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Melanoma News

GENE SIGNATURE OF INVASIVENESS
Global transcript profiling identified a signature featuring decreased expression of developmental and lineage specification genes (MITF, EDNRB, DCT, TYR) and increased expression of genes involved in interaction with the extracellular environment (PLAUR, VCAN, HIF1-alpha).
Source: Jeffs AR, PLoS One 2009, 4:e8461

POLY-EPITOPE VACCINE
Poly-epitope vaccination yielded high rates of immunological responses but only one partial response and five disease stabilizations in 41 patients with advanced melanoma.
Source: Dangoor A, Cancer Immunol Immunother 2009 Epub ahead of print

ROLE OF INFLAMMASOME
An in vitro model suggests that IL-1-mediated autoinflammation contributes to development and progression of human melanoma.
Source: Okamoto M, J Biol Chem 2010, 285:6477-88

ABCA1 AND CURCUMIN RESISTANCE
Overexpression of the ATP binding cassette gene ABCA1 determines resistance to Curcumin in M14 melanoma cells (ABCA1 should be considered as response marker).
Source: Bachmeier BE, Mol Cancer 2009, 8:129

HISTOLOGICAL REGRESSION AND SN STATUS
Primary melanoma histological regression is not an independent predictor of sentinel node (SN) status in a cohort of 397 patients.
Source: Socrier Y, Br J Dermatol 2009, Epub ahead of print

BORTEZOMIB + TEMOZOLOMIDE
In a phase I trial of bortezomib + temozolomide (n=19) the investigators defined the doses for phase II trials; one partial response and 4 disease stabilizations were observed.
Source: Su Y, Clin Cancer Res 2010, 16:348-57

E2F1 AND MELANOMA METASTASIS
In a xenograft model, inhibition of E2F1 expression (which targets EGFR expression) via small hairpin RNA (shRNA) shows anti-melanoma potential in vivo.
Source: Alla V, J Natl Cancer Inst 2010, 102:127-33

ELAFIN ANTI-MELANOMA ACTIVITY
In a xenograft model, protease inhibitor elafin shows anti-melanoma potential in vivo.
Source: Yu KS, Int J Cancer 2009, Epub ahead of print

SYNERGISM LBW242 + TLR3 LIGAND
In an in vitro model, SMAC mimetic LBW242 synergizes with TLR3 ligand Poly I:C to induce apoptosis of human melanoma cells.
Source: Weber A, Cell Death Differ 2009, Epub ahead of print

IPILIMUMAB PHASE II TRIAL
In a phase II dose-ranging trial (n=217) of this anti-CTLA4 antibody for metastatic melanoma, the best overall response rate was 11.1% for 10 mg/kg, 4.2% for 3 mg/kg, and 0% for 0.3 mg/kg (trend test P=0.0015).
Source: Wolchok JD, Lancet Oncol 2010, 11:155-64

ROLE OF PKC-BETA
PKC-beta expression is reduced in melanoma cell lines and its re-expression inhibits colony formation in soft agar, indicating a potential role of PKC-beta in tumor growth.
Source: Voris JP, Pigment Cell Melanoma Res 2009, Epub ahead of print

VEGF RECEPTOR EXPRESSION
In a large series of melanoma specimens (n=468), VEGFR2 expression was higher in metastatic melanoma, while VEGFR3 expression was higher in primary melanoma.
Source: Mehnert JM, Hum Pathol 2010, 41:375-84

2-DEOXY-D-GLUCOSE AND TRAIL
2-deoxy-D-glucose (2-DG) sensitizes human melanoma cells to TRAIL-induced apoptosis through XBP1-mediated upregulation of TRAILR2.
Source: Liu H, Mol Cancer 2009, 8:122

KIT MUTATION IN MUCOSAL MELANOMA
The Authors report on one case of anal mucosal melanoma positive for activating KIT mutation responding to imatinib and review the literature on similar cases (n=12).
Source: Satzger I, Dermatology 2010, 220:77-81

SORAFENIB + TEMOZOLOMIDE
In a 4-arm phase II RCT (n=167), the median progression free survival for patients on arm A, B, C, and D was 5.9, 4.2, 2.2, and 3.5 months, respectively.
Source: Amaravadi RK, Clin Cancer Res 2009, 15:7711-8

AKT ACTIVATION IN MELANOMA
In human melanoma metastases (n=96), phosphorylated AKT is more frequent in BRAF mutated than NRAS mutated specimens, is almost always associated with PTEN loss and is more frequent in brain metastases.
Source: Davies MA, Clin Cancer Res 2009, 15:7538-46

MEK + CDK4 INHIBITION
Combined inhibition of MEK and CDK4 leads to human melanoma cell apoptosis (in vitro) more potently than either inhibition alone.
Source: Li J, Cancer Invest 2009, Epub ahead of print

FALSE NEGATIVE SENTINEL NODES
In a large series of patients undergoing sentinel node (SN) biopsy (n=2451), the false negative rate was 10.8%, and the survival of patients with false negative SN was not worse than that of patients with true positive SN.
Source: Scoggins CR, Ann Surg Oncol 2010, 17:709-17

HEPARIN-DERIVED OLIGOSACCHARIDES
In a xenogtaft model, heparin-derived 4-18 unit oligosaccharides shows significant anti-melanoma activity.
Source: Kenessey I, Thromb Haemost 2009, 102:1265-73

M8 STILBENE PRECLINICAL ACTIVITY
In a xenogtaft model, 3,3',4,4',5,5'-Hexahydroxystilbene (M8) shows significant anti-melanoma activity.
Source: Paulitschke V, J Invest Dermatol 2009, Epub ahead of print

NANOTECHNOLOGY NEWS
In an in vivo preclinical model, single-walled carbon nanotube-conjugated doxorubicin shows increased therapeutic index against melanoma as compared to doxorubicin alone.
Source: Chaudhuri P, Nanotechnology 2010, 21:025102

DOCETAXEL + TEMOZOLOMIDE
In a retrospective study, this combination regimen has modest activity in patients with metastatic melanoma resistant to first line chemotherapy.
Source: Yoon C, Melanoma Res 2010, 20:43-7

CARBOXYLESTERASE AND CPT-11
Forced expression of carboxylesterase (which converts CPT-11 into SN-38) in neural stem cells significantly increases the anti-melanoma activity of CPT-11.
Source: Gutova M, Curr Stem Cell Res Ther 2009, Epub ahead of print

JWA AND MELANOMA
The microtubule-associated protein JWA suppresses melanoma metastasis in vivo, likely by inhibiting integrin alpha V beta 3 signaling.
Source: Bai J, Oncogene 2009, Epub ahead of print

PARTHENOLIDE PRECLINICAL ACTIVITY
Parthenolide, a sesquiterpene lactone from the medical herb feverfew, shows anticancer activity against human melanoma cells in vitro.
Source: Lesiak K, Melanoma Res 2010, 20:21-34

CAMPTOTHECIN ENHANCERS
Both bortezomib (NFkB inhibitor) and KINK-1 (IKKB inhibitor) can enhance the anti-melanoma activity of camptothecin in a preclinical model.
Source: Amschler K, J Invest Dermatol 2009, Epub ahead of print

DIMETHYLFUMARATE (DMF)
DMF increases the anti-melanoma effect of dacarbazine in a xenograft model.
Source: Valero T, J Invest Dermatol 2009, Epub ahead of print

NETRIN-1 AND MELANOMA
Netrin-1 is overexpressed in melanoma as compared to melanocytes and increases melanoma cell migratory potential in vitro.
Source: Kaufmann S, Cell Oncol 2009, 31:415-22

CELASTROL + TEMOZOLOMIDE
Celastrol enhances the anti-melanoma effect of temozolomide in a preclinical model, likely by inhibiting NFkB activity.
Source: Chen M, Mol Cancer Res 2009, 7:1946-53

MELANOMA FIBROBLASTS
Fibroblasts derived from metastatic melanomas can have strong immunosuppressive activity through NK cell modulation.
Source: Balsamo M, Proc Natl Acad Sci USA 2009, Epub ahead of print

HYPOXIA INDUCIBLE FACTOR 1 ALPHA (HIF1-alpha)
HIF1-alpha is overexpressed during melanoma progression and its inhibition has therapeutic potential in a preclinical model.
Source: Mills CN, Mol Cancer 2009, 8:104

THALIDOMIDE + TEMOZOLOMIDE
In a phase II trial (n=64), thalidomide plus temozolomide do not appear to provide a clinical benefit that exceeds dacarbazine alone.
Source: Clark JI, Cancer 2010, 116:424-31

MAINTENANCE BIOTHERAPY
In a phase II trial (n=133), maintenance biotherapy after induction concurrent biochemotherapy appears to improve the survival of patients with metastatic melanoma.
Source: O'Day SJ, J Clin Oncol 2009, 27:6207-12

IMMUNE PROFILE AND MITOTIC INDEX
Immune profile and mitotic index of metastatic melanoma lesions enhance clinical staging in predicting patient survival.
Source: Bogunovic D, Proc Natl Acad Sci USA 2009, 106:20429-34

c-JUN, PKDK1 AND AKT
c-Jun is a transcriptional regulator of PDK1 expression, which highlights key mechanisms underlying c-Jun oncogenic activity and provides new insight into the nature of upregulated Akt and PKC in melanoma.
Source: Lopez-Bergami P, J Biol Chem 2010, 285:903-13

ROLE OF DE-N-ACETYL-GM3
De-N-acetyl GM3 (a derivative of ganglioside GM3) promotes melanoma cell migration and invasion through urokinase plasminogen activator receptor signaling-dependent MMP-2 activation.
Source: Liu JW, Cancer Res 2009, 69:8662-9

TM9SF4 AND MELANOMA CANNIBALISM
Tumor cannibalism is a characteristic of malignancy and metastatic behavior: silencing of TM9SF4 inhibits cannibal activity of human melanoma cells, representing a potential new target for anticancer strategies.
Source: Lozupone F, EMBO Rep 2009, 10:1348-54

NFkB INHIBITION IN UVEAL MELANOMA
Pharmacological inhibition of NFkB reduces proliferation and induces apoptosis of human uveal metastatic melanoma cells in vitro.
Source: Dror R, Invest Ophthalmol Vis Sci 2009, Epub ahead of print

PARP INHIBITION BY PJ-34
Inhibition of PARP activity by PJ-34 leads to growth impairment and cell death in M14 melanoma cell line.
Source: Chevanne M, J Cell Physiol 2010, 222:401-10

3-MARKER PROGNOSTIC SIGNATURE
The expression of 3 biomarkers (NCOA3, SPP1, RGS1) independently predicts survival of patients with melanoma.
Source: Kashani-Sabet M, Clin Cancer Res 2009, 15:6987-92

5-MARKER PROGNOSTIC SIGNATURE
The expression of 5 biomarkers (ATF2, p21/WAF1, p16/INK4A, beta-catenin) independently predicts survival of patients with melanoma.
Source: Gould Rothberg BE, J Clin Oncol 2009, 27:5772-80

GMCSF AND ONCOLYTIC VIRUS
In a phase II clinical trial of a GMCSF-encoding oncolytic herpesvirus, promising tumor response (26%) and survival (52% at 2 years) rates were observed.
Source: Senzer NN, J Clin Oncol 2009, 27:5763-71

BRAF V600E AND MAP2
Oncogenic BRAF V600E induces expression of neuronal differentiation marker MAP2 in melanoma cells by promoter demethylation and downregulation of transcription repressor HES1.
Source: Maddodi N, J Biol Chem 2010, 285:242-54

ROLE OF Treg CELL DEPLETION
In a RET transgenic mouse model of melanoma, depletion of CD25+Foxp3+ regulatory T cells with anti-CD25 mAb does not prevent tumor development.
Source: Kimpfler S, J Immunol 2009, 183:6330-7

ELESCLOMOL PLUS PACLITAXEL
In a phase II randomized trial (n=81), elesclomol (oxidative stress inducer) improved the therapeutic activity of paclitaxel in terms of progression free survival.
Source: O'Day S, J Clin Oncol 2009, 27:5452-8

VITAMIN D3 SERUM LEVELS
In a cohort of 872 patients, serum levels of vitamin D3 correlated with primary melanoma thickness and patients' survival.
Source: Newton-Bishop JA, J Clin Oncol 2009, 27:5439-44

LOCOREGIONAL RELAPSE AND NODE STATUS
The rate of locoregional (including in transit) metastases in patients with tumor-positive sentinel node (n=141) and patients with palpable nodal involvement (n=178) is similar.
Source: Veenstra HJ, Ann Surg Oncol 2009, Epub ahead of print

CONJUNCTIVAL MELANOMA INCIDENCE
In a Swedish study, the incidence of conjunctival melanoma significantly increased during the period 1960 to 2005.
Source: Triay E, Br J Ophthalmol 2009, 93:1524-8

STAT3 INHIBITION
In a xenograft model, STAT3 inhibition by antisense technology suppresses melanoma growth in vivo.
Source: Yang L, Cancer Biol Ther 2009, 8:2065-72

HYPERTENSION DRUGS AND MELANOMA RISK
In a case-control study (cases=1272), the use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers was not significantly associated with melanoma risk.
Source: Koomen ER, Cancer Epidemiol 2009, 33:391-5

SKIN SELF-EXAMINATION (SSE)
In a retrospective study (n=321), SSE was associated with decreased tumor thickness (adjusted ratio, 0.75; 95% CI: 0.66-0.85 for ever versus never use).
Source: Pollitt RA, Cancer Epidemiol Biomarkers Prev 2009, 18:3018-23

SENTINEL NODE TUMOR BURDEN
The EORTC Melanoma Group has released the recommendations on the measurement of sentinel node tumor burden for prognostic purpose.
Source: van Akkooi AC, Eur J Cancer 2009, 45:2736-42

SURGERY FOR LIVER METASTASIS
A non randomized study (n=255) showed longer survival for patients undergoing radical versus non radical hepatic resection for melanoma metastasis.
Source: Mariani P, Eur J Surg Oncol 2009, 35:1192-7

BIOMARKERS OF RESPONSE TO IL-2
Serum VEGF and fibronectin can predict clinical response to high dose interleukin-2 (n=59).
Source: Sabatino M, J Clin Oncol 2009, 27:2645-52

RANTES + GP100 VACCINE
In a gene therapy model, vaccination with chemokine RANTES and melanoma antigen gp100 is more effective than with gp100 alone.
Source: Aravindaram K, Gene Ther 2009, 16:1329-39

MODIFIED HEPARINS
Modified heparins inhibit integrin alpha(IIb)beta(3) mediated adhesion of melanoma cells to platelets in vitro and in vivo.
Source: Zhang C, Int J Cancer 2009, 125:2058-65

CDKN2A MUTATION RATE IN FAMILIAL MELANOMA
An Italian study showed that CDKN2A is mutated in 68/204 (33%) families with at least two members affected with melanoma.
Source: Bruno W, J Am Acad Dermatol 2009, 61:775-82

D2-40 DOES NOT PREDICT SENTINEL NODE STATUS
D2-40/S-100 dual immunohistochemistry increases the sensitivity of detection of lymphatic invasion in melanoma but does not predict sentinel lymph node involvement (n=27).
Source: Petitt M, J Am Acad Dermatol 2009, 61:819-28

D2-40 PROGNOSTIC AND PREDICTIVE VALUE
Expression of D2-40 (lymphatic invasion biomarker) in primary melanoma predicts sentinel lymph node status and correlates with survival (n=60).
Source: Petersson F, J Cutan Pathol 2009, 36:1157-63

ROLE OF MMP-13
Stromal expression of matrix metalloproteinase-13 is required for melanoma invasion and metastasis, as demonstrated in a gene knockout model.
Source: Zigrino P, J Invest Dermatol 2009, 129:2686-93

KIT EXPRESSION AND MUTATION
In a series of 173 melanomas, eighty-two percent (12 of 14) of cases positive for KIT mutation showed KIT expression in more than 50% of the cells.
Source: Torres-Cabala CA, Mod Pathol 2009, 22:1446-56

IGFBP7 AND MUTATED BRAF
In melanomas carrying oncogenic mutated BRAF, IGFBP7 is epigenetically silenced; systemically administered recombinant IGFBP7 suppresses the growth of BRAF-positive primary tumors in xenografted mice.
Source: Wajapeyee N, Mol Cancer Ther 2009, 8:3009-14

ADJUVANT IFN FOR UVEAL MELANOMA
In a non randomized trial, low dose adjuvant interferon alpha provides no survival benefit to patients with high risk uveal melanoma.
Source: Lane AM, Ophthalmology 2009, 116:2206-12

PHORBOL ESTER PARADOXICAL ACTIVITY
The tumor-promoting phorbol ester TPA inhibits melanoma growth by inactivation of STAT3 through a PKC activated tyrosine phosphatase.
Source: Oka M, J Biol Chem 2009, 284:30416-23

ADAM10 and L1-CAM
ADAM10 is overexpressed in metastatic as compared to primary melanoma; it is associated with melanoma invasiveness and releases L1-CAM, which is responsible for chemoresistance.
Source: Lee SB, J Invest Dermatol 2009, Epub ahead of print

EAPB0203 PRECLINICAL ACTIVITY
In a xenografted mouse in vivo model, EAPB0203 (a novel imidazo[1,2-a]quinoxaline derivative) is more effective than fotemustine against melanoma.
Source: Khier S, Eur J Pharm Sci 2009, Epub ahead of print

RAPAMYCIN PRECLINICAL ACTIVITY
In a mouse syngeneic model, mTOR inhibitor rapamycin inhibits lung metastasis through downregulation of alpha V integrin expression and upregulation of apoptosis signaling.
Source: Yang Z, Cancer Sci 2009, Epub ahead of print

NESTIN, SOX9 AND SOX10
SOX9 and SOX10 are highly expressed in melanoma and seem to have a regulatory role in Nestin expression; nestin and SOX9 may be negative prognostic markers.
Source: Bakos RM, Exp Dermatol 2009, Epub ahead of print

INDUCIBLE NITRIC OXIDE SYNTHASE (iNOS)
In patients with uveal melanoma (n=90), iNOS expression is not an independent prognostic factor at multivariable survival analysis.
Source: Johansson CC, Int J Cancer 2009, Epub ahead of print

CAFFEIC ACID PHENETYL ESTER (CAPE)
In an mouse melanoma model, CAPE shows anti-melanoma activity in vivo.
Source: Kudugunti SK, Invest New Drugs 2009, Epub ahead of print

BRAF, NFAT AND COX2
Oncogenic BRAF V600E activates NFAT2 and NFAT4 via MEK/ERK signaling, which leads to COX2 upregulation in metastatic melanoma.
Source: Flockhart RJ, Br J Cancer 2009, 101:1448-55

US-GUIDED FNAC AND SNB
Ultrasound-guided fine needle aspiration cytology of sentinel nodes is highly accurate and can lead to significant reduction of SN biopsy procedures.
Source: Voit CA, J Clin Oncol 2009, 27:4994-5000

PARKINSON DISEASE AND MELANOMA
A cohort study (n=157,036) showed a significant association between a positive family history of melanoma and risk of PD (multivariate relative risk = 1.85; 95%CI = 1.2-2.8).
Source: Gao X, Neurology 2009, 73:1286-91

ADH-1 FOR ISOLATED LIMB INFUSION
In a phase I trial (n=16), isolated limb infusion with melphalan combined with ADH-1 (a N-cadherin inhibitor) yielded a high complete response rate (50%).
Source: Beasley GM, Cancer 2009, 115:4766-74

PHOTOACUSTIC FLOW CYTOMETRY
Two color photoacustic flow cytometry with diode laser can reliably detect up to 1 melanoma cell per ml, which can be relevant for searching circulating melanoma cells.
Source: Galanzha EI, Cancer Res 2009, 69:7926-34

SNF5 TUMOR SUPPRESSOR GENE
SNF5, the core subunit of SWI/SNF complex, is downregulated in melanoma, which correlates with poor patients' prognosis; in vitro, SNF5 knockdown causes chemoresistance.
Source: Lin H, Clin Cancer Res 2009, 15:6404-11

MC1R VARIANTS AND MELANOMA RISK
In this case-control study (n=1,185), red hair color (RHC) and non-RHC melanocortin receptor 1 (MC1R) variants were the major contributors for melanoma risk in the German and Spanish population, respectively.
Source: Scherer D, Int J Cancer 2009, 125:1868-75

YM155 PHASE II TRIAL
In this trial (n=34), YM155 (a survivin inhibitor) failed to demonstrate significant anti-melanoma activity.
Source: Lewis KD, Invest New Drugs 2009, Epub ahead of print

MELANOMA THICKNESS TRENDS
An analysis of the SEER database revealed that over the past 20 years the proportion of melanoma in situ has increased, while thick melanoma proportion has remained substantially unchanged.
Source: Criscione VD, J Invest Dermatol 2009, Epub ahead of print

MIR-15B AND MELANOMA
MicroRNA-15b represents is an independent prognostic factor and increases melanoma cell proliferation and survival.
Source: Satzger I, Int J Cancer 2009, Epub ahead of print

LACUNARITY ANALYSIS
Lacunarity analysis (a simple statistical measure used for the analysis of fractal and multi-scaled images) of digitized dermoscopic images could help clinicians to diagnose cutaneous melanoma.
Source: Gilmore S, PLoS One 2009, 4:e7449

CD40L PLUS TLR AGONISTS
In an in vivo mouse melanoma model, nanoparticle-delivered multimeric soluble CD40L DNA show synergistic therapeutic effect combined with toll-like receptor (TLR) agonists.
Source: Stone GW, PLoS One 2009, 4:e7334

EXCISION MARGINS META-ANALYSIS
According to a Cochrane meta-analysis of randomized controlled trials, primary melanoma excision margins (wide vs narrow) do not affect patients' overall survival.
Source: Sladden MJ, Cochrane Database Syst Rev 2009, CD004835

WARNING ON PI-103
In an in vivo mouse melanoma model, PI-103 - a dual PI3K (p110alpha)/mTOR inhibitor - has no synergistic effect with sorafenib (BRAF/CRAF inhibitor), may cause immunosuppression, inhibit apoptosis and ultimately favor tumor growth.
Source: López-Fauqued M, Int J Cancer 2009, Epub ahead of print

KIT AND HIF-1 alpha
c-Kit mutant melanocytes show activation of PI3K pathway that is not sufficient for transformation; combination with HIF-1 forced expression leads to Ras/Raf/Mek/Erk pathway activation and melanocyte transformation.
Source: Monsel G, Oncogene 2009, Epub ahead of print

TYRO3 AND MITF
The receptor protein tyrosine kinase TYRO3 is an upstream regulator of MITF expression; its knockdown shows antimelanoma activity in a xenograft model and acts as a chemosensitizer.
Source: Zhu S, Proc Natl Acad Sci USA 2009, 106:17025-30

ROR2 AND WNT5A
The orphan tyrosine kinase receptor ROR2 mediates Wnt5A signaling in metastatic melanoma and its silencing shows antimelanoma activity in an in vivo mouse model.
Source: O'Connell MP, Oncogene 2009, Epub ahead of print

PAEP FUNCTIONAL CHARACTERIZATION
Silencing of PAEP (progestagen-associated endometrial protein) shows anti-melanoma activity in a xenograft model.
Source: Ren S, J Cell Mol Med 2009, Epub ahead of print

EPAC AND MIGRATION
Silencing of EPAC (an effector molecule of cAMP) inhibits melanoma cell migration.
Source: Baljinnyam E, Am J Physiol Cell Physiol 2009, 297:C802-13

MT1 MELATONIN RECEPTOR
MT1 melatonin receptor is expressed in primary melanoma and correlates with tumor thickness.
Source: Danielczyk K, Anticancer Res 2009, 29:3887-95

MITF AND BRAF V600E
In an in vitro model of human melanoma, silencing of MITF synergically increases the cytotoxic effect of BRAF V600E silencing.
Source: Kido K, Cancer Sci 2009, 100:1863-9

TREMELIMUMAB + VACCINE
In a phase I-II trial (n=16), MART-1 peptide-pulsed dendritic cells and tremelimumab resulted in objective and durable tumor responses at the higher range of the expected response rate with either agent alone.
Source: Pandha HS, Clin Cancer Res 2009, 15:6158-66

ONCOLYTIC REOVIRUS
In a murine in vivo melanoma model, oncolytic Reovirus increases the antitumor activity of cisplatin.
Source: Pandha HS, Clin Cancer Res 2009, 15:6158-66

ADJUVANT RADIOTHERAPY
In a retrospective study (n=77), adjuvant radiotherapy after lymph node dissection yields a high locoregional control rate, although distant metastases remain the major cause of mortality.
Source: Conill C, Clin Transl Oncol 2009, 11:688-93

SNB RECOMMENDATIONS
The European Association of Nuclear Medicine (EANM) and the EORTC have jointly released the recommendations for sentinel node biopsy in melanoma.
Source: Chakera AH, Eur J Nucl Med Mol Imaging 2009, 36:1713-42

HSV2 MUTANT DeltaPK
The growth defective herpes simplex virus type 2 mutant deltaPK shows significant antitumor activity in a xenograft model of human melanoma.
Source: Colunga AG, Gene Ther 2009, Epub ahead of print

MELANOMA INHIBITORY ACTIVITY (MIA)
MIA protein is highly expressed and secreted by malignant melanoma cells and plays an important role in melanoma development, progression and tumor cell invasion.
Source: Schmidt J, Int J Cancer 2009, 125:1587-94

CAVEOLIN-1
In an in vitro model, caveolin-1 promotes human melanoma progression as indicated by enhanced proliferation, migration, invasion and foci formation in semisolid medium.
Source: Felicetti F, Int J Cancer 2009, 125:1514-22

ARTEMISININ
Artemisinin (an antimalarial drug) reduces human melanoma cell migration by downregulating alpha V beta 3 integrin and metalloproteinase-2.
Source: Buommino E, Invest New Drugs 2009, 27:412-8

FAMILIAL MELANOMA IDENTIFICATION
In this review article, the Authors found that CDKN2A germline mutations (responsible for about 2% of melanomas) are more frequent in individuals with 3 or more primary invasive melanomas.
Source: Leachman SA, J Am Acad Dermatol 2009, 61:677.e1-14

MOESIN AND INVASION
In a 3D model, moesin orchestrates cortical polarity of melanoma cells, which may drive tumor vertical migration instead of superficial spreading.
Source: Estecha A, J Cell Sci 2009, 122(Pt 19):3492-501

MELANOMA REPROGRAMMING
Mouse melanoma cells can be reprogrammed into induced pluripotent stem cells, which suggests that cancer cells remain susceptible to transcription factor-mediated reprogramming.
Source: Utikal J, J Cell Sci 2009, 122(Pt 19):3502-10

PET VERSUS CT FOR STAGING
In a prospective comparison (n=251), PET and CT were equivqlent in upstaging; treatment changed in 19% of patients (79% using both scans, 17% only by PET, 4% only by CT).
Source: Bastiaannet E, J Clin Oncol 2009, 27:4774-80

WT1 AND MELANOMA DIAGNOSIS
Wilms' tumor 1 (WT1) protein expression is not helpful for the diagnosis of skin melanoma in a series of 45 cases.
Source: Rosner K, J Cutan Pathol 2009, 36:1077-82

SILIBININ AND MITOMYCIN-C
In an in vitro model, silibinin (a flavonoid from plant-derived silymarin) protects melanoma cells from mitomycin-C cytotoxicity.
Source: Jiang YY, J Pharmacol Sci 2009, 111:137-46

MELANOMA SPONTANEOUS REGRESSION
A review of the literature on the phenomenon of metastatic melanoma spontaneous regression reveals a total of 76 reported cases since 1866.
Source: Kalialis LV, Melanoma Res 2009, 19:275-82

ESTROGENS AND TUMOR THICKNESS
A retrospective Dutch study (n=687), use of estrogens is not associated with primary melanoma thickness.
Source: Koomen ER, Melanoma Res 2009, 19:327-32

GALLIUM COMPLEX KP46
In an in vitro model, gallium complex KP46 shows strong anti-melanoma activity.
Source: Valiahdi SM, Melanoma Res 2009, 19:283-93

GALECTIN-3 AND PROGNOSIS
Serum levels of galectin-3 may have an independent prognostic value in stage III-IV melanoma patients.
Source: Vereecken P, Melanoma Res 2009, 19:316-20

LAMININ-421 AND MIGRATION
In an in vitro model, antibody blockage of lymphatic endothelial cell laminin-421 inhibits migratory ability of melanoma cells.
Source: Saito N, Pigment Cell Melanoma Res 2009, 22:601-10

FOLATE RECETOR ALPHA AND METHOTREXATE
In an in vitro model, folate receptor mediated sequestration of methotrexate (MTX) in melanosomes may be targeted to overcome melanoma resistance to MTX.
Source: Sánchez del Campo L, Pigment Cell Melanoma Res 2009, 22:588-600

CREB AND CYR61
In an in vivo model, stable silencing of cAMP-response element-binding protein (CREB) expression in human metastatic melanoma cell lines suppresses tumor growth and experimental metastasis by downregulating cysteine-rich protein 61 (CCN1/CYR61) expression.
Source: Dobroff AS, J Biol Chem 2009, 284:26194-206

INDUCING MELANOMA DIFFERENTIATION
Induction of terminal differentiation in melanoma cells by downregulation of beta-amyloid precursor protein (APP) impairs cell proliferation and improves chemosensitivity.
Source: Bothelho MG, J Invest Dermatol 2009, Epub ahead of print

MART1 + P40 VACCINE
In a pilot study (n=14), vaccination with Melan-A/Mart-1 peptide and Klebsiella protein P40 as an adjuvant induced ex vivo detectable tumor antigen specific T cell responses in 6 patients.
Source: Lienard D, J Immunother 2009, Epub ahead of print

NEW MELANOMA ANTIGEN MELOE-2
An additional open reading frame (ORF) on meloe cDNA encodes a new melanoma antigen, MELOE-2, recognized by melanoma-specific T cells in the HLA-A2 context.
Source: Godet Y, Cancer Immunol Immunother 2009, Epub ahead of print

LOSARTAN PRECLINICAL ACTIVITY
In an in vivo murine melanoma model, inhibition of angiotensin II receptor 1 (AT1) by losartan limits tumor angiogenesis and growth.
Source: Otake AH, Cancer Chemother Pharmacol 2009, Epub ahead of print

EARLY VS LATE ONSET MELANOMA
Using the SEER database, investigators found epidemiological differences between early and late onset melanomas.
Source: Anderson WF, Cancer 2009, 115:4176-85

CAR-T CELLS PRECLINICAL ACTIVITY
In a xenograft model, immunotherapy of metastatic human melanoma using chimeric antigen receptors (CAR) engineered ganglioside GD2-specific T cells increases the survival of tumor-bearing animals.
Source: Yvon E, Clin Cancer Res 2009, 15:5852-60

GPIbalpha AND METASTASIS
In a mouse in vivo model, platelet glycoprotein Ib alpha (GPIbalpha) inhibition promotes melanoma metastasis.
Source: Erpenbeck L, J Invest Dermatol 2009, Epub ahead of print

PET META-ANALYSIS
A meta-analysis of 24 sudies shows that (18)F-FDG positron emission tomography is not useful to detect regional metastases, but could be useful to detect distant metastases.
Source: Jiménez-Requena F, Eur J Nucl Med Mol Imaging 2009, Epub ahead of print

ERBB4 MUTATIONS
ERBB4/HER4 mutations were found in 19% of individuals with melanoma (n=79); melanoma cells expressing mutant ERBB4 had reduced cell growth after shRNA-mediated knockdown of ERBB4 or treatment with ERBB inhibitor lapatinib.
Source: Prickett TD, Nat Genet 2009, 41:1127-32

SYNTAXIN-7
Using an antibody-based proteomics approach, investigators found that Syntaxin-7 (STX7) is selectively expressed in melanocytes and melanoma.
Source: Strömberg S, J Proteome Res 2009, 8:1639-46

OBESITY AND PROGRESSION
In a mouse melanoma model, obesity enhances melanoma growth in vivo, possibily by upregulation of VEGF pathways.
Source: Brandon EL, Cancer Biol Ther 2009, Epub ahead of print

MENADIONE AND SIAH2
Menadione is a specific inhibitor of SIAH2 ubiquitin ligase; in vivo, it inhibits the growth of xenograft melanoma.
Source: Shah M, Pigment Cell Melanoma Res 2009, 22:799-808

POSITIVE NON-SENTINEL LYMPH NODE (NSLN)
Among node-positive melanoma patients (n=429), presence of a positive NSLN is a highly significant poor prognostic sign, which warrants completion lymph node dissection after a positive SLN.
Source: Ghaferi AA, Ann Surg Oncol 2009, 16:2978-84

DNA REPAIR GENE POLYMORPHISMS
A meta-analysis (cases=4,195) reveals that XPD/ERCC2 single nucleotide polymorphism rs13181 is associated with risk of melanoma development.
Source: Mocellin S, Carcinogenesis 2009, 30:1735-43

MELANOSOMES AND CHEMORESISTANCE
In an vitro model, melanosome dynamics (e.g. biogenesis, density, status and structural integrity) modulates the drug resistance of melanoma cells.
Source: Chen KG, J Natl Cancer Inst 2009, 101:1259-71

PAR1, PAFR AND METASTASIS
Protease-activated receptor-1 (PAR1) and platelet-activating factor receptor (PAFR) induce melanoma cell adhesion molecule (MCAM/MUC18) expression and favor melanoma metastasis.
Source: Melnikova VO, J Biol Chem 2009, 284:28845-55

FKBP51 AND RADIOSENSITIZATION
Inhibition of FK506-binding protein 51 (FKBP51, an immunophilin with isomerase activity) greatly enhances radiotherapy efficacy in a xenograft melanoma model.
Source: Romano S, Cell Death Differ 2009, Epub ahead of print

NEW TNM STAGING SYSTEM
The latest version of the AJCC TNM staging system for cutaneous melanoma has been released (based on 30,946 cases). Main changes: 1) mitotic rate (added); 2) Clark level (removed). Main limit: no molecular biomarker has been implemented. The details are available in the TNM Staging section of the MMMP website.
Source: Balch CM, J Clin Oncol 2009, Epub ahead of print

SYNDECANS AND WNT5A
Heparan sulfate proteoglycans syndecan 1 and 4 are key components of the Wnt5A autocrine signaling, the activation of which leads to increased metastasis of melanoma.
Source: O'Connell MP, J Biol Chem 2009, 284:28704-12

US SCAN FOR PRIMARY THICKNESS
In a small study (n=53), preoperative 10-MHz sonography could discriminate thick (> 1 mm) from thin melanomas with promising accuracy.
Source: Vilana R, AJR Am J Roentgenol 2009, 193:639-43

CHEST X-RAY QUESTIONED
In 248 patients undergoing SNB, preoperative chest X-ray did not identify pulmonary metastasis and did not change planned treatment strategies.
Source: Vermeeren L, J Surg Res 2009, Epub ahead of print

NOVEL PET RADIOTRACER
A new melanoma positron emission tomography (PET) imaging radiotracer has been developed with high tumor-to-body contrast ratio and rapid renal clearance.
Source: Greguric I, J Med Chem 2009, 52:5299-302

4-HYDROXYCOUMARIN PRECLINICAL ACTIVITY
Anticoagulat 4-hydroxycoumarin (4-HC) resulted effective against melanoma in an in vivo mouse model.
Source: Salinas-Jazmín N, Cancer Chemother Pharmacol 2009, Epub ahead of print

LUMCORIN AND MIGRATION
In an in vitro study, lumcorin (a peptide derived from human lumican) inhibits melanoma migration.
Source: Zeltz C, FEBS Lett 2009, 583:3027-32

MELANOMA DETECTION ABILITY
An Australial study showed that the ability of skin cancer clinics to detect melanoma is similar to that of mainstream general practice and worse than specialist practice.
Source: Hansen C, J Am Acad Dermatol 2009, 61:599-604

WHOLE BRAIN RADIOTHERAPY (WBRT)
A small retrospective study (n=51) suggests that patients with brain metastases from melanoma receiving WBRT alone may benefit from dose escalation beyond 10x3 Gy.
Source: Rades D, Int J Radiat Oncol Biol Phys 2009, Epub ahead of print

MELANOMA EPIDEMIC
In a study conduced in East Anglia, melanoma incidence increased from 9.39 to 13.91 cases/100,000/year, while overall mortality only increased from 2.16 to 2.54 cases/100,000/year.
Source: Levell NJ, Br J Dermatol 2009, 161:630-4

DTIC +/- PF3512676
In a phase II-III RCT, the addition of CpG oligodeoxynucleotide PF-3512676 does not add significant tumor response advantage to dacarbazine alone.
Source: Weber J, Cancer 2009, 115:3944-54

HLA MOLECULES EXPRESSION
Investigators have assessed the expression of HLA class I and II molecules in a large panel of human melanoma cell lines.
Source: Mendez R, Cancer Immunol Immunother 2009, 58:1507-15

ADHESION MOLECULES EXPRESSION
Investigators have assessed the expression of adhesion molecules and ligands for receptors involved in cell-mediated cytotoxicity in a large panel of human melanoma cell lines.
Source: Casado JG, Cancer Immunol Immunother 2009, 58:1517-26

IPILIMUMAB PLUS BUDESONIDE
A phase II RCT showed that budesonide (an oral non-absorbed corticostroid) does not prevent dyarrhea in patients taking anti-CTLA4 ipilimumab.
Source: Weber J, Clin Cancer Res 2009, 15:5591-8

CXCL8 AND ITS RECEPTORS
In a human melanoma preclinical model, CXCL8 induces cell proliferation and angiogenesis; inhibition of its receptors (CXCR1 and CXCR2) shows promising therapeutic potential.
Source: Gabellini C, Eur J Cancer 2009, 45:2618-27

NBDHEX PRECLINICAL ACTIVITY
6-(7-Nitro-2,1,3-benzoxadiazol-4-ylthio)hexanol (NBDHEX) induces JNK activation and apoptosis, and appears effective against human melanoma in both in vitro and in vivo preclinical models.
Source: Pellizzari Tregno F, Eur J Cancer 2009, 45:2606-17

TIL AND SENTINEL NODE STATUS
An Italian study (n=404) showed a significant correlation between the presence of tumor infiltrating lymphocytes (TIL) and sentinel node status.
Source: Mandalà M, Eur J Cancer 2009, 45:2537-45

IMIDAZO[1,2-a]QUINOXALINE ANALOGUES
New imidazo[1,2-a]quinoxaline analogues have been synthesized that inhibit human melanoma growth in vitro more than imiquimod and fotemustine.
Source: Deleuze-Masquefa C, Eur J Med Chem 2009, 44:3406-11

PD1 BLOCKADE
In an in vitro human model, programmed death-1 (PD-1) blockade reverses the suppression of melanoma antigen-specific CTL by CD4+ CD25(Hi) regulatory T cells.
Source: Wang W, Int Immunol 2009, 21:1065-77

OBATOCLAX AND TUNICAMYCIN
Human melanoma cells under endoplasmic reticulum stress (induced by tunicamycin) are more susceptible to apoptosis induced by the BH3 mimetic obatoclax.
Source: Jiang CC, Neoplasia 2009, 11:945-55

US-BASED THICKNESS PREDICTION
A review of the literature showed that high resolution ultrasound imaging correctly predicts excision margins in 72% of cases.
Source: Machet L, Ultrasound Med Biol 2009, 35:1411-20

PIGMENTATION GENE POLYMORPHISMS
In an Australian study, multiple pigmentation gene polymorphisms account for 12% of risk of skin melanoma.
Source: Duffy DL, J Invest Dermatol 2009, Epub ahead of print

RET G691S POLYMORPHISM
This germline RET polymorphism is frequently found in melanoma and responds to GDNF (glial cell line-derived neurotrophic factor), which promotes melanoma progression.
Source: Narita N, Oncogene 2009, 28:3058-68

ADJUVANT RADIOTHERAPY
Patients with clinically advanced, high-risk, lymph node-metastatic melanoma may benefit from adjuvant radiotherapy.
Source: Agrawal S, Cancer 2009, Epub ahead of print

MCL-1 AND ABT-737
In an in vitro melanoma models, RNA silencing of Mcl-1 enhances apoptosis induced by ABT-737 (a small-molecule inhibitor of Bcl-2, Bcl-XL and Bcl-W).
Source: Keuling AM, PLoS One 2009, 4:e6651

PAR-1 AND CONNEXIN-43
Protease-activated receptor-1 (PAR-1) promotes melanoma progression by enhancing connexin-43 expression.
Source: Villares GJ, Cancer Res 2009, 69:6730-7

DEK: A CHEMORESISTANCE ONCOGENE
Inhibition of DEK (a gene often overexpressed in advanced melanoma due to gain of chromosome 6p) expression by RNA interference restores melanoma sentitivity to chemotherapy agents.
Source: Khodadoust MS, Cancer Res 2009, 69:6405-13

NKG2D LIGANDS AND PROGNOSIS
At multivariable survival analysis, serum levels of ULBP2 (a NKG2D ligand able to neutralize cytotoxic lymphocytes) correlate with the prognosis of melanoma patients (n=200).
Source: Paschen A, Clin Cancer Res 2009, 15:5208-15

SNB IN YOUNG ADULTS
In an Australian study, SLN positivity rate was higher in young melanoma patients (n=55) than in adults (25% vs 17%), while non-SLN positivity and melanoma-specific death rates were lower.
Source: Howman-Giles R, Ann Surg Oncol 2009, Epub ahead of print

CD28/CTLA4/ICOS SNPs
In a large German study (cases=763), the SNPs of three immune related genes (CD28, CTLA4 and ICOS) do not appear to be associated with melanoma risk or prognosis.
Source: Bouwhuis MG, Cancer Immunol Immunother 2009, Epub ahead of print

METRONOMIC CYCLOPHOSPHAMIDE (mCP)
In a small retrospective study (n=13) of oral mCP in elderly patients with unresectable melanoma, the control rate (partial + stable disease) was 46% and the median survival was 8 months.
Source: Borne E, Invest New Drugs 2009, Epub ahead of print

PI3K/AKT, mTOR AND BRAF
Co-inhibition of PI3K/AKT and BRAF (but not mTOR) synergically inhibits human uveal melanoma cells proliferation in vitro.
Source: Babchia N, Invest Ophthalmol Vis Sci 2009, Epub ahead of print

PIGMENT EPITHELIUM-DERIVED FACTOR (PEDF)
In a mouse ocular melanoma model, constitutive overexpression of PEDF inhibits tumor growth and metastasis.
Source: Yang H, Invest Ophthalmol Vis Sci 2009, Epub ahead of print

dsRNA MIMIC TO KILL MELANOMA
In a mouse model, polyinosine-polycytidylic acid - a double strand RNA mimic - induces melanoma autophagy downstream of an exacerbated endosomal maturation program.
Source: Tormo D, Cancer Cell 2009, 16:103-14

FISH AND MELANOMA DIAGNOSIS
By detecting chromosomal alterations, fluorescence in situ hybridization (FISH) can be helpful for the diagnosis of melanoma.
Source: Gerami P, Am J Surg Pathol 2009, 33:1146-56

MICROMORPHOMETRY OF SLN METASTASIS
In 116 patients with tumor-positive sentinel lymph nodes (SLN), invasion depth and diameter of the metastasis correlate best with additional nodal disease; invasion depth best predicts overall survival.
Source: van der Ploeg IM, Ann Surg 2009, 250:301-4

SPARC AND OCULAR MELANOMA
SPARC (secreted protein acidic and rich in cysteine) is expressed in human uveal melanoma and its abrogation reduces tumor cell proliferation in vitro.
Source: Maloney SC, Anticancer Res 2009, 29:3059-64

OCULAR MELANOMA METASTASIS
In a large series of ocular melanomas (n=8033), the main factors predictive of metastasis by multivariate analysis included age, ciliary body location, increasing tumor diameter and thickness.
Source: Shields CL, Arch Ophthalmol 2009, 127:989-98

MELANOMA INCIDENCE FROM CHOROIDAL NEVUS
An analysis of 2514 consecutive cases of choroidal nevi showed that transformation into melanoma occurs in 2%, 9% and 13% of eyes at 1, 5 and 10 years, respectively.
Source: Shields CL, Arch Ophthalmol 2009, 127:981-7

NECK LYMPH NODE DISSECTION AND RADIOTHERAPY
In a retrospective study, regional disease control rate is higher with extended (vs selective) neck dissection and with (vs without) adjuvant radiotherapy.
Source: Hamming-Vrieze O, Arch Otolaryngol Head Neck Surg 2009, 135:795-800

VITAMIN D RECEPTOR (VDR) SNP
In a Polish study (n=763), four VDR signle nucleotide polymorphisms (rs1544410, rs731236, rs10735810, rs4516035) are not associated with melanoma risk.
Source: Gapska P, Cancer Epidemiol 2009, 33:103-7

RENAL TRANSPLANT AND MELANOMA
In an Australian study, immunosuppression after kidney transplant increases the risk of melanoma.
Source: Vajdic CM, Cancer Epidemiol Biomarkers Prev 2009, 18:2297-303

PHASE I TRIAL OF INO-1001 + TMZ
Myelosuppression and elevation of transaminases are the dose-limiting toxicities of INO-1001 (a PARP inhibitor) + temozolomide in patients with unresectable stage III-IV melanoma.
Source: Bedikian AY, Cancer Invest 2009, 27:756-63

ROLE OF TEM-8
In a mouse melanoma model, tumor growth is delayed in tumor endothelial marker 8 (TEM8)-deficient animals.
Source: Cullen M, Cancer Res 2009, 69:6021-6

METRONOMIC THERAPY
Combination metronomic chemotherapy regimens are an effective treatment of advanced human melanoma metastasis in immunodeficient mice.
Source: Cruz-Munoz W, Clin Cancer Res 2009, 15:4867-74

AUTOLOGOUS VACCINE AND SURVIVAL
In a small trial (n=47), 2,4-dinitrophenyl-conjugated autologous melanoma cell vaccine is capable of inducing effective antimelanoma CD4 T-cell activity associated with improved survival.
Source: Lotem, M, Clin Cancer Res 2009, 15:4968-77

TARGETED RADIONUCLIDE THERAPY
In a preclinical study, the quinoxaline derivative ICF01012 is selectively uptaken by malignant cells and is active against murine and human melanoma.
Source: Bonnet-Duquennoy M, Int J Cancer 2009, 125:708-16

MICRORNA-155
In vitro, mir-155 ectopic expression inhibits melanoma cell proliferation and promotes apoptosis.
Source: Levati L, Int J Oncol 2009, 35:393-400

RIG-I AND MDA-5
Retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated antigen 5 (MDA-5) helicases sense viral RNA in infected cells and initiate antiviral responses; in human melanoma cells they also initiate a proapoptotic signaling pathway independently of type I interferons (IFN).
Source: Besch R, J Clin Invest 2009, 119:2399-411

LYMPHOSCINTIGRAPHY AND SLN STATUS
A significant association exists between the lymphoscintigraphy pattern of 88 patients with melanoma and the status of their sentinel lymph nodes (SLN).
Source: Solari N, Melanoma Res 2009, 19:243-51

PHYSICAL ACTIVITY AND MELANOMA RISK
In a Canadian study, occupational physical activity is associated with melanoma risk: it is unclear whether sunlight exposure can explain these findings.
Source: Lee TK, Melanoma Res 2009, 19:260-6

PHASE II TRIAL OF DHA-PACLITAXEL
The efficacy of docosahexaenoic acid (DHA)-paclitaxel as a first-line therapy for metastatic melanoma does not exceed that seen with other single-agent chemotherapies such as dacarbazine.
Source: Homsi J, Melanoma Res 2009, 19:238-42

NUCLEAR PTEN
In an in vitro melanoma model, nuclear PTEN is involved in G2 progression possibly through the modulation of CDC2.
Source: Jacob AI, Melanoma Res 2009, 19:203-10

GERM-LINE MDM2 MUTATION
In a small series of patients with melanoma (n=28), MDM2 polymorphism G309 may be responsible for MDM2 overexpression and p53 suppression.
Source: Gluck I, Melanoma Res 2009, 19:199-202

DESATINIB AND KIT-MUTATANT MELANOMA
Two patients with advanced melanoma harboring the c-KIT L576P mutation (the most common KIT mutation in mucosal, acral lentiginous and chronically sun-damaged melanomas) showed >50% tumor response to tyrosine kinase receptor inhibitor desatinib.
Source: Woodman SE, Mol Cancer Ther 2009, 8:2079-85

NEW MELANOMA RISK LOCUS
In a large European study based on 317K tagging SNP, genome-wide screening identified the 9p21 locus as a novel melanoma risk biomarker.
Source: Bishop DT, Nat Genet 2009, 41:920-5

PDGFR-alpha GENE THERAPY
In a mouse melanoma model, platelet-derived growth factor receptor alpha gene therapy inhibits tumor growth in vivo.
Source: Faraone D, Neoplasia 2009, 11:732-42

PD0325901 PRECLINICAL ACTIVITY
PD0325901, a novel MEK inhibitor, inhibits human melanoma growth in vivo (xenograft model) independently of BRAF mutational status.
Source: Ciuffreda L, Neoplasia 2009, 11:720-31

3D SKIN ANALYSIS
In a small series (cases = 11), statistical analysis of 3D skin surface disruptions may help differentiation between melanoma and benign lesions.
Source: Ding Y, Skin Res Technol 2009, 15:262-70

TALABOSTAT TRIAL
In a phase II trial of cisplatin + talabostat (an immunostimulatory dipeptidyl peptidase inhibitor) in stage IV melanoma patients, no advantage was observed over cisplatin alone.
Source: Eager RM, BMC Cancer 2009, 9:263

BMP-7 INHIBITION
Bone morphogenetic protein 7 induces mesenchymal-to-epithelial transition in melanoma cells, leading to inhibition of metastasis.
Source: Na YR, Cancer Sci 2009, Epub ahead of print

14-3-3 PROTEIN ISOFORM SIGMA
Epigenetic silencing of 14-3-3sigma might contribute to melanoma progression via loss of cell cycle control, impaired cell senescence and support to migration.
Source: Schultz J, Mol Cancer 2009, 8:53

PLEXIN-B1 AND BRAF
Plexin B1 is repressed by oncogenic B-Raf signaling and functions as a tumor suppressor in human melanoma cells.
Source: Argast GM, Oncogene 2009, 28:2697-709

NRG1/ERBB3 PATHWAY
Neuregulin (NRG) signaling through the receptor tyrosine kinase ERBB3 may inhibit melanocyte differentiation and promote cell migration and proliferation.
Source: Buac K, Pigment Cell Melanoma Res 2009, Epub ahead of print

SYNDECAN-2 AND MIGRATION
Syndecan-2, a transmembrane heparan-sulfate proteoglycan whose expression is enhanced by fibroblasts growth factor-2 (FGF2), stimulates the migratory potential of melanoma cells.
Source: Lee JH, J Biol Chem 2009, Epub ahead of print

EMD 273063 (hu14.18-IL2)
In a phase I-II trial (n=9), a humanized anti-GD2 monoclonal antibody fused to interleukin-2 increased tumor infiltration by T-cells but did not induced tumor response in stage IV melanoma patients.
Source: Ribas A, J Transl Med 2009, 7:68

S-100B AND PROGNOSIS
In patients with stage III melanoma (n=56), serum S100B correlates with disease free survival at multivariable analysis.
Source: Kruijff S, Ann Surg Oncol 2009, Epub ahead of print

ADH-1 + ISOLATED LIMB PERFUSION (ILP)
Systemic ADH-1 (a cyclic pentapeptide that disrupts N-cadherin adhesion complexes) shows synergistic activity with melphalan ILP in patients with in transit melanoma metastases.
Source: Beasley GM, Cancer 2009, Epub ahead of print

CEACAM1 AND PROGNOSIS
In patients with melanoma (n=64), serum CEACAM1 levels are a negative prognostic factor at multivariable survival analysis.
Source: Markel G, Cancer Immunol Immunother 2009, Epub ahead of print

RANTES + GP100 VACCINE
In a mouse in vivo melanoma model, vaccination with chemokine RANTES and gp100 is more effective than gp100 alone.
Source: Aravindaram K, Gene Ther 2009, Epub ahead of print

TIMP-2, NFKB AND IL-8
Tissue inhibitor of metalloproteinase-2 (TIMP-2) induces nuclear factor kappa B (NFkB) activity which in turn activates interleukin-8 (IL-8) expression.
Source: Sun J, J Mol Signal 2009, 4:4

EM011 PRECLINICAL ACTIVITY
In a syngeneic murine in vivo model, the tubulin-binding agent EM011 shows significant anti-melanoma activity with no toxicity.
Source: Anaja R, Int J Cancer 2009, Epub ahead of print

SRC AND UVEAL MELANOMA
The SRC kinase is associated with ERK1/2 activation in primary uveal melanoma but metastatic cell lines are resistant to SRC inhibition.
Source: Maat W, Br J Cancer 2009, 101:312-9

HUMAN ENDOGENOUS RETROVIRUSES (HERV)
Retrovirus-like particles and the expression of HERV mRNA and proteins have been demonstrated in melanoma tissue and might be implicated in melanomagenesis.
Source: Singh S, Br J Dermatol 2009, Epub ahead of print

MUTATED EGFR INDUCES MELANOMA
In a medaka fish transgenic melanoma model, a mutated EGFR is sufficient to induce malignant melanoma with a 100% penetrance.
Source: Schartl M, J Invest Dermatol 2009, Epub ahead of print

LUNG METASTASECTOMY
In a small series of patients undergoing resection of isolated pulmonary metastases, tumor doubling time, Glut-1 and CD31 expression were significant predictors of survival.
Source: Lee JH, Ann Surg Oncol 2009, Epub ahead of print

VITAMIN D RECEPTOR (VDR) POLYMORPHISMS
In a meta-analysis of 3,769 melanoma cases, the VDR FokI T allele and the BsmI A allele are associated with increased and decreased melanoma risk, respectively.
Source: Randerson-Moor JA, Eur J Cancer 2009, Epub ahead of print

PULSED ELECTRIC FIELD THERAPY
In an in vivo mouse model, pulsed electric field therapy disrupts the melanoma's blood supply and causes complete remission without recurrence.
Source: Nucitelli R, Int J Cancer 2009, 125:438-45

SEASON OF DIAGNOSIS
In a population-based study (n=26,060), season of diagnosis has no impact on survival from malignant melanoma.
Source: Jayasekara H, Int J Cancer 2009, 125:488-90

OXALIPLATIN + DOCETAXEL + GM-CSF
A phase II trial (n=19) demonstrated that combining oxaliplatin + docetaxel + GM-CSF yields no objective tumor response in previously treated advanced melanoma patients.
Source: Locke F, Cancer Chemother Pharmacol 2009, Epub ahead of print

MACROPHAGE MARKERS OF PROGNOSIS
Serum levels of CD163 (n=227) and tumor infiltration by CD68+ macrophages (n=190) independently correlates with survival of TNM stage I-II melanoma patients.
Source: Jensen TO, J Clin Oncol 2009, 27:3330-7

THYROID GENE EXPRESSION
Induction of thyroid gene expression by MAP kinase and PI3K/Akt pathways inhibition sensitizes melanoma cells to radioiodine therapy.
Source: Hou P, PLoS One 2009, 4:e6200

ASA AND MELANOMA RISK
A large Dutch population-based case-control study suggested that continuous use of low-dose acetylsalicylic acid (ASA) may be associated with reduced melanoma risk in women.
Source: Joosse A, J Invest Dermatol 2009, Epub ahead of print

FABP7 EXPRESSION
Immunohistochemistry analysis of 37 paired primary and metastatic melanomas revealed that fatty acid-binding protein-7 (FABP7) is more expressed in primary (73%) than metastatic (27%) samples.
Source: Goto Y, J Invest Dermatol 2009, Epub ahead of print

CXCR1 or CXCR2 KNOCKDOWN
In a human melanoma xenograft model, RNA interference mediated knockdown of CXCR1 or CXCR2 (receptors for chemokine CXCL-8) inhibits tumor growth.
Source: Singh S, Int J Cancer 2009, Epub ahead of print

SKI KNOCKDOWN
In a human melanoma xenograft model, RNA interference mediated knockdown of SKI (an antagonist of TGF-beta signaling) inhibits tumor growth.
Source: Chen D, Pigment Cell Melanoma Res 2009, Epub ahead of print

BRAF AND MC1R MUTATIONS
In 123 Australian patients, BRAF-mutant melanomas were less frequent in people with high levels of lifetime sun exposure, with no association between germline MC1R status and somatic BRAF mutations.
Source: Hacker E, J Invest Dermatol 2009, Epub ahead of print

GALECTIN-3: PROGNOSTIC ROLE
Serum levels of galectin-3 have an independent prognostic value in patients with stage III-IV cutaneous melanoma patients.
Source: Vereecken P, Melanoma Res 2009, Epub ahead of print

GAB2 AMPLIFICATION
Among acral and mucosal melanomas (n=23), GAB2 is amplified in 26% of cases and might be critical for melanomas arising from sun-protected sites.
Source: Chernoff KA, Clin Cancer Res 2009, 15:4288-91

ANTI HMW-MAA ANTIBODY
The melanoma specific 9.2.27PE immunotoxin (which recognizes the high molecular weight melanoma associated antigen, HMW-MAA) efficiently kills melanoma cells in vitro.
Source: Risberg K, Int J Cancer 2009, 125:23-33

ADJUVANT GM-CSF
Granulocyte-macrophage colony stimulating factor (GM-CSF) administered as adjuvant therapy in 98 patients with stage II-IV melanoma yielded a 60% 5-year disease-specific survival rate.
Source: Spitler LE, J Immunother 2009, 32:632-7

INTERFERING WITH DNMT3A
In a mouse model, knockdown of DNA methyltransferase 3a (DNMT3A) by RNA interference inhibits melanoma growth and metastasis.
Source: Deng T, Biochem Biophys Res Commun 2009, 387:611-6

CPK PREDICTS ILI TOXICITY
In 171 patients undergoing isolated limb infusion (ILI) for in transit metastases, creatine phosphokinase (CPK) serum levels correlate with locoregional toxicity.
Source: Santillan AA, Ann Surg Oncol 2009, 16:2570-8

VITAMIN D SERUM LEVELS
In 205 patients with cutaneous melanoma, vitamin D serum levels are higher in stage IV as compared to stage I disease.
Source: Nürnberg B, Anticancer Res 2009, 29:3669-74

VITAMIN D AND PPAR
Vitamin D inhibits melanoma cell proliferation in vitro, the effect being modulated by peroxisome proliferator-activated receptor (PPAR) signaling.
Source: Sertznig P, Anticancer Res 2009, 29:3647-58

GNAQ MUTATIONS AND UVEAL MELANOMA
GNAQ mutations are frequent in uveal melanoma (53%) but are not correlated with disease free survival of 75 patients.
Source: Bauer J, Br J Cancer 2009, 101:813-5

ERYTHROPOIETIN AND MELANOMA
Overexpression of functional erythropoietin receptor (EpoR) expression in melanoma metastasis specimens might be a warning for the treatment of anemia in these patients.
Source: Mirmohammadsadegh A, J Invest Dermatol 2009, Epub ahead of print

BIMODAL MELANOMA PATHWAYS
Epidemiological data support that early-onset melanoma may represent gene-intermittent sun exposure interaction while late-onset melanoma may reflect chronic exposure sun damage.
Source: Anderson WF, Cancer 2009, Epub ahead of print

DELIMOTECAN PRECLINICAL ACTIVITY
In a xenograft model, delimotecan (a camptothecin analog bound to carboxymethyl dextran) is active against a DTIC-resistant human melanoma cell line.
Source: Bigioni M, Int J Cancer 2009, Epub ahead of print

AUTOANTIBODIES AND RESPONSE TO IFNalpha
In two randomized trials of adjuvant interferon-alpha, appearance of autoantibodies was not associated with melanoma patient relapse-free survival.
Source: Bouwhuis MG, J Natl Cancer Inst 2009, 101:869-77

RETINOIC ACID AND MELANOMA
In an in vitro model, retinoic acid receptor gamma (RARg) inhibits melanoma invasiveness by inducing expression of carbohydrate sulfotransferase-10 (CHST10).
Source: Zhao X, Cancer Res 2009, 69:5218-25

C10, A TLR3 INHIBITOR
In a xenograft model, phenylmethimazole (C10) decreases toll like receptor-3 (TLR3) and non-canonical WNT5a signaling, and shows anti-melanoma activity.
Source: Schwartz AL, Clin Cancer Res 2009, 15:4114-22

STROMAL MMP-13 AND INVASIVENESS
In a mouse model, melanoma invasion and metastasis are reduced in matrix metalloproteinase-13 (MMP-13) knockout animals as compared to wild-type littermates.
Source: Zigrino P, J Invest Dermatol 2009, Epub ahead of print

SALIVARY MARKERS OF ADVANCED MELANOMA
In a mouse melanoma model, microarray analysis showed that salivary transcriptomes were significantly different in tumor-bearing mice vs controls.
Source: Gao K, PLoS One 2009, 4:e5875

IDO INHIBITORS DISCOVERY
In a mouse melanoma model, potent competitive inhibitors of IDO (indoleamine 2,3-dioxygenase; a tumor immune escape related enzyme) have been discovered.
Source: Yue EW, J Med Chem 2009, Epub ahead of print

TAXOL + CISPLATIN + DTIC
In a phase I-II trial (n=46), paclitaxel + cisplatin + dacarbazine optimal doses were determined, the overall response rate being 41% (2 CR + 17 PR).
Source: Papadopoulos NE, Am J Clin Oncol 2009, Epub ahead of print

ONCOLYTIC + IL18 GENE THERAPY
In a mouse model, oncolytic adenoviral vector encoding IL-18 showed greater anti-melanoma activity than oncolytic virus or IL-18 gene therapy alone.
Source: Zheng JN, Cancer Gene Ther 2009, Epub ahead of print

CLINICAL TRIAL OF XENOGENEIC VACCINE
A phase I trial showed that a human and mouse gp100 DNA vaccine is safe and can lead to immune response in patients with early stage melanoma.
Source: Yuan J, Cancer Immun 2009, 9:5

UVEAL MELANOMA METASTASIS DETECTION
In a small study (n=27), 18-FDG PET-CT and S-100B serum levels are useful to detect liver metastases from cutaneous but not uveal melanoma.
Source: Strobel K, Eur J Nucl Med Mol Imaging 2009, Epub ahead of print

WFDC1: CANDIDATE MELANOMA SUPPRESSOR
In a human melanoma xenograft model, WFDC1 overexpression resulted in a significant delay of tumor growth, which likely involves upregulation of DKK1 (a WNT pathway inhibitor).
Source: Liu S, Clin Exp Metastasis 2009, Epub ahead of print

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