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1.
Medicine (Baltimore) ; 101(35): e30471, 2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36107519

RESUMO

Early diagnosis of malignant melanoma is critical for effective treatment and reduced patient mortality. However, current clinical and histological variables show limited accuracy in diagnosis. Serum or urine level of 5-S-cysteinyldopa (5-S-CD) is a commonly used melanoma biomarker in Japan owing to its increased sensitivity compared with other melanoma markers. However, its use as a diagnostic marker has shown some limitations. Therefore, here we examined the combination of 5-S-CD with melanoma inhibitory activity, which showed sensitivity in detecting melanoma comparable with that of 5-S-CD, and interleukin-8, a cytokine linked with melanoma progression, in a cohort of Japanese patients with melanoma. Our results revealed that the triple combination of 5-S-CD, melanoma inhibitory activity, and interleukin-8 showed high diagnostic accuracy in detecting melanoma compared with each of the individual factors. Importantly, the triple marker showed specificity and utility in detecting early-stage melanoma. Our results suggest the utility of the triple marker as a diagnostic biomarker for melanoma patients.


Assuntos
Cisteinildopa , Melanoma , Biomarcadores Tumorais , Citocinas , Humanos , Interleucina-8 , Melanoma/patologia , Neoplasias Cutâneas
2.
Lipids Health Dis ; 20(1): 166, 2021 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-34801038

RESUMO

BACKGROUND AND OBJECTIVES: Laparoscopic colorectal surgery causes a lower stress response than open surgery. Adiponectin is mainly derived from adipocytes and has antidiabetic, antioxidative, and anti-inflammatory capabilities. The objective of the present study was to investigate the protein expression of adiponectin in adipose tissue, and the serum levels of adiponectin, oxidative stress markers and proinflammatory factors during laparoscopic colorectal surgery and open surgery periods. METHODS: Forty patients aged 60 to 80, with American Society of Anesthesiologists (ASA) I ~ II who underwent radical resection of colorectal cancer were recruited to the study. Laparoscopic group and open group included 20 patients each. Mesenteric adipose tissue and venous blood before (T1) and at the end (T2) of surgery were collected to examine adiponectin levels, and venous blood was collected to examine serum levels of oxidative stress related markers (superoxide dismutase (SOD), glutathione (GSH), lipid peroxide (LPO), malondialdehyde (MDA)), and inflammation-related factors (interleukin (IL)-1ß, interleukin (IL)-6, tumor necrosis factor-α (TNF-α)). RESULTS: Protein and serum levels of adiponectin were analyzed, and adiponectin levels were significantly increased at T2 than T1 in the laparoscopic surgery, while adiponectin levels were significantly higher in the laparoscopic surgery than in the open surgery at T2. In addition, the serum levels of SOD and GSH were significantly higher in the laparoscopic surgery than in open surgery at T2. However, the serum levels of LPO, TNF-α, IL-1ß, and IL-6 were significantly lower in the laparoscopic group than in open group at T2. CONCLUSION: Laparoscopic surgery induced higher levels of adiponectin in both adipose tissue and the bloodstream. Oxidative stress and the inflammatory response were lower during laparoscopic colorectal surgery than during conventional open surgery. These data suggest that adipose tissue may alleviate the stress response during laparoscopic surgery by releasing adiponectin in patients with colorectal cancer.


Assuntos
Adiponectina/metabolismo , Tecido Adiposo/metabolismo , Neoplasias Colorretais/cirurgia , Laparoscopia/efeitos adversos , Adiponectina/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Neoplasias Colorretais/metabolismo , Cisteinildopa/análogos & derivados , Feminino , Glutationa , Humanos , Peróxidos Lipídicos/sangue , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo , Estresse Fisiológico/fisiologia , Superóxido Dismutase/sangue
3.
Int J Mol Sci ; 22(3)2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33573055

RESUMO

Two types of melanin pigments, brown to black eumelanin and yellow to reddish brown pheomelanin, are biosynthesized through a branched reaction, which is associated with the key intermediate dopaquinone (DQ). In the presence of l-cysteine, DQ immediately binds to the -SH group, resulting in the formation of cysteinyldopa necessary for the pheomelanin production. l-Cysteine prefers to bond with aromatic carbons adjacent to the carbonyl groups, namely C5 and C2. Surprisingly, this Michael addition takes place at 1,6-position of the C5 (and to some extent at C2) rather than usually expected 1,4-position. Such an anomaly on the reactivity necessitates an atomic-scale understanding of the binding mechanism. Using density functional theory-based calculations, we investigated the binding of l-cysteine thiolate (Cys-S-) to DQ. Interestingly, the C2-S bonded intermediate was less energetically stable than the C6-S bonded case. Furthermore, the most preferred Cys-S--attacked intermediate is at the carbon-carbon bridge between the two carbonyls (C3-C4 bridge site) but not on the C5 site. This structure allows the Cys-S- to migrate onto the adjacent C5 or C2 with small activation energies. Further simulation demonstrated a possible conversion pathway of the C5-S (and C2-S) intermediate into 5-S-cysteinyldopa (and 2-S-cysteinyldopa), which is the experimentally identified major (and minor) product. Based on the results, we propose that the binding of Cys-S- to DQ proceeds via the following path: (i) coordination of Cys-S- to C3-C4 bridge, (ii) migration of Cys-S- to C5 (C2), (iii) proton rearrangement from cysteinyl -NH3+ to O4 (O3), and (iv) proton rearrangement from C5 (C2) to O3 (O4).


Assuntos
Benzoquinonas/química , Cisteína/análogos & derivados , Cisteinildopa/química , Di-Hidroxifenilalanina/análogos & derivados , Sítios de Ligação , Cisteína/química , Teoria da Densidade Funcional , Di-Hidroxifenilalanina/química , Melaninas/química , Modelos Moleculares , Prótons
4.
Int J Mol Sci ; 21(2)2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31936623

RESUMO

Melanoma is one of the most lethal and malignant cancers and its incidence is increasing worldwide, and Japan is not an exception. Although there are numerous therapeutic options for melanoma, the prognosis is still poor once it has metastasized. The main concern after removal of a primary melanoma is whether it has metastasized, and early detection of metastatic melanoma would be effective in improving the prognosis of patients. Thus, it is very important to identify reliable methods to detect metastases as early as possible. Although many prognostic biomarkers (mainly for metastases) of melanoma have been reported, there are very few effective for an early diagnosis. Serum and urinary biomarkers for melanoma diagnosis have especially received great interest because of the relative ease of sample collection and handling. Several serum and urinary biomarkers appear to have significant potential both as prognostic indicators and as targets for future therapeutic methods, but still there are no efficient serum and urinary biomarkers for early detection, accurate diagnosis and prognosis, efficient monitoring of the disease and reliable prediction of survival and recurrence. Levels of 5-S-cysteinyldopa (5SCD) in the serum or urine as biomarkers of melanoma have been found to be significantly elevated earlier and to reflect melanoma progression better than physical examinations, laboratory tests and imaging techniques, such as scintigraphy and echography. With recent developments in the treatment of melanoma, studies reporting combinations of 5SCD levels and new applications for the treatment of melanoma are gradually increasing. This review summarizes the usefulness of 5SCD, the most widely used and well-known melanoma marker in the serum and urine, compares 5SCD and other useful markers, and finally its application to other fields.


Assuntos
Biomarcadores Tumorais/metabolismo , Cisteinildopa/metabolismo , Melanoma/metabolismo , Neoplasias Cutâneas/metabolismo , Cisteinildopa/sangue , Monitoramento de Medicamentos , Humanos , Melanoma/sangue , Melanoma/patologia , Metaboloma , Neoplasias Cutâneas/sangue , Neoplasias Cutâneas/patologia
5.
J Dermatol ; 45(11): 1340-1344, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30144152

RESUMO

Along with the expansion of therapeutic options for metastatic melanoma, the development of useful biomarkers is urgently required to predict and monitor treatment response. Serum 5-S-cysteinyldopa (5-S-CD) has been identified as a diagnostic marker of malignant melanoma, but its utility as a biomarker for emerging therapeutic agents remains unknown. We assessed serum 5-S-CD in 12 metastatic melanoma patients (median age, 76 years; six men and six women) who had been treated with nivolumab (Nivo) at Shinshu University Hospital between 2014 and 2016. Serum 5-S-CD and lactate dehydrogenase levels before and at 3-6 weeks of Nivo treatment were obtained and their changes were compared with clinical responses as defined by the Response Evaluation Criteria in Solid Tumors criteria (version 1.1). A decrease of 10 nmol/L or more of serum 5-S-CD was observed only in partial response patients (2/3 cases, 67%), while an increase of 10 nmol/L or more of serum 5-S-CD was witnessed only in progressive disease patients (4/8 cases, 50%). Serum 5-S-CD changes were within ±10 nmol/L in the remaining six patients (partial response, one; stable disease, one; progressive disease, four). The results of the four moderately affected progressive disease patients were suspected to have been influenced by small-sized metastatic lesions, a mixed response that included diminished and enlarged metastatic lesions, prior therapy to Nivo with BRAF inhibitors or radiation, or the development of brain metastasis. Serum 5-S-CD in the early phase of Nivo treatment may be helpful to predict therapeutic response in metastatic melanoma.


Assuntos
Biomarcadores Tumorais/sangue , Cisteinildopa/sangue , Melanoma/tratamento farmacológico , Nivolumabe/uso terapêutico , Neoplasias Cutâneas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Humanos , L-Lactato Desidrogenase/sangue , Masculino , Melanoma/sangue , Melanoma/patologia , Pessoa de Meia-Idade , Prognóstico , Critérios de Avaliação de Resposta em Tumores Sólidos , Neoplasias Cutâneas/sangue , Neoplasias Cutâneas/patologia , Adulto Jovem
6.
Pigment Cell Melanoma Res ; 31(3): 384-392, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29160957

RESUMO

Melanin from several insect samples was isolated and subjected to chemical degradation and HPLC analysis for melanin markers. Quantification of different melanin markers reveals that insect melanins are significantly different from that of the mammalian epidermal melanins. The eumelanin produced in mammals is derived from the oxidative polymerization of both 5,6-dihydroxyindole and 5,6-dihydroxyindole-2-carboxylic acids. The pheomelanin is formed by the oxidative polymerization of cysteinyldopa. Thus, dopa is the major precursor for both eumelanin and pheomelanin in mammals. But insect eumelanin appears to be mostly made from 5,6-dihydroxyindole and originates from dopamine. More importantly, our study points out the wide spread occurrence of pheomelanin in many insect species. In addition, cysteinyldopamine and not cysteinyldopa is the major precursor for insect pheomelanin. Thus, both eumelanin and pheomelanin in insects differ from higher animals using dopamine and not dopa as the major precursor.


Assuntos
Cisteinildopa/metabolismo , Indóis/metabolismo , Melaninas/biossíntese , Sarcofagídeos/metabolismo , Animais , Drosophila melanogaster , Humanos , Especificidade da Espécie
7.
J Dermatol ; 44(4): 449-454, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27786364

RESUMO

With the recent development of novel molecular targeted drugs for advanced stage malignant melanoma (MM), including RAF and mitogen-activated protein kinase kinase inhibitors and immune checkpoint blockers, the early detection of relapse is important for managing patients with MM. In this study, we retrospectively analyzed two conventional serum biomarkers, 5-S-cysteinyl-dopa and lactate dehydrogenase, in patients with MM (n = 140) who were treated at a single Japanese institute from June 2007 to June 2015. At the initial hospital visit, serum 5-S-cysteinyl-dopa levels were significantly increased in patients with stages III (n = 38) and IV (n = 20) MM compared with patients with stages 0-II (n = 62) MM. In addition, in patients with stages III and IV MM, serum 5-S-cysteinyl-dopa levels of more than 15.0 nmol/L at initial hospital visit correlated with a poor prognosis. In 11 of 14 patients whose disease progressed during follow up (mostly from stages III-IV), serum 5-S-cysteinyl-dopa levels exceeded the normal limit of 10.0 nmol/L during the clinical detection of distant metastases. These results indicate the usefulness of measuring serum 5-S-cysteinyl-dopa levels at initial hospital visit and during follow up for early and effective therapeutic interventions using newly developed molecular targeted drugs.


Assuntos
Cisteinildopa/sangue , L-Lactato Desidrogenase/sangue , Melanoma/sangue , Recidiva Local de Neoplasia/sangue , Neoplasias Cutâneas/sangue , Biomarcadores Tumorais/sangue , Di-Hidroxifenilalanina , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Japão/epidemiologia , Estimativa de Kaplan-Meier , Masculino , Melanoma/mortalidade , Melanoma/patologia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia
8.
Australas J Dermatol ; 57(2): 145-9, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26931184

RESUMO

TNM staging is mainly used to evaluate the prognosis of melanoma patients. Serum biomarkers such as 5-S-cysteinyldopa (5-S-CD) have occasionally been used but most do not respond until the tumour burden becomes high. Recently, circulating melanoma cells (CMC) have been reported as a possible new biomarker to detect metastasis, monitor treatment response and predict prognosis. The object of this exploratory study was to evaluate the efficacy of CMC to detect metastasis and predict prognosis by cross-sectional and prospective observational analyses, respectively. Altogether 15 patients with stages II-IV melanoma were enrolled and CMC were enumerated by CellSearch system with cut-off values of two cells/7.5 mL. Serum 5-S-CD and lactate dehydrogenase (LDH) were also measured. The sensitivity of CMC and 5-S-CD for the detection of metastasis was 33 and 50%, respectively. The combination of CMC and 5-S-CD showed a sensitivity of 67%, the best performance among CMC, 5-S-CD, LDH and any combination of two of the markers. Additionally, a 30-month prospective observation showed that CMC could segregate patients with poorer prognosis. The median survival time for the patients with <2 CMC and those with ≥2 CMC was 19.5 and 4.5 months, respectively. The limitation of this study is the small sample size. These preliminary results indicate CMC may complement the efficacy of 5-S-CD to detect metastasis and can be a prognostic marker. Although there is still room for improvement to maximise the sensitivity, the CellSearch system is reproducible, standardised and suitable for multi-centre studies.


Assuntos
Biomarcadores Tumorais/sangue , Melanoma/sangue , Melanoma/diagnóstico , Células Neoplásicas Circulantes , Neoplasias Cutâneas/sangue , Neoplasias Cutâneas/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Cisteinildopa/sangue , Feminino , Humanos , L-Lactato Desidrogenase/sangue , Masculino , Melanoma/secundário , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Sensibilidade e Especificidade , Neoplasias Cutâneas/patologia , Taxa de Sobrevida
9.
Exp Dermatol ; 22(11): 748-9, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24433182

RESUMO

Leptin is known to be abnormally expressed in a variety of cancers, and leptin receptors have been reported to be expressed on human melanoma cells. In this study, we evaluated the possibility that the serum levels of leptin receptor could be a tumor marker of malignant melanoma (MM). Serum samples were obtained from 71 patients with MM, and the serum levels of leptin receptor were measured by double-determinant ELISA. Interestingly, serum levels of leptin receptor decreased gradually with the stages of MM, being highest at in situ and lowest at stage IV. There was also a trend of reverse correlation between tumor thickness and serum levels of leptin receptor. To our knowledge, this is the first report investigating the serum levels of leptin receptor in MM, and serum leptin receptor levels may be used as a useful tumor marker of MM.


Assuntos
Biomarcadores Tumorais/sangue , Melanoma/sangue , Receptores para Leptina/sangue , Neoplasias Cutâneas/sangue , Índice de Massa Corporal , Estudos de Casos e Controles , Linhagem Celular Tumoral , Cisteinildopa/sangue , Progressão da Doença , Feminino , Humanos , Resistência à Insulina , Leptina/sangue , Masculino , Melanoma/diagnóstico , Neoplasias Cutâneas/diagnóstico
12.
Talanta ; 84(2): 280-6, 2011 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-21376945

RESUMO

The incidence of malignant melanoma has increased over the past decades, particularly in Caucasian population. This disease presents defavourable prognosis in terms of survey, especially when detection occurs at the metastatic phase. Reliable analytical methods for biomarker determination are thus an interesting tool in pathology detection and follow-up. In this context, a method using SPE-LC-ESI-MS-MS for the determination of 5-S-cysteinyldopa (5-SCD) in human plasma was optimized. The presence of matrix effect was investigated in details while 5-SCD stability was studied according to FDA requirements for the validation of bioanalytical methods. Pre-study and in-study validations of the entire method were then successfully performed by applying the approach based on total measurement error and accuracy profiles over a concentration ranges from 1.6 to 200 ng/ml. Good results with respect to accuracy, trueness and precision were obtained. The maximum risk of observing future measurements falling outside the acceptance limits during routine analysis was also estimated.


Assuntos
Biomarcadores Tumorais/sangue , Cromatografia Líquida/métodos , Cisteinildopa/sangue , Melanoma/sangue , Extração em Fase Sólida/métodos , Espectrometria de Massas em Tandem/métodos , Calibragem , Humanos , Limite de Detecção , Padrões de Referência , Reprodutibilidade dos Testes
13.
Exp Dermatol ; 20(3): 288-90, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21323749

RESUMO

The possible role of melanocyte as a modulator of the inflammation and keratinocyte hyperproliferation in psoriasis has been hypothesised but never demonstrated on experimental basis. Aim of the present study was to assess whether plasma levels of 5-S-cysteinyldopa (CD), a metabolite reflecting melanocyte activity, undergo changes in association with psoriasis together with those of typical lipid peroxidation markers thiobarbituric acid reactive substances (TBARS). A group of 16 patients with psoriasis at different stage as indicated by the psoriasis area and severity index (PASI) were enrolled against an age and sex matched control group. Both TBARS (P<0.05) and CD (P<0.005) levels were higher than controls with statistical significance. After 1 month therapy the levels of either biomarkers decreased with respect to the starting values although with marked individual differences. CD may represent a novel and sensitive biomarker for the follow up of psoriasis and evaluation of the efficacy of therapeutic regimens beyond PASI determination.


Assuntos
Cisteinildopa/sangue , Melanócitos/metabolismo , Psoríase/sangue , Adulto , Idoso , Biomarcadores/sangue , Sangue/metabolismo , Feminino , Humanos , Peroxidação de Lipídeos , Masculino , Pessoa de Meia-Idade , Psoríase/diagnóstico , Psoríase/metabolismo , Psoríase/terapia , Indução de Remissão , Índice de Gravidade de Doença , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo
14.
J Nat Prod ; 74(4): 675-82, 2011 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-21341762

RESUMO

Biomimetic oxidation of the pheomelanin precursor 5-S-cysteinyldopa in the presence of Zn(2+) ions led to the isolation of two isomeric products, one of which could be identified as the benzothiazolylthiazinodihydroisoquinoline 5, while the other proved too unstable for a complete characterization. Both these products were converted into more stable oxidized forms, which after ethylchloroformate derivatization were characterized as the ethyl ester/ethoxycarbonyl isoquinolines 8 and 9. Compound 5 exhibited absorption characteristics similar to those of red hair pheomelanin, including a main band around 400 nm in acids. Similarly to red hair pheomelanin and synthetic pigments, 5 afforded on chemical degradation a thiazolylpyridinecarboxylic acid fragment. Model chemical studies allowed the proposal of a formation mechanism for the benzothiazole and dihydroisoquinoline systems in compound 5.


Assuntos
Benzotiazóis/metabolismo , Cisteinildopa/biossíntese , Cor de Cabelo/fisiologia , Isoquinolinas/metabolismo , Melaninas/biossíntese , Melaninas/química , Modelos Químicos , Pigmentos Biológicos/biossíntese , Benzotiazóis/química , Cisteinildopa/química , Cabelo/química , Cabelo/metabolismo , Humanos , Isoquinolinas/química , Melaninas/fisiologia , Estrutura Molecular , Oxirredução , Pigmentos Biológicos/química , Estereoisomerismo , Zinco/química
15.
PLoS One ; 4(9): e7229, 2009 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-19789711

RESUMO

BACKGROUND: Melanin, a high-molecular weight pigment that is ubiquitous in nature, protects melanized microorganisms against high doses of ionizing radiation. However, the physics of melanin interaction with ionizing radiation is unknown. METHODOLOGY/PRINCIPAL FINDINGS: We rationally designed melanins from either 5-S-cysteinyl-DOPA, L-cysteine/L-DOPA, or L-DOPA with diverse structures as shown by elemental analysis and HPLC. Sulfur-containing melanins had higher predicted attenuation coefficients than non-sulfur-containing melanins. All synthetic melanins displayed strong electron paramagnetic resonance (2.14.10(18), 7.09.10(18), and 9.05.10(17) spins/g, respectively), with sulfur-containing melanins demonstrating more complex spectra and higher numbers of stable free radicals. There was no change in the quality or quantity of the stable free radicals after high-dose (30,000 cGy), high-energy ((137)Cs, 661.6 keV) irradiation, indicating a high degree of radical stability as well as a robust resistance to the ionizing effects of gamma irradiation. The rationally designed melanins protected mammalian cells against ionizing radiation of different energies. CONCLUSIONS/SIGNIFICANCE: We propose that due to melanin's numerous aromatic oligomers containing multiple pi-electron system, a generated Compton recoil electron gradually loses energy while passing through the pigment, until its energy is sufficiently low that it can be trapped by stable free radicals present in the pigment. Controlled dissipation of high-energy recoil electrons by melanin prevents secondary ionizations and the generation of damaging free radical species.


Assuntos
Melaninas/fisiologia , Tolerância a Radiação , Animais , Células CHO , Cricetinae , Cricetulus , Cryptococcus neoformans/metabolismo , Cisteína/química , Cisteinildopa/química , Radicais Livres , Raios gama , Levodopa/química , Compostos de Manganês/farmacologia , Melaninas/metabolismo , Peso Molecular , Óxidos/farmacologia , Oxigênio/química , Radiação Ionizante
16.
Blood Purif ; 28(3): 209-15, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19648740

RESUMO

BACKGROUND: Diffuse hyperpigmentation is common in patients with chronic renal failure undergoing hemodialysis (HD) or peritoneal dialysis (PD). We previously reported that serum levels of 5-S-cysteinyldopa (5SCD, a pheomelanin precursor) and pheomelanin were significantly elevated in HD patients. METHODS: Skin color was assessed using a Mexameter that measures the melanin index (MI) and the erythema index (EI). The upper inner arms (non-sun-exposed site) and the foreheads (sun-exposed site) of HD and PD patients and control subjects were analyzed. RESULTS: MI values on the upper inner arms and on the foreheads of HD and PD patients were significantly higher than in controls. In HD patients, significant correlations were found for serum 5SCD levels with MI and EI on the upper inner arm, and for EI on the forehead. In PD patients, no such correlations were found. CONCLUSIONS: Hyperpigmentation in HD patients results partly from accumulation of pheomelanin in the skin.


Assuntos
Cisteinildopa/sangue , Falência Renal Crônica/sangue , Melaninas/sangue , Diálise Renal , Pigmentação da Pele , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Diálise Peritoneal
17.
Pigment Cell Melanoma Res ; 22(5): 563-79, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19627559

RESUMO

Melanin is a natural pigment produced within organelles, melanosomes, located in melanocytes. Biological functions of melanosomes are often attributed to the unique chemical properties of the melanins they contain; however, the molecular structure of melanins, the mechanism by which the pigment is produced, and how the pigment is organized within the melanosome remains to be fully understood. In this review, we examine the current understanding of the initial chemical steps in the melanogenesis. Most natural melanins are mixtures of eumelanin and pheomelanin, and so after presenting the current understanding of the individual pigments, we focus on the mixed melanin systems, with a critical eye towards understanding how studies on individual melanin do and do not provide insight in the molecular aspects of their structures. We conclude the review with a discussion of important issues that must be addressed in future research efforts to more fully understand the relationship between molecular and functional properties of this important class of natural pigments.


Assuntos
Melaninas , Benzoquinonas/química , Benzoquinonas/metabolismo , Benzotiazóis/química , Benzotiazóis/metabolismo , Cisteinildopa/química , Cisteinildopa/metabolismo , Di-Hidroxifenilalanina/análogos & derivados , Di-Hidroxifenilalanina/química , Di-Hidroxifenilalanina/metabolismo , Humanos , Iris/química , Iris/ultraestrutura , Melaninas/química , Melaninas/metabolismo , Melanócitos/metabolismo , Melanossomas/química , Melanossomas/metabolismo , Estrutura Molecular
18.
Pigment Cell Melanoma Res ; 22(4): 474-86, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19493317

RESUMO

Pheomelanogenesis is a complex pathway that starts with the oxidation of tyrosine (or DOPA, 3,4-dihydroxyphenylalanine) by tyrosinase in the presence of cysteine, which results in the production of 5-S-cysteinyldopa and its isomers. Beyond that step, relatively little has been clarified except for a possible intermediate produced, dihydro-1,4-benzothiazine-3-carboxylic acid (DHBTCA). We therefore carried out a detailed study on the course of pheomelanogenesis using DOPA and cysteine and the physiological enzyme tyrosinase. To elucidate the later stages of pheomelanogenesis, chemical degradative methods of reductive hydrolysis with hydroiodic acid and alkaline peroxide oxidation were applied. The results show that: (1) DHBTCA accumulates after the disappearance of the cysteinyldopa isomers, (2) DHBTCA is then oxidized by a redox exchange with dopaquinone to form ortho-quinonimine, which leads to the production of pheomelanin with a benzothiazine moiety, and (3) the benzothiazine moiety gradually degrades to form a benzothiazole moiety. This latter process is consistent with the much higher ratio of benzothiazole-derived units in human red hair than in mouse yellow hair. These findings may be relevant to the (photo)toxic effects of pheomelanin.


Assuntos
Alanina/análogos & derivados , Benzotiazóis/química , Di-Hidroxifenilalanina/química , Melaninas/química , Tiazinas/química , Ácidos/química , Alanina/química , Alanina/metabolismo , Animais , Benzotiazóis/metabolismo , Cisteína/química , Cisteína/metabolismo , Cisteinildopa/química , Cisteinildopa/metabolismo , Di-Hidroxifenilalanina/metabolismo , Cor de Cabelo , Humanos , Hidrólise , Compostos de Iodo/química , Melaninas/metabolismo , Camundongos , Monofenol Mono-Oxigenase/química , Monofenol Mono-Oxigenase/metabolismo , Oxirredução , Peróxidos/química , Tiazinas/metabolismo
20.
Ann Thorac Surg ; 87(4): 1264-6, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19324166

RESUMO

Malignant melanoma originating outside the skin is very rare, whereas primary malignant melanoma of the lung is extremely rare. 5-S-Cysteinyldopa (5-S-CD), a melanin metabolite, has been reported to be a prognostic marker for cutaneous malignant melanoma. This is the first report in the English language literature dealing with primary malignant melanoma of the lung using serum 5-S-Cysteinyldopa levels to monitor the effects of surgery and chemotherapy.


Assuntos
Cisteinildopa/sangue , Neoplasias Pulmonares/sangue , Melanoma/sangue , Idoso , Biomarcadores/sangue , Humanos , Neoplasias Pulmonares/cirurgia , Masculino , Melanoma/cirurgia , Pneumonectomia
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