Melanoma

Although a combination with photodynamic therapy (PDT) is a potential means to improve the immune checkpoint blockade (ICB)-based anticancer immunotherapy, this strategy is subjected to the extremely poor light penetration in melanoma. Herein, we develop a lipid (LP)-based micellar nanocarrier encapsulating sonosensitizer chlorin e6 (Ce6) in the core, conjugating anti-PD-L1 antibody (aPD-L1) to the interlayer through MMP-2-cleavable peptide, and bearing a PEG coating sheddable at low pH value (≈6.5) of tumor microenvironment...

No abstract text is available yet for this article.

BACKGROUND: Some studies have suggested a relationship between type 2 diabetes mellitus (T2DM) and increased incidence of melanoma. Efforts are underway to identify preventable and treatable factors associated with greater melanoma aggressiveness, but no studies to date have examined the relationship between T2DM and the aggressiveness of cutaneous melanoma at diagnosis. OBJECTIVES: To explore potential associations between T2DM, glycaemic control and metformin treatment and the aggressiveness of cutaneous melanoma...

PURPOSE: The concept of a radioresistant (RR) phenotype has been challenged with use of stereotactic body radiotherapy (SBRT). We compared outcomes following SBRT to RR spinal metastases to a radiosensitive cohort. METHODS: Renal cell, melanoma, sarcoma, gastro-intestinal, and thyroid spinal metastases were identified as RR and prostate cancer (PCA) as radiosensitive. The primary endpoint was MRI-based local failure (LF). Secondary endpoints included overall survival (OS) and vertebral compression fracture (VCF)...

Dendritic cells are potently activated by the synergistic action of CD40 stimulation in conjunction with signaling through toll like receptors, subsequently priming T cells. Cancer vaccines targeting the activation of dendritic cells in this manner show promise in murine models and are being developed for human patients. While the efficacy of vaccines based on CD40 and toll like receptor stimulation has been established, further investigation is needed to understand the mechanism of tumor control and how vaccination alters tumor infiltrating immune cells...

Retraction of this publication has been requested by the authors due to problems with reproducibility. Reference: Pengcheng Liu, Ruili Du, Xin Yu. Ursolic Acid Exhibits Potent Anticancer Effects in Human Metastatic Melanoma Cancer Cells (SK-MEL-24) via Apoptosis Induction, Inhibition of Cell Migration and Invasion, Cell Cycle Arrest, and Inhibition of Mitogen-Activated Protein Kinase (MAPK)/ERK Signaling Pathway Med Sci Monit 2019; 25:1283-1290. 10.12659/MSM.913069.

OBJECTIVE: To analyse ocular and systemic findings of patients presenting with systemic metastasis. METHODS AND ANALYSIS: It is an international, multicentre, internet-enabled, registry-based retrospective data analysis. Patients were diagnosed between 2001 and 2011. Data included: primary tumour dimensions, extrascleral extension, ciliary body involvement, American Joint Committee on Cancer (AJCC)-tumour, node, metastasis staging, characteristics of metastases...

No abstract text is available yet for this article.

The prediction of metastatic properties from molecular analyses still poses a major challenge. Here we aimed at the classification of metastasis-related cell properties by proteome profiling making use of cutaneous and brain-metastasizing variants from single melanomas sharing the same genetic ancestry. Previous experiments demonstrated that cultured cells derived from these xenografted variants maintain a stable phenotype associated with a differential metastatic behavior: The brain metastasizing variants produce more spontaneous micro-metastases than the corresponding cutaneous variants...

Pathway analyses are key methods to analyze 'omics experiments. Nevertheless, integrating data from different 'omics technologies and different species still requires considerable bioinformatics knowledge. Here we present the novel ReactomeGSA resource for comparative pathway analyses of multi-omics datasets. ReactomeGSA can be used through Reactome's existing web interface and the novel ReactomeGSA R Bioconductor package with explicit support for scRNA-seq data. Data from different species is automatically mapped to a common pathway space...

BACKGROUND: Melanoma is the leading cause of death due to cutaneous malignancy and its incidence is on the rise. Several signaling pathways, including receptor tyrosine kinases, have a role in the development and progression of melanocytic lesions and malignant melanoma. Among those, the hepatocyte growth factor (HGF)/c-met axis is emerging as a critical player because it can play a role in drug resistance. Indeed, 50% of melanoma patients present BRAF mutations, however, all responders develop resistance to the inhibitors typically within one year of treatment...

Solid lipid particles (SLPs) can sustainably encapsulate and release therapeutic agents over long periods, modifying their biodistribution, toxicity, and side effects. To date, no studies have been reported using SLPs loaded with doxorubicin chemotherapy for the treatment of metastatic cancer. This study characterizes the effect of doxorubicin-loaded carnauba wax particles in the treatment of lung metastatic malignant melanoma in vivo. Compared with the free drug, intravenously administrated doxorubicin-loaded SLPs significantly reduce the number of pulmonary metastatic foci in mice...

Immune checkpoint inhibitors (ICIs) are being increasingly utilised in a variety of advanced malignancies. Despite promising outcomes in certain patients, the majority will not derive benefit and are at risk of potentially serious immune-related adverse events (irAEs). The development of predictive biomarkers is therefore critical to personalise treatments and improve outcomes. A number of biomarkers have shown promising results, including from tumour (programmed cell death ligand 1 (PD-L1), tumour mutational burden (TMB), stimulator of interferon genes (STING) and apoptosis-associated speck-like protein containing a CARD (ASC)), from blood (peripheral blood mononuclear cells (PBMCs), circulating tumour DNA (ctDNA), exosomes, cytokines and metal chelators) and finally the microbiome...

S100B, a biomarker of malignant melanoma, interacts with the p53 protein and diminishes its tumor suppressor function, which makes this S100 family member a promising therapeutic target for treating malignant melanoma. However, it is a challenge to design inhibitors that are specific for S100B in melanoma versus other S100-family members that are important for normal cellular activities. For example, S100A1 is most similar in sequence and structure to S100B, and this S100 protein is important for normal skeletal and cardiac muscle function...

Background: Brain metastases are observed in more than 40% of all patients with stage 4 melanoma. In recent years, more extensive use of stereotactic radiation (STRT) and the advent of immune checkpoint inhibitors have positively impacted outcomes in patients with metastatic melanoma.brain metastases. Here, we examined real world clinical outcomes of patients presenting with melanoma brain metastases (MBMs). Methods: This retrospective review evaluated MBMs patients treated at The Ottawa Hospital from April 2000 to July 2017...

Cytotoxic T-lymphocyte associated protein-4 (CTLA-4) and the Programmed Death Receptor 1 (PD-1) are immune checkpoint molecules that are well-established targets of antibody immunotherapies for the management of malignant melanoma. The monoclonal antibodies Ipilimumab, Pembrolizumab and Nivolumab, designed to interfere with T-cell inhibitory signals to activate immune responses against tumours, were originally approved as monotherapy. Treatment with a combination of immune checkpoint inhibitors may improve outcomes compared to monotherapy in certain patient groups and these clinical benefits may be derived from unique immune mechanisms of action...

BACKGROUND AND OBJECTIVE: Long-term benefits can be predicted by the incorporation of more intelligent systems in lasers and other devices. Such systems can produce more reliable zones of thermal injury when used in association with non-invasive monitoring and precise laser energy delivery. The more classical endpoint of tumor destruction with radiofrequency or long-pulsed (LP) 1064 nm laser is the non-specific appearance of tissue graying and tissue contraction. Herein we discuss combining non-invasive LP 1064 nm Nd:YAG treatment with the assistance of optical coherence tomography (OCT) and the forward-looking infrared (FLIR) thermal camera while testing literature-based formulae for thermal destruction...

Neoadjuvant therapy with ipilimumab in combination with high dose IFNα was evaluated in patients with locally/regionally advanced melanoma in a previously reported clinical trial [NCT01608594]. In this study, peripheral immune cell profiling was performed in order to investigate the underlying mechanisms of tumor immune susceptibility and resistance. Peripheral blood mononuclear cells (PBMCs) from treated patients (N = 28) were collected at baseline and then at 6-weeks, 3-months and 12-months. High complexity (14-color) flow cytometry, designed to detect key immunological biomarkers was used to evaluate the frequencies of immune cell subsets...

Due to hurdles, including resistance, adverse effects, and poor bioavailability, among others linked with existing therapies, there is an urgent unmet need to devise new, safe, and more effective treatment modalities for skin cancers. Herein, a series of flavonol-based derivatives of fisetin, a plant-based flavonoid identified as an anti-tumorigenic agent targeting the mammalian targets of rapamycin (mTOR)-regulated pathways, were synthesized and fully characterized. New potential inhibitors of receptor tyrosine kinases (c-KITs), cyclin-dependent kinase-2 (CDK2), and mTOR, representing attractive therapeutic targets for melanoma and non-melanoma skin cancers (NMSCs) treatment, were identified using inverse-docking, in vitro kinase activity and various cell-based anticancer screening assays...

BACKGROUND: Malignant melanoma is an immunogenic skin cancer with an increasing global incidence. Advanced stages of melanoma have poor prognoses. Currently, there are no reliable parameters to predict a patient's response to immune checkpoint inhibitor (ICI) therapy. METHODS: This study highlights the relevance of a distinct immune signature in the blood for response to ICI therapy and overall survival (OS). Therefore, the immune cell composition in the peripheral blood of 45 melanoma patients prior to ICI therapy was analyzed by flow cytometry and complete blood count...