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)

Fibrin plays an important role in wound healing and regeneration, and enjoys widespread use in surgery and tissue engineering. The enzymatic activity of Factor XIIIa was employed to covalently incorporate exogenous bioactive peptides within fibrin during coagulation. Fibrin gels were formed with incorporated peptides from laminin and N-cadherin alone and in combination at concentrations up to 8.2 mol peptide per mole of fibrinogen. Neurite extension in vitro was enhanced when gels were augmented with exogenous peptide, with the maximal improvement reaching 75%. When this particular fibrin derivative was evaluated in rats in the repair of the severed dorsal root within polymeric tubes, the number of regenerated axons was enhanced by 85% relative to animals treated with tubes filled with unmodified fibrin. These results demonstrate that it is possible to enhance the biological activity of fibrin by enzymatically incorporating exogenous oligopeptide domains of morphoregulatory proteins.
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PMID:Enzymatic incorporation of bioactive peptides into fibrin matrices enhances neurite extension. 1074 22

Recent advances in mouse genetics have identified molecular changes that are critical for melanocyte maturation and differentiation. This review briefly summarizes the current knowledge of distinct steps in melanocyte development, and identifies for each step the most important molecules such as the growth factors stem cell factor and endothelin-3, with their respective receptors. Classical cadherins, i.e. E-cadherin, N-cadherin and P-cadherin, determine melanocyte positioning in the skin. During naevus and melanoma development, the two growth factor signalling pathways are downregulated, whereas cadherin expression shifts concomitantly with re-positioning of the naevus and melanoma cells in the skin. Loss of E-cadherin and gain of N-cadherin by melanoma cells has profound consequences for the regulatory cross-talk between various types of cells in the skin. Naevus and melanoma cells that do not express E-cadherin are resistant to control by keratinocytes and establish close communications with fibroblasts and endothelial cells. However, forced expression of E-cadherin in melanoma cells can reverse the malignant phenotype by re-establishing the control of keratinocytes over the melanoma cells. Even highly aggressive metastatic melanoma cells can be signalled to turn off the expression of genes associated with tumour invasion and metastasis, suggesting that this strategy could be utilized in the therapy of melanoma.
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PMID:Lessons from melanocyte development for understanding the biological events in naevus and melanoma formation. 1098 64

Slug (Snai2), a member of the Snail family of zinc finger transcription factors, plays a role in the epithelial-to-mesenchymal transformation (EMT) that occurs during melanocyte emigration from the neural crest. A role for Slug in the EMT-like loss of cell adhesion and increased cell motility exhibited during melanoma progression has also been proposed. Our immunohistochemical studies of melanoma arrays, however, revealed that Slug expression was actually higher in nevi than in primary or metastatic melanomas. Moreover, Slug expression in melanomas was not associated with decreased expression of E-cadherin, the canonical Slug target in EMT. Comparisons of endogenous Slug and E-cadherin expression in cultured normal human melanocytes and melanoma cell lines supported our immunohistochemical findings. Expression of exogenous Slug in melanocytes and melanoma cells in vitro, however, suppressed E-cadherin expression, enhanced N-cadherin expression, and stimulated cell migration and invasion. Interestingly, both in tumors and cultured cell lines, there was a clear relationship between expression of Slug and MITF, a transcription factor known to regulate Slug expression during development. Taken together, our findings suggest that Slug expression during melanomagenesis is highest early in the process and that persistent Slug expression is not required for melanoma progression. The precise role of Slug in melanomagenesis remains to be elucidated and may be related to its interactions with other drivers of EMT, such as Snail.
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PMID:Slug expression during melanoma progression. 2250 51

Methyl-CpG binding domain protein 3 (MBD3) belongs to the methyl-CpG binding protein family. MBD3 facilitates the initiation of neural stem cell reprogramming. Melanoma originates in melanocytes derived from neural crest stem cells; therefore, we investigated the role of MBD3 in melanoma. MBD3 was overexpressed in melanoma compared with pigmented nevi. MBD3 knockdown had no effect on the proliferation of melanoma cells (A375 and A2058 cells). Contrarily, it significantly reduced the migration and invasion of A375 cells, but had no significant effect on A2058 cells. Furthermore, MBD3 knockdown reduced N-cadherin protein levels and matrix metalloproteinase-2 (MMP-2) activity in A375 cells, but had no significant effect on A2058 cells. Based on these results, the MBD3 expression level may be a useful biomarker for the diagnosis of melanoma. Thus, MBD3 has potential as a novel therapeutic target for some melanoma patients.
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PMID:Methyl-CpG binding domain protein 3: a new diagnostic marker and potential therapeutic target of melanoma. 3296 82