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Query: UMLS:C0025202 (melanoma)
 69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The incidence rate of malignant melanoma has shown a rapid worldwide rise in recent years. The staging and management of head and neck melanoma presents some unique challenges. Surgery remains the cornerstone of treatment, while sentinel node biopsy is the most accurate staging modality for regional disease. The complex regional anatomy and lymphovascular drainage of this region may account for the increased biologic aggressiveness and treatment challenges of this disease. Improved understanding of the radiobiology of melanoma has resulted in new adjuvant radiotherapy approaches, yielding improved control rates. The treatment outcomes of metastatic head and neck melanoma remain disappointing but important progress has been made in the understanding of melanoma biology.
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PMID:Cutaneous head and neck melanoma: the old and the new. 1836 88

Melanoma is a highly invasive tumor with elevated mortality rates. Progression and aggressiveness appear related to the achievement of an angiogenic phenotype. Melanoma cells express several angiogenic factors, including fibroblast growth factor (FGF)-1 and FGF-2. The autocrine production and release of FGFs and the subsequent activation of FGF receptors, have a central role in melanoma tumor progression. We demonstrated that FGF-1 is secreted from a human melanoma cell line, A375, under conditions of serum deprivation. The release of FGF-1 is inhibited by the copper chelator ammonium tetrathiomolybdate, suggesting a role of copper in the secretory pathway, and is triggered by activation of phosphatidylinositol 3-kinase (PI3K)/Akt intracellular signaling. Interestingly, overexpression or activation of Akt has been correlated with poor prognosis in melanoma patients. Our data indicate a novel role for Akt in supporting the progression of human melanomas and advocate the need for new treatments targeting PI3K/Akt signaling pathway, to control tumor development and progression.
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PMID:The release of fibroblast growth factor-1 from melanoma cells requires copper ions and is mediated by phosphatidylinositol 3-kinase/Akt intracellular signaling pathway. 1840 Mar 76

Transforming growth factor-beta (TGF-beta) plays a complex role during carcinogenesis. It may either act as a tumor suppressor through its broad antiproliferative potential or as a tumor promoter either via direct effects on tumor cell aggressiveness or indirectly by modulating stromal responses, angiogenesis and immune surveillance. Increased production of TGF-beta by cancer cells is often associated with tumor grade. Melanoma cells largely escape cell cycle arrest normally induced by TGF-beta in normal melanocytes, yet produce active TGF-beta and are capable of efficient transcriptional responses to the growth factor. In this review, we summarize the current knowledge about the role played by TGF-beta in melanoma progression and hypothesize about the appropriateness of targeting TGF-beta signaling for therapeutic intervention.
Pigment Cell Melanoma Res 2008 Apr
PMID:Transforming growth factor-beta in cutaneous melanoma. 1851 May 88

Poly(ADP-ribose) polymerase (PARP)-1, which plays a key role in DNA repair, inflammation and transcription, has recently been shown to be involved in angiogenesis. The aim of this study was to investigate PARP-1 role in melanoma aggressiveness and chemoresistance in vivo using clones stably silenced for PARP-1 expression. Whilst the growth characteristics of PARP-1-deficient melanoma cells were comparable to those of PARP-1-proficient cells in vitro, their tumourigenic potential in vivo was significantly compromised. In fact, mice challenged intra-muscle with PARP-1-deficient cells showed a delayed development of measurable tumour nodules, which were also significantly reduced in size with respect to those of mice inoculated with PARP-1-proficient cells. Moreover, animals challenged intra-cranially with PARP-1-deficient cells, a model that mimics CNS localisation of melanoma, showed an increased survival. Immunohistochemical analyses of PARP-1-depleted melanoma grafts indicated a reduced expression of the angiogenesis marker PECAM-1/CD31 and of the pro-inflammatory mediators TNF-alpha and GITR. Notably, PARP-1-silenced melanoma was extremely sensitive to temozolomide, an anticancer agent used for the treatment of metastatic melanoma. These results provide novel evidence for a direct role of PARP-1 in tumour aggressiveness and chemoresistance.
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PMID:Stable depletion of poly (ADP-ribose) polymerase-1 reduces in vivo melanoma growth and increases chemosensitivity. 1844 Feb 22

While tumour incidence is known to augment with age, paradoxically tumour growth and metastasis were often found to proceed at a slower rate at late ages. This age-related biological behaviour of tumours actually imposes a differential therapeutic approach to the old cancer patient. Several mechanisms of the age-related reduced tumour progression have been demonstrated: decreased tumour cell proliferation, increased apoptotic cell death, decreased angiogenesis and anti-tumoural immune response changes. We postulated that it might be possible to design age-adjusted treatment modalities based on the mechanisms responsible for the reduced tumour progression rate in the aged. Based on these mechanisms, we compared the effect of different treatments (apoptosis-inducing agents, Hydrocortisone and Adriamycin, anti-angiogenic agent, TNP-470, and immunomodulators-Levamisole and BCG) on two experimental tumours (B16 melanoma and AKR lymphoma) growing in young and old mice. Most treatments showed, in both tumours, a higher inhibitory effect on tumours growing in old mice than on those developing in young ones, to our knowledge, a feature not described before for anti-tumoural agents. We suggest that designing ageing conditions in tumours of young patients might possibly alleviate neoplastic aggressiveness in these patients as well.
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PMID:Designing ageing conditions in tumour microenvironment-a new possible modality for cancer treatment. 1845 52

Metastasis is the deadliest phase of cancer progression. Experimental models using immunodeficient mice have been used to gain insights into the mechanisms of metastasis. We report here the identification of a "metastasis aggressiveness gene expression signature" derived using human melanoma cells selected based on their metastatic potentials in a xenotransplant metastasis model. Comparison with expression data from human melanoma patients shows that this metastasis gene signature correlates with the aggressiveness of melanoma metastases in human patients. Many genes encoding secreted and membrane proteins are included in the signature, suggesting the importance of tumor-microenvironment interactions during metastasis.
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PMID:Gene expression changes in an animal melanoma model correlate with aggressiveness of human melanoma metastases. 1850 21

Autotaxin (ATX) is a prometastatic enzyme initially isolated from the conditioned medium of human melanoma cells that stimulates a myriad of biological activities, including angiogenesis and the promotion of cell growth, survival, and differentiation through the production of lysophosphatidic acid (LPA). ATX increases the aggressiveness and invasiveness of transformed cells, and ATX levels directly correlate with tumor stage and grade in several human malignancies. To study the role of ATX in the pathogenesis of malignant melanoma, we developed antibodies and small-molecule inhibitors against recombinant human protein. Immunohistochemistry of paraffin-embedded human tissue shows that ATX levels are markedly increased in human primary and metastatic melanoma relative to benign nevi. Chemical screens identified several small-molecule inhibitors with binding constants ranging from nanomolar to low micromolar. Cell migration and invasion assays with melanoma cell lines show that ATX markedly stimulates melanoma cell migration and invasion, an effect suppressed by ATX inhibitors. The migratory phenotype can be rescued by the addition of the enzymatic product of ATX, LPA, confirming that the observed inhibition is linked to suppression of LPA production by ATX. Chemical analogues of the inhibitors show structure-activity relationships important for ATX inhibition and indicate pathways for their optimization. These studies suggest that ATX is an approachable molecular target for the rational design of chemotherapeutic agents directed against malignant melanoma.
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PMID:Identification of small-molecule inhibitors of autotaxin that inhibit melanoma cell migration and invasion. 1885 38

Galectin-3 is a ss-galactoside-binding lectin. It participates in a variety of normal and pathologic processes, including cancer progression. In this study, we evaluated the pattern of expression of galectin-3 in cutaneous squamous cell carcinoma (SCC) and basal cell carcinoma (BCC), and its correlation with the grade of differentiation in SCC and tumor size. Galectin-3 expression was evaluated by immunohistochemistry in 31 SCCs, 30 BCCs, and 29 non-tumoral skin samples. Galectin-3 expression was higher in normal epidermis than in non-melanoma skin cancers, except for cytoplasmic immunoreactivity in SCC. Cytoplasmic galectin-3 immunoreactivity was significantly higher than nuclear immunoreactivity in non-melanoma skin cancers. Cytoplasmic galectin-3 immunoreactivity was significantly higher in SCC than in both circumscribed and infiltrative BCCs, but no difference was detected between these two types of BCC. Cytoplasmic galectin-3 immunoreactivity predominated within SCCs (p=0.000), and a positive correlation was detected between tumor size and cytoplasmic immunoreactivity (r=0.385, p=0.043). There was no correlation between galectin-3 staining and tumor differentiation and lymph node metastasis. Decreased nuclear galectin-3 expression and cytoplasmic immunoreactivity in tumors are important factors in the progression from the normal to the cancerous state in non-melanoma skin cancers. We speculate that cytoplasmic galectin-3 expression may be one of the factors that contribute to tumor aggressiveness in SCC.
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PMID:Immunohistochemical galectin-3 expression in non-melanoma skin cancers. 1895 31

Malignant melanoma is a cancer whose incidence is rising rapidly. Extensive studies of primary tumors and tumor-derived cell lines revealed that inappropriate activation of signal transducer and activator of transcription (STAT) proteins, particularly of STAT3 and 5, occurs with high frequency in various human cancers. We reported that in the Xiphophorus fish melanoma model, constitutive activation of STAT5 correlates with the aggressiveness of melanoma. Investigations in human melanoma mainly focussed on the function of STAT1, but we have shown recently that STAT5 is also activated in human melanoma. The objectives of this investigation were to get more information about the function of STAT5 in melanoma. Here we demonstrate that in murine melanocytes activation of STAT5 measured by its tyrosine phosphorylation and translocation to the nucleus parallels upregulation with its target gene bcl-XL. This indicates a role for STAT5 in antiapoptotic signaling in pigment cells. In human melanoma cell lines, we found that constitutive activation of STAT5 correlates with expression of bcl-XL. Expression of dominant negative STAT5 in the human melanoma cell line A375 leads to a reduced bcl-XL expression and a dramatic increase of apoptotic cells. In contrast to STAT1, which is known to transduce antiproliferative effects of interferons, our data support a significant role for STAT5 in melanoma cell proliferation and survival via the activation of the antiapoptotic protein bcl-XL. Keeping in mind that interferons activate both STAT proteins, STAT5 activation could be of importance in interferon resistance of melanoma.
Melanoma Res 2008 Dec
PMID:STAT5 contributes to antiapoptosis in melanoma. 1901 10

Increased expression of autotaxin in tumors including glioblastoma, breast, renal, ovarian, lung, and thyroid cancers is associated with increased tumor aggressiveness. Autotaxin promotes metastasis as well as cell growth, survival, and migration of cancer cells. These actions could depend on the noncatalytic effects of autotaxin on cell adhesion, or the catalytic activity of autotaxin, which converts lysophosphatidylcholine into lysophosphatidate in the extracellular fluid surrounding the tumor. Both lysophosphatidylcholine (LPC) and lysophosphatidate have been reported to stimulate migration through their respective G-protein coupled receptors. The present study determines the roles of autotaxin, LPC, and lysophosphatidate in controlling the migration of two cancer cell lines: MDA-MB-231 breast cancer cells, which produce little autotaxin and MDA-MB-435 melanoma cells that secrete significant levels of autotaxin. LPC alone was unable to stimulate the migration of either cell type unless autotaxin was present. Knocking down autotaxin secretion, or inhibiting its catalytic activity, blocked cell migration by preventing lysophosphatidate production and the subsequent activation of LPA(1/3) receptors. We conclude that inhibiting autotaxin production or activity could provide a beneficial adjuvant to chemotherapy for preventing tumor growth and metastasis in patients with high autotaxin expression in their tumors.
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PMID:Inhibition of autotaxin production or activity blocks lysophosphatidylcholine-induced migration of human breast cancer and melanoma cells. 1920 29


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