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Metastatic melanoma is hallmarked by its ability of phenotype switching to more slowly proliferating, but highly invasive cells.,Here, we tested the impact of signal transducer and activator of transcription 3 (STAT3) on melanoma progression in association with melanocyte inducing transcription factor (MITF) expression... | Background.,There are several circulatory biomarkers that are involved in forecasting the clinical outcome of cutaneous melanoma.,Serum/plasma vitamin D status is one of the markers intensively studied in this type of cutaneous cancer.,The combination of validated serum biomarkers (like LDH) with new biomarkers such as... | 1 |
Previous studies suggested a protective effect of vitamin D against skin cancer development.,However, epidemiologic studies on orally taken vitamin D and risk of skin cancer (basal cell carcinoma [BCC], squamous cell carcinoma [SCC], and melanoma) are few.,We prospectively evaluated whether total, dietary and supplemen... | Epidemiological evidence shows that people with thicker, or higher stage, melanomas have lower vitamin D status compared to those with thinner tumours.,Evidence from experimental studies is inconsistent, but some suggest that administration of vitamin D metabolites can decrease tumour aggressiveness.,Determine the rela... | 1 |
Oncogene-driven metabolic rewiring is an adaptation to low nutrient and oxygen conditions in the tumor microenvironment that enables cancer cells of diverse origin to hyperproliferate.,Aerobic glycolysis and enhanced reliance on glutamine utilization are prime examples of such rewiring.,However, tissue of origin as wel... | Serum lactate dehydrogenase (LDH) is a prognostic factor for patients with stage IV melanoma.,To gain insights into the biology underlying this prognostic factor, we analyzed total serum LDH, serum LDH isoenzymes, and serum lactate in up to 49 patients with metastatic melanoma.,Our data demonstrate that high serum LDH ... | 1 |
Tip110, an important regulator of several oncogenic proteins, was significantly downregulated in human metastatic melanoma cells exposed to a hypoxic condition.,Therefore, in this study, we set to determine whether differential expression of Tip110 could be an important indicator for melanoma tumorigenesis and metastas... | Extensive research has demonstrated a tumor‐promoting role of increased WNT5A expression in malignant melanoma.,However, very little light has been shed upon how WNT5A expression is up‐regulated in melanoma.,A potential regulator of WNT5A expression is the pro‐inflammatory cytokine Interleukin (IL)‐6, which shares the ... | 1 |
Mitogen activated-protein kinase pathway inhibitors (MAPKis) improve treatment outcome in patients with disseminated BRAFV600 mutant cutaneous malignant melanoma (CMM) but responses are of limited duration due to emerging resistance.,Although extensive research in mechanisms of resistance is being performed, predictive... | Almost 50% of metastatic melanoma patients harbor a BRAFV600 mutation andthe introduction of BRAF inhibitors has improved their treatment options.,BRAF inhibitors vemurafenib and dabrafenib achieved improved overall survival over chemotherapy and have been approved for the treatment of BRAF-mutated metastatic melanoma.... | 1 |
Effective treatment options are limited for patients with advanced (metastatic or unresectable) melanoma who progress after immune checkpoint inhibitors and targeted therapies.,Adoptive cell therapy using tumor-infiltrating lymphocytes has demonstrated efficacy in advanced melanoma.,Lifileucel is an autologous, central... | Supplemental Digital Content is available in the text.,The overall survival (OS) of patients with metastatic uveal melanoma is short, the evidence for effectiveness of treatments is limited, and no consensus on the choice of treatment exists.,We aimed to advance interpretation of OS as an outcome by pooling peer-review... | 1 |
Neoantigen-specific T cells are increasingly viewed as important immunotherapy effectors, but physically isolating these rare cell populations is challenging.,Here, we describe a sensitive method for the enumeration and isolation of neoantigen-specific CD8+ T cells from small samples of patient tumor or blood.,The meth... | MicroRNA (miRNA) signatures are not only found in cancer tissue but also in blood of cancer patients.,Specifically, miRNA detection in blood offers the prospect of a non-invasive analysis tool.,Using a microarray based approach we screened almost 900 human miRNAs to detect miRNAs that are deregulated in their expressio... | 1 |
Autophagy maintains homeostasis and is induced upon stress.,Yet, its mechanistic interaction with oncogenic signaling remains elusive.,Here, we show that in BRAFV600E-melanoma, autophagy is induced by BRAF inhibitor (BRAFi), as part of a transcriptional program coordinating lysosome biogenesis/function, mediated by the... | Activated RAS promotes dimerization of members of the RAF kinase family1-3.,ATP-competitive RAF inhibitors activate ERK signaling4-7 by transactivating RAF dimers4.,In melanomas with mutant BRAF(V600E), levels of RAS activation are low and these drugs bind to BRAF(V600E) monomers and inhibit their activity.,This tumor-... | 1 |
NLRP3 inflammasome was introduced as a double-edged sword in tumorigenesis and influenced immunotherapy response by modulating host immunity.,However, a systematic assessment of the NLRP3-inflammasome-related genes across human cancers is lacking, and the predictive role of NLRP3 inflammasome in cancer immunotherapy (C... | Cutaneous melanoma represents one of the deadliest types of skin cancer.,The prognosis strongly depends on the disease stage, thus early detection is crucial.,New therapies, including BRAF and MEK inhibitors and immunotherapies, have significantly improved the survival of patients in the last decade.,However, intrinsic... | 1 |
Gamma-delta (γδ) T lymphocytes are primed to potently respond to pathogens and transformed cells by recognizing a broad range of antigens.,However, adoptive immunotherapy with γδT cells has exhibited mixed treatment responses.,Better understanding of γδT cell biology and stratifying healthy donors for allogeneic adopti... | Targeted BRAF inhibition (BRAFi) and combined BRAF and MEK inhibition (BRAFi+MEKi) therapies have significantly improved clinical outcomes in patients with metastatic melanoma.,Unfortunately, the efficacy is beset by the acquisition of drug resistance1-6.,Here we investigated molecular mechanisms underlying acquired re... | 1 |
To evaluate the results of restaging completely resected stage IIIB/C melanoma prior to start of adjuvant therapy.,One hundred twenty patients with stage IIIB or IIIC (AJCC 2009) melanoma who underwent complete surgical resection were screened for inclusion in our trial investigating adjuvant dendritic cell therapy (NC... | Patients with high-risk stage II/III resected melanoma commonly develop distant metastases.,At present, we cannot differentiate between patients who will recur or those who are cured by surgery.,We investigated if circulating tumor DNA (ctDNA) can predict relapse and survival in patients with resected melanoma.,We carr... | 1 |
The determination of NRAS and BRAF mutation status is a major requirement in the treatment of patients with metastatic melanoma.,Mutation specific antibodies against NRASQ61R and BRAFV600E proteins could offer additional data on tumor heterogeneity.,The specificity and sensitivity of NRASQ61R immunohistochemistry have ... | Apoptosis-associated speck-like protein containing a CARD (ASC) was originally named because it triggered apoptosis in certain tumors.,More recently, however, ASC was found to be a central adaptor protein of inflammasome which mediates the secretion of pro-tumorigenic inflammation.,Here we examined the role of ASC in t... | 1 |
Patients with early stage, radial growth phase (RGP) melanoma have a 97% survival rate; however, when the melanoma progresses to the invasive vertical growth phase (VGP), survival rates decrease to 15%.,The targets of many clinical trials are the known genetic and molecular mechanisms involved in melanoma progression, ... | While immunotherapies are rapidly becoming mainstays of cancer treatment, significant gaps remain in our understanding of how to optimally target them, alone or in combination.,Here we describe a novel method to monitor levels of immune cells and pathways in expression data from solid tumors using pre-defined groups or... | 1 |
Skin is a highly plastic tissue that undergoes tissue turnover throughout life, but also in response to injury.,YAP and Hedgehog signalling play a central role in the control of epidermal stem/progenitor cells in the skin during embryonic development, in postnatal tissue homeostasis and in skin carcinogenesis.,However,... | Despite that basal cell carcinoma (BCC) is curative in the vast majority of cases, some patients are at high risk of recurrence and, in a few patients, lesions can progress to a point unsuitable for local therapy and prognosis is quite poor.,The aim of the present work is to review clinical and pathologic characteristi... | 1 |
Aberrant expression of miRNAs and their biogenesis factors has been frequently observed in different types of cancer.,We recently reported that expression of DICER1 is reduced in metastatic melanoma.,Nevertheless, so far very little is known about the expression pattern of other miRNA biogenesis factors in this type of... | MicroRNAs-221 and -222 are highly upregulated in several solid tumors, including melanomas.,We demonstrate that the proto-oncogene ETS-1, involved in the pathogenesis of cancers of different origin, is a transcriptional regulator of miR-222 by direct binding to its promoter region.,Differently from 293FT cells or early... | 1 |
The non-coding microRNAs (miRNA) have tissue- and disease-specific expression patterns.,They down-regulate target mRNAs, which likely impacts on most fundamental cellular processes.,Differential expression patterns of miRNAs are currently being exploited for identification of biomarkers for early disease diagnosis, pre... | The incidence of malignant melanoma is increasing faster than that for any other cancer.,Histological examination of skin excision biopsies remains the standard method for melanoma diagnosis and prognosis.,Significant morphological overlap between benign and malignant lesions complicates diagnosis, and tumour thickness... | 1 |
Drug resistance remains a vexing problem in the treatment of cancer patients.,While many studies have focused on cell autonomous mechanisms of drug resistance, we hypothesized that the tumor microenvironment may confer innate resistance to therapy.,Here we developed a co-culture system to systematically assay the abili... | Notoriously resistant malignant melanoma is one of the most increasing forms of cancer worldwide; there is thus a precarious need for new treatment options.,The Wee1 kinase is a major regulator of the G2/M checkpoint, and halts the cell cycle by adding a negative phosphorylation on CDK1 (Tyr15).,Additionally, Wee1 has ... | 1 |
The coronavirus disease 2019 (COVID-19) pandemic has led to lockdowns for much of the world.,In Italy, all health procedures not directly related to COVID-19 were reduced or suspended, thus limiting patient access to hospitals.,Any delay in cancer treatment presents the additional risk of tumors progressing from being ... | The UK healthcare system, including skin cancer departments, has been profoundly affected by the COVID‐19 pandemic.,Despite service capacity and a worldwide increase in incidence, anecdotal reports suggest a decline in skin cancer diagnoses following COVID‐19.,To determine if there has been a decrease in skin cancer di... | 1 |
Cellular plasticity is a state in which cancer cells exist along a reversible phenotypic spectrum, and underlies key traits such as drug resistance and metastasis.,Melanoma plasticity is linked to phenotype switching, where the microenvironment induces switches between invasive/MITFLO versus proliferative/MITFHI states... | Live imaging and genetic studies of the initial interactions between leukocytes and transformed cells in zebrafish larvae indicate an attractant role for H2O2 and suggest that blocking these early interactions reduces expansion of transformed cell clones.,It has not previously been possible to live image the earliest i... | 1 |
Melanoma is the most aggressive and dangerous form of skin cancer that develops from transformed melanocytes.,It is crucial to identify melanoma at its early stages, in situ, as it is “curable” at this stage.,However, after metastasis, it is difficult to treat and the five-year survival is only 25%.,In recent years, a ... | Tumor-infiltrating lymphocytes (TILs) have been successfully used for adoptive cell transfer (ACT) immunotherapy; however, due to their scarce availability, this therapy is possible for a limited fraction of cutaneous melanoma patients.,We assessed whether an effective protocol for ex vivo T-cell expansion from periphe... | 1 |
Approximately one-half of advanced (unresectable or metastatic) melanomas harbor a mutation in the BRAF gene, with V600E being the most common mutation.,Targeted therapy with BRAF and MEK inhibitors is associated with significant long-term treatment benefit in patients with BRAF V600-mutated melanoma.,Therefore, molecu... | Since patients diagnosed with BRAF V600E and V600K mutated advanced melanoma show response to treatment with MAP kinase inhibitors, several sensitive methods have been developed to determine the V600 allele status of melanoma patients.,Vemurafenib (Zelboraf) and dabrafenib (Tafinlar) are specific BRAF V600 inhibitors r... | 1 |
During embryonic development Wnt family members and bone morphogenetic proteins (BMPs) cooperatively induce epithelial-mesenchymal transition (EMT) in the neural crest.,Wnt and BMPs are reactivated during malignant transformation in melanoma.,We previously demonstrated that the BMP-antagonist noggin blocked the EMT phe... | Hypoxia-Inducible Factor 1 (HIF-1) is a transcription factor that is a critical mediator of the cellular response to hypoxia.,Enhanced levels of HIF-1α, the oxygen-regulated subunit of HIF-1, is often associated with increased tumour angiogenesis, metastasis, therapeutic resistance and poor prognosis.,It is in this con... | 1 |
Treatment of BRAF‐mutant melanomas with MAP kinase pathway inhibitors is paradigmatic of the promise of precision cancer therapy but also highlights problems with drug resistance that limit patient benefit.,We use live‐cell imaging, single‐cell analysis, and molecular profiling to show that exposure of tumor cells to R... | Transcriptional reprogramming of proliferative melanoma cells into a phenotypically distinct invasive cell subpopulation is a critical event at the origin of metastatic spreading.,Here we generate transcriptome, open chromatin and histone modification maps of melanoma cultures; and integrate this data with existing tra... | 1 |
The identification of novel antimetastatic therapeutic targets is necessary for improved treatment of patients with acquired BRAF inhibitor‐resistant (BRAFi‐R) melanoma, in whom metastasis is a major concern.,Our present study focused on the identification of such targets to explore novel antimetastatic therapeutic opt... | Ganglioside GD3 is widely expressed in human malignant melanomas, and has been reported to be involved in the increased cell proliferation and invasion.,In this study, we established GM3-, GM2-, GM1-, GD3-, or GD2-expressing melanoma cell lines by transfecting cDNAs of glyscosyltransferases, and effects of individual g... | 1 |
Anti-PD-1 therapy is used as a front-line treatment for many cancers, but mechanistic insight into this therapy resistance is still lacking.,Here we generate a humanized (Hu)-mouse melanoma model by injecting fetal liver-derived CD34+ cells and implanting autologous thymus in immune-deficient NOD-scid IL2Rγnull (NSG) m... | The prognosis of metastatic melanoma is very poor, due to the development of drug resistance.,Cancer stem cells (CSCs) may play a crucial role in this mechanism, contributing to disease relapse.,We first characterized CSCs in melanoma cell lines.,We observed that A375 (but not BLM) cells are able to form melanospheres ... | 1 |
Drastically elevated glycolytic activity is a prominent metabolic feature of cancer cells.,Until recently it was thought that tumor cells shift their entire energy production from oxidative phosphorylation (OXPHOS) to glycolysis.,However, new evidence indicates that many cancer cells still have functional OXPHOS, despi... | Inherited CDKN2A mutation is a strong risk factor for cutaneous melanoma.,Moreover, carriers have been found to have poor melanoma-specific survival.,In this study, responses to novel immunotherapy agents in CDKN2A mutation carriers with metastatic melanoma were evaluated.,CDKN2A mutation carriers that have developed m... | 1 |
How targeted therapies and immunotherapies shape tumours and thereby influence subsequent therapeutic responses is poorly understood.,Here, we show in melanoma patients and mouse models that when tumours relapse following targeted therapy with MAPK pathway inhibitors, they are cross-resistant to immunotherapies, despit... | Transcriptomic signatures designed to predict melanoma patient responses to PD-1 blockade have been reported but rarely validated.,We now show that intra-patient heterogeneity of tumor responses to PD-1 inhibition limit the predictive performance of these signatures.,We reasoned that resistance mechanisms will reflect ... | 1 |
There is growing evidence that tripartite motif-containing protein 44 (TRIM44) plays crucial role in tumor development.,However, the underlying mechanism of this deubiquitinating enzyme remains unclear.,Large clinical samples were used to detect TRIM44 expression and its associations with clinicopathological features a... | Metastatic melanoma (mM) and renal cell carcinoma (mRCC) are often treated with anti-PD-1 based therapy, however not all patients respond and further therapies are needed.,High dose interleukin-2 (HD IL-2) can lead to durable responses in a subset of mM and mRCC patients.,The efficacy and toxicity of HD IL-2 therapy fo... | 1 |
The low efficiency of currently-used anti-cancer therapies poses a serious challenge, especially in the case of malignant melanoma, a cancer characterized by elevated invasiveness and relatively high mortality rate.,The role of the tumor microenvironment in the progression of melanoma and its acquisition of resistance ... | Cutaneous melanoma shows a high metastatic potential based on its ability to overcome the immune system’s control.,The mechanisms activated for these functions vary extremely and are also represented by the production of a number of extracellular vesicles including exosomes.,Other vesicles showing a potential role in t... | 1 |
Organ transplant recipients (OTRs) have a 100‐fold increased risk of cutaneous squamous cell carcinoma (cSCC).,We prospectively evaluated the association between β genus human papillomaviruses (βPV) and keratinocyte carcinoma in OTRs.,Two OTR cohorts without cSCC were assembled: cohort 1 was transplanted in 2003‐2006 (... | The role of the E6 oncoprotein from high-risk members of the α human papillomavirus genus in anogenital cancer has been well established.,However, far less is known about the E6 protein from the β human papillomavirus genus (β-HPVs).,Some β-HPVs potentially play a role in non-melanoma skin cancer development, although ... | 1 |
Cancer cell phenotype largely depends on oxygen availability.,The atmospheric oxygen concentration (21%) used in in vitro studies is much higher than in any human tissue.,Using well-characterized patient-derived melanoma cell lines, we compared: (i) activities of several signaling pathways, and (ii) the effects of vemu... | Melanoma arises from neural crest‐derived melanocytes which reside mostly in the skin in an adult organism.,Epithelial-mesenchymal transition (EMT) is a tumorigenic programme through which cells acquire mesenchymal, more pro‐oncogenic phenotype.,The reversible phenotype switching is an event still not completely unders... | 1 |
Melanomas can switch to a dedifferentiated cell state upon exposure to cytotoxic T cells.,However, it is unclear whether such tumor cells pre-exist in patients and whether they can be resensitized to immunotherapy.,Here, we chronically expose (patient-derived) melanoma cell lines to differentiation antigen-specific cyt... | While cancer immunotherapies including checkpoint blockade antibodies, adoptive T cell therapy, and even some vaccines have given rise to major clinical responses with durability in many cases, a subset of patients who initially respond subsequently develop secondary resistance to therapy.,Tumor-intrinsic mechanisms of... | 1 |
Malignant melanoma of the skin (CMM) is associated with ultraviolet radiation exposure, but the mechanisms and even the wavelengths responsible are unclear.,Here we use a mammalian model to investigate melanoma formed in response to precise spectrally defined ultraviolet wavelengths and biologically relevant doses.,We ... | Objective To estimate the burden of melanoma resulting from sunbed use in western Europe.,Design Systematic review and meta-analysis.,Data sources PubMed, ISI Web of Science (Science Citation Index Expanded), Embase, Pascal, Cochrane Library, LILACS, and MedCarib, along with published surveys reporting prevalence of su... | 1 |
The progressive infiltration of immune cells is associated with the progression of melanoma.,Specifically, Th17 cells in melanoma microenvironment have both antitumor and protumor effects.,It is now necessary to understand the contradictory data associated with how Th17 cells play a role in melanoma.,This review will s... | Melanin possess radioprotective and scavenging properties, and its presence can affect the behavior of melanoma cells, its surrounding environment and susceptibility to the therapy, as showed in vitro experiments.,To determine whether melanin presence in melanoma affects the efficiency of radiotherapy (RTH) we evaluate... | 1 |
Melanoma cells driven by mutant B-RAF are highly resistant to chemotherapeutic treatments.,Recent Phase 1 results with PLX4032/RG7204/Vemurafenib, which selectively inhibits B-RAF/MEK/ERK1/2 signaling in mutant B-RAF cells, has given encouragement to this struggling field.,Nearly all patients in the phase 1-3 studies s... | Ipilimumab, a fully human monoclonal antibody that blocks cytotoxic T-lymphocyte antigen-4, has demonstrated an improvement in overall survival in two phase III trials of patients with advanced melanoma.,The primary objective of the current trial was to prospectively explore candidate biomarkers from the tumor microenv... | 1 |
Melanoma accounts for 1.7% of global cancer diagnoses and is the fifth most common cancer in the US.,Melanoma incidence is rising in developed, predominantly fair-skinned countries, growing over 320% in the US since 1975.,However, US mortality has fallen almost 30% over the past decade with the approval of 10 new targe... | Cutaneous melanoma is the solid neoplasia with the highest growing incidence among all tumors.,It spreads predictably to the lymphatic vessels and sentinel lymph node, and when the latter is affected the prognosis worsens dramatically.,Sentinel lymph node biopsy is considered when thickness of the primary tumor exceeds... | 1 |
Uveal melanoma (UM), the most common ocular malignancy, is characterized by GNAQ/11 mutations.,Hippo/YAP and Ras/mitogen-activated protein kinase (MAPK) emerge as two important signaling pathways downstream of G protein alpha subunits of the Q class (GαQ/11)-mediated transformation, although whether and how they contri... | Uveal melanoma (UM) is uniformly refractory to all available systemic chemotherapies, thus creating an urgent need for novel therapeutics.,In this study, we investigated the sensitivity of UM cells to ICG-001, a small molecule reported to suppress the Wnt/β-catenin-mediated transcriptional program.,We used a panel of U... | 1 |
Clinical translation of therapeutic nuclear acid, particularly those targeting tumor progression, has been hampered by the intrinsic weaknesses of nuclear acid therapeutic including poor systemic stability, rapid clearance, low membrane permeability and lack of targeting ability.,Small nuclear acid engineered into carr... | Melanoma treatment has been revolutionized by antibody-based immunotherapies.,IFNγ secretion by CD8+ T cells is critical for therapy efficacy having anti-proliferative and pro-apoptotic effects on tumour cells.,Our study demonstrates a genetic evolution of IFNγ resistance in different melanoma patient models.,Chromosom... | 1 |
No standard treatment has been defined for metastatic uveal melanoma (mUM).,Although clinical trials testing Nivolumab/Pembrolizumab for cutaneous melanoma did not include mUM, anti PD-1 agents are commonly used for this disease.,In this prospective observational cohort single arm study, we investigated efficacy and sa... | Mucosal melanoma represents ~1% of all melanomas, frequently having a poor prognosis due to diagnosis at a late stage of disease.,Mucosal melanoma differs from cutaneous melanoma not only in terms of poorer clinical outcome but also on the molecular level having e.g. less BRAF and more frequent KIT mutations than cutan... | 1 |
The prognosis of patients with metastatic melanoma has substantially improved over the last years with the advent of novel treatment strategies, mainly immune checkpoint inhibitors and BRAF and MEK inhibitors.,Given the survival benefit provided in the metastatic setting and the evidence from prospective clinical trial... | Supplemental Digital Content is available in the text.,Management of PD-1 blockade resistance in metastatic melanoma (MM) remains challenging.,Immunotherapy or chemotherapy alone provides limited benefit in this setting.,Chemo-immunotherapy (CIT) has demonstrated favorable efficacy and safety profiles in lung cancer.,O... | 1 |
The heterogeneous behavior of patients with melanoma makes prognostication challenging.,To address this, a gene expression profile (GEP) test to predict metastatic risk was previously developed.,This study evaluates the GEP’s prognostic accuracy in an independent cohort of cutaneous melanoma patients.,This multi-center... | The mitogen-activated protein-kinase pathway consisting of the kinases RAF, MEK, and ERK is central to cell proliferation and survival and is deregulated in more than 90% of melanomas.,MEK inhibitors are currently trialled in the clinic, but despite efficient target inhibition, cytostatic rather than cytotoxic activity... | 1 |
We characterized the mutational landscape of human skin cutaneous melanoma (SKCM) using data obtained from The Cancer Genome Atlas (TCGA) project.,We analyzed next-generation sequencing data of somatic copy number alterations and somatic mutations in 303 metastatic melanomas.,We were able to confirm preeminent drivers ... | Recently, melanoma has become the most malignant and commonly occurring skin cancer.,Melanoma is not only the major source (75%) of deaths related to skin cancer, but also it is hard to be treated by the conventional drugs.,Recent research indicated that angiogenesis is an important factor for tumor initiation, expansi... | 1 |
Annual solar ultraviolet radiation (UVR) is mostly determined by latitude and altitude.,Over the last decades, increasing UVR ground levels have been observed.,Exposure to UVR is associated with a life-time risk to develop melanoma, a malign skin cancer.,Thus, we hypothesized that melanoma incidence in Austria is assoc... | Unprotected leisure time exposure to ultraviolet radiation from the sun or artificial tanning beds is the most important environmental risk factor for melanoma, a malignant skin cancer with increasing incidences over the past decades.,The aim of the present study was to assess the impact of skin health information prov... | 1 |
To identify CD8+ T cell-related factors and the co-expression network in melanoma and illustrate the interactions among CD8+ T cell-related genes in the melanoma tumor microenvironment.,We obtained melanoma and paracancerous tissue mRNA matrices from TCGA-SKCM and GSE65904.,The CIBERSORT algorithm was used to assess CD... | The ETS family modulates immune response and drug efficiency to targeted therapies, but their role in melanoma is largely unclear.,In this study, the ETS family was systematically analyzed in multiple public data sets.,Bioinformatics tools were used to characterize the function of ETV7 in melanoma.,A prognostic model w... | 1 |
Local acidification of stroma is proposed to favour pre-metastatic niche formation but the mechanism of initiation is unclear.,We investigated whether Human Melanoma-derived exosomes (HMEX) could reprogram human adult dermal fibroblasts (HADF) and cause extracellular acidification.,HMEX were isolated from supernatants ... | Tumor cells evade the immune surveillance by up-regulating surface expression of PD-L1, which interacts with PD-1 on T cells to elicit the immune checkpoint response1,2.,Anti-PD-1 antibodies have shown remarkable promise in treating tumors, including metastatic melanoma2-4.,However, patient response rate is low4,5.,A b... | 1 |
Lysyl oxidase-like 3 (LOXL3) is a member of the lysyl oxidase family comprising multifunctional enzymes with depicted roles in extracellular matrix maturation, tumorigenesis, and metastasis.,In silico expression analyses followed by experimental validation in a comprehensive cohort of human cell lines revealed a signif... | Melanomas are highly radioresistant tumors, mainly due to efficient DNA double-strand break (DSB) repair.,Dbait (which stands for DNA strand break bait) molecules mimic DSBs and trap DNA repair proteins, thereby inhibiting repair of DNA damage induced by radiation therapy (RT).,First, the cytotoxic efficacy of Dbait in... | 1 |
Melanomas are malignant tumors that originate from melanocytes.,They are most frequently localized in the skin, but 5% of all melanomas interest also extracutaneous sites as mucosal surfaces, parenchymatous organs, the retroperitoneum area, and the ocular ball.,The purpose of this study was to investigate the epidemiol... | Our understanding of the molecular pathways that underlie melanoma remains incomplete.,Although several published microarray studies of clinical melanomas have provided valuable information, we found only limited concordance between these studies.,Therefore, we took an in vitro functional genomics approach to understan... | 1 |
Merkel Cell Polyomavirus (MCPyV) is the etiological agent of the majority of Merkel Cell Carcinomas (MCC).,MCPyV positive MCCs harbor integrated, defective viral genomes that constitutively express viral oncogenes.,Which molecular mechanisms promote viral integration, if distinct integration patterns exist, and if inte... | TOC Summary: This virus may be part of normal human flora and harmless in most adults.,Merkel cell polyomavirus (MCV) is a recently discovered virus that causes 80% of Merkel cell carcinomas.,We examined data for 564 gay/bisexual male participants >18 years of age in the Multicenter AIDS Cohort Study in Pittsburgh, Pen... | 1 |
Uveal melanoma represents ∼85% of all ocular melanomas and up to 50% of patients develop metastatic disease.,Metastases are most frequently localised to the liver and, as few patients are candidates for potentially curative surgery, this is associated with a poor prognosis.,There is currently little published evidence ... | Up to 50% of patients with uveal melanoma (UM) develop metastatic disease with limited treatment options.,The immunomodulating agent ipilimumab has shown an overall survival (OS) benefit in patients with cutaneous metastatic melanoma in two phase III trials.,As patients with UM were excluded in these studies, the Derma... | 1 |
Melanoma is a highly aggressive malignant skin tumor as well as the primary reason for skin cancer‐specific deaths.,We first identified immune‐related long noncoding RNA (lncRNA) prognostic signature and found potential immunotherapeutic targets for melanoma cancer.,RNA‐seq data and clinical features of melanoma sample... | Growing evidence suggests that long non‐coding RNAs NORAD and miR‐205 play a significant role in regulating cancer progression and metastasis.,In this study, high expression of NORAD was firstly observed in melanoma tissues and human malignant melanoma cell lines, our aim was to study the interaction of them in the pro... | 1 |
Our research has focused on in vitro and in vivo evaluations of a new Carmustine (BCNU)-loaded clinoptilolite-based delivery system.,Two clinoptilolite ionic forms-hydrogen form (HCLI) and sodium form (NaCLI)-were prepared, allowing a loading degree of about 5-6 mg BCNU/g of zeolite matrix due to the dual porous featur... | Anthracycline chemotherapeutics, e.g. doxorubicin and daunorubicin, are active against a broad spectrum of cancers.,Their cytotoxicity is mainly attributed to DNA intercalation, interference with topoisomerase activity, and induction of double-stranded DNA breaks.,Since modification of anthracyclines can profoundly aff... | 1 |
Upregulation of the histone methyltransferase enzyme EZH2 and its histone modification H3K27me3 has been linked to melanoma progression, metastasis, and resistance to immune checkpoint blockade (ICB).,In clinical trials, EZH2 inhibitors are currently tested to overcome resistance to ICB.,The aim of this study is to eva... | Wnt5a has been implicated in melanoma progression and metastasis, although the exact downstream signaling events that contribute to melanoma metastasis are poorly understood.,Wnt5a signaling results in acyl protein thioesterase 1 (APT1) mediated depalmitoylation of pro-metastatic cell adhesion molecules CD44 and MCAM, ... | 1 |
Metastatic melanoma is the most aggressive and obstinate skin cancer with poor prognosis.,Variant novel applicable regimens have emerged during the past decades intensively, while the most profound approaches are oncogene-targeted therapy and T-lymphocyte mediated immunotherapy.,Although targeted therapies generated re... | Excessive extracellular matrix (ECM) remodeling and a reactive stroma can affect T-cell infiltration and T-cell activity in the tumor and hereby influence response to immune checkpoint inhibitors (ICI).,In the pursuit of finding biomarkers that predict treatment response, we evaluated the association between serum biom... | 1 |
The MITF and SOX10 transcription factors regulate the expression of genes important for melanoma proliferation, invasion and metastasis.,Despite growing evidence of the contribution of long noncoding RNAs (lncRNAs) in cancer, including melanoma, their functions within MITF-SOX10 transcriptional programmes remain poorly... | Malignant melanoma is a class of malignant tumors derived from melanocytes. lncRNAs have been considered as pro-/anti-tumor factors in progression of cancers.,The function of lncRNA TUG1 on growth of melanoma was investigated in this study.,The TUG1 and miR-129-5p expression were examined via qRT-PCR.,The protein expre... | 1 |
Therapies targeting signaling molecules mutated in cancers can often have striking short-term effects, but the emergence of resistant cancer cells is a major barrier to full cures1,2.,Resistance can result from a secondary mutations3,4, but other times there is no clear genetic cause, raising the possibility of non-gen... | MITF (microphthalmia-associated transcription factor) is a frequently amplified lineage-specific oncogene in human melanoma, whose role in intrinsic drug resistance has not been systematically investigated.,Utilizing chemical inhibitors for major signaling pathways/cellular processes, we witness MITF as an elicitor of ... | 1 |
Pembrolizumab demonstrated robust antitumor activity and safety in the phase Ib KEYNOTE-001 study (NCT01295827) of advanced melanoma.,Five-year outcomes in all patients and treatment-naive patients are reported herein.,Patients whose disease progressed following initial response and who received a second course of pemb... | Melanoma incidence rates have continued to increase in the United States, and risk behaviors remain high.,Melanoma is responsible for the most skin cancer deaths, with about 9,000 persons dying from it each year.,CDC analyzed current (2011) melanoma incidence and mortality data, and projected melanoma incidence, mortal... | 1 |
Tumour blood vessels are gateways for distant metastasis.,Recent studies have revealed that tumour endothelial cells (TECs) demonstrate distinct phenotypes from their normal counterparts.,We have demonstrated that features of TECs are different depending on tumour malignancy, suggesting that TECs communicate with surro... | The incidence of malignant melanoma is increasing.,The majority of patients are diagnosed in early stages when the disease is highly curable.,However, the more advanced or metastatic cases have always been a challenge for clinicians.,The poor prognosis for patients with melanoma is now changing as numerous of promising... | 1 |
Melanoma is a highly aggressive disease that is difficult to treat due to rapid tumor growth, apoptotic resistance, and high metastatic potential.,The MET tyrosine kinase receptor promotes many of these cellular processes, and while MET is often overexpressed in melanoma, the mechanism driving this overexpression is un... | Past studies have shown that upregulation of the anti-apoptotic Bcl-2 family protein Mcl-1 is a major adaptive mechanism of melanoma cells to endoplasmic reticulum (ER) stress, and has an important role in resistance of the cells to apoptosis.,In this study, we show that the increase in transcription of Mcl-1 in melano... | 1 |
Conventional clinico-pathological features in melanoma patients should be integrated with new molecular diagnostic, predictive, and prognostic factors coming from the expanding genomic profiles.,Cutaneous melanoma (CM), even differing in biological behavior according to sun-exposure levels on the skin areas where it ar... | To reveal the clonal architecture of melanoma and associated driver mutations, whole genome sequencing (WGS) and targeted extension sequencing were used to characterize 124 melanoma cases.,Significantly mutated gene analysis using 13 WGS cases and 15 additional paired extension cases identified known melanoma genes suc... | 1 |
Phenotypic changes during cancer progression are associated with alterations in gene expression, which can be exploited to build molecular signatures for tumor stage identification and prognosis.,However, it is not yet known whether the relative abundance of transcript isoforms may be informative for clinical stage and... | A key focus in cancer research is the discovery of biomarkers that accurately diagnose early lesions in non-invasive tissues.,Several studies have identified malignancy-associated DNA methylation changes in blood, yet no general cancer biomarker has been identified to date.,Here, we explore the potential of blood DNA m... | 1 |
SIRT2, an NAD+-dependent histone deacetylase, has been shown to play a pivotal role in various physiological processes, however, its role in cancer is currently controversial.,In recent years, SIRT2 has been described as both a tumor suppressor and oncogene with divergent expression and function in various malignancies... | Hepatic metastasis develops in ~ 50% of uveal melanoma (UM) patients with no effective treatments.,Although GNAQ/GNA11 mutations are believed to confer pathogenesis of UM, the underlying mechanism of liver metastasis remains poorly understood.,Given that profound epigenetic evolution may occur in the long journey of ci... | 1 |
Oncogene-driven metabolic rewiring is an adaptation to low nutrient and oxygen conditions in the tumor microenvironment that enables cancer cells of diverse origin to hyperproliferate.,Aerobic glycolysis and enhanced reliance on glutamine utilization are prime examples of such rewiring.,However, tissue of origin as wel... | Advances in melanoma treatment through targeted inhibition of oncogenic BRAF are limited owing to the development of acquired resistance.,The involvement of BRAFV600E in metabolic reprogramming of melanoma cells provides a rationale for co-targeting metabolism as a therapeutic approach.,We examined the effects of dichl... | 1 |
Epithelial-to-mesenchymal transition (EMT), in which epithelial cells loose their polarity and become motile mesenchymal cells, is a determinant of melanoma metastasis.,We compared gene expression signatures of mesenchymal-like melanoma cells with those of epithelial-like melanoma cells, and identified Thrombospondin 1... | We compared gene expression signatures of aggressive amelanotic (Amela) melanomas with those of slowly growing pigmented melanomas (Mela), identifying pathways potentially responsible for the aggressive Amela phenotype.,Both tumors develop in mice upon conditional deletion in melanocytes of Ink4a/Arf tumor suppressor g... | 1 |
The discovery of the role of the RAS/RAF/MEK/ERK pathway in melanomagenesis and its progression have opened a new era in the treatment of this tumor.,Vemurafenib was the first specific kinase inhibitor approved for therapy of advanced melanomas harboring BRAF-activating mutations, followed by dabrafenib and encorafenib... | Immune checkpoint inhibitors1 result in impressive clinical responses2-5 but optimal results will require combination with each other6 and other therapies.,This raises fundamental questions about mechanisms of non-redundancy and resistance.,Here, we report major tumor regressions in a subset of patients with metastatic... | 1 |
Cutaneous squamous cell carcinoma (cuSCC) comprises 15-20% of all skin cancers, accounting for over 700,000 cases in USA annually.,Most cuSCC arise in association with a distinct precancerous lesion, the actinic keratosis (AK).,To identify potential targets for molecularly targeted chemoprevention, here we perform inte... | The non-malignant cells of the tumour stroma have a critical role in tumour biology.,Studies dissecting the interplay between cancer cells and stromal cells are required to further our understanding of tumour progression and methods of intervention.,For proof-of-principle of a multi-modal approach to dissect the differ... | 1 |
Periodic acid-Schiff (PAS) positive patterns of vasculogenic mimicry (VM) have been associated with poor prognosis in uveal melanoma (UM).,We examined these patterns with digital image analysis and transmission electron microscopy, and correlated them with BAP-1 expression, gene expression class, macrophage infiltratio... | Hypoxia-Inducible Factor 1 (HIF-1) is a transcription factor that is a critical mediator of the cellular response to hypoxia.,Enhanced levels of HIF-1α, the oxygen-regulated subunit of HIF-1, is often associated with increased tumour angiogenesis, metastasis, therapeutic resistance and poor prognosis.,It is in this con... | 1 |
The immune system employs several checkpoint pathways to regulate responses, maintain homeostasis and prevent self-reactivity and autoimmunity.,Tumor cells can hijack these protective mechanisms to enable immune escape, cancer survival and proliferation.,Blocking antibodies, designed to interfere with checkpoint molecu... | TP53 has been proved to be associated with cytotoxic T-cell induced apoptosis, however, the association between TP53 and the benefit of immunotherapy in melanoma has not been studied.,In the present study, we examined the relationship between TP53 mutation and response to CTLA-4 blockade in metastatic melanoma by analy... | 1 |
CC-115 is a dual inhibitor of the mechanistic target of rapamycin (mTOR) kinase and the DNA-dependent protein kinase (DNA-PK) that is currently being studied in phase I/II clinical trials.,DNA-PK is essential for the repair of DNA-double strand breaks (DSB).,Radiotherapy is frequently used in the palliative treatment o... | Therapies that target the programmed death-1 (PD-1) receptor have shown unprecedented rates of durable clinical responses in patients with various cancer types.1-5 One mechanism by which cancer tissues limit the host immune response is via upregulation of PD-1 ligand (PD-L1) and its ligation to PD-1 on antigen-specific... | 1 |
Current treatment modalities for disseminated cutaneous malignant melanoma (CMM) improve survival; however, relapses are common.,A number of receptor tyrosine kinases (RTKs) including EGFR and MET have been reported to be involved in CMM metastasis and in the development of resistance to therapy, targeting the mitogen-... | Vasculogenic mimicry (VM) describes functional vascular channels composed only of tumor cells and its presence predicts poor prognosis in melanoma patients.,Inhibition of this alternative vascularization pathway might be of clinical importance, especially as several anti-angiogenic therapies targeting endothelial cells... | 1 |
The principles governing evolution of tumors exposed to targeted therapy are poorly understood.,Here we modeled the selection and propagation of BRAF amplification (BRAFamp) in patient-derived tumor xenografts (PDX) treated with a direct ERK inhibitor, alone or in combination with other pathway inhibitors.,Single cell ... | Treatment of advanced melanoma has been improved with the advent of the BRAF inhibitors.,However, a limitation to such treatment is the occurrence of resistance.,Several mechanisms have been identified to be responsible for the development of resistance, either MEK-dependent or MEK-independent.,In order to overcome res... | 1 |
Obesity is a risk factor for malignancy; however, its prognostic role in patients with metastatic melanoma is controversial.,We aim to investigate the prognostic role of body mass index (BMI) in patients with metastatic melanoma receiving mitogen-activated pathway kinase inhibitors (MAPKi), immune checkpoint inhibitors... | Vitamin D deficiency (≤20 ng/mL) is associated with an increased incidence and worse prognosis of various types of cancer including melanoma.,A retrospective, single-center study of individuals diagnosed with melanoma from January 2007 through June 2013 who had a vitamin D (25(OH)D3) level measured within one year of d... | 1 |
The low efficiency of currently-used anti-cancer therapies poses a serious challenge, especially in the case of malignant melanoma, a cancer characterized by elevated invasiveness and relatively high mortality rate.,The role of the tumor microenvironment in the progression of melanoma and its acquisition of resistance ... | Melanoma is one of the most aggressive solid tumors and includes a stromal microenvironment that regulates cancer growth and progression.,The components of stromal microenvironment such as fibroblasts, fibroblast aggregates and cancer-associated fibroblasts (CAFs) can differently influence the melanoma growth during it... | 1 |
Approximately one‐third of Merkel cell carcinoma (MCC) patients eventually develop distant metastatic disease.,Little is known about whether the location of the primary lesion is predictive of initial distant metastatic site, or if survival likelihood differs depending on the metastatic site.,Such data could inform ima... | Viruses can inhibit host autophagy through multiple mechanisms, and evasion of autophagy plays an important role in immune suppression and viral oncogenesis.,Merkel cell polyomavirus (MCPyV) T‐antigens are expressed and involved in the pathogenesis of a large proportion of Merkel cell carcinoma (MCC).,Yet, how MCPyV in... | 1 |
The discovery of BRAF mutations in the majority of patients with metastatic melanoma combined with the identification of highly selective BRAF inhibitors have revolutionized the treatment of patients with metastatic melanoma.,The first highly specific BRAF inhibitor, vemurafenib, began clinical testing in 2008 and move... | BRAF is a serine/threonine protein kinase activating the MAP kinase/ERK-signaling pathway.,About 50 % of melanomas harbors activating BRAF mutations (over 90 % V600E).,BRAFV600E has been implicated in different mechanisms underlying melanomagenesis, most of which due to the deregulated activation of the downstream MEK/... | 1 |
Drug addiction denotes the dependency of tumors on the same therapeutic drugs to which they have acquired resistance.,Observations from cultured cells1-3, animal models4 and patients5-7 raise the possibility that cancer drug addiction can instigate a potential cancer vulnerability, which may be used therapeutically.,Ho... | Transcriptional reprogramming of proliferative melanoma cells into a phenotypically distinct invasive cell subpopulation is a critical event at the origin of metastatic spreading.,Here we generate transcriptome, open chromatin and histone modification maps of melanoma cultures; and integrate this data with existing tra... | 1 |
Metastatic melanoma is the most aggressive and obstinate skin cancer with poor prognosis.,Variant novel applicable regimens have emerged during the past decades intensively, while the most profound approaches are oncogene-targeted therapy and T-lymphocyte mediated immunotherapy.,Although targeted therapies generated re... | The incidence of melanoma is increasing worldwide, and the prognosis for patients with high-risk or advanced metastatic melanoma remains poor despite advances in the field.,A systematic literature review of treatments for advanced, metastatic disease was conducted to present the success of current treatments and the pr... | 1 |
Immunologic responses to anti-PD-1 therapy in melanoma patients occur rapidly with pharmacodynamic T cell responses detectable in blood by 3 weeks.,It is unclear, however, whether these early blood-based observations translate to the tumor microenvironment.,We conducted a study of neoadjuvant/adjuvant anti-PD-1 therapy... | Real‐world data on treatment patterns/outcomes in patients with advanced melanoma, while scarce, are useful for health technology assessments that govern patient access in many countries.,We collected retrospective data on treatment patterns among patients in France, Germany and the UK with Stage IIIB/IIIC melanoma wit... | 1 |
An impressive clinical success has been observed in treating a variety of cancers using immunotherapy with programmed cell death‐1 (PD‐1) checkpoint blockade.,However, limited response in most patients treated with anti‐PD‐1 antibodies remains a challenge, requiring better understanding of molecular mechanisms limiting... | Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematologic malignancy for which there is still no effective therapy.,In order to identify genetic alterations useful for a new treatment design, we used whole-exome sequencing to analyze 14 BPDCN patients and the patient-derived CAL-1 cell l... | 1 |
The incidence of melanoma continues to rise globally and is increasing at a rate greater than any other cancer.,To systematically search for new genes involved in melanomagenesis, we collated exome sequencing data from independent melanoma cohort datasets, including those in the public domain.,We identified recurrent m... | Mitogen-Activated Protein Kinase (MAPK) pathway activation has been implicated in many types of human cancer.,BRAF mutations that constitutively activate MAPK signalling and bypass the need for upstream stimuli occur with high prevalence in melanoma, colorectal carcinoma, ovarian cancer, papillary thyroid carcinoma, an... | 1 |
Combination concepts of radiotherapy and immune checkpoint inhibition are currently of high interest.,We examined imaging findings, acute toxicity, and local control in patients with melanoma brain metastases receiving programmed death 1 (PD-1) inhibitors and/or robotic stereotactic radiosurgery (SRS).,Twenty-six patie... | Melanoma brain metastasis is associated with an extremely poor prognosis, with a median overall survival of 4-5 months.,Since 2011, the overall survival of patients with stage IV melanoma has been significantly improved with the advent of new targeted therapies and checkpoint inhibitors.,We analyze the survival outcome... | 1 |
The therapeutic landscape for advanced melanoma has recently been transformed by several novel agents (immune checkpoint inhibitors and molecular‐targeted agents).,The prospective, multi‐site, observational study IMAGE (ipilimumab: management of advanced melanoma in real practice) included a retrospective cohort to des... | Ipilimumab improves survival in patients with advanced melanoma.,The activity and safety of ipilimumab outside of a clinical trial was assessed in an expanded access programme (EAP).,Ipilimumab was available upon physician request for patients aged 16 or over with pretreated stage III (unresectable)/IV melanoma, for wh... | 1 |
Previous analysis of COMBI-d (NCT01584648) demonstrated improved progression-free survival (PFS) and overall survival (OS) with combination dabrafenib and trametinib versus dabrafenib monotherapy in BRAF V600E/K-mutant metastatic melanoma.,This study was continued to assess 3-year landmark efficacy and safety after ≥36... | Checkpoint inhibitors are revolutionizing treatment options and expectations for patients with melanoma.,Ipilimumab, a monoclonal antibody against cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), was the first approved checkpoint inhibitor.,Emerging long-term data indicate that approximately 20% of ipilimumab-trea... | 1 |
Herein, we describe the use of systemic immunotherapy for both locally advanced and metastatic conjunctival melanoma.,Current treatments for advanced conjunctival melanoma typically result in poor local control leading to disfiguring orbital exenteration surgery.,Locoregional spread of conjunctival malignant melanoma t... | Immune checkpoint inhibitors1 result in impressive clinical responses2-5 but optimal results will require combination with each other6 and other therapies.,This raises fundamental questions about mechanisms of non-redundancy and resistance.,Here, we report major tumor regressions in a subset of patients with metastatic... | 1 |
Effective management of melanoma depends heavily on early diagnosis.,When detected in early non-metastatic stages, melanoma is almost 100% curable by surgical resection, however when detected in late metastatic stages III and IV, 5-year survival rates drop to ~50% and 10-25%, respectively, due to limited efficacy of cu... | Patients with metastatic melanoma bearing V600 mutations in BRAF oncogene clinically benefit from the treatment with BRAF inhibitors alone or in combination with MEK inhibitors.,However, a limitation to such treatment is the occurrence of resistance.,Tackling the adaptive changes helping cells survive from drug treatme... | 1 |
Epidermal squamous cell carcinoma (SCC) is a common and highly invasive form of cancer.,SCC arises due to ultraviolet light exposure and is associated with increased expression of pro-cancer genes and reduced expression of cancer suppressors.,Actin-Like Protein 6A (ACTL6A, BAF53a) is an important protein subunit of the... | Cutaneous Squamous Cell Carcinoma (cSCC) is the most common and fastest-increasing cancer with metastatic potential.,Long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) are novel regulators of gene expression.,To identify mRNAs, lncRNAs and circRNAs, which can be involved in cSCC, RNA-seq was performed on nine ... | 1 |
Patients with high-risk stage II/III resected melanoma commonly develop distant metastases.,At present, we cannot differentiate between patients who will recur or those who are cured by surgery.,We investigated if circulating tumor DNA (ctDNA) can predict relapse and survival in patients with resected melanoma.,We carr... | Metastatic melanoma is a highly heterogeneous tumor; thus, methods to analyze tumor-derived cells circulating in blood should address this diversity.,Taking this into account, we analyzed, using multiparametric flow cytometry, the co-expression of the melanoma markers melanoma cell adhesion molecule and melanoma-associ... | 1 |
Malignant melanoma is a class of malignant tumors derived from melanocytes. lncRNAs have been considered as pro-/anti-tumor factors in progression of cancers.,The function of lncRNA TUG1 on growth of melanoma was investigated in this study.,The TUG1 and miR-129-5p expression were examined via qRT-PCR.,The protein expre... | Dysregulation of miR-183 has been recently elucidated in several carcinomas.,However, the expression patterns and mechanisms of miR-183 involved in malignant melanoma remain unidentified.,Here, we found down-regulation of miR-183 in melanoma tissues and cells.,Decreased level of miR-183 was relevant to poor overall sur... | 1 |
Although clinical guidelines exist, the management of patients with cutaneous melanoma (CM) is a complex process that may vary between different care providers with potential dysfunctions ultimately mirrored in the overall patient satisfaction.,The aim of the present study was to investigate the CM management as relate... | Effective management of melanoma depends heavily on early diagnosis.,When detected in early non-metastatic stages, melanoma is almost 100% curable by surgical resection, however when detected in late metastatic stages III and IV, 5-year survival rates drop to ~50% and 10-25%, respectively, due to limited efficacy of cu... | 1 |
Fibroblast growth factor (FGF)/Fibroblast growth factor receptor (FGFR) signaling regulates various cellular processes during the embryonic development and in the adult organism.,In the skin, fibroblasts and keratinocytes control proliferation and survival of melanocytes in a paracrine manner via several signaling mole... | Melanoma arises from neural crest‐derived melanocytes which reside mostly in the skin in an adult organism.,Epithelial-mesenchymal transition (EMT) is a tumorigenic programme through which cells acquire mesenchymal, more pro‐oncogenic phenotype.,The reversible phenotype switching is an event still not completely unders... | 1 |
Oncogenic mutations in BRAF and NRAS occur in 70% of melanomas.,In this study, we identify a microRNA, miR-146a, that is highly upregulated by oncogenic BRAF and NRAS.,Expression of miR-146a increases the ability of human melanoma cells to proliferate in culture and form tumors in mice, whereas knockdown of miR-146a ha... | The non-coding microRNAs (miRNA) have tissue- and disease-specific expression patterns.,They down-regulate target mRNAs, which likely impacts on most fundamental cellular processes.,Differential expression patterns of miRNAs are currently being exploited for identification of biomarkers for early disease diagnosis, pre... | 1 |
The application of current channelrhodopsin-based optogenetic tools is limited by the lack of strict ion selectivity and the inability to extend the spectra sensitivity into the near-infrared (NIR) tissue transmissible range.,Here we present an NIR-stimulable optogenetic platform (termed 'Opto-CRAC') that selectively a... | Calcium signaling mediated by STIM1 and Orai1 activates Src to promote invadopodium assembly while simultaneously promoting MT1-MMP recycling to the plasma membrane to promote ECM degradation.,Ca2+ signaling has been increasingly implicated in cancer invasion and metastasis, and yet, the underlying mechanisms remained ... | 1 |
In response to the dynamic intra‐tumor microenvironment, melanoma cells adopt distinct phenotypic states associated with differential expression of the microphthalmia‐associated transcription factor (MITF).,The response to hypoxia is driven by hypoxia‐inducible transcription factors (HIFs) that reprogram metabolism and... | We have recently reported a potential alternative tumor suppressor function for p16 relating to its capacity to regulate oxidative stress and observed that oxidative dysregulation in p16-depleted cells was most profound in melanocytes, compared to keratinocytes or fibroblasts.,Moreover, in the absence of p16 depletion ... | 1 |
Metastasis development represents an important threat for melanoma patients, even when diagnosed at early stages and upon removal of the primary tumor.,In this scenario, determination of prognostic biomarkers would be of great interest.,Serum contains information about the general status of the organism and therefore r... | Over the past decade, several immunotherapies have been approved for the treatment of melanoma.,The most prominent of these are the immune checkpoint inhibitors, which are antibodies that block the inhibitory effects on the immune system by checkpoint receptors, such as CTLA-4, PD-1 and PD-L1.,Preclinically, blocking t... | 1 |
Micro RNAs (miRs) have emerged as key regulators during oncogenesis.,They have been found to regulate cell proliferation, differentiation, and apoptosis.,Mir-125b has been identified as an oncomir in various forms of tumours, but we have previously proposed that miR-125b is a suppressor of lymph node metastasis in cuta... | The incidence of malignant melanoma is increasing faster than that for any other cancer.,Histological examination of skin excision biopsies remains the standard method for melanoma diagnosis and prognosis.,Significant morphological overlap between benign and malignant lesions complicates diagnosis, and tumour thickness... | 1 |
Alterations in connexin 43 (Cx43) expression and/or gap junction (GJ)-mediated intercellular communication are implicated in cancer pathogenesis.,Herein, we have investigated the role of Cx43 in melanoma cell proliferation and apoptosis sensitivity in vitro, as well as metastatic capability and tumour growth in vivo.,C... | Ipilimumab, an antibody that enhances T-cell activation, may augment immunogenicity of tumor cells that are injured by radiation therapy.,We hypothesized that patients with melanoma brain metastasis treated with both ipilimumab and radiotherapy would have improved overall survival, and that the sequence of treatments m... | 1 |
Immunotherapy is regarded as one of the major breakthroughs in cancer treatment.,Despite its success, only a subset of patients responds-urging the quest for predictive biomarkers.,We hypothesize that artificial intelligence (AI) algorithms can automatically quantify radiographic characteristics that are related to and... | We evaluated neoadjuvant ipilimumab in patients with surgically operable regionally advanced melanoma in order to define markers of activity in the blood and tumor as assessed at baseline (before ipilimumab) and early on-treatment.,Patients were treated with ipilimumab (10 mg/kg intravenously every 3 weeks ×2 doses) br... | 1 |
Adaptive responses have been demonstrated to limit activity to targeted therapies.,Saei et al. show that loss of USP28/FBW7-mediated BRAF degradation is observed in a proportion of melanoma patients and can be responsible for resistance through upregulation of MAPK signaling pathway.,RAF kinase inhibitors are clinicall... | The development of acquired drug resistance hampers the long-term success of B-RAF inhibitor (B-RAFi) therapy for melanoma patients.,Here we show V600EB-RAF copy number gain as a mechanism of acquired B-RAFi resistance in four out of twenty (20%) patients treated with B-RAFi.,In cell lines, V600EB-RAF over-expression a... | 1 |
In the KEYNOTE-022 study, pembrolizumab with dabrafenib and trametinib (triplet) improved progression-free survival (PFS) versus placebo with dabrafenib and trametinib (doublet) without reaching statistical significance.,Mature results on PFS, duration of response (DOR), and overall survival (OS) are reported.,The doub... | Melanoma is an aggressive malignancy of melanocytes and most commonly arises in the skin.,In 2002, BRAF gene mutations were identified in melanoma, and this finding resulted in the development of several small-molecule molecular inhibitors that specifically targeted the BRAF V600E mutation.,The development of targeted ... | 1 |
Oncogene-driven metabolic rewiring is an adaptation to low nutrient and oxygen conditions in the tumor microenvironment that enables cancer cells of diverse origin to hyperproliferate.,Aerobic glycolysis and enhanced reliance on glutamine utilization are prime examples of such rewiring.,However, tissue of origin as wel... | The importance of mitochondria as oxygen sensors as well as producers of ATP and reactive oxygen species (ROS) has recently become a focal point of cancer research.,However, in the case of melanoma, little information is available to what extent cellular bioenergetics processes contribute to the progression of the dise... | 1 |
We recently demonstrated that upregulation of a chemokine receptor CCR6 and its ligand CCL20 led to metastasis of advanced cutaneous T-cell lymphoma (CTCL) cells, suggesting the involvement of CCL20-CCR6 interaction in initiating CTCL cell metastasis.,In this study, we determined whether this interaction is functional ... | Cutaneous T cell lymphoma (CTCL) is a non-Hodgkin lymphoma of skin-homing T lymphocytes.,We performed exome and whole genome DNA sequence and RNA sequencing on purified CTCL and matched normal cells.,The results implicate mutations in 17 genes in CTCL pathogenesis, including genes involved in T cell activation and apop... | 1 |
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