Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Different results have been reported on the expression of epidermal growth factor receptor (EGFR) in human melanocytic lesions, which may be due to different methodologic approaches. Therefore, we compared EGFR expression in six human melanoma cell lines by utilizing the monoclonal antibodies 2E9, 425, and 225, applying four immunocytochemical staining procedures. The results were compared with those obtained by a multiple point ligand binding assay. In addition, Northern blot analysis was performed. A three-step immunoperoxidase method using the monoclonal antibody 2E9 proved most sensitive. Staining intensities, estimated semiquantitatively, correlated well with the quantitative data obtained by the ligand-binding assay. Expression on the mRNA level was also in agreement with these results. Immunohistochemical staining of a large series of human cutaneous melanocytic lesions using the method selected showed differential EGFR expression in various stages of melanocytic tumor progression: 19% of common nevocellular nevi; 61% of dysplastic nevi, 89% of primary cutaneous melanomas, and 91% of melanoma metastases showed staining of the melanocytic cells. Intralesional heterogeneity of EGFR expression was present. Although the mean percentage of positive melanocytic cells in positive lesions did not increase with progression, mean staining intensity was stronger in malignant lesions compared to benign lesions. Ligand binding assays showed that EGFR expression in the highly metastasizing cell lines MV3 and BLM was at least 40 times higher than in the cell lines IF6, 530, M14, and Mel57, which do not or only sporadically metastasize after subcutaneous inoculation in nude mice. Although the differences between the various stages of progression are not absolute, we provide further evidence that EGFR expression increases in human melanocytic tumor progression.
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PMID:Increasing epidermal growth factor receptor expression in human melanocytic tumor progression. 162 28

The osmotic water permeability Pf of brush border (BBM) and basolateral (BLM) membrane vesicles from rat small intestine and renal cortex was studied by means of stopped-flow spectrophotometry. Scattered light intensity was used to follow vesicular volume changes upon osmotic perturbation with hypertonic mannitol solutions. A theoretical analysis of the relationship of scattered light intensity and vesicular volume justified a simple exponential approximation of the change in scattered light intensity. The rate constants extracted from fits to an exponential function were proportional to the final medium osmolarity as predicted by theory. For intestinal membranes, computer analysis of optical responses fitted well with a single-exponential treatment. For renal membranes a double-exponential treatment was needed, implying two distinct vesicle populations. Pf values for BBM and BLM preparations of small intestine were equal and amount to 60 microns/sec. For renal preparations, Pf values amount to 600 microns/sec for the fast component, BBM as well as BLM, and to 50 (BBM) and 99 (BLM) microns/sec for the slow component. The apparent activation energy for water permeation in intestinal membranes was 13.3 +/- 0.6 and in renal membranes 1.0 +/- 0.3 kCal/mole, between 25 and 35 degrees C. The mercurial sulfhydryl reagent pCMBS inhibited completely and reversibly the high Pf value in renal brush border preparations. These observations suggest that in intestinal membranes water moves through the lipid matrix but that in renal plasma membranes water channels may be involved. From the high Pf values of renal membrane vesicles a transcellular water permeability for proximal tubules can be calculated which amounts to approximately 1 cm/sec. This value allows for an entirely transcellular route for water flow during volume reabsorption.
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PMID:Osmotic water permeabilities of brush border and basolateral membrane vesicles from rat renal cortex and small intestine. 376 62

The base-release activity of oxygen adduct of bleomycin-Fe(II) complex [BLM-Fe(II)] from DNA decreased with a half-life of 5.2 minutes, when incubated at 0 degrees C in 0.05 M Tris-HCl buffer at pH 7.8 in the absence of DNA. Under the same condition, however, visible and ESR spectra showed that the adduct was immediately converted into the ferric complex. The ESR study further indicated the simultaneous formation of two kinds of the low-spin BLM-Fe(III) complex. One of them disappeared in parallel with the decrease of the base-release activity and transformed into the other. The latter Fe(III) complex was stable but inactive. However, by addition of hydrogen peroxide to the latter, the former was regenerated and the base-release activity appeared. Oxygen concentration measurements by oxygraph showed that one mole of BLM-Fe(II) consumed approximately 0.5 mole of molecular oxygen instantly, but did not any more thereafter in the absence of a reducing agent. While in the presence of 2-mercaptoethanol, the oxygen consumption proceeded biphasically, and equimolar oxygen was consumed by BLM-Fe(II) in the first rapid reaction. These results suggest that oxygen adduct of BLM-Fe(II) is reduced by one electron transfer from an external electron donor and the resulting BLM-Fe(III)-O2H- [or its deprotonated form: BLM-Fe(III)-O2(2)-] shows the activity to break DNA accompanying the base-release.
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PMID:An active intermediate formed in the reaction of bleomycin-Fe(II) complex with oxygen. 616 29

Recombinant human erythropoietin (Epo) is used to prevent and treat tumor-related anemia and improve quality of life in cancer patients. Recent evidence suggested that Epo may adversely affect the survival of selected cancer patients by promoting tumor growth, inhibition of apoptosis, and induction of migration. Epo unfolds its effect on the Epo receptor (EpoR). We show--to the best of our knowledge for the first time--significantly increased EpoR expression in clinical melanoma metastases and primary melanomas in comparison with different sets of nevi by quantitative real-time reverse transcriptase-PCR, immunohistochemistry, and western blot analysis. When assessing the functionality of the EpoR-signaling pathway, recombinant human Epo led to the phosphorylation of JAK-2, signal transducers and activators of transcription 3 (STAT3), and ERK1/2 in several of the melanoma cell lines that were analyzed. Besides, Epo counteracted cisplatin-induced cell death in BLM and MV3 cells. Finally, Epo promoted cell migration of MV3 cells, whereas inhibition of the JAK/STAT and ERK1/2 pathways reduced Epo-mediated migration. In summary, we show the overexpression of functional EpoR expression in about half of the analyzed clinical melanoma metastasis specimens and show anti-apoptotic as well as pro-migratory effects of Epo, which is of importance for the treatment of anemia in advanced melanoma.
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PMID:Role of erythropoietin receptor expression in malignant melanoma. 1953 48

Melanoma progression is a multistep progression from a common melanocytic nevus through the radial growth phase, the invasive vertical growth phase finally leading to metastatic spread into distant organs. Migration and invasion of tumor cells requires secretion of proteases to facilitate remodeling of the extracellular matrix including basement membranes. Here we used a reconstructed skin model to investigate melanoma growth and invasion in vitro. Using this model we show that the dermoepidermal basement membrane prevents the invasion of metastatic melanoma BLM and MV3 cells in the absence of a stratified epidermis. In the reconstructed skin model, matrix metalloproteinase-9, a protease activated early in melanoma development, is secreted by the keratinocytes and subsequently activated by an unknown soluble factor secreted by the melanoma cells. The dynamic interplay between keratinocytes and melanoma cells is further shown by an altered growth pattern of melanoma cells and the finding that a reconstructed epidermis induces invasion. Overall, our findings show that the invasive behavior of melanoma cells is determined by the melanoma cells themselves, but that the interplay between surrounding keratinocytes and the melanoma cells plays an important role in melanoma invasion.
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PMID:Keratinocytes drive melanoma invasion in a reconstructed skin model. 2070 63

ALK-fused spitzoid neoplasms represent a distinctive group of melanocytic lesions. To date, few studies addressed genetic and chromosomal alterations in these lesions beyond the ALK rearrangements. Our objective was to study genetic alterations, including ALK gene fusions, telomerase reverse transcriptase promoter (TERT-p) mutations, chromosomal copy number changes, and mutations in other genes. We investigated 29 cases of Spitz lesions (11 Spitz nevi and 18 atypical Spitz tumors), all of which were ALK immunopositive. There were 16 female and 13 male patients, with age ranging from 1 to 43 years (mean, 18.4 years). The most common location was the lower extremity. Microscopically, all neoplasms were polypoid or dome shaped with a plexiform, predominantly dermally located proliferation of fusiform to spindled melanocytes with mild to moderate pleomorphism. The break-apart test for ALK was positive in 17 of 19 studied cases. ALK fusions were detected in 23 of 26 analyzable cases by Archer FusionPlex Solid Tumor Kit. In addition to the previously described rearrangements, 3 novel fusions, namely, KANK1-ALK, MYO5A-ALK, and EEF2-ALK, were found. Fluorescence in situ hybridization for copy number changes yielded one case with the loss of RREB1 among 21 studied cases. TERT-p hotspot mutation was found in 1 of 23 lesions. The mutation analysis of 271 cancer-related genes using Human Comprehensive Cancer Panel was performed in 4 cases and identified in each case mutations in several genes with unknown significance, except for a pathogenic variant in the BLM gene. Our study confirms that most ALK fusion spitzoid neoplasms can be classified as atypical Spitz tumors, which occurs in young patients with acral predilection and extends the spectrum of ALK fusions in spitzoid lesions, including 3 hitherto unreported fusions. TERT-p mutations and chromosomal copy number changes involving 6p25 (RRB1), 11q13 (CCND1), 6p23 (MYB), 9p21 (CDKN2A), and 8q24 (MYC) are rare in these lesions. The significance of mutation in other genes remains unknown.
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PMID:A Clinicopathological Study of 29 Spitzoid Melanocytic Lesions With ALK Fusions, Including Novel Fusion Variants, Accompanied by Fluorescence In Situ Hybridization Analysis for Chromosomal Copy Number Changes, and Both TERT Promoter and Next-Generation Sequencing Mutation Analysis. 3270 92