Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0025202 (melanoma)
 69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Production of the pigment eumelanin is controlled by alpha-melanocyte stimulating hormone (alpha-MSH) stimulation of melanocortin 1 receptor (Mc1r), whereas production of pheomelanin results from agouti antagonism of alpha-MSH signalling through Mc1r. The role of agouti in mouse pigmentation has been extensively investigated but a role for agouti signalling protein (ASIP) in human pigmentation has not been determined. To determine whether ASIP regulates known melanogenic genes in humans, ASIP was over-expressed in a human melanoma cell line. Levels of mRNA and protein were measured in genes known to be up or down-regulated by agouti in the mouse, namely microphthalmia (Mitf), tyrosinase (Tyr), tyrosinase-related protein 1 (Tyrp1), dopachrome tautomerase (Dct), Mc1r, silver, initiation transcription factor 2 (Itf2) and mini chromosome maintenance protein 6 (Mcm6). These melanogenic genes were not found to be significantly up or down-regulated by ASIP at the transcriptional level in human melanoma cells. However, ASIP down-regulation of tyrp1 was observed at the translational level. To identify novel genes that may be regulated by ASIP in melanoma cells, microarrays were used to determine differences in gene expression between the control and ASIP transfected melanoma cells. The expression level of human RNAs were determined by microarray analysis using a 19,200 cDNA and a 19,200 oligonucleotide array representing 13,000 and 18,864 individual genes, respectively. Genes observed to be modulated by ASIP were confirmed by quantitative real-time polymerase chain reaction. Results identify five genes, namely PPARbeta, eIF-4B, RRM2, MINOR and EVI2B that are down-regulated by ASIP, indicating a likely role for ASIP in human melanogenesis.
 ...
PMID:Agouti signal protein regulation in human melanoma cells. 1251 27

In this article, some of the advantages and limitations of DNA microarray technologies for gene expression profiling are summarized. As a model experiment, DermArray DNA microarrays were utilized to identify potential biomarkers of cultured normal human melanocytes in two different experimental comparisons. In the first case, melanocyte RNA was compared with vastly dissimilar non-melanocytic RNA samples of normal skin keratinocytes and fibroblasts. In the second case, melanocyte RNA was compared with a primary cutaneous melanoma line (MS7) and a metastatic melanoma cell line (SKMel-28). The alternative approaches provide dramatically different lists of 'normal melanocyte' biomarkers. The most robust biomarkers were identified using principal component analysis bioinformatic methods related to likelihood ratios. Only three of 25 robust biomarkers in the melanocyte-proximal study (i.e. melanocytes vs. melanoma cells) were coincidentally identified in the melanocyte-distal study (i.e. melanocytes vs. non-melanocytic cells). Selected up-regulated biomarkers of melanocytes (i.e. TRP-1, melan-A/MART-1, silver/Pmel17, and nidogen-2) were validated by qRT-PCR. Some of the melanocytic biomarkers identified here may be useful in molecular diagnostics, as potential molecular targets for drug discovery, and for understanding the biochemistry of melanocytic cells.
 ...
PMID:DNA microarrays and likelihood ratio bioinformatic methods: discovery of human melanocyte biomarkers. 1275 97

A phase I clinical trial was conducted in patients with stage III/IV breast cancer who were treated with the anti-idiotype mAb 1E10 specific to an Ab1 mAb able to react specifically with N-glycolyl-containing gangliosides and with antigens expressed on human melanoma and breast carcinoma cells. Patients were treated with 1 or 2 mg of aluminum hydroxide-precipitated 1E10 mAb every other week for six injections. Two patients at each dose were reimmunized 7-9 months after completing the induction phase. In hyperimmune sera from eight of the nine patients who received at least four doses of anti-Id vaccine preparations, strong specific responses were observed both against 1E10 mAb and NeuGc-GM3 ganglioside (Ab3 Id+Ag+). Nonclassical Ab1' antibodies (Id-Ag+) were also elicited by 1E10 mAb vaccine treatment. There were no differences between the two levels of dose tested in relation to toxicity and immunogenicity. No evidence of serious or unexpected effects was observed.
 ...
PMID:Immune responses in breast cancer patients immunized with an anti-idiotype antibody mimicking NeuGc-containing gangliosides. 1276 76

To exploit alloreactive T-cell responses known as the graft-versus-tumor effect, allogeneic hematopoietic stem cell transplantation is being explored as experimental therapy in selected solid tumors, including metastatic melanoma. However, donor T-cell responses are often delayed and associated with severe graft-versus-host disease. Posttransplant adoptive immunotherapy using tumor-specific cytotoxic T lymphocytes (CTL) of donor origin might provide immediate graft-versus-tumor effects but not graft-versus-host disease. Therefore, the aim of the current study was to define in vitro conditions for the expansion of allogeneic major histocompatibility complex-matched CTLs targeting melanoma-associated antigens (MAA). The CTLs were generated from peripheral blood mononuclear cells (PBMCs) of HLA-A*0201+ healthy donors by repetitive stimulations with HLA-A*0201-restricted MAA-derived peptides. Melanoma reactivity, as determined by lysis of peptide-pulsed T2 cells and HLA-A2+/Ag+ melanoma cells, was detected using in vitro expanded CTL targeting MAA peptides AAGIGILTV(MT(27-35)), IMDQVPFSV(G(209-2M)), and YMDGTMSQV(T(368-376)). In contrast, FLWGPRALV(MAGE3(271)-(279)) and VLPDVFIRCV(GnT-V(nt38-67)) induced peptide-specific recognition of T2 target cells only, whereas ITDQVPFSV(G(209-217)), KTWGQYWQV(G9(154)), MLLAVLYCL(T(1-9)), and tumor lysate could not induce specific CTLs. Specific cytolytic activity was accompanied by interferon-gamma secretion. Peptide-pulsed dendritic cells were required only for the initial stimulation of CTLs and could be substituted by PBMCs during restimulations. The median expansion rate of CTL was five to six times, regardless of whether dendritic cells or PBMCs were used after the initial stimulation. The results delineate the conditions for effective ex vivo expansion of melanoma-specific CTLs from PBMCs of healthy donors to be used as an adjunct in allogeneic cell therapy of metastatic melanoma.
 ...
PMID:Generation of melanoma-specific cytotoxic T lymphocytes for allogeneic immunotherapy. 1280 79

Beta-ray emitting Ru-106/Rh-106 ophthalmic applicators have been used for close to 4 decades in the treatment of choroidal melanoma. The form factor of these applicators is a spherically concave silver bowl with an inner radius of curvature between 12 and 14 mm, and a total shell thickness of 1 mm. The radioactive nuclide is deposited in a layer 0.1 mm below the concave surface of the applicator. Calculation of dose distributions for clinical treatment planning purposes is complicated by the concave nature of the distributed source, the asymmetric shape of the active region of some applicators, imperfections in the manufacturing process which can result in an inhomogeneous distribution of activity across the active surface, and absorption and scatter in the 0.1 mm layer of silver which seals and protects the radioactive layer. A semi-empirical method of calculating dose distributions for these applicators is described which is fundamentally compatible with treatment planning systems that use the AAPM TG43 brachytherapy formalism. Dose to water is estimated by summing a "patch source" dose function over a discrete number of overlapping patches uniformly distributed over the active surface of the applicator. The patch source dose function differs conceptually from a point source dose function in that it is intended to represent the macroscopic behavior of a small, disk-like region of the applicator. The patch source dose function includes an anisotropy term to account for angular variation in absorption and scatter as particles traverse the 0.1 mm silver window. It geometrically models the nearfield of a patch with properties akin to both a small disk and infinite plane, and models the farfield as if the patch were a point. This allows a manageable number of discrete patches (300 to 1000) to provide accuracy appropriate for clinical treatment planning. This approach has the advantages of using familiar concepts and data structures, it is computationally quick, and it readily adapts to asymmetric applicator shapes and inhomogeneities in the radionuclide distribution. A method for optimizing the patch source dose function parameters is presented, and the dosimetric calculations are compared with published Monte Carlo calculations and measurements.
 ...
PMID:A patch source model for treatment planning of ruthenium ophthalmic applicators. 1285 46

We report a case of silver tattooing of the nasal mucosa in a silver polisher. The concern in such cases is mainly due to the suspicion of melanoma. The diagnosis was confirmed by using the Laser Ablation Inductively Coupled Plasma Mass Spectrometry (LA-ICP-MS) method, which revealed the presence of two types of silver isotopes, at 107 and 109 m/z.
 ...
PMID:The Sheffield nose--an occupational disease? 1286 81

Even in the twenty-first century, welding is still a common and a highly skilled occupation. The hazardous agents associated with welding processes are acetylene, carbon monoxide, oxides of nitrogen, ozone, phosgene, tungsten, arsenic, beryllium, cadmium, chromium, cobalt, copper, iron, lead, manganese, nickel, silver, tin, and zinc. All welding processes involve the potential hazards for inhalation exposures that may lead to acute or chronic respiratory diseases. According to literature described earlier it has been suggested that welding fumes cause the lung function impairment, obstructive and restrictive lung disease, cough, dyspnea, rhinitis, asthma, pneumonitis, pneumoconiosis, carcinoma of the lungs. In addition, welding workers suffer from eye irritation, photokeratitis, cataract, skin irritation, erythema, pterygium, non-melanocytic skin cancer, malignant melanoma, reduced sperm count, motility and infertility. Most of the studies have been attempted previously to evaluate the effects of welding fumes. However, no collectively effort illuminating the general effects of welding fumes on different organs or systems or both in human has not been published. Therefore, the aim of this review is to gather the potential toxic effects of welding fumes documented by individual efforts and provide informations to community on hazards of welding.
 ...
PMID:Health hazards of welding fumes. 1464 49

Melanosomes, specific organelles produced only by melanocytes, undergo a unique maturation process that involves their transition form amorphous rounded vesicles to fibrillar ellipsoid organelles, during which they move from the perinuclear to the distal areas of the cells. This depends upon the trafficking and processing of gp100 (also known as Pmel17 and the silver protein), a protein of great interest, because it elicits immune responses in melanoma patients but in which specific function(s) remains elusive. In this study, we have used biochemical and immunochemical approaches to more critically assess the synthesis, processing, glycosylation, and trafficking of gp100. We now report that gp100 is processed and sorted in a manner distinct from other melanosomal proteins (such as tyrosinase, Tyrp1 and Dct) and is predominantly delivered directly to immature melanosomes following its rapid processing in the endoplasmic reticulum and cis-Golgi. Following its arrival, gp100 is cleaved at the amino and at the carboxyl termini in a series of specific steps that result in the reorganization of immature melanosomes to the fibrillar mature melanosomes. Once this structural reorganization occurs, melanogenic enzymes begin to be targeted to the melanosomes, which are then competent to synthesize melanin pigment.
 ...
PMID:Epitope mapping of the melanosomal matrix protein gp100 (PMEL17): rapid processing in the endoplasmic reticulum and glycosylation in the early Golgi compartment. 1509 15

Ultraviolet radiation stimulates pigmentation in human skin, but the mechanism(s) whereby this increase in melanin production (commonly known as tanning) occurs is not well understood. Few studies have examined the molecular consequences of UV on human skin of various racial backgrounds in situ. We investigated the effects of UV on human skin of various races before and at different times after a single 1 minimal erythemal dose UV exposure. We measured the distribution of DNA damage that results, as well as the melanin content/distribution and the expression of various melanocyte-specific genes. The density of melanocytes at the epidermal:dermal junction in different types of human skin are remarkably similar and do not change significantly within 1 wk after UV exposure. The expression of melanocyte-specific proteins (including TYR (tyrosinase), TYRP1 (tyrosinase-related protein 1), DCT (tyrosinase-related protein 2), MART1 (melanoma antigens recognized by T-cells) gp100 (Pmel17/silver), and MITF (micropthalmia transcription factor)) increased from 0 to 7 d after UV exposure, but the melanin content of the skin increased only slightly. The most significant change, however, was a change in the distribution of melanin from the lower layer upwards to the middle layer of the skin, which was more dramatic in the darker skin. These results provide a basis for understanding the origin of different skin colors and responses to UV within different races.
 ...
PMID:Mechanisms of skin tanning in different racial/ethnic groups in response to ultraviolet radiation. 1595 11

We have previously generated a murine anti-idiotype (Ab2) monoclonal antibody (mAb) to a murine Ab1 mAb, named P3, which selectively binds Neu-glycolyl (NeuGc)-sialic acid on several monosialo- and disialogangliosides, and also reacts with sulfatides and antigens expressed in human melanoma and breast tumors. This Ab2 mAb, designated as 1E10, induced anti-anti-idiotype antibodies (Ab3) in mice and cancer patients. These Ab3 generated by 1E10 mAb were characterized by bearing P3 mAb idiotopes (Ab3, Id +). But when the specificity of these Ab3 antibodies was tested, no specific humoral response against NeuGc-containing gangliosides was detected in sera from immunized mice. However, hyperimmune sera from melanoma and breast cancer patients vaccinated with this Ab2 mAb were able to react specifically with these gangliosides. The different expression of NeuGc-containing gangliosides in the normal tissues of mice and humans could explain these results. In order to demonstrate these findings in other animal species with a different NeuGc-sialic acid expression, we performed similar studies in monkeys and chickens. In monkeys, as in most mammals, NeuGc-containing gangliosides are self-antigens. In contrast, chickens, like humans, lack the expression of these antigens in normal tissues. Here we report that the antibody response against NeuGc-containing gangliosides induced by immunization with 1E10 mAb was completely different in both species. No specific antibody response against these gangliosides was detected in hyperimmune monkey sera. In contrast, a strong and specific Ab3 response against GM3(NeuGc) and GM2(NeuGc) gangliosides (Ab3, Ag+) was generated in chickens due to the administration of 1E10 mAb.
 ...
PMID:Generation of anti-Neu-glycolyl-ganglioside antibodies by immunization with an anti-idiotype monoclonal antibody: A self versus non-self-matter. 1607 30


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>