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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
MeSH Review


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Disease relevance of Melanoma


Psychiatry related information on Melanoma

  • Thus, melanoma cells, like other epidermal cells, exhibit the capacity to release the immunomodulating cytokine IL-1 and, therefore, probably have the potency to influence host defense mechanisms directed against malignant melanoma [7].
  • PURPOSE: A study was performed to assess the usefulness of a radiolabeled monoclonal antibody (MoAb; technetium 99m NR-ML-05 Fab) as a detecting agent, as well as to evaluate its role in the overall decision-making process in the management of cutaneous malignant melanoma [8].
  • The relationship between dietary habits and subsequent risk of cutaneous malignant melanoma (CMM) was studied in 25,708 men and 25,049 women aged 16-56 years attending a Norwegian health screening in 1977-1983 [9].
  • On whole body images, the anti-Fab HMWA appears to be more tumor selective than Fab preparations that target the p97 antigen for melanoma, and there is less uptake in liver [10].
  • Variables associated with self-detected melanomas were female sex, young age, absence of atypical nevi, knowledge of the ABCD rule, habit of performing skin self-examination [11].

High impact information on Melanoma

  • Differentiation antigens coded by genes such as tyrosinase are also recognized on human melanoma by autologous CTL [12].
  • A gene family named MAGE codes for antigens recognized by autologous CTL on a melanoma tumor [12].
  • Melanomas also commonly show impairment of the p16(INK4A)-CDK4-Rb and ARF-HDM2-p53 tumor suppressor pathways [13].
  • TERT amplification also occurs in melanoma [13].
  • These findings indicate that melanocyte-specific factors present before neoplastic transformation can have a pivotal role in governing melanoma progression [14].

Chemical compound and disease context of Melanoma


Biological context of Melanoma


Anatomical context of Melanoma


Gene context of Melanoma

  • Mutations associated with familial melanoma impair p16INK4 function [32].
  • Clinically, primary human melanoma expression microarrays revealed tight nearest neighbor linkage for MITF and BCL2 [36].
  • This linkage helps explain the vital roles of both Mitf and Bcl2 in the melanocyte lineage and the well-known treatment resistance of melanoma [36].
  • Activating mutations in one RAF gene, BRAF, have been found in a high proportion of melanomas and in a small fraction of other cancers [37].
  • Screening of primary tumours and linkage analysis of familial melanoma pedigrees have identified many potential mutations in p16, but the functional significance of these sequence variants has remained unclear [38].
  • Treatment of GRM1-expressing human melanoma cells with a GRM1 antagonist (LY367385 or BAY36-7620) or a glutamate release inhibitor (riluzole) leads to a suppression of cell proliferation as well as a decrease in levels of extracellular glutamate [39].
  • Mechanistic studies showed that inhibition of (V600E)B-Raf significantly reduced the constitutive secretion of IL-8 from melanoma cells as well as the capacity of endogenous IL-8 production from the melanoma-PMN microenvironment [40].
  • In a novel mouse model for melanoma, stabilized beta-catenin bypasses the requirement for p16(Ink4a) mutations and, together with an activated N-Ras oncogene, leads to melanoma with high penetrance and short latency [41].
  • A monoclonal antibody reactive with the N-terminal tail of EDNBR was found to internalize rapidly into melanoma cells [42].
  • Results show that KIT mutations are more common in vulvar melanomas than other types of mucosal melanomas and that both the RAF/MEK/ERK and PI3K/AKT pathways are activated in mucosal melanoma specimens [43].
  • Our study reveals a novel mechanism that TAMs enhance angiogenesis and melanoma growth via ADM and provides potential targets for melanoma therapies [44].

Analytical, diagnostic and therapeutic context of Melanoma


  1. Expression of the integrin alpha 4 beta 1 on melanoma cells can inhibit the invasive stage of metastasis formation. Qian, F., Vaux, D.L., Weissman, I.L. Cell (1994) [Pubmed]
  2. Vitamin C preferential toxicity for malignant melanoma cells. Bram, S., Froussard, P., Guichard, M., Jasmin, C., Augery, Y., Sinoussi-Barre, F., Wray, W. Nature (1980) [Pubmed]
  3. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Dong, H., Strome, S.E., Salomao, D.R., Tamura, H., Hirano, F., Flies, D.B., Roche, P.C., Lu, J., Zhu, G., Tamada, K., Lennon, V.A., Celis, E., Chen, L. Nat. Med. (2002) [Pubmed]
  4. Progress in human tumour immunology and immunotherapy. Rosenberg, S.A. Nature (2001) [Pubmed]
  5. Interleukin-10 therapy--review of a new approach. Asadullah, K., Sterry, W., Volk, H.D. Pharmacol. Rev. (2003) [Pubmed]
  6. Gene expression signatures for tumor progression, tumor subtype, and tumor thickness in laser-microdissected melanoma tissues. Jaeger, J., Koczan, D., Thiesen, H.J., Ibrahim, S.M., Gross, G., Spang, R., Kunz, M. Clin. Cancer Res. (2007) [Pubmed]
  7. Expression and release of interleukin-1 by different human melanoma cell lines. Köck, A., Schwarz, T., Urbanski, A., Peng, Z., Vetterlein, M., Micksche, M., Ansel, J.C., Kung, H.F., Luger, T.A. J. Natl. Cancer Inst. (1989) [Pubmed]
  8. Role of technetium 99m-labeled monoclonal antibody in the management of melanoma patients. Blend, M.J., Ronan, S.G., Salk, D.J., Gupta, T.K. J. Clin. Oncol. (1992) [Pubmed]
  9. Diet and risk of cutaneous malignant melanoma: a prospective study of 50,757 Norwegian men and women. Veierød, M.B., Thelle, D.S., Laake, P. Int. J. Cancer (1997) [Pubmed]
  10. Use of I-131 labeled, murine Fab against a high molecular weight antigen of human melanoma: preliminary experience. Larson, S.M., Carrasquillo, J.A., McGuffin, R.W., Krohn, K.A., Ferens, J.M., Hill, L.D., Beaumier, P.L., Reynolds, J.C., Hellström, K.E., Hellström, I. Radiology. (1985) [Pubmed]
  11. Self-detected cutaneous melanomas in Italian patients. Carli, P., De Giorgi, V., Palli, D., Maurichi, A., Mulas, P., Orlandi, C., Imberti, G., Stanganelli, I., Soma, P., Dioguardi, D., Catricala, C., Betti, R., Paoli, S., Bottoni, U., Lo Scocco, G., Scalvenzi, M., Giannotti, B. Clin. Exp. Dermatol. (2004) [Pubmed]
  12. Tumor antigens recognized by T lymphocytes. Boon, T., Cerottini, J.C., Van den Eynde, B., van der Bruggen, P., Van Pel, A. Annu. Rev. Immunol. (1994) [Pubmed]
  13. Use of human tissue to assess the oncogenic activity of melanoma-associated mutations. Chudnovsky, Y., Adams, A.E., Robbins, P.B., Lin, Q., Khavari, P.A. Nat. Genet. (2005) [Pubmed]
  14. The melanocyte differentiation program predisposes to metastasis after neoplastic transformation. Gupta, P.B., Kuperwasser, C., Brunet, J.P., Ramaswamy, S., Kuo, W.L., Gray, J.W., Naber, S.P., Weinberg, R.A. Nat. Genet. (2005) [Pubmed]
  15. Adjuvant dacarbazine in cutaneous melanoma. Runne, U., Pullmann, H., Féaux de Lacroix, W. N. Engl. J. Med. (1983) [Pubmed]
  16. Tamoxifen in malignant melanoma. Nesbit, R.A., Woods, R.L., Tattersall, M.H., Fox, R.M., Forbes, J.F., MacKay, I.R., Goodyear, M. N. Engl. J. Med. (1979) [Pubmed]
  17. Treatment of metastatic malignant melanoma with dacarbazine plus tamoxifen. Cocconi, G., Bella, M., Calabresi, F., Tonato, M., Canaletti, R., Boni, C., Buzzi, F., Ceci, G., Corgna, E., Costa, P. N. Engl. J. Med. (1992) [Pubmed]
  18. Interferon and cimetidine for malignant melanoma. Hill, N.O., Pardue, A., Khan, A., Hill, R.W., Aleman, C., Hilario, R., Hill, J.M., Osther, K. N. Engl. J. Med. (1983) [Pubmed]
  19. A randomized trial of levamisole versus placebo as adjuvant therapy in malignant melanoma. Spitler, L.E., Sagebiel, R. N. Engl. J. Med. (1980) [Pubmed]
  20. Role of p53 up-regulated modulator of apoptosis and phosphorylated Akt in melanoma cell growth, apoptosis, and patient survival. Karst, A.M., Dai, D.L., Cheng, J.Q., Li, G. Cancer Res. (2006) [Pubmed]
  21. UV causation of melanoma in Xiphophorus is dominated by melanin photosensitized oxidant production. Wood, S.R., Berwick, M., Ley, R.D., Walter, R.B., Setlow, R.B., Timmins, G.S. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  22. Tunicamycin sensitizes human melanoma cells to tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis by up-regulation of TRAIL-R2 via the unfolded protein response. Jiang, C.C., Chen, L.H., Gillespie, S., Kiejda, K.A., Mhaidat, N., Wang, Y.F., Thorne, R., Zhang, X.D., Hersey, P. Cancer Res. (2007) [Pubmed]
  23. Therapeutic window for melanoma treatment provided by selective effects of the proteasome on Bcl-2 proteins. Wolter, K.G., Verhaegen, M., Fernández, Y., Nikolovska-Coleska, Z., Riblett, M., de la Vega, C.M., Wang, S., Soengas, M.S. Cell Death Differ. (2007) [Pubmed]
  24. Melanoma activation of 3-o-(3,4,5-trimethoxybenzoyl)-(-)-epicatechin to a potent irreversible inhibitor of dihydrofolate reductase. Sánchez-del-Campo, L., Tárraga, A., Montenegro, M.F., Cabezas-Herrera, J., Rodríguez-López, J.N. Mol. Pharm. (2009) [Pubmed]
  25. Correlation of somatic mutations and clinical outcome in melanoma patients treated with Carboplatin, Paclitaxel, and sorafenib. Wilson, M.A., Zhao, F., Letrero, R., D'Andrea, K., Rimm, D.L., Kirkwood, J.M., Kluger, H.M., Lee, S.J., Schuchter, L.M., Flaherty, K.T., Nathanson, K.L. Clin. Cancer Res. (2014) [Pubmed]
  26. Phase II Study of Nilotinib in Melanoma Harboring KIT Alterations Following Progression to Prior KIT Inhibition. Carvajal, R.D., Lawrence, D.P., Weber, J.S., Gajewski, T.F., Gonzalez, R., Lutzky, J., O'Day, S.J., Hamid, O., Wolchok, J.D., Chapman, P.B., Sullivan, R.J., Teitcher, J.B., Ramaiya, N., Giobbie-Hurder, A., Antonescu, C.R., Heinrich, M.C., Bastian, B.C., Corless, C.L., Fletcher, J.A., Hodi, F.S. Clin. Cancer Res. (2015) [Pubmed]
  27. Increased risk of pancreatic cancer in melanoma-prone kindreds with p16INK4 mutations. Goldstein, A.M., Fraser, M.C., Struewing, J.P., Hussussian, C.J., Ranade, K., Zametkin, D.P., Fontaine, L.S., Organic, S.M., Dracopoli, N.C., Clark, W.H. N. Engl. J. Med. (1995) [Pubmed]
  28. Germline mutations in the p16INK4a binding domain of CDK4 in familial melanoma. Zuo, L., Weger, J., Yang, Q., Goldstein, A.M., Tucker, M.A., Walker, G.J., Hayward, N., Dracopoli, N.C. Nat. Genet. (1996) [Pubmed]
  29. EWS and ATF-1 gene fusion induced by t(12;22) translocation in malignant melanoma of soft parts. Zucman, J., Delattre, O., Desmaze, C., Epstein, A.L., Stenman, G., Speleman, F., Fletchers, C.D., Aurias, A., Thomas, G. Nat. Genet. (1993) [Pubmed]
  30. Melanoma mouse model implicates metabotropic glutamate signaling in melanocytic neoplasia. Pollock, P.M., Cohen-Solal, K., Sood, R., Namkoong, J., Martino, J.J., Koganti, A., Zhu, H., Robbins, C., Makalowska, I., Shin, S.S., Marin, Y., Roberts, K.G., Yudt, L.M., Chen, A., Cheng, J., Incao, A., Pinkett, H.W., Graham, C.L., Dunn, K., Crespo-Carbone, S.M., Mackason, K.R., Ryan, K.B., Sinsimer, D., Goydos, J., Reuhl, K.R., Eckhaus, M., Meltzer, P.S., Pavan, W.J., Trent, J.M., Chen, S. Nat. Genet. (2003) [Pubmed]
  31. Homozygotes for CDKN2 (p16) germline mutation in Dutch familial melanoma kindreds. Gruis, N.A., van der Velden, P.A., Sandkuijl, L.A., Prins, D.E., Weaver-Feldhaus, J., Kamb, A., Bergman, W., Frants, R.R. Nat. Genet. (1995) [Pubmed]
  32. Mutations associated with familial melanoma impair p16INK4 function. Ranade, K., Hussussian, C.J., Sikorski, R.S., Varmus, H.E., Goldstein, A.M., Tucker, M.A., Serrano, M., Hannon, G.J., Beach, D., Dracopoli, N.C. Nat. Genet. (1995) [Pubmed]
  33. Tumor-infiltrating lymphocytes and interleukin-2 in melanomas. Sondel, P.M., Sosman, J.A., Hank, J.A., Kohler, P.C., Storer, B. N. Engl. J. Med. (1989) [Pubmed]
  34. Localization of matrix metalloproteinase MMP-2 to the surface of invasive cells by interaction with integrin alpha v beta 3. Brooks, P.C., Strömblad, S., Sanders, L.C., von Schalscha, T.L., Aimes, R.T., Stetler-Stevenson, W.G., Quigley, J.P., Cheresh, D.A. Cell (1996) [Pubmed]
  35. A p16INK4a-insensitive CDK4 mutant targeted by cytolytic T lymphocytes in a human melanoma. Wölfel, T., Hauer, M., Schneider, J., Serrano, M., Wölfel, C., Klehmann-Hieb, E., De Plaen, E., Hankeln, T., Meyer zum Büschenfelde, K.H., Beach, D. Science (1995) [Pubmed]
  36. Bcl2 regulation by the melanocyte master regulator Mitf modulates lineage survival and melanoma cell viability. McGill, G.G., Horstmann, M., Widlund, H.R., Du, J., Motyckova, G., Nishimura, E.K., Lin, Y.L., Ramaswamy, S., Avery, W., Ding, H.F., Jordan, S.A., Jackson, I.J., Korsmeyer, S.J., Golub, T.R., Fisher, D.E. Cell (2002) [Pubmed]
  37. Tumorigenesis: RAF/RAS oncogenes and mismatch-repair status. Rajagopalan, H., Bardelli, A., Lengauer, C., Kinzler, K.W., Vogelstein, B., Velculescu, V.E. Nature (2002) [Pubmed]
  38. Tumour-derived p16 alleles encoding proteins defective in cell-cycle inhibition. Koh, J., Enders, G.H., Dynlacht, B.D., Harlow, E. Nature (1995) [Pubmed]
  39. Metabotropic glutamate receptor 1 and glutamate signaling in human melanoma. Namkoong, J., Shin, S.S., Lee, H.J., Marín, Y.E., Wall, B.A., Goydos, J.S., Chen, S. Cancer Res. (2007) [Pubmed]
  40. Targeting mutant (V600E) B-Raf in melanoma interrupts immunoediting of leukocyte functions and melanoma extravasation. Liang, S., Sharma, A., Peng, H.H., Robertson, G., Dong, C. Cancer Res. (2007) [Pubmed]
  41. Beta-catenin induces immortalization of melanocytes by suppressing p16INK4a expression and cooperates with N-Ras in melanoma development. Delmas, V., Beermann, F., Martinozzi, S., Carreira, S., Ackermann, J., Kumasaka, M., Denat, L., Goodall, J., Luciani, F., Viros, A., Demirkan, N., Bastian, B.C., Goding, C.R., Larue, L. Genes Dev. (2007) [Pubmed]
  42. An antibody-drug conjugate targeting the endothelin B receptor for the treatment of melanoma. Asundi, J., Reed, C., Arca, J., McCutcheon, K., Ferrando, R., Clark, S., Luis, E., Tien, J., Firestein, R., Polakis, P. Clin. Cancer Res. (2011) [Pubmed]
  43. KIT Pathway Alterations in Mucosal Melanomas of the Vulva and Other Sites. Omholt, K., Grafström, E., Kanter-Lewensohn, L., Hansson, J., Ragnarsson-Olding, B.K. Clin. Cancer Res. (2011) [Pubmed]
  44. Tumor-Associated Macrophages Promote Angiogenesis and Melanoma Growth via Adrenomedullin in a Paracrine and Autocrine Manner. Chen, P., Huang, Y., Bong, R., Ding, Y., Song, N., Wang, X., Song, X., Luo, Y. Clin. Cancer Res. (2011) [Pubmed]
  45. Tamoxifen and chemotherapy for refractory metastatic malignant melanoma. McKeage, M.J., Lorentzos, A., Gore, M.E. N. Engl. J. Med. (1993) [Pubmed]
  46. Use of tumor-infiltrating lymphocytes and interleukin-2 in the immunotherapy of patients with metastatic melanoma. A preliminary report. Rosenberg, S.A., Packard, B.S., Aebersold, P.M., Solomon, D., Topalian, S.L., Toy, S.T., Simon, P., Lotze, M.T., Yang, J.C., Seipp, C.A. N. Engl. J. Med. (1988) [Pubmed]
  47. Paroxetine for the prevention of depression induced by high-dose interferon alfa. Musselman, D.L., Lawson, D.H., Gumnick, J.F., Manatunga, A.K., Penna, S., Goodkin, R.S., Greiner, K., Nemeroff, C.B., Miller, A.H. N. Engl. J. Med. (2001) [Pubmed]
  48. Lentiviral vector retargeting to P-glycoprotein on metastatic melanoma through intravenous injection. Morizono, K., Xie, Y., Ringpis, G.E., Johnson, M., Nassanian, H., Lee, B., Wu, L., Chen, I.S. Nat. Med. (2005) [Pubmed]
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