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1.
BMC Cancer ; 17(1): 562, 2017 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-28835228

RESUMO

BACKGROUND: Previous studies have investigated the protective effect of vitamin D serum levels, at diagnosis and during the follow-up period after treatment, on melanoma outcome. In the present study we assess whether vitamin D supplementation, in the follow-up period after diagnosis and surgical resection of the primary tumor, has a protective effect on relapse of cutaneous malignant melanoma and whether this protective effect correlates with vitamin D levels in serum and Vitamin D Receptor immunoreactivity in the primary tumor. METHODS/DESIGN: This study is a multicenter randomized double blind placebo- controlled phase III trial. Patients between the age of 18 and 80 years diagnosed and treated surgically for a melanoma stage IB-III are eligible for randomization in a 1:1 ratio to active treatment or placebo. The study drug is taken each month and consists of either 100,000 International Unit cholecalciferol or arachidis oleum raffinatum used as a placebo. The primary endpoint is relapse free survival. The secondary endpoints are 25 hydroxyvitamin D3 serum levels at diagnosis and at 6 month intervals, melanoma subtype, melanoma site and stage of melanoma at diagnosis according to the 2009 American Joint Committee on Cancer melanoma staging and classification. At randomization a bloodsample is taken for DNA analysis. The study is approved by the local Ethics Committees. DISCUSSION: If we can confirm our hypothesis that vitamin D supplementation after removal of the tumor has a protective effect on relapse of cutaneous malignant melanoma we may reduce the burden of CMM at several levels. Patients, diagnosed with melanoma may have a better clinical outcome and improved quality of life. There will be a decrease in health care costs related to treatment of metastatic disease and there will be a decrease in loss of professional years, which will markedly reduce the economic burden of the disease. TRIAL REGISTRATION: Clinical Trial.gov, NCT01748448 , 05/12/2012.


Assuntos
Protocolos Clínicos , Suplementos Nutricionais , Melanoma/epidemiologia , Neoplasias Cutâneas/epidemiologia , Vitamina D , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Bélgica/epidemiologia , Calcifediol/sangue , Progressão da Doença , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Melanoma/etiologia , Melanoma/mortalidade , Melanoma/patologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Avaliação de Resultados da Assistência ao Paciente , Receptores de Calcitriol/genética , Receptores de Calcitriol/metabolismo , Fatores de Risco , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Vitamina D/administração & dosagem , Vitamina D/efeitos adversos , Adulto Jovem , Melanoma Maligno Cutâneo
2.
J Eur Acad Dermatol Venereol ; 29(10): 2024-31, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26307449

RESUMO

BACKGROUND: The healthy human skin with its effective antimicrobial defense system forms an efficient barrier against invading pathogens. There is evidence suggesting that the composition of this chemical barrier varies between diseases, making the easily collected sweat an ideal candidate for biomarker discoveries. OBJECTIVE: Our aim was to provide information about the normal composition of the sweat, and to study the chemical barrier found at the surface of skin. METHODS: Sweat samples from healthy individuals were collected during sauna bathing, and the global protein panel was analysed by label-free mass spectrometry. SRM-based targeted proteomic methods were designed and stable isotope labelled reference peptides were used for method validation. RESULTS: Ninety-five sweat proteins were identified, 20 of them were novel proteins. It was shown that dermcidin is the most abundant sweat protein, and along with apolipoprotein D, clusterin, prolactin-inducible protein and serum albumin, they make up 91% of secreted sweat proteins. The roles of these highly abundant proteins were reviewed; all of which have protective functions, highlighting the importance of sweat glands in composing the first line of innate immune defense system, and maintaining the epidermal barrier integrity. CONCLUSION: Our findings with regard to the proteins forming the chemical barrier of the skin as determined by label-free quantification and targeted proteomics methods are in accordance with previous studies, and can be further used as a starting point for non-invasive sweat biomarker research.


Assuntos
Proteínas/análise , Fenômenos Fisiológicos da Pele/imunologia , Suor/química , Adulto , Albuminas/análise , Apolipoproteínas D/análise , Proteínas de Transporte/análise , Clusterina/análise , Feminino , Glicoproteínas/análise , Humanos , Imunidade Inata , Masculino , Espectrometria de Massas , Proteínas de Membrana Transportadoras , Peptídeos/análise , Proteômica , Adulto Jovem
3.
J Eur Acad Dermatol Venereol ; 29(10): 1938-44, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25753249

RESUMO

BACKGROUND: The precise role of total body (18) F-fluorodeoxyglucose-positron emission tomography/computed tomography (PET/CT) in the clinical management of patients with cutaneous malignant melanoma (CMM) is not well established. OBJECTIVE: The purpose of this study was to investigate the diagnostic accuracy of PET/CT in early- and late-stage patients with high-risk CMM. METHODS: We retrospectively analysed various imaging, histopathological and clinical data from 97 patients also examined by PET/CT during a 5-year period (2007-2011). Three groups were assessed: stage I/II, resected stage III and unresectable stage III/stage IV. RESULTS: The median follow-up time of living patients was 43.48 ± 19.67 (15-142) months. We observed a high diagnostic accuracy in all stages (91.3%, 92.5% and 96.2% respectively). PET/CT appeared to be reliable diagnostic tool even for the detection of small lymph node metastases. PET/CT was informative in 14 of 19 cases wherein another imaging examination provided inconclusive results regarding lesion dignity. However, PET/CT was less suitable for properly evaluating the dignity of a lung lesion. A true positive scan was twice as likely in clinically negative patients with resected stage III disease than in patients with stage I/II disease (35.9% and 14.5%, P = 0.007). CONCLUSIONS: These results confirm that PET/CT is an important diagnostic tool in the management of patients with high-risk CMM, but it cannot replace the standard of care examinations. More accurate clinicopathological and timing criteria must be defined to best utilize the advantages of this imaging method.


Assuntos
Melanoma/diagnóstico por imagem , Melanoma/secundário , Tomografia por Emissão de Pósitrons , Neoplasias Cutâneas/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adulto , Idoso , Idoso de 80 Anos ou mais , Reações Falso-Negativas , Reações Falso-Positivas , Feminino , Fluordesoxiglucose F18 , Humanos , Metástase Linfática , Masculino , Melanoma/patologia , Pessoa de Meia-Idade , Imagem Multimodal , Estadiamento de Neoplasias , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Fatores de Risco , Sensibilidade e Especificidade , Neoplasias Cutâneas/patologia , Adulto Jovem
4.
J Eur Acad Dermatol Venereol ; 27(3): e320-7, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22817475

RESUMO

BACKGROUND: The formation of metastases and the efficacy of systemic therapies in cutaneous malignant melanoma (CMM) depend on the characteristics of the tumour cells and the host immune response. Aberrant expression of metallothionein (MT) has been observed in several types of cancers with poor prognoses. OBJECTIVE: To perform an immunohistochemical study on primary CMM comparing the MT expression of tumours without metastases (n = 23) to that of samples with haematogenous metastases (n = 23) and to examine the correlation between MT staining and immunological markers relevant in CMM progression. METHODS: The immunohistochemical labelling of different tumour sections was analysed using tissue microarrays for the evaluation of the suitability of this method in future studies. RESULTS: Our results suggest that MT overexpression is significantly more frequent in primary CMM with haematogenous metastases (P = 0.018) and that the overexpression is independent of the Breslow tumour thickness (R = 0.102, P = 0.501). Interestingly, MT overexpression of the tumour cells was correlated with the presence of tumour-infiltrating CD68(+) macrophages (P = 0.003), a known predictive factor for melanoma progression, thereby suggesting a role for MT in the development of a defective host immune response. Furthermore, the presence of CD163(+) macrophages infiltrating the tumours correlated with metastasis formation (P < 0.001), whereas the presence CD1a(+) dendritic cells surrounding the tumours was associated with a lower risk of haematogenous spread (P = 0.003). CONCLUSION: Our results demonstrate that MT may represent a suitable prognostic factor that can characterize the metastasising ability of CMM and the tumour-promoting host immune response.


Assuntos
Macrófagos/patologia , Melanoma/metabolismo , Metalotioneína/metabolismo , Neoplasias Cutâneas/metabolismo , Antígenos CD/imunologia , Progressão da Doença , Feminino , Humanos , Macrófagos/imunologia , Masculino , Melanoma/imunologia , Melanoma/patologia , Metástase Neoplásica , Fatores de Risco , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/patologia
5.
Clin Exp Dermatol ; 33(5): 602-5, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18462440

RESUMO

Three children (two boys and one girl) from the same family presented with photosensitivity, hyperpigmentation, hypertrichosis, mild skin fragility, blistering and scarring in childhood. On examination, the cutaneous lesions were found to have improved since their previous examinations. Laboratory tests showed raised plasma and urine carboxyporphyrins and decreased uroporphyrinogen decarboxylase enzyme activity in red blood cells. Triggering factors for porphyria were not detected except for a hepatitis C virus infection in the younger boy. The girl's clinical symptoms recurred in late adolescence, after iron and oestrogen treatments. Mutation analysis of the UROD gene detected two missense mutations, 19 A-->G M1V (novel) and 703C-->T P235S (previously reported), in an uncommon compound heterozygous manner in the three siblings.


Assuntos
Mutação de Sentido Incorreto/genética , Porfiria Cutânea Tardia/enzimologia , Uroporfirinogênio Descarboxilase/genética , Adolescente , Adulto , Criança , Análise Mutacional de DNA , Feminino , Heterozigoto , Humanos , Masculino , Linhagem , Uroporfirinogênio Descarboxilase/metabolismo
6.
Orv Hetil ; 142(47): 2635-9, 2001 Nov 25.
Artigo em Húngaro | MEDLINE | ID: mdl-11778362

RESUMO

The development of clinically overt porphyria cutanea tarda (PCT) can be attributed to joint effects of genetic predisposition and environmental factors. Regarding exogen factors, studies from several countries published in the last years gave an account of significantly higher frequency of chronic hepatitis C virus (HCV) infection in PCT patients compared to the normal population. At the Department of Dermatology of University of Debrecen the prevalence of positive anti-HCV antibodies has been found in approximately 55% of PCT patients diagnosed from 1990 to 1999, which is comparable to the average prevalence rate seen in Southern-European countries. The majority of male patients were anti-HCV positive and consumed regularly alcohol, whereas every female patient had taken contraceptives. Liver enzymes were only slightly elevated in the majority of the patients and liver biopsy had to be performed only in three patients duo to chronic hepatitis. Our findings emphasise how important the screening of PCT patients for anti-HCV antibody considering that it might be important quo ad vitam for young men.


Assuntos
Hepatite C/complicações , Hepatite C/epidemiologia , Porfiria Cutânea Tardia/virologia , Adulto , Alcoolismo/complicações , Anticoncepcionais Orais/efeitos adversos , Feminino , Anticorpos Anti-Hepatite C/sangue , Humanos , Hungria/epidemiologia , Masculino , Pessoa de Meia-Idade , Porfiria Cutânea Tardia/etiologia , Fatores de Risco
7.
J Invest Dermatol ; 115(3): 435-40, 2000 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10951280

RESUMO

Chromosomal defects are frequently present in malignant and premalignant skin disorders; however, it is not known whether ultraviolet radiation from sunlight plays a role in their induction. To obtain information on the ability of ultraviolet A and ultraviolet B to induce chromosomal aberrations, cultured melanocytes and fibroblasts were exposed to physiologic doses of ultraviolet A or ultraviolet B and, for comparison, to gamma rays. As a measure of chromosomal aberrations, the formation of micronuclei was determined. To obtain sufficient statistical data on induced micronuclei and cell kinetics, a flow cytometry method has been modified and applied. The flow cytometry method analysis is based on staining the DNA with ethidium bromide and the cell membranes with 1,6-diphenyl-1,3,5,-hexatriene. We observed dose-dependent micronuclei formation after gamma or ultraviolet B irradiation in both cell types and also for ultraviolet A in fibroblasts. The yield of micronuclei induced in fibroblasts by ultraviolet A was only a factor 15 smaller than that induced by ultraviolet B (313 nm). The results indicate that 10 kJ per m2 (equivalent to 1 minimal erythema dose) of ultraviolet B and 150 kJ per m2 of ultraviolet A (0.2 minimal erythema dose) can induce 1% of micronuclei in fibroblasts, equivalent to the induction due to 0.6 Gy of gamma radiation. In conclusion, physiologic doses of sunlight can induce chromosomal aberrations at a level comparable with that observed after exposure to approximately 1 Gy of ionizing radiation. Therefore, sunlight can be considered a potential inducer of chromosomal aberrations in skin cells, which may contribute to skin carcinogenesis.


Assuntos
Aberrações Cromossômicas/fisiologia , Pele/citologia , Pele/efeitos da radiação , Raios Ultravioleta , Ciclo Celular/efeitos da radiação , Células Cultivadas , Relação Dose-Resposta à Radiação , Fibroblastos/efeitos da radiação , Citometria de Fluxo/métodos , Raios gama , Humanos , Lasers , Melanócitos/efeitos da radiação , Micronúcleos com Defeito Cromossômico/efeitos da radiação , Doses de Radiação , Luz Solar/efeitos adversos , Fatores de Tempo
8.
Biochim Biophys Acta ; 1478(1): 1-8, 2000 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-10719169

RESUMO

The proteinase of bovine leukemia virus (BLV) was cloned into pMal-c2 vector with N-terminal or with N- as well as C-terminal flanking sequences, and expressed in fusion with maltose binding protein. The proteinase self-processed itself from the fusion protein during expression and formed inclusion bodies. The enzyme was purified from inclusion bodies by cation-exchange chromatography followed by gel filtration. Specificity of the enzyme was compared to that of human T-cell leukemia proteinase type 1. Although the two viruses belong to the same subfamily of retroviruses, the differences in their proteinase specificity, based on kinetics with oligopeptide substrates representing naturally occurring cleavage sites as well as on inhibition pattern, appear to be pronounced.


Assuntos
Endopeptidases/genética , Vírus da Leucemia Bovina/enzimologia , Sequência de Aminoácidos , Ácido Aspártico Endopeptidases/metabolismo , Sítios de Ligação , Clonagem Molecular , Endopeptidases/isolamento & purificação , Endopeptidases/metabolismo , Inibidores Enzimáticos/farmacologia , Escherichia coli/genética , Cinética , Dados de Sequência Molecular , Proteínas Recombinantes de Fusão/metabolismo , Alinhamento de Sequência , Especificidade por Substrato
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