OBJECTIVE: Melanin gives some natural protection against the harmful effects of ultraviolet radiation; however, excessive production of melanin causes skin hyperpigmentation. Depigmenting cosmetics can be used to control this process; however, depigmenting agents commonly used have some disadvantages, such as low bioavailability, photosensitization, cellular toxicity, and insolubility. Natural sources of melanogenic inhibitors have become important alternatives to synthetic ones. The objective of this review was to summarize the results of studies on natural extracts that have been reported in the literature to inhibit the process of melanogenesis, giving a view on their suitability for potential use in new cosmetic formulations for skin-lightening.
METHODS: A systematic literature search was carried out using the descriptors: \"melanogenesis\", \"tyrosinase\", \"tyrosinase inhibition\", and \"natural agents\".
METHODS: Publications were selected based on our designated inclusion and exclusion criteria, and a total of 15 studies met these criteria.
METHODS: The following were used in the review of each paper which met the criteria: the name of the plant (all of the natural extracts turned out to be from plants), the method used to obtain the plant extract, the method for evaluating anti-tyrosinase activity, the main results, and the conclusions.
RESULTS: All evaluated natural agents demonstrated anti-tyrosinase effect. The species Leathesia difformis, Morus alba, Orostachys japonicus, Heracleum moellendorffii, Coix lacryma-jobi (adlay), Inula brittanica, and Gailardia aristata stood out from the others due to their application as potential inhibitors of more than three proteins related to melanogenesis, including the cyclic adenosine monophosphate response element-binding protein, microphthalmia-associated transcription factor, tyrosinase, tyrosinase-related protein-1, tyrosinase-related protein-2, and dopachrome tautomerase.
CONCLUSIONS: The plants present an anti-tyrosinase effect that must be better explored in the new cosmetic formulations. The anti-melanogenic effects of the plant are mainly related to the presence of phenolic and antioxidant compounds.
OBJECTIVE: La mélanine offre une certaine protection naturelle contre les effets nocifs des rayons ultraviolets ; cependant, une production excessive de mélanine provoque une hyperpigmentation cutanée. Les cosmétiques dépigmentants peuvent servir à contrôler ce processus ; cependant, les agents dépigmentants couramment utilisés présentent certains inconvénients, comme une biodisponibilité faible, une photosensibilité, une toxicité cellulaire et une insolubilité. Les sources naturelles d’inhibiteurs de la mélanogénèse sont devenues des alternatives importantes aux inhibiteurs synthétiques. L’objectif de cette revue était de résumer les résultats des études sur les extraits naturels signalés dans la littérature comme inhibant le processus de mélanogenèse, en donnant un aperçu de leur adéquation à une utilisation potentielle dans de nouvelles formulations cosmétiques pour l’éclaircissement de la peau. SOURCES DES DONNÉES: Une recherche systématique dans la littérature a été réalisée à l’aide des descripteurs : « mélanogenèse », « tyrosinase », ‘inhibition de la tyrosinase » et « agents naturels ». Sélection des études : Les publications ont été sélectionnées d’après nos critères d’inclusion et d’exclusion désignés et un total de 15 études remplissaient ces critères. EXTRACTION DES DONNÉES: Les éléments suivant ont été utilisés dans l’examen de chaque article répondant aux critères : le nom de la plante (tous les extraits naturels se sont avérés provenir des plantes), la méthode utilisée pour obtenir l’extrait végétal, la méthode d’évaluation de l’activité anti-tyrosinase, les principaux résultats et les conclusions. SYNTHÈSE DES DONNÉES: Tous les agents naturels évalués ont démontré un effet anti-tyrosinase. Les espèces Leathesia difformis, Morus alba, Orostachys japonicus, ,Heracleum moellendorffii, Coix lacryma-jobi (adlay), Inula brittanica, et Gailardia aristata se sont distinguées des autres en raison de leur application comme inhibiteurs potentiels de plus de trois protéines liées à la mélanogenèse, dont la protéine de liaison d’élément de réponse d’adénosine monophosphate cyclique, du facteur de transcription associé à la microphtalmie, la tyrosinase, la protéine liée à la tyrosinase-1, la protéine liée à la tyrosinase-2 et la dopachrome tautomérase.
CONCLUSIONS: Les plantes présentent un effet anti-tyrosinase qui doit être exploré plus en profondeur dans les nouvelles formulations cosmétiques. Les effets inhibiteurs de la mélanogénèse des plantes sont principalement dus à la présence de composés phénoliques et antioxydants.

Multipotent mesenchymal stem/stromal cells (MSCs) have strong tropism towards cancer cells, thus being tested as tools for the targeted delivery of therapeutic substances for the treatment of melanoma. However, different experimental approaches for melanoma induction and MSC treatment can have a direct impact on the outcomes. Systematic search was carried out in three databases (PubMed, Scopus, and Web of Science) to include all studies, where stem cells were used as intervention for animal models for melanoma. Selected articles were classified according to SYRCLE\'s risk of bias tool for animals\' studies. Experimental variables and published data for tumor incidence and growth were extracted from the eligible articles and standardized using Hedge\'s G for random effects meta-analysis and meta-regression. From 627 entries, 11 articles were eligible for meta-analysis. All studies tested the effects of a single injection of mesenchymal stem/stromal cells (MSCs) (from bone marrow or adipose tissue) admixed with B16 mouse melanoma cells (B16-F0 or B16-F10) or with human melanoma cells (A375 or M4Beu) in mice. Mean SYRCLE score was 3.09 out of 10. Results from random effects meta-analysis indicate that MSCs favored both tumor incidence and tumor growth (p = 0.001) in melanoma. Our results show that MSCs are protumorigenic in co-injection mice models for melanoma, increasing both tumor incidence and growth.

Vinflunine is a new Vinca alkaloid uniquely fluorinated, by the use of superacid chemistry, in a little exploited region of the catharanthine moiety. In vitro investigations have confirmed the mitotic-arresting and tubulin-interacting properties of vinflunine shared by other Vinca alkaloids. However, differences in terms of the inhibitory effects of vinflunine on microtubules dynamics and its tubulin binding affinities have been identified which appear to distinguish it from the other Vinca alkaloids. Vinflunine induced smaller spirals with a shorter relaxation time, effects, which might be associated with reduced neurotoxicity. Studies investigating the in vitro cytotoxicity of vinflunine in combination therapy have revealed a high level of synergy when vinflunine was combined with either cisplatin, mitomycin C, doxorubicin or 5-fluorouracil. Furthermore, although vinflunine appears to participate in P-glycoprotein-mediated drug resistance mechanisms, it has proved only a weak substrate for this protein and a far less potent inducer of resistance than vinorelbine. Vinflunine was identified in preclinical studies as having marked antitumour activity in vivo against a large panel of experimental tumour models, with tumour regressions being recorded in human renal and small cell lung cancer tumour xenografts. Overall its level of activity was superior to that of vinorelbine in many of the experimental models used. Interestingly, an in vivo study using a well vascularised adenocarcinoma of the colon has suggested that vinflunine mediates its antitumour activity at least in part via an antivascular mechanism, even at sub-cytotoxic doses. Therefore, these data provide a favourable preclinical profile for vinflunine, supporting its promising candidacy for clinical development. Phase I evaluations of vinflunine have been completed in Europe and phase II clinical trials are now ongoing.

Melanoma is a particularly aggressive malignant tumour of the skin that is influenced by genetic, environmental and physiological elements. Since current therapy for melanoma is limited and associated with high toxicity and side effects, development of alternative approaches is imperative. The importance of dendritic cells (DCs) in immunity against tumours is now well established. DC immunotherapy for melanoma is possible but must be considered in terms of effectiveness and clinical viability. The source of DCs to be used in adoptive therapy as well as the nature and method of delivery of the priming antigen are important factors. The most suitable DC appears to be cells derived by culture from hemopoietic progenitor cells (HPC) in bone marrow or DC progenitors in peripheral blood. Generation of an effective anti-tumour immune response will be dependent upon the presentation of multiple melanoma-specific antigens by both major histocompatibility complex (MHC) class I and class II molecules and stimulation of both tumour-specific cytotoxic T lymphocytes (Tc) and T helper type 1 (Thl) cells. Different techniques for delivery of the priming antigen offer different advantages. DCs can be pulsed with peptide, protein or tumour cell lysate, transfected with viral vectors or naked nucleic acid and tumour/DC hybridomas can also be generated. Repeated antigen administration into neighbouring lymph nodes appears to be the most effective method for promoting a systemic anti-tumour response. Adjuvant therapies can also enhance immune responses and lead to total tumour clearance. The importance of DC immunotherapy in clinically different stages of disease will also be an important consideration.

We have established cell lines from benign cutaneous melanocytic lesions and from melanoma-affected lymph nodes of monodelphis domestica, the laboratory opossum (a South American marsupial now widely maintained in captive colonies for experimental purposes). Unlike melanoma cell lines currently available from humans and other mammals, the opossum lines are derived from cells transformed in vivo by experimentally controlled exposure to ultraviolet B (UVB) radiation of known spectral composition. Differences in the patterns of protein expression among cell lines at different stages of the UVB-induced melanoma cascade can be identified by proteome analysis and will provide a useful basis for comparisons with human and mouse melanoma cell lines. Powerful new two-dimensional (2D) gel electrophoresis technologies and sophisticated bioinformatics programs make it possible to carry out qualitative and quantitative analyses of the entire protein complement expressed by the genome (proteome) of a specific cell type. One area of biology particularly well suited to proteome analysis is carcinogenesis. It is now feasible, for example, to attempt to characterize the full repertoire of proteins, including all the antigenic determinants at the cell surface and in the cytosol, during the carcinogenic cascade from normal progenitor cells, to benign tumor cells, and finally, to highly invasive metastatic cells. Proteome analyses have been initiated with the cell lines from M. domestica.

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BACKGROUND: Matrix metalloproteinases are a homologous family of proteolytic enzymes. Collectively, these proteinases are capable of degrading all components of the extracellular matrix, including proteolytically resistant fibrillar collagens. Extracellular matrices constitute the principal barrier to tumour growth and spread, and there is now experimental evidence that malignant tumours utilise matrix metalloproteinases to overcome this barrier. Inhibitors of matrix metalloproteinases may therefore be of therapeutic value in the treatment of metastatic disease.
METHODS: This review describes the activity of matrix metalloproteinases inhibitors (MMPIs), in experimental tumour models and in phase I/II clinical studies.
RESULTS: Studies with MMPIs in vitro have shown that these agents are not cytotoxic but can inhibit the degradation of extracellular matrix by tumour cells. In experimental tumour models in vivo, MMPI treatment caused inhibition of tumour growth and metastatic spread in both rodent syngeneic and human xenograft models. MMPIs have also been shown to inhibit angiogenesis, a process essential for the rapid growth of most malignancies.
CONCLUSIONS: MMPI therapy has the potential to arrest tumour growth and spread. As a non-cytotoxic \'tumourostatic\' approach it may offer an ideal complement to surgery, radiotherapy and chemotherapy in the successful long-term treatment of metastatic disease.

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Cutaneous malignant melanoma (CMM) rates have been increasing in the United States at an average rate of about 4% per year. In 1987, it was estimated that there would be 25,800 cases and 5,800 deaths from CMM in the United States. The exact cause of the increase in unknown, but there is evidence to suggest that increasing exposure to the ultraviolet B (UVB) radiation present in sunlight may be partly responsible. The evidence includes: 1. the fact that higher CMM incidence rates are observed in people with lesser amounts of skin pigment (which blocks penetration of UV); 2. a correlation of higher CMM rates with decreasing latitude and increasing UVB levels; 3. the observation that freckles and nevi (precursors to CMM) are induced by solar exposure; 4. differences in CMM rates between natives and immigrants to sunny climates; 5. high rates of CMM in patients who cannot repair UVB-induced DNA damage; and 6. the indication that sun exposure at early ages and of an intermittent nature results in higher CMM risks. With the concern that depletion of stratospheric ozone could result in increasing levels of UVB, it has become important to understand the relationship between UVB and CMM in order to estimate the increases in CMM that would be expected with ozone depletion. When empirical relationships between UVB and CMM incidence and mortality rates were derived and used to estimate the impact of stratospheric ozone depletion, a 1% depletion of ozone was predicted to result in increases of 1%-2% in CMM incidence and 0.8%-1.5% in CMM mortality.

There are only a few reports on the relative biological effectiveness (RBE) of thermal neutrons and 10B(n,alpha)7Li reactions either in vitro or in vivo. The data in this paper summarize almost all previously published in vitro data. Because only a few reactors are available for biomedical purposes, it is difficult to make a comparison of data from experiments using the same kind of radiation, and also to make a comparison of data from experiments using the different kinds of radiations. However, it is indispensable for boron neutron capture therapy to make a radiobiological analysis. More intensive study, including repair process and oxygen effect, is necessary for establishing the fundamental basis of the clinical application of boron neutron capture therapy.