alpha-2 , Magnetic Resonance Imaging , Male , Orbital Neoplasms/complications , Orbital Neoplasms/diagnosis , Orbital Neoplasms/urine , Recombinant Proteins , Skin Neoplasms/complications , Skin Neoplasms/diagnosis , Skin Neoplasms/urine , Tomography, X-Ray Computed
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