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Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Eight common nevi and 11 dysplastic nevi were evaluated for the presence of basic fibroblast growth factor, platelet-derived growth factor, transforming growth factor-alpha, interleukin-1-alpha, and interleukin-1-beta by immunohistochemical labelling with highly specific monoclonal antibodies. Basic fibroblast growth factor was abundant in the nevus cells and keratinocytes of nevi. Dysplastic nevus cells on average stained less intensely for basic fibroblast growth factor than did common nevus cells. In both types of nevi, basic fibroblast growth factor was identified in the basement membranes at the dermoepidermal junction and surrounding nevus cell nests and individual nevus cells. Labelling of nevus cells for transforming growth factor-alpha was variable, while there was moderate labelling for platelet-derived growth factor and light labelling for interleukin-1-alpha. Only two nevi, both dysplastic, stained (very faintly) for interleukin-1-beta. It is possible that these cytokines, especially basic fibroblast growth factor, act in autocrine fashion to maintain nevocellular growth and may also contribute to the epidermal hyperplasia and fibrosis frequently observed in nevi.
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PMID:Immunohistochemical localization of cytokines in nevi. 794 49

Basic fibroblast growth factor (bFGF) is a mitogen for normal human melanocytes and keratinocytes in culture. Experiments in vitro suggest that keratinocytes supply bFGF to melanocytes through a paracrine mechanism and that the aberrant expression of bFGF in melanomas confers growth independence from bFGF-producing cells. To determine whether bFGF is expressed in vivo, we examined a series of benign and malignant melanocytic lesions in situ using bFGF riboprobes on tissue sections, and correlated bFGF expression with histologic phenotype. Seventeen melanocytic neoplasms were studied, including four common acquired nevi, four dysplastic nevi, four primary malignant melanomas, and five metastatic melanomas. Nevic cells in benign intradermal nevi showed low signal intensity (1+), whereas compound and dysplastic nevi showed 2+ to 3+ expression in the junctional nevic cell population and 1+ expression in the dermal nevic cell population. Melanocytes in primary melanomas had intermediate (2+) and those in metastatic melanomas had low (1+) levels of bFGF gene transcripts. Fibroblasts expressed high levels (3+) and epidermal and adnexal keratinocytes moderate (2+) levels of bFGF in all cases studied. Basic FGF expression in endothelial cells, known to produce and respond to this growth factor in vitro, was lower than that in the fibroblast and keratinocyte cell population and, in 10 of 17 cases, no bFGF mRNA was detectable. This study shows that bFGF is expressed in nevomelanocytes in vivo in all melanocytic lesions studied and thus cannot be used as a marker for transformation. The presence of bFGF gene transcripts in the various dermal cell types and in keratinocytes suggests that it may act as an autocrine and paracrine growth factor in regulating cellular proliferation in the skin.
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PMID:Localization of basic fibroblast growth factor mRNA in melanocytic lesions by in situ hybridization. 200 52

Recent evidence suggests that TGF beta, a substance synthetized and released by Retinal Pigment Epithelial (RPE) cells, might play a role in fibrotic preretinal proliferation. We measured the concentration of this factor by radioreceptor assay in samples of vitreous obtained from 17 patients by vitrectomy. Seven had uncomplicated Retinal Detachment (RD) and 10 had either Proliferative Vitreoretinopathy (PVR) or Epimacular Membranes (EM). In the RD group, the mean concentration of TGF beta was 0.06 p mole/ml of vitreous, and in the PVR group, 0.21 p mole/ml. The total mitogenic activity of native vitreous and the amounts of a and b FGF in each sample were also measured, but were not different in the 2 groups. These results suggest that TGF beta is involved in the mechanism of excessive repair which characterises preretinal proliferation.
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PMID:[Transforming growth factor beta in the vitreous of patients with epiretinal proliferation]. 225 Sep 41

Basic fibroblast growth factor (bFGF) is an angiogenic and mitogenic polypeptide produced by diverse cell types including cell lines derived from malignant melanomas but not from normal melanocytes. However, there is no consensus concerning in vivo expression of bFGF in melanocytic lesions due in part to the small numbers of cases studied to date. To evaluate further the possible differential expression of bFGF in melanocytic lesions, we examined 110 formalin-fixed, paraffin-embedded metastatic and primary invasive melanomas, melanomas in situ, nevi with architectural disorder and cytological atypia, and ordinary benign melanocyte nevi by nucleic acid in situ hybridization. All metastatic and primary invasive melanomas studied expressed bFGF mRNA, whereas melanomas in situ and benign melanocyte nevi were negative. Melanomas in situ with features of tumor regression and a majority of nevi with architectural disorder and cytological atypia also contained bFGF mrNA. The results suggest that in vivo bFGF expression is not requisite for malignant transformation per se, but appears to correlate more with invasion or fibroblastic reactions adjacent to the melanocyte lesions.
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PMID:Differential expression of basic fibroblast growth factor (bFGF) in melanocytic lesions demonstrated by in situ hybridization. Implications for tumor progression. 831 Nov 16

We analyzed fatty acid make up of cells and organs from autoimmune and immunologically normal mice to determine whether intrinsic differences in composition might be associated with an inflammatory phenotype. Macrophages (MO) isolated from 4-6-week-old MRL lpr/lpr mice were cultured with phorbol ester (PMA), fibroblast growth factor-1 (FGF-1), fibroblast growth factor-2 (FGF-2) and medium control to determine whether these cell signals might induce membrane fatty acid changes. Individual phospholipid analysis showed 8.4- and 5.1-fold increases in phosphatidylcholine arachidonate (20:4) mole % over baseline values following culture with FGF-1 and FGF-2, respectively. Unfractionated analysis on kidney and liver extracts from 4-6 week MRL lpr/lpr, 16-20 week lpr and 12-20 week MRL +/-/+/- mice demonstrated no significant intrastrain fatty acid differences. Higher levels of 20:4 in 4-6 week lpr mice were noted compared to 16-20 week lpr or +/+ mice in kidney, and liver samples (P < 0.05). It is possible that membrane changes precipitated by microenvironmental cytokine concentrations may contribute to the expression of autoimmune disease in this model.
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PMID:Environmental influences on fatty acid composition of membranes from autoimmune MRL lpr/lpr mice. 880 29

In a previous study, we showed by immunohistochemical analysis that basic fibroblast growth factor (bFGF) is expressed strongly and homogeneously in naevus-cell naevus (NCN), while that in malignant melanoma (MM) is heterogeneous and sometimes non-existent. In order to elucidate the role of bFGF in these pigmented tumours, the expression of its receptors must be determined. In this study, we performed an immunohistochemical analysis of FGF receptors 1, 2 and 3 (FGFR-1, FGFR-2 and FGFR-3, respectively) in NCN and MM and compared their expression and localization with those of bFGF. The expression of bFGF and its three receptors was also examined in melanoma cell lines. None of the 10 NCN that showed strong, homogeneous staining for bFGF expressed FGFR-1 or FGFR-3 proteins; six weakly expressed FGFR-2 protein. Ten primary and 10 metastatic MM showed heterogeneous expression for the three receptors, with larger populations of FGFR-3-negative cells in the primary than in the metastatic tumours. Western blot analysis showed homogeneous expression of bFGF protein in all four melanoma cell lines tested, while FGFR proteins had a heterogeneous distribution in the different cell lines. Cultured NCN and normal melanocytes showed no immunoreactive band for FGFR-1 protein, the only protein tested. Our results suggested that tumour-derived bFGF is involved in melanoma formation through an autocrine mechanism, but is involved mostly through a paracrine or other mechanisms in NCN.
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PMID:Expression of fibroblast growth factor receptors in naevus-cell naevus and malignant melanoma. 929 79

Melanocytes, the pigment forming cells of the skin, form an almost nonproliferating cell population located to the lowermost part of the epidermis. Normally melanocytes are not found higher in the epidermis or in the dermis. Nevi consist of melanocytes with altered growth characteristics and localization. The common pigmented nevus, a benign skin lesion, develops when melanocytes proliferate in the dermo-epidermal junction or in the dermis. Here we report growth characteristics of in vitro cultured normal human melanocytes and dermal nevus-derived melanocytes. As previously reported, nevus cells have a moderate to high FGF-2 expression level. Here we demonstrate that dermal nevus cells are able to survive in three-dimensional type 1 collagen culture, while normal human melanocytes rapidly undergo apoptosis. Melanocytes also, however, survive in collagen cultures in the presence of exogenous FGF-2. The survival of nevus cells in collagen is suppressed by protamine, an inhibitor of FGF-mediated cell stimulation. The in vivo growth environment of dermal nevus cells consists largely of type I and type III collagens. The results suggest that FGF-2 expression by nevus cells allows them to adapt to grow in the dermis. FGF-2 obviously has importance as a melanocyte survival factor and probably also in the development of malignant melanoma.
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PMID:FGF expression allows nevus cells to survive in three-dimensional collagen gel under conditions that induce apoptosis in normal human melanocytes. 1041 28

Basic fibroblast growth factor (bFGF or FGF-2) is produced by nearly all melanomas in vitro and in vivo but not by normal melanocytes, which require exogenous bFGF for growth. In this study, we transduced normal human melanocytes to overexpress two forms of bFGF: (bFGF-Long and bFGF-Short) using replication-deficient adenovirus 5 vectors. bFGF-Long induced the 17.8, 22.5, 23.1 and 24.2 kDa forms of bFGF, whereas bFGF-Short induced only the 17.8 kDa mature form. Growth of cultured melanocytes transduced with either vector was similar to that of nevus and melanoma cells and was independent of exogenous bFGF and of insulin/insulin-like growth factor 1, and cyclic AMP enhancers, requiring only phorbol ester as an exogenous mitogen. Like primary melanoma cells, transduced normal melanocytes grew anchorage independently in soft agar. When injected into the dermis of human skin grafted to mice, bFGF-transduced melanocytes proliferated for at least 20 days, whereas cells from control cultures showed poor survival and no proliferation. These results demonstrate that bFGF upregulation is a critical component in melanoma progression.
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PMID:Basic fibroblast growth factor induces a transformed phenotype in normal human melanocytes. 1059 49

Acne in Apert syndrome and unilateral segmental acneiform nevus are associated with mutations of fibroblast growth factor receptor 2 (FGFR2), which are likely to be involved in the pathogenesis of acne. Translational animal and cellular models, developmental biology studies and clinical observations have contributed to our understanding of FGF-FGFR2 signaling in the pilosebaceous follicle. The importance of FGF-FGFR2 signaling in mesenchymal-epithelial interaction for skin appendage formation, pilosebaceous follicle homeostasis, comedogenesis and sebaceous gland proliferation is explored. Overstimulation of FGFR2 signaling with increased expression of interleukin-1alpha explains acne in Apert syndrome und nevus comedonicus. Androgen-mediated up-regulation of FGFR2 signaling could be the initiating signal in the pathogenesis of acne. The gain of function FGFR2 mutations in Apert syndrome and unilateral acneiform nevus are most helpful model diseases for uncovering the fundamental process of androgen-dependent mesenchymal-epithelial FGF-FGFR2 signaling in acne in Apert syndrome, nevus comedonicus and acne vulgaris.
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PMID:FGFR2 signaling and the pathogenesis of acne. 1900 61

Increased fibroblast growth factor receptor-2 (FGFR2) signaling has been proposed to be involved in acne pathogenesis and explains acne lesions in Apert syndrome and unilateral acneiform nevus associated with gain-of-function point mutations of FGFR2. If, indeed, increased FGFR2 signaling plays a major pathogenic role in follicular hyperkeratinization and sebaceous gland hypertrophy in acne, effective anti-acne drugs may attenuate increased FGFR2 signaling. The purpose of this article is to elucidate the hypothesis that known anti-acne agents may operate by downregulation of increased FGFR2 signaling. Anti-androgens suppress FGF-ligand expression, benzoyl peroxide induces FGFR2 downregulation by lysosomal receptor degradation, azelaic acid inhibits mitochondrial ATP formation required for receptor tyrosine kinase phosphorylation, tetracyclines inhibit the expression, and activity of FGFR2b downstream matrix metalloproteinases, and retinoids attenuate the FGFR2 pathway at several regulatory levels of the signal transduction cascade critical for cell cycle control, cell proliferation, differentiation, and lipogenesis. Erythromycin, a P-450 inhibitor, may interfere with FGFR2 signaling by its inhibitory effect on retinoid catabolism. The gain-of-function mutations of FGFR2 in Apert syndrome and unilateral acneiform nevus, and the proposed synergistic inhibitory interactions of anti-acne agents at various levels of the FGFR2-signaling cascade underline the role of FGFR2 signaling in the pathogenesis of acne.
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PMID:Anti-acne agents attenuate FGFR2 signal transduction in acne. 1922 42


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