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LOW DOSE IFN WITH VS WITHOUT HIGH DOSE IFN
In a RCT (n=674), the addition of a high dose interferon alpha (HDI) induction phase to a 2-year low-dose adjuvant IFN treatment schedule did not improve the survival.
Source: Hauschild A, J Clin Oncol 2009, Epub ahead of print
JASPINE-B ANTI-MELANOMA EFFECT
In an in vitro model, Jaspine-B (a derivative of a marine sponge) inhibits sphingomyelin synthase (SMS, which converts ceramide into sphingomyelin) and induces melanoma cell apoptosis.
Source: Salma Y, Biochem Pharmacol 2009, Epub ahead of print
EB1 REGULATES MELANOMA MIGRATION
In an in vitro model, inhibition of microtubule end binding protein EB1 decreases melanoma migration by interfering with the balance between lamellipodial and filopodial protrusion.
Source: Schober JM, Cancer Lett 2009, Epub ahead of print
HN1 EXPRESSION AND MELANOMA DIFFERENTIATION
In murine melanoma cells, inhibition of HN1 expression a differentiated phenotype that includes increased melanogenesis and cell cycle arrest.
Source: Laughlin KM, Differentiation 2009, Epub ahead of print
PCR POSITIVITY OF SENTINEL LYMPH NODES
In a small series of patients histologically negative SLN (n=76), tyrosinase gene expression (detected by PCR) correlates with overall but not disease free survival.
Source: Cao MG, Clin Exp Dermatol 2009, Epub ahead of print
STEREOTACTIC RADIOTHERAPY FOR UVEAL MELANOMA
In a small series of patients (n=64), stereotactic radiotherapy offers a non-invasive alternative to enucleation and brachytherapy at the expense of a higher toxicity rate.
Source: Krema H, Br J Ophthalmol 2009, Epub ahead of print
LIMB INFUSION IN STAGE IV MELANOMA
Isolated limb infusion (ILI) can be used as palliative treatment in stage IV melanoma patients with advanced, symptomatic limb disease.
Source: Kroon HM, Ann Surg Oncol 2009, 16:1193-201
MICROSCOPIC SATELLITOSIS
Microscopic satellitosis is associated with higher likelihood of lymph node metastasis and lower survival rate.
Source: Kimsey TF, Ann Surg Oncol 2009, 16:1176-83
CARBOPLATIN, VINORELBINE AND IL-2
In a phase II trial (n=22), carboplatin + vinorelbine + subcutaneous IL-2 yielded partial response and stable disease in one and nine patients, respectively.
Source: Vuoristo MS, Anticancer Res 2009, 29:1755-9
PREDICTION OF RESPONSE TO HACE
Angiographic pattern (infiltrative vs nodular) predicts survival after hepatic arterial chemoembolization (HACE) for liver metastasis from uveal melanoma.
Source: Dayani PN, Arch Ophthalmol 2009, 127:628-32
RAPAMYCIN-LY294002: FAILED SYNERGISM
In an in vitro model, LY294002 suppresses AKT activation by rapamycin (due to mTOR complex-2 activation) but without significant impact on rapamycin anti-melanoma efficacy.
Source: Werzowa J, Br J Dermatol 2009, 160:955-64
MART-1 EPITOPE LOW EXPRESSION
Melan-A/MART-1 is one of the most frequently used targets for anti-melanoma vaccines in HLA-A2+ patients: however, its expression is lost in many melanoma cell lines.
Source: Sorensen RB, Cancer Immunol Immunother 2009, 58:665-75
ANTI-MELANOMA VACCINE PROLONGS SURVIVAL
In a phase III randomized controlled trial, gp100:209-217(210M) peptide vaccination prolongs survival of metastatic melanoma patients treated with IL-2 (as compared to IL-2 alone).
Source: Schwartzentruber DJ, J Clin Oncol 27:18s, 2009 (suppl; abstr CRA9011)
ELESCLOMOL PLUS PACLITAXEL TRIAL
In a phase III randomized controlled trial, elesclomol does not significantly improve progression free survival of metastatic melanoma patients treated with paclitaxel (as compared to paclitaxel alone).
Source: Hauschild A, J Clin Oncol 27:18s, 2009 (suppl; abstr LBA9012)
SAA AND CRP AS PROGNOSTIC MARKERS
In a large series of stage I-IV melanoma patients (n=596), serum amyloid-A (SAA) and C-reactive protein (CRP) are independent prognostic factors.
Source: Findeisen P, J Clin Oncol 2009, 27:2199-208
PI3K: A CANDIDATE MELANOMA TARGET
In a large series (540 nevi and 523 melanomas), PI3K subunits p85 and p110 alpha are overexpressed in melanoma; pretreatment pS6 levels correlate with sensitivity to PI3K inhibitor LY294002.
Source: Aziz SA, Clin Cancer Res 2009, 15:3029-36
IFN-alpha AND STAT3 ACTIVATION
Analyzing 24 primary cultures established from melanoma lymph node metastasis, investigators found that in a subset of cases (17%) IFN-alpha activates STAT3, which in turn correlates with shorter disease free survival.
Source: Humpoliková-Adámková L, Eur J Cancer 2009, 45:1315-23
VEGFR3 AND MELANOMA PROGNOSIS
In a small series of patients with metastatic melanoma (n=60), tumoral expression and circulating levels of VEGFR3 (Flt-4) correlate negatively with prognosis.
Source: Mouawad R, Eur J Cancer 2009, 45:1407-14
SIROLIMUS AND CHEMOTHERAPY
In two patients with advanced melanoma, mTOR inhibitor sirolimus combined with paclitaxel and carboplatin yielded significant disease remission.
Source: Meier F, J Am Acad Dermatol 2009, 60:863-8
MASPIN, A CANDIDATE MELANOMA SUPPRESSOR
Maspin, a serpin peptidase inhibitor, is lost in the radial to vertical growth phase transition and inversely correlates with angiogenesis and melanoma thickness.
Source: Chu R, J Am Acad Dermatol 2009, 60:758-66
SUBMICROSCOPIC METASTASIS TO SENTINEL NODES
Patients harboring submicroscopic (less than 0.1 mm) disease in their sentinel lymph nodes (SLN) show poorer prognosis as compared to those with negative SLN.
Source: Olilla DW, J Am Coll Surg 2009, 208:924-9
MELANOMA KILLING BY NK CELLS
Natural cytotoxicity receptors (NCR) and DNAX accessory molecule-1 (DNAM-1) mediate natural killer (NK) cell recognition and lysis of human and mouse melanoma cell lines in vitro and in vivo.
Source: Lakshmikanth T, J Clin Invest 2009, 119:1251-63
PD-1 INHIBITS ANTI-MELANOMA IMMUNITY
In an in vitro human melanoma model, inhibition of co-inhibitory molecule PD-1 improves the expansion of NY-ESO-1 specific CD8+ T cells.
Source: Fourcade J, J Immunol 2009, 182:5240-9
PYRIMETHAMINE SYNERGIZES WITH TEMOZOLOMIDE
In an in vitro human melanoma model, pyrimethamine synergically increases the cytotoxicity of temozolomide via inhibition of folate metabolism.
Source: Chen M, Mol Cancer Res 2009, 7:703-12
XBP-1 AND MICROTUBULE-TARGETING DRUGS
Knockdown of XBP-1 (endoplasmic reticulum stress protein that activates the PI3K/Akt pathway) enhances docetaxel and vincristine-induced apoptosis of human melanoma cells.
Source: Jiang CC, Neoplasia 2009, 11:436-47
MSH MIMETIC FOR MELANOMA IMAGING
A novel radiolabeled MSH mimetic (CHX-A''-Re(Arg(11))CCMSH) has been developed in a mouse melanoma model for tumor imaging.
Source: Wei L, Nucl Med Biol 2009, 36:345-54
NOXA, ABT-737 AND CHEMOTHERAPY
Endogenous NOXA determines the strong proapoptotic synergism of ABT-737 (a BH3-mimetic) with chemotherapeutic agents in human melanoma cells.
Source: Weber A, Transl Oncol 2009, 2:73-83
MELANOMA PATHOLOGY REPORT IN EUROPE
A survey by the European Society of Pathology shows that melanoma pathology reports significantly vary across laboratories, although most key features are consistently reported.
Source: Batistatou A, Virchows Arch 2009, 454:505-511
MITF/SOX10 MUTATIONS IN MELANOMA
In 50 metastatic melanoma tumor lines, MITF pathway mutations are found in over 20% of cases, MITF and SOX10 being mutated in a mutually exclusive fashion.
Source: Cronin JC, Pigment Cell Melanoma Res 2009, Epub ahead of print
H-CADHERIN AND MELANOMA INVASIVENESS
Like E-cadherin, loss of H-cadherin expression (which occurs in 80% of melanoma cell lines tested) enhances melanoma invasiveness.
Source: Kuphal S, Pigment Cell Melanoma Res 2009, Epub ahead of print
SRC, PKC AND INTEGRIN Alpa V Beta3
In human melanoma cells, misregulated expression of PKC-alpha and PKC-delta and elevated SRC activity is required for efficient alpha V beta3-mediated invasion.
Source: Putnam AJ, Cell Commun Signal 2009, 7:10
REFLECTANCE CONFOCAL MICROSCOPY
In a series of 143 patients (154 skin tumors, of which 100 melanocytic and 54 non-melanocytic), reflectance confocal microscopy (RCM) can help diagnose skin melanoma.
Source: Segura S, J Am Acad Dermatol 2009, Epub ahead of print
PHOSPHATIDYLSERINE MICROVESCICLES
In a mouse model, tumor-derived microvesicles favor the establishment of melanoma metastasis in a phosphatidyl-dependent manner.
Source: Lima LG, Cancer Lett 2009, Epub ahead of print
NEW MOUSE MELANOMA MODEL
In a transgenic mouse expressing BRAF V600E targeted to melanocytes, melanoma develops most often when CDKN2A is lost and when AKT and MAPK pathways are overactivated.
Source: Goel VK, Oncogene 2009, Epub ahead of print
BORTEZOMIB, IFN-alpha AND STAT1
Bortezomib synergically increases interferon (IFN) alpha-induced apoptosis of melanoma cells, likely by prolonging IFN-alpha induced STAT1 phosphorylation.
Source: Lesinski GB, Cancer Immunol Immunother 2009, Epub ahead of print
SERUM PROTEOMIC PROFILE
Mass spectrometry-based proteomic profiling of melanoma patient's serum identified increased transthyretin and angiotensinogen (AGT) levels, while vitamin D binding protein (DBP) levels were decreased.
Source: Greco M, Cancer Lett 2009, Epub ahead of print
ID2, TGF-beta AND MELANOMA PROLIFERATION
Transition to increased aggressiveness in melanoma cells requires ID2 upregulation to suppress TGF-beta induction of p15(Ink4b) and thus circumvent TGF-beta-mediated inhibition of proliferation.
Source: Schlegel NC, Pigment Cell Melanoma Res 2009, Epub ahead of print
LUMICAN INHIBITS MELANOMA MIGRATION
Lumican (a small leucine-rich proteoglycan of the extracellular matrix) inhibits human melanoma cell migration via alterations of focal adhesion complexes.
Source: Brézillon S, Cancer Lett 2009, Epub ahead of print
CALPAIN-3 VARIANTS AND APOPTOSIS
Calpain-3 variants can play a pro-apoptotic role in melanoma cells and their downregulation, as observed in highly aggressive lesions, could contribute to melanoma progression.
Source: Moretti D, Carcinogenesis 2009, Epub ahead of print
MELANOMA EPIDEMIOLOGY CHANGES IN CANADA
In a Canadian study, melanoma incidence decreases in young people (less than 40y), is stable in middle age people (40-60y) and increases in older people (greater than 50y).
Source: Pruthi DK, J Am Acad Dermatol 2009, Epub ahead of print
APOPTOSIS GENES DYSREGULATED IN MELANOMA
High throughput analysis of gene expression reveals the presence of two types of malignant melanoma, each with a specific set of dysregulated survival-apoptosis genes.
Source: Su DM, Mol Cancer Ther 2009, Epub ahead of print
BAICALEIN AND MELANOMA PROLIFERATION
Baicalein induces proliferation inhibition in B16F10 murine melanoma cells by generating reactive oxygen species via 12-lipoxygenase (12-LOX).
Source: Chou DS, Free Radic Biol Med 2009, 46:1197-203
LOMEGUATRIB PLUS TEMOZOLOMIDE
In a phase I trial, lomeguatrib (a MGMT inhibitor) was evaluated in an extended dosing regimen with temozolomide, the results being disappointing (overall response rate = 6.25%).
Source: Kefford RF, Br J Cancer 2009, 100:1245-9
METASTATIC UVEAL MELANOMA: LACK OF EFFECTIVE THERAPY
In a review of the literature, investigators found no evidence of survival benefit of any method of treatment for any subgroup of patients with metastatic uveal melanoma.
Source: Augsburger JJ, Am J Ophthalmol 2009, Epub ahead of print
ATM INHIBITION FAVORS TRAIL APOPTOSIS
Suppression of an ataxia telangiectasia mutated (ATM)-dependent STAT3-mediated antiapoptotic pathway sensitizes human melanoma cells to TRAIL-mediated apoptosis.
Source: Ivanov VN, Cancer Res 2009, 69:3510-9
PHOSPHORYLATED 4E-BP1 AND PROGNOSIS
In patients with melanoma (n=72), high phosphorylated 4E-BP1 (a mRNA translation inhibitor targeted by both PI3K/AKT and RAS/BRAF) correlates with worse prognosis.
Source: O'Reilly KE, Clin Cancer Res 2009, 15:2872-8
MELANOMA MORTALITY IN IRELAND
Over the past few decades, melanoma incidence in Northen Ireland is rising both in males and females, but mortality rates are increasing in males only.
Source: Montella A, Eur J Cancer 2009, Epub ahead of print
CD11b+ CD15+ GRANULOCYTES IN UVEAL MELANOMA
Activated CD11b+ CD15+ granulocytes expand in the blood of uveal melanoma patients and may contribute to immune evasion by inhibiting T cell function.
Source: McKenna KC, Invest Ophthalmol Vis Sci 2009, Epub ahead of print
MINERVA/FAM129B AND MELANOMA
In a functional proteomics study, investigators identified MINERVA/FAM129B as a BRAF signaling target playing a key role in melanoma cell invasion into three-dimensional collagen matrix.
Source: Old WM, Mol Cell 2009, 34:115-31
BRAF(V600E) AND p16(INK4a)
Oncogenic BRAF induces melanocyte senescence and melanoma in mice; p16(INK4a) is not required to induce melanocyte senescence or for tumor progression (although it regulates tumor penetrance and latency).
Source: Dhomen N, Cancer Cell 2009, 15:294-303
SORAFENIB + CHEMOTHERAPY
In a phase III randomized trial (n=270), addition of sorafenib to second-line chemotherapy (paclitaxel + carboplatin) does not improve progression free survival or tumor response in patients with metastatic melanoma.
Source: Hauschild A, J Clin Oncol 2009, Epub ahead of print
BLUE LIGHT AND UVEAL MELANOMA
In an in vitro model, blue light increases the proliferation rate of uveal melanoma (UM) cells, which suggests the use of lenses filtering blue light in patients with UM.
Source: Di Cesare S, J Exp Clin Cancer Res 2009, 28:48
THERAPEUTIC EFFECT OF ATP
In a human xenograft model, adenosine 5'-triphosphate (ATP) shows anti-melanoma activity in vivo (50% tumor response), likely through engagement of P2Y(1) and P2X(7) puinergic receptors.
Source: White N, Purinergic Signal 2009, Epub ahead of print
HLA EXPRESSION ALTERATIONS
Analysis of 91 human melanoma cell lines showed alterations in HLA class I and II expression in the majority of cases (67%), loss of HLA-B expression being the commonest.
Source: Mendez R, Cancer Immunol Immunother 2009, Epub ahead of print
SYK-INDUCED SENESCENCE
Re-expression of spleen tyrosine kinase (SYK) in human melanoma cells following treatment with demethylating agent 5-aza-2-deoxycytidine induces cell senescence.
Source: Bailet O, Cancer Res 2009, 69:2748-56
MDM2 SNP309 AND EARLY ONSET
MDM2 single nucleotide polymorphism (SNP)-309 (GG genotype) is associated with early onset of melanoma in women.
Source: Firoz EF, Clin Cancer Res 2009, 15:2573-80
KARENITECIN + VALPROIC ACID TRIAL
In a phase I-II trial (n=39), the combination of karenitecin (topoisomarase I inhibitor) with valproic acid (histone deacetylase inhibitor) is associated with disease stabilization in 47% of patients.
Source: Daud AI, Clin Cancer Res 2009, 15:2479-87
RADIOIMMUNOTHERAPY FOR MELANOMA
In a human metastatic melanoma model, radioimmunotherapy (RIT) with melanin-binding antibodies in combination with dacarbazine yields tumor response rates higher than either modality alone.
Source: Revskaya E, Clin Cancer Res 2009, 15:2373-9
CXCR2 AND CXCR1 INHIBITORS
Small molecule antagonists for chemokine receptors CXCR2 and CXCR1 inhibit human melanoma growth by decreasing cell proliferation, survival and angiogenesis.
Source: Singh S, Clin Cancer Res 2009, 15:2380-6
PPAR-GAMMA AGONISTS
Peroxisome proliferator-activated receptor-gamma (PPARgamma) agonists attenuate proliferation and modulate Wnt/beta-catenin signalling in human melanoma.
Source: Smith AG, Int J Biochem Cell Biol 2009, 41:844-52
IFN-GAMMA MIGHT FAVOR IMMUNE ESCAPE
By downregulating NKG2D ligand expression, interferon-gamma might facilitate escape of MHC class I-negative melanoma cells from NKG2D-mediated killing by NK cells.
Source: Schwinn N, Int J Cancer 2009, 124:1594-604
SOX AND NESTIN EXPRESSION
SOX9 and SOX10 (but not BRN2) are required for expression of nestin (an intermediate filament protein involved in neuroectodermal cell stemness) in human melanoma.
Source: Flammiger A, J Invest Dermatol 2009, 129:945-53
META-ANALYSIS OF PROGNOSTIC BIOMARKERS
In this systematic review and meta-analysis of the literature, melanoma expression of MCAM/MUC18, MMP-2, Ki-67 and PCNA was associated with worse survival rates, while p16/INK4A with better prognosis.
Source: Gould Rothberg BE, J Natl Cancer Inst 2009, 101:452-74
RESISTANCE TO ONCOSTATIN-M
Defective activations of STAT3 Ser727 and PKC isoforms might be responsible for oncostatin M resistance in metastatic melanoma cells.
Source: Lacreusette A, J Pathol 2009, 217:665-76
CT STAGING FOR PRIMARY MELANOMA
In patients with thick melanoma (Breslow > 2 mm), CT staging changed the therapeutic management only in subjects with clinical signs/symptoms of metastatic disease (11/127, 8.6%).
Source: Sawyer A, J Plast Reconstr Aesthet Surg 2009, 62:453-6
ADDITIONAL POSITIVE LYMPH NODES
In patients with positive sentinel lymph node in the groin basin (n=150), additional positive nodes were found in 24% of cases following completion lymph node dissection.
Source: Santinami M, Melanoma Res 2009, 19:112-8
STATINS AND AJOENE SYNERGISM
In murine melanoma cells, statins (atorvastatin and pravastatin) and ajoene interfere with mevalonate pathway and are synergically cytotoxic.
Source: Ledezma E, Melanoma Res 2009, 19:69-74
BIOCHEMOTHERAPY TRIAL
In a phase II trial (n=60), the combinaiton of fotemustine, cisplatin, interferon-alpha and interleukin-2 yielded a 18% overall tumor response rate.
Source: Ridolfi L, Melanoma Res 2009, 19:100-5
MELANIN IN UVEAL MELANOMA
Low melanin content and eumelanin/pheomelanin ratio may make uveal melanoma cells more susceptible to mutagenic effects of ultraviolet radiation.
Source: Hu DN, Melanoma Res 2009, 19:75-9
NVP-BEZ235 PRECLINICAL ACTIVITY
In a mouse melanoma model, NVP-BEZ235 (a dual PI3K/mTOR inhibitor) shows antitumor activity in vivo by targeting tumor growth and interfering with angiogenesis.
Source: Marone R, Mol Cancer Res 2009, 7:601-13
MCL-1 AND MELANOMA ANOIKIS
Anti-apoptotic protein Mcl-1 is upregulated by mutated BRAF and inhibits melanoma apoptosis following to lack of cell adhesion (anoikis).
Source: Boisvert-Adamo K, Mol Cancer Res 2009, 7:549-56
MSH-BASED SPECT IMAGING
In a mouse melanoma model, single-photon emission computed tomography (SPECT) using (111)In-labeled MSH was superior to positron emission tomography (PET) imaging.
Source: Guo H, Nucl Med Biol 2009, 36:267-76
RUNX3 AND MELANOMA
RUNX3 is a tumor suppressor gene whose expression is downregulated in human melanoma, where its expression is regulated by microRNA miR-532-5p.
Source: Kitago M, Clin Cancer Res 2009, Epub ahead of print
BORON NEUTRON CAPTURE THERAPY
In a pilot study, seven patients with multiple subcutaneous melanoma metastases were treated with BNCT: overall response and G3 toxicity rates were 69% and 30%, respectively.
Source: Menéndez PR, Appl Radiat Isot 2009, Epub ahead of print
MMP SOMATIC MUTATIONS
Matrix metalloproteinases (MMP) are mutated in 23% of melanomas; one MMP-8 inactivating mutation provides human melanoma with metastatic potential in an in vivo model.
Source: Palavalli LH, Nat Genet 2009, Epub ahead of print
TAA EXPRESSION AND PROGNOSIS
Gene expression of tumor associated antigens Melan-A, tyrosinase, Na-17A, MAGE-1, MAGE-3 and Ny-ESO-1 does not correlate with patients' prognosis (except for stage III subgroup).
Source: Vourc'h-Jourdain M, Arch Dermatol Res 2009, Epub ahead of print
LIVER METS FROM UVEAL MELANOMA
In a large retrospective series of patients with liver metastatic disease from ocular melanoma (n=798), radical surgery appears the best therapeutic option.
Source: Mariani P, Eur J Surg Oncol 2009, Epub ahead of print
LYMPH NODE RATIO
Using the data from the SEER database, the Authors show that lymph node ratio (N-ratio) is an independent prognostic factor among patients with node-positive cutaneous melanoma.
Source: Xing Y, Cancer 2009, Epub ahead of print
SERUM AMYLOID AS PROGNOSTIC MARKER
In a large series of patients (n=596), proteomic profiling identifies serum amyloid-A (SAA) as an independent prognostic factor (multivariable survival analysis).
Source: Findeisen P, J Clin Oncol 2009, Epub ahead of print
DERMOSCOPY VERSUS ARTIFICIAL INTELLIGENCE
A meta-analysis shows that dermoscopy and artificial intelligence perform equally well for diagnosis of melanocytic skin lesions; plus, there is no significant difference in the diagnostic performance of various dermoscopy algorithms.
Source: Rajpara SM, Br J Dermatol 2009, Epub ahead of print
NPrCAP/M NANOPARTICLE AND HYPERTHERMIA
In a murine in vivo melanoma model, NPrCAP/M (a magnetite nanoparticle) selectively accumulates in melanoma and leads to melanoma regression following hyperthermia treatment with external alternating magnetic field.
Source: Sato M, J Invest Dermatol 2009, Epub ahead of print
GAMMA-GT AND RESISTANCE TO ATO
Gamma-glutamyltransferase (gamma-GT) induces catalase activity, lowers reactive oxygen species (ROS) levels and is associated with resistance to arsenic trioxide (ATO)-induced apoptosis.
Source: Giommarelli C, Free Radic Biol Med 2009, Epub ahead of print
E-CADHERIN AND THE CXCR4/CXCL12 AXIS
E-cadherin expression inhibits the invasive activity of human melanoma cells induced by the chemokine receptor CXCR4 and its ligand CXCL12.
Source: Molina-Ortiz I, J Biol Chem 2009, Epub ahead of print
NOX4, ROS AND MELANOMA
Superoxide-generating NADPH oxidase-4 (NOX4) is upregulated in melanoma and its inhibition leads to G2/M cell cycle arrest through CDK and Cdc25 inhibition.
Source: Yamaura M, Cancer Res 2009, 69:2647-54
MELANOMA ASSOCIATED RETINOPATHY
The Authors present a case of paraneoplastic retinopathy with retina detachments and autoantibodies against interphotoreceptor retinoid binding protein (IRBP).
Source: Bianciotto CG, Br J Ophthalmol 2009, Epub ahead of print
HISTAMINE, H2O2 AND MELANOMA
In vitro, histamine inhibits human melanoma cell proliferation at least in part by increasing hydrogen peroxide (H2O2) levels.
Source: Medina VA, Free Radic Biol Med 2009, Epub ahead of print
RND3 PROMOTES INVASIVENESS
In a 3D model, RND3 (a Rho family GTPase whose expression is regulated by mutant BRAF) promotes human melanoma invasiveness by suppressing RhoA-mediated actin cytoskeletal organization.
Source: Klein RM, Cancer Res 2009, 69:2224-33
REPEAT ISOLATED LIMB INFUSION
In patients with recurrent in transit metastases (n=48), repeat isolated limb infusion (ILI) with melphalan and actinomycin-D can yield high tumor response rates and encouraging survival rates.
Source: Kroon HM, Cancer 2009, Epub ahead of print
BRAF(V600E) AND PTEN LOSS: A BAD SYNERGISM
In an in vivo mouse model, activation of BRAF and loss of PTEN induce melanoma development with 100% penetrance; treatment with MEK and mTOR inhibitors leads to shrinkage of established melanomas.
Source: Dankort D, Nat Genet 2009, Epub ahead of print
NY-ESO-1 VACCINE TRIAL
In a trial of vaccination with NY-ESO-1 full length protein formulated with Iscomatrix immunological adjuvant, no tumor response was observed in patients with metastatic melanoma.
Source: Nicholaou T, Clin Cancer Res 2009, 15:2166-73
IL-21 FOR METASTATIC MELANOMA
In a pilot trial, intravenous interleukin-21 (IL-21, a cytokine with immunostimulatory properties), yielded one complete and one partial response in patients with metastatic melanoma (n=24).
Source: Davis ID, Clin Cancer Res 2009, 15:2123-9
THERAPEUTIC INHIBITION OF MELANOGENESIS
In an in vitro model, inhibition of melanin synthesis by tyrosinase inhibitors increase toxicity of cyclophosphamide and lymphocytes against human melanoma cells.
Source: Slominski A, Int J Cancer 2009, 124:1470-7
SERUM PROTEOMICS FOR MELANOMA DIAGNOSIS
In a pilot study (n=60), serum protein profiling (based on mass spectrometry) could discriminate melanoma patients from healthy volunteers with high accuracy (98%).
Source: Caron J, J Cancer Res Clin Oncol 2009, Epub ahead of print
REALGAR NANOPARTICLES
In a mouse melanoma model, realgar (an arsenic sulfide mineral) nanoparticles are effective to treat melanoma in vivo with little toxicity.
Source: Zhao QH, Med Oncol 2009, Epub ahead of print
LYMPHATIC DRAINAGE AND AGING
Lymphatic function declines with age, which may help clarify findings of reduced nodal positivity and increased in-transit disease in older patients.
Source: Conway WC, Ann Surg Oncol 2009, Epub ahead of print
HERV-K AND MELANOMA PROGRESSION
In vitro data suggest that human melanoma progression is favored by the activation of human endogenous retrovirus K (HERV-K).
Source: Serafino A, Exp Cell Res 2009, 315:849-62
USE OF SNB IN USA
In a survey conducted in the USA (n=16,598), sentinel node biopsy (SNB) was performed in 48.7% and 13.3% of patients with stage IB-II and IA melanoma, respectively.
Source: Bilimoria KY, J Clin Oncol 2009, Epub ahead of print
VERSICAN CONTROL IN MELANOMA
In human melanoma cells, expression of versican (a large chondroitin sulfate proteoglycan overexpressed by melanoma and involved in metastatization) is controlled by transcription factors AP-1 and TCF.
Source: Domenzain-Reyna C, J Biol Chem 2009, Epub ahead of print
REXINOID AND ROSIGLITAZONE SYNERGISM
In a human xenograft model, rexinoid (retinoid X receptor [RXR] agonist) shows synergic anti-melanoma activity with rosiglitazone (peroxisome proliferator activated receptor-gamma [PPAR-gamma] agonist).
Source: Klopper JP, Mol Cancer 2009, 8:16
OSTEOPONTIN AND MIA AS SERUM MARKERS
In a small series (n=32), both osteopontin and melanoma-inhibitory-activity (MIA) protein levels were higher in the plasma of patients with metastatic as compared to non-metastatic uveal melanoma.
Source: Haritoglou I, Ophthalmologica 2009, 223:239-43
MELANOMA-RISK MC1R SNP IN JEWS
In a Jewish population (cases, n=132), the R151C single nucleotide polymorphism (SNP) of the MC1R gene has been found associated with the risk of developing melanoma.
Source: Galore-Haskel G, Eur J Cancer 2009, Epub ahead of print
SURVIVIN AND MELANOMA PROGNOSIS
In a small series of patients with cutaneous (n=52) and mucosal (n=25) melanoma, nuclear staining for anti-apoptotic factor survivin is an independent prognostic factor.
Source: Chen N, Hum Pathol 2009, Epub ahead of print
NOVEL MELANOMA-RISK SNP
In a Spanish case-control study (cases, n=205), two single nucleotide polymorphisms (SNP) of pigmentation-related genes (OCA2 R419Q and MYO7A S1666C) are associated with increased melanoma risk.
Source: Fernandez LP, Exp Dermatol 2009, Epub ahead of print
FUNCTIONAL EFFECTS OF CDKN2A GERMLINE MUTATIONS
Functional evaluation of 20 CDKN2A germ-line mutations identified in melanoma-prone families or patients have led to the identification of 18 novel loss-of-function variants.
Source: Kannengiesser C, Hum Mutat 2009, 30:564-74
STANDARDS FOR LYMPH NODE DISSECTION
In a large Australian series of radical lymph node dissections (RLND, n=2039) for melanoma, the mean number of lymph nodes resected were 21.9, 14.5 and 19.5 for axilla, groin and neck dissection, respectively.
Source: Spillane AJ, Ann Surg 2009, 249:473-80
PUFA OPPOSE MELANOMA METASTASIS
In mice fed with n-3 polyunsaturated fatty acids (PUFA)-rich diet and injected with a highly metastatic murine melanoma cell line, enhanced apoptosis and reduced angiogenesis are associated with the inhibition of lung colonisation.
Source: Mannini A, Br J Nutr 2009, 101:688-93
TIMP-1-GPI, HYPERTHERMIA AND FAS
In an in vitro model, tissue inhibitor of matrix metalloproteinase-1 linked to a glycosylphosphatidylinositol anchor (TIMP-1-GPI) and hyperthermia kill melanoma cells synergically and increase sensitivity to FAS-mediated apoptosis.
Source: Djafarzadeh R, Cancer Immunol Immunother 2009, 58:361-71
EPHA2 PROMOTES INVASIVENESS
In a murine melanoma model, EPHA2 (ephrin receptor tyrosine kinase) prompts invasion of malignant cells shifting from mesenchymal to amoeboid-like motility style.
Source: Parri M, Cancer Res 2009, 69:2072-81
BMF AND RESISTANCE TO MEK INHIBITION
In human melanoma cell lines, resistance to MEK inhibition is linked to the lack of cytosolic translocation of Bcl-2 modifying factor (BMF), which remains sequestered to the cytoskeleton through dynein light chain 2 (DLC2) binding.
Source: VanBrocklin MW, Cancer Res 2009, 69:1985-94
HSP90 INHIBITION AND HYPERTHERMIA
In a murine melanoma in vivo model, geldanamycin (heat shock protein 90 inhibitor) synergically increases the anti-melanoma effect of hyperthermia.
Source: Ito A, Cancer Sci 2009, 100:558-64
GENE METHYLATION AND PROGNOSIS
The CpG island methylator phenotype (CIMP, associated with hypermethylation of tumor suppressor genes [TSG] and multiple non-coding methylated-in-tumor [MINT] loci) correlates with prognosis of melanoma patients (n=122).
Source: Tanemura A, Clin Cancer Res 2009, 15:1801-7
ID2 AND VE-CADHERIN IN UVEAL MELANOMA
In human uveal melanoma, inhibitor of DNA binding 2 (ID2) activates VE-cadherin expression; downregulation of ID2 expression inhibits vasculogenic mimicry in 3D cultures of uveal melanoma.
Source: Su F, Graefes Arch Clin Exp Ophthalmol 2009, 247:411-9
GRP78 EXPRESSION AND PROGNOSIS
In a series of 171 patients, expression of glucose-regulated protein 78 (GRP78, an ER stress related factor) correlates with known prognostic factors and survival.
Source: Zhuang L, Histopathology 2009, 54:462-70
FGF2 AND UVEAL MELANOMA
Fibroblast growth factor 2 (FGF2) and its receptor (FGFR1) are overexpressed in uveal melanoma cells whose proliferation rate is strongly reduced by depletion of endogenous FGF2.
Source: Lefčvre G, Invest Ophthalmol Vis Sci 2009, 50:1047-57
TEMOZOLOMIDE / BMS-345541 SYNERGISM
In a xenograft model of human melanoma, the antitumor activity of TMZ, BMS-345541 (IKK-beta inhibitor) and BAY 54-9085 (BRAF inhibitor) depends on inhibition of NFkB; plus, TMZ and BMS-345541 show therapeutic synergism.
Source: Yang J, Mol Cancer Ther 2009, 8:636-47
PRIMARY ORAL MELANOMA INCIDENCE
Analyzing the Cancer Incidence in Five Continents volume IX (CI5-IX) database, oral melanoma was found to represent 0.26% of all oral cavity cancers (age-world-standardized incidence rate [ASR(W)]: 0.01 per 100,000 persons-year in all regions).
Source: Sortino-Rachou AM, Oral Oncol 2009, 45:254-8
NQ14 ANTI-MELANOMA IN VITRO ACTIVITY
In an in vitro murine model, 1,4-naphthoquinone (NQ14) shows anti-melanoma activity mainly through the induction of oxidative stress.
Source: Kumar MR, Toxicol In Vitro 2009, 23:242-50
TIME TO LYMPH NODE METASTASIS AND PROGNOSIS
In patients with thick melanoma (>4 mm) of the lower extremities (n=185), time to regional lymph node metastasis correlates with survival independently of other prognostic factors.
Source: Herman K, World J Surg 2009, 33:469-74
HAX1 siRNA AND MELANOMA APOPTOSIS
HS1-associated protein X-1 (Hax-1) is an anti-apoptotic factor whose inhibition by small interfering RNA (siRNA) causes apoptosis of human melanoma cells in vitro.
Source: Li WB, Cell Biol Int 2009, Epub ahead of print
CHIMERIC PROTEIN ABRaA-VEGF
ABRaA-VEGF, a fusion protein made of abrin-a toxin A-chain (ABRaA) and VEGF(121) (a VEGF-A isoform), inhibits growth of B16-F10 murine melanoma in vivo.
Source: Smagur A, Acta Biochim Pol 2009, Epub ahead of print
ONCOLYTIC VIRUS ENCODING IL-2
In an in vivo animal model of melanoma, Newcastle disease virus (NDV) has significant antitumor activity, which is enhanced if the virus is engineered to express IL-2.
Source: Zamarin D, Gene Ther 2009, Epub ahead of print
LASER TOMOGRAPHY FOR MELANOMA DIAGNOSIS
Multiphoton laser tomography (MLT) can detect fluorescence emitted by biomolecules (e.g. melanin) and might help diagnose melanoma by identifying melanoma-specific emission spectra.
Source: Dimitrow E, Exp Dermatol 2009, Epub ahead of print
TRP53 AND RB1 LOSS DOES NOT CAUSE MELANOMA
Dual loss of Rb1 and Trp53 (an animal homologue of human p53) in melanocytes perturbs melanocyte homeostasis and genetic stability in vitro but does not cause melanoma (or pigmentation defects) in vivo.
Source: Tonks ID, Pigment Cell Melanoma Res 2009, Epub ahead of print
GANGLIOSIDES AND DENDRITIC CELLS
Melanoma gangliosides GM3 and GD3 may impair antitumor immune response by causing apoptosis of dendritic cells.
Source: Bennaceur K, Glycobiology 2009, Epub ahead of print
ON MSLT-I TRIAL STATISTICAL ANALYSIS
Concern is reported regarding the possibility that survival advantage claimed in the pivotal MSLT-I trial for patients having early versus delayed lymphadenectomy is due to prognostic difference in the two sub-groups non-randomly compared.
Source: Thomas JM, J Plast Reconstr Aesthet Surg 2009, Epub ahead of print
PALLADIUM BRACHYTHERAPY FOR UVEAL MELANOMA
In a large retrospective series (n=400), palladium-103 plaque brachytherapy yielded 5- and 10-year metastasis-free survival rates of 92% and 86% respectively, which appears superior to other forms of radiation.
Source: Finger PT, Ophthalmology 2009, Epub ahead of print
EPHA2 PROMOTES MELANOMA PROGRESSION
In human melanoma samples, EphA2 (ephrin receptor tyrosine kinase) expression correlates with metastatic potential. In preclinical models, EphA2 inhibition leads to decreased tumor progression in vitro and in vivo.
Source: Margaryan NV, Cancer Biol Ther 2009, Epub ahead of print
NK CELLS AND UVEAL MELANOMA
In uveal melanoma, low Human Leucocyte Antigen (HLA) class I expression on primary tumours is associated with a decreased risk of metastasis: new evidence lends support to this hypothesis.
Source: Maat W, Invest Ophthalmol Vis Sci 2009, Epub ahead of print
BVT POLYCHEMOTHERAPY
In 28 patients with pretreated relapsed stage IV cutaneous melanoma, the BVT regimen (bleomycin + vinorelbine + trofosfamide) yielded partial response and stable disease in 11% and 18% of cases, respectively.
Source: Atzpodien J, Cancer Chemother Pharmacol 2009, Epub ahead of print
NEW ANTIBODY FOR CTC SORTING
High molecular weight melanoma-associated antigen (HMW-MAA)-specific monoclonal antibodies bound to immunomagnetic beads have been successfully used to detect circulating tumor cells (CTC) in patients with melanoma (n=57).
Source: Kitago M, Clin Chem 2009, Epub ahead of print
SODIUM PUMP THERAPEUTIC INHIBITION
The sodium pump alpha-1 subunit is widely expressed by melanoma and its inhibition by cardenolides (notably UNBS1450, currently under clinical investigation) leads to anti-melanoma effects in vitro.
Source: Mathieu V, J Cell Mol Med 2009, Epub ahead of print
MELANOMA STEM CELL IMMUNOGENICITY
In an in vitro model, CD133 positive melanoma cells with clonogenic/self renewal potential express cancer/testis antigens (e.g. NY-ESO1) and can be recognized and destroyed by antigen-specific CD8+ T-cells.
Source: Gedye C, Cancer Immunol Immunother 2009, Epub ahead of print
THIN MELANOMA AND SENTINEL NODE STATUS
In a meta-analysis (n=3651) of sentinel lymph node (SLN) biopsy in thin melanoma (thickness equal/less than 1 mm), pooled SLN positivity rate was 5.6%.
Source: Warycha MA, Cancer 2009, 115:869-79
PEPTIDE VACCINE +/- GMCSF OR IFNalpha
In a phase II trial (n=120) of peptide vaccine alone or combined with either GM-CSF or IFN-alpha, neither cytokine increased immune response, which correlated with prolonged patients' survival.
Source: Kirkwood JM, Clin Cancer Res 2009, 15:1443-51
ANGIOPOIETIN-2 SERUM LEVELS AND PROGNOSIS
In stage I to IV melanoma patients (n=98), serum levels of angiopoietin-2 (which acts as an autocrine regulator of melanoma cell migration and invasion) are associated with disease progression.
Source: Helfrich I, Clin Cancer Res 2009, 15:1384-92
SYNERGISM OF BORTEZOMIB + FENRETINIDE
In a xenograft melanoma model, the combination of endoplasmic reticulum stress-inducing agents bortezomib and fenretinide shows synergistic anti-tumor activity.
Source: Hill DS, Clin Cancer Res 2009, 15:1192-8
NEVUS DENSITY AND MELANOMA RISK IN WOMEN
Aggregate data from 10 case-control studies of melanoma in women suggest that high nevus counts are strongly associated with melanoma of the trunk but less so if at all of the head and neck.
Source: Olsen CM, Int J Cancer 2009, 124:937-44
VACCINIA VIRUS-BASED METASTASIS DETECTION
In an animal model, real-time intraoperative detection of melanoma lymph node metastases is possible using recombinant vaccinia virus GLV-1h68 expressing green fluorescent protein (GFP).
Source: Kelly KJ, Int J Cancer 2009, 124:911-8
HEPATIC RADIOEMBOLIZATION FOR OCULAR MELANOMA
The first report on Yttrium-90 microspheres (radioembolization) for the treatment of liver metastasis from ocular melanoma shows tumor response in all patients (n=11) with one complete response.
Source: Kennedy AS, Cancer Invest 2009, Epub ahead of print
STAT3 INDUCTION BY INTERFERON-ALPHA
Although in a minority of patients (4/24, 17%), interferon-alpha (IFNa) treatment induces STAT3 activation in melanoma cells, which correlates with shorter survival rates.
Source: Humpoliková-Adámková L, Eur J Cancer 2009, Epub ahead of print
MIR-221 TARGETS C-KIT IN MELANOMA
This study rules out loss of AP2 as an explanation for c-KIT downregulation in melanoma, whereas it identifies microRNA mir-221 as the suppressor of the receptor tyrosine kinase.
Source: Igoucheva O, Biochem Biophys Res Commun 2009, 379:790-4
ANCESTRAL HLA 62.1 AND PROGNOSIS
The ancestral HLA haplotype (AHH) 62.1 [(A2) B15 Cw3 DRB1*04] (which is associated with autoimmune diseases) correlates with both longer metastasis-free interval and shorter survival after metastasis occurrence.
Source: Helgadottir H, Cancer Immunol Immunother 2009, Epub ahead of print
NIMESULIDE ANTI-MELANOMA ACTIVITY
In an in vitro murine melanoma model, the NSAID nimesulide decreases tumor cell proliferation by decreasing levels of polyamines (spermidine and spermine) and enhancing transglutaminase activity.
Source: Gismondi A, Amino Acids 2009, Epub ahead of print
CtBP1 AND MELANOMA INVASIVENESS
The gene transcription co-repressor CtBP1 (C-terminal binding protein 1) is lost in melanoma cells, which leads to increased melanoma inhibitory activity (MIA) expression and melanoma invasiveness.
Source: Winklmeier A, BMC Cancer 2009, 9:52
FILAMIN-A AND EGFR IN MELANOMA
The actin-binding protein filamin A (FLNa) is necessary for both kinase activation and intracellular trafficking of epidermal growth factor receptor (EGFR) in an in vitro human melanoma model.
Source: Fiori JL, Endocrinology 2009, Epub ahead of print
AUTOIMMUNITY AND ANTI-MELANOMA IMMUNE RESPONSE
Melanoma inhibitor of apoptosis protein (ML-IAP) specific cytotoxic T lymphocytes from melanoma patients cross-react with an epitope of SS56, a target antigen in some autoimmune diseases.
Source: Bćk Sřrensen R, J Invest Dermatol 2009, Epub ahead of print
MELANOMA microRNA PROFILE
In this article the Authors describe the first study on microarray-based miRNA profiling of melanocytes and melanoma cell lines derived from either primary tumors or metastatic melanomas.
Source: Mueller DW, J Invest Dermatol 2009, Epub ahead of print
MELANOMA SENESCENCE GENES
In contrast with previous studies, these Authors suggest that cultured human melanocytes can initiate an effective oncogene-mediated senescence program in the absence of p16/INK4a and p14/ARF proteins.
Source: Haferkamp S, J Invest Dermatol 2009, Epub ahead of print
ISOSELENOCYANATES AS ANTI-MELANOMA DRUGS
In an in vivo preclinical model of melanoma, isoselenocyanates inhibit AKT3 activity, induce melanoma cell apoptosis and decrease tumor development without significant toxicity.
Source: Sharma A, Clin Cancer Res 2009, Epub ahead of print
MIR-182: NOVEL MELANOMA ONCOGENE
The microRNA 182 (mir-182) is increasignly expressed from primary to metastatic melanomas and promotes metastasis in an in vivo murine melanoma model by repressing FOXO3 and MITF.
Source: Segura MF, Proc Natl Acad Sci USA 2009, 106:1814-9
SYNTAXIN POLYMORPHISMS AND MELANOMA RISK
In a large Australian series (cases, n= 1560), none of the 26 single nucleotide polymorphisms (SNP) of the syntaxin-17 (STX17) gene is associated with melanoma risk.
Source: Zhao ZZ, Melanoma Res 2009, Epub ahead of print
THERAPEUTIC POTENTIAL OF AUTOTAXIN INHIBITION
In a preclinical study, knocking down autotaxin secretion, or inhibiting its catalytic activity, blocks melanoma cell migration by preventing lysophosphatidate production and the subsequent activation of LPA(1/3) receptors.
Source: Gaetano CG, Mol Carcinog 2009, Epub ahead of print
INCREASING THE YIELD OF THERAPEUTIC T-CELLS
In a preclinical study, incubation of antigen-sensitized T lymphocytes in IL-7 + IL-15 increases yield of cells capable of inducing regression of melanoma metastases compared to culture in IL-2.
Source: Le HK, Cancer Immunol Immunother 2009, Epub ahead of print
NUMBER OF SLN AND PROGNOSIS
In a large series (n=970), the number of sentinel lymph nodes (SLN) is associated with melanoma thickness and lymphovascular invasion, but it does not correlate with patients' survival.
Source: Schmidt CR, Ann Surg Oncol 2009, Epub ahead of print
PROGNOSTIC ROLE OF RHOC EXPRESSION
The protein exression of RAS homolog GTP binding protein member C (RhoC) is associated with thicker melanomas, presence of lymphatic metastases and shorter survival rates, though without being an independent predictor.
Source: Boone B, J Cutan Pathol 2009, Epub ahead of print
PROGNOSTIC ROLE OF LYMPHOVASCULAR INVASION
In a small series of patients with melanoma (n=60), detection of lymphovascular invasion (by immunohistochemistry with anti-D2-40) correlates with sentinel lymph node status and patients prognosis.
Source: Petersson F, J Cutan Pathol 2009, Epub ahead of print
VITAMIN D AND MELANOMA RISK
In a cohort study (n=68,611), vitamin D intake is not associated with the risk of developing cutaneous melanoma (after adjustment for melanoma risk factors).
Source: Asgari MM, J Invest Dermatol 2009, Epub ahead of print
NODULAR MELANOMA PRESENTATION
Data from an Australian study of Queensland residents diagnosed with melanoma show that men, older individuals, and those not screened by a physician in the past 3 years are more likely to have nodular melanoma of greater thickness.
Source: Geller AC, Cancer 2009, Epub ahead of print
CK-18 EXPRESSION AND MELANOMA PROGNOSIS
In a series of primary melanomas (n=80), cytokeratin-18 (CK-18) mRNA is expressed in one third of samples (as assessed by in-situ hybridization, ISH) and inversely correlates with patients prognosis.
Source: Chen N, Melanoma Res 2009, Epub ahead of print
CXCR4 AND MT1-MMP IN MELANOMA METASTASIS
In an in vivo model, chemokine receptor CXCR4 and metalloproteinase MT1-MMP play a key role respectively in the early and late phase of melanoma metastasis to the lungs.
Source: Bartolomé RA, Am J Pathol 2009, 174:602-12
FTIR SPECTROSCOPY DETECTS DRUG RESISTANCE
In a reagent-free in vitro model, Fourier transform infrared (FTIR) spectroscopy can distinguish between drug-resistant and drug-sensitive human melanoma cells.
Source: Zwielly A, Analyst 2009, 134:294-300
MUC-18 BLOOD LEVELS AND MELANOMA STAGE
In 100 patients with TNM stage I to IV melanoma, higher mRNA levels of MUC-18/MCAM (detected in the peripheral blood by means of RT-PCR) are associated with more advanced disease.
Source: Rapanotti MC, Br J Dermatol 2009, 160:338-44
STRESS, NOREPINEPHRINE AND MELANOMA
According to an in vitro study, norepinephrine (a catecholamine stress hormone) might promote melanoma progression by increasing the expression of factors implicated in angiogenesis and metastasis, such as VEGF, IL-8 and IL-6.
Source: Yang EV, Brain Behav Immun 2009, 23:267-75
ASNA1 AND RESISTANCE TO CISPLATIN/ARSENITE
Expression of ASNA1 (an ATPase involved in efflux of arsenite and antimonite) is associated with melanoma resistance to both cisplatin and arsenite in vitro.
Source: Hemmingsson O, Cancer Chemother Pharmacol 2009, 63:491-9
FORSKOLIN, cAMP AND VASCULOGENIC MIMICRY
In an in vitro human melanoma model, Forskolin (an adenylate cyclase activator) increases cAMP levels and inhibits vasculogenic mimicry, likely by PKA-independent activation of Epac/Rap1, PKA- and Epac-independent inactivation of ERK1/2, and inhibition of PI3K/Akt.
Source: Lissitzky JC, Cancer Res 2009, 69:802-9
TGF-BETA2 AND MELANOMA BRAIN METASTASIS
In an in vivo murine melanoma model, TGFB2 (transforming growth factor beta 2) is responsible for tumor localization in the brain parenchyma, with potential implications for melanoma therapy.
Source: Zhang C, Cancer Res 2009, 69:828-35
CADHERIN-7 REGULATES MELANOMA MIGRATION
Cadherin-7 - an adhesion molecule that binds melanoma migration-promoting molecule MIA - is upregulated in metastatic as compared to primary melanomas: its upregulation in metastatic melanoma inhibits cell migration.
Source: Winklmeier A, Cancer Sci 2009, 100:261-8
ENDOTHELIAL CELL ANTI-MELANOMA VACCINE
In a murine melanoma model, animal vaccination with syngeneic endothelial cells inhibited subcutaneous tumor growth and appearance of lung metastasis.
Source: Yoshiura K, J Exp Clin Cancer Res 2009, 28:13
FIRST GENE POLYMORPHISMS & MELANOMA RISK DATABANK
The first systematic database of gene polymorphisms and melanoma risk is now available as MMMP Biomap.
Source: MMMP Biomap #32
PREDICTING RESPONSE TO SORAFENIB + CHEMOTHERAPY
In a preliminary study (n=46), high VEGFR2 and low ERK1/2 expression levels are associated with greater melanoma response rates in patients treated with sorafenib + carboplatin + paclitaxel (SCP).
Source: Jilaveanu L, Clin Cancer Res 2009, 15:1076-85
PDSS2: NEW MELANOMA SUPPRESSOR GENE
Prenyl diphosphate synthase subunit 2 (PDSS2, chromosome 6q21) is downregulated in most melanoma specimens and totally abrogates the tumorigenicity of human melanoma cell line UACC-903 in nude mice.
Source: Fung JM, Clin Cancer Res 2009, 15:797-803
MIC-1: NEW MELANOMA ONCOGENE
Macrophage inhibitory cytokine (MIC-1) is highly expressed in melanoma cells, and its inhibition leads to significant decrease in tumorigenicity of three melanoma cell lines.
Source: Boyle GM, J Invest Dermatol 2009, 129:383-91
MELANOMA SENESCENCE: NOT PRECLUDED
Hyperactivation of the MAPK pathway following activation of an inducible form of oncogenic CRAF induces a senescence-like proliferation arrest in BRAF mutant melanoma cells, which argues against changes in melanoma cells completely precluding senescence.
Source: Houben R, J Invest Dermatol 2009, 129:406-14
ERK - P38 SYNERGISM IN MELANOMA
Unlike carcinoma cells, in melanoma cells MAPK-ERK and MAPK-p38 activity is not mutually exclusive and instead synergically increases melanoma migration and proliferation.
Source: Estrada Y, Pigment Cell Melanoma Res 2009, 22:66-76
ONCOGENIC BRAF INHIBITS HOMEOSTATIC LKB1-AMPK PATHWAY
The tumor suppressor LKB1-AMPK pathway is suppressed in melanoma cells with the BRAF V600E mutation (LKB1 is phosphorylated by ERK and RSK, two kinases downstream of BRAF, which compromises LKB1 ability to bind and activate AMPK).
Source: Zheng B, Mol Cell 2009, 33:237-47
IKB-GAMMA PROMOTES MELANOMA PROGRESSION
In an in vivo mouse melanoma model, ribozyme-mediated targeting of IkB-gamma (a member of a family of proteins that inhibit the nuclear localization of NFkB) inhibits tumor invasion and metastasis.
Source: Torabian SZ, Am J Pathol 2009, Epub ahead of print
SPECT/CT FOR SENTINEL LYMPH NODE MAPPING
In a series of 85 patients with melanoma and with conventional lymphoscintigrams that were difficult to interpret, the hybrid single-photon emission computed tomography camera with integrated CT was useful in 35% of cases.
Source: Van der Ploeg IM, Ann Surg Oncol 2009, Epub ahead of print
MULTIPHOTON LASER TOMOGRAPHY: NEW DIAGNOSTIC TOOL
In a pilot study (n=83), this in vivo non-invasive tissue imaging tool shows promising diagnostic power, with sensitivity values up to 95% (range: 71-95%) and specificity values up to 97% (range: 69-97%).
Source: Dimitrow E, J Invest Dermatol 2009, Epub ahead of print
WNT3a/b-CATENIN AND MELANOMA PROGRESSION
In contrast to colorectal cancer, elevated levels of nuclear beta-catenin in melanoma correlate with improved survival, possibly because WNT3a induces cell differentiation.
Source: Chien AJ, Proc Natl Acad Sci USA 2009, 106:1193-8
CHILDHOOD MELANOMA GENETICS
As compared to familial cases (n=23), melanomas in childhood and adolescence (n=21) show frequent loss of INK4A and gain of KIT at the somatic level.
Source: Daniotti M, J Invest Dermatol 2009, Epub ahead of print
PET/CT SCAN IN PRIMARY STAGING OF MELANOMA
In a small series of patients (n=56), contrast-enhanced FDG-PET/CT scan has a low sensitivity on initial staging of disease (N-stage sensitivity: 38.5%; M-stage sensitivity: 41.7%).
Source: Veit-Haibach P, Eur J Nucl Med Mol Imaging 2009, Epub ahead of print
MOBILE PHONE AND RISK OF UVEAL MELANOMA
In a case-control study (455 cases), risk of uveal melanoma was not associated with the use of mobile phone. Moreover, no trend for cumulative measures of exposure was found.
Source: Stang A, J Natl Cancer Inst 2009, 101:120-3
SKIN/IRIS NEVI AND RISK OF UVEAL MELANOMA
In a meta-analysis of 7 studies (2122 cases), risk of uveal melanoma was found to be associated with atypical and common cutaneous nevi, cutaneous freckles and iris nevi.
Source: Weis E, Ophthalmology 2009, Epub ahead of print
CIRCULATING VEGFR3 AND MELANOMA PROGNOSIS
In a preliminary study, serum levels of VEGFR3 (vascular endothelial growth factor receptor 3) correlate with tumor burden and survival in patients with metastatic melanoma.
Source: Mouawad R, Eur J Cancer 2009, Epub ahead of print
BI-69A11: NOVEL ANTI-MELANOMA DRUG
In a human xenograft melanoma model, BI-69A11 - an AKT/PKB inhibitor - causes significant tumor regression in vivo.
Source: Gaitonde S, Pigment Cell Melanoma Res 2009, Epub ahead of print
IDENTIFICATION OF HIGH RISK UVEAL MELANOMA BY CGH
Genomic profiling of uveal melanoma by Bacterial Artificial Chromosome Comparative Genomic Hybridization (BAC-CGH) array has led to the identification of prognostic subgroups among patients with disomy 3 or monosomy 3.
Source: Trolet J, Invest Ophthalmol Vis Sci 2009, Epub ahead of print
MAGE-11 ACTIVATES THE HIF1-alpha PATHWAY
The melanoma/cancer-testis antigen MAGE11 activates the hypoxia response (including angiogenesis) by inhibiting PHD2, the prolyl hydroxylase that targets HIF1-alpha (hypoxia inducible factor 1 alpha) to proteasomal degradation.
Source: Aprelikova O, Cancer Res 2009, 69:616-24
RAP1GAP: NOVEL MELANOMA SUPPRESSOR GENE
Rap1GAP (an inhibitor of RAS family member RAP1A/KREV1) is suppressed in melanoma via promoter hypermethylation, which leads to malignant cell survival, proliferation and migration through activation of ERK and integrin pathways.
Source: Zheng H, Cancer Res 2009, 69:449-57
HOST CXCR2 AND MELANOMA AGGRESSIVENESS
In a human xenograft melanoma model, host CXCR2 (receptor for angiogenic factor IL-8) depletion inhibits tumor growth and metastasis.
Source: Singh S, Cancer Res 2009, 69:411-5
HDAC INHIBITION PLUS CHEMOIMMUNOTHERAPY
In a phase I-II trial of valproic acid (histone deacetylase [HDAC] inhibitor) plus chemoimmunotherapy (DTIC + IFN-alpha), this combination regimen did not produce results overtly superior to standard therapy in patients with advanced melanoma.
Source: Rocca A, Br J Cancer 2009, 100:28-36
IL-18 FOR METASTATIC MELANOMA
In a phase II trial of recombinant interleukin-18 (an immunostimulatory cytokine), no significant tumor response was observed among 64 patients with metastatic melanoma (1 partial response + 4 stable disease).
Source: Tarhini AA, Cancer 2009, 115:859-68
ONE MONTH VS ONE YEAR INTERFERON-ALPHA
In a phase III RCT of adjuvant IFN-alpha 2b, patients with high risk melanoma were randomized to one month induction phase or to induction + maintenance regimen (one year): no difference in overall or disease free survival was observed.
Source: Pectasides D, J Clin Oncol 2009, Epub ahead of print
HERV-K RETROVIRUS AND MELANOMA PROGRESSION
Phenotypic and functional modifications of melanoma progression are accompanied by the activation of human endogenous retrovirus K expression (HERV-K). Downregulation of HERV-K expression by RNA interference prevents this progression in vitro.
Source: Serafino A, Exp Cell Res 2009, Epub ahead of print
INCREASING MELANOMA BURDEN IN USA
According to population-based data from non-Hispanic whites in USA, melanoma incidence increased at a rate of 3.1% per year (P=0.001). Statistically significant rises occurred for all histologic subtypes and tumor thicknesses (including those >4 mm).
Source: Linos E, J Invest Dermatol 2009, Epub ahead of print
