Disease relevance of Melanoma

• These results suggest that integrin alpha 4 beta 1 could play a role in controlling melanoma cell metastasis at the invasive stage [1].
• Vitamin C preferential toxicity for malignant melanoma cells [2].
• In contrast, B7-H1 is abundant in human carcinomas of lung, ovary and colon and in melanomas [3].
• Studies of the administration of interleukin-2 to patients with metastatic melanoma or kidney cancer have shown that immunological manipulations can mediate the durable regression of metastatic cancer [4].
• So IL-10 overexpression was found in certain tumors as melanoma and several lymphomas and is considered to promote further tumor development [5].
• Overall, 308 genes were identified that showed significant differential expression between primary melanomas and melanoma metastases (false discovery rate<or=0.05) [6].

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

• Adjuvant dacarbazine in cutaneous melanoma [15].
• Tamoxifen in malignant melanoma [16].
• The presence of estrogen receptors in melanomas has been suggested, and occasional responses to antiestrogen therapy have been reported [17].
• Interferon and cimetidine for malignant melanoma [18].
• A randomized trial of levamisole versus placebo as adjuvant therapy in malignant melanoma [19].
• We show that, by combining ad-PUMA and API-2 treatments, human melanoma tumor growth can be inhibited by >80% in vivo compared with controls [20].
• These results confirm the hypothesis that melanin-photosensitized radical production is the major causative step of melanoma in this model and demonstrate that the wavelengths and mechanisms of melanoma causation in different models are dependent on the presence of melanin [21].
• The transcription factor CCAAT/enhancer-binding protein homologous protein seemed to be involved in the up-regulation of TRAIL-R2 by tunicamycin, but its role varied between different melanoma lines [22].
• Using a specific RNA interference approach, the survival of bortezomib-treated melanoma cells was found to rely primarily on Mcl-1, and to a lesser extent on Bcl-x(L) (but not on Bcl-2) [23].
• The treatment of melanoma cells with TMECG also affected cellular folate transport and the gene expression of DHFR, which supported the antifolate nature of this compound [24].
• A trend toward improved clinical response in patients with NRAS-mutant melanoma treated with CPS was observed, possibly due to the effect of sorafenib on CRAF [25].
• Nilotinib may achieve disease control in patients with melanoma harboring KIT alterations and whose disease progressed after imatinib therapy [26].

Biological context of Melanoma

• A gene on chromosome 9p, p16INK4, has been implicated in the pathogenesis of cutaneous malignant melanoma in 19 melanoma-prone families [27].
• Germline mutations in the p16INK4a binding domain of CDK4 in familial melanoma [28].
• EWS and ATF-1 gene fusion induced by t(12;22) translocation in malignant melanoma of soft parts [29].
• To assess whether this insertional mutagenesis event results in alteration of transcriptional regulation, we analyzed Grm1 and two flanking genes for aberrant expression in melanomas from TG3 mice [30].
• Homozygotes for CDKN2 (p16) germline mutation in Dutch familial melanoma kindreds [31].

Anatomical context of Melanoma

• The recent detection of p16INK4 (MTS1) mutations in familial melanoma kindreds, many human tumour cell lines, and primary tumours is consistent with this idea [32].
• Although we did not detect its expression in normal mouse melanocytes, Grm1 was ectopically expressed in the melanomas from TG3 mice [30].
• Tumor-infiltrating lymphocytes and interleukin-2 in melanomas [33].
• MMP-2 and alpha v beta 3 were specifically colocalized on angiogenic blood vessels and melanoma cells in vivo [34].
• A p16INK4a-insensitive CDK4 mutant targeted by cytolytic T lymphocytes in a human melanoma [35].

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

• Tamoxifen and chemotherapy for refractory metastatic malignant melanoma [45].
• Use of tumor-infiltrating lymphocytes and interleukin-2 in the immunotherapy of patients with metastatic melanoma. A preliminary report [46].
• BCL2's regulation by Mitf was verified in melanocytes and melanoma cells and by chromatin immunoprecipitation of the BCL2 promoter [36].
• METHODS: In a double-blind study of 40 patients with malignant melanoma who were eligible for high-dose interferon alfa therapy, we randomly assigned 20 patients to receive the antidepressant paroxetine and 20 to receive placebo [47].
• Lentiviral vector retargeting to P-glycoprotein on metastatic melanoma through intravenous injection [48].

References