Melanoma

PURPOSE OF THE REVIEW: Clinical data on salvage chemotherapy used after checkpoints inhibitors in oncology are reviewed, with a special focus on recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). RECENT FINDINGS: Converging evidence is emerging about high response and/or disease control rates associated with salvage chemotherapy after immunotherapy failure in advanced solid tumours. This phenomenon is mainly reported in retrospective studies for "hot tumours" such as R/M HNSCC, melanoma, lung, urothelial or gastric cancers, but also in haematological malignancies...

Telomere length (TL), which is maintained by hTERT (component of telomerase) and/or TRF1/TRF2 (core components of shelterin) via different mechanisms, is essential for chromosomal stability and cell survival. Folates comprise a group of essential B9 vitamin that involve in DNA synthesis and methylation. This study aimed to evaluate the effects of folic acid (FA) and 5-methyltetrahydrofolate (5-MeTHF) on TL, chromosome stability, and cell survival of telomerase-negative BJ and telomerase-positive A375 cells in vitro...

BACKGROUND: Uveal melanoma is the most common primary intraocular tumor in adults. In Sweden, at least 100 patients are diagnosed with the disease each year. Almost half of the patients develop metastases, with a median survival time of 1 year once metastases are detected. The primary ocular tumor is typically treated with either enucleation or brachytherapy, and no adjuvant treatment is added. Melatonin is an indolamine hormone that has improved survival in previous trials with patients diagnosed with various cancers, including advanced cutaneous melanoma...

BACKGROUND: G47∆ is a triple-mutated oncolytic herpes simplex virus type 1 (HSV-1) recently approved as a new drug for malignant glioma in Japan. As the next-generation, we develop armed oncolytic HSV-1 using G47∆ as the backbone. Because oncolytic HSV-1 elicits specific antitumor immunity, interleukin 12 (IL-12) can function as an effective payload to enhance the efficacy. METHODS: We evaluate the optimal methods for expressing IL-12 as a payload for G47∆-based oncolytic HSV-1...

The EWSR1::CREM fusion gene, caused by a chromosomal translocation t(10;22)(p11;q12), has been discovered in divergent malignancies, ranging from low-grade to highly malignant cancers. The translocation gives rise to a chimeric protein, EWSR1::CREM. The molecular mechanisms behind the oncogenic properties of the EWSR1::CREM protein have not previously been systematically characterized. In this study, we performed transcriptional profiling of the melanoma cell line CHL-1, with depletion of endogenous EWSR1::CREM protein using siRNA mediated knockdown...

BACKGROUND: Halo nevus, also called Sutton's nevus, is a nevus cell nevus surrounded by vitiligo thought to be caused by a T-cell mediated immune response to the nevus antigen. The immune microenvironment is mysterious, however, as vitiligo often does not improve even when the nevus cells are removed. OBJECTIVES: To analyze the clinical course and immune microenvironment of patients with halo nevus who had undergone nevus excision. METHODS: We collected 54 halo nevus patients and performed multivariate analysis and immunohistochemical analysis, including multiplexed immune cell phenotyping and spatial single-cell analyses using the PhenoCycler® assay...

No abstract text is available yet for this article.

Ferroptosis, a form of cell death caused by iron-dependent peroxidation of lipids, plays an important role in cancer. Recent studies have shown that long noncoding RNAs (lncRNAs) are involved in the regulation of ferroptosis in tumor cells and are also closely related to tumor immunity. Immune cell infiltration in the tumor microenvironment affects the prognosis and clinical outcome of immunotherapy in melanoma patients, and immune cell classification may be able to accurately predict the prognosis of melanoma patients...

An imatinib controlled release film-forming system (FFS) was developed based on the drug ion-pair and newly designed oligomeric ionic liquids (OILs) for the topical therapy of cutaneous melanoma, which avoided the systemic side-effect of oral administration and maintained a long local therapy effect. The OILs significantly improved the drug release capacity about 1.5-fold, and the formability and stability of FFSs (verified by AFM/PLM). The in vivo anti-tumor efficacy studies in melanoma tumor bearing mice showed that compared with the oral capsules, the topical application of the optimized imatinib FFS significantly (p < 0...

PURPOSE: The aim of our study was to explore the impact of the COVID-19 pandemic on reported cancer cases in Bavaria, Germany, by comparing pre-pandemic (March 2019 to February 2020) and pandemic period (March 2020 to February 2021). METHODS: Data on incident cases were retrieved from the Bavarian Cancer Registry (until 22nd April 2022). We included patients with malignant and in situ neoplasms reported by pathology departments with consistent reporting. We calculated the number of incident cases during the COVID-19 pandemic and the pre-pandemic period with 95% confidence intervals (CI) with Bonferroni correction (α = 0...

Non-melanoma skin cancer (NMSC) is a tumor that arises from human keratinocytes, showing abnormal control of cell proliferation and aberrant stratification. Cutaneous basal cell carcinoma (cBCC) and cutaneous squamous cell carcinoma (cSCC) are the most common sub-types of NMSC. From a molecular point of view, we are still far from fully understanding the molecular mechanisms behind the onset and progression of NMSC and to unravel targetable vulnerabilities to leverage for their treatment, which is still essentially based on surgery...

Upon activation by RAS, RAF-family kinases initiate signaling through the MAP kinase cascade to control cell growth, proliferation, and differentiation. Among RAF isoforms (ARAF, BRAF, and CRAF), oncogenic mutations are by far most frequent in BRAF. The BRAFV600E mutation drives more than half of all malignant melanoma and is also found in many other cancers. Selective inhibitors of BRAFV600E (vemurafenib, dabrafenib, encorafenib) are used clinically for these indications, but they are not effective inhibitors in the context of oncogenic RAS, which drives dimerization and activation of RAF, nor for malignancies driven by aberrantly dimerized truncation/fusion variants of BRAF...

BACKGROUND: The clinical diagnosis of face and scalp lesions (FSL) is challenging due to overlapping features. Dermatologists encountering diagnostically 'unclear' lesions may benefit from artificial intelligence support via convolutional neural networks (CNN). METHODS: In a web-based classification task, dermatologists (n = 64) diagnosed a convenience sample of 100 FSL as 'benign', 'malignant', or 'unclear' and indicated their management decisions ('no action', 'follow-up', 'treatment/excision')...

The degree of overdiagnosis in common cancer screening trials is uncertain due to inadequate design of trials, varying definition and methods used to estimate overdiagnosis. Therefore, we aimed to quantify the risk of overdiagnosis for the most widely implemented cancer screening programmes and assess the implications of design limitations and biases in cancer screening trials on the estimates of overdiagnosis by conducting an overview and re-analysis of systematic reviews of cancer screening. We searched PubMed and the Cochrane Library from their inception dates to November 29, 2021...

Immunotherapy with immune checkpoint inhibitors (ICIs) changed the treatment management in several solid metastatic tumors with very poor prognosis, in particular in melanoma stage IV since its introduction in 2011. However, it is not yet fully understood why some patients respond to ICIs and others not, and it is also unclear why melanomas are the most sensitive tumors to ICI treatment. Selection criteria for patient stratification are needed and several approaches are under evaluation. These include the PD-L1 expression in the tumor samples, assessment of the tumor mutational burden as well as radiological and molecular imaging techniques, such as positron emission tomography (PET)-CT and PET-MRI with F-18-flurodeoxyglucose (FDG) or novel radiopharmaceuticals...

Cyclin-dependent kinases 2 (CDK2) is a serine/threonine-protein kinase, which plays a key role in the regulation of cell cycle and is related to the occurrence and development of melanoma. In this study, we identified potent inhibitors for CDK2 by combining a multistage virtual screening strategy with bioassay validations. The biochemical activity of compounds was validated with ADP-Glo™ Kinase assay in vitro, and the results indicated that the biochemical activity of compound 1 (C1) was better than other selected compounds...

No abstract text is available yet for this article.

Mutations in NRAS promote tumorigenesis and drug resistance. As this protein is often considered an undruggable target, it is urgent to develop novel strategies to suppress NRAS for anticancer therapy. Recent reports indicated that a G-quadruplex (G4) structure formed in the untranslated region of NRAS mRNA can downregulate NRAS translation, suggesting a potential NRAS suppression strategy. Here, we developed a novel cell-based method for large-scale screening of NRAS G4 ligand using the G-quadruplex-triggered fluorogenic hybridization probe and successfully identified the clinically used agent Octenidine as a potent NRAS repressor...

INTRODUCTION: Studies aimed at a direct research of human herpes viruses (HHVs) in the tumor material and eye media have not been carried out so far. Research goal to establish the frequency of detection HHVs DNA in the biomaterial of the eye and blood and to assess the specific humoral immunity to the causative agents of herpes virus infections in patients with uveal melanoma. MATERIALS AND METHODS: 38 patients with the uveal tract tumor were examined for the presence of DNA of HHV types 1 and 2 (HSV-1, 2), Cytomegalovirus (CMV), Varicella Zoster virus (VZV), EpsteinBarr virus (EBV) and herpes viruses 6 and 8 types (HHV-6, HHV-8) in tumor tissue, vitreous body, aqueous humour and blood plasma by real-time polymerase chain reaction; blood serum was studied by enzyme-linked immunosorbent assay (ELISA) for IgG and IgM antibodies to HHVs...

The lungs represent a frequent target for metastatic melanoma as they offer a high-oxygen environment for tumor development. The overexpression of the WT1 protein has been associated with the occurrence of melanoma. In this study, we evaluated the effects of silencing the WT1 protein by siRNA in both in vitro in the B16F10 melanoma cell line and in vivo in a murine model of lung metastatic melanoma. We did this by implementing a novel respiratory delivery strategy of a neutral DOPC liposomal-siRNA system (L-siRNA)...